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months, there was a significant reduction in the incidence of the combined endpoint of all-cause mortality and all-cause hospitalization in the two arms receiving CRT compared with the medical therapy only arm (56 versus 68 percent). The CRT-D arm, but not the CRT-P arm, experienced a significant improvement in the secondary endpoint of all-cause mortality alone. https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 11/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate DANISH trial The Danish Study to Assess the Efficacy of ICDs in Patients with Non- Ischemic Systolic Heart Failure on Mortality (DANISH) randomly assigned 1116 patients with symptomatic systolic HF (LVEF 35 percent) not caused by ischemic heart disease to an ICD with guideline-directed optimal medical therapy or medical therapy alone [37]. Over a median follow- up of 5.6 years, no significant difference was noted in the primary outcome of total mortality (120 deaths [21.6 percent] in the ICD group compared with 131 deaths [23.4 percent] in the group without an ICD; HR 0.87, 95% CI 0.68-1.12). A significant reduction was noted in the prespecified secondary outcome of SCD in the group receiving ICDs (24 deaths [4.3 percent] compared with 46 sudden deaths [8.2 percent] in the no ICD group; HR 0.50, 95% CI 0.31-0.82), as well as nonsignificant trends toward reduction in total cardiovascular mortality and increased device infections in the ICD group. Compared with prior primary prevention ICD trials, the overall mortality rate of patients in the DANISH trial was low, likely due to improved medical therapy for HF (notably a much higher utilization of ACE-I/ARB and beta blockers than in the older trials) and the use of CRT, which was not available during the older primary prevention trials. Because of this, the DANISH trial may have been underpowered to show a mortality benefit of ICD therapy. Finally, as there are competing causes of death with increasing age, one might not expect the same benefit of ICD therapy in older patients, who may have greater comorbidities which could contribute to nonarrhythmic causes of death. Our experts feel that it would be premature to use data from the DANISH study as the sole basis to withhold potentially life-saving ICD therapy from all patients with nonischemic cardiomyopathy. Instead, the results actually support the use of ICDs in younger patients who have a cardiomyopathy not caused by ischemic heart disease. For those patients who are likely to have a strong response to CRT or who are not considered good candidates for ICD therapy, a CRT-P device may be more suitable and compatible with therapeutic goals. Meta-analyses of ICD trials in nonischemic cardiomyopathy Several updated meta- analyses have been published that include patients with nonischemic cardiomyopathy receiving an ICD for primary prevention from the same original five ICD trials (CAT, AMIOVIRT, DEFINITE, SCD-HeFT, and COMPANION) as well as patients from the DANISH trial [38-46]. When considering all six trials collectively, each of the meta-analyses demonstrated a significant benefit of the ICD on all-cause mortality in patients with nonischemic cardiomyopathy (19 to 24 percent hazard reduction compared with medical therapy alone). When only patients who also received CRT in the COMPANION and DANISH trials were analyzed, there was a nonsignificant trend toward reduction in all-cause mortality among patients with an ICD (approximately 25 to 30 percent hazard reduction with nonsignificant confidence intervals) [38,40,43]. Despite the lack of a significant incremental benefit of the ICD in the two trials that included CRT, it is currently https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 12/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate premature to withhold ICD therapy in all patients with nonischemic cardiomyopathy who require concomitant CRT. Adequately powered randomized studies are needed before recommending a change in current practice guidelines. GUIDELINE-DIRECTED MEDICAL THERAPY For patients who meet criteria for insertion of an implantable cardioverter-defibrillator (ICD) for the primary prevention of SCD, in the absence of a contraindication, we recommend optimizing guideline-directed medical therapy prior to ICD implantation. Heart failure therapy Several of the components of appropriate medical therapy after a myocardial infarction (MI) reduce SCD as well as overall mortality. While these data are derived from trials in patients with ischemic heart disease, we can infer that many of the same benefits should apply to SCD risk reduction in patients with nonischemic cardiomyopathy. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the management of heart failure with reduced ejection fraction in adults".) Beta blockers In addition to reducing overall mortality in patients with an acute MI, beta blockers also reduced the risk of SCD [47,48]. The SCD benefit is better established in patients with chronic HF. (See "Acute myocardial infarction: Role of beta blocker therapy" and "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy", section on 'Heart failure therapy'.) Post-MI patients with an ICD also appear to derive a benefit from beta blockers. In a cohort of 691 patients with ischemic cardiomyopathy who received an ICD in the MADIT-II trial, the 433 patients treated with a beta blocker had significantly lower mortality (hazard ratio [HR] 0.43) compared with those not taking beta blockers; additionally, patients in the highest quartile of beta blocker dose had a significant reduction in the risk of ventricular tachyarrhythmias requiring ICD discharge (HR 0.48) [49]. ACE inhibitors A meta-analysis of 15,104 patients in 15 trials of acute MI found that angiotensin-converting enzyme (ACE) inhibitor therapy reduced the risk of SCD (odds ratio 0.80, 95% CI 0.70-0.92, absolute benefit approximately 1.4 percent) as well as overall and cardiovascular mortality [50]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials".) Angiotensin II receptor blockers Angiotensin II receptor blockers (ARBs) are often used for patients who cannot tolerate ACE inhibitors. At appropriate doses, it is likely that ARBs https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 13/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate reduce the risk of SCD to the same degree as ACE inhibitors [51]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use".) Angiotensin receptor-neprilysin inhibitor The combination of an ARB and neprilysin inhibitor, known as angiotensin receptor-neprilysin inhibitor or ARNI, is another therapy for use in patients with HF and reduced LVEF (HFrEF). A randomized double-blind trial (PARADIGM-HF) in patients with HFrEF found that sacubitril-valsartan reduced cardiovascular mortality and hospitalization for HF as well as all-cause mortality compared with a standard dose of the ACE inhibitor enalapril [52]. The ARNI combination is administered in conjunction with other HF therapies, in place of an ACE inhibitor or ARB. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Primary components of therapy'.) Statins Statins given to patients who have had an acute MI improve overall mortality. Although data are limited and inconclusive, part of the benefit may result from a lower rate of SCD, which may reflect a direct effect of statin therapy [53-55]. (See "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome".) Mineralocorticoid receptor antagonists Among post-MI patients who have left ventricular (LV) dysfunction and HF and/or diabetes, eplerenone significantly reduced both overall mortality and SCD (relative risk for SCD 0.79, 95% CI 0.64-0.97) [56]. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Mineralocorticoid receptor antagonist'.) Sodium glucose co-transporter 2 inhibitors (SGLT-2 inhibitors) Evidence as to whether SGLT-2 inhibitors reduced SCD and/or ventricular arrhythmias in patients with HF is mixed and has not been directly studied. In a post-hoc analysis of the DAPA-HF trial of persons with New York Heart Association (NYHA) class II to IV HF and LVEF <40 percent, the SGLT-2 inhibitor dapagliflozin reduced occurrence of the composite outcome of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death compared with placebo [57]. Among participants randomized to dapagliflozin, 140 of 2373 patients (5.9 percent) experienced the composite outcome compared with 175 of 2371 patients (7.4 percent) in the placebo group (HR 0.79, 95% CI 0.63-0.99). The effect was consistent across each of the composite outcome components. While a prior meta-analysis of 34 randomly controlled trials in participants with type 2 diabetes mellitus or HF also showed that SGLT-2 inhibitors reduced SCD compared with placebo or active control (OR 0.72 95% CI 0.54-0.97), this result just achieved statistical significance, and there was no significant difference in incident ventricular arrhythmia or cardiac arrest [58]. (See "Primary pharmacologic therapy https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 14/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate for heart failure with reduced ejection fraction", section on 'Sodium-glucose co-transporter 2 inhibitors'.) Despite the proven benefits, some patients are not receiving guideline-directed medical therapy at the time of ICD implantation. In a 2011 study analyzing 175,757 first-time ICD recipients, using data from the National Cardiovascular Data Registry, 25.7 percent of ICD recipients without a documented contraindication were reported as not receiving optimal medical therapy at the time of ICD implantation, including 18.7 percent who were reported as not receiving an ACE inhibitor or ARB and 10.7 percent who were reported as not receiving a beta blocker [59]. While some of these gaps may reflect issues of coding and documentation, these data suggest an opportunity for significant improvement in the treatment of patients with evidence-based, cost-effective therapies that could potentially result in improvement in cardiomyopathy and avoidance of an ICD. Although current guidelines suggest at least three months of guideline- directed medical therapy in patients with symptomatic HF and left ventricular ejection fraction (LVEF) 35 percent, the ideal duration of guideline-directed medical therapy prior to prophylactic ICD implantation remains uncertain. However, data demonstrate that a relevant proportion of patients with newly diagnosed HF may show recovery of LVEF >35 percent beyond three months after initiation of HF therapy, allowing left ventricular reverse remodeling to occur during intensified treatment [60]. Antiarrhythmic drugs Randomized clinical trials do not support the routine use of prophylactic antiarrhythmic drug therapy, other than beta blockers, to prevent SCD in patients with HF [1,61-64]. The lack of overall benefit from prophylactic antiarrhythmic drug therapy is due to both incomplete suppression of ventricular arrhythmias and the risk of proarrhythmia [62,63,65-69]. Given the established superiority of an ICD in high-risk patients, class I and class III antiarrhythmic drugs no longer have an established role for the primary prevention of SCD. Among the antiarrhythmic drugs, amiodarone has the advantage of a relatively low rate of proarrhythmia, less negative inotropic effect, and higher efficacy for suppression of tachyarrhythmias. While amiodarone is not approved for use in the primary prevention of arrhythmias, this was a common off-label use of the drug [22]. In addition, amiodarone is frequently used for the treatment of atrial fibrillation as it is considered relatively "safe," from a cardiac standpoint, with low risk for proarrhythmia in the setting of HF [70]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Antiarrhythmic drugs' and "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias'.) SPECIAL POPULATIONS https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 15/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Class IV heart failure Class IV HF is a state that may be transitory and therefore associated with heterogeneous prognosis. Once class IV HF is refractory (stage D HF), life expectancy is generally less than one year unless cardiac transplantation is performed or a left ventricular assist device is implanted. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Cardiac transplantation'.) The role of implantable cardioverter-defibrillator (ICD) therapy for primary prevention of SCD in patients with New York Heart Association (NYHA) class IV HF with a narrow QRS complex has not been studied. NYHA class IV patients were generally excluded from randomized primary prevention ICD trials due to high expected mortality rate from pump failure, and only a small number were included in cardiac resynchronization therapy combined with ICD (CRT-D) trials. However, a nonrandomized series of patients awaiting cardiac transplantation suggested a higher likelihood of survival to transplantation with ICD therapy, regardless of whether the ICD indication was well established [71]. Given these considerations, for ambulatory patients with NYHA class IV HF, a left ventricular ejection fraction (LVEF) 35 percent and a narrow QRS complex (ie, no dyssynchrony), who are awaiting cardiac transplantation outside the hospital, ICD implantation may be considered as a bridge to transplantation. However, there are very limited data to support this recommendation [2,71]. According to the 2017 Guideline for the Management of Patients with Ventricular Arrhythmias, "in patients with HFrEF who are awaiting heart transplant and who otherwise would not qualify for an ICD (eg, NYHA class IV and/or use of inotropes) with a plan to discharge home, an ICD is reasonable (class IIa recommendation, B-NR)." A wearable defibrillator vest may be considered as an alternative in selected patients [72,73]. Older adults and patients with comorbidities Because of the competing risks of arrhythmic and nonarrhythmic death, some investigators have expressed concern that older adults and those with multiple or severe comorbidities might be less likely to derive benefit from an ICD [74-77]. The mean age of patients in randomized primary prevention ICD trials ranged from 60 to 67 years, and patients over 75 to 80 years comprised a relatively small proportion of these cohorts. Because most older adult patients as well as those patients with severe comorbidities (such as advanced kidney disease) were excluded from most of the major ICD trials, the survival benefit from ICD implantation in such populations is less well defined. The decision to recommend an ICD should be made on a case-by-case basis based on shared decision making, taking into account patient values and preferences. Age or comorbidity alone should not be a sole exclusion for ICD implantation. As part of the 2017 AHA/ACC/HRS guideline for management of ventricular arrhythmias and prevention of SCD, a systematic review was performed to specifically assess the impact of https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 16/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate primary prevention ICD therapy among older patients and patients with significant morbidities [78]. The following findings were noted: Older adults While the systematic review identified 10 studies of primary prevention ICD use among older adults, because of concerns about overlapping patients between some of the studies, the final "minimal overlap" meta-analysis included four studies with unique patient populations. Compared with patients without ICD implantation, patients who received a primary prevention ICD had a 25 percent reduction in total mortality (hazard ratio [HR] 0.75, 95% CI 0.67-0.83). Patients with comorbidities Among 10 studies of primary prevention ICD use in patients with a variety of comorbidities (including renal disease, chronic obstructive pulmonary disease, and diabetes, among others), ICD implantation for primary prevention was associated with a 28 percent reduction in total mortality (HR 0.72, 95% CI 0.65-0.79), with similar findings in the "minimal overlap" meta-analysis, which included only five studies (HR 0.71, 95% CI 0.61-0.82). Patients with renal disease Patients with chronic kidney disease requiring dialysis have increased mortality and reported high rates of SCD. Among five studies (two post-hoc analyses of randomized trial data and three observational studies) specifically looking at patients with varying degrees of chronic renal disease, primary prevention ICD use was associated with a 29 percent reduction in total mortality (HR 0.71, 95% CI 0.60-0.85). (See "Evaluation of sudden cardiac arrest and sudden cardiac death in dialysis patients".) Following the systematic review for the 2017 AHA/ACC/HRS guidelines, additional studies have been published evaluating the role of primary prevention ICDs in older patients and those with severe kidney disease. While randomized trial data are absent, clinicians have shown a preference for using the totally subcutaneous ICD (S-ICD) in patients with severe kidney disease (in particular among patients who undergo regular hemodialysis) in order to reduce the risk of intravascular infection in this population [79]. In a retrospective multi-center cohort of 300 patients receiving a primary prevention ICD or CRT-D, which included 150 patients 80 years old (mean age 82 years, 76 percent with one or fewer comorbidities) and 150 patients <80 years old (mean age 62 years, matched for sex and type of heart disease), similar numbers of patients received an appropriate shock (19.4 percent of older patients versus 21.6 percent of younger patients) with no significant difference in complication rates over mean follow-up of three years [80]. These data suggest that, compared with younger patients, primary prevention ICDs can be safely implanted in selected patients 80 years old with few or no comorbidities. https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 17/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate In patients on dialysis who did not meet standard indications for ICD therapy, the ICD2 trial was published suggesting no benefit from primary prevention ICDs [81]. In the ICD2 trial, 200 patients on dialysis who had an LVEF 35 percent without HF symptoms and no documented VT were randomized to ICD implantation with optimal medical therapy or to not receive an ICD. Following randomization of 188 patients, the trial was stopped prematurely due to futility, with no significant improvement among ICD recipients in five- year rates of SCD (9.7 versus 7.9 percent without ICD; HR 1.3, 95% CI 0.5-3.3) or overall survival (50.6 versus 54.4 percent without ICD; HR 1.0, 95% CI 0.7-1.5). While the results may be partially explained by the lower than expected observed rates of SCD in the study (annual rate of 2 percent versus expected rate of 5 to 6 percent), the data do not support extending primary prevention ICD use in dialysis beyond the standard indications. However, it should be noted that transvenous ICDs (often dual chamber systems) were utilized and significant complications occurred, including adverse events related to the ICD implantation procedure in 13 percent and ICD explantation (primarily due to bacteremia) in 7.5 percent. These results cannot necessarily be extrapolated to totally subcutaneous systems, which are frequently utilized in patients on dialysis as they appear to be associated with lower rates of bacteremia than transvenous systems. (See 'Our approach for patients with ischemic cardiomyopathy' above and 'Our approach for patients with nonischemic dilated cardiomyopathy' above and "Subcutaneous implantable cardioverter defibrillators".) GAPS IN THE GUIDELINES Possible indications not addressed by guidelines The HRS/ACC/AHA Expert Consensus Statement on the Use of ICD Therapy in Patients Who Are Not Included or Not Represented in Clinical Trials evaluated important clinical situations for which implantable cardioverter- defibrillator (ICD) therapy might be beneficial in selected populations that were not consistently included in randomized clinical trials and may not be included in guideline documents [82]. This document includes discussion related to the following topics: Use of an ICD in patients with an abnormal troponin that is not due to a myocardial infarction (MI). Use of an ICD within 40 days after a MI, such as patients with preexisting left ventricular (LV) dysfunction or those requiring non-elective permanent pacing. Use of an ICD within the first 90 days after revascularization, such as patients with preexisting LV dysfunction or those requiring non-elective permanent pacing. https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 18/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Use of an ICD within the first nine months after initial diagnosis of nonischemic cardiomyopathy. Recommendations were made based on available evidence as well as consensus opinion. Many clinical scenarios where gaps in evidence exist for ICD therapy are also discussed in the 2013 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy (CRT) [83]. Patients undergoing generator replacement with improved LVEF and/or no prior ICD therapies An additional clinical scenario that is not fully covered in professional society guidelines and consensus documents is the management of patients who have received a primary prevention ICD who have improved or normalized LV function, have never received appropriate ICD therapy, and have either reached the point of elective replacement for their device or require reimplantation after system extraction (ie, due to infection) [74,84-89]. Among a subset of 1273 patients from the SCD-HeFT trial (624 randomized to ICD, 649 randomized to placebo) who had repeat assessment of left ventricular ejection fraction (LVEF) at a mean of 13.5 months post-randomization, 371 patients (29 percent) showed improvement to LVEF >35 percent (186 [29.8 percent] in ICD group versus 185 [28.5 percent] in placebo group) [84]. There was a similar reduction in all-cause mortality with the ICD in both the LVEF 35 percent group (adjusted hazard ratio [HR] 0.64, 95% CI 0.48- 0.85) and the LVEF >35 percent group (adjusted HR 0.62, 95% CI 0.29-1.30). Among 752 patients from the MADIT-CRT study with mild HF symptoms, 7.3 percent had normalized LVEF to >50 percent after cardiac resynchronization therapy (CRT; so-called "super-responders"); these "super-responders" had a low rate of ventricular arrhythmias, with only 3 of 55 super-responders (5 percent) having treated VT (none requiring an ICD shock) at a mean follow-up of 2.2 years [85]. Among 231 patients with an ICD placed for primary prevention, 26 percent had shown enough improvement in LVEF to no longer meet implant criteria at the time of elective generator replacement [86]. Patients in whom LVEF improved had a lower rate of appropriate therapy after generator replacement (2.8 percent per year) than those whose LVEF remained 35 percent (10.7 percent per year). Among a prospective cohort of 538 patients from the PROSE-ICD study who received a primary prevention ICD and had subsequent reassessment of LVEF, 40 percent of patients had >5 percent improvement in LVEF (over 4.9 years of follow-up), of whom 25 percent had improvement in LVEF to >35 percent [87]. Risk of an appropriate shock was significantly lower (but not completely eliminated) in patients with improved LVEF. https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 19/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Among a cohort of 1421 patients with an ICD (49 percent primary prevention, 51 percent secondary prevention) scheduled to undergo generator replacement an average of 3.5 years following initial implantation, 471 patients (33 percent) had received an appropriate shock prior to replacement [90]. Following generator replacement, 435 patients (31 percent) received an appropriate ICD therapy during mean follow-up of 2.7 years. Patients with prior appropriate ICD therapy were significantly more likely to receive additional therapy following generator replacement (HR 3.0, 95% CI 2.4-3.7). With limited observational data and no randomized trial data to guide decision making for patients with normalized LVEF, clinicians need to weigh a number of factors when planning generator replacement or system reimplantation in such patients, including original indication, possibility of relapse in LV dysfunction, overall prognosis, comorbidities, and patient preference. The 2013 ACC/HRS/AHA Appropriate Use Criteria suggest that replacement of CRT-D with CRT-P devices "may be appropriate" in selected patients who underwent initial ICD implantation for primary prevention indications if substantial improvement in LV function is noted (LVEF now >35 percent, and particularly if 50 percent), if no clinically relevant ventricular arrhythmias have occurred [83]. However, due to the paucity of prospective data on this topic, it is also considered appropriate to replace a CRT-D device with a new CRT-D device in situations where LV function has improved [83]. PROGNOSTIC SIGNIFICANCE OF ICD SHOCKS AND DEVICE PROGRAMMING Among patients with HF receiving implantable cardioverter-defibrillators (ICDs) for primary prevention in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), an appropriate shock, as compared with no appropriate shock, was associated with substantially increased all-cause mortality (hazard ratio [HR] 5.7, 95% CI 4.0-8.1) [91]. An inappropriate shock, as compared with no inappropriate shock, was also associated with a significant increase in mortality (HR 2.0, 95% CI 1.3-3.1). The most common cause of death among patients who received any ICD shock was progressive HF. Other studies have also shown that appropriate or inappropriate shocks are associated with increased mortality [92,93]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Prognosis of heart failure".) Several trials have underscored the importance of reducing both appropriate and inappropriate shocks through optimizing ICD programming. The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) study found improved survival in ICD recipients who were randomly assigned to ICD programming with a high rate cutoff and/or long detection times, both of which were associated with fewer ICD shocks compared with conventional programming [94]. The Avoiding Defibrillator Therapies For Non-sustained https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 20/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Arrhythmias In ICD Patients (ADVANCE) III trial found a similar benefit for extended detection time in reducing both appropriate and inappropriate ICD shocks [95]. The 2015 HRS/EHRA/APHRS/SOLAECE Expert Consensus Statement on Optimal Implantable Cardioverter- Defibrillator Programming and Testing outlines the importance of proper ICD programming in reducing unnecessary therapy [96]. (See "Implantable cardioverter-defibrillators: Optimal programming".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Implantable cardioverter-defibrillators (The Basics)") Beyond the Basics topic (see "Patient education: Implantable cardioverter-defibrillators (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS While implantable cardioverter-defibrillators (ICDs) are highly efficacious in the treatment of ventricular tachyarrhythmias and prevention of sudden cardiac death (SCD), they are https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 21/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate costly, require ongoing follow-up, and have acute procedural and long-term risks (eg, infection, device and lead malfunction, etc). In addition, only a subset of patients with cardiomyopathy develop sustained ventricular tachyarrhythmias or SCD. Therefore, risk stratification of patients prior to considering ICD therapy is important for targeting therapy to patients at highest risk of SCD and minimizing the number of ICD implantations in patients who are unlikely to benefit. (See 'Risk stratification strategies' above.) Recommendations for selecting the optimal patients for ICD therapy are based largely upon the entry criteria in the major trials. Prior to recommending ICD therapy for the primary prevention of SCD, there should be a reasonable expectation of survival with a good functional status for at least one year regardless of the indication for ICD therapy. For patients who meet criteria for insertion of an ICD for the primary prevention of SCD, in the absence of a contraindication, we recommend optimizing guideline-directed medical therapy with a beta blocker and either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker prior to ICD implantation (Grade 1A). (See 'Guideline-directed medical therapy' above and "Overview of the management of heart failure with reduced ejection fraction in adults".) For patients with cardiomyopathy due to ischemic heart disease, left ventricular ejection fraction (LVEF) 35 percent, and associated heart failure (HF) with New York Heart Association (NYHA) functional class II or III status, we recommend ICD therapy for primary prevention of SCD (Grade 1A). Patients should be evaluated at least 40 days post-myocardial infarction (MI) and more than three months following revascularization. (See 'Ischemic cardiomyopathy' above.) For patients with cardiomyopathy due to ischemic heart disease, LVEF 30 percent, and NYHA functional class I status, we recommend ICD therapy for primary prevention of SCD (Grade 1B). Patients should be evaluated at least 40 days post-MI and more than three months following revascularization. (See 'Ischemic cardiomyopathy' above.) For patients with nonischemic dilated cardiomyopathy, LVEF 35 percent, and associated HF with NYHA functional class II or III symptoms, we suggest ICD therapy for primary prevention of SCD rather than optimal medical therapy alone (Grade 2B). ICDs are very effective at reducing total mortality and mortality from SCD, although the benefits of an ICD on total mortality may be diminished in the setting of guideline- directed optimal medical therapy and cardiac resynchronization therapy (CRT). All patients receiving an ICD for primary prevention of SCD should be treated with at least https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 22/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate three months of guideline-directed medical therapy prior to ICD implantation. (See 'Nonischemic dilated cardiomyopathy' above.) For patients with an LVEF 35 percent, HF with NYHA functional class III or IV status, and a QRS duration 120 milliseconds, we recommend implantation of a combined CRT-D device (biventricular pacing combined with an ICD) rather than an ICD alone (Grade 1A). Strongest consideration for the CRT component should be given for those patients with left bundle branch block (LBBB) QRS morphology, those with QRS duration 150 milliseconds, and those dependent upon ventricular pacing due to atrioventricular block. (See 'Trials of primary prevention ICDs in nonischemic dilated cardiomyopathy' above and "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) The role of ICD therapy for primary prevention of SCD in patients with HF and NYHA class IV status who have a narrow QRS complex has not been well-studied, as NYHA class IV patients have generally been excluded from randomized primary prevention ICD trials due to high expected mortality rate. For ambulatory patients with NYHA class IV HF, an LVEF 35 percent, and a narrow QRS complex (ie, no dyssynchrony) who are awaiting cardiac transplantation outside the hospital, it is reasonable to consider ICD implantation as a bridge to transplantation. (See 'Class IV heart failure' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, and Scott Manaker, MD, PhD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353:2001. 2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 23/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate 3. Al-Khatib SM, Hellkamp AS, Fonarow GC, et al. Association between prophylactic implantable cardioverter-defibrillators and survival in patients with left ventricular ejection fraction between 30% and 35%. JAMA 2014; 311:2209. 4. Bilchick KC, Stukenborg GJ, Kamath S, Cheng A. Prediction of mortality in clinical practice for medicare patients undergoing defibrillator implantation for primary prevention of sudden cardiac death. J Am Coll Cardiol 2012; 60:1647. 5. Hong C, Alluri K, Shariff N, et al. Usefulness of the CHA2DS2-VASc Score to Predict Mortality in Defibrillator Recipients. Am J Cardiol 2017; 120:83. 6. Zeitler EP, Hellkamp AS, Fonarow GC, et al. Primary prevention implantable cardioverter- defibrillators and survival in older women. JACC Heart Fail 2015; 3:159. 7. Zhang Y, Guallar E, Blasco-Colmenares E, et al. Clinical and serum-based markers are associated with death within 1 year of de novo implant in primary prevention ICD recipients. Heart Rhythm 2015; 12:360. 8. Nevzorov R, Goldenberg I, Konstantino Y, et al. Developing a risk score to predict mortality in the first year after implantable cardioverter defibrillator implantation: Data from the Israeli ICD Registry. J Cardiovasc Electrophysiol 2018; 29:1540. 9. Bilchick KC, Wang Y, Cheng A, et al. Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators. J Am Coll Cardiol 2017; 69:2606. 10. Kristensen SL, Levy WC, Shadman R, et al. Risk Models for Prediction of Implantable Cardioverter-Defibrillator Benefit: Insights From the DANISH Trial. JACC Heart Fail 2019; 7:717. 11. Levy WC, Li Y, Reed SD, et al. Does the Implantable Cardioverter-Defibrillator Benefit Vary With the Estimated Proportional Risk of Sudden Death in Heart Failure Patients? JACC Clin Electrophysiol 2017; 3:291. 12. Levy WC, Hellkamp AS, Mark DB, et al. Improving the Use of Primary Prevention Implantable Cardioverter-Defibrillators Therapy With Validated Patient-Centric Risk Estimates. JACC Clin Electrophysiol 2018; 4:1089. 13. Shadman R, Poole JE, Dardas TF, et al. A novel method to predict the proportional risk of sudden cardiac death in heart failure: Derivation of the Seattle Proportional Risk Model. Heart Rhythm 2015; 12:2069. 14. Rouleau JL, Talajic M, Sussex B, et al. Myocardial infarction patients in the 1990s their risk |
costly, require ongoing follow-up, and have acute procedural and long-term risks (eg, infection, device and lead malfunction, etc). In addition, only a subset of patients with cardiomyopathy develop sustained ventricular tachyarrhythmias or SCD. Therefore, risk stratification of patients prior to considering ICD therapy is important for targeting therapy to patients at highest risk of SCD and minimizing the number of ICD implantations in patients who are unlikely to benefit. (See 'Risk stratification strategies' above.) Recommendations for selecting the optimal patients for ICD therapy are based largely upon the entry criteria in the major trials. Prior to recommending ICD therapy for the primary prevention of SCD, there should be a reasonable expectation of survival with a good functional status for at least one year regardless of the indication for ICD therapy. For patients who meet criteria for insertion of an ICD for the primary prevention of SCD, in the absence of a contraindication, we recommend optimizing guideline-directed medical therapy with a beta blocker and either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker prior to ICD implantation (Grade 1A). (See 'Guideline-directed medical therapy' above and "Overview of the management of heart failure with reduced ejection fraction in adults".) For patients with cardiomyopathy due to ischemic heart disease, left ventricular ejection fraction (LVEF) 35 percent, and associated heart failure (HF) with New York Heart Association (NYHA) functional class II or III status, we recommend ICD therapy for primary prevention of SCD (Grade 1A). Patients should be evaluated at least 40 days post-myocardial infarction (MI) and more than three months following revascularization. (See 'Ischemic cardiomyopathy' above.) For patients with cardiomyopathy due to ischemic heart disease, LVEF 30 percent, and NYHA functional class I status, we recommend ICD therapy for primary prevention of SCD (Grade 1B). Patients should be evaluated at least 40 days post-MI and more than three months following revascularization. (See 'Ischemic cardiomyopathy' above.) For patients with nonischemic dilated cardiomyopathy, LVEF 35 percent, and associated HF with NYHA functional class II or III symptoms, we suggest ICD therapy for primary prevention of SCD rather than optimal medical therapy alone (Grade 2B). ICDs are very effective at reducing total mortality and mortality from SCD, although the benefits of an ICD on total mortality may be diminished in the setting of guideline- directed optimal medical therapy and cardiac resynchronization therapy (CRT). All patients receiving an ICD for primary prevention of SCD should be treated with at least https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 22/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate three months of guideline-directed medical therapy prior to ICD implantation. (See 'Nonischemic dilated cardiomyopathy' above.) For patients with an LVEF 35 percent, HF with NYHA functional class III or IV status, and a QRS duration 120 milliseconds, we recommend implantation of a combined CRT-D device (biventricular pacing combined with an ICD) rather than an ICD alone (Grade 1A). Strongest consideration for the CRT component should be given for those patients with left bundle branch block (LBBB) QRS morphology, those with QRS duration 150 milliseconds, and those dependent upon ventricular pacing due to atrioventricular block. (See 'Trials of primary prevention ICDs in nonischemic dilated cardiomyopathy' above and "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) The role of ICD therapy for primary prevention of SCD in patients with HF and NYHA class IV status who have a narrow QRS complex has not been well-studied, as NYHA class IV patients have generally been excluded from randomized primary prevention ICD trials due to high expected mortality rate. For ambulatory patients with NYHA class IV HF, an LVEF 35 percent, and a narrow QRS complex (ie, no dyssynchrony) who are awaiting cardiac transplantation outside the hospital, it is reasonable to consider ICD implantation as a bridge to transplantation. (See 'Class IV heart failure' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, and Scott Manaker, MD, PhD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353:2001. 2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. 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Changes in Follow-Up Left Ventricular Ejection Fraction Associated With Outcomes in Primary Prevention Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy Device Recipients. J Am Coll Cardiol 2015; 66:524. 88. Madeira M, Ant nio N, Milner J, et al. Who still remains at risk of arrhythmic death at time of implantable cardioverter-defibrillator generator replacement? Pacing Clin Electrophysiol 2017; 40:1129. 89. Weng W, Sapp J, Doucette S, et al. Benefit of Implantable Cardioverter-Defibrillator Generator Replacement in a Primary Prevention Population-Based Cohort. JACC Clin Electrophysiol 2017; 3:1180. 90. Witt CM, Waks JW, Mehta RA, et al. Risk of Appropriate Therapy and Death Before Therapy After Implantable Cardioverter-Defibrillator Generator Replacement. Circ Arrhythm Electrophysiol 2018; 11:e006155. 91. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008; 359:1009. 92. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008; 51:1357. 93. Dichtl W, Wolber T, Paoli U, et al. Appropriate therapy but not inappropriate shocks predict survival in implantable cardioverter defibrillator patients. Clin Cardiol 2011; 34:433. 94. Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012; 367:2275. 95. Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard- detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA 2013; 309:1903. 96. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm 2016; 13:e50. Topic 91077 Version 39.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 31/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate GRAPHICS Modes of death based on heart failure severity As the severity of heart failure symptoms worsens, the mode of death is less likely to be arrhythmic sudden cardiac death and more likely to be due to heart failure. NYHA: New York Heart Association; CHF: congestive heart failure. Graphic 98258 Version 2.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 32/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Summary of primary prevention implantable cardioverter-defibrillator (ICD) trials Number Enrollment/follow- Ischemic/non- Med Trial of Entry criteria up ischemic CMP thera patients Ischemic CMP (late post-MI) trials MADIT-I 1991 to 1996 Mean follow-up 27 196 100%/0% Prior MI BB - NSVT on ECG ACE/A months monitoring 58% LVEF 35% MRA NYHA I/II/III AAD Inducible VT during EPS MUSTT 1990 to 1996 Mean follow-up 39 months 704 100%/0% Prior MI BB - 4 NSVT on ECG monitoring ACE/A 75% LVEF 40% MRA NYHA I/II/III AAD Inducible VT during EPS CABG-Patch 1993 to 1996 900 100%/0% <80 years old BB - Mean follow-up 32 months Scheduled for elective CABG ACE-I MRA LVEF <36% AAD Abnormal SAECG MADIT-II 1997 to 2001 Mean follow-up 20 1232 100%/0% Prior MI BB - 7 LVEF 35% ACE/A 70% months NYHA I/II/III MRA AAD Ischemic CMP (early post-MI) trials DINAMIT 1998 to 2003 674 100%/0% 6 to 40 days BB - Mean follow-up 30 post-MI ACE-I months LVEF 35% MRA https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 33/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Impaired AAD autonomic function (depressed HR variability or elevated average 24- hour HR on Holter monitoring) IRIS 1999 to 2007 Mean follow-up 37 898 100%/0% 5 to 31 days BB - post-MI ACE-I months LVEF 40% and HR 90 BPM on first MRA AAD ECG or NSVT Combined ischemic and nonischemic CMP trial SCD-HeFT 1997 to 2003 Mean follow-up 45 2521 52%/48% HF for 3 months BB - ACE/A 85% months LVEF 35% NYHA II/III MRA AAD rand to amio addit 7% cross amio Nonischemic CMP trials DEFINITE 1998 to 2003 458 0%/100% Nonischemic BB - Mean follow-up 29 months CMP ACE/A LVEF 35% 97% NYHA I/II/III MRA PVCs or NSVT AAD COMPANION 2000 to 2002 1520 55%/45% LVEF 35% BB - Median follow-up of 16 months NYHA III/IV ACE/A requiring hospitalization 69% MRA AAD https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 34/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate within prior year DANISH 2008 to 2014 Mean follow-up 68 1114 0%/100% Nonischemic BB - CMP ACE/A months LVEF 35% 97% NYHA II/III (or MRA IV if CRT planned) CRT - AAD AAD: antiarrhythmic drugs; ACE-I: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; BB: beta blocker; BPM: beats per minute; CABG: coronary artery bypass graft surgery; CMP: cardiomyopathy; CRT: cardiac resynchronization therapy; HF: heart failure; ECG: electrocardiogram; EPS: electrophysiologic study; ICD: implantable cardioverter-defibrillator; LVEF: left ventricular ejection fraction; MI: myocardial infarction; MRA: mineralocorticoid receptor antagonist; NR: not reported (likely near zero given early date of trial); NSVT: nonsustained ventricular tachycardia; NYHA: New York Heart Association; PVC: premature ventricular contraction; SAECG: signal averaged electrocardiogram; SCA: sudden cardiac arrest; VT: ventricular tachycardia. Epicardial ICDs were predominantly used in the CABG Patch trial, as patients were all undergoing CABG. This is not consistent with contemporary practice. Some patients with NYHA class IV functional status were enrolled in MADIT-II, but the requirement was to be NYHA class I/II/III at the time of enrollment. Graphic 98261 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 35/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 36/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 37/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Pacing leads for cardiac resynchronization therapy Two leads (right atrial and right ventricular leads) permit pacing of the right atrium and right ventricle. The third lead (coronary sinus lead), which is advanced through the coronary sinus into a venous branch that runs along the free wall of the left ventricle, paces the lateral wall and enables synchronized left ventricular contraction. Graphic 79450 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 38/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Implantable defibrillator versus conventional drug therapy Kaplan-Meier cumulative survival curves in the MADIT trial showing that selected high-risk patients (prior infarction, left ventricular ejection fraction 35 percent, nonsustained ventricular tachycardia, and an inducible sustained ventricular tachyarrhythmia not supressible with procainamide) have a better survival rate with an implantable defibrillator compared with conventional therapy with antiarrhythmic drugs (p = 0.009). The number of patients at each time period is noted at the bottom. Data from: Moss AJ, Hall WJ, Cannom DS, et al for the Multicenter Automatic De brillator Implantation Trial Investigators, N Engl J Med 1996; 335:1933. Graphic 76854 Version 2.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 39/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate ICD reduces sudden death in MUSTT The MUSTT trial enrolled 704 patients with coronary artery disease, nonsustained ventricular tachycardia (VT), and a left ventricular ejection fraction 40 percent who had sustained VT induced during electrophysiologic (EP) study. Kaplan-Meier estimates show that the incidence of cardiac arrest or death from arrhythmia is significantly lower in those receiving an implantable cardioverter-defibrillator (ICD) compared with those receiving no therapy or those with EP-guided (EPG) antiarrhythmic drug (AAD) therapy. Data from: Buxton AE, Lee KL, Fisher JD, et al. N Engl J Med 1999; 341:1882. Graphic 68247 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 40/43 7/6/23, 3:35 PM |
surgery; CMP: cardiomyopathy; CRT: cardiac resynchronization therapy; HF: heart failure; ECG: electrocardiogram; EPS: electrophysiologic study; ICD: implantable cardioverter-defibrillator; LVEF: left ventricular ejection fraction; MI: myocardial infarction; MRA: mineralocorticoid receptor antagonist; NR: not reported (likely near zero given early date of trial); NSVT: nonsustained ventricular tachycardia; NYHA: New York Heart Association; PVC: premature ventricular contraction; SAECG: signal averaged electrocardiogram; SCA: sudden cardiac arrest; VT: ventricular tachycardia. Epicardial ICDs were predominantly used in the CABG Patch trial, as patients were all undergoing CABG. This is not consistent with contemporary practice. Some patients with NYHA class IV functional status were enrolled in MADIT-II, but the requirement was to be NYHA class I/II/III at the time of enrollment. Graphic 98261 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 35/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 36/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 37/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Pacing leads for cardiac resynchronization therapy Two leads (right atrial and right ventricular leads) permit pacing of the right atrium and right ventricle. The third lead (coronary sinus lead), which is advanced through the coronary sinus into a venous branch that runs along the free wall of the left ventricle, paces the lateral wall and enables synchronized left ventricular contraction. Graphic 79450 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 38/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Implantable defibrillator versus conventional drug therapy Kaplan-Meier cumulative survival curves in the MADIT trial showing that selected high-risk patients (prior infarction, left ventricular ejection fraction 35 percent, nonsustained ventricular tachycardia, and an inducible sustained ventricular tachyarrhythmia not supressible with procainamide) have a better survival rate with an implantable defibrillator compared with conventional therapy with antiarrhythmic drugs (p = 0.009). The number of patients at each time period is noted at the bottom. Data from: Moss AJ, Hall WJ, Cannom DS, et al for the Multicenter Automatic De brillator Implantation Trial Investigators, N Engl J Med 1996; 335:1933. Graphic 76854 Version 2.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 39/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate ICD reduces sudden death in MUSTT The MUSTT trial enrolled 704 patients with coronary artery disease, nonsustained ventricular tachycardia (VT), and a left ventricular ejection fraction 40 percent who had sustained VT induced during electrophysiologic (EP) study. Kaplan-Meier estimates show that the incidence of cardiac arrest or death from arrhythmia is significantly lower in those receiving an implantable cardioverter-defibrillator (ICD) compared with those receiving no therapy or those with EP-guided (EPG) antiarrhythmic drug (AAD) therapy. Data from: Buxton AE, Lee KL, Fisher JD, et al. N Engl J Med 1999; 341:1882. Graphic 68247 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 40/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Prophylactic ICD does not improve survival in high- risk patients after CABG The CABG-Patch trial randomized 900 patients with a low ejection fraction and a positive signal-averaged electrocardiogram to an implantable cardioverter-defibrillator or no defibrillator after coronary artery bypass graft surgery. There was no difference in mortality at a mean follow-up of 32 months. Data from: Bigger JT, for the Coronary Artery Bypass Graft (CABG) Patch Trial Investigators, N Engl J Med 1997; 337:1569. Graphic 78888 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 41/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate ICD improves survival in MADIT II Kaplan-Meier estimates of the probability of survival in the MADIT II trial in 1232 patients who had a myocardial infarction more than 30 days prior to enrollment (and more than three months if bypass surgery was performed) and an LVEF 30 percent. The patients were randomly assigned to a prophylactic ICD or conventional medical therapy. The study was prematurely terminated after an average follow-up of 20 months because the ICD significantly reduced all- cause mortality (14.2 versus 19.8 percent for conventional therapy, hazard ratio 0.65, 95% CI 0.51-0.93). The survival benefit was largely due to a reduction in sudden death. LVEF: left ventricular ejection fraction; ICD: implantable cardioverter- defibrillator. Data from: Moss AJ, Zareba W, Hall WJ, et al. N Engl J Med 2002; 346:877. Graphic 63529 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 42/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Contributor Disclosures Joseph E Marine, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Andrea M Russo, MD, FACC, FHRS Grant/Research/Clinical Trial Support: BMS/Pfizer [Anticoagulant]; Boston Scientific [Arrhythmia]; Kestra [Arrhythmia]; Medilynx [Arrhythmia]; Medtronic [Arrhythmia]. Consultant/Advisory Boards: Abbott [Arrhythmia]; Atricure [Arrhythmia]; Biosense Webster [Arrhythmia]; Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]; PaceMate [Arrhythmia]. Speaker's Bureau: Biotronik [Arrhythmia]; Medtronic [Arrhythmia]. Other Financial Interest: ABIM [Cardiovascular board]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 43/43 |
7/6/23, 3:34 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy : Joseph E Marine, MD, FACC, FHRS, Andrea M Russo, MD, FACC, FHRS : Bradley P Knight, MD, FACC, Samuel L vy, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 02, 2023. INTRODUCTION Life-threatening ventricular arrhythmias, including sustained ventricular tachycardia (VT) and ventricular fibrillation (VF), are common in patients with heart failure (HF) and cardiomyopathy and may lead to sudden cardiac death (SCD). Secondary prevention of SCD refers to medical or interventional therapy undertaken to prevent SCD in patients who have experienced symptomatic life-threatening sustained VT/VF or have been successfully resuscitated from sudden cardiac arrest. The secondary prevention of SCD in patients with HF and cardiomyopathy will be reviewed here, with emphasis on the role of implantable cardioverter-defibrillators (ICDs). The different types of ventricular arrhythmias, the effects of HF therapy on ventricular arrhythmias, and the role of electrophysiologic testing are discussed separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) The approaches to the treatment of ventricular arrhythmias related to specific heart muscle diseases, such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and isolated left ventricular noncompaction, are discussed elsewhere. (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis" and "Isolated left ventricular noncompaction in adults: Clinical manifestations and diagnosis" and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".) EPIDEMIOLOGY https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 1/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate While the exact percentages and mode of death in patients with HF vary with HF class and type of cardiomyopathy, progressive pump failure, unexpected SCD, and SCD during episodes of clinical worsening of HF each account for approximately one-third of deaths in HF patients [1]. Ventricular tachycardia (VT) and ventricular fibrillation (VF) are the most common arrhythmic causes of SCD, although bradyarrhythmias and pulseless electrical activity (PEA) are responsible in 5 to 33 percent of cases [2,3]. More severe HF is associated with a higher overall mortality rate and a higher absolute rate of SCD, but a decreasing proportion of SCD to total deaths. This trend was illustrated in the MERIT- HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure) trial in which patients with increasing HF class (NYHA class II, III and IV) had increasing rates of SCD at one year (6.3, 10.5, and 18.6 percent, respectively), but a decreasing percentage of deaths that were classified as SCD (64, 59, and 33 percent, respectively) [4]. Patients who have received an implantable cardioverter-defibrillator (ICD) for secondary prevention have significantly higher rates of recurrent ventricular arrhythmias triggering appropriate ICD intervention than recipients of primary prevention ICDs, approximately threefold higher in one national registry from Israel [5]. Although ICD therapy improves survival of patients who suffered prior sudden cardiac arrest, mortality remains high. The mechanisms of death in such patients were illustrated in analyses from several secondary prevention ICD studies [6-8]: Nonarrhythmic cardiac death, usually progressive HF 45 to 50 percent Arrhythmic death 20 to 35 percent Noncardiac death, primarily renal and pulmonary disease 20 to 30 percent Arrhythmic death can occur despite recognition and termination of tachyarrhythmias by the ICD [9]. These deaths often result from PEA, also called electromechanical dissociation (EMD), or acute cardiac mechanical dysfunction [7-9]. PEA or bradyarrhythmias may be the mechanism of SCD in up to 40 percent of patients [7,8]. However, post-mortem interrogation of ICDs demonstrated that 25 percent of sudden deaths in ICD patients (representing 5 percent of all deaths) were caused by inability to defibrillate VF [8]. This situation may occur with VT/VF storm or refractory myocardial ischemia/infarction. SECONDARY PREVENTION OF SCD Patients with HF or cardiomyopathy who survive an episode of sudden cardiac arrest (SCA) or experience sustained ventricular tachycardia (VT) are at high risk of future sustained arrhythmic events and SCD. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 2/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Our approach We proceed with implantable cardioverter-defibrillator (ICD) implantation in most survivors of SCA due to sustained VT or ventricular fibrillation (VF), after completely reversible causes are excluded. (See 'Reversible causes of SCA or sustained VT' below.) Antiarrhythmic medications and/or catheter ablation should be used as adjunctive therapy to ICD implantation to suppress recurrent ventricular arrhythmias that lead to ICD therapy. These recommendations are in agreement with 2017 guidelines published by the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) [10]. In rare instances, class III antiarrhythmic drugs, such as sotalol or amiodarone, and/or catheter ablation may be selected as primary therapy for patients who refuse or who are not considered candidates for ICD therapy. Reversible causes of SCA or sustained VT In some survivors of SCA or sustained VT, a transient or reversible cause (eg, acute myocardial ischemia [MI], electrolyte disturbances, medication-related proarrhythmia, etc) can be identified which is felt to have caused the acute problem. Initial treatment should be directed at the underlying disorder. However, prior to concluding that SCA was due to a reversible cause, a thorough evaluation should be performed, usually involving a heart rhythm specialist. For example, in a patient who presents with VF and is found to have mild hypokalemia, it is generally not appropriate to assign the cause of the SCA just to the low potassium level. Correction of a reversible cause of SCA or sustained VT is most likely to be adequate in one of several settings: Polymorphic VT or VF that is preceded by clear evidence of MI or acute MI In such cases, revascularization is often adequate for the purpose of reducing the risk of SCD. However, some of these patients will later qualify for a primary prevention ICD due to severe left ventricular (LV) systolic dysfunction (MADIT II criteria) or systolic dysfunction and HF (SCD- HeFT criteria). Guideline-directed medical therapy should be applied, and follow-up evaluation with a cardiologist soon after discharge should be arranged for additional risk stratification. A repeat evaluation of LV function is recommended >40 days post-MI and >90 days after revascularization to determine if the patient qualifies for ICD implantation based on primary prevention indications [10]. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) Polymorphic VT in the setting of acquired QT prolongation In such cases, withdrawal of the offending drug and avoidance of other QT prolonging medications may be adequate to reduce the risk of SCD. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 3/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate VF occurring in the setting of Wolff-Parkinson-White syndrome in patients with a structurally normal heart These patients are adequately treated with catheter ablation of the accessory pathway. (See "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome".) Idiopathic monomorphic VT occurring in the setting of a structurally normal heart Such patients are usually adequately treated with medical therapy or catheter ablation. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) VT/VF occurring in the setting of intentional or accidental drug overdose Examples include cocaine, amphetamines, digoxin, tricyclic antidepressants, and antiarrhythmic drugs. In most other cases, life-threatening ventricular arrhythmias should not be attributed solely to a reversible disorder, and patients should be evaluated according to standard approaches to secondary prevention. Evidence for use of ICD therapy Most patients with HF or cardiomyopathy who have sustained VT or VF are candidates for ICD therapy. The indications for ICD implantation for secondary prevention of SCD are presented here ( table 1), while those for primary prevention are discussed separately. (See 'Our approach' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) AVID trial In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, 1016 patients who presented with (a) resuscitated VF, (b) sustained VT with syncope, or (c) sustained VT with BP <80 mmHg or significant symptoms (near-syncope, CHF, or angina) suggesting hemodynamic compromise and LV ejection fraction (LVEF) 40 percent were randomized to treatment with either an ICD or antiarrhythmic drugs (primarily amiodarone [96 percent]) [11]. The following findings were noted: The trial was stopped when a significant survival benefit was observed in patients receiving the ICD compared with those treated with antiarrhythmic agents (sotalol or amiodarone). The unadjusted survival for the ICD versus drug groups was 89 versus 82 percent at one year, 82 versus 75 percent at two years, and 75 versus 65 percent at three years. The major effect of the ICD was to prevent arrhythmic death (4.7 versus 10.8 percent with antiarrhythmic drugs); nonarrhythmic cardiac death was equivalent, while patients treated with antiarrhythmic drugs had an insignificantly greater incidence of noncardiac death, primarily from renal and pulmonary causes [6]. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 4/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate In patients with an LVEF 35 percent, there was no significant difference in survival between ICD and antiarrhythmic drugs (83.4 versus 82.7 percent at two years), while in those with an LVEF between 20 and 34 percent, survival was significantly better with the ICD (83 versus 72 percent) [12]. Among the relatively small number of patients with an LVEF <20 percent, survival tended to be better with the ICD (72 versus 64 percent), but the difference did not reach statistical significance. CASH trial In the Cardiac Arrest Survival in Hamburg (CASH) trial, 349 survivors of cardiac arrest due to documented VT or VF were randomly assigned to treatment with an ICD, metoprolol, propafenone, or amiodarone [13]. Assignment to propafenone was discontinued prematurely when interim analysis revealed a 61 percent higher mortality than that seen in patients randomized to ICD therapy. After a mean follow-up of 57 months, there was a non-significant reduction in total mortality in patients receiving an ICD compared with those treated with amiodarone or metoprolol (36.4 versus 44.9 percent). The secondary end point of SCD was significantly reduced by the ICD compared with drug therapy (13 versus 33 percent). CIDS trial In the Canadian Implantable Defibrillator Study (CIDS) 659 patients with resuscitated VT/VF or syncope deemed to be secondary to VT/VF were randomly assigned to amiodarone or ICD therapy and followed for five years [14]. In those treated with an ICD, there were non-significant reductions in total mortality (8.3 versus 10.2 percent per year) and SCD (3 versus 4.5 percent per year). Meta-analysis A significant mortality benefit with ICD therapy was noted in the AVID trial, while nonsignificant trends toward reduced mortality with ICD therapy were noted in the CASH and CIDS trials. The lack of statistical significance in the last two trials could have represented a beta error as the trials were underpowered to detect a significant difference of the magnitude observed. In addition, it is possible that patients considered by their clinicians to be good candidates for ICD therapy would be less likely to be enrolled and subjected to randomization, thus favoring the control group. In a meta-analysis of the AVID, CASH, and CIDS trials along with a fourth smaller trial, the following findings were noted [15]: Patients with an ICD had a significant reduction in total mortality compared with those receiving antiarrhythmic therapy (hazard ratio [HR] 0.75, 95% CI 0.64-0.87). Patients with an ICD had a 50 percent reduction in SCD (HR 0.50, 95% CI 0.34-0.62). https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 5/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate The absolute reduction in all-cause mortality was 7 percent, meaning that 15 patients needed to be treated to prevent one death. A second meta-analysis of AVID, CIDS, and CASH came to similar conclusions, finding a 28 percent relative risk reduction in all-cause mortality and a 50 percent reduction in arrhythmic death [16]. Patients with LVEF >35 percent had less benefit from ICD therapy than those with EF 35 percent. A subsequent meta-analysis of AVID, CIDS, and CASH further quantitated the benefit of the ICD in secondary prevention patients, finding a two-year absolute risk reduction in total mortality of 8 percent, with a number needed to treat to achieve mortality benefit of 13 [17]. Contemporary observational cohort studies The evidence supporting ICD therapy for secondary prevention rests upon randomized clinical trials that were conducted in the 1980s and 1990s. However, more contemporary observational studies or registries support these findings. In a cohort of 6996 patients with new onset ventricular arrhythmia in the setting of preexisting coronary heart disease and HF (from the National Veterans Administration database), 1442 patients had an ICD implanted [18]. At three-year follow-up, the patients who received an ICD had significant reductions in all-cause and cardiovascular mortality compared with those without an ICD (37 versus 55 percent and 23 versus 36 percent, respectively; adjusted odds ratio 0.52 for all-cause mortality and 0.56 for cardiovascular mortality), with no difference in noncardiac death. The benefit occurred despite a significantly lower frequency of use of angiotensin converting enzyme (ACE) inhibitors, beta blockers, and statins. This reduction in risk of death (28 percent) was similar to that seen in AVID (31 percent). In a smaller study of 357 patients who received an ICD for secondary prevention with much longer follow-up (mean 82 months), 208 persons (59 percent) received an ICD therapy for ventricular tachyarrhythmia, while 44 percent of participants died without receiving any ICD therapy [19]. An analysis of the NCDR ICD Registry evaluated mortality in 46,685 patients with ICDs implanted for secondary prevention indications in contemporary practice [20]. The mortality rate in this registry at one year was 10 percent compared with 8 to 11 percent among ICD patients enrolled in the secondary prevention randomized clinical trials (AVID, CIDS, CASH). Overall, the magnitude of the benefit of ICD therapy for secondary prevention in this real-world cohort was similar to or greater than that in the randomized trials, although mortality also remains high due to significant comorbidities. Effect in older patients Randomized clinical trials evaluating the role of the ICD for secondary prevention included only a minority of patients who were 75 years old. A meta- analysis of pooled individual patient data from three major randomized trials (CASH, CIDS, and AVID) comparing ICD with antiarrhythmic therapy for secondary prevention included 252 patients (out of 1866 total, or 13.5 percent) who were 75 years old [21]. This meta-analysis https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 6/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate suggested that the survival benefit from ICD therapy may be reduced in older patients compared with younger patients [21-23]. In contrast, other studies have shown older patients to benefit equally from primary or secondary prevention ICD therapy as younger patients [24,25]. While clinical trials enrolled relatively few older adult patients, the National Cardiovascular Data Registry ICD Registry provides the ability to examine outcomes in much larger numbers of patients in real-life clinical practice. In an analysis of 12,420 Medicare patients who were ages 65 years or older (mean age 75 years) who underwent initial ICD implantation between 2006 and 2009 for secondary prevention of SCD, the overall risk of death at two years was 21.8 percent [26]. However, there was a twofold difference in total mortality between patients 80 years of age and those who were ages 65 to 69 years (28.9 versus 14.7 percent; adjusted risk ratio 2.01, 95% CI 1.85-2.33). The study did not include a control group of similarly matched patients without an ICD; therefore no conclusions can be drawn about any potential total mortality benefit from placing the ICD for secondary prevention. However, nearly four in five patients over age 65 years who received an ICD for secondary prevention were alive two years later, indicating that age alone should not be the deciding criterion for ICD placement. Rather, multiple clinical factors should be considered including comorbidities, functional status, and competing risks of mortality, with the patient and family engaged in a shared decision-making process. This is highlighted in the guidelines, which state In patients with ventricular arrhythmias or at increased risk for SCD, clinicians should adopt a shared decision-making approach in which treatment decisions are based not only on the best available evidence but also on the patients health goals, preferences, and values (class I, LOE B-NR) [10]. These results suggest that ICD use in older patients should be individualized. Patients with few comorbidities may benefit, while those with significant other illnesses may be more likely to die of non-arrhythmic causes. Clinicians should consider issues of competing mortality risk, co- morbidities, risk of complications, and patient preferences for end-of-life care. Effect in heart failure Patients who are being evaluated for an ICD for secondary prevention and who have at least class II HF symptoms, significant LV systolic dysfunction, left bundle branch block, and a QRS duration 150 milliseconds should be strongly considered for an ICD that also provides cardiac resynchronization therapy (CRT). Some patients with a QRS duration of 120 to <150 milliseconds, those with non-LBBB conduction delays, and class I ischemic patients may also be candidates for CRT [27] or physiological pacing. This is discussed in greater detail elsewhere. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Use of an ICD'.) https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 7/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Patients with syncope Some of the randomized trials of ICDs for the secondary prevention of SCD included patients with syncope and either spontaneous or induced sustained VT. For patients with HF or cardiomyopathy who have had syncope and either induced or spontaneous VT, we recommend treatment with an ICD for secondary prevention of SCD [10]. Based upon observational data from patients with nonischemic cardiomyopathy, severe LV dysfunction, and unexplained syncope, ICD implantation is also often appropriate. Most patients with ischemic cardiomyopathy and an LVEF 35 percent qualify for ICD therapy even without syncope based upon the results of the MADIT-II [28] and SCD-HeFT trials [29] . The best approach for managing patients with an LVEF >35 percent and unexplained syncope is not clear and likely varies according to the etiology of the cardiomyopathy. For such patients with an ischemic cardiomyopathy, we generally perform an invasive electrophysiology (EP) study and, if the patient has inducible VT, implant an ICD. For patients with a nonischemic cardiomyopathy, an EP study is less informative, although it may reveal conduction abnormalities or bundle branch reentrant VT. In such patients, decisions regarding ICD implantation should be individualized based upon clinical circumstances, type of heart muscle disease, and patient preference. Cardiac MRI can be a useful test to detect scarring and fibrosis; in some cardiomyopathies, the presence of these can predict arrythmia sudden cardiac death. The 2017 AHA/ACC/HRS guidelines recommend the use of an ICD in patients with significant LV dysfunction due to ischemic cardiomyopathy who have unexplained syncope [10]. However, regardless of the history of syncope, many such patients will already qualify for an ICD for primary prevention of SCD based upon SCD-HeFT criteria, and patients with ischemic cardiomyopathy and severe LV dysfunction (ie, LVEF 30 to 35 percent) generally qualify for an ICD based upon MADIT-II [28] or SCD-HeFT criteria [29]. Patients with transient or reversible disorders Patients with a life-threatening ventricular tachyarrhythmia due to a transient or reversible cause (often an ischemic event) have been thought to have a low risk for recurrent SCA after correction of the underlying precipitant. However, many such patients remain at high risk for SCA, and the full clinical context should be considered before concluding that VT/VF is entirely due to a transient or reversible cause [30,31]. As examples: While acute ischemic events occur in patients who may have had an antecedent MI or multivessel disease, the presence of scar from a prior MI and progression of CHD both increase the risk of future events. In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients identified with a potentially transient or correctable cause for VT/VF (such as an ischemic event, electrolyte abnormalities, or drug reactions) remained at high https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 8/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate risk for death [30]. (See "Prognosis and outcomes following sudden cardiac arrest in adults".) In a retrospective single-center cohort study of 1433 patients with SCA between 2000 and 2012 who survived to hospital discharge, 792 patients (55 percent) were felt to have a reversible and correctable cause, which included evidence of acute MI or ischemia, significant electrolyte or metabolic abnormality, or recent antiarrhythmic medication or illicit drug use, with 207 patients (26 percent) with a reversible cause receiving an ICD [32]. Over a mean follow-up of 3.8 years, 319 patients (40 percent) died, with ICD recipients having a significantly lower mortality risk (HR 0.61 compared with patients without an ICD, 95% CI 0.47-0.80). The benefit was consistent across all subgroups with the exception of patients whose reversible cause was MI/ischemia, in whom no mortality benefit was seen. While patients with SCA in the setting of MI did not receive a mortality benefit from ICD therapy, it should be noted that all of these patients underwent coronary revascularization before being classified as having a reversible cause of SCA. Additionally, 32 of the ICD recipients (15 percent) received an appropriate ICD therapy during follow-up, including 21 percent of the group without MI/ischemia, suggesting that SCA in the setting of a perceived reversible cause may not always be related to the putative reversible cause. While this study is limited by its retrospective, nonrandomized nature, it suggests caution on the part of clinicians evaluating patients after cardiac arrest not to overestimate the potential for reversibility of arrhythmic risk, particularly outside of the setting of acute MI. The 2017 AHA/ACC/HRS guidelines for the management of ventricular arrhythmias and the prevention of sudden cardiac death recommend ICD therapy for patients who either survive SCA or experience hemodynamically unstable VT or stable VT not due to "reversible causes" if meaningful survival greater than one year is expected [10]. As defined in AVID, "potentially reversible causes" may include acute MI, transient ischemia, electrolyte imbalance, antiarrhythmic drug proarrhythmia, hypoxia, electrocution, drowning, or sepsis. Clinical judgment is needed to discern which causes are entirely transient or reversible. General opinion would support the following: Patients who experience cardiac arrest due to polymorphic VT or VF in the setting of acute ischemia or an MI should be treated with revascularization for the purpose of reducing the risk of SCD. Patients may be eligible for ICD therapy if they are considered ineligible for complete revascularization. In general, patients with polymorphic VT or VF who also have electrolyte disorders should be evaluated and treated in the same manner as other patients, including evaluation for https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 9/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate ICD therapy unless the electrolyte abnormalities are proved to be the cause of the arrhythmia. Patients who experience sustained monomorphic VT in the setting of antiarrhythmic drug use or electrolyte abnormalities should be evaluated and treated in the same manner as other patients presenting with sustained VT. Antiarrhythmic drugs or electrolyte abnormalities should not be assumed to be the sole cause of sustained monomorphic VT. Patients who experience polymorphic VT in the setting of acquired QT prolongation due to drug therapy should be advised to avoid exposure to all agents associated with QT prolongation. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) SCD despite ICD implantation In the trials of ICD therapy for the secondary prevention of SCD, approximately 20 to 35 percent of the deaths in patients with an ICD were due to SCD. These deaths may result from pulseless electrical activity (PEA), pulmonary embolus, ruptured aortic aneurysm, VT below rate detection cutoff, and, rarely, from ICD failure or under-detection of VF. Post-mortem interrogation of ICDs revealed that the most common mechanism of SCD in patients was VT/VF treated with an appropriate shock followed by PEA [8]. Increasingly frequent and refractory episodes of VT/VF may reflect the terminal stage of severe HF, and such patients may succumb from VT/VF storm despite appropriate function of the ICD. (See 'Epidemiology' above.) Other treatment options In addition to the ICD, several other pharmacologic and nonpharmacologic therapies have been evaluated in survivors of SCD. None is considered an adequate alternative to ICD therapy in most clinical circumstances, but each has a role in selected patients. Antiarrhythmic drugs Antiarrhythmic drugs may be used to improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or who decline ICD implantation. In the presence of HF and/or structural heart disease, antiarrhythmic drug therapy is limited to a small number of choices (ie, amiodarone, sotalol, mexiletine) [10]. In patients who require an antiarrhythmic drug, we typically prefer amiodarone in patients with HF and LV dysfunction due to its superior efficacy and demonstration of short-term safety in patients with HF and structural heart disease. Sotalol or mexiletine may be alternative drugs for selected patients with structural heart disease who have an ICD. Often, a beta blocker is coadministered with antiarrhythmic drugs, which do not have intrinsic beta-blocker activity. Beta blockers are often separately indicated in patients with ventricular arrhythmias due to coexistent HF, LV dysfunction, and/or coronary artery disease. In https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 10/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate addition, beta blockers have important antiarrhythmic action which may reduce recurrence of ventricular arrhythmias. (See 'Beta blockers' below.) In survivors of SCA, the need for adjunctive antiarrhythmic drug therapy is not uncommon, with an antiarrhythmic drug being added to ICD therapy in 22 percent at two years in the AVID trial and in 28 percent at five years in the CIDS trial [11,14]. In patients who have an ICD in place, there are two main indications for concomitant antiarrhythmic drug therapy. To reduce the frequency of ventricular arrhythmias In the AVID trial, frequent ICD shocks were the primary reason for adding an antiarrhythmic drug (64 percent) [33]. Frequent shocks impact quality of life. (See "Cardiac implantable electronic devices: Long-term complications", section on 'Quality of life'.) To suppress supraventricular arrhythmias Arrhythmias other than VT or VF may cause symptoms or result in "inappropriate" discharges. Atrial fibrillation is by far the most common of these arrhythmias. Dofetilide may also be a useful agent for treatment of atrial fibrillation in patients with underlying structural heart disease. Amiodarone is generally the preferred antiarrhythmic choice and was shown in the OPTIC trial to be more effective than sotalol. However, this drug has more long-term side effects and drug interactions than other antiarrhythmic agents. In some circumstances, therefore, it may be more appropriate to use sotalol or mexiletine, despite the superior efficacy of amiodarone. In addition, amiodarone may result in an increase in the defibrillation threshold, which could adversely affect ICD shock efficacy and increase VT cycle length, which should be considered during device programming. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Amiodarone: Clinical uses", section on 'Drug interactions' and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Choice of pharmacologic therapy'.) While antiarrhythmic drugs are sometimes required to reduce the frequency of shocks and improve a person's quality of life, a systematic review of 17 studies involving nearly 6000 ICD recipients showed that shock prevention using antiarrhythmic therapy resulted in no improvement in mortality [34]. (See "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Antiarrhythmic drugs'.) Other medical therapies Beta blockers The majority of patients who receive an ICD will be treated with a beta blocker as part of the therapy for their underlying heart disease. Beta blockers confer an https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 11/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate additional survival benefit in patients with an MI, HF, congenital long QT syndrome, or catecholaminergic polymorphic VT. Additional benefits of beta-blockers in ICD patients may include reduction in inappropriate ICD shocks from sinus tachycardia and atrial fibrillation with a rapid ventricular response. Careful attention to ICD programming, including programming a long detection delay, may also reduce unnecessary ICD therapy [35,36]. (See "Beta blockers in the management of chronic coronary syndrome".) Among survivors of SCA who were eligible but not randomized in the AVID trial, beta-blocker use was associated with improved survival in patients who were not treated with specific antiarrhythmic therapy (adjusted RR 0.47, 95% CI 0.25-0.88) [37]. Lipid-lowering therapy Most patients with CHD who have an ICD are treated with lipid- lowering therapy. However, data on the effect of lipid-lowering therapy on ventricular arrhythmia are mixed. [38,39]. Among 362 patients with CHD who received an ICD in the AVID trial, there was a significant reduction in the risk of recurrence of VT or VF in the 83 patients receiving lipid-lowering therapy (adjusted HR 0.40, 95% CI 0.15 to 0.58). Reduction in VT/VF was also seen among statin-treated patients in one primary prevention ICD trial [40]. However, there are still no randomized controlled trials to suggest that lipid-lowering therapy confers an independent antiarrhythmic effect in patients with VT/VF. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".) There are mixed data on whether the administration of fish oil reduces the risk of recurrent ventricular tachyarrhythmias. A meta-analysis of three fish oil trials showed no overall effect of fish oil treatment on the risk of ICD discharge [41]. Ranolazine Initially developed as an antianginal therapy, some studies have suggested that ranolazine has antiarrhythmic properties, including one trial in which ranolazine reduced the frequency of both supraventricular and ventricular arrhythmias within seven days of an acute coronary syndrome. This prompted investigators to study the effectiveness of ranolazine in reducing ventricular arrhythmias in patients with an ICD in the RAID trial, which randomized 1012 high-risk patients with ischemic or nonischemic cardiomyopathy and an ICD to receive either ranolazine (1000 mg twice daily) or placebo in addition to usual care [42,43]. During a mean follow-up of 28 months, there was a non-significant reduction in the primary end point of death or appropriate ICD shock among patients in the ranolazine group compared with placebo (HR 0.84; 95% CI 0.67-1.05), with a pre-specified secondary analysis identifying a significant reduction in recurrent ICD therapies (ATP and shocks) in the ranolazine group (HR 0.70; 95% CI 0.51-0.96). Compliance in the study was poor, however, with 50 percent of patients receiving ranolazine and 40 percent of patients receiving placebo discontinuing the medication. Until further data become available, suggesting a benefit, ranolazine should not be used routinely to https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 12/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate prevent VT/VF in patients with an ICD, but there may be select patients (eg, those with frequent ICD therapies in spite of maximal medical therapy) in whom its use is reasonable. Catheter ablation Similar to antiarrhythmic drugs, catheter ablation may be used as adjunctive therapy to improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or refuse ICD placement. Catheter ablation alone without an ICD is rarely appropriate for patients who survive cardiac arrest due to VT/VF or who have VT associated with structural heart disease. Radiofrequency ablation (RFA) is often an effective treatment for VT, particularly monomorphic VT due to reentry. In patients with a prior MI, the border zone of the infarct is frequently the site of the reentrant circuit, and these sites are often amenable to endocardial catheter ablation [44]. In contrast, patients with nonischemic cardiomyopathy may have multiple endocardial reentrant circuits, epicardial or mid-myocardial circuits, or other mechanisms of VT (eg, triggered arrhythmias or polymorphic VT) [45]. Due to the presence of more complex arrhythmic substrate, endocardial RFA is less effective in patients with nonischemic cardiomyopathy, and an epicardial approach may be required [46]. Catheter ablation may also be effective in selected patients with polymorphic VT or VF associated with triggering PVCs arising in the right ventricular outflow tract or His-Purkinje system [47]. (See "Overview of catheter ablation of cardiac arrhythmias".) Catheter ablation of VT is considered in three settings: As an adjunct to an ICD in patients who have frequent ventricular arrhythmias and ICD therapies. (See "Electrical storm and incessant ventricular tachycardia", section on 'Catheter ablation'.) As an alternative to an ICD in patients who do not want or are not candidates for an ICD. As prophylactic adjunctive therapy in patients who initially presented with sustained VT and received ICD therapy. A meta-analysis of five trials showed that this approach reduces the risk of VT recurrence by 35 percent with no effect on mortality [48]. Arrhythmia surgery Ischemic cardiomyopathy Reentrant VT circuits associated with a chronic myocardial infarct scar can be surgically resected. Arrhythmia surgery was used more commonly prior to the advent of RFA, particularly in patients with an LV aneurysm and sustained monomorphic VT. The successes of ICD implantation and RFA have made surgery for ventricular arrhythmias appropriate only in rare circumstances. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Surgical therapy'.) https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 13/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Nonischemic cardiomyopathy Surgical treatment of VT/VF in patients with nonischemic cardiomyopathy has not been well studied, but likely has a lower success rate than in ischemic cardiomyopathy, given that the underlying myocardial disease tends to be diffuse without a discrete scar or aneurysm present. In selected patients, however, there remains a role |
during device programming. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Amiodarone: Clinical uses", section on 'Drug interactions' and "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Choice of pharmacologic therapy'.) While antiarrhythmic drugs are sometimes required to reduce the frequency of shocks and improve a person's quality of life, a systematic review of 17 studies involving nearly 6000 ICD recipients showed that shock prevention using antiarrhythmic therapy resulted in no improvement in mortality [34]. (See "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Antiarrhythmic drugs'.) Other medical therapies Beta blockers The majority of patients who receive an ICD will be treated with a beta blocker as part of the therapy for their underlying heart disease. Beta blockers confer an https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 11/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate additional survival benefit in patients with an MI, HF, congenital long QT syndrome, or catecholaminergic polymorphic VT. Additional benefits of beta-blockers in ICD patients may include reduction in inappropriate ICD shocks from sinus tachycardia and atrial fibrillation with a rapid ventricular response. Careful attention to ICD programming, including programming a long detection delay, may also reduce unnecessary ICD therapy [35,36]. (See "Beta blockers in the management of chronic coronary syndrome".) Among survivors of SCA who were eligible but not randomized in the AVID trial, beta-blocker use was associated with improved survival in patients who were not treated with specific antiarrhythmic therapy (adjusted RR 0.47, 95% CI 0.25-0.88) [37]. Lipid-lowering therapy Most patients with CHD who have an ICD are treated with lipid- lowering therapy. However, data on the effect of lipid-lowering therapy on ventricular arrhythmia are mixed. [38,39]. Among 362 patients with CHD who received an ICD in the AVID trial, there was a significant reduction in the risk of recurrence of VT or VF in the 83 patients receiving lipid-lowering therapy (adjusted HR 0.40, 95% CI 0.15 to 0.58). Reduction in VT/VF was also seen among statin-treated patients in one primary prevention ICD trial [40]. However, there are still no randomized controlled trials to suggest that lipid-lowering therapy confers an independent antiarrhythmic effect in patients with VT/VF. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".) There are mixed data on whether the administration of fish oil reduces the risk of recurrent ventricular tachyarrhythmias. A meta-analysis of three fish oil trials showed no overall effect of fish oil treatment on the risk of ICD discharge [41]. Ranolazine Initially developed as an antianginal therapy, some studies have suggested that ranolazine has antiarrhythmic properties, including one trial in which ranolazine reduced the frequency of both supraventricular and ventricular arrhythmias within seven days of an acute coronary syndrome. This prompted investigators to study the effectiveness of ranolazine in reducing ventricular arrhythmias in patients with an ICD in the RAID trial, which randomized 1012 high-risk patients with ischemic or nonischemic cardiomyopathy and an ICD to receive either ranolazine (1000 mg twice daily) or placebo in addition to usual care [42,43]. During a mean follow-up of 28 months, there was a non-significant reduction in the primary end point of death or appropriate ICD shock among patients in the ranolazine group compared with placebo (HR 0.84; 95% CI 0.67-1.05), with a pre-specified secondary analysis identifying a significant reduction in recurrent ICD therapies (ATP and shocks) in the ranolazine group (HR 0.70; 95% CI 0.51-0.96). Compliance in the study was poor, however, with 50 percent of patients receiving ranolazine and 40 percent of patients receiving placebo discontinuing the medication. Until further data become available, suggesting a benefit, ranolazine should not be used routinely to https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 12/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate prevent VT/VF in patients with an ICD, but there may be select patients (eg, those with frequent ICD therapies in spite of maximal medical therapy) in whom its use is reasonable. Catheter ablation Similar to antiarrhythmic drugs, catheter ablation may be used as adjunctive therapy to improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or refuse ICD placement. Catheter ablation alone without an ICD is rarely appropriate for patients who survive cardiac arrest due to VT/VF or who have VT associated with structural heart disease. Radiofrequency ablation (RFA) is often an effective treatment for VT, particularly monomorphic VT due to reentry. In patients with a prior MI, the border zone of the infarct is frequently the site of the reentrant circuit, and these sites are often amenable to endocardial catheter ablation [44]. In contrast, patients with nonischemic cardiomyopathy may have multiple endocardial reentrant circuits, epicardial or mid-myocardial circuits, or other mechanisms of VT (eg, triggered arrhythmias or polymorphic VT) [45]. Due to the presence of more complex arrhythmic substrate, endocardial RFA is less effective in patients with nonischemic cardiomyopathy, and an epicardial approach may be required [46]. Catheter ablation may also be effective in selected patients with polymorphic VT or VF associated with triggering PVCs arising in the right ventricular outflow tract or His-Purkinje system [47]. (See "Overview of catheter ablation of cardiac arrhythmias".) Catheter ablation of VT is considered in three settings: As an adjunct to an ICD in patients who have frequent ventricular arrhythmias and ICD therapies. (See "Electrical storm and incessant ventricular tachycardia", section on 'Catheter ablation'.) As an alternative to an ICD in patients who do not want or are not candidates for an ICD. As prophylactic adjunctive therapy in patients who initially presented with sustained VT and received ICD therapy. A meta-analysis of five trials showed that this approach reduces the risk of VT recurrence by 35 percent with no effect on mortality [48]. Arrhythmia surgery Ischemic cardiomyopathy Reentrant VT circuits associated with a chronic myocardial infarct scar can be surgically resected. Arrhythmia surgery was used more commonly prior to the advent of RFA, particularly in patients with an LV aneurysm and sustained monomorphic VT. The successes of ICD implantation and RFA have made surgery for ventricular arrhythmias appropriate only in rare circumstances. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Surgical therapy'.) https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 13/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Nonischemic cardiomyopathy Surgical treatment of VT/VF in patients with nonischemic cardiomyopathy has not been well studied, but likely has a lower success rate than in ischemic cardiomyopathy, given that the underlying myocardial disease tends to be diffuse without a discrete scar or aneurysm present. In selected patients, however, there remains a role for surgical treatment. In a study of eight patients in whom percutaneous ablation was not an option, successful reduction in VT was reported in six of eight nonischemic cardiomyopathy patients (75 percent) treated with surgical cryoablation [49]. Cardiac transplantation Cardiac transplantation is occasionally required for patients with incessant life-threatening ventricular arrhythmias, which cannot be controlled by medication or catheter ablation. ICD therapy is generally contraindicated in patients with uncontrollable incessant VT/VF, and such patients should proceed to mechanical support and transplantation if they are candidates. (See "Heart transplantation in adults: Indications and contraindications", section on 'Indications for transplantation'.) Another scenario involves patients who are listed for cardiac transplantation who experience cardiac arrest or symptomatic VT while on the waiting list. In such patients, there is an important role for the ICD as a bridge to transplantation [50-54]. In one study, 16 patients with a mean LVEF of 15 percent who were listed for heart transplantation underwent ICD implantation for ventricular arrhythmias refractory to medical therapy [50]. The ICD delivered appropriate shocks for tachyarrhythmias associated with near syncope in all but one of the patients. Twelve patients underwent transplantation after a mean of 156 days. In another study of 60 patients listed for heart transplantation who survived resuscitation from sustained VT/VF, ICD implantation was associated with significantly improved survival. Only 1 of 30 ICD patients (19 transplanted) versus 7 of 30 non-ICD patients (14 transplanted) died on the waiting list [55]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 14/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Beyond the Basics topic (see "Patient education: Heart failure (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Reversible causes In some survivors of sudden cardiac arrest (SCA) or sustained ventricular tachycardia (VT), a transient or reversible cause (eg, acute myocardial ischemia [MI], electrolyte disturbances, medication-related proarrhythmia, etc) can be identified as being responsible for the SCA. Initial treatment should be directed at the underlying disorder. However, prior to concluding that SCA was due to a reversible cause, a thorough evaluation should be performed, typically involving a heart rhythm specialist. (See 'Reversible causes of SCA or sustained VT' above.) Secondary prevention Patients with HF and cardiomyopathy who survive an episode of SCA or have hemodynamically unstable VT or stable VT are typically treated with implantable cardioverter-defibrillator (ICD) therapy for secondary prevention if meaningful survival greater than one year is expected. (See 'Secondary prevention of SCD' above.) For survivors of SCA or sustained VT without a clearly reversible cause, we recommend ICD implantation rather than antiarrhythmic drug therapy (Grade 1A). (See 'Evidence for use of ICD therapy' above.) For survivors of SCA or sustained VT who are identified as having a definite transient or reversible cause (eg, acute MI, acute infarction, severe electrolyte disturbances, medication-related proarrhythmia, etc), in particular those whose cardiac rhythm is polymorphic VT or ventricular fibrillation (VF), we do not recommend ICD implantation if the etiology is clearly understood, the underlying cause is fully treated, and the https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 15/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate condition is unlikely to recur (Grade 1B). (See 'Reversible causes of SCA or sustained VT' above and 'Patients with transient or reversible disorders' above.) For patients with HF or cardiomyopathy who have had syncope and either induced or spontaneous VT, we recommend treatment with an ICD for secondary prevention of SCD (Grade 1A). (See 'Patients with syncope' above.) For patients with nonischemic cardiomyopathy, significant LV dysfunction, and unexplained syncope, we suggest ICD implantation (Grade 2B). Most patients with an ischemic cardiomyopathy and left ventricular ejection fraction 35 percent already qualify for an ICD based upon the results of the MADIT-II and SCD-HeFT trials. (See 'Patients with syncope' above and 'Our approach' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Antiarrhythmic drugs These may be used to improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or who decline ICD implantation. In patients who require an antiarrhythmic drug, we typically prefer amiodarone in patients with HF and LV dysfunction due to its superior efficacy and demonstration of short-term safety in such patients. Sotalol and mexiletine may be useful alternative drugs for selected patients. (See 'Antiarrhythmic drugs' above.) Catheter ablation Similar to antiarrhythmic drugs, catheter ablation may be used as adjunctive therapy to improve quality of life in patients with frequent ventricular tachyarrhythmias leading to ICD shocks, or in those patients who are not candidates for or refuse ICD placement. Catheter ablation alone without an ICD is rarely appropriate for patients who survive cardiac arrest due to VT/VF or who have VT associated with structural heart disease. (See 'Catheter ablation' above.) The majority of patients who receive an ICD will be treated with a beta blocker as part of the therapy for their underlying heart disease. (See 'Beta blockers' above.) ACKNOWLEDGMENT The authors and UpToDate thank Dr. Phillip Podrid, Dr. Jie Cheng, Dr. Scott Manaker, and Dr. Leonard Ganz, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 16/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate REFERENCES 1. Narang R, Cleland JG, Erhardt L, et al. Mode of death in chronic heart failure. A request and proposition for more accurate classification. Eur Heart J 1996; 17:1390. 2. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators. Eur Heart J 1997; 18:41. 3. Greenberg H, Case RB, Moss AJ, et al. Analysis of mortality events in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II). J Am Coll Cardiol 2004; 43:1459. 4. 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Comparison of outcome of implantable cardioverter defibrillator implantation in patients with severe versus moderately severe left ventricular dysfunction secondary to atherosclerotic coronary artery disease. Am J Cardiol 1997; 80:1305. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 18/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate 24. Huang DT, Sesselberg HW, McNitt S, et al. Improved survival associated with prophylactic implantable defibrillators in elderly patients with prior myocardial infarction and depressed ventricular function: a MADIT-II substudy. J Cardiovasc Electrophysiol 2007; 18:833. 25. Duray G, Richter S, Manegold J, et al. Efficacy and safety of ICD therapy in a population of elderly patients treated with optimal background medication. J Interv Card Electrophysiol 2005; 14:169. 26. Betz JK, Katz DF, Peterson PN, et al. Outcomes Among Older Patients Receiving Implantable Cardioverter-Defibrillators for Secondary Prevention: From the NCDR ICD Registry. J Am Coll Cardiol 2017; 69:265. 27. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 28. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877. 29. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225. 30. Wyse DG, Friedman PL, Brodsky MA, et al. Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up. J Am Coll Cardiol 2001; 38:1718. 31. Viskin S, Halkin A, Olgin JE. Treatable causes of sudden death: not really "treatable" or not really the cause? J Am Coll Cardiol 2001; 38:1725. 32. Ladejobi A, Pasupula DK, Adhikari S, et al. Implantable Defibrillator Therapy in Cardiac Arrest Survivors With a Reversible Cause. Circ Arrhythm Electrophysiol 2018; 11:e005940. 33. Steinberg JS, Martins J, Sadanandan S, et al. Antiarrhythmic drug use in the implantable defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study. Am Heart J 2001; 142:520. 34. Ha AH, Ham I, Nair GM, et al. Implantable cardioverter-defibrillator shock prevention does not reduce mortality: a systemic review. Heart Rhythm 2012; 9:2068. 35. Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard- detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA 2013; 309:1903. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 19/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate 36. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm 2016; 13:e50. 37. Exner DV, Reiffel JA, Epstein AE, et al. Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 1999; 34:325. 38. Mitchell LB, Powell JL, Gillis AM, et al. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 2003; 42:81. 39. De Sutter J, Tavernier R, De Buyzere M, et al. Lipid lowering drugs and recurrences of life- threatening ventricular arrhythmias in high-risk patients. J Am Coll Cardiol 2000; 36:766. 40. Vyas AK, Guo H, Moss AJ, et al. Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol 2006; 47:769. 41. Jenkins DJ, Josse AR, Beyene J, et al. Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis. CMAJ 2008; 178:157. 42. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST- segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 2007; 116:1647. 43. Zareba W, Daubert JP, Beck CA, et al. Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial. J Am Coll Cardiol 2018; 72:636. 44. Wissner E, Stevenson WG, Kuck KH. Catheter ablation of ventricular tachycardia in ischaemic and non-ischaemic cardiomyopathy: where are we today? A clinical review. Eur Heart J 2012; 33:1440. 45. Soejima K, Stevenson WG, Sapp JL, et al. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low- voltage scars. 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Jeevanandam V, Bielefeld MR, Auteri JS, et al. The implantable defibrillator: an electronic bridge to cardiac transplantation. Circulation 1992; 86:II276. 51. Grimm M, Wieselthaler G, Avanessian R, et al. The impact of implantable cardioverter- defibrillators on mortality among patients on the waiting list for heart transplantation. J Thorac Cardiovasc Surg 1995; 110:532. 52. Bolling SF, Deeb GM, Morady F, et al. Automatic internal cardioverter defibrillator: a bridge to heart transplantation. J Heart Lung Transplant 1991; 10:562. 53. Lorga-Filho A, Geelen P, Vanderheyden M, et al. Early benefit of implantable cardioverter defibrillator therapy in patients waiting for cardiac transplantation. Pacing Clin Electrophysiol 1998; 21:1747. 54. Saba S, Atiga WL, Barrington W, et al. Selected patients listed for cardiac transplantation may benefit from defibrillator implantation regardless of an established indication. J Heart Lung Transplant 2003; 22:411. 55. Grimm M, Grimm G, Zuckermann A, et al. ICD therapy in survivors of sudden cardiac death awaiting heart transplantation. Ann Thorac Surg 1995; 59:916. Topic 946 Version 38.0 https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 21/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate GRAPHICS [1] Summary of secondary prevention ICD trials NCDR [2] [3] [4] Study AVID CASH CIDS [5] Cohort Years 1993 to 1997 1987 to 1998 1990 to 1997 2006 to 2009 Patients 1016 191 659 46,685 Mean age (years) 65 11 58 11 63 9 66 14 Male (%) 78 79 85 73 Follow-up (months) 18 12 57 34 36 None CAD (%) 81 73 83 64 Nonischemic (%) 15 12 10 23 LVEF 32 13 46 19 34 14 36 15 Presenting arrhythmia (%) VF 45 100 45 51 VT with LOC 21 0 16 NR VT without LOC 34 0 24 27 Syncope 0 0 15 22 BB (%) 42 0 33 84 ACE-I/ARB (%) 69 45 NR 72 One-year mortality (%): Control/ICD 17.7/10.7 15.2/8.1 11.2/9.5 NA/10.4 Two-year mortality (%): 25.3/18.4 27.2/17.2 21.0/14.8 NA/16.4 Control/ICD ICD: implantable cardioverter-defibrillator; CAD: coronary artery disease; LVEF: left ventricular ejection fraction; VF: ventricular fibrillation; VT: ventricular tachycardia; LOC: loss of consciousness; BB: beta blocker; ACE-I: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; NR: not recorded; NA: not applicable. References: 1. Borne R, Katz D, Betz J, et al. Implantable Cardioverter-De brillators for Secondary Prevention of Sudden Cardiac Death: A Review. J Am Heart Assoc 2017; 6:e005515. https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 22/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate 2. Antiarrhythmics versus Implantable De brillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable de brillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337:1576. 3. Kuck KH, Cappato R, Siebels J, R ppel R. Randomized comparison of antiarrhythmic drug therapy with implantable de brillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 2000; 102:748. 4. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable de brillator study (CIDS): a randomized trial of the implantable cardioverter de brillator against amiodarone. Circulation 2000; 101:1297. 5. Katz DF, Peterson P, Borne RT, et al. Survival after secondary prevention ICD placement: an analysis from the NCDR ICD Registry. JACC Clin Electrophysiol 2017; 3:20. Graphic 116653 Version 1.0 https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 23/24 7/6/23, 3:35 PM Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy - UpToDate Contributor Disclosures Joseph E Marine, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Andrea M Russo, MD, FACC, FHRS Grant/Research/Clinical Trial Support: BMS/Pfizer [Anticoagulant]; Boston Scientific [Arrhythmia]; Kestra [Arrhythmia]; Medilynx [Arrhythmia]; Medtronic [Arrhythmia]. Consultant/Advisory Boards: Abbott [Arrhythmia]; Atricure [Arrhythmia]; Biosense Webster [Arrhythmia]; Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]; PaceMate [Arrhythmia]. Speaker's Bureau: Biotronik [Arrhythmia]; Medtronic [Arrhythmia]. Other Financial Interest: ABIM [Cardiovascular board]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/secondary-prevention-of-sudden-cardiac-death-in-heart-failure-and-cardiomyopathy/print 24/24 |
7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features : Philip J Podrid, MD, FACC : James Hoekstra, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 16, 2022. INTRODUCTION Sudden cardiac death in the setting of an acute myocardial infarction (MI) is most frequently the result of a ventricular tachyarrhythmia. The appearance of a sustained ventricular tachyarrhythmia following an MI, such as ventricular tachycardia (VT) or ventricular fibrillation (VF), in the early period post-MI may be the harbinger of ongoing myocardial ischemia, the development of proarrhythmic myocardial scar tissue, elevated sympathetic tone or increase in circulating catecholamines, or an electrolyte disturbance such as hypokalemia. In-hospital mortality approaches 20 percent or more in patients who develop VT or VF following an MI. As such, rapid identification and treatment of these arrhythmias can be life-saving. Although all patients with a prior MI have an elevated risk of malignant arrhythmias, the magnitude of risk varies from patient to patient, with reduced left ventricular ejection fraction being the most prominent risk stratifier. This topic will focus on the incidence, mechanisms, and clinical features of ventricular arrhythmias during and after acute MI. Treatment for established ventricular arrhythmias during acute MI and in the post-MI patient, using defibrillation with or without antiarrhythmic medications, is discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 1/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate INCIDENCE While many studies have evaluated the incidence of ventricular arrhythmias in the peri-infarct period, comparison of these studies is difficult due to differences in populations (percutaneous intervention therapy versus fibrinolytic therapy versus no therapy), type of infarct (ST segment elevation MI [STEMI] versus non-ST segment elevation MI [NSTEMI] versus both), and arrhythmia reported (ventricular tachycardia [VT] versus ventricular fibrillation [VF] versus both). The clinical significance of different types of ventricular ectopy following MI also varies markedly. Ventricular arrhythmias, ranging from isolated premature ventricular complexes/contractions (PVCs; also referred to a premature ventricular beats, premature ventricular depolarizations, ventricular premature complexes, or ventricular premature beats) to VF, are common in the immediate post-infarction period (ie, within the first 48 hours). Observations in the pre- fibrinolytic era found the following range of incidence [1-3]: PVCs 10 to 93 percent VT 3 to 39 percent VF 4 to 20 percent Life-threatening ventricular arrhythmias, VT and VF, are infrequent but serious complications of an acute STEMI. The largest experience on the incidence of VT and VF during an acute STEMI comes from the GUSTO-1 trial of 40,895 patients who were treated with thrombolytic therapy [4]. The overall incidence of sustained VT or VF was 10.3 percent: 3.5 percent developed VT, 4.1 percent VF, and 2.7 percent both VT and VF. Approximately 80 to 85 percent of these arrhythmias occurred in the first 48 hours. Rates of VT and VF have declined with time. In a study of 11,825 patients with acute MI between 1986 and 2011, there was a decrease in the incidence of both VT (from 14.3 to 10.5 percent) and VF (from 8.2 to 1.7 percent) over the 25 years reviewed [3]. Sustained ventricular arrhythmias are less common in patients with an acute NSTEMI or unstable angina compared to patients with STEMI, as illustrated in a pooled analysis of four major trials of over 25,000 such patients [5]. The overall incidence of VT or VF was 2.1 percent, lower than the 10.3 percent incidence in GUSTO-1 in STEMI [6]. VT occurred in 0.8 percent, VF in 1 percent, and VT and VF in 0.3 percent. The median time to arrhythmia was 78 hours. Early versus late arrhythmias The definition of "early" versus "late" ventricular arrhythmias can vary among cardiologists and electrophysiologists and is also changing with time. Most now consider "late" arrhythmias to be those that occur beyond 24 to 48 hours post-MI onset. Late VT https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 2/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate is a predictor of a worse prognosis [4]. Among post-MI patients who survived for 30 days, subsequent one-year mortality was significantly higher among those who had late VT (24.7 percent) compared with those without sustained ventricular arrhythmia (2.7 percent) [4]. Pre-revascularization (fibrinolytic/PCI) era versus PCI era In the era of early percutaneous coronary intervention (PCI), VT (especially non-sustained VT) remains fairly common. In the MERLIN-TIMI 36 study of 6355 patients with non-ST elevation acute coronary syndromes who underwent seven days of continuous electrocardiographic (ECG) monitoring following their presentation to the hospital to assess for VT and ischemia, 25.3 percent were found to have VT (20 percent VT without ischemia, 5.3 percent VT with ischemia) [7]. Compared with patients with neither VT nor ischemia on continuous ECG monitoring, patients with VT without concurrent ischemia had a significantly increased risk of both cardiovascular death and sudden cardiac death (SCD; adjusted hazard ratio [HR] 2.2 and 2.3, respectively). Patients with VT and ischemia had an even higher risk of both cardiovascular death and SCD (adjusted HR 5.4 and 6.5, respectively). ST elevation MI Data regarding the incidence of ventricular arrhythmias at the time of acute STEMI come from studies of patients treated with either fibrinolysis or primary PCI. Although the incidence of ventricular arrhythmias is probably lower with contemporary therapies [4,5,8-11], these data are also probably underestimating the true incidence of arrhythmias because patients with prehospital SCD may not have been included in studies of fibrinolysis or primary PCI. The risk factors for and the prognosis of early VT or VF in patients with STEMI are discussed separately. (See 'Monomorphic ventricular tachycardia' below.) Fibrinolytic therapy Among patients with acute MI in the fibrinolytic era, the incidence of VF has ranged from 3.7 to 6.7 percent in large studies [4,5,10-13]. The largest experience in patients (40,895) with acute STEMI treated with fibrinolytic therapy comes from the GUSTO-1 trial [4]. The overall incidence of sustained VT or VF was 10.2 percent (3.5 percent developed VT, 4.1 percent VF, and 2.7 percent both VT and VF). Approximately 80 to 85 percent of these arrhythmias occurred in the first 48 hours. Two limitations of fibrinolytic trials are the exclusion of patients who died of SCD in the prehospital arena, which affects the total denominator of patients, as well as the fact that fibrinolysis and reperfusion may lead to reperfusion arrhythmias, falsely increasing the incidence of MI-associated arrhythmias. Primary PCI Reported rates of primary VF among patients with STEMI treated with primary PCI range from 6 to 9 percent in different studies. Among 5745 STEMI patients with planned PCI enrolled in the APEX AMI trial, VT or VF occurred in 329 (5.7 percent), with most events (282, or 86 percent) occurring within the https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 3/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate first 48 hours [14]. In a study of 13,253 patients with STEMI transported by ambulance in one city between 2006 and 2014, 749 patients (5.6 percent) had witnessed pre-hospital cardiac arrest [15]. In a study from the Spanish Codi AMI network which included 10.965 patients with STEMI treated with primary PCI between 2010 and 2014, 949 patients (8.7 percent) experienced primary VF [16]. Non-ST elevation MI The best data on the incidence of sustained ventricular arrhythmias in patients with acute NSTEMI or unstable angina come from a pooled analysis of four major trials of over 25,000 patients with a non-ST elevation acute coronary syndrome (NSTEMI or unstable angina) [5]. The overall incidence of sustained VT or VF was 2.1 percent, which is lower than the 10.2 percent STEMI incidence in GUSTO-1 [4]. VT occurred in 0.8 percent, VF in 1 percent, and VT and VF in 0.3 percent. The median time to arrhythmia was 78 hours. MECHANISMS OF ARRHYTHMOGENESIS Ventricular arrhythmias in the setting of acute MI result from an interplay among three basic components: The damaged myocardium, which produces a substrate capable of developing reentrant circuits or associated with enhanced automaticity Arrhythmia triggers, including variations in cycle length and heart rate Modulating factors, such as electrolyte imbalance (eg, hypokalemia), dysfunction of the autonomic nervous system (eg, increased sympathetic activity), continued ischemia, and impaired left ventricular (LV) function The proper milieu for the development and maintenance of ventricular arrhythmias is ultimately based upon the rapid and profound effects that acute myocardial ischemia has on the electrophysiologic characteristics of the myocyte. Changes in the resting membrane potential and in the inward and outward ionic fluxes during the action potential lead to alterations in conduction, refractoriness, and automaticity of cardiac muscle cells, all of which contribute to the occurrence of ventricular arrhythmias [17]. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) in the setting of MI result from the complex interaction of multiple factors, including: Myocardial ischemia (with resulting local electrolyte abnormalities) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 4/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Necrosis Reperfusion Healing Scar formation Autonomic changes (especially activation of the sympathetic nervous system and elevated levels of catecholamines) These events produce the mechanisms that initiate arrhythmias and the substrate for arrhythmia perpetuation. Arrhythmia pathogenesis varies at different stages in this process. For ventricular arrhythmias occurring more than 48 to 72 hours after an acute MI, scar formation is of primary importance. Acute phase (first 30 minutes) arrhythmias A distinction must be made between the acute phase of myocardial ischemia/MI (during the first 30 minutes) and the subacute phase (6 to 48 hours post-MI) when considering the mechanisms responsible for peri-infarction ventricular arrhythmias. Acute and delayed arrhythmias are distinguished by clinical arrhythmia type, cellular mechanisms, and immediate prognostic implications. Arrhythmias occurring within the first 30 minutes of experimental coronary artery occlusion demonstrate the following bimodal distribution [18]: Arrhythmias occurring after the first 2 to 10 minutes are known as "immediate" or phase 1a ventricular arrhythmias and have a peak incidence after five minutes of ischemia. Reentry is the likely dominant mechanism for these arrhythmias. "Delayed" or phase 1b arrhythmias occur after approximately 10 to 60 minutes of coronary artery occlusion. Abnormal automaticity as well as reentry are likely the dominant mechanisms for these arrhythmias. Delayed phase (6 to 48 hours) arrhythmias Delayed-phase arrhythmias generally occur between six hours and as long as one to two days after the onset of the MI. The most frequently observed ventricular arrhythmias are [19,20]: Premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) Nonsustained VT (NSVT; three or more sequential PVCs lasting less than 30 seconds) Accelerated idioventricular rhythm, which is generally felt to be due to reperfusion of the occluded artery but is neither sensitive nor specific for definitive reperfusion Chronic phase arrhythmias During the chronic, healing phase of an acute MI (more than 48 hours), the typical patient with sustained monomorphic VT (SMVT) has had a large, often https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 5/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate complicated infarct with an LV ejection fraction 30 percent [21,22]. The VT in this situation is usually reentrant and scar mediated. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis".) New ischemia can be superimposed upon this substrate with the appearance of a variety of ventricular arrhythmias, most commonly polymorphic VT or VF but also including NSVT and SMVT [23]. Thus, revascularization and anti-ischemic therapy may be part of the antiarrhythmic regimen. Autonomic imbalance, electrolyte abnormalities, and the proarrhythmic effects of antiarrhythmic drugs can also contribute to the appearance of SMVT or other ventricular arrhythmias. LV remodeling after an MI produces structural changes in the myocardium that may also be factors in the pathogenesis of ventricular arrhythmia. Reperfusion arrhythmias Ventricular arrhythmias in some patients have been thought to be related to reperfusion, which may be spontaneous or occurring within a period of minutes after reperfusion has been achieved via fibrinolysis or mechanical means [24-26]. The evidence is best for an accelerated idioventricular rhythm (AIVR) as a reperfusion arrhythmia [25-29], although AIVR is neither a sensitive nor very specific marker for successful reperfusion, as it may occur in other situations. (See "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction", section on 'Primary failure'.) Serious ventricular arrhythmia induced by reperfusion does not appear to be a major clinical problem [29,30]. As an example, large trials of intravenous thrombolytic therapy did not demonstrate any increase in life-threatening arrhythmias that could be attributed to reperfusion, although frequent PVCs and AIVRs did occur [8,9]. Similar findings have been noted after primary percutaneous coronary intervention [29]. CLINICAL FEATURES Premature ventricular complex/contraction Premature ventricular complexes/contractions (PVC; also referred to a premature ventricular beats, premature ventricular depolarizations, ventricular premature complexes, or ventricular premature beats), which are typically asymptomatic, are common after acute MI with a reported incidence as high as 93 percent [1]. The early occurrence of PVCs does not predict short- or long-term mortality, but frequent and/or multiform PVCs that persist more than 48 to 72 hours after an MI may be associated with an increased long-term arrhythmic risk, especially in patients with reduced left ventricular ejection fraction (LVEF) [31,32]. In the GISSI-2 trial, which evaluated 8676 patients with ST elevation MI (STEMI) treated with thrombolytic therapy who underwent 24-hour Holter monitoring before https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 6/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate discharge, more than 10 PVCs per hour was a significant predictor for both total (relative risk [RR] 1.62, 95% CI 1.16-2.26) and sudden mortality (RR 2.24, 95% CI 1.22-4.08). [31]. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) PVCs produce few or no symptoms in the vast majority of patients, although some individuals may be incapacitated by palpitations or dizziness. PVCs rarely cause true hemodynamic compromise, except when they occur frequently in a patient with severely depressed LV function or when they are associated with an underlying bradycardia. The most common symptoms resulting from PVCs are palpitations secondary to the hypercontractility of a post-PVC beat or a feeling that the heart has stopped secondary to a post-PVC pause. Less often, frequent PVCs can result in a pounding sensation in the neck, lightheadedness, or near syncope. Accelerated idioventricular rhythm An accelerated idioventricular rhythm (AIVR), which has also been called "slow ventricular tachycardia," arises below the atrioventricular (AV) node (within the ventricular myocardium) and has, by definition, a rate between 50 and 100 beats/minute ( waveform 1) [33]. It may be the result of pacemaker failure, and therefore be an escape rhythm, or it may represent an abnormal ectopic focus in the ventricle that is accelerated by sympathetic stimulation and circulating catecholamines. The clinical presentation of AIVR can vary, but given the relatively slow rate and transient nature patients are frequently asymptomatic. Some patients may notice palpitations or lightheadedness, and there may be some associated hypotension if the rate results in a drop in cardiac output. AIVR occurs in up to 50 percent of patients with acute MI, although it is not always documented on ECG as it may be transient. Some studies have suggested an association with reperfusion following fibrinolytic therapy [25]. However, AIVR is neither a sensitive nor very specific marker for successful reperfusion. Monomorphic ventricular tachycardia Ventricular tachycardia (VT) is defined as three or more consecutive PVCs lasting less than 30 seconds, originating below the AV node (within the ventricular myocardium), with a heart rate greater than 100 beats/minute ( waveform 2). VT is considered sustained if it lasts more than 30 seconds or is associated with hemodynamic collapse requiring prompt therapy. The presence of a single, consistent QRS morphology suggests that each beat arises from the same location (or the same reentrant circuit) and activates the ventricle in the same sequence. This uniformity should be present in all 12 ECG leads. As a result, a 12-lead ECG should be obtained in stable patients in order to fully characterize the VT morphology. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 7/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate The clinical presentation may include palpitations, worsening ischemic symptoms due to the elevated heart rate, and hemodynamic compromise or collapse. Patients with faster tachycardias and worse LV systolic function are less likely to tolerate the arrhythmia. Another concern is that sustained monomorphic VT (SMVT) may produce ischemia, which may be an important concern for the degeneration of SMVT into ventricular fibrillation (VF). The impact of NSVT on mortality was evaluated in 6560 patients with non-ST-elevation acute coronary syndrome [34]. Only 1.2 percent of patients without VT experienced sudden cardiac death (SCD). Compared with patients with no VT, patients with four to seven beats of NSVT (2.9 percent SCD; adjusted hazard ratio [HR] 2.3, 95% CI 1.5-3.5) and patients with eight or more beats of NSVT (4.3 percent SCD; adjusted HR 2.8, 95% CI 1.5-4.9) had a higher risk of SCD. The probable mechanism and the prognostic significance of NSVT depend upon the time at which it occurs in relation to infarction. In the early stage of an evolving infarction (ie, the first 6 to as many as 48 hours), monomorphic VT may result from transient arrhythmogenic phenomena in ischemic and infarcting tissue, such as abnormal automaticity, triggered activity, and reentrant circuits created by heterogeneous conduction and repolarization. In the first 24 to 48 hours after an infarction, nonsustained VT (NSVT) is usually due to abnormal automaticity or triggered activity in the region of ischemia or infarction. In comparison, NSVT that occurs later is more often due to reentry. SMVT in any other setting is considered a marker of permanent arrhythmic substrate (ie, fibrosis and reentry) and an increased long-term risk of arrhythmia recurrence and SCD. Because of the physiologic and mechanistic link between SMVT and permanent substrate, it is not clear that SMVT at any point, even early after an MI, should be attributed to transient phenomena. Furthermore, SMVT in the setting of an acute MI may reflect permanent substrate from a prior infarction. As a result, the prognostic significance of SMVT in the early period after an MI is unclear. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis".) In fact, studies suggest that early SMVT is associated with higher in-hospital mortality due to cardiac arrest and possibly to exacerbation of ischemia and extension of the infarct [4,11,35-39], and may be a higher risk substrate than polymorphic VT [40]. Whether early SMVT is associated with an increased long-term mortality risk among contemporary patients undergoing revascularization who survive to hospital discharge is less well studied [4,11,14,35,37]. The SWEDEHEART registry included 2200 STEMI patients who underwent revascularization within 48 hours of presentation [40]. Among these patients, 150 had hemodynamically unstable VT, 35 had monomorphic VT, and 115 had nonmonomorphic VT https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 8/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate (ie, polymorphic VT or VF). Mortality at eight years was higher in those with monomorphic compared with the nonmonomorphic VT (63 versus 37 percent). Among patients who did not have early hemodynamically significant VT, mortality was 27 percent. Polymorphic VT Compared with monomorphic VT and VF, polymorphic VT (with changing QRS morphology and axis and irregularly irregular rate in the absence of QT prolongation) is much less common in the setting of an acute MI, occurring in 0.3 percent of patients in one report [41]. When polymorphic VT ( waveform 3) does occur early after an acute MI, usually within the first 12 hours after the onset of symptoms, it is typically associated with symptoms or signs of recurrent myocardial ischemia [41]. Even if signs and symptoms are absent, myocardial ischemia, which is the most common cause, should be suspected. Polymorphic VT frequently accompanies episodes of coronary vasospasm (Prinzmetal's angina). In some patients, the arrhythmia may be the only manifestation of ischemia (without angina or other more typical symptoms) [41]. The arrhythmia is not consistently related to electrolyte abnormalities, sinus bradycardia, preceding sinus pauses, or an abnormally long QT interval [41]. Polymorphic VT with prolonged QT interval of a sinus complex is termed "torsades de pointes," which has a different etiology and treatment. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) When polymorphic VT develops, the type and intensity of symptoms will vary depending upon the rate and duration of VT along with the presence or absence of significant comorbid conditions. Patients with polymorphic VT and symptoms typically present with one or more of the following: sudden cardiac arrest, syncope/presyncope, "seizure-like" activity, or palpitations. Importantly, polymorphic VT that persists for more than 10 to 15 seconds often degenerates into VF. Ventricular fibrillation VF is the most frequent mechanism of SCD. It is a rapid, disorganized ventricular arrhythmia, resulting in no uniform ventricular activation or contraction, no cardiac output, and no recordable blood pressure. As such, patients invariably present with sudden collapse (syncope and/or sudden cardiac arrest). The ECG in VF shows rapid (300 to 400 beats/minute), irregular, shapeless QRST undulations of variable amplitude, morphology, and interval ( waveform 4). Over time, these waveforms, which are initially coarse, decrease in amplitude and become finer undulations. Ultimately, asystole occurs. The majority of episodes of VF occur within the first 48 to 72 hours after the onset of symptoms [4,5,10]. It is presumably a manifestation of ischemia and is associated with lack of perfusion via the infarct-related artery [37,42]. Factors that are associated with an increased risk of VF include [5,10,14,43-46]: https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 9/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate STEMI Early repolarization (see "Early repolarization") Hypokalemia Hypotension Larger infarcts (based upon myocardial enzyme levels) Male gender History of smoking Preinfarction angina (see "Myocardial ischemic conditioning: Clinical implications") Pre-PCI Thrombolysis in MI (TIMI) flow grade 0 Inferior infarction Total baseline ST segment deviation Killip Class ( table 1) greater than I Prognosis after early VF The occurrence of VF among patients with an acute STEMI, if occurring within the first 48 hours, is associated with an increase in early mortality (eg, in- hospital mortality) but little or no increase in mortality at one to two years among patients who survive to hospital discharge [4,10,37-39,47]. These data are quite old; similar data do not exist in contemporary patients treated with early revascularization. Data are more limited in patients with a non-STEMI (NSTEMI). In a pooled analysis of patients with NSTEMI or unstable angina, VF was a significant predictor of increased mortality at both 30 days and six months (adjusted HR 23 and 15, respectively) [5]. The increase in risk was largely due to more deaths in the first 30 days. Late arrhythmias Late VT and VF are related to healing of the MI. Usually this reflects the development of scar tissue, which serves as an arrhythmogenic substrate that can promote the development of VT/VF. Fibrosis present in the scar leads to areas of conduction block with interdigitation of viable myocardium; the ensuing slowing of conduction at the border of the infarct can lead to stable reentry circuits and subsequent arrhythmias [48]. In general, late VT/VF is thought to portend risk of recurrent malignant arrhythmia and is usually treated specifically. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) In the CARISMA study, which prospectively observed 297 patients with a history of MI and LVEF of 40 percent or less (on excellent contemporary medical therapy) for late arrhythmias using an insertable cardiac monitor (also sometimes referred to as an implantable cardiac monitor or an implantable loop recorder), 13 percent of patients had at least one episode of NSVT (defined in this study as 16 or more beats, but less than 30 seconds in duration), 3 percent had an episode of sustained VT, and 3 percent had an episode of VF [49]. Over an average follow-up of two https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 10/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate years, there was a nonsignificant trend toward increased mortality in patients with any ventricular arrhythmia. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias" and "Society guideline links: ST-elevation myocardial infarction (STEMI)" and "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)".) SUMMARY AND RECOMMENDATIONS Ventricular arrhythmias, ranging from isolated premature ventricular complexes/contractions (PVCs; also referred to a premature ventricular beats, premature ventricular depolarizations, ventricular premature complexes, or ventricular premature beats) to ventricular fibrillation (VF), are common in the immediate post-MI period. In the era of early percutaneous coronary intervention (PCI) and aggressive medical therapy, approximately 25 percent of patients with a non-ST elevation acute coronary syndrome experience ventricular tachycardia (VT) within the initial seven days, an event that portends a significantly greater risk of dying compared with patients without VT. (See 'Incidence' above.) VT and VF in the setting of MI result from the complex interaction of multiple factors, including myocardial ischemia, necrosis, reperfusion, healing, and scar formation. Ventricular arrhythmias in the setting of acute MI result from an interplay among three basic components: injured myocardium, which is capable of developing reentrant circuits; arrhythmia triggers (eg, spontaneous PVCs, variations in cycle length); and modulating factors (eg, electrolyte imbalance, ongoing ischemia, autonomic nervous system). (See 'Mechanisms of arrhythmogenesis' above.) PVCs are common after acute MI with a reported incidence as high as 93 percent. PVCs produce few or no symptoms in the vast majority of patients, although some individuals may be incapacitated by palpitations or dizziness. The early occurrence of PVCs does not predict short- or long-term mortality. (See 'Premature ventricular complex/contraction' above.) Accelerated idioventricular rhythm, which is generally felt to be due to reperfusion of the occluded artery, occurs in up to 50 percent of patients with acute MI. The clinical https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 11/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate presentation of AIVR can vary, but given the relatively slow rate and transient nature patients are frequently asymptomatic, although some patients may notice palpitations or lightheadedness, and there may be some associated hypotension if the rate results in a drop in cardiac output. (See 'Accelerated idioventricular rhythm' above.) VT is considered sustained if it lasts more than 30 seconds or is associated with hemodynamic collapse requiring prompt therapy. The clinical presentation may include palpitations, worsening ischemic symptoms due to the elevated heart rate, and hemodynamic compromise or collapse. Patients with faster tachycardias and worse LV systolic function are less likely to tolerate the arrhythmia. (See 'Monomorphic ventricular tachycardia' above.) Polymorphic VT (in the absence of QT prolongation of a sinus complex) is much less common in the setting of an acute MI, but when polymorphic VT occurs early after an acute MI, usually within the first 12 hours after the onset of symptoms, it is typically associated with symptoms or signs of recurrent myocardial ischemia. Patients with polymorphic VT and symptoms typically present with one or more of the following: sudden cardiac arrest, syncope/presyncope, "seizure-like" activity, or palpitations. Importantly, polymorphic VT that persists for more than 10 to 15 seconds often degenerates into VF. (See 'Polymorphic VT' above.) VF is the most frequent mechanism of SCD. It is a rapid, disorganized ventricular arrhythmia, resulting in no uniform ventricular contraction, no cardiac output, and no recordable blood pressure. As such, patients invariably present with sudden collapse (syncope and/or sudden cardiac arrest). (See 'Ventricular fibrillation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Bigger JT Jr, Dresdale FJ, Heissenbuttel RH, et al. Ventricular arrhythmias in ischemic heart disease: mechanism, prevalence, significance, and management. Prog Cardiovasc Dis 1977; 19:255. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 12/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 2. O'Doherty M, Tayler DI, Quinn E, et al. Five hundred patients with myocardial infarction monitored within one hour of symptoms. Br Med J (Clin Res Ed) 1983; 286:1405. 3. 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Myocardial ischemia and ventricular tachycardia on continuous electrocardiographic monitoring and risk of cardiovascular outcomes after non-ST-segment elevation acute coronary syndrome (from the MERLIN-TIMI 36 Trial). Am J Cardiol 2011; 108:1373. 8. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988; 2:349. 9. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Lancet 1986; 1:397. 10. Volpi A, Cavalli A, Santoro L, Negri E. Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database. Am J Cardiol 1998; 82:265. 11. Henkel DM, Witt BJ, Gersh BJ, et al. Ventricular arrhythmias after acute myocardial infarction: a 20-year community study. Am Heart J 2006; 151:806. 12. Thompson CA, Yarzebski J, Goldberg RJ, et al. Changes over time in the incidence and case- fatality rates of primary ventricular fibrillation complicating acute myocardial infarction: perspectives from the Worcester Heart Attack Study. Am Heart J 2000; 139:1014. 13. Sarter BH, Finkle JK, Gerszten RE, Buxton AE. What is the risk of sudden cardiac death in patients presenting with hemodynamically stable sustained ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996; 28:122. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 13/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 14. Mehta RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention. JAMA 2009; 301:1779. 15. Karam N, Bataille S, Marijon E, et al. Incidence, Mortality, and Outcome-Predictors of Sudden Cardiac Arrest Complicating Myocardial Infarction Prior to Hospital Admission. Circ Cardiovasc Interv 2019; 12:e007081. 16. Garc a-Garc a C, Oliveras T, Rueda F, et al. Primary Ventricular Fibrillation in the Primary Percutaneous Coronary Intervention ST-Segment Elevation Myocardial Infarction Era (from the "Codi IAM" Multicenter Registry). Am J Cardiol 2018; 122:529. 17. Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69:1049. 18. Di Diego JM, Antzelevitch C. Ischemic ventricular arrhythmias: experimental models and their clinical relevance. Heart Rhythm 2011; 8:1963. 19. Campbell RW, Murray A, Julian DG. Ventricular arrhythmias in first 12 hours of acute myocardial infarction. Natural history study. Br Heart J 1981; 46:351. 20. Northover BJ. Ventricular tachycardia during the first 72 hours after acute myocardial infarction. Cardiology 1982; 69:149. 21. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983; 52:1190. 22. DiMarco JP, Lerman BB, Kron IL, Sellers TD. Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode. J Am Coll Cardiol 1985; 6:759. 23. Stambler BS, Akosah KO, Mohanty PK, et al. Myocardial ischemia and induction of sustained ventricular tachyarrhythmias: evaluation using dobutamine stress echocardiography- electrophysiologic testing. J Cardiovasc Electrophysiol 2004; 15:901. 24. Gressin V, Louvard Y, Pezzano M, Lardoux H. Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction. Am J Cardiol 1992; 69:152. 25. Gorgels AP, Vos MA, Letsch IS, et al. Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute |
presentation of AIVR can vary, but given the relatively slow rate and transient nature patients are frequently asymptomatic, although some patients may notice palpitations or lightheadedness, and there may be some associated hypotension if the rate results in a drop in cardiac output. (See 'Accelerated idioventricular rhythm' above.) VT is considered sustained if it lasts more than 30 seconds or is associated with hemodynamic collapse requiring prompt therapy. The clinical presentation may include palpitations, worsening ischemic symptoms due to the elevated heart rate, and hemodynamic compromise or collapse. Patients with faster tachycardias and worse LV systolic function are less likely to tolerate the arrhythmia. (See 'Monomorphic ventricular tachycardia' above.) Polymorphic VT (in the absence of QT prolongation of a sinus complex) is much less common in the setting of an acute MI, but when polymorphic VT occurs early after an acute MI, usually within the first 12 hours after the onset of symptoms, it is typically associated with symptoms or signs of recurrent myocardial ischemia. Patients with polymorphic VT and symptoms typically present with one or more of the following: sudden cardiac arrest, syncope/presyncope, "seizure-like" activity, or palpitations. Importantly, polymorphic VT that persists for more than 10 to 15 seconds often degenerates into VF. (See 'Polymorphic VT' above.) VF is the most frequent mechanism of SCD. It is a rapid, disorganized ventricular arrhythmia, resulting in no uniform ventricular contraction, no cardiac output, and no recordable blood pressure. As such, patients invariably present with sudden collapse (syncope and/or sudden cardiac arrest). (See 'Ventricular fibrillation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Bigger JT Jr, Dresdale FJ, Heissenbuttel RH, et al. Ventricular arrhythmias in ischemic heart disease: mechanism, prevalence, significance, and management. Prog Cardiovasc Dis 1977; 19:255. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 12/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 2. O'Doherty M, Tayler DI, Quinn E, et al. Five hundred patients with myocardial infarction monitored within one hour of symptoms. Br Med J (Clin Res Ed) 1983; 286:1405. 3. Tran HV, Ash AS, Gore JM, et al. Twenty-five year trends (1986-2011) in hospital incidence and case-fatality rates of ventricular tachycardia and ventricular fibrillation complicating acute myocardial infarction. Am Heart J 2019; 208:1. 4. Newby KH, Thompson T, Stebbins A, et al. Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators. Circulation 1998; 98:2567. 5. Al-Khatib SM, Granger CB, Huang Y, et al. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes. Circulation 2002; 106:309. 6. Sobel BE, Corr PB, Robison AK, et al. Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. J Clin Invest 1978; 62:546. 7. Harkness JR, Morrow DA, Braunwald E, et al. Myocardial ischemia and ventricular tachycardia on continuous electrocardiographic monitoring and risk of cardiovascular outcomes after non-ST-segment elevation acute coronary syndrome (from the MERLIN-TIMI 36 Trial). Am J Cardiol 2011; 108:1373. 8. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988; 2:349. 9. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Lancet 1986; 1:397. 10. Volpi A, Cavalli A, Santoro L, Negri E. Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database. Am J Cardiol 1998; 82:265. 11. Henkel DM, Witt BJ, Gersh BJ, et al. Ventricular arrhythmias after acute myocardial infarction: a 20-year community study. Am Heart J 2006; 151:806. 12. Thompson CA, Yarzebski J, Goldberg RJ, et al. Changes over time in the incidence and case- fatality rates of primary ventricular fibrillation complicating acute myocardial infarction: perspectives from the Worcester Heart Attack Study. Am Heart J 2000; 139:1014. 13. Sarter BH, Finkle JK, Gerszten RE, Buxton AE. What is the risk of sudden cardiac death in patients presenting with hemodynamically stable sustained ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996; 28:122. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 13/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 14. Mehta RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention. JAMA 2009; 301:1779. 15. Karam N, Bataille S, Marijon E, et al. Incidence, Mortality, and Outcome-Predictors of Sudden Cardiac Arrest Complicating Myocardial Infarction Prior to Hospital Admission. Circ Cardiovasc Interv 2019; 12:e007081. 16. Garc a-Garc a C, Oliveras T, Rueda F, et al. Primary Ventricular Fibrillation in the Primary Percutaneous Coronary Intervention ST-Segment Elevation Myocardial Infarction Era (from the "Codi IAM" Multicenter Registry). Am J Cardiol 2018; 122:529. 17. Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69:1049. 18. Di Diego JM, Antzelevitch C. Ischemic ventricular arrhythmias: experimental models and their clinical relevance. Heart Rhythm 2011; 8:1963. 19. Campbell RW, Murray A, Julian DG. Ventricular arrhythmias in first 12 hours of acute myocardial infarction. Natural history study. Br Heart J 1981; 46:351. 20. Northover BJ. Ventricular tachycardia during the first 72 hours after acute myocardial infarction. Cardiology 1982; 69:149. 21. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983; 52:1190. 22. DiMarco JP, Lerman BB, Kron IL, Sellers TD. Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode. J Am Coll Cardiol 1985; 6:759. 23. Stambler BS, Akosah KO, Mohanty PK, et al. Myocardial ischemia and induction of sustained ventricular tachyarrhythmias: evaluation using dobutamine stress echocardiography- electrophysiologic testing. J Cardiovasc Electrophysiol 2004; 15:901. 24. Gressin V, Louvard Y, Pezzano M, Lardoux H. Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction. Am J Cardiol 1992; 69:152. 25. Gorgels AP, Vos MA, Letsch IS, et al. Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction. Am J Cardiol 1988; 61:231. 26. Goldberg S, Greenspon AJ, Urban PL, et al. Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction. Am https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 14/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Heart J 1983; 105:26. 27. Miller FC, Krucoff MW, Satler LF, et al. Ventricular arrhythmias during reperfusion. Am Heart J 1986; 112:928. 28. Yoshida Y, Hirai M, Yamada T, et al. Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias. Circulation 2000; 101:624. 29. Wehrens XH, Doevendans PA, Ophuis TJ, Wellens HJ. A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J 2000; 139:430. 30. Hackett D, McKenna W, Davies G, Maseri A. Reperfusion arrhythmias are rare during acute myocardial infarction and thrombolysis in man. Int J Cardiol 1990; 29:205. 31. Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation 1993; 87:312. 32. Yap YG, Duong T, Bland JM, et al. Prognostic impact of demographic factors and clinical features on the mode of death in high-risk patients after myocardial infarction a combined analysis from multicenter trials. Clin Cardiol 2005; 28:471. 33. Rothfeld, EL, Zucker, et al. Idioventricular rhythm in acute myocardial infarction. Circulation 1968; 37:203. 34. Scirica BM, Braunwald E, Belardinelli L, et al. Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations from the metabolic efficiency with ranolazine for less ischemia in non-ST- elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 2010; 122:455. 35. Eldar M, Sievner Z, Goldbourt U, et al. Primary ventricular tachycardia in acute myocardial infarction: clinical characteristics and mortality. The SPRINT Study Group. Ann Intern Med 1992; 117:31. 36. Mont L, Cinca J, Blanch P, et al. Predisposing factors and prognostic value of sustained monomorphic ventricular tachycardia in the early phase of acute myocardial infarction. J Am Coll Cardiol 1996; 28:1670. 37. Berger PB, Ruocco NA, Ryan TJ, et al. Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial. J Am Coll Cardiol 1993; 22:1773. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 15/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 38. Tofler GH, Stone PH, Muller JE, et al. Prognosis after cardiac arrest due to ventricular tachycardia or ventricular fibrillation associated with acute myocardial infarction (the MILIS Study). Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol 1987; 60:755. 39. Goldberg RJ, Gore JM, Haffajee CI, et al. Outcome after cardiac arrest during acute myocardial infarction. Am J Cardiol 1987; 59:251. 40. Demidova MM, lfarsson , Carlson J, et al. Relation of Early Monomorphic Ventricular Tachycardia to Long-Term Mortality in ST-Elevation Myocardial Infarction. Am J Cardiol 2022; 163:13. 41. Wolfe CL, Nibley C, Bhandari A, et al. Polymorphous ventricular tachycardia associated with acute myocardial infarction. Circulation 1991; 84:1543. 42. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute myocardial infarction. N Engl J Med 2003; 348:933. 43. Gheeraert PJ, Henriques JP, De Buyzere ML, et al. Preinfarction angina protects against out- of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery. J Am Coll Cardiol 2001; 38:1369. 44. Gheeraert PJ, De Buyzere ML, Taeymans YM, et al. Risk factors for primary ventricular fibrillation during acute myocardial infarction: a systematic review and meta-analysis. Eur Heart J 2006; 27:2499. 45. Naruse Y, Tada H, Harimura Y, et al. Early repolarization is an independent predictor of occurrences of ventricular fibrillation in the very early phase of acute myocardial infarction. Circ Arrhythm Electrophysiol 2012; 5:506. 46. Tikkanen JT, Wichmann V, Junttila MJ, et al. Association of early repolarization and sudden cardiac death during an acute coronary event. Circ Arrhythm Electrophysiol 2012; 5:714. 47. Jensen GV, Torp-Pedersen C, Hildebrandt P, et al. Does in-hospital ventricular fibrillation affect prognosis after myocardial infarction? Eur Heart J 1997; 18:919. 48. de Bakker JM, van Capelle FJ, Janse MJ, et al. Slow conduction in the infarcted human heart. 'Zigzag' course of activation. Circulation 1993; 88:915. 49. Bloch Thomsen PE, Jons C, Raatikainen MJ, et al. Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study. Circulation 2010; 122:1258. Topic 1060 Version 38.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 16/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate GRAPHICS ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 17/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate 12-lead ECG sustained monomorphic VT The electrocardiogram (ECG) hallmark for the diagnosis of sustained monomorphic ventricular tachycardia (S is a wide complex tachycardia with the obvious presence of atrioventricular (AV) dissociation. AV dissociation suggested by the presence of fusion complexes (which reflect a supraventricular impulse coming from above AV node fusing with an impulse generated in the ventricle) or captured complexes (which reflect an impulse coming from above the AV node that depolarizes the ventricles when they are no longer refractory but befor next ventricle-generated complex). Beats 12, 17, and 22 on this ECG likely represent capture beats. Graphic 111254 Version 1.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 18/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Single lead electrocardiogram (ECG) showing polymorphic ventricular tachycardia (VT) This is an atypical, rapid, and bizarre form of ventricular tachycardia that is characterized by a continuously changing axis of polymorphic QRS morphologies. Graphic 53891 Version 5.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 19/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate ECG 12-lead ventricular fibrillation 12-lead ECG showing course ventricular fibrillation. ECG: electrocardiogram. Graphic 118944 Version 1.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 20/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Killip classification of acute myocardial infarction Class I No evidence of heart failure Class II Findings consistent with mild to moderate heart failure (eg, S3 gallop, lung rales less than one-half way up the posterior lung fields, or jugular venous distension) Class III Overt pulmonary edema Class IV Cardiogenic shock Graphic 65592 Version 7.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 21/22 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-incidence-mechanisms-and-clinical-features/print 22/22 |
7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment : Philip J Podrid, MD, FACC : James Hoekstra, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 14, 2023. INTRODUCTION Sudden cardiac death (SCD) in the setting of an acute myocardial infarction (MI) is most frequently the result of a ventricular tachyarrhythmia. The appearance of a sustained ventricular tachyarrhythmia following an MI, such as ventricular tachycardia (VT) or ventricular fibrillation (VF), in the early period post-MI may be the harbinger of ongoing myocardial ischemia, the development of proarrhythmic myocardial scar tissue, elevated sympathetic tone or increase in circulating catecholamines, or an electrolyte disturbance such as hypokalemia. In-hospital mortality approaches 20 percent or more in patients who develop VT or VF following an MI. As such, rapid identification and treatment of these arrhythmias can be life-saving. Although all patients with a prior MI have an elevated risk of malignant arrhythmias, the magnitude of risk varies from patient to patient, with reduced left ventricular ejection fraction being the most prominent risk stratifier. This topic will focus on the prevention and treatment of ventricular arrhythmias during and immediately after acute MI. The incidence, mechanisms, and clinical features of ventricular arrhythmias during acute MI, as well as treatment of ventricular arrhythmias late post-MI (using defibrillation with or without antiarrhythmic medications) is discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 1/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate PREVENTION Frequent ventricular premature beats (VPBs), VT, and ventricular fibrillation (VF) are all associated with increased long-term mortality following acute MI. An acute MI may be an ST- segment elevation MI (STEMI) or non-ST-segment elevation MI (NSTEMI). Most of the data available are in patients with a STEMI. While the data may also apply to patients with an NSTEMI, information in these patients is more limited. The following is a summary of the multi-modality approach to prevention of ventricular arrhythmias following MI (STEMI), which includes treatment of ischemia, electrolyte supplementation (if needed), and beta blockers. Treatment of symptomatic arrhythmias (should they arise) is discussed elsewhere. (See 'Treatment' below.) Revascularization/treatment of myocardial ischemia Patients with ventricular arrhythmias, especially polymorphic VT, in the setting of an acute MI should receive aggressive treatment for both the arrhythmia and myocardial ischemia. Therapy for ischemia usually includes drugs (eg, beta blockers, nitrates) and in most cases primary percutaneous coronary intervention or far less frequently, coronary artery bypass grafting for revascularization [1]. Fibrinolytic therapy is also effective but is used infrequently and generally only when PCI is not immediately available. The acute and long-term treatments of ischemic heart disease are discussed in detail separately. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".) Electrolyte supplementation In the post-MI setting, we maintain levels of serum potassium 4 mEq/L and serum magnesium 2 mg/dL. The dose and route of potassium and/or magnesium are discussed elsewhere. (See "Clinical manifestations and treatment of hypokalemia in adults" and "Hypomagnesemia: Evaluation and treatment".) Hypokalemia is a risk factor for VF in the setting of an acute MI, and concomitant hypomagnesemia, which is detected in approximately 40 percent of cases of hypokalemia, prevents the correction of hypokalemia [2]. In the GISSI-2 trial, the likelihood of VF among patients with a serum potassium <3.6 mEq/L was almost twice as high as among patients with a higher serum potassium (odds ratio 1.97) [3]. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Ventricular fibrillation'.) The MAGIC trial showed no benefit to empiric magnesium supplementation in acute MI patients [4]. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 2/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Beta blockers Oral beta blockers are administered universally to all patients without contraindications who experience an acute MI [5]. In addition to other beneficial effects, the immediate administration of a beta blocker during an acute MI reduces the risk of VF. In a systematic review, the overall mortality in 31 long-term trials that included almost 25,000 patients was 9.7 percent; beta blockers reduced the odds of death by 23 percent (95% CI 15-31 percent) [6]. These benefits are seen following both STEMI and NSTEMI ( figure 1) [7]. The details of beta blocker use are discussed separately. (See "Acute myocardial infarction: Role of beta blocker therapy".) Beta blockers are of use as the etiology of ventricular arrhythmia in the early or acute stages of an MI is in part related to enhanced automaticity, resulting from elevated catecholamines and beta receptor stimulation. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) Antiarrhythmic drugs We do not administer prophylactic antiarrhythmic agents in the post- infarction period. The prophylactic administration of class IC antiarrhythmic agents (eg, encainide, flecainide) in the post-MI period is associated with increased mortality and is not recommended [8- 10]. Due to the suggestion of possible harm and unsure benefit, the routine prophylactic administration of lidocaine in the acute MI period is not recommended [11]. Unlike the other antiarrhythmic drugs, prophylactic amiodarone is not associated with an increase in mortality. However, its unselected use in all patients does not appear to improve outcomes. As such, we do not administer prophylactic amiodarone in the post-MI period. The use of these agents is reserved for patients with documented ventricular tachyarrhythmias. (See 'Treatment' below.) Heart failure therapy Although not considered antiarrhythmic drugs, angiotensin converting enzyme (ACE) inhibitors, aldosterone antagonists, angiotensin II receptor blockers (ARBs), and combination ARB and neprilysin inhibitor all reduce the incidence of SCD in patients with heart failure (HF). Reduced SCD rates have been reported specifically in post-MI populations with ACE inhibitors and aldosterone antagonists, and in a broader population of HF patients, approximately 50 percent of whom had a prior infarction, with an ARB. These topics are discussed separately. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials", section on 'Effect on sudden death'.) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 3/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Wearable defibrillator for primary prevention Among patients with left ventricular ejection fraction (LVEF) 35 percent who are less than 40 days post-MI, we discuss the potential benefits and risks of wearable cardioverter-defibrillator (WCD) use ( picture 1) and consider providing it to motivated patients with NYHA functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for implantable cardioverter-defibrillator (ICD) implantation after 40 days. However, one study has not shown improvement in mortality in such patients as a result of WCD use [12]. In another analysis of this trial, it was reported that the lack of benefit might be in part related to poor compliance among patients prescribed the WCD [13]. The role of the WCD is discussed in detail separately. (See "Wearable cardioverter-defibrillator".) TREATMENT Ventricular premature beats In the post-MI patient with ventricular premature beats (VPBs) that cause significant or disabling symptoms (eg, palpitations, lightheadedness), beta blockers are administered, although most patients will already be taking them. In the rare circumstance that more aggressive antiarrhythmic therapy is considered for control of refractory symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm, although there is an appreciable incidence of side effects with long-term amiodarone therapy. Mexiletine, which is a class IB agent that resembles lidocaine, also appears safe in the post-MI patient, and although there are no randomized trials in this population, it may be effective for arrhythmia suppression [14,15]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) There is no role for chronic antiarrhythmic drug therapy to suppress asymptomatic VPBs. (See 'Prevention' above.) VPBs, particularly if frequent (more than 10 per hour) or complex (ie, couplets or non-sustained ventricular tachycardia) appear to be associated with a worse prognosis in patients with a prior MI. Based upon this association, trials of both class I and class III antiarrhythmic medications were conducted to determine if suppression of ventricular ectopy would reduce SCD. Patients with frequent asymptomatic VPBs post-MI were randomly assigned to receive suppressive antiarrhythmic therapy or placebo in an effort to suppress the ectopy [8,9]. The CAST study, which randomly assigned patients to treatment with encainide, flecainide, moricizine, or placebo, was prematurely terminated when it was noted that, despite suppression of VPBs, total mortality among the patients receiving encainide and flecainide was significantly increased compared with those on placebo (7.7 versus 3.0 percent); this was due primarily to an excess in arrhythmic deaths ( figure 2). https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 4/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate The CAST II study, which limited treatment to moricizine or placebo, was also terminated early due to an increased risk of death or cardiac arrest in the first 14 days of therapy among patients treated with moricizine (2.6 versus 0.5 percent with placebo) [9]. The CAMIAT study, which randomly assigned patients with frequent ( 10 per hour) or repetitive VPBs to amiodarone or placebo (approximately 60 percent were also treated with a beta blocker), showed that although arrhythmia suppression was more common with amiodarone (84 versus 35 percent with placebo), there was no significant difference in yearly all-cause or cardiac mortality (4.0 versus 5.2 percent) [16]. Nonsustained VT For patients with symptomatic (eg, palpitations, lightheadedness) nonsustained ventricular tachycardia (NSVT) after an MI, beta blockers are administered, although most patients should already be taking them. If antiarrhythmic drug therapy is considered due to persistent symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm, although there is an appreciable incidence of side effects with long-term amiodarone therapy. An alternative agent is mexiletine as it is safe and has been found to be effective for arrhythmia suppression in other groups of patients [14,15]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) In the absence of data specific to patients with NSVT, we do not prescribe chronic antiarrhythmic drug therapy to suppress asymptomatic NSVT. The presence of NSVT in post-MI patients with an LVEF 40 percent is an indication for further risk stratification, if the patient does not already meet criteria for ICD placement (LVEF 30 percent without heart failure symptoms, or LVEF 35 percent with NYHA class II or III heart failure). Electrophysiologic testing prior to hospital discharge may be appropriate in patients with late NSVT (ie, more than 24 to 48 hours into acute MI). (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) The development of NSVT one week or later post-MI carries at least a twofold increase in the risk of SCD [17]. The risk of NSVT is even further increased in post-MI patients with significantly diminished LV function (LVEF less than 40 percent). In this setting, the risk of SCD is increased more than fivefold [17,18]. Large randomized trials of antiarrhythmic drugs limited to patients with NSVT have not been performed. However, many of the patients included in the CAST and CAMIAT (39 percent) trials had NSVT. These trials showed an increased mortality in patients treated with class IC antiarrhythmic medications [8] and no significant reduction in overall mortality with amiodarone [16]. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 5/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Accelerated idioventricular rhythm An accelerated idioventricular rhythm (AIVR), which has also been called "slow VT," arises below the atrioventricular (AV) node and has, by definition, a rate between 50 and 100 beats/minute ( waveform 1). Most episodes are transient, benign, and require no treatment. Furthermore, pharmacologic therapy is contraindicated if there is complete heart block and an escape ventricular rhythm (which is not actually AIVR), since suppression of the pacemaker focus can result in profound bradycardia and possibly asystole. AIVR is most often seen in the peri-infarction period. AIVR often occurs after reperfusion therapy (PCI or fibrinolytic therapy) and is felt to be a reperfusion arrhythmia. It is likely the result of enhanced automaticity of ectopic foci in the ventricular myocardium. AIVR occurring after the peri-infarction period is uncommon. When it occurs, reversible causes should be sought such as digitalis toxicity, hypokalemia, or hypomagnesemia. There are no convincing data linking AIVR to sustained VT, ventricular fibrillation (VF), or a worse prognosis. Thus, no therapy is warranted for asymptomatic arrhythmias, while symptomatic arrhythmias can be treated with a beta blocker (if the patient is not already receiving this therapy), antiarrhythmic drugs, or perhaps ablation. Polymorphic VT Polymorphic VT associated with a normal QT interval is an uncommon arrhythmia following an acute MI ( waveform 2 and waveform 3). When it occurs, it is often associated with signs or symptoms of recurrent or ongoing myocardial ischemia [19]. Even if there are no signs or symptoms of myocardial ischemia, underlying myocardial ischemia is the most likely etiology. If polymorphic VT lasts for more than 8 to 10 seconds, it often degenerates into VF. This type of polymorphic VT generally fails to respond to class I antiarrhythmic drugs, magnesium, or overdrive pacing but may respond to intravenous amiodarone or lidocaine [19]. In patients treated with primary percutaneous coronary intervention who then manifest polymorphic ventricular tachycardia , revisualization of the coronary arteries is frequently warranted. An intraaortic balloon pump or other mechanical unloading therapy may help stabilize these patients. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Polymorphic VT'.) Revascularization has traditionally been considered to be adequate therapy for polymorphic VT due to ischemia in the absence of acute MI. However, more recent data suggest that ICD implantation in addition to revascularization may be optimal [20]. There is a second form of polymorphic VT that develops during the healing phase (at 3 to 11 days) and occurs in association with QT prolongation [21]. This arrhythmia resembles an acquired long QT syndrome and is treated in a similar fashion. One report of eight such patients found that defibrillation (if the arrhythmia is sustained), magnesium, lidocaine, beta blockers, and rapid overdrive pacing were effective therapies [21]. Mexiletine, which is similar to lidocaine https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 6/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate but is an oral medication, may be of benefit. In general, the QT interval shortened within 10 days, and long-term outcomes were uneventful. More commonly, polymorphic VT results from either acquired or congenital long QT interval and in this situation it is called torsades de pointes. Acquired QT prolongation may result from class IA or class III antiarrhythmic drugs, which can prolong the QT interval. An exception is amiodarone, which rarely produces torsades de pointes when used alone. Amiodarone should be discontinued if the burden of polymorphic VT increases, which is a possible sign of proarrhythmia. Many other drugs, including antibiotics, psychotropic agents, antihistamines, and GI medications may prolong the QT interval. Magnesium supplementation may be of benefit, even in the absence of hypomagnesemia. Bradycardia frequently facilitates the initiation of torsades de pointes VT in a susceptible patient with drug-induced QT prolongation as the QT interval lengthens further with slower heart rates. Increasing the heart rate, as with temporary pacing, may help prevent recurrent episodes. Although increasing the heart rate with intravenous isoproterenol or dobutamine may also be effective, this should be done with caution in the patient with an acute myocardial infarction. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes" and "Temporary cardiac pacing", section on 'Indications'.) Sustained monomorphic VT and VF Unstable, poorly-tolerated arrhythmias are a life- threatening emergency that are treated according to established advanced cardiac life support (ACLS) protocols [22]. VF is almost universally lethal if not treated. VF does not self-terminate nor does it revert with antiarrhythmic drugs. Defibrillation (nonsynchronized delivery of a shock) is the definitive therapy for VF. If available, a biphasic waveform defibrillator is preferable since the success rate for defibrillation is higher than with monophasic waveforms. The 2015 American Heart Association (AHA) guidelines for adult ACLS recommended that, for biphasic defibrillators, the initial shock should be at 120 to 200 joules, with subsequent shocks at the highest available biphasic energy level (200 joules for most devices) [22]. For monophasic defibrillators, nonescalating shocks beginning at 360 joules should be used. (See "Advanced cardiac life support (ACLS) in adults" and "Basic principles and technique of external electrical cardioversion and defibrillation".) Hemodynamically unstable or pulseless sustained monomorphic VT (SMVT) without identifying a distinct QRS should be treated with unsynchronized electrical shocks (ie, defibrillation and not cardioversion, which is the delivery of an electrical shock synchronized to the QRS complex). If available, a biphasic waveform defibrillator is preferable since the success rate for defibrillation is higher than with monophasic https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 7/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate waveforms. For biphasic defibrillators, the initial shock should be at 120 to 200 joules, with subsequent shocks at the highest available biphasic energy level (200 joules for most devices). For monophasic defibrillators, nonescalating shocks beginning at 360 joules should be used. (See "Cardioversion for specific arrhythmias", section on 'Ventricular tachycardia'.) SMVT (in which a distinct QRS complex can be identified) associated with angina, pulmonary edema, or hypotension (systolic blood pressure <90 mmHg) should be treated immediately with synchronized electrical cardioversion using an initial energy of 50 to 100 joules. Subsequent shocks at increasing energy can be given as necessary. Brief anesthesia is desirable if hemodynamically tolerable. SMVT that is hemodynamically tolerated and asymptomatic can be treated initially with intravenous amiodarone (or lidocaine or procainamide). Synchronized electrical cardioversion with brief anesthesia should be performed if VT persists after the administration of the initial 150 mg of amiodarone (or 100 to 300 mg of lidocaine). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Stable patients' and "Cardioversion for specific arrhythmias", section on 'Ventricular tachycardia'.) Recurrent nonsustained and sustained VT, particularly polymorphic, should trigger consideration of investigation for ischemia, possibly (but not always) involving the infarct- related artery. (See 'Revascularization/treatment of myocardial ischemia' above.) Patients who manifest sustained VT or polymorphic VT more than 24 to 48 hours after acute MI should generally undergo ICD implantation prior to hospital discharge. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) The acute and long-term management of SMVT and VF in patients with a prior MI are discussed in detail separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Electrical storm Electrical storm is defined as multiple recurrent episodes of VF. The optimal therapy of electrical storm in patients with an acute MI is uncertain but is likely no different than in patients with electrical storm in any setting and includes defibrillation, antiarrhythmic medications, beta blockers, treatment of myocardial ischemia, and long-term therapies to prevent recurrent arrhythmias (eg, catheter ablation, cardiac sympathetic denervation, etc). (See "Electrical storm and incessant ventricular tachycardia".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 8/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST- elevation myocardial infarction (STEMI)" and "Society guideline links: Ventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Ventricular fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS Revascularization Patients with ventricular arrhythmias, especially polymorphic VT, in the setting of an acute MI should receive aggressive treatment for both the arrhythmia and myocardial ischemia. Therapy for ischemia usually includes drugs (eg, beta blockers, nitrates) and either primary percutaneous coronary intervention or coronary artery bypass grafting for revascularization. (See 'Revascularization/treatment of myocardial ischemia' above.) Preventive therapies Other therapies that reduce ventricular arrhythmias during and immediately after acute MI include maintaining levels of serum potassium 4.0 mEq/L and https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 9/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate serum magnesium 2.0 mg/dL, administering beta blockers, and appropriate therapies for heart failure, when present. (See 'Prevention' above.) Antiarrhythmic drugs The prophylactic administration of antiarrhythmic agents to asymptomatic patients during and immediately after acute MI has at best no benefit and potentially can cause harm. The use of these agents is reserved for patients with documented ventricular tachyarrhythmias. (See 'Antiarrhythmic drugs' above and 'Treatment' above.) Ventricular premature beats In the post-MI patient with ventricular premature beats or nonsustained VT that cause significant or disabling symptoms (eg, palpitations, lightheadedness), beta blockers are administered, although most patients will already be taking them. In the rare circumstance that more aggressive antiarrhythmic therapy is considered for control of refractory symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm. (See 'Ventricular premature beats' above.) Accelerated idioventricular rhythm Most episodes of accelerated idioventricular rhythm (AIVR) are transient, benign, and require no treatment. Furthermore, pharmacologic therapy is contraindicated if there is complete heart block and an escape ventricular rhythm (which is not actually AIVR), since suppression of the pacemaker focus can result in profound bradycardia and possibly asystole. (See 'Accelerated idioventricular rhythm' above.) Polymorphic VT This is associated with a normal QT interval, is an uncommon arrhythmia, and is often associated with signs or symptoms of recurrent or ongoing myocardial ischemia, in which case revisualization of the coronary arteries is usually warranted. Polymorphic VT that results from acquired long QT interval is called torsades de pointes and is usually related to medications. (See 'Polymorphic VT' above.) Poorly-tolerated arrhythmias Sustained monomorphic VT or VF is a life-threatening emergency that is treated according to established advanced cardiac life support (ACLS) protocols. (See "Advanced cardiac life support (ACLS) in adults" and 'Sustained monomorphic VT and VF' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 10/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 2. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 1992; 152:40. 3. Volpi A, Cavalli A, Santoro L, Negri E. Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database. Am J Cardiol 1998; 82:265. 4. Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 2002; 360:1189. 5. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O'Gara PT, et al. 2013 ACCF/AHA guideline for the management of ST- elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61:e78. 6. Freemantle N, Cleland J, Young P, et al. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318:1730. 7. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998; 339:489. 8. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781. 9. Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992; 327:227. 10. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA 1993; 270:1589. 11. Sadowski ZP, Alexander JH, Skrabucha B, et al. Multicenter randomized trial and a systematic https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 11/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate overview of lidocaine in acute myocardial infarction. Am Heart J 1999; 137:792. 12. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable Cardioverter-Defibrillator after Myocardial Infarction. N Engl J Med 2018; 379:1205. 13. Olgin JE, Lee BK, Vittinghoff E, et al. Impact of wearable cardioverter-defibrillator compliance on outcomes in the VEST trial: As-treated and per-protocol analyses. J Cardiovasc Electrophysiol 2020; 31:1009. 14. Stein J, Podrid PJ, Lampert S, et al. Long-term mexiletine for ventricular arrhythmia. Am Heart J 1984; 107:1091. 15. Mendes L, Podrid PJ, Fuchs T, Franklin S. Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia. J Am Coll Cardiol 1991; 17:1396. 16. Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349:675. 17. Bigger JT Jr, Fleiss JL, Rolnitzky LM. Prevalence, characteristics and significance of ventricular tachycardia detected by 24-hour continuous electrocardiographic recordings in the late hospital phase of acute myocardial infarction. Am J Cardiol 1986; 58:1151. 18. Mukharji J, Rude RE, Poole WK, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol 1984; 54:31. 19. Wolfe CL, Nibley C, Bhandari A, et al. Polymorphous ventricular tachycardia associated with acute myocardial infarction. Circulation 1991; 84:1543. 20. Natale A, Sra J, Axtell K, et al. Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: does bypass surgery suffice? J Cardiovasc Electrophysiol 1994; 5:988. 21. Halkin A, Roth A, Lurie I, et al. Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome. J Am Coll Cardiol 2001; 38:1168. 22. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. Topic 118996 Version 15.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 12/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate GRAPHICS Beta blockers are equally effective after a Q wave or non-Q wave MI Analysis of data from 201,752 patients with a myocardial infarction (MI) demonstrates that the reduction in mortality at two years with beta blockers is similar in those with a Q wave (14.2 versus 23.6 percent for those not receiving beta blockers) or non-Q wave MI (14.4 versus 23.9 percent). Data from Gottlieb SS, McCarter RJ, Vogel RA. N Engl J Med 1998; 339:489. Graphic 79592 Version 2.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 13/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Wearable cardioverter-defibrillator The wearable cardioverter-defibrillator consists of a vest incorporating two defibrillation electrodes and four sensing electrocardiographic electrodes connected to a waist unit containing the monitoring and defibrillation electronics. Reproduced with permission from: ZOLL Medical Corporation. Copyright 2012. All rights reserved. Graphic 60103 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 14/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Encainide and flecainide increase cardiac mortality Results of the Cardiac Arrhythmia Suppression Trial (CAST) in patients with ventricular premature beats after myocardial infarction. Patients receiving encainide or flecainide had, when compared with those receiving placebo, a significantly lower rate of avoiding a cardiac event (death or resuscitated cardiac arrest) (left panel, p = 0.001) and a lower overall survival (right panel, p = 0.0006). The cause of death was arrhythmia or cardiac arrest. Data from Echt DS, Liebson PR, Mitchell B, et al. N Engl J Med 1991; 324:781. Graphic 59975 Version 5.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 15/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 16/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG_1 showing polymorphic ventricular tachycardia in ischemia Continuous rhythm strip revealing several episodes of nonsustained ventricular tachycardia (VT) occurring during an acute ischemic event. The QRS complexes are variable in morphology and RR intervals; thus, the VT is polymorphic. The QT interval is normal. This form of VT should be distinguished from torsade de pointes in which polymorphic VT is associated with QT interval prolongation. Graphic 54538 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 17/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG_2 showing polymorphic ventricular tachycardia in ischemia Continuous rhythm strip showing an episode of very rapid polymorphic ventricular tachycardia which is often referred to as ventricular flutter. The QT interval is normal and the QRS complex morphology is highly variable. The patient had an underlying sinus tachycardia, suggesting increased sympathetic activity secondary to an ischemic event. Graphic 67322 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 18/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 19/19 |
7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment : Philip J Podrid, MD, FACC : James Hoekstra, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 14, 2023. INTRODUCTION Sudden cardiac death (SCD) in the setting of an acute myocardial infarction (MI) is most frequently the result of a ventricular tachyarrhythmia. The appearance of a sustained ventricular tachyarrhythmia following an MI, such as ventricular tachycardia (VT) or ventricular fibrillation (VF), in the early period post-MI may be the harbinger of ongoing myocardial ischemia, the development of proarrhythmic myocardial scar tissue, elevated sympathetic tone or increase in circulating catecholamines, or an electrolyte disturbance such as hypokalemia. In-hospital mortality approaches 20 percent or more in patients who develop VT or VF following an MI. As such, rapid identification and treatment of these arrhythmias can be life-saving. Although all patients with a prior MI have an elevated risk of malignant arrhythmias, the magnitude of risk varies from patient to patient, with reduced left ventricular ejection fraction being the most prominent risk stratifier. This topic will focus on the prevention and treatment of ventricular arrhythmias during and immediately after acute MI. The incidence, mechanisms, and clinical features of ventricular arrhythmias during acute MI, as well as treatment of ventricular arrhythmias late post-MI (using defibrillation with or without antiarrhythmic medications) is discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 1/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate PREVENTION Frequent ventricular premature beats (VPBs), VT, and ventricular fibrillation (VF) are all associated with increased long-term mortality following acute MI. An acute MI may be an ST- segment elevation MI (STEMI) or non-ST-segment elevation MI (NSTEMI). Most of the data available are in patients with a STEMI. While the data may also apply to patients with an NSTEMI, information in these patients is more limited. The following is a summary of the multi-modality approach to prevention of ventricular arrhythmias following MI (STEMI), which includes treatment of ischemia, electrolyte supplementation (if needed), and beta blockers. Treatment of symptomatic arrhythmias (should they arise) is discussed elsewhere. (See 'Treatment' below.) Revascularization/treatment of myocardial ischemia Patients with ventricular arrhythmias, especially polymorphic VT, in the setting of an acute MI should receive aggressive treatment for both the arrhythmia and myocardial ischemia. Therapy for ischemia usually includes drugs (eg, beta blockers, nitrates) and in most cases primary percutaneous coronary intervention or far less frequently, coronary artery bypass grafting for revascularization [1]. Fibrinolytic therapy is also effective but is used infrequently and generally only when PCI is not immediately available. The acute and long-term treatments of ischemic heart disease are discussed in detail separately. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".) Electrolyte supplementation In the post-MI setting, we maintain levels of serum potassium 4 mEq/L and serum magnesium 2 mg/dL. The dose and route of potassium and/or magnesium are discussed elsewhere. (See "Clinical manifestations and treatment of hypokalemia in adults" and "Hypomagnesemia: Evaluation and treatment".) Hypokalemia is a risk factor for VF in the setting of an acute MI, and concomitant hypomagnesemia, which is detected in approximately 40 percent of cases of hypokalemia, prevents the correction of hypokalemia [2]. In the GISSI-2 trial, the likelihood of VF among patients with a serum potassium <3.6 mEq/L was almost twice as high as among patients with a higher serum potassium (odds ratio 1.97) [3]. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Ventricular fibrillation'.) The MAGIC trial showed no benefit to empiric magnesium supplementation in acute MI patients [4]. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 2/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Beta blockers Oral beta blockers are administered universally to all patients without contraindications who experience an acute MI [5]. In addition to other beneficial effects, the immediate administration of a beta blocker during an acute MI reduces the risk of VF. In a systematic review, the overall mortality in 31 long-term trials that included almost 25,000 patients was 9.7 percent; beta blockers reduced the odds of death by 23 percent (95% CI 15-31 percent) [6]. These benefits are seen following both STEMI and NSTEMI ( figure 1) [7]. The details of beta blocker use are discussed separately. (See "Acute myocardial infarction: Role of beta blocker therapy".) Beta blockers are of use as the etiology of ventricular arrhythmia in the early or acute stages of an MI is in part related to enhanced automaticity, resulting from elevated catecholamines and beta receptor stimulation. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) Antiarrhythmic drugs We do not administer prophylactic antiarrhythmic agents in the post- infarction period. The prophylactic administration of class IC antiarrhythmic agents (eg, encainide, flecainide) in the post-MI period is associated with increased mortality and is not recommended [8- 10]. Due to the suggestion of possible harm and unsure benefit, the routine prophylactic administration of lidocaine in the acute MI period is not recommended [11]. Unlike the other antiarrhythmic drugs, prophylactic amiodarone is not associated with an increase in mortality. However, its unselected use in all patients does not appear to improve outcomes. As such, we do not administer prophylactic amiodarone in the post-MI period. The use of these agents is reserved for patients with documented ventricular tachyarrhythmias. (See 'Treatment' below.) Heart failure therapy Although not considered antiarrhythmic drugs, angiotensin converting enzyme (ACE) inhibitors, aldosterone antagonists, angiotensin II receptor blockers (ARBs), and combination ARB and neprilysin inhibitor all reduce the incidence of SCD in patients with heart failure (HF). Reduced SCD rates have been reported specifically in post-MI populations with ACE inhibitors and aldosterone antagonists, and in a broader population of HF patients, approximately 50 percent of whom had a prior infarction, with an ARB. These topics are discussed separately. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials", section on 'Effect on sudden death'.) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 3/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Wearable defibrillator for primary prevention Among patients with left ventricular ejection fraction (LVEF) 35 percent who are less than 40 days post-MI, we discuss the potential benefits and risks of wearable cardioverter-defibrillator (WCD) use ( picture 1) and consider providing it to motivated patients with NYHA functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for implantable cardioverter-defibrillator (ICD) implantation after 40 days. However, one study has not shown improvement in mortality in such patients as a result of WCD use [12]. In another analysis of this trial, it was reported that the lack of benefit might be in part related to poor compliance among patients prescribed the WCD [13]. The role of the WCD is discussed in detail separately. (See "Wearable cardioverter-defibrillator".) TREATMENT Ventricular premature beats In the post-MI patient with ventricular premature beats (VPBs) that cause significant or disabling symptoms (eg, palpitations, lightheadedness), beta blockers are administered, although most patients will already be taking them. In the rare circumstance that more aggressive antiarrhythmic therapy is considered for control of refractory symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm, although there is an appreciable incidence of side effects with long-term amiodarone therapy. Mexiletine, which is a class IB agent that resembles lidocaine, also appears safe in the post-MI patient, and although there are no randomized trials in this population, it may be effective for arrhythmia suppression [14,15]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) There is no role for chronic antiarrhythmic drug therapy to suppress asymptomatic VPBs. (See 'Prevention' above.) VPBs, particularly if frequent (more than 10 per hour) or complex (ie, couplets or non-sustained ventricular tachycardia) appear to be associated with a worse prognosis in patients with a prior MI. Based upon this association, trials of both class I and class III antiarrhythmic medications were conducted to determine if suppression of ventricular ectopy would reduce SCD. Patients with frequent asymptomatic VPBs post-MI were randomly assigned to receive suppressive antiarrhythmic therapy or placebo in an effort to suppress the ectopy [8,9]. The CAST study, which randomly assigned patients to treatment with encainide, flecainide, moricizine, or placebo, was prematurely terminated when it was noted that, despite suppression of VPBs, total mortality among the patients receiving encainide and flecainide was significantly increased compared with those on placebo (7.7 versus 3.0 percent); this was due primarily to an excess in arrhythmic deaths ( figure 2). https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 4/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate The CAST II study, which limited treatment to moricizine or placebo, was also terminated early due to an increased risk of death or cardiac arrest in the first 14 days of therapy among patients treated with moricizine (2.6 versus 0.5 percent with placebo) [9]. The CAMIAT study, which randomly assigned patients with frequent ( 10 per hour) or repetitive VPBs to amiodarone or placebo (approximately 60 percent were also treated with a beta blocker), showed that although arrhythmia suppression was more common with amiodarone (84 versus 35 percent with placebo), there was no significant difference in yearly all-cause or cardiac mortality (4.0 versus 5.2 percent) [16]. Nonsustained VT For patients with symptomatic (eg, palpitations, lightheadedness) nonsustained ventricular tachycardia (NSVT) after an MI, beta blockers are administered, although most patients should already be taking them. If antiarrhythmic drug therapy is considered due to persistent symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm, although there is an appreciable incidence of side effects with long-term amiodarone therapy. An alternative agent is mexiletine as it is safe and has been found to be effective for arrhythmia suppression in other groups of patients [14,15]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) In the absence of data specific to patients with NSVT, we do not prescribe chronic antiarrhythmic drug therapy to suppress asymptomatic NSVT. The presence of NSVT in post-MI patients with an LVEF 40 percent is an indication for further risk stratification, if the patient does not already meet criteria for ICD placement (LVEF 30 percent without heart failure symptoms, or LVEF 35 percent with NYHA class II or III heart failure). Electrophysiologic testing prior to hospital discharge may be appropriate in patients with late NSVT (ie, more than 24 to 48 hours into acute MI). (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) The development of NSVT one week or later post-MI carries at least a twofold increase in the risk of SCD [17]. The risk of NSVT is even further increased in post-MI patients with significantly diminished LV function (LVEF less than 40 percent). In this setting, the risk of SCD is increased more than fivefold [17,18]. Large randomized trials of antiarrhythmic drugs limited to patients with NSVT have not been performed. However, many of the patients included in the CAST and CAMIAT (39 percent) trials had NSVT. These trials showed an increased mortality in patients treated with class IC antiarrhythmic medications [8] and no significant reduction in overall mortality with amiodarone [16]. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 5/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Accelerated idioventricular rhythm An accelerated idioventricular rhythm (AIVR), which has also been called "slow VT," arises below the atrioventricular (AV) node and has, by definition, a rate between 50 and 100 beats/minute ( waveform 1). Most episodes are transient, benign, and require no treatment. Furthermore, pharmacologic therapy is contraindicated if there is complete heart block and an escape ventricular rhythm (which is not actually AIVR), since suppression of the pacemaker focus can result in profound bradycardia and possibly asystole. AIVR is most often seen in the peri-infarction period. AIVR often occurs after reperfusion therapy (PCI or fibrinolytic therapy) and is felt to be a reperfusion arrhythmia. It is likely the result of enhanced automaticity of ectopic foci in the ventricular myocardium. AIVR occurring after the peri-infarction period is uncommon. When it occurs, reversible causes should be sought such as digitalis toxicity, hypokalemia, or hypomagnesemia. There are no convincing data linking AIVR to sustained VT, ventricular fibrillation (VF), or a worse prognosis. Thus, no therapy is warranted for asymptomatic arrhythmias, while symptomatic arrhythmias can be treated with a beta blocker (if the patient is not already receiving this therapy), antiarrhythmic drugs, or perhaps ablation. Polymorphic VT Polymorphic VT associated with a normal QT interval is an uncommon arrhythmia following an acute MI ( waveform 2 and waveform 3). When it occurs, it is often associated with signs or symptoms of recurrent or ongoing myocardial ischemia [19]. Even if there are no signs or symptoms of myocardial ischemia, underlying myocardial ischemia is the most likely etiology. If polymorphic VT lasts for more than 8 to 10 seconds, it often degenerates into VF. This type of polymorphic VT generally fails to respond to class I antiarrhythmic drugs, magnesium, or overdrive pacing but may respond to intravenous amiodarone or lidocaine [19]. In patients treated with primary percutaneous coronary intervention who then manifest polymorphic ventricular tachycardia , revisualization of the coronary arteries is frequently warranted. An intraaortic balloon pump or other mechanical unloading therapy may help stabilize these patients. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Polymorphic VT'.) Revascularization has traditionally been considered to be adequate therapy for polymorphic VT due to ischemia in the absence of acute MI. However, more recent data suggest that ICD implantation in addition to revascularization may be optimal [20]. There is a second form of polymorphic VT that develops during the healing phase (at 3 to 11 days) and occurs in association with QT prolongation [21]. This arrhythmia resembles an acquired long QT syndrome and is treated in a similar fashion. One report of eight such patients found that defibrillation (if the arrhythmia is sustained), magnesium, lidocaine, beta blockers, and rapid overdrive pacing were effective therapies [21]. Mexiletine, which is similar to lidocaine https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 6/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate but is an oral medication, may be of benefit. In general, the QT interval shortened within 10 days, and long-term outcomes were uneventful. More commonly, polymorphic VT results from either acquired or congenital long QT interval and in this situation it is called torsades de pointes. Acquired QT prolongation may result from class IA or class III antiarrhythmic drugs, which can prolong the QT interval. An exception is amiodarone, which rarely produces torsades de pointes when used alone. Amiodarone should be discontinued if the burden of polymorphic VT increases, which is a possible sign of proarrhythmia. Many other drugs, including antibiotics, psychotropic agents, antihistamines, and GI medications may prolong the QT interval. Magnesium supplementation may be of benefit, even in the absence of hypomagnesemia. Bradycardia frequently facilitates the initiation of torsades de pointes VT in a susceptible patient with drug-induced QT prolongation as the QT interval lengthens further with slower heart rates. Increasing the heart rate, as with temporary pacing, may help prevent recurrent episodes. Although increasing the heart rate with intravenous isoproterenol or dobutamine may also be effective, this should be done with caution in the patient with an acute myocardial infarction. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes" and "Temporary cardiac pacing", section on 'Indications'.) Sustained monomorphic VT and VF Unstable, poorly-tolerated arrhythmias are a life- threatening emergency that are treated according to established advanced cardiac life support (ACLS) protocols [22]. VF is almost universally lethal if not treated. VF does not self-terminate nor does it revert with antiarrhythmic drugs. Defibrillation (nonsynchronized delivery of a shock) is the definitive therapy for VF. If available, a biphasic waveform defibrillator is preferable since the success rate for defibrillation is higher than with monophasic waveforms. The 2015 American Heart Association (AHA) guidelines for adult ACLS recommended that, for biphasic defibrillators, the initial shock should be at 120 to 200 joules, with subsequent shocks at the highest available biphasic energy level (200 joules for most devices) [22]. For monophasic defibrillators, nonescalating shocks beginning at 360 joules should be used. (See "Advanced cardiac life support (ACLS) in adults" and "Basic principles and technique of external electrical cardioversion and defibrillation".) Hemodynamically unstable or pulseless sustained monomorphic VT (SMVT) without identifying a distinct QRS should be treated with unsynchronized electrical shocks (ie, defibrillation and not cardioversion, which is the delivery of an electrical shock synchronized to the QRS complex). If available, a biphasic waveform defibrillator is preferable since the success rate for defibrillation is higher than with monophasic https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 7/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate waveforms. For biphasic defibrillators, the initial shock should be at 120 to 200 joules, with subsequent shocks at the highest available biphasic energy level (200 joules for most devices). For monophasic defibrillators, nonescalating shocks beginning at 360 joules should be used. (See "Cardioversion for specific arrhythmias", section on 'Ventricular tachycardia'.) SMVT (in which a distinct QRS complex can be identified) associated with angina, pulmonary edema, or hypotension (systolic blood pressure <90 mmHg) should be treated immediately with synchronized electrical cardioversion using an initial energy of 50 to 100 joules. Subsequent shocks at increasing energy can be given as necessary. Brief anesthesia is desirable if hemodynamically tolerable. SMVT that is hemodynamically tolerated and asymptomatic can be treated initially with intravenous amiodarone (or lidocaine or procainamide). Synchronized electrical cardioversion with brief anesthesia should be performed if VT persists after the administration of the initial 150 mg of amiodarone (or 100 to 300 mg of lidocaine). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Stable patients' and "Cardioversion for specific arrhythmias", section on 'Ventricular tachycardia'.) Recurrent nonsustained and sustained VT, particularly polymorphic, should trigger consideration of investigation for ischemia, possibly (but not always) involving the infarct- related artery. (See 'Revascularization/treatment of myocardial ischemia' above.) Patients who manifest sustained VT or polymorphic VT more than 24 to 48 hours after acute MI should generally undergo ICD implantation prior to hospital discharge. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) The acute and long-term management of SMVT and VF in patients with a prior MI are discussed in detail separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Electrical storm Electrical storm is defined as multiple recurrent episodes of VF. The optimal therapy of electrical storm in patients with an acute MI is uncertain but is likely no different than in patients with electrical storm in any setting and includes defibrillation, antiarrhythmic medications, beta blockers, treatment of myocardial ischemia, and long-term therapies to prevent recurrent arrhythmias (eg, catheter ablation, cardiac sympathetic denervation, etc). (See "Electrical storm and incessant ventricular tachycardia".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 8/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST- elevation myocardial infarction (STEMI)" and "Society guideline links: Ventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Ventricular fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS Revascularization Patients with ventricular arrhythmias, especially polymorphic VT, in the setting of an acute MI should receive aggressive treatment for both the arrhythmia and myocardial ischemia. Therapy for ischemia usually includes drugs (eg, beta blockers, nitrates) and either primary percutaneous coronary intervention or coronary artery bypass grafting for revascularization. (See 'Revascularization/treatment of myocardial ischemia' above.) Preventive therapies Other therapies that reduce ventricular arrhythmias during and immediately after acute MI include maintaining levels of serum potassium 4.0 mEq/L and https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 9/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate serum magnesium 2.0 mg/dL, administering beta blockers, and appropriate therapies for heart failure, when present. (See 'Prevention' above.) Antiarrhythmic drugs The prophylactic administration of antiarrhythmic agents to asymptomatic patients during and immediately after acute MI has at best no benefit and potentially can cause harm. The use of these agents is reserved for patients with documented ventricular tachyarrhythmias. (See 'Antiarrhythmic drugs' above and 'Treatment' above.) Ventricular premature beats In the post-MI patient with ventricular premature beats or nonsustained VT that cause significant or disabling symptoms (eg, palpitations, lightheadedness), beta blockers are administered, although most patients will already be taking them. In the rare circumstance that more aggressive antiarrhythmic therapy is considered for control of refractory symptoms, we prefer amiodarone, as it is likely to be effective and unlikely to cause significant harm. (See 'Ventricular premature beats' above.) Accelerated idioventricular rhythm Most episodes of accelerated idioventricular rhythm (AIVR) are transient, benign, and require no treatment. Furthermore, pharmacologic therapy is contraindicated if there is complete heart block and an escape ventricular rhythm (which is not actually AIVR), since suppression of the pacemaker focus can result in profound bradycardia and possibly asystole. (See 'Accelerated idioventricular rhythm' above.) Polymorphic VT This is associated with a normal QT interval, is an uncommon arrhythmia, and is often associated with signs or symptoms of recurrent or ongoing myocardial ischemia, in which case revisualization of the coronary arteries is usually warranted. Polymorphic VT that results from acquired long QT interval is called torsades de pointes and is usually related to medications. (See 'Polymorphic VT' above.) Poorly-tolerated arrhythmias Sustained monomorphic VT or VF is a life-threatening emergency that is treated according to established advanced cardiac life support (ACLS) protocols. (See "Advanced cardiac life support (ACLS) in adults" and 'Sustained monomorphic VT and VF' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 10/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 2. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 1992; 152:40. 3. Volpi A, Cavalli A, Santoro L, Negri E. Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database. Am J Cardiol 1998; 82:265. 4. Magnesium in Coronaries (MAGIC) Trial Investigators. Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 2002; 360:1189. 5. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O'Gara PT, et al. 2013 ACCF/AHA guideline for the management of ST- elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61:e78. 6. Freemantle N, Cleland J, Young P, et al. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318:1730. 7. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998; 339:489. 8. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781. 9. Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992; 327:227. 10. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA 1993; 270:1589. 11. Sadowski ZP, Alexander JH, Skrabucha B, et al. Multicenter randomized trial and a systematic https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 11/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate overview of lidocaine in acute myocardial infarction. Am Heart J 1999; 137:792. 12. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable Cardioverter-Defibrillator after Myocardial Infarction. N Engl J Med 2018; 379:1205. 13. Olgin JE, Lee BK, Vittinghoff E, et al. Impact of wearable cardioverter-defibrillator compliance on outcomes in the VEST trial: As-treated and per-protocol analyses. J Cardiovasc Electrophysiol 2020; 31:1009. 14. Stein J, Podrid PJ, Lampert S, et al. Long-term mexiletine for ventricular arrhythmia. Am Heart J 1984; 107:1091. 15. Mendes L, Podrid PJ, Fuchs T, Franklin S. Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia. J Am Coll Cardiol 1991; 17:1396. 16. Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349:675. 17. Bigger JT Jr, Fleiss JL, Rolnitzky LM. Prevalence, characteristics and significance of ventricular tachycardia detected by 24-hour continuous electrocardiographic recordings in the late hospital phase of acute myocardial infarction. Am J Cardiol 1986; 58:1151. 18. Mukharji J, Rude RE, Poole WK, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol 1984; 54:31. 19. Wolfe CL, Nibley C, Bhandari A, et al. Polymorphous ventricular tachycardia associated with acute myocardial infarction. Circulation 1991; 84:1543. 20. Natale A, Sra J, Axtell K, et al. Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: does bypass surgery suffice? J Cardiovasc Electrophysiol 1994; 5:988. 21. Halkin A, Roth A, Lurie I, et al. Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome. J Am Coll Cardiol 2001; 38:1168. 22. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. Topic 118996 Version 15.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 12/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate GRAPHICS Beta blockers are equally effective after a Q wave or non-Q wave MI Analysis of data from 201,752 patients with a myocardial infarction (MI) demonstrates that the reduction in mortality at two years with beta blockers is similar in those with a Q wave (14.2 versus 23.6 percent for those not receiving beta blockers) or non-Q wave MI (14.4 versus 23.9 percent). Data from Gottlieb SS, McCarter RJ, Vogel RA. N Engl J Med 1998; 339:489. Graphic 79592 Version 2.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 13/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Wearable cardioverter-defibrillator The wearable cardioverter-defibrillator consists of a vest incorporating two defibrillation electrodes and four sensing electrocardiographic electrodes connected to a waist unit containing the monitoring and defibrillation electronics. Reproduced with permission from: ZOLL Medical Corporation. Copyright 2012. All rights reserved. Graphic 60103 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 14/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Encainide and flecainide increase cardiac mortality Results of the Cardiac Arrhythmia Suppression Trial (CAST) in patients with ventricular premature beats after myocardial infarction. Patients receiving encainide or flecainide had, when compared with those receiving placebo, a significantly lower rate of avoiding a cardiac event (death or resuscitated cardiac arrest) (left panel, p = 0.001) and a lower overall survival (right panel, p = 0.0006). The cause of death was arrhythmia or cardiac arrest. Data from Echt DS, Liebson PR, Mitchell B, et al. N Engl J Med 1991; 324:781. Graphic 59975 Version 5.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 15/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 16/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG_1 showing polymorphic ventricular tachycardia in ischemia Continuous rhythm strip revealing several episodes of nonsustained ventricular tachycardia (VT) occurring during an acute ischemic event. The QRS complexes are variable in morphology and RR intervals; thus, the VT is polymorphic. The QT interval is normal. This form of VT should be distinguished from torsade de pointes in which polymorphic VT is associated with QT interval prolongation. Graphic 54538 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 17/19 7/6/23, 3:34 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate ECG_2 showing polymorphic ventricular tachycardia in ischemia Continuous rhythm strip showing an episode of very rapid polymorphic ventricular tachycardia which is often referred to as ventricular flutter. The QT interval is normal and the QRS complex morphology is highly variable. The patient had an underlying sinus tachycardia, suggesting increased sympathetic activity secondary to an ischemic event. Graphic 67322 Version 3.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 18/19 7/6/23, 3:35 PM Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-arrhythmias-during-acute-myocardial-infarction-prevention-and-treatment/print 19/19 |
7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular arrhythmias during pregnancy : Louise Harris, MBChB, Sing-Chien Yap, MD, PhD, Candice Silversides, MD, MS, FRCPC : Hugh Calkins, MD, Heidi M Connolly, MD, FACC, FASE : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 01, 2022. INTRODUCTION Arrhythmias are the most common cardiac complication encountered during pregnancy in women with and without structural heart disease [1-3]. In the United States, the incidence of pregnancy-related hospitalizations with arrhythmias has increased between 2000 and 2012 primarily due to increases in the incidence of atrial fibrillation and ventricular tachycardia [4]. Arrhythmias may manifest for the first time during pregnancy, or pregnancy can trigger exacerbations in women with known preexisting arrhythmias [1,5-7]. The prevalence, clinical presentation and management of ventricular arrhythmias will be reviewed. Cardiac arrest during pregnancy, general management of ventricular arrhythmias and cardiac arrest, electrocardiographic (ECG) characteristics of ventricular arrhythmias, and issues relating to supraventricular arrhythmias during pregnancy are discussed in detail elsewhere. (See "Sudden cardiac arrest and death in pregnancy" and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Advanced cardiac life support (ACLS) in adults" and "ECG tutorial: Ventricular arrhythmias" and "Supraventricular arrhythmias during pregnancy" and "Wide QRS complex tachycardias: Approach to management".) GENERAL APPROACH Women with established arrhythmias or structural heart disease are at highest risk of developing arrhythmias during pregnancy. Due to surgical advances, the number of women of childbearing age with congenital heart disease has increased and this group of women is at https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 1/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate particularly high risk for arrhythmias ( figure 1) [1,2,8-12] (see "Pregnancy in women with congenital heart disease: General principles"). Since arrhythmias are frequently associated with acquired or structural heart disease, any woman who presents with an arrhythmia during pregnancy should undergo clinical evaluation for structural heart disease (including an ECG and a transthoracic echocardiogram). (See 'VT in women with structural heart disease' below.) In general, the approach to the treatment of arrhythmias in pregnancy is similar to that in the non-pregnant patient. However, due to the theoretical or known adverse effects of antiarrhythmic drugs on the fetus, antiarrhythmic drugs are generally reserved for the treatment of arrhythmias associated with significant symptoms or hemodynamic compromise [13-15]. Treatment strategies during pregnancy are hampered by the lack of randomized trials in this cohort of women. Choice of therapy, for the most part, is based on limited data from animal studies, case reports, observational studies, and clinical experience. Use of antiarrhythmic drugs in pregnancy requires attention to potential alterations in pharmacokinetics as well as fetal risk. For most antiarrhythmic drugs, adequate and well- controlled studies in pregnant women are lacking, and therefore potential risks cannot be ruled out [16,17]. Another consideration is potential adverse effects in the infant during breastfeeding ( table 1). Antiarrhythmic drug safety during pregnancy, teratogenic risk, pharmacokinetic changes, and breastfeeding are discussed further separately. (See "Supraventricular arrhythmias during pregnancy", section on 'Issues regarding antiarrhythmic drug treatment'.) MECHANISM OF ARRHYTHMOGENESIS IN PREGNANCY The exact mechanism of increased arrhythmia burden during pregnancy is unclear but has been attributed to hemodynamic, hormonal, and autonomic changes related to pregnancy. The hemodynamic changes of pregnancy have been well studied and these changes likely contribute to the development of arrhythmias during pregnancy [18,19]. Intravascular volume increases, augmenting the preload on the ventricles, and increasing both atrial and ventricular size [18,20-23]. Atrial and ventricular myocardial stretch may contribute to arrhythmogenesis due to stretch-activated ion channel activity causing membrane depolarization, shortened refractoriness, slowed conduction, and spatial dispersion of refractoriness and conduction [24- 27]. There is also an increase in resting heart rate that has been associated with markers of arrhythmogenesis such as late potentials, premature ventricular contractions, and depressed heart rate variability [28]. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 2/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Few studies have been published on the influence of hormonal and autonomic changes on arrhythmogenesis in pregnancy. Although catecholamine levels do not appear to change during pregnancy, there is an increase in adrenergic responsiveness during pregnancy [29-33]. Estrogen has been shown to increase the number of myocardial alpha-adrenergic receptors [34]. This increased adrenergic activity may contribute to enhanced automaticity and triggered activity [35]. (See "Enhanced cardiac automaticity".) PALPITATIONS Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. The differential diagnosis of palpitations is extensive and the diagnostic evaluation of pregnant women with palpitations does not differ from nonpregnant women. (See "Evaluation of palpitations in adults".) One study compared 110 pregnant women with symptoms suggestive of possible arrhythmia (palpitations: 87 percent; dizziness: 13 percent; syncope/presyncope: 6 percent) with 52 pregnant women evaluated for an asymptomatic functional murmur [36]. Prevalence of supraventricular and ventricular ectopic activity on 24-hour Holter ambulatory monitoring was similar in the symptomatic and control groups. Only 10 percent of symptomatic episodes were accompanied by the presence of an arrhythmia [36]. A sensation of palpitations during pregnancy in the absence of concomitant cardiac arrhythmias may be related to the high output state, including increased heart rate, decreased peripheral resistance, and increased stroke volumes. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".) PREMATURE VENTRICULAR COMPLEX/CONTRACTION Premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) is frequently detected in pregnant women. The prevalence is dependent upon the duration of observation and the clinical presentation. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation".) In the above referenced study of 110 symptomatic and 52 asymptomatic pregnant women, the prevalence of isolated PVCs was similar in symptomatic and asymptomatic women (49 versus 40 percent) [36]. However, frequent PVCs ( 50 PVCs per 24 hours) were more common in symptomatic women (22 versus 4 percent). There was a significant reduction in the frequency of https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 3/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate combined atrial and ventricular ectopic activity in the nine women in whom Holter monitoring was repeated postpartum. Clinical presentation PVCs produce few or no symptoms in the majority of women, although some women may experience symptoms of palpitations or dizziness. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Clinical presentation and ECG findings'.) Management during pregnancy The management of PVCs in pregnancy is discussed separately. (See "Premature ventricular complexes: Treatment and prognosis", section on 'Pregnancy'.) VENTRICULAR TACHYARRHYTHMIAS Ventricular tachyarrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF]) are rare during pregnancy [37]. The management of ventricular arrhythmias needs to be tailored to the individual. The following are among the clinical factors that should be considered: Etiology of the VT (catecholamine sensitive versus noncatecholamine sensitive) Frequency and duration of VT (nonsustained versus sustained) Severity of associated symptoms Presence and severity of underlying heart disease Ventricular function Causes VT can be seen in pregnant women without apparent structural heart disease [38-40] but is often associated with structural heart disease. The risk of recurrent VT during pregnancy is particularly high (27 percent) in women with structural heart disease and a history of VT [7]. Types of cardiac disease associated with VT in pregnancy include: Hypertrophic cardiomyopathy (HCM) [1,7,41,42] Peripartum cardiomyopathy [43,44] Arrhythmogenic right ventricular cardiomyopathy [45-50] Congenital heart disease [1,7,51-53] Valvular heart disease [1] Primary electrical disease (eg, long QT syndrome [LQTS] [54,55], Brugada syndrome [56], catecholaminergic polymorphic VT [CPVT] [57], etc) Myocardial infarction with or without coronary artery disease has been observed during pregnancy [58-63] and may be complicated by VT or VF [61,62]. Women with primary electrical https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 4/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate diseases are also at risk of VT. Other medical conditions associated with VT during pregnancy are hypomagnesemia [64-66], hypertensive crises [67,68], and thyrotoxicosis [69]. (See "Significance of hypomagnesemia in cardiovascular disease" and "Gestational hypertension" and "Overview of thyroid disease and pregnancy" and "Cardiovascular effects of hyperthyroidism".) Idiopathic VT Monomorphic VT without apparent structural heart disease is considered idiopathic. The most common type of idiopathic VT is repetitive monomorphic VT, which usually originates from the right ventricular outflow tract (ECG "signature": left bundle branch block and inferior axis) or, less often, from the left ventricular outflow tract (ECG pattern: right bundle branch block and inferior axis or left bundle and inferior axis but earlier precordial transition than for right ventricular outflow tract tachycardia). Another type is idiopathic left VT, which originates from the inferior aspect of the midseptum and has the morphologic pattern of right bundle branch block with left axis deviation (QRS axis around -60 ). (See "Ventricular tachycardia in the absence of apparent structural heart disease" and "Nonsustained VT in the absence of apparent structural heart disease".) A study of seven women presenting with new-onset idiopathic VT during pregnancy found that the VT was often catecholamine sensitive and that the VT was often suppressed in women who received beta blockers [39]. There were no maternal or fetal complications in this series. There is one case report of sudden death in a woman with idiopathic VT who died in the third trimester, three weeks after initiation of procainamide therapy [70]. Management during pregnancy Idiopathic VT rarely degenerates into an unstable rhythm and usually has a benign prognosis [39,71]. Treatment of repetitive monomorphic VT with cardioselective beta blockers may be effective in pregnant women with idiopathic VT even in the absence of a clear relationship to adrenergic tone [39,71-75]. Sotalol can be used as an alternative. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Treatment of RMVT'.) The less common idiopathic left VT appears to respond well to verapamil, both for the termination of acute episodes and the prevention of recurrences [76,77]. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Treatment of ILVT'.) Long QT syndrome Although VT during pregnancy has been reported in women with LQTS [78], the increase in heart rate seen during pregnancy may serve to shorten the QT interval and therefore may be partially protective. In women with LQTS, the risk of VT is especially high in the postpartum period [55]. Increased risk of VT during the postpartum period may be related to a https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 5/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate decrease in the heart rate and an associated increase in the QT interval. The physiologic stress and altered sleep patterns associated with caring for a newborn infant may also contribute to an increase in adrenergically mediated cardiac events. The effect of pregnancy was evaluated in a retrospective analysis of 422 women (111 probands and 311 first-degree relatives) entered into the International LQTS registry [55]. Most of the probands had a personal history of syncope or aborted cardiac arrest. The following findings were noted: Probands were significantly more likely to have cardiac events (syncope, aborted cardiac arrest, or sudden cardiac death) in the 40-week postpartum interval than during the prepregnancy period of 40 weeks (23.4 versus 3.8 percent). The increase in risk was distributed throughout the postpartum period. The incidence of first cardiac events during pregnancy was slightly but not significantly increased compared with the prepregnancy period (9.0 versus 3.8 percent). The postpartum increase in risk also applied to first cardiac events (9.0 versus 1.8 and 0 percent during and before pregnancy). Treatment with beta blockers was independently associated with a decrease in risk for cardiac events in probands during all three intervals (odds ratio 0.023). The average probability of having a cardiac event during the postpartum period in probands was 2 percent (1 in 50 pregnancies). Treatment with a beta blocker lowered the risk to 1 in 2500 pregnancies. The risks associated with pregnancy may be different among various LQTS genotypes (see "Congenital long QT syndrome: Epidemiology and clinical manifestations", section on 'Influence of genotype on triggers'). The influence of genotype is illustrated by the following observations: In a series of 388 LQTS patients referred for genetic testing, postpartum cardiac events were more commonly reported in patients with LQT2 mutation (13 of 80, 16 percent) than in patients with LQT1 (1 of 103, <1 percent). [79]. In a series limited to women with a single LQT1 mutation, cardiac event rates associated with pregnancy were low (2.6 percent) [80]. These events occurred only in women with a prior history of symptoms who were not taking beta blockers. Management during pregnancy We agree with the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death and the 2011 https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 6/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate European Society of Cardiology guidelines on the management of cardiovascular diseases during pregnancy. The guidelines recommended that pregnant women with LQTS who have had symptoms benefit from continued beta blocker therapy throughout pregnancy and postpartum, unless there are definite contraindications [81,82]. Brugada syndrome There are limited reports of pregnancies in women with Brugada syndrome. In one retrospective single-center study including 104 women (219 deliveries) with Brugada syndrome, six women (6 percent) experienced recurrent syncope during pregnancy [83]. Five women continued to experience syncope after delivery and four women received an implantable cardioverter-defibrillator (ICD), as syncope is regarded a high-risk feature for ventricular arrhythmias. No serious events were reported during the peripartum period. In three women with Brugada syndrome and an ICD, no noteworthy problems were reported during pregnancy. There is one case report of electrical storm during pregnancy [56]. The use of low- dose isoproterenol infusion followed by oral quinidine has been used to treat VT and normalize the ECG [56]. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'High-risk patients'.) Catecholaminergic polymorphic ventricular tachycardia One retrospective study from the Netherlands and Canada evaluated the outcome of pregnancy in 96 women with CPVT who had 228 pregnancies [57]. Most patients (82 percent) had pregnancies before CPVT diagnosis (median age at CPVT diagnosis 40.7 years). Pregnancy and postpartum cardiac events included syncope (5 percent) and an aborted cardiac arrest (1 percent), which occurred in women who were not taking beta blockers. The combined pregnancy and postpartum arrhythmic risk (2.14 events per 100 patient-years) was not elevated compared with the nonpregnant period (1.46 events per 100 patient-years). VT in women with structural heart disease A large prospective multicenter study in women with heart disease reported four cases of sustained VT in 1315 pregnancies [84]. Causes Hypertrophic cardiomyopathy In general, women with HCM tolerate pregnancy well [42,85], although several case reports have described cardiac complications and sudden death during pregnancy [41,42,86-88]. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Pregnancy'.) The largest study investigating mortality and morbidity in pregnant women with HCM included 100 women who had a total of 199 live births [42]. Two sudden cardiac deaths occurred during pregnancy in women with high-risk features. One of the women had severe left ventricular hypertrophy (30 mm maximal wall thickness) and a resting outflow gradient of 115 mmHg. She https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 7/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate died suddenly four days after delivery after complaining of palpitations. The other woman had a family history of eight deaths in young relatives, five of which were sudden. This patient developed recurrent episodes of sustained VT during labor. The ROPAC registry examined outcomes in 60 pregnancies and reported a high prevalence of ventricular tachyarrhythmias (10 percent, 6 of 60 patients) [89]. Two of six patients with VT were known to have heart failure, and most cases occurred in the third trimester. Management of pregnancy and delivery in women with HCM is discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Pregnancy'.) Congenital heart disease The prevalence of sustained VT during pregnancy in women with congenital heart disease (CHD) has been reported to range from 4.5 to 15.9 per 1000 pregnancies [1,51] (see "Pregnancy in women with congenital heart disease: General principles" and "Pregnancy in women with congenital heart disease: Specific lesions"). Prevalence rates are strongly influenced by the types of cardiac lesions in the study population. In a prospective multicenter study in women with CHD, two cases of sustained VT occurred in 445 pregnancies. One woman had an unrepaired intracardiac shunt and the other had repaired congenital aortic stenosis [1]. A multicenter study from Japan reported two cases of sustained VT during 126 pregnancies [51]. Both cases of VT occurred in women with repaired tetralogy of Fallot and both were successfully treated with intravenous lidocaine. Seven pregnancies were complicated by nonsustained VT, none of which were treated. Peripartum cardiomyopathy Peripartum cardiomyopathy is a rare and sometimes life- threatening condition defined as development of systolic heart failure in the last month of pregnancy or within five months of delivery. The incidence varies widely among various populations. The clinical presentation includes symptoms of new-onset heart failure such as dyspnea, cough, orthopnea, and hemoptysis. A large retrospective study of 9841 hospitalizations for women with peripartum cardiomyopathy demonstrated a prevalence of VT of 4.2 percent [90]. These ventricular arrhythmias can be refractory to pharmacologic treatment (eg, lidocaine, metoprolol, amiodarone) and direct current cardioversion [43,44,91]. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis".) Arrhythmogenic right ventricular cardiomyopathy Most pregnancies in women with arrhythmogenic right ventricular cardiomyopathy are tolerated well [45-50,92]. Pregnancies were managed successfully by close monitoring and antiarrhythmic drugs when necessary. https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 8/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Data from the combined Johns Hopkins/Dutch ARVD/C registry provided information on 26 women during 39 pregnancies (>13 weeks) [93]. A single episode of sustained ventricular arrhythmia complicated five pregnancies (13 percent) of five women without a prior history of sustained ventricular arrhythmias. Interruption of beta blockers was associated with two of these events. Previous studies have shown that withdrawal of beta blockers during pregnancy may exacerbate the occurrence of VT during pregnancy [47,50]. Among a cohort of 120 Chinese women with 224 pregnancies between 1995 and 2018, adverse cardiac events were reported in only 12 pregnancies (5.4 percent), with only two episodes of syncope and one episode of sustained VT [92]. Eight of the 12 reported adverse events related to the development of, or increase in, PVC frequency. Management of VT during pregnancy in women with structural heart disease Management of acute episodes Acute treatment of sustained ventricular arrhythmias in pregnant women is similar to that in nonpregnant women. Ventricular arrhythmias in the presence of structural heart disease are potentially life-threatening and require immediate evaluation for hemodynamic instability to determine whether electrical cardioversion or defibrillation is indicated [81]. In hemodynamically well-tolerated VT, pharmacological cardioversion may be acceptable. Pharmacological options include intravenous procainamide, amiodarone, or lidocaine [81]; the choice of pharmacological agents should be tailored to the individual case. For women at risk for VT during labor and delivery, it is important to ensure that appropriate cardiac medications and external defibrillators are available in the delivery suites. Electrical cardioversion Urgent or elective electrical cardioversion can be performed at all stages of pregnancy [15,94-100]. Electrical cardioversion is indicated for any sustained VT with hemodynamic compromise [81] and can be considered for drug-refractory VT. Electrical cardioversion does not result in compromise of blood flow to the fetus [101]. While there is a theoretical risk of inducing an arrhythmia in the fetus, this risk is very small due to the high fibrillation threshold and small amount of energy reaching the fetus [15,94,102]. Nonetheless, fetal rhythm monitoring is recommended once viability is reached because of rare reported cases of cardioversion precipitating fetal distress and requiring emergency cesarean delivery [103]. Electrode placement is similar to the nonpregnant patient, but in order to maximize current, placement over breast tissue should be avoided. Shock outputs used should be similar to those recommended in the nonpregnant patient. (See "Basic principles and technique of external electrical cardioversion and defibrillation" and "Cardioversion for specific arrhythmias".) https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 9/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Prophylactic pharmacologic therapy during pregnancy The risk of recurrent VT and sudden death in women with structural heart disease can be substantial and the benefits of prophylactic drug therapy may outweigh the potential fetal adverse effects of these drugs (see "Overview of sudden cardiac arrest and sudden cardiac death"). The risk of sudden death is further increased when concomitant left ventricular dysfunction is present. Depending on the underlying cardiac condition, beta-1 selective beta blockers alone, antiarrhythmic drugs alone, or both in combination can be effective [81]. Gestational exposure to amiodarone is associated with neonatal hypothyroidism and hyperthyroidism. Small-for- gestational-age infants are reported with gestational exposure to the combination of amiodarone and beta blockers [104]. In some cases, sotalol can be considered if beta-blocker therapy is ineffective. Because of potential fetal side effects, all women should be counseled about the potential risks and benefits of drug therapy. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring" and "Amiodarone: Clinical uses".) Although some have used class IA (eg, quinidine, procainamide) or IC (eg, flecainide) drugs as prophylactic treatment for VT during pregnancy [105,106], these drugs are not generally recommended since they have not improved survival in the nonpregnant population with structural heart disease, presumably because of proarrhythmic effects [107]. Implantable cardioverter-defibrillator Women with an implantable cardioverter- defibrillator (ICD) can have a successful pregnancy with good fetal outcome [108-110]. Indications for ICD placement are discussed separately, but in general, pregnant women who have an indication for ICD should have the ICD implanted using strategies to minimize radiation during the procedure. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) In a retrospective multicenter study of pregnancy outcomes in women with ICDs (n = 44), 25 percent (11 of 44) of the pregnancies were complicated by at least one shock [108]. All ICDs were implanted for secondary prevention and the underlying cardiac diseases were primary electrical diseases (ie, LQTS, idiopathic VF) or structural heart diseases (ie, cardiomyopathy, congenital heart disease, arrhythmogenic right ventricular cardiomyopathy). Pregnancy was not associated with an increase in ICD-related complications or an increase in the number of shocks (0.07 versus 0.06 shocks per month) compared with the preconception period [108]. The experience with ICD implantation during pregnancy is limited [111]; however, pacemaker implantation during pregnancy can be accomplished and total radiation dose can be reduced by using echocardiographic guidance [112,113]. https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 10/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate For some women with potentially reversible risk factors for sudden death (eg, women with peripartum cardiomyopathy in whom ventricular function may improve), an external wearable automatic defibrillator (LifeVest) can be considered during pregnancy or early postpartum. Radiofrequency catheter ablation The success rate of radiofrequency catheter ablation of monomorphic VT is between 80 to 100 percent [114-118] and may be considered in women who are using antiarrhythmic therapy and are contemplating pregnancy (see "Overview of catheter ablation of cardiac arrhythmias"). Currently, there is only limited experience with catheter ablation of VT during pregnancy [119,120]. Most experience with radiofrequency catheter ablation during pregnancy has been for cases of supraventricular tachycardia [120-128]. These procedures are generally not performed during pregnancy, mainly due to concerns of ionizing radiation exposure to the fetus. However, in rare cases, women with severe and drug-resistant VT during pregnancy may be considered for an ablation procedure. The risk of radiation exposure for the fetus during a typical ablation is small (<1 mGy at all periods of gestation) and is mainly attributable to scatter from the thorax of the mother [129]. Ablation using intracardiac echocardiography and electroanatomic mapping without fluoroscopy may be an alternative. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Fetal risks'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Ventricular tachyarrhythmias are frequently associated with acquired or structural heart disease and therefore any woman who presents with a ventricular arrhythmia during pregnancy should undergo clinical evaluation for structural heart disease (including an ECG and a transthoracic echocardiogram). (See 'General approach' above and 'VT in women with structural heart disease' above.) Monomorphic ventricular tachycardia (VT) without apparent structural heart disease is considered idiopathic. The most common type originates from the right ventricular outflow tract, and this form of VT can often be successfully treated with beta blockers or verapamil. (See 'Idiopathic VT' above.) https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 11/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Women with the long QT syndrome are at risk for VT, especially in the postpartum period. Pregnant women with long QT syndrome should be treated with beta blocker therapy throughout pregnancy and postpartum. (See 'Long QT syndrome' above.) Acute treatment of sustained ventricular arrhythmias in pregnant women is similar to that in nonpregnant women. Ventricular arrhythmias in the presence of structural heart disease are potentially life-threatening and require immediate evaluation for hemodynamic instability to determine whether electrical cardioversion or defibrillation is indicated. (See 'Management of acute episodes' above.) In women with structural heart disease and a history of VT, the benefits of prophylactic drug therapy may outweigh the potential fetal adverse effects of these drugs. 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Topic 13601 Version 28.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 21/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate GRAPHICS Prevalence of arrhythmias during pregnancy in women with congenital heart disease AOS: aortic stenosis; ASD: atrial septal defect; AVSD: atrioventricular septal defect; CC-TGA: congenital corrected transposition of the great arteries; CHD: congenital heart disease; PAVSD: pulmonary atresia with ventricular septal defect; TGA: transposition of the great arteries; TOF: tetralogy of Fallot. Data from: Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007; 49:2303. Graphic 61986 Version 4.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 22/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Antiarrhythmic drugs in pregnancy Drug Pregnancy Breastfeeding Amiodarone Has been associated with serious adverse effects. Congenital goiter/hypothyroidism and hyperthyroidism can occur after in utero exposure. Other potential risks Not recommended because of potential risk of hypothyroidism in neonate. include prolonged QT interval in neonates. Beta blockers No evidence of increased risk of teratogenesis, but some (particularly atenolol) may impair fetal growth when used for a prolonged duration in the The AAP considers these agents compatible with breastfeeding, but newborns should be observed for signs of beta blockade. second and third trimesters. Use only Atenolol is a weak base that will accumulate in milk. Accumulation is in the third trimester is associated with reduced placental weight. enhanced by its water-soluble, low protein binding, little or no hepatic Newborns of patients taking these drugs near delivery are at risk of bradycardia, hypoglycemia, and other metabolism, and renal excretion properties. Because it has been symptoms of beta blockade. associated with beta-blocking effects and cyanosis in nursing infants, it is best avoided during breastfeeding. Among this class of drugs, atenolol appears to have the most unfavorable effect on birthweight. Sotalol Sotalol, which has both beta blocker Sotalol is concentrated in breast milk, and type III antiarrhythmic properties, is not teratogenic, and its use has not with milk levels several-fold higher than those in maternal plasma, so been associated with fetal growth close monitoring for bradycardia, restriction. Its use near birth has been associated with newborn bradycardia. hypotension, respiratory distress, and hypoglycemia is advised. Adenosine No evidence of increased risk of No information. Because of very short teratogenesis or increased risk of adverse fetal/neonatal effects. half-life, it is unlikely to have any adverse effects on the neonate. Digoxin No evidence of increased risk of The AAP considers digoxin compatible teratogenesis or increased risk of adverse fetal/neonatal effects. with breastfeeding. Verapamil No evidence of increased risk of The AAP considers verapamil teratogenesis or increased risk of adverse fetal/neonatal effects. compatible with breastfeeding. Procainamide No evidence of increased risk of The AAP classifies procainamide as teratogenesis or increased risk of compatible with breastfeeding. https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 23/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate adverse fetal/neonatal effects. However, the long-term effects of exposure in the nursing infant are unknown, particularly with respect to potential drug toxicity (eg, development of antinuclear antibodies and lupus-like syndrome). Quinidine No evidence of increased risk of The AAP considers quinidine teratogenesis. In therapeutic doses, the oxytocic properties of quinidine compatible with breastfeeding. have been rarely observed, but high doses can produce this effect and may result in preterm labor or abortion. Flecainide Developmental toxicity has been noted The AAP considers flecainide in animals, but there is limited information on human risk from early compatible with breastfeeding. pregnancy exposure. This risk appears to be low when used for refractory fetal arrhythmia. It may be the treatment of choice for tachycardia in hydropic fetuses. AAP: American Academy of Pediatrics. Adapted from: Briggs GG, Freeman RK, Ya e SJ. Drugs in Pregnancy and Lactation, 8th edition. Philadelphia: Lippincott Williams & Wilkins. Graphic 50716 Version 8.0 https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 24/25 7/6/23, 3:34 PM Ventricular arrhythmias during pregnancy - UpToDate Contributor Disclosures Louise Harris, MBChB No relevant financial relationship(s) with ineligible companies to disclose. Sing- Chien Yap, MD, PhD Grant/Research/Clinical Trial Support: Medtronic [Ventricular arrhythmias]. Consultant/Advisory Boards: Boston Scientific [Ventricular arrhythmias]. All of the relevant financial relationships listed have been mitigated. Candice Silversides, MD, MS, FRCPC No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Heidi M Connolly, MD, FACC, FASE No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-arrhythmias-during-pregnancy/print 25/25 |
7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy : Philip J Podrid, MD, FACC : Wilson S Colucci, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Ventricular arrhythmias, including premature ventricular complexes or beats, ventricular premature complexes or beats, ventricular tachycardia, and ventricular fibrillation, are common in patients with heart failure (HF) and cardiomyopathy, both ischemic and nonischemic in nature [1-3]. The etiology and types of arrhythmias, clinical presentation, diagnosis, and management of ventricular arrhythmias in patients with HF and/or cardiomyopathy will be reviewed here. The secondary and primary prevention of sudden cardiac death in these patients, including a review of the causes of death in HF, and the importance of ventricular arrhythmias in other causes of cardiomyopathy, such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, are discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death" and "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis".) TYPES OF ARRHYTHMIA Premature ventricular complexes (PVCs) PVCs occur in 70 to 95 percent of patients with heart failure (HF), and they may be frequent (including bigeminy or trigeminy) and complex (ie, https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 1/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate multifocal, couplets, or triplets/nonsustained ventricular tachycardia) [4-7]. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "Premature ventricular complexes: Treatment and prognosis".) Among patients with cardiomyopathy, PVCs may be clinically significant for the following reasons: PVCs (particularly when complex, ie, multifocal, couplets [ie, two PVCs in a row], or triplets [ie, three PVCs in a row, often called nonsustained VT]) may be predictors of more malignant arrhythmias and sudden cardiac death (SCD). In patients with a prior myocardial infarction (MI), PVCs are associated with an increased risk of death. By contrast, PVCs do not appear to be associated with a worse prognosis in patients with nonischemic cardiomyopathy, although data are limited [8]. PVCs can cause symptoms, usually palpitations. Symptoms are generally mild, and most patients require no specific therapy. Beta blockers can help to control symptoms (particularly palpitations related to the post-extrasystolic potentiation of myocardial contractility) although they will not usually suppress the PVCs, but most patients with HF and cardiomyopathy already have an indication for a beta blocker. Because of the proarrhythmic risks of antiarrhythmic drugs (which are particularly increased in patients with HF) other than beta blockers, these medications are not used in the routine treatment of PVCs. In the rare circumstance in which a patient is severely symptomatic despite beta blockers, amiodarone or dofetilide appears to be safe in patients with HF, and radiofrequency catheter ablation may also be an option. In rare cases, very frequent PVCs cause a reduction in left ventricular ejection fraction or even less frequently exacerbate left ventricular (LV) dysfunction. In such cases, radiofrequency catheter ablation is a safe and possibly an effective therapy that can reduce the number of PVCs and often restore LV function toward normal. (See "Arrhythmia- induced cardiomyopathy", section on 'Frequent ventricular ectopy'.) Nonsustained ventricular tachycardia Runs of nonsustained ventricular tachycardia (NSVT) have been observed on ambulatory monitoring in 50 to 80 percent of patients with HF or cardiomyopathy [4,7,9]. We define NSVT as three or more consecutive ventricular beats at a rate of greater than 100 beats/minute with a duration of less than 30 seconds (or self-terminating) and no associated hemodynamic collapse. The clinical significance of NSVT can be considered in a similar manner to that of PVCs: https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 2/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate NSVT may be predictive of future malignant arrhythmias and mortality. An association between NSVT and mortality has been shown in patients with ischemic and hypertrophic cardiomyopathy but not in most other forms of cardiomyopathy. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) Among 1080 patients with class III and IV HF in the PROMISE study, the frequency of NSVT was a significant independent predictor of both sudden and non-sudden death mortality [4]. NSVT is often asymptomatic, but some patients experience palpitations, lightheadedness, presyncope, or dyspnea. Because many of the symptoms that may be attributed to NSVT are vague and nonspecific, it is important to try to correlate symptoms to episodes of NSVT before initiating therapy. In patients with symptoms due to NSVT, options include beta blockers (for which most patients already have an indication), catheter ablation, and, in rare cases of severe and refractory symptoms, amiodarone or dofetilide. In patients with an ischemic cardiomyopathy, the occurrence of nonsustained polymorphic ventricular tachycardia (VT) may be the result of active ischemia. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management".) In rare cases, very frequent NSVT can contribute to or exacerbate LV dysfunction. (See "Arrhythmia-induced cardiomyopathy", section on 'Ventricular arrhythmias'.) Accelerated idioventricular rhythm An accelerated idioventricular rhythm (AIVR), which has also been called "slow VT," arises below the atrioventricular (AV) node (within the ventricular myocardium) and has, by definition, a rate between 60 and 100 beats/minute. When the AIVR is an accelerated rhythm, there is AV dissociation present, but the rate of the QRS complexes is faster than the atrial rate. AIVR occurs in approximately 8 percent of patients with HF or cardiomyopathy [10]. It also occurs in up to 50 percent of patients during an acute MI, most commonly in patients undergoing revascularization (ie, a reperfusion arrhythmia). Most episodes of AIVR are transient and require no treatment. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Accelerated idioventricular rhythm'.) Sustained VT or VF In contrast to the high prevalence of PVCs and NSVT in patients with HF or cardiomyopathy, sustained VT (monomorphic or polymorphic) is unusual, occurring in 5 percent of patients [4,7,9]. Patients with spontaneous sustained VT or resuscitated ventricular fibrillation (VF) are at high risk for SCD [11,12]. Patients with HF or cardiomyopathy (especially with an LVEF 35 percent) who are survivors of SCD due to unstable VT or VF, with or without recurrent stable sustained VT, are typically treated with an implantable cardioverter-defibrillator https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 3/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate for secondary prevention. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) PATHOGENESIS There are multiple factors responsible for ventricular arrhythmias in patients with heart failure (HF) and cardiomyopathy. These include: Underlying structural myocardial disease Mechanical factors Neurohormonal factors Electrolyte abnormalities Myocardial ischemia Drugs Underlying structural myocardial disease Extensive myocardial damage and fibrosis (including scar from prior myocardial infarction), myocardial infiltration or inflammation, or the loss of cell-to-cell coupling in patients with dilated cardiomyopathy provides the proper substrate for reentry, the mechanism thought to be responsible for most ventricular arrhythmias. A focal mechanism may also contribute to ventricular arrhythmia in patients with a nonischemic cardiomyopathy, probably from an ectopic focus or triggered activity arising from either early afterdepolarizations or delayed afterdepolarizations, without evidence of reentry. Mechanical factors Mechanical factors that can alter the electrophysiologic properties (electromechanical feedback) of myocardial tissue in HF include an increase in wall stress and left ventricular dilation [13,14]. It has been shown that a stretching of atrial or ventricular myocardium can enhance automaticity and result in arrhythmia. Since regions of the heart differ in mechanical function, electromechanical feedback that can cause PVCs may result in an increase in dispersion of action potential duration and membrane recovery. These effects can increase the incidence of arrhythmias, particularly sustained VT or VF. Among 311 patients in the SOLVD (Studies of Left Ventricular Dysfunction) trial, for example, there was a direct correlation between left ventricular end-diastolic volume and the prevalence of ventricular arrhythmia [15]. Neurohormonal factors HF results in the activation of the sympathetic nervous and renin- angiotensin systems and withdrawal of parasympathetic tone, resulting in increased heart rate, reduced heart rate variability, and depressed baroreceptor sensitivity. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 4/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Neurohormonal activation can promote arrhythmia formation via a variety of mechanisms: Catecholamines are arrhythmogenic by virtue of their ability to enhance automaticity, precipitate triggered activity, and alter conduction and refractoriness, which may promote reentry. Angiotensin II can indirectly promote arrhythmia formation via low potassium or magnesium levels, resulting from potassium and magnesium loss in the urine. It can also potentiate the effects of the sympathetic nervous system through central or peripheral actions. Both systems may be arrhythmogenic because the associated vasoconstriction alters loading conditions, affecting wall stress and mechanical factors as described above. Electrolyte abnormalities Patients with HF often have electrolyte abnormalities, particularly diuretic-induced hypokalemia and hypomagnesemia, which may be directly arrhythmogenic [16]. Hyperkalemia, as may occur with the use of ACE inhibitors or ARBs, results in slowing of conduction through the myocardium, which may also be a precondition for arrhythmia. In addition, stimulation of beta-2 receptors by circulating epinephrine can transiently lower the plasma potassium concentration by enhancing potassium entry into cells. In the SOLVD trial, for example, non-potassium-sparing diuretic use at baseline was associated with a lower serum concentration of potassium and a higher incidence of arrhythmic death compared with no diuretic use (3.1 versus 1.7 deaths per 100 patient-years) [17]. (See "Use of diuretics in patients with heart failure".) Myocardial ischemia Myocardial ischemia, through its effects on electrolyte shifts, acidosis, heterogeneity of electrophysiologic properties, and other mediators, may lead to alteration in the electrophysiologic milieu, including regional alterations in conduction and refractoriness and enhanced automaticity. These alterations may be enhanced by hypokalemia, increased catecholamine levels, digitalis, and antiarrhythmic agents. While monomorphic ventricular tachycardia (VT) is not usually due to active ischemia, polymorphic VT or ventricular fibrillation (VF) are often ischemia-induced arrhythmias. Drugs The drugs used to treat HF can directly or indirectly precipitate arrhythmia formation. Diuretic-induced electrolyte disturbances may be directly arrhythmogenic. Drugs may be proarrhythmic by prolonging the QT interval ( table 1) (eg, antiarrhythmic medications, certain antifungal and antibiotic agents, certain psychoactive drugs, etc) and predisposing to acquired long QT syndrome and polymorphic VT (which, associated with https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 5/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate QT prolongation, is termed torsades de pointes). (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) Phosphodiesterase inhibitors Phosphodiesterase inhibitors are positive inotropic agents that increase intracellular calcium, which can increase cyclic AMP and precipitate afterdepolarizations, resulting in triggered activity. They can also exacerbate ventricular arrhythmias by inducing ischemia [18]. A number of trials have shown that one such agent, milrinone, increased the frequency of all forms of spontaneous arrhythmia [19-21] and, in a long-term survival trial (PROMISE), was associated with a 20 percent excess in mortality compared with placebo [22]. Sympathomimetic drugs Studies with sympathomimetic agents (eg, dobutamine, albuterol) have shown an increased frequency of ventricular arrhythmias and/or increased mortality [23]. The use of sympathomimetic drugs is also associated with an increased incidence of hospitalization for arrhythmia, especially atrial fibrillation, VT, and VF [24]. Digoxin There have been conflicting data on the effect of digoxin on the frequency and clinical significance of arrhythmias in HF. Two relatively large studies found that digoxin did not significantly affect the frequency of ventricular arrhythmias in patients with congestive HF [21,25]. Conversely, other studies in patients with HF after acute myocardial infarction (MI) reported an excess mortality in patients who had complex ventricular arrhythmias who were treated with digitalis [26,27]; however, other reports did not confirm this increased risk in post-MI patients [28,29]. The largest trial evaluating the efficacy of digoxin in HF, the DIG trial, randomly assigned approximately 6800 patients with HF to digoxin or placebo; all patients were also treated with an angiotensin converting enzyme inhibitor and, if necessary, a diuretic [30]. Digoxin was associated with an increase in non-HF cardiac mortality, which included a trend towards increased mortality from arrhythmia. This trend counterbalanced the fewer deaths from progressive HF in patients treated with digoxin, leading to no effect on overall patient survival. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) For patients who take digoxin, periodic monitoring of serum levels should be performed, as higher serum digoxin levels have been associated with worse outcomes. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification", section on 'Monitoring serum digoxin'.) CLINICAL MANIFESTATIONS https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 6/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate The type and intensity of symptoms, if present, will vary depending upon the type and duration of the ventricular arrhythmia along with the patient s overall clinical status and significant comorbid conditions. Patients with ventricular premature beats who notice symptoms typically present with palpitations or dizziness, though the vast majority of patients experience few or no symptoms. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Symptoms'.) Patients with nonsustained ventricular tachycardia (NSVT) who notice symptoms typically present with one or more of palpitations, chest pain, shortness of breath, or syncope/presyncope. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management", section on 'History and associated symptoms'.) Patients with sustained VT may briefly experience the onset of symptoms prior to the abrupt loss of consciousness and sudden cardiac arrest if VT results in hemodynamic collapse. For patients without immediate sudden cardiac arrest, the type and intensity of symptoms are similar to NSVT and will vary depending upon the rate and duration of sustained monomorphic VT along with the presence and severity of underlying heart disease and the presence or absence of significant comorbid conditions. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'History and associated symptoms'.) Syncope in the setting of severe cardiomyopathy and HF requires special consideration. Although these patients may have syncope due to any of the usual causes, they are more likely than other patients to have an arrhythmic etiology. Thus, syncope in this population requires careful evaluation. This evaluation sometimes includes an electrophysiology study, both to exclude the possibility of a bradyarrhythmic cause and to attempt to induce ventricular arrhythmias. Patients in whom no etiology of syncope is found are said to have unexplained syncope. Extended ambulatory ECG monitoring (with an event recorder, patch monitoring, or implantable loop recorder) is often used to establish the etiology for unexplained syncope. Syncope is associated with an increased risk of sudden cardiac death in patients with HF and cardiomyopathy, even if an arrhythmic cause cannot be identified [31-34]. (See 'Diagnostic evaluation' below.) Sleep disordered breathing (SDB), presenting as either obstructive sleep apnea or central sleep apnea syndrome (including Cheyne-Stokes breathing) occurs commonly in patients with HF and is associated with increased cardiac mortality. In a study of 283 patients with HF (170 with no or mild SDB, and 113 with untreated SDB) who already had an implantable cardioverter- https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 7/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate defibrillator (ICD), time periods to first monitored ventricular arrhythmias (VT or ventricular fibrillation) and to first appropriate ICD therapy were significantly shorter in patients with SDB [35]. (See "Sleep-disordered breathing in heart failure", section on 'Arrhythmias'.) DIAGNOSTIC EVALUATION An electrocardiogram (ECG) should be part of the standard evaluation for any patient with suspected premature ventricular complexes (PVCs), nonsustained ventricular tachycardia (NSVT), or sustained VT. The diagnostic evaluation beyond an ECG will vary depending upon the particular arrhythmia in question and the patient s prior investigations, but additional testing may include one or more of ambulatory ECG monitoring, exercise testing, echocardiography, and invasive electrophysiology (EP) studies. The diagnostic evaluation of PVCs, NSVT, and sustained VT is discussed in detail separately. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Additional testing' and "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management", section on 'Diagnostic evaluation' and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Additional diagnostic evaluation'.) EP studies can demonstrate the mechanisms of induced or spontaneous arrhythmias and characterize the function of the sinus node, the AV node, and the His-Purkinje system. Thus, EP studies can assist in the diagnosis of unexplained symptoms (eg, palpitations or syncope) and arrhythmias. NSVT can be an indication for EP study and possible implantable cardioverter- defibrillator (ICD) therapy in selected patients with a prior myocardial infarction (MI) and ischemic cardiomyopathy who do not otherwise meet criteria for prophylactic ICD implantation. The ability to induce ventricular arrhythmias is not predictive of sudden cardiac death risk in patients with nonischemic cardiomyopathy. Thus, EP testing does not have a role in risk stratification in these patients. In contemporary patient management, however, EP studies are used only in a small minority of patients, typically in the following situations: Patients with structural heart disease and syncope of uncertain etiology (especially if NSVT is present). Patients with a remote MI and NSVT who do not otherwise meet criteria for prophylactic ICD implantation (eg, left ventricular ejection fraction [LVEF] 35 percent). Patients with nonischemic cardiomyopathy and NSVT who do not otherwise meet criteria for prophylactic ICD implantation (eg, LVEF 35 percent). https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 8/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Patients with cardiomyopathy felt to be at high risk, but who are in a "waiting period" prior to ICD implantation (eg, newly diagnosed nonischemic cardiomyopathy and NSVT). DIAGNOSIS The diagnosis of sustained ventricular tachycardia (VT) should be suspected in a patient who presents with either sudden cardiac arrest, syncope, or sustained palpitations, particularly in a patient with a known history of structural heart disease. The diagnosis of nonsustained VT (NSVT) or premature ventricular complexes (PVCs) is more commonly suspected in a patient with intermittent palpitations, which may or may not be associated with other symptoms. The diagnosis of sustained VT, NSVT, or PVCs is typically confirmed following review of an ECG acquired during the arrhythmia. The ECG in patients with VT (sustained or nonsustained) will show a wide QRS complex tachycardia often with the presence of AV dissociation (manifest as an atrial rate slower than the ventricular rate), while the ECG in patients with PVCs will show one or more isolated PVCs . (See "Wide QRS complex tachycardias: Approach to the diagnosis" and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Diagnosis'.) MANAGEMENT The management of ventricular arrhythmias in patients with heart failure (HF) and cardiomyopathy is multifaceted and includes: HF management Arrhythmia control Consideration of an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention of sudden cardiac death (SCD) Heart failure therapy Patients with HF and ventricular arrhythmias should have their HF treated aggressively. Standard therapy for HF due to systolic dysfunction consists of the following: A beta blocker such as carvedilol, metoprolol succinate, or bisoprolol An angiotensin receptor neprilysin inhibitor (ARNI), angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) An aldosterone antagonist in selected patients Diuretics if there is evidence of fluid overload or to prevent recurrent fluid overload https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 9/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate In addition, digoxin and intravenous inotropic agents (eg, milrinone, dobutamine) are occasionally used for acute symptom control, while diuretics are given for congestive symptoms. Many of these drugs can affect the incidence of arrhythmic death in patients with HF or cardiomyopathy. Some of the key points of various HF therapies will be discussed here, while more extended discussions can be found in the related topics. Beta blockers A substantial part of the survival benefit seen with beta blockers in patients with HF is due to a significant reduction in SCD [36-38]. As examples, there were significantly fewer SCDs in trials using carvedilol. In the MERIT-HF trial, there were significantly fewer SCDs (3.9 versus 6.6 percent) and fewer deaths from worsening of HF (1.5 versus 2.9 percent) with metoprolol compared with placebo, while in CIBIS-II, the survival benefit from beta blocker therapy was primarily due to a reduction in SCD (3.6 versus 6.3 percent), with only a nonsignificant trend toward fewer deaths from HF [36]. ACE inhibitors and ARBs ACE inhibitors improve survival in all stages of HF. However, there are conflicting data as to whether ACE inhibitors reduce SCD. A meta-analysis of trials of 15,104 patients within 14 days of an acute myocardial infarction found that ACE inhibitor therapy modestly but significantly reduced the risk of SCD (odds ratio 0.80, absolute benefit approximately 1.4 percent) [39]. However, as noted above, 45 percent of patients who died suddenly in AIRE had severe or worsening HF prior to their death, and only 39 percent of sudden deaths were thought to be due to arrhythmia [40]. The ARBs appear to be as or perhaps slightly less beneficial than ACE inhibitors in patients with HF [41]. The major ARB trial CHARM noted a clear survival benefit but did not report data on SCD [42]. ELITE II, which directly compared losartan with captopril, found a higher rate of SCD with losartan that was not statistically significant [41]. This might suggest that ARBs alone are unlikely to have a major impact on SCD in HF patients. Conversely, however, the addition of ARB to ACE inhibitor therapy in patients with HF in the CHARM-Added trial was found to reduce the rate of SCD, as well as the rate of death from worsening HF [43]. Angiotensin receptor neprilysin inhibitors (ARNI) For some patients, an ARNI such as sacubitril-valsartan can be substituted in place of ACE inhibitor (or single-agent ARB) therapy for patients who have tolerated an ACE inhibitor or ARB. However, some experts recommend the ARNI sacubitril-valsartan as initial oral therapy (in place of ACE inhibitor or single-agent ARB) in hemodynamically stable patients. Aldosterone antagonists The aldosterone antagonists spironolactone and eplerenone significantly reduce overall mortality and SCD in patients with advanced HF [44,45]. They https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 10/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate also reduce the frequency of VPBs and nonsustained ventricular tachycardia (NSVT) [46]. These benefits may reflect a reduction in aldosterone effect on the heart and/or the maintenance of a higher serum potassium concentration. Cardiac resynchronization therapy Cardiac resynchronization therapy appears to reduce the incidence of ventricular tachyarrhythmias in patients with HF and cardiomyopathy. This is discussed in greater detail separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) Arrhythmia control The initial management of a patient with sustained VT depends on the hemodynamic stability of the patient ( algorithm 1). Emergency management is required in unstable patients, typically with electrical cardioversion and occasionally antiarrhythmic medications. Additional time may be spent determining the etiology and treating any underlying precipitating factors in patients who are hemodynamically stable (although treatment for such patients should usually be promptly administered). Subsequent management of the patient will be guided by the initial presentation (ie, hemodynamically stable or unstable) and the initial approach to treatment [47]. A full discussion of the treatment of sustained VT is presented separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Treatment'.) Patients with symptomatic NSVT or PVCs should usually be treated with beta blockers as the initial therapy. While beta blockers do not usually reduce the frequency of these arrhythmias, they may be effective for reducing or eliminating symptoms. For patients who have very frequent, symptomatic NSVT or PVCs not controlled by medications, catheter ablation can be effective for reducing or eliminating associated symptoms. Antiarrhythmic medications are generally reserved for patients with severely symptomatic NSVT despite therapy with beta blockers who are not candidates for catheter ablation of the VT. A full discussion of the treatment of NSVT and PVCs is presented separately. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management", section on 'Treatment'.) Prevention of SCD Patients who have been resuscitated from sudden cardiac arrest (due to either sustained VT or ventricular fibrillation) are candidates for, and generally should receive, an ICD for secondary prevention of SCD. Patients who present with sustained VT in the setting of cardiomyopathy and patients with NSVT and/or syncope and inducible sustained ventricular arrhythmia at electrophysiology testing should also generally receive an ICD for secondary prevention. Additionally, many patients with HF and cardiomyopathy (and left ventricular ejection fraction 35 percent) are candidates for ICD implantation as primary prevention of SCD. Secondary and primary prevention of SCD in HF and cardiomyopathy are discussed separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 11/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Heart failure in adults" and "Society guideline links: Ventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Background Ventricular arrhythmias, including premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF), are common in patients with heart failure (HF) and cardiomyopathy, occurring in up to 95 percent of this population. (See 'Types of arrhythmia' above.) Pathogenesis Multiple factors may be responsible for ventricular arrhythmias in patients with HF and cardiomyopathy, including underlying structural heart disease, mechanical factors, neurohormonal factors, electrolyte disturbances, myocardial ischemia, and medications. (See 'Pathogenesis' above.) https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 12/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Clinical manifestations The type and intensity of symptoms, if present, will vary depending upon the type and duration of the ventricular arrhythmia along with the patient s overall clinical status and significant comorbid conditions. Patients may experience few or no symptoms with PVCs or short runs of nonsustained VT, or may present with syncope or sudden cardiac arrest due to sustained VT or VF. (See 'Clinical manifestations' above.) Diagnostic evaluation An ECG should be part of the standard evaluation for any patient with suspected PVCs, VT, or VF. The diagnostic evaluation beyond an ECG will vary depending upon the particular arrhythmia in question and the patient s prior investigations, but additional testing may include one or more of ambulatory ECG monitoring, exercise testing, echocardiography, and invasive electrophysiology studies. (See 'Diagnostic evaluation' above.) Management The management of ventricular arrhythmias in patients with HF and cardiomyopathy is multifaceted and includes HF therapy, arrhythmia control, and consideration of an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention of sudden cardiac death (SCD). Heart failure Standard therapy for HF due to systolic dysfunction consists of a beta blocker; an angiotensin receptor neprilysin inhibitor, angiotensin converting enzyme inhibitor, or an angiotensin II receptor blocker (ARB); and in selected patients, an aldosterone antagonist. Digoxin and other inotropic agents are occasionally used for symptom control, while diuretics are given for congestive symptoms. (See 'Heart failure therapy' above.) Arrhythmia control The initial management of a patient with sustained VT depends on the hemodynamic stability of the patient ( algorithm 1), with emergency management required in unstable patients. Subsequent management of VT will be guided by the initial presentation (ie, hemodynamically stable or unstable) and the initial approach to treatment. Patients with symptomatic NSVT or PVCs should usually be treated with beta blockers as the initial therapy. (See 'Arrhythmia control' above.) Prevention of SCD Patients who have been resuscitated from sudden cardiac arrest (due to either sustained VT or VF) are candidates for, and generally should receive, an ICD for secondary prevention of SCD. Additionally, many patients with HF and cardiomyopathy (and left ventricular ejection fraction 35 percent) are candidates for ICD implantation as primary prevention of SCD. (See "Secondary prevention of sudden https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 13/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Hynes BJ, Luck JC, Wolbrette DL, et al. Arrhythmias in Patients with Heart Failure. Curr Treat Options Cardiovasc Med 2002; 4:467. 2. Francis GS. Development of arrhythmias in the patient with congestive heart failure: pathophysiology, prevalence and prognosis. Am J Cardiol 1986; 57:3B. 3. Holmes J, Kubo SH, Cody RJ, Kligfield P. Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography. Am J Cardiol 1985; 55:146. 4. Teerlink JR, Jalaluddin M, Anderson S, et al. Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators. Circulation 2000; 101:40. 5. Podrid PJ, Fogel RI, Fuchs TT. Ventricular arrhythmia in congestive heart failure. Am J Cardiol 1992; 69:82G. 6. von Olshausen K, Sch fer A, Mehmel HC, et al. Ventricular arrhythmias in idiopathic dilated cardiomyopathy. Br Heart J 1984; 51:195. 7. Meinertz T, Hofmann T, Kasper W, et al. Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy. Am J Cardiol 1984; 53:902. 8. Packer M. Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation 1992; 85:I50. 9. Singh SN, Fisher SG, Carson PE, Fletcher RD. Prevalence and significance of nonsustained ventricular tachycardia in patients with premature ventricular contractions and heart failure treated with vasodilator therapy. Department of Veterans Affairs CHF STAT Investigators. J Am Coll Cardiol 1998; 32:942. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 14/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate 10. Grimm W, Hoffmann J, Menz V, et al. Significance of accelerated idioventricular rhythm in idiopathic dilated cardiomyopathy. Am J Cardiol 2000; 85:899. 11. Poll DS, Marchlinski FE, Buxton AE, et al. Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy. Circulation 1984; 70:451. 12. Milner PG, Dimarco JP, Lerman BB. Electrophysiological evaluation of sustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy. Pacing Clin Electrophysiol 1988; 11:562. 13. White CW, Mirro MJ, Lund DD, et al. Alterations in ventricular excitability in conscious dogs during development of chronic heart failure. Am J Physiol 1986; 250:H1022. 14. Dean JW, Lab MJ. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet 1989; 1:1309. 15. Koilpillai C, Qui ones MA, Greenberg B, et al. Relation of ventricular size and function to heart failure status and ventricular dysrhythmia in patients with severe left ventricular dysfunction. Am J Cardiol 1996; 77:606. 16. Gottlieb SS, Baruch L, Kukin ML, et al. Prognostic importance of the serum magnesium |
condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Background Ventricular arrhythmias, including premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF), are common in patients with heart failure (HF) and cardiomyopathy, occurring in up to 95 percent of this population. (See 'Types of arrhythmia' above.) Pathogenesis Multiple factors may be responsible for ventricular arrhythmias in patients with HF and cardiomyopathy, including underlying structural heart disease, mechanical factors, neurohormonal factors, electrolyte disturbances, myocardial ischemia, and medications. (See 'Pathogenesis' above.) https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 12/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Clinical manifestations The type and intensity of symptoms, if present, will vary depending upon the type and duration of the ventricular arrhythmia along with the patient s overall clinical status and significant comorbid conditions. Patients may experience few or no symptoms with PVCs or short runs of nonsustained VT, or may present with syncope or sudden cardiac arrest due to sustained VT or VF. (See 'Clinical manifestations' above.) Diagnostic evaluation An ECG should be part of the standard evaluation for any patient with suspected PVCs, VT, or VF. The diagnostic evaluation beyond an ECG will vary depending upon the particular arrhythmia in question and the patient s prior investigations, but additional testing may include one or more of ambulatory ECG monitoring, exercise testing, echocardiography, and invasive electrophysiology studies. (See 'Diagnostic evaluation' above.) Management The management of ventricular arrhythmias in patients with HF and cardiomyopathy is multifaceted and includes HF therapy, arrhythmia control, and consideration of an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention of sudden cardiac death (SCD). Heart failure Standard therapy for HF due to systolic dysfunction consists of a beta blocker; an angiotensin receptor neprilysin inhibitor, angiotensin converting enzyme inhibitor, or an angiotensin II receptor blocker (ARB); and in selected patients, an aldosterone antagonist. Digoxin and other inotropic agents are occasionally used for symptom control, while diuretics are given for congestive symptoms. (See 'Heart failure therapy' above.) Arrhythmia control The initial management of a patient with sustained VT depends on the hemodynamic stability of the patient ( algorithm 1), with emergency management required in unstable patients. Subsequent management of VT will be guided by the initial presentation (ie, hemodynamically stable or unstable) and the initial approach to treatment. Patients with symptomatic NSVT or PVCs should usually be treated with beta blockers as the initial therapy. (See 'Arrhythmia control' above.) Prevention of SCD Patients who have been resuscitated from sudden cardiac arrest (due to either sustained VT or VF) are candidates for, and generally should receive, an ICD for secondary prevention of SCD. Additionally, many patients with HF and cardiomyopathy (and left ventricular ejection fraction 35 percent) are candidates for ICD implantation as primary prevention of SCD. (See "Secondary prevention of sudden https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 13/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Hynes BJ, Luck JC, Wolbrette DL, et al. Arrhythmias in Patients with Heart Failure. Curr Treat Options Cardiovasc Med 2002; 4:467. 2. Francis GS. Development of arrhythmias in the patient with congestive heart failure: pathophysiology, prevalence and prognosis. Am J Cardiol 1986; 57:3B. 3. Holmes J, Kubo SH, Cody RJ, Kligfield P. Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography. Am J Cardiol 1985; 55:146. 4. Teerlink JR, Jalaluddin M, Anderson S, et al. Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators. Circulation 2000; 101:40. 5. Podrid PJ, Fogel RI, Fuchs TT. Ventricular arrhythmia in congestive heart failure. Am J Cardiol 1992; 69:82G. 6. von Olshausen K, Sch fer A, Mehmel HC, et al. Ventricular arrhythmias in idiopathic dilated cardiomyopathy. Br Heart J 1984; 51:195. 7. Meinertz T, Hofmann T, Kasper W, et al. Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy. Am J Cardiol 1984; 53:902. 8. Packer M. Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation 1992; 85:I50. 9. Singh SN, Fisher SG, Carson PE, Fletcher RD. Prevalence and significance of nonsustained ventricular tachycardia in patients with premature ventricular contractions and heart failure treated with vasodilator therapy. Department of Veterans Affairs CHF STAT Investigators. J Am Coll Cardiol 1998; 32:942. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 14/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate 10. Grimm W, Hoffmann J, Menz V, et al. Significance of accelerated idioventricular rhythm in idiopathic dilated cardiomyopathy. Am J Cardiol 2000; 85:899. 11. Poll DS, Marchlinski FE, Buxton AE, et al. Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy. Circulation 1984; 70:451. 12. Milner PG, Dimarco JP, Lerman BB. Electrophysiological evaluation of sustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy. Pacing Clin Electrophysiol 1988; 11:562. 13. White CW, Mirro MJ, Lund DD, et al. Alterations in ventricular excitability in conscious dogs during development of chronic heart failure. Am J Physiol 1986; 250:H1022. 14. Dean JW, Lab MJ. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet 1989; 1:1309. 15. Koilpillai C, Qui ones MA, Greenberg B, et al. Relation of ventricular size and function to heart failure status and ventricular dysrhythmia in patients with severe left ventricular dysfunction. Am J Cardiol 1996; 77:606. 16. Gottlieb SS, Baruch L, Kukin ML, et al. Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. J Am Coll Cardiol 1990; 16:827. 17. Cooper HA, Dries DL, Davis CE, et al. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation 1999; 100:1311. 18. Stambler BS, Wood MA, Ellenbogen KA. Sudden death in patients with congestive heart failure: future directions. Pacing Clin Electrophysiol 1992; 15:451. 19. Holmes JR, Kubo SH, Cody RJ, Kligfield P. Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias. Am Heart J 1985; 110:800. 20. Anderson JL, Askins JC, Gilbert EM, et al. Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone. Am Heart J 1986; 111:466. 21. DiBianco R, Shabetai R, Kostuk W, et al. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989; 320:677. 22. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991; 325:1468. 23. Dies F, Krell MJ, Whitlow P, et al. Intermittent dobutamine in ambulatory outpatients with chronic cardiac failure. Circulation 1986; 74(Suppl II):II. 24. Bouvy ML, Heerdink ER, De Bruin ML, et al. Use of sympathomimetic drugs leads to increased risk of hospitalization for arrhythmias in patients with congestive heart failure. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 15/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Arch Intern Med 2000; 160:2477. 25. Gradman A, Deedwania P, Cody R, et al. Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group. J Am Coll Cardiol 1989; 14:564. 26. Moss AJ, Davis HT, Conard DL, et al. Digitalis-associated cardiac mortality after myocardial infarction. Circulation 1981; 64:1150. 27. Bigger JT Jr, Fleiss JL, Rolnitzky LM, et al. Effect of digitalis treatment on survival after acute myocardial infarction. Am J Cardiol 1985; 55:623. 28. Ryan TJ, Bailey KR, McCabe CH, et al. The effects of digitalis on survival in high-risk patients with coronary artery disease. The Coronary Artery Surgery Study (CASS). Circulation 1983; 67:735. 29. Muller JE, Turi ZG, Stone PH, et al. Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study. N Engl J Med 1986; 314:265. 30. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336:525. 31. Middlekauff HR, Stevenson WG, Stevenson LW, Saxon LA. Syncope in advanced heart failure: high risk of sudden death regardless of origin of syncope. J Am Coll Cardiol 1993; 21:110. 32. Fonarow GC, Feliciano Z, Boyle NG, et al. Improved survival in patients with nonischemic advanced heart failure and syncope treated with an implantable cardioverter-defibrillator. Am J Cardiol 2000; 85:981. 33. Grimm W, Hoffmann J J , M ller HH, Maisch B. Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%. J Am Coll Cardiol 2002; 39:780. 34. Knight BP, Goyal R, Pelosi F, et al. Outcome of patients with nonischemic dilated cardiomyopathy and unexplained syncope treated with an implantable defibrillator. J Am Coll Cardiol 1999; 33:1964. 35. Bitter T, Westerheide N, Prinz C, et al. Cheyne-Stokes respiration and obstructive sleep apnoea are independent risk factors for malignant ventricular arrhythmias requiring appropriate cardioverter-defibrillator therapies in patients with congestive heart failure. Eur Heart J 2011; 32:61. 36. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353:2001. 37. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 16/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate 1996; 334:1349. 38. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353:9. 39. Domanski MJ, Exner DV, Borkowf CB, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999; 33:598. 40. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators. Eur Heart J 1997; 18:41. 41. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355:1582. 42. Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362:759. 43. Solomon SD, Wang D, Finn P, et al. Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation 2004; 110:2180. 44. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341:709. 45. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309. 46. Ramires FJ, Mansur A, Coelho O, et al. Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol 2000; 85:1207. 47. Santangeli P, Rame JE, Birati EY, Marchlinski FE. Management of Ventricular Arrhythmias in Patients With Advanced Heart Failure. J Am Coll Cardiol 2017; 69:1842. Topic 968 Version 29.0 https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 17/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate GRAPHICS Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial ischemia or infarction, especially with prominent T-wave inversions GnRH agonist/antagonist therapy Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders particularly hypokalemia and hypomagnesemia Starvation Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via Intracranial disease Hypothyroidism electrolyte disturbances Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate insecticides AV block: Second or third degree Medications* High risk Adagrasib Cisaparide (restricted availability) Lenvatinib Selpercatinib Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine (intracoronary) Vandetanib Dofetilide Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 18/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Capecitabine Entrectinib Isoflurane Quetiapine Carbetocin Erythromycin Levofloxacin (systemic) Ribociclib Certinib Escitalopram Risperidone Lofexidine Chloroquine Etelcalcetide Saquinavir Meglumine antimoniate Citalopram Fexinidazole Sevoflurane Clarithromycin Flecainide Sparfloxacin Midostaurin Clofazimine Floxuridine Sunitinib Moxifloxacin Clomipramine Fluconazole Tegafur Nilotinib Clozapine Fluorouracil (systemic) Terbutaline Olanzapine Crizotinib Thioridazine Ondansetrol (IV > oral) Flupentixol Dabrafenib Toremifene Gabobenate dimeglumine Dasatinib Vemurafenib Osimertinib Deslurane Voriconazole Oxytocin Gemifloxacin Domperidone Pazopanib Gilteritinib Doxepin Pentamidine Halofantrine Doxifluridine Pilsicainide Haloperidol (oral) Pimozide Imipramine Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- lumefantrine Glasdegib Mizolastine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine (rare reports) Nortriptyline Benperidol Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus (systemic) Olodaterol Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 19/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Degarelix Lefamulin Pasireotide Triclabendazole Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- norethindrone Periciazine Tropisetron Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide in Eliglustat Primaquine Vorinostat overdose Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. [1,2] . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 20/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 21/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Algorithm for initial treatment of SMVT in responsive patients with a pulse SMVT: sustained monomorphic ventricular tachycardia; CV: cardioversion. Hemodynamically unstable patients have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure. Hemodynamically stable patients should have none of these findings. Initial choice of pharmacologic agents includes: Intravenous lidocaine (1 to 1.5 mg/kg [typically 75 to 100 mg] at a rate of 25 to 50 mg/minute; lower doses of 0.5 to 0.75 mg/kg can be repeated every 5 to 10 minutes as needed), which may be more effective in the setting of acute myocardial ischemia or infarction Intravenous procainamide (20 to 50 mg/minute until arrhythmia terminates or a maximum dose of 17 mg/kg is administered) Intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours; bolus can be repeated if VT recurs) Electrical cardioversion should be synchronized if possible, using 100-joule biphasic shock or 200- joule monophasic shock. If first shock is unsuccessful, energy level should be escalated on subsequent shocks. Conditions associated with SMVT include myocardial ischemia, electrolyte disturbances (eg, hypokalemia, hypomagnesemia), drug-related proarrhythmia, and heart failure. https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 22/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Graphic 108831 Version 1.0 https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 23/24 7/6/23, 3:34 PM Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Wilson S Colucci, MD Grant/Research/Clinical Trial Support: Merck [Heart failure]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-arrhythmias-overview-in-patients-with-heart-failure-and-cardiomyopathy/print 24/24 |
7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wearable cardioverter-defibrillator : Mina K Chung, MD : Richard L Page, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 22, 2023. INTRODUCTION The implantable cardioverter-defibrillator (ICD) has been shown to improve survival from sudden cardiac arrest and to improve overall survival in several populations at high risk for sudden cardiac death (SCD). However, there remain situations in which implantation of an ICD is immediately not feasible (eg, patients with an active infection), may be of uncertain benefit, may not be covered by third-party payers (eg, early post-myocardial infarction, patients with limited life expectancy or new onset systolic heart failure), or when an ICD must be removed (eg, infection). In cases where ICD implantation must be deferred, a wearable cardioverter-defibrillator (WCD) offers an alternative approach for the prevention of SCD. The WCD (LifeVest [Zoll Medical Corporation] or Assure [Kestra Medical Technologies, Inc]) is an external device capable of automatic detection and defibrillation of ventricular tachycardia and ventricular fibrillation ( picture 1 and figure 1). While the WCD can be worn for years, typically the device is used for several months as temporary protection against SCD. The indications, efficacy, and limitations of the wearable cardioverter-defibrillator will be discussed here. Detailed discussions of the roles of the ICD are presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 1/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate DESCRIPTION AND FUNCTIONS OF THE WCD The WCD is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) [1]. The approved devices do not have pacing capabilities and therefore are unable to provide therapy for bradycardic events or antitachycardic pacing. Wearing the WCD The WCD is composed of dry, nonadhesive monitoring electrodes, defibrillation electrodes incorporated into a chest strap or vest assembly, and a defibrillation battery and monitor unit ( picture 1). The Assure WCD garment has two styles designed for female and male body habitus and different sizes. The monitoring electrodes are positioned circumferentially around the chest and provide two to four surface electrocardiogram (ECG) leads. The defibrillation electrodes are positioned in a vest assembly for apex-posterior defibrillation. Proper fitting is required to achieve adequate skin contact to avoid noise and frequent alarms. Detection and delivery of shocks Arrhythmia detection by the WCD is programmed using ECG rate and morphology criteria. The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline electrocardiographic template. Typical programming is reflected in default device settings: VT detection 150 beats per minute (LifeVest) or 170 beats per minute (Assure). Programmable ranges for LifeVest are 120 to 250 beats per minute, not to exceed the VF detection rate; for Assure they are, 130 to the programmed VF threshold minus 10 beats per minute. VF detection 200 beats per minute. Programmable ranges are 120 to 250 beats per minute (LifeVest) or 180 to 220 beats per minute (Assure). Treatment with 150 joules (LifeVest) or 170 joules (Assure) shocks for up to five shocks. For the Zoll LifeVest WCD, the tachycardia detection rate is programmable for VF between 120 and 250 beats per minute, and the VF shock delay can be programmed from 25 to 55 seconds. The VT detection rate is programmable between 120 bpm to the VF setting with a VT shock delay https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 2/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate of 60 to 180 seconds. VT signals can allow synchronized shock delivery on the R wave, but if the R wave cannot be identified, unsynchronized shocks will be delivered. For the Kestra Assure WCD, the tachycardia detection rate is programmable for VF between 180 and 220 beats per minute, and for VT detection programmable from 130 beats per minute up to the programmed VF rate: 10 beats per minute. Detection utilizes a segment-based analysis of 4.8-second segments that continuously overlap by 2.4 seconds. VF confirmation requires two out of two segments (approximately 5 seconds), and VT confirmation requires 15 out of 19 segments (approximately 45 seconds). The first and last segments must be in the programmed treatment zone. If an arrhythmia is detected, vibration and audible alarms are initiated. A flashing red light and shock icon are activated on the Assure monitor. Although shocks may be transmitted to bystanders in physical contact with the patient being shocked by a WCD, a voice cautions the patient and bystanders to the impending shock. Patients are trained to hold a pair of response buttons on the LifeVest device or press the alert button on the Assure device during these alarms to avoid receiving a shock while awake. A patient's response serves as a test of consciousness; if no response occurs and a shock is indicated, the device charges, extrudes gel from the defibrillation electrodes, and delivers up to five biphasic shocks at preprogrammed energy levels (ranging from 75 to 150 joules for the LifeVest device and 170 joules for the Assure device). The LifeVest device includes a default sleep time from 11 PM to 6 AM, programmable in one-hour increments, which allows additional time for deep sleepers, if they awaken, to abort shocks. Efficacy in terminating VT/VF Shock efficacy with the WCD appears to be similar to that reported with implantable cardioverter-defibrillators (ICDs). However, sudden cardiac death may still occur in those not wearing the device, those with improper positioning of the device, due to bystander interference, due to the inability of the WCD to detect the ECG signal, or due to bradyarrhythmias. These results highlight the importance of patient education and promotion of compliance while using the WCD. The efficacy of the WCD has been tested for induced ventricular tachyarrhythmias as well as for spontaneous events during clinical trials and postmarket studies. When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in up to 100 percent of cases [1-7]. In a study of induced VT/VF in the electrophysiology laboratory, the WCD successfully detected and terminated VT/VF with 100 percent first-shock success [2]. The following large registry studies of patients with WCDs showed high shock success rates: https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 3/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In a US postmarket study of 8453 patients who wore a WCD after myocardial infarction, 146 VT/VF events occurred in 133 patients, and the overall shock success rate for terminating VT/VF was 82 percent, with 91 percent immediate survival [6]. In this study, shock success resulting in survival was 95 percent in revascularized and 84 percent in non-revascularized patients, suggesting that lower efficacy rates may be related to ischemic events. In the WEARIT-II registry of 2000 patients who wore a WCD for a median of 90 days, 120 episodes of sustained VT/VF were seen in 41 patients [7]. For 90 of the episodes, patients pressed the response buttons to abort shock delivery, with the majority of sustained VT episodes terminating spontaneously following use of the response button. All of the remaining 30 VT/VF episodes in 22 different patients were successfully terminated with a single shock. Among 6043 German patients who wore the device between April 2010 and October 2013, 94 patients were shocked for sustained VT/VF, with the WCD successfully terminating VT/VF in 88 patients (94 percent) [8]. The WCD appears equally efficacious among patients with and without myocardial ischemia immediately prior to VT/VF detection and shock (as defined by 0.1 mV ST-segment changes on ECG), with first shock termination rates of 96 percent in both groups [9]. Avoiding inappropriate shocks When electronic noise occurs, which may potentially be interpreted at VT or VF, the WCD emits a noise alarm. This electronic noise can often be minimized or eliminated by changing body position or tightening of the electrode belt, and shocks can be avoided by pushing the response buttons. While a dual-chamber ICD with an atrial lead would seemingly have greater ability to discriminate between supraventricular tachycardia (SVT) and VT, the incidence of inappropriate shocks due to atrial fibrillation, sinus tachycardia, or other supraventricular arrhythmias in clinical studies of WCDs has been low. The LifeVest WCD uses a two-channel proprietary vectorcardiogram morphology matching algorithm to prevent shocks during SVT if the QRS is unchanged, and inappropriate shocks can also be averted when the patient presses the response buttons. The Assure WCD uses a four-channel ECG with a single noise-free channel required for analysis and an algorithm that excludes noisy and low amplitude channels ( figure 2). (See 'Inappropriate shocks' below.) In a small study of the 60 patients with a permanent pacemaker, in which a variety of pacing modes (AAI, VVI, DDD) and configurations (unipolar, bipolar) were tested, unipolar DDD pacing triggered VT/VF detection in six patients (10 percent), while no other pacing modes or configurations triggered arrhythmia detection [10]. As such, patients whose pacemaker is https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 4/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate programmed to unipolar DDD pacing should be evaluated for pacemaker reprogramming to a bipolar mode prior to WCD usage. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, of 163 WCD-detected episodes, four were VT/VF and 159 were non-VT/VF with three false-positive shock alarm markers recorded, corresponding to a very low rate of inappropriate detection [11]. No ICD-recorded VT/VF episodes meeting WCD programmed criteria were missed. Median daily use was high at 23 hours. Bradycardia/asystole Neither of the approved WCDs deliver antibradycardic pacing, but they do record the ventricular rate when the heart rate decreases or asystole occurs: For the LifeVest device, asystole recordings are triggered when ventricular heart rates drop below 10 beats per minute or 16 seconds of asystole, and the device automatically records the event with 120 seconds preceding the onset. If using the secure website in conjunction with the WCD, alerts can be configured to prompt the healthcare provider that a patient is experiencing bradycardia or an asystole. For the Assure device, asystole is detected when there is no detected heart rate for >20 seconds (five of seven segments with heart rate 0 beats per minute or amplitude <100 uV); prolonged heart rates below 30 beats per minute may be detected as bradycardia. When asystole or bradycardia is detected, a loud alarm is triggered to attract bystanders and instruct them to call 911 and begin CPR if the patient is unconscious. The alert can be silenced by pressing the alert button or it resolves when a heart rate >30 bpm is detected for >30 seconds. Storage of ECGs and compliance data In addition to delivering therapeutic shocks for life- threatening ventricular arrhythmias, the WCD stores data regarding tachyarrhythmias, bradycardia/asystole (see 'Bradycardia/asystole' above), patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted via a modem to the manufacturer's network. Treatments, patient compliance, ECG records, and system performance can be viewed using a secure website. The WCD stores ECGs from arrhythmia detections, usage, and compliance trends: For the LifeVest system: The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline ECG template. The monitoring software captures 30 seconds of ECG https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 5/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate signal prior to the determination of VT or VF and continuously records until 15 seconds after the alarms stop. Patients can perform manual recordings by pressing response buttons for three seconds, which records the prior 30 seconds plus the next 15 seconds. Data on patient compliance, ECG signal quality, alarm history, and noise occurrence are recorded, including time/date stamps for device on/off switching, monitor connection to the electrodes, and electrode-to-skin contact. Compliance may be determined by assessing the time that the user had the device turned on, the belt connected, and at least one monitoring electrode contacting the skin. For the Assure system: Up to 120 seconds of data are recorded prior to arrhythmia onset detection, confirmation, and therapy are detected, and up to 60 seconds are detected after rate recovery or conversion. Patient activity is also stored, utilizing an accelerometer located in the hub component in the middle of the patient's back. Daily usage is recorded in one-minute increments when the sensors are in contact with the patient's skin. INDICATIONS The WCD is indicated as temporary therapy for patients with a high risk for sudden cardiac death (SCD) [1,12-16]. Our recommended approach is consistent with that of the 2016 science advisory from the American Heart Association (also endorsed by the Heart Rhythm Society) and the 2017 AHA/ACC/HRS guideline [16,17]. Examples of persons who may benefit from the temporary use of a WCD include: Patients with a permanent implantable cardioverter-defibrillator (ICD) that must be explanted, or those with a delay in implanting a newly indicated ICD (eg, due to systemic infection). (See 'Bridge to indicated or interrupted ICD therapy' below.) Patients with reduced left ventricular (LV) systolic function (LVEF 35 percent) who have had a myocardial infarction (MI) within the past 40 days. (See 'Early post-MI patients with LV dysfunction' below.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 6/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Patients with reduced LV systolic function (LVEF 35 percent) who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months. (See 'Patients with LV dysfunction early after coronary revascularization' below.) Patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function (LVEF 35 percent) that is potentially reversible. (See 'Newly diagnosed nonischemic cardiomyopathy' below.) Patients with severe heart failure who are awaiting heart transplantation. (See 'Bridge to heart transplant' below.) A 2019 systematic review and meta-analysis, which included 33,242 WCD users from 28 studies (the randomized VEST trial and 27 nonrandomized studies), assessed the likelihood of WCD therapy in a broad range of patient populations, including both primary/secondary prevention and ischemic/nonischemic cardiomyopathy patients. The incidence of appropriate shocks was 5 per 100 persons over three months (1.67 percent per month) with mortality while wearing the device noted to be 0.7 per 100 persons over three months [18]. Bridge to indicated or interrupted ICD therapy In some patients with an indication for ICD placement, implantation of the device may be delayed due to comorbid conditions, including [16,17]: Infection Recovery from surgery Lack of vascular access In addition, patients with a preexisting ICD who develop device infection or endocarditis usually require system extraction to effectively treat the infection. Unless the patient is pacemaker dependent, reimplantation in many patients is deferred until the infection is completely cleared after an appropriate course of antibiotics. The WCD may provide protection against ventricular tachyarrhythmias during these periods until an ICD can be implanted [4,5,16]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".) In a review of 8058 patients who were prescribed the WCD after ICD removal because of infection, median time to reimplantation was 50 days, and 334 (4 percent) experienced 406 ventricular tachycardia/ventricular fibrillation (VT/VF) events, with 348 events treated by the WCD and 54 treatments averted by conscious patients [19]. The one-year cumulative event rate was 10 percent. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 7/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Early post-MI patients with LV dysfunction Among patients with LV ejection fraction (LVEF) 35 percent who are less than 40 days post-MI, there are conflicting data on the benefits of a WCD for primary prevention against SCD. Following discussion of the potential benefits and risks, use of the WCD within this 40-day window could be considered among motivated patients who have LVEF 35 percent and in New York Heart Association (NYHA) functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD implantation after 40 days [16,17]. Patients should be reminded of the importance of compliance with the WCD in order to optimize any potential benefits on prevention of arrhythmic death. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, while the patient is taking appropriate medical therapy, ICD implantation is indicated [16]. After ICD implantation, use of the WCD would be discontinued. Despite advances in the treatment of acute coronary syndromes with early revascularization and effective medical therapies that have reduced mortality, some residual risk of SCD remains in the early period following an MI, especially in the setting of severely reduced LVEF (2.3 percent/month for patients with LVEF 30 percent) [4,20]. However, there are conflicting data on the utility of an ICD in the early post-MI period. In an analysis of 712 patients with a history of MI who were enrolled in the SCD-HeFT trial, there was no evidence of differential mortality benefit with ICDs as a function of time after MI, indicating that the potential benefit of ICD therapy is not restricted only to remote MIs [21]. In the DINAMIT (674 patients) and IRIS (898 patients) trials, which randomized patients with LVEF 35 percent to either early ICD implantation 6 to 40 days after acute MI or medical therapy alone, there was no significant improvement in overall mortality [22,23]. Despite a reduction in arrhythmic deaths among patients with an ICD, there was a higher risk of nonarrhythmic deaths during this early period, resulting in similar overall mortality rates. Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within 40 days of acute MI [16]. However, due to the risk of SCD in some patients early post- MI, the WCD has been studied in this patient population. In the VEST trial, 2302 patients with an acute MI and LVEF 35 percent were randomly assigned (within seven days of hospital discharge) in a 2:1 ratio to wear the WCD in addition to usual medical treatment (1524 patients) or to receive standard medical treatment alone (778 patients) [24]. Over an average follow-up of 84 days, patients in the https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 8/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate WCD group had no significant improvement in the primary outcome of arrhythmic death (25 patients [1.6 percent] versus 19 patients [2.4 percent] with medical therapy alone; relative risk [RR] 0.67; 95% CI 0.37-1.21). Compliance with medical therapy was excellent in both groups, likely contributing to fewer than expected events and the trial possibly being underpowered. However, compliance with WCD usage was markedly lower than expected (median and mean daily wear times of 18 and 14 hours, respectively), with over half of patients assigned to the WCD not wearing it by the end of the 90-day study. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. Asystolic events not treated by the WCD likely also contributed to the nonsignificant primary outcome results of the trial. A subsequent as-treated and per- protocol analysis of VEST (censoring participants at the time they stopped wearing the WCD) reported a significant reduction in total and arrhythmic mortality among participants wearing the WCD compared with control participants (total mortality hazard ratio 0.25; CI 0.13-0.43; arrhythmic death hazard ratio 0.09; CI 0.02-0.39) [25]. The VEST study also demonstrates the challenges in trying to improve mortality in the post- MI population. Not all patients will survive despite initial appropriate and successful shocks for VT or VF. Of nine patients wearing the WCD with arrhythmic death in the VEST trial, four had been initially successfully treated but subsequently died. Of six patients who had an appropriate shock from the WCD but died during the study, two developed post-VT/VF asystole. Similar WCD shock rates (between 1.5 and 2 percent within 90 days post-MI) have been reported in observational studies [3,5,6]. In registry data from two large registries (involving 3569 and 8453 patients, respectively), similar rates of WCD shocks have been seen (1.7 and 1.6 percent of patients, respectively) [5,6]. Patients with LV dysfunction early after coronary revascularization Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD [16]. LVEF should be reassessed three months following CABG or PCI. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG or PCI, implantation of an ICD is usually indicated [16]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) While professional society guidelines do not specifically exclude ICD implantation for patients with LV dysfunction within three months of revascularization, reimbursement in some countries https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 9/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate may be denied. As an example, in the United States the national coverage decision for the Centers for Medicare & Medicaid Service (CMS) excludes coverage for primary prevention ICDs if patients have had CABG surgery or PCI within the past three months. This is based upon the clinical profile of subjects included in the major ICD trials for primary prevention of SCD in ischemic cardiomyopathy [12,13,26,27]. Despite this exclusion period, patients with LV dysfunction (eg, LVEF 30 percent) have been shown to have significantly higher rates of mortality early after PCI or CABG based on large National Cardiovascular Data Registry (NCDR) and Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database studies, respectively [28,29]. Patients with significant LV dysfunction have higher 30-day mortality rates after coronary artery bypass graft (CABG) surgery than patients with normal LV function. While these persons have an increased risk of SCD due to ventricular arrhythmias, they are also at risk for nonarrhythmic causes of death. There are limited data on the utility of an ICD in the early post-CABG period, as several ICD studies of primary prevention have excluded patients within one to three months after coronary revascularization [12-14]. However, the CABG Patch trial did not report a survival benefit from epicardial ICD implantation at the time of CABG in patients with LVEF 35 percent [27]. (See "Early cardiac complications of coronary artery bypass graft surgery" and "Early noncardiac complications of coronary artery bypass graft surgery".) Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within three months of CABG [16]. However, due to the risk of SCD in some patients early post-CABG, the WCD has been studied in this patient population, in whom wearing the WCD may provide protection from SCD during healing and potential recovery of LV function [3,16,17]. The potential utility for a WCD in this setting is illustrated by the following studies: In a nonrandomized comparison of nearly 5000 patients with LVEF 35 percent from two separate cohorts who underwent revascularization with CABG or percutaneous coronary intervention (PCI) (809 patients discharged with a WCD from a national registry and 4149 patients discharged without WCD from Cleveland Clinic CABG and PCI registries), patients discharged with the WCD had significantly lower 90-day mortality rates (3 versus 7 percent) [30]. While patients using a WCD appear to have improved outcomes, only 1.3 percent of the WCD group received an appropriate therapy while wearing the device, thereby indicating that the majority of the mortality benefit was not attributable to life-saving therapies from the WCD. In a German cohort of 354 patients who wore the WCD, including approximately 90 patients in the early post-CABG period, 7 percent received a shock for a ventricular tachyarrhythmia during the three months of WCD use [4]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 10/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In a study of 3569 patients in the United States using the WCD, among which 9 percent of WCD use was early post-CABG, appropriate shocks for a ventricular tachyarrhythmia occurred in 0.8 percent of these patients over a mean follow-up of 47 days [5,31]. Newly diagnosed nonischemic cardiomyopathy In selected patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function that is potentially reversible, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function [16,17]. While a benefit from ICD implantation has long been recognized in patients with significant LV systolic dysfunction related to underlying ischemic heart disease, an increase in SCD risk and potential benefit from an ICD has also been demonstrated in patients with a nonischemic cardiomyopathy in several studies [14,32]: In SCD-HeFT, which compared ICD implantation with amiodarone treatment alone or placebo for primary prevention of SCD in patients with ischemic or nonischemic heart failure and LVEF 35 percent, patients who received an ICD had significantly improved survival [14]. However, patients within three months of their initial heart failure diagnosis were excluded from this study. In DEFINITE, which compared ICD implantation with standard medical therapy to standard medical therapy alone for primary prevention of SCD in patients with a nonischemic cardiomyopathy, nonsustained VT, and LVEF 35 percent, there was a trend toward improved mortality in patients who received an ICD, regardless of duration since diagnosis [32]. Following DEFINITE, another study reported similar occurrences of lethal arrhythmias irrespective of diagnosis duration in patients with a nonischemic cardiomyopathy and LVEF 35 percent [33]. Major society guidelines recommend implantation of an ICD for nonischemic cardiomyopathy with LVEF 35 percent, provided that a reversible cause of transient LV dysfunction has been excluded and that response to optimal medical therapy has been assessed [16]. The guidelines do not specify a waiting period prior to reassessing LVEF. In the United States, however, the Center for Medicare Services (CMS) requires a three-month period of optimal medical therapy prior to reimbursement for ICD placement for primary prevention (if repeat LVEF assessment continues to show LVEF 35 percent). (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Nonischemic dilated cardiomyopathy'.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 11/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In patients felt to be at high risk of SCD while undergoing a trial of optimal medical therapy, the WCD may provide protection against SCD while awaiting improvement in LV function, although the event rates in this population appear to be lower than patients with ischemic cardiomyopathy [16]. In a post-approval study of the WCD, 0.7 percent of patients prescribed a WCD for recently diagnosed nonischemic cardiomyopathy required shocks for a ventricular tachyarrhythmia over a mean follow-up period of 57 days [5,31]. Among a single-center cohort of 254 patients with newly diagnosed nonischemic cardiomyopathy treated with the WCD between 2004 and 2015 (median duration of treatment 61 days, total follow-up 56.7 patient-years) who were highly compliant with using the WCD (median wear time 22 hours per day), no patients received an appropriate shock, and only three patients (1.2 percent) received an inappropriate shock [34]. This was compared with 6 of 271 patients (2.2 percent) with newly diagnosed ischemic cardiomyopathy who received an appropriate shock; in this group, two (0.7 percent) received inappropriate shocks. Of interest, 39 percent of nonischemic and 32 percent of ischemic cardiomyopathy patients experienced improvement in LVEF to >35 percent, obviating the need for an ICD. In a prospective study of the WCD in advanced heart failure patients (SWIFT), 75 patients hospitalized with heart failure (66 percent nonischemic cardiomyopathy) were prescribed a WCD for three months. Among the nonischemic cardiomyopathy patients, one had recurrent supraventricular tachycardia and another had multiple ventricular premature beats detected, but no WCD therapies were delivered [35]. In the WEARIT II registry, which included 927 patients with nonischemic cardiomyopathy, over a median wear time of 90 days, the treated event rate was 1 percent, compared with 3 percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. |
percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. In the US post-approval registry study, 23 of 3569 patients (0.6 percent) experienced asystole, with an associated mortality of 74 percent [5]. In the post-myocardial infarction (MI) registry of 8453 patients, 34 died (0.4 percent) with bradycardia-asystole events [6]. In the WEARIT-II registry, 6 of 2000 patients (0.3 percent) had asystole, and all three of the deaths that occurred while wearing the WCD during the study (0.2 percent) occurred following an asystole event [7]. The WCD cannot provide antitachycardia pacing for VT, which can reduce patient shocks, when effective. When considering these limitations, an implantable cardioverter-defibrillator (ICD) would be preferred, if indicated, in a patient who is pacemaker-dependent or in whom antitachycardia pacing is desired as the initial therapy for VT. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Use in patients with a preexisting permanent pacemaker With certain precautions, the WCD can be used in patients with a preexisting permanent pacemaker. The manufacturer recommends that the device not be worn if the pacemaker stimulus artifact exceeds 0.5 millivolts, as this may mask underlying ventricular fibrillation and prevent appropriate device therapy. Conversely, the VT threshold of the WCD should be set higher than the maximal pacing rate to avoid an inappropriate WCD shock due to oversensing paced beats. Following any WCD shock, the patient's pacemaker should be interrogated to ensure that there has been no damage to the pacemaker or any changes in the pacemaker setting. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 15/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Inappropriate shocks Both the WCD and the ICD may inappropriately deliver shocks due to electronic noise, device malfunction, or detection of supraventricular tachycardia above the preprogrammed rate criteria. Studies of ICDs have reported an incidence of inappropriate shock of 0.2 to 2.3 percent of patients per month [32,45-51]. Comparable rates of inappropriate shocks have been reported among users of the WCD, with rates ranging from 0.5 to 1.4 percent per month [3-7]. In a systematic review and meta-analysis which included 33,242 patients from 28 studies (the randomized VEST trial and 27 nonrandomized studies), inappropriate shocks occurred at a rate of 2 per 100 persons over three months (0.67 percent per month) [18]. Inappropriate shocks with a WCD can be potentially reduced due to the ability to abort shocks while awake by pressing response buttons. (See 'Avoiding inappropriate shocks' above.) Patient compliance and complaints Patients may not comply with wearing the WCD for a variety of reasons, chief among them device size and weight, skin rash, itching, and problems sleeping. However, efficacy of the WCD in the prevention of sudden cardiac death is highly dependent on patient compliance and appropriate use of the device [3-5,7]. In the WEARIT/BIROAD study, 23 percent of the 289 subjects withdrew before reaching a study endpoint, with size and weight of the monitor being the most frequent reason for withdrawal [3]. Skin rash and/or itching were also reported by 6 percent of patients. In the US postmarket study, median and mean daily use were 21.7 hours and 19.9 hours, respectively [5]. Daily use was >90 percent (>21.6 hours) in 52 percent of patients and >80 percent (>19.2 hours) in 71 percent of patients. Longer duration of monitoring correlated with higher compliance rates. WCD use was stopped prematurely in 14 percent, primarily because of comfort issues related to the size and weight of the WCD. In the WEARIT-II registry, median daily use was 22.5 hours [7]. Similar to the US postmarket study, longer duration of monitoring (15 or more days) was associated with higher rates of compliance. In the nationwide German cohort, median daily use among 6043 patients was 23.1 hours for a median of 59 days [8]. Lower rates of compliance were reported in a study of 147 patients from two academic medical centers in Boston, in which median daily use was 21 hours for a median of 50 days [52]. In an international registry of 708 patients, appropriate WCD shock was documented in 2.2 percent, inappropriate shock in 0.5 percent, and mean wear time was 21.2 4.3 hours/day (and was lower in younger patients) [53]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 16/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate In the WEARIT-France cohort study of 1157 patients, median daily wear time was 23.4 hours, with younger age associated with lower compliance [54]. In the VEST randomized trial after MI, median and mean daily wear times were only 18 and 14 hours, respectively, with over half of patients assigned to the WCD not wearing it by the end of the 90-day study [24]. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. In the as-treated and per-protocol analysis of VEST [25], better WCD compliance was predicted by cardiac arrest during index MI, higher creatinine, diabetes, prior heart failure, ejection fraction 25 percent, Polish enrolling center, and number of WCD alarms. Worse compliance was associated with being divorced, Asian race, higher body mass index, prior PCI, or any WCD shock. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, median daily use was high at 23 hours [11]. Rates of WCD discontinuation appear similar to reported rates of compliance with other prescribed therapies. One study reported that 15 percent of patients stop using aspirin, ACE inhibitors and beta-blockers within 30 days of a MI [55]. Improved compliance and acceptance of the WCD may be seen with newer devices, which are 40 percent smaller in size and weight or which offer multiple sizes and gender-specific fitting. USE OF THE WCD IN CHILDREN In December 2015, the US Food and Drug Administration (FDA) approved the WCD for use in children, although the WCD was used off-label prior to FDA approval [56]. As such, there are relatively few peer-reviewed publications documenting experience with the WCD in children [57- 59]. In a retrospective review of all patients <18 years of age who were prescribed the WCD between 2009 and 2016 (n = 455 patients), median duration of use was 33 days and wear time 20.6 hours [59]. Eight patients received at least one shock (seven episodes of ventricular tachycardia/ventricular fibrillation [VT/VF] in six patients, two inappropriate shocks due to oversensing), with four of the seven episodes of VT/VF terminated with a single shock and all seven episodes successfully terminated by the WCD. There were seven deaths (1.5 percent); none were wearing the WCD at the time of death. Children require special attention to assure compliance and correct fitting for optimal use. A variety of device harness sizes are available, but the smallest option may still be too large for https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 17/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate smaller children. Additional data on clinical efficacy, compliance, and complications should be collected in children as WCD use increases. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Introduction The wearable cardioverter-defibrillator (WCD) is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) ( picture 1). In cases where the need for an implantable cardioverter- defibrillator (ICD) is felt to be temporary or implantation of the ICD must be deferred, a WCD may be an acceptable alternative approach for the prevention of sudden cardiac death (SCD). (See 'Description and functions of the WCD' above.) Device functions In addition to delivering therapeutic shocks for life-threatening ventricular arrhythmias, the WCD stores data regarding arrhythmias, patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted to the manufacturer's network. (See 'Storage of ECGs and compliance data' above.) Efficacy When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in nearly 100 percent of cases. In addition, inappropriate shock rates from the WCD appear to be comparable to and in some studies lower than those reported for ICDs. (See 'Efficacy in terminating VT/VF' above and 'Inappropriate shocks' above.) Indications The WCD is an option as temporary therapy for select patients with a high risk for SCD: Among patients with left ventricular ejection fraction (LVEF) 35 percent who are less than 40 days post-myocardial infarction (MI), we discuss the potential benefits and risks of WCD use and offer it to highly motivated patients with NYHA functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 18/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate implantation after 40 days. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, despite appropriate medical therapy, ICD implantation is indicated and should be considered. (See 'Early post-MI patients with LV dysfunction' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD. LVEF should be reassessed three months following CABG. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG, implantation of an ICD is usually indicated. (See 'Patients with LV dysfunction early after coronary revascularization' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) In selected patients with severe but potentially reversible cardiomyopathy, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See 'Newly diagnosed nonischemic cardiomyopathy' above.) Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD in whom ICD implantation is often recommended. The WCD may be a reasonable noninvasive alternative approach, particularly for patients whose anticipated waiting time to transplant is short if an ICD is not already present. (See 'Bridge to heart transplant' above.) Some patients with an indication for an ICD may require a delay in ICD implantation due to comorbid conditions (ie, infection, recovery from surgery, lack of vascular access). Additionally, some patients who have an ICD need it removed due to infection. In such patients, the WCD may provide protection against ventricular tachyarrhythmias until an ICD can be implanted or reimplanted. (See 'Bridge to indicated or interrupted ICD therapy' above.) Device limitations Limitations of the WCD (compared with a traditional ICD) include the lack of pacemaker functionality, the requirement for patient interaction and compliance, and potential discomfort due to the size and weight of the device. (See 'Limitations and precautions' above.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 19/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Sharma PS, Bordachar P, Ellenbogen KA. Indications and use of the wearable cardiac defibrillator. Eur Heart J 2016. 2. Reek S, Geller JC, Meltendorf U, et al. Clinical efficacy of a wearable defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks. Pacing Clin Electrophysiol 2003; 26:2016. 3. Feldman AM, Klein H, Tchou P, et al. Use of a wearable defibrillator in terminating tachyarrhythmias in patients at high risk for sudden death: results of the WEARIT/BIROAD. Pacing Clin Electrophysiol 2004; 27:4. 4. Klein HU, Meltendorf U, Reek S, et al. Bridging a temporary high risk of sudden arrhythmic death. Experience with the wearable cardioverter defibrillator (WCD). Pacing Clin Electrophysiol 2010; 33:353. 5. Chung MK, Szymkiewicz SJ, Shao M, et al. Aggregate national experience with the wearable cardioverter-defibrillator: event rates, compliance, and survival. J Am Coll Cardiol 2010; 56:194. 6. Epstein AE, Abraham WT, Bianco NR, et al. Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction. J Am Coll Cardiol 2013; 62:2000. 7. 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Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry. Circulation 2012; 125:1501. 29. Shahian DM, O'Brien SM, Sheng S, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation 2012; 125:1491. 30. Zishiri ET, Williams S, Cronin EM, et al. Early risk of mortality after coronary artery revascularization in patients with left ventricular dysfunction and potential role of the wearable cardioverter defibrillator. Circ Arrhythm Electrophysiol 2013; 6:117. 31. Verdino RJ. The wearable cardioverter-defibrillator: lifesaving attire or "fashion faux pas?". J Am Coll Cardiol 2010; 56:204. 32. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350:2151. 33. Makati KJ, Fish AE, England HH, et al. Equivalent arrhythmic risk in patients recently diagnosed with dilated cardiomyopathy compared with patients diagnosed for 9 months or more. Heart Rhythm 2006; 3:397. 34. Singh M, Wang NC, Jain S, et al. Utility of the Wearable Cardioverter-Defibrillator in Patients With Newly Diagnosed Cardiomyopathy: A Decade-Long Single-Center Experience. J Am Coll Cardiol 2015; 66:2607. 35. Barsheshet A, Kutyifa V, Vamvouris T, et al. Study of the wearable cardioverter defibrillator in advanced heart-failure patients (SWIFT). J Cardiovasc Electrophysiol 2017; 28:778. 36. Salehi N, Nasiri M, Bianco NR, et al. The Wearable Cardioverter Defibrillator in Nonischemic Cardiomyopathy: A US National Database Analysis. Can J Cardiol 2016; 32:1247.e1. 37. Duncker D, K nig T, Hohmann S, et al. Avoiding Untimely Implantable Cardioverter/Defibrillator Implantation by Intensified Heart Failure Therapy Optimization https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 22/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Supported by the Wearable Cardioverter/Defibrillator-The PROLONG Study. J Am Heart Assoc 2017; 6. 38. Saltzberg MT, Szymkiewicz S, Bianco NR. Characteristics and outcomes of peripartum versus nonperipartum cardiomyopathy in women using a wearable cardiac defibrillator. J Card Fail 2012; 18:21. 39. Lang CC, Hankins S, Hauff H, et al. Morbidity and mortality of UNOS status 1B cardiac transplant candidates at home. J Heart Lung Transplant 2003; 22:419. 40. Opreanu M, Wan C, Singh V, et al. Wearable cardioverter-defibrillator as a bridge to cardiac transplantation: A national database analysis. J Heart Lung Transplant 2015; 34:1305. 41. Gronda E, Bourge RC, Costanzo MR, et al. Heart rhythm considerations in heart transplant candidates and considerations for ventricular assist devices: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates 2006. J Heart Lung Transplant 2006; 25:1043. 42. Cantillon DJ, Tarakji KG, Kumbhani DJ, et al. Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator. Heart Rhythm 2010; 7:466. 43. Wan C, Herzog CA, Zareba W, Szymkiewicz SJ. Sudden cardiac arrest in hemodialysis patients with wearable cardioverter defibrillator. Ann Noninvasive Electrocardiol 2014; 19:247. 44. Wan C, Szymkiewicz SJ, Klein HU. The impact of body mass index on the wearable cardioverter defibrillator shock efficacy and patient wear time. Am Heart J 2017; 186:111. 45. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation 2005; 111:2898. 46. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008; 359:1009. 47. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008; 51:1357. 48. Klein RC, Raitt MH, Wilkoff BL, et al. Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. J Cardiovasc Electrophysiol 2003; 14:940. 49. Wilkoff BL, Ousdigian KT, Sterns LD, et al. A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 23/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate randomized multicenter EMPIRIC trial. J Am Coll Cardiol 2006; 48:330. 50. Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 2008; 52:541. 51. Wilkoff BL, Hess M, Young J, Abraham WT. Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 2004; 15:1002. 52. Leyton-Mange JS, Hucker WJ, Mihatov N, et al. Experience With Wearable Cardioverter- Defibrillators at 2 Academic Medical Centers. JACC Clin Electrophysiol 2018; 4:231. 53. El-Battrawy I, Kovacs B, Dreher TC, et al. Real life experience with the wearable cardioverter- defibrillator in an international multicenter Registry. Sci Rep 2022; 12:3203. 54. Garcia R, Combes N, Defaye P, et al. Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study. Europace 2021; 23:73. 55. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006; 166:1842. 56. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm466852.htm (Access ed on December 21, 2015). 57. Everitt MD, Saarel EV. Use of the wearable external cardiac defibrillator in children. Pacing Clin Electrophysiol 2010; 33:742. 58. Collins KK, Silva JN, Rhee EK, Schaffer MS. Use of a wearable automated defibrillator in children compared to young adults. Pacing Clin Electrophysiol 2010; 33:1119. 59. Spar DS, Bianco NR, Knilans TK, et al. The US Experience of the Wearable Cardioverter- Defibrillator in Pediatric Patients. Circ Arrhythm Electrophysiol 2018; 11:e006163. Topic 15824 Version 35.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 24/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate GRAPHICS Wearable cardioverter-defibrillator The wearable cardioverter-defibrillator consists of a vest incorporating two defibrillation electrodes and four sensing electrocardiographic electrodes connected to a waist unit containing the monitoring and defibrillation electronics. Reproduced with permission from: ZOLL Medical Corporation. Copyright 2012. All rights reserved. Graphic 60103 Version 3.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 25/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Electrocardiogram sensing (A) Five ECG electrodes are positioned circumferentially around the torso at the level of the subxiphoid process, labelled left front (LF), right front (RF), left back (LB), right back (RB), and right leg drive (RLD). Red dashed arrows represent the four differential ECG vectors derived using RLD as a ground reference. (B) Garment interior depicting five embedded, cushioned ECG electrodes and defibrillation pads (two posterior and one anterior). ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140856 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 26/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate ASSURE WCD System noise management The A WCD employs three levels of protection to achieve a low false alarm rate due to noise. Level 1 (blue) minimize noise. Level 2 (red) detect and remove noise that does occur. Level 3 (yellow) allow time for remaining noise to subside before alarming. A-WCD: ASSURE WCD System; VT: ventricular tachycardia; VF: ventricular fibrillation; ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140843 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 27/28 7/6/23, 3:34 PM Wearable cardioverter-defibrillator - UpToDate Contributor Disclosures Mina K Chung, MD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 28/28 |
7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Bundle branch reentrant ventricular tachycardia : David J Callans, MD : Peter J Zimetbaum, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 15, 2022. INTRODUCTION Bundle branch reentrant ventricular tachycardia (BBRVT) is a unique arrhythmia because the tachycardia circuit is dependent exclusively on the specialized conduction system. This has two important implications: a large portion of the circuit can be recorded directly, and the circuit is uniquely sensitive to the effects of focal ablation. The circuit involves antegrade conduction over the right bundle branch and retrograde conduction over the left bundle branch; the His bundle is adjacent to but separate from the circuit. BBRVT can be very rapid (often >200 beats per minute), often resulting in syncope or cardiac arrest. It is a relatively rare arrhythmia, usually seen in patients with advanced structural heart disease, and it forms part of the differential diagnosis of wide complex tachycardias (in addition to myocardial VT, supraventricular tachycardia [SVT] with aberrancy of the left bundle branch, and pre-excited tachycardias using nodofascicular or atrial fascicular bypass tracts). (See "Wide QRS complex tachycardias: Approach to the diagnosis".) A related disorder, intrafascicular reentry (also called idiopathic left ventricular tachycardia), utilizes the separate fascicles of the left bundle branch. It, too, is typically observed in patients with advanced structural heart disease but may also be seen in patients with structurally normal hearts [1,2]. Both arrhythmias depend on conduction delay in the His-Purkinje system. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Idiopathic left ventricular tachycardia'.) https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 1/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate The mechanisms, clinical features, diagnosis, and treatment of BBRVT will be discussed here. The general approach to wide QRS complex tachycardias as well as the treatment of VT of other etiologies (ie, ischemic, scar-related) are discussed separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis".) EPIDEMIOLOGY The exact incidence of BBRVT has been difficult to quantify, given that the diagnosis is typically only confirmed following invasive electrophysiology studies. Several small series have reported incidences ranging from as low as 3 to as high as 20 percent, but most series are likely subject to referral bias, making the true incidence of BBRVT in the general population difficult to define [3- 6]. MECHANISM AND THE RESULTANT ELECTROCARDIOGRAM (ECG) With BBRVT, the arrhythmia begins when one or more premature ventricular beats arise and conduct into both the right bundle branch, where retrograde activation is blocked due to refractoriness from the preceding normally conducted antegrade beat, and into the left bundle branch, which has a shorter refractory period than the right bundle branch ( figure 1). As a result, the impulse conducts retrogradely up the left bundle branch to the bundle of His, although the His bundle is not an essential component of the circuit. The impulse then conducts antegradely down the right bundle branch, activating the ventricle at the termination of the right bundle branch. For this reason, the QRS during VT has a left bundle branch block (LBBB) pattern and may closely resemble the sinus rhythm QRS if baseline LBBB is present. If the timing is right and slow conduction through the circuit allows for recovery from refractoriness of all of the component parts, sustained reentry may be established. It is important to consider that although we speak of LBBB as an electrocardiographic pattern, the phenomena is typically a delay rather than a block, as retrograde complete LBBB would make this arrhythmia circuit impossible. CLINICAL FEATURES BBRVT, usually seen in patients with advanced structural heart disease, occurs with both ischemic and nonischemic heart disease [3,7,8]. The heart disease is usually severe with cardiomegaly and a history of heart failure (HF); however, BBRVT may occur in the absence of https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 2/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate structural heart disease in the setting of isolated conduction disturbances in the His-Purkinje system [9]. Symptoms Patients with BBRVT may variably experience palpitations. In most instances, patients will present with presyncope, syncope, or sudden cardiac arrest (SCA). Because BBRVT rates are typically rapid (>200 beats per minute) and because BBRVT most commonly occurs in patients with advanced structural heart disease, hemodynamic instability leading to syncope or SCA is common. ECG findings When VT develops, antegrade conduction down the right bundle branch with delayed depolarization of the left ventricle results in a VT with a typical left bundle branch block (LBBB) appearance ( waveform 1). In some patients, however, the reverse sequence of conduction occurs, leading to a right bundle branch block (RBBB) appearance. The PR interval may be normal or prolonged. The mean electrical axis is usually about +30 , but a conduction defect in the left anterior fascicle will produce a marked leftward (superior) axis deviation ( figure 2). In sinus rhythm, most patients with BBRVT have a prolonged QRS (nonspecific conduction delay or LBBB), and most have a prolonged His-to-ventricle (HV) interval. Most patients have a similar ECG during sinus rhythm because of the underlying prolongation of the HV interval ( waveform 1). A prolonged HV interval has been put forth as a prerequisite for developing sustained reentry within the bundle branches [3,10-13]. However, HV prolongation in sinus rhythm is not present in all cases, suggesting that BBRVT can result from functional conduction abnormalities in the His-Purkinje system [14]. EPS findings During invasive electrophysiology study (EPS), the most important recording is the His bundle recording during induced VT. During BBRVT, the HV is typically similar to, or a little longer than, the HV that is recorded in sinus rhythm. During other forms of VT, the HV is usually negative (ie, shorter than sinus rhythm). In addition, if there are irregularities in the cycle length, changes in the His-to-His interval precede changes in the V-to-V interval. DIFFERENTIAL DIAGNOSIS The differential diagnosis of BBRVT includes all of the usual causes of wide QRS complex tachycardia, including: VT of other types (monomorphic, polymorphic) SVT with aberrant conduction SVT with pre-excitation https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 3/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate SVT with ventricular pacing Artifact mimicking wide QRS complex tachycardia BBRVT has a rather "typical" left bundle branch block (LBBB) pattern as does an SVT with pre- existing or functional BBB. In comparison, an "atypical" LBBB pattern (slurring of the initial QRS forces) favors myocardial VT or pre-excited tachycardia. While the presence of BBRVT may be suspected from the surface ECG, definitively establishing the diagnosis often requires electrophysiologic testing to differentiate this arrhythmia from other forms of VT. The general approach to wide complex tachycardias is discussed separately. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Differential diagnosis of WCT' and "Wide QRS complex tachycardias: Approach to the diagnosis".) DIAGNOSIS The diagnosis of BBRVT is suggested from the surface ECG recorded during VT. BBRVT is suggested on the surface ECG by the following characteristics: Left bundle branch block (LBBB) morphology (although so-called "reverse" BBRVT may also occur, with activation of the ventricles over the left bundle branch, producing a right bundle branch block [RBBB] QRS morphology) The His-to-ventricle (HV) interval during VT is typically longer than during sinus rhythm During spontaneous changes in cycle length, changes in the H-H interval precede and predict changes in the V-V interval Typically, however, confirmation of the diagnosis is made during invasive electrophysiology studies (EPS). During BBRVT, the HV is typically similar to, or a little longer than, the HV that is recorded in sinus rhythm, in contrast to the HV findings in other forms of VT. TREATMENT Treatment is frequently necessary in BBRVT, since BBRVT typically occurs in the presence of significant heart disease and often leads to hemodynamic compromise that can result in presyncope, syncope, or SCA. Radiofrequency catheter ablation is curative in most patients, although some patients may also be candidates for an implantable cardioverter-defibrillator (ICD) for secondary or primary prevention based on the presence of other structural heart disease. Antiarrhythmic drug therapy is rarely used given the high risk of BBRVT recurrence. https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 4/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Catheter ablation For patients with symptomatic BBRVT, we recommend treatment with radiofrequency catheter ablation, rather than antiarrhythmic drug therapy or ICD implantation alone. This approach is based on the high efficacy of catheter ablation for curing BBRVT, the significant hemodynamic compromise which results from BBRVT in most patients, and the relatively poor efficacy of antiarrhythmic drug therapy in treating this arrhythmia. This approach is consistent with the guidance provided by multiple professional society guidelines [15]. The 2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias recommended catheter ablation for reducing the risk of recurrent BBRVT [16,17]. Reentrant fascicular tachycardia has also been treated successfully using ablation [1,2]. Because the circuit of BBRVT is so well defined and because the main circuit components (right bundle branch, left bundle branch) are easy to locate, catheter ablation for BBRVT is conceptually and mechanically simple. Most commonly, catheter ablation of the right bundle branch is performed, leading to complete right bundle branch block (RBBB). In this procedure, a catheter is inserted into the femoral vein and passed through the tricuspid valve until a right bundle electrogram is recorded. Ablation at this site typically leads to nearly immediate production of RBBB, which predicts the absence of recurrent VT ( waveform 1 and waveform 2 and waveform 3). BBRVT has also been treated by ablation of the left bundle [18,19]. This provides the theoretical advantage of preventing the need for pacing, as the relatively normal right bundle branch remains unaffected. It is not so often performed, however, since this procedure requires arterial access and localization of the left bundle is more difficult than the right bundle. In addition, the majority of patients with BBRVT require ICD therapy anyway. (See 'ICD therapy' below.) Multiple small observational studies have demonstrated nearly universal success of catheter ablation [2,4,8,10,11,19-23]. The largest observational series described a cohort of 32 patients (treated between 2005 and 2016) who had successful ablation of the right or left bundle branch at a single center. The procedure was well tolerated, with only one patient developing complete heart block; over a mean follow-up of almost eight years, no patient had recurrent BBRVT [24]. The efficacy and safety of catheter ablation is also supported by indirect evidence and more extensive experience in other settings, including for both ventricular and supraventricular arrhythmias. (See "Overview of catheter ablation of cardiac arrhythmias" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation' and "Atrioventricular nodal reentrant tachycardia", section on 'Catheter ablation' and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Catheter ablation'.) https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 5/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Antiarrhythmic drug therapy BBRVT is often resistant to antiarrhythmic drug therapy [10,11]. In a study of catheter ablation for BBRVT in the 1990s, seven patients were treated successfully with catheter ablation after failure of a mean of 3 1 antiarrhythmic drugs [10]. In a different non-randomized study from the 1990s comparing the efficacy of catheter ablation and antiarrhythmic drugs, ablation successfully eliminated the arrhythmia in all patients, while only 62 percent of patients treated with antiarrhythmic drugs had no recurrent VT [11]. As such, we limit use of antiarrhythmic drugs for the treatment of BBRVT to two subsets of patients: Patients who are not a candidate for, or refuse, catheter ablation Patients with recurrent symptomatic VT following catheter ablation in whom antiarrhythmic drug therapy is administered to reduce the likelihood of recurrent ICD shocks. ICD therapy Following catheter ablation for BBRVT, repeat electrophysiologic studies generally reveal an inability to induce BBRVT. However, VT of myocardial origin can be induced in some cases, although only a small number of patients have been studied. Because of the concurrent underlying structural heart disease, outcomes are often quite poor in patients followed after successful ablation of BBRVT. Sudden cardiac death (SCD) has been reported, and progressive HF is frequent [23,25]. Due to the severity of underlying cardiac disease, many patients are candidates for ICD therapy for the primary or secondary prevention of SCD following catheter ablation for BBRVT [15]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Summary and recommendations' and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 6/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Bundle branch reentrant ventricular tachycardia (BBRVT) is a unique arrhythmia because the tachycardia circuit is dependent exclusively on the specialized conduction system. The circuit most commonly involves antegrade conduction over the right bundle branch and retrograde conduction over the left bundle branch; the His bundle is adjacent to but separate from the circuit. (See 'Introduction' above.) Patients with BBRVT typically have advanced structural heart disease, either ischemic or nonischemic heart disease. Presyncope, syncope, or sudden cardiac arrest are the common presenting symptoms of BBRVT. (See 'Clinical features' above.) The diagnosis of BBRVT is suggested from the surface electrocardiogram (ECG), on which BBRVT has a rather "typical" left bundle branch block pattern. While the presence of BBRVT may be suspected from the surface ECG, definitively establishing the diagnosis often requires electrophysiologic testing to differentiate this arrhythmia from other forms of VT. (See 'ECG findings' above and 'Diagnosis' above.) For patients with symptomatic BBRVT, we recommend treatment with radiofrequency catheter ablation, rather than antiarrhythmic drug therapy or implantable cardioverter defibrillator (ICD) implantation alone (Grade 1B). This approach is based on the high efficacy of catheter ablation for curing BBRVT, the significant hemodynamic compromise which results from BBRVT in most patients, general safety and tolerability of catheter ablation, and the relatively poor efficacy and greater side effects of antiarrhythmic drug therapy in treating this arrhythmia. (See 'Treatment' above.) Depending on the severity of concurrent underlying structural heart disease in patients with BBRVT, many patients are candidates for ICD therapy for the primary or secondary https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 7/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate prevention of sudden cardiac death following catheter ablation for BBRVT. (See 'ICD therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Crijns HJ, Smeets JL, Rodriguez LM, et al. Cure of interfascicular reentrant ventricular tachycardia by ablation of the anterior fascicle of the left bundle branch. J Cardiovasc Electrophysiol 1995; 6:486. 2. Lopera G, Stevenson WG, Soejima K, et al. Identification and ablation of three types of ventricular tachycardia involving the his-purkinje system in patients with heart disease. J Cardiovasc Electrophysiol 2004; 15:52. 3. Caceres J, Jazayeri M, McKinnie J, et al. Sustained bundle branch reentry as a mechanism of clinical tachycardia. Circulation 1989; 79:256. 4. Delacretaz E, Stevenson WG, Ellison KE, et al. Mapping and radiofrequency catheter ablation of the three types of sustained monomorphic ventricular tachycardia in nonischemic heart disease. J Cardiovasc Electrophysiol 2000; 11:11. 5. Cantillon DJ, Bianco C, Wazni OM, et al. Electrophysiologic characteristics and catheter ablation of ventricular tachyarrhythmias among patients with heart failure on ventricular assist device support. Heart Rhythm 2012; 9:859. 6. Romero J, Santangeli P, Pathak RK, et al. Bundle branch reentrant ventricular tachycardia: review and case presentation. J Interv Card Electrophysiol 2018; 52:385. 7. Lloyd EA, Zipes DP, Heger JJ, Prystowsky EN. Sustained ventricular tachycardia due to bundle branch reentry. Am Heart J 1982; 104:1095. 8. Nogami A. Purkinje-related arrhythmias part I: monomorphic ventricular tachycardias. Pacing Clin Electrophysiol 2011; 34:624. 9. Chen H, Shi L, Yang B, et al. Electrophysiological Characteristics of Bundle Branch Reentry Ventricular Tachycardia in Patients Without Structural Heart Disease. Circ Arrhythm Electrophysiol 2018; 11:e006049. 10. Cohen TJ, Chien WW, Lurie KG, et al. Radiofrequency catheter ablation for treatment of bundle branch reentrant ventricular tachycardia: results and long-term follow-up. J Am Coll Cardiol 1991; 18:1767. 11. Blanck Z, Dhala A, Deshpande S, et al. Bundle branch reentrant ventricular tachycardia: cumulative experience in 48 patients. J Cardiovasc Electrophysiol 1993; 4:253. https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 8/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate 12. Merino JL, Peinado R, Fern ndez-Lozano I, et al. Transient entrainment of bundle-branch reentry by atrial and ventricular stimulation: elucidation of the tachycardia mechanism through analysis of the surface ECG. Circulation 1999; 100:1784. 13. Merino JL, Peinado R, Fernandez-Lozano I, et al. Bundle-branch reentry and the postpacing interval after entrainment by right ventricular apex stimulation: a new approach to elucidate the mechanism of wide-QRS-complex tachycardia with atrioventricular dissociation. Circulation 2001; 103:1102. 14. Li YG, Gr nefeld G, Israel C, et al. Bundle branch reentrant tachycardia in patients with apparent normal His-Purkinje conduction: the role of functional conduction impairment. J Cardiovasc Electrophysiol 2002; 13:1233. 15. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 16. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17:e2. 17. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias: Executive summary. Heart Rhythm 2020; 17:e155. 18. Blanck Z, Deshpande S, Jazayeri MR, Akhtar M. Catheter ablation of the left bundle branch for the treatment of sustained bundle branch reentrant ventricular tachycardia. J Cardiovasc Electrophysiol 1995; 6:40. 19. Schmidt B, Tang M, Chun KR, et al. Left bundle branch-Purkinje system in patients with bundle branch reentrant tachycardia: lessons from catheter ablation and electroanatomic mapping. Heart Rhythm 2009; 6:51. 20. Tchou P, Jazayeri M, Denker S, et al. Transcatheter electrical ablation of right bundle branch. A method of treating macroreentrant ventricular tachycardia attributed to bundle branch reentry. Circulation 1988; 78:246. 21. Volkmann H, K hnert H, Dannberg G, Heinke M. Bundle branch reentrant tachycardia treated by transvenous catheter ablation of the right bundle branch. Pacing Clin Electrophysiol 1989; 12:258. 22. Tai YT, Lee KL. Pleomorphic ventricular tachycardia with antegrade His-bundle activation: elucidation by multiple His-bundle recordings. J Cardiovasc Electrophysiol 1994; 5:350. https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 9/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate 23. Mehdirad AA, Keim S, Rist K, Tchou P. Long-term clinical outcome of right bundle branch radiofrequency catheter ablation for treatment of bundle branch reentrant ventricular tachycardia. Pacing Clin Electrophysiol 1995; 18:2135. 24. Pathak RK, Fahed J, Santangeli P, et al. Long-Term Outcome of Catheter Ablation for Treatment of Bundle Branch Re-Entrant Tachycardia. JACC Clin Electrophysiol 2018; 4:331. 25. Blanck Z, Akhtar M. Ventricular tachycardia due to sustained bundle branch reentry: diagnostic and therapeutic considerations. Clin Cardiol 1993; 16:619. Topic 899 Version 27.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 10/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate GRAPHICS Mechanism of bundle branch reentrant ventricular tachycardia Schematic representation of the reentrant circuit in bundle branch reentrant ventricular tachycardia (BBRVT) showing a ventricular premature beat that blocks in the right bundle branch (RBB), conducts slowly up the left bundle branch (LBB), activates the bundle of His, and returns antegradely down the RBB. If the RBB has recovered its excitability from the preceding beat, the circuit is completed, and the reentrant circuit may become repetitive. AV: atrioventricular; PVC: premature ventricular contraction. Graphic 75164 Version 5.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 11/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Surface 12-lead ECG in bundle branch reentrant ventricular tachycardia Left panel: 12 lead ECG during sinus rhythm; there is a left bundle branch block- type intraventricular conduction delay. Right panel: 12 lead ECG during VT; there is a remarkable similarity in QRS morphology during VT and sinus rhythm. The HV interval during sinus rhythm was 65 milliseconds, suggesting underlying His-Purkinje conduction disease. ECG: electrocardiogram; VT: ventricular tachycardia. Graphic 67679 Version 5.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 12/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate EP study in BBRVT Twelve surface ECG leads and intracardiac recordings from the ablation catheter (Carto D: placed at the location of the distal His recording), a decapolar His catheter (H1,2 to H9,10), and the RV catheter are shown during BBRVT. There are spontaneous cycle length variations in the tachycardia. Changes in the H-H interval predict the subsequent changes in the V-V interval, suggesting the dependence of the tachycardia on the His Purkinje network. This finding strongly supports the diagnosis of BBRVT. ECG: electrocardiogram; RV: right ventricular; BBRVT: bundle branch reentrant ventricular tachycardia. Graphic 79400 Version 2.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 13/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Intracardiac and surface ECG recordings during electrophysiologic study of bundle branch reentrant ventricular tachycardia Shown are five surface ECG leads (I, II, aVF, V1, V6) and intracardiac recordings from the high right atrium (HRA3-4), His bundle region (HBE1-2), and the right ventricular apex (RVA3-4). The atrial and ventricular (V) electrograms are dissociated, confirming a ventricular tachycardia; however, a His bundle depolarization (H) precedes each ventricular electrogram. Further testing confirmed the diagnosis of bundle branch reentrant ventricular tachycardia (BBRVT), a macroreentrant ventricular tachycardia involving the left and right bundle branches. During typical BBRVT, the wavefront goes down the right bundle, across the interventricular septum, and then retrograde up the left bundle, with passive retrograde activation of the His bundle. Since both bundle branches are necessary parts of the macroreentry circuit, catheter ablation of the right bundle branch is curative. Graphic 77331 Version 4.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 14/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Intracardiac and surface ECG tracings during radiofrequency catheter ablation of the right bundle branch in a patient with BBRVT Shown are five surface ECG leads (I, II, aVF, V1, V6) and intracardiac recordings from the His bundle region (HBE2-3,1-2), the right ventricular apex (RVA3-4), and a mapping catheter (USER1) positioned distal to the His catheter along the RV septum. Application of radiofrequency (RF) energy to the tip of the mapping catheter causes two accelerated beats with a typical left bundle branch block (LBBB) morphology (black arrow), likely from heating and activating the right bundle branch. After these beats, complete right bundle branch block (RBBB) is present (red arrow), as evidenced by the change in QRS morphology, particularly in lead V1. Following right bundle branch ablation, the HV interval increased to 105 milliseconds, though no infranodal A-V block was noted. Right bundle branch reentrant tachycardia was no longer inducible. A permanent pacemaker was placed because of the markedly prolonged HV interval. H: His bundle electrogram; A: atrial electrogram; V: ventricular electrogram; ECG: electrocardiogram; RV: right ventricular. Graphic 80017 Version 6.0 https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 15/16 7/6/23, 3:39 PM Bundle branch reentrant ventricular tachycardia - UpToDate Contributor Disclosures David J Callans, MD Consultant/Advisory Boards: Abbott [Catheter ablation, leadless pacing, clinical events committee member for Nanosense trial]; Biosense Webster [Catheter ablation]; Boston Scientific [Catheter ablation, directing fellows programs]; Medtronic [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/bundle-branch-reentrant-ventricular-tachycardia/print 16/16 |
7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Catecholaminergic polymorphic ventricular tachycardia : Alfred Buxton, MD : Peter J Zimetbaum, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 14, 2022. INTRODUCTION Polymorphic (or polymorphous) ventricular tachycardia (VT) is defined as a ventricular rhythm at a rate greater than 100 beats per minute (bpm) with a continuously varying QRS complex morphology in any recorded electrocardiographic (ECG) lead. The simultaneous recording of more than one ECG lead is often necessary to detect these changes. Most polymorphic VTs are rapid (often >200 bpm), but an absolute rate has not been established, and VT at a slower rate can manifest changing QRS morphology [1]. Some episodes of polymorphic VT cause hemodynamic collapse, and some degenerate into ventricular fibrillation (VF); however, many episodes terminate spontaneously. Polymorphic VTs are classified based upon their association with a normal or prolonged QT interval. Spontaneous polymorphic VT in the presence of a normal QT interval usually occurs in the setting of coronary heart disease or nonischemic cardiomyopathy. However, some patients have no structural heart disease or may have a familial syndrome. Catecholaminergic polymorphic VT (CPVT) will be reviewed here. Polymorphic VT associated with a prolonged QT interval, which has a different etiology and mechanism, is known as torsades de pointes ("twisting of points") and is discussed separately. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations", section on 'Polymorphic VT/torsades de pointes' and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) EPIDEMIOLOGY https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 1/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate CPVT, also known as familial CPVT, occurs in the absence of structural heart disease or known associated syndromes [2-11]. This disorder typically begins in childhood or adolescence, although cases have been reported with initial presentation in the fourth decade of life [5]. Affected patients may have a family history of juvenile sudden death or stress-induced syncope [3,5]. CPVT may also present sporadically as a de novo mutation in individuals with no family history [5,12]. CPVT occurs with similar frequency in males and females, but males are more likely to present at an earlier age (in childhood or adolescence), while females are more likely to present at an older age (20 years, mean) [5]. GENETICS Pathogenic variants in several genes have been identified in patients with CPVT. The most common variants are in the cardiac ryanodine receptor gene (an autosomal dominant form) and the calsequestrin 2 gene (autosomal recessive). Both mutations appear to act by inducing diastolic calcium release from the sarcoplasmic reticulum. The resulting intracellular calcium overload leads to delayed afterdepolarizations and triggered activity, which can induce ventricular tachycardia and fibrillation. Mutations in these two genes have been recognized in only 70 percent of patients with CPVT, implying that other genes play a role [13]. More recently, an analysis of published studies found other pathogenic variants that are associated with CPVT; these variants are much less common than RyR2 and CASQ2 and are described in more detail below [14]. Cardiac ryanodine receptor An autosomal dominant form of CPVT was initially linked to chromosome 1q42-q43 [6]. Subsequent studies identified mutations in the gene for the human cardiac ryanodine receptor (RyR2), which is also called the cardiac sarcoplasmic calcium release channel [5,7,8,15,16]. One report suggested that abnormal RyR2 channels may account for at least one in every seven cases of sudden unexplained death [17]. RyR2 mediates the release of calcium from the sarcoplasmic reticulum that is required for myocardial contraction. The FK506 binding protein (FKBP12.6) stabilizes RyR2, preventing aberrant activation. In familial polymorphic VT, mutations in RYR2 change RyR2's protein structure, which prevents regulation by FKBP12.6 and results in increased RyR2 channel activity during adrenergic stimulation (eg, simulated exercise, beta adrenergic stimulation) [15,18]. In these settings, the "leaky" RyR2 channels increase diastolic calcium release and can trigger life-threatening ventricular arrhythmias, probably via delayed afterdepolarizations [15,18,19]. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 2/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Two other types of RYR2 mutations differ from those associated with familial polymorphic VT in structurally normal hearts. A large genomic deletion in RYR2 that leads to polymorphic VT and extended phenotypes (including sinoatrial node and atrioventricular node dysfunction, atrial fibrillation, atrial standstill, and dilated left ventricular cardiomyopathy) has been identified in 16 members of two separate families [20]. Another mutation in RYR2 is responsible for exercise-induced familial polymorphic VT occurring in arrhythmogenic right ventricular cardiomyopathy [21-23]. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics".) The frequency with which RyR2 mutations occur in patients with CPVT was assessed in a series of 30 probands and 118 family members [5]. RyR2 mutations were detected in 14 of the 30 probands (47 percent) and in nine family members, four of whom were silent carriers. The patients with RyR2 mutations, compared with those without such mutations, had events at a younger age (age at first syncope 8 versus 20 years), and male sex was an important risk factor for syncope. Calsequestrin 2 The calsequestrin 2 protein is the major calcium reservoir within the sarcoplasmic reticulum of cardiac myocytes. This protein is bound physically and functionally to the ryanodine receptor, where it binds large amounts of calcium [24]. The mechanism by which the reported mutation causes ventricular arrhythmias is not clearly established. A second genetic form of CPVT, with autosomal recessive inheritance, involves the calsequestrin 2 gene (CASQ2) [9,25,26]. This form was first identified in seven related Bedouin families [9]. These families included nine children who died suddenly at an average age of seven years and 12 others with a history of recurrent syncope or seizures beginning at six years of age. The 12 symptomatic patients had a relative resting bradycardia and polymorphic VT induced by exercise or isoproterenol infusion. Other genetic variants Other genes that are strongly associated with CPVT and display autosomal recessive inheritance patterns encode the following proteins [14]: Triadin This protein is associated with the release of calcium ions from the sarcoplasmic reticulum and the triggering of muscular contraction. Specific pathogenic variants in the triadin gene (TRDN) are associated with CPVT. Trans-2,3-enoyl-CoA reductase-like This protein is in the steroid 5-alpha reductase family and is located in the endoplasmic reticulum of cardiomyocytes. Mutations in the gene for this protein (TECRL) are associated with CPVT. Calmodulin This protein is expressed in all eukaryotic cells and has many functions; one is to activate smooth muscle contraction. Pathogenic variants in calmodulin may https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 3/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate contribute to CPVT (CALM1, CALM2, CALM3), although the evidence for this is less robust than for variants in TRDN and TERCL. CLINICAL PRESENTATION Signs and symptoms The clinical presentation of CPVT is variable, including some patients who are asymptomatic and identified as part of familial screening. Symptomatic affected patients typically present with syncope or cardiac arrest due to VT or ventricular fibrillation (VF) precipitated by emotional or physical stress [5,11,27]. The VT morphology may vary continuously, from beat to beat, or may appear as a bidirectional VT [5,10]. Presentation with VF is less common, but sudden death may be the initial manifestation [5]. When VT develops, the type and intensity of symptoms will vary depending upon the rate and duration of VT along with the presence or absence of significant comorbid conditions. Patients with CPVT and symptoms typically present with one or more of the following: Sudden cardiac arrest Syncope or presyncope "Seizure-like" activity Palpitations Bidirectional VT has been considered virtually pathognomonic for digitalis intoxication. However, it may also occur in patients with CPVT [5,10]. Of note, in both cases, the arrhythmia is thought to result from intracellular calcium overload, leading to delayed afterdepolarizations, causing triggered activity. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Bidirectional ventricular tachycardia'.) RyR2 mutations have also been associated with neurodevelopmental disorders. Among a cohort of 421 patients with CPVT and RyR2 mutations, 34 patients (8 percent) were found to have intellectual disabilities, a rate significantly higher than the expected rate of 1 percent in the general population [28]. Risk of cardiac events The clinical features of familial polymorphic VT were evaluated in two unrelated families with 24 members who had experienced exercise-induced VT or syncope or had an episode of cardiac arrest [6]. Some of the family members had delayed clinical manifestations, which necessitated continued observation and repeated evaluation. The cumulative incidence of sudden cardiac death by the age of 30 was 31 percent. Only one heterozygous carrier was clinically unaffected, suggesting high disease penetrance by adulthood. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 4/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate There are few studies of predictors of cardiac events in CPVT. One study of 133 children with CPVT showed that probands had a higher rate of cardiac events compared with relatives (38 versus 15 percent; hazard ratio 4.4; 95% CI 1.46-13.30) [29]. Neither age at diagnoses nor sex were associated with cardiac events. ECG characteristics All patients with suspected CPVT should have a 12-lead ECG performed. The ECG during sinus rhythm is generally normal. Two types of polymorphic VTs have been described in patients with CPVT [30]: "Typical" polymorphic VT with continuously varying QRS morphology, similar to that seen in patients with acute ischemia or nonischemic cardiomyopathies Bidirectional tachycardia, demonstrating alternans of the QRS complexes in the limb leads Patients with CPVT may also develop supraventricular tachycardias (primarily atrial tachycardias) [31,32]. DIAGNOSTIC TESTING AND DIAGNOSIS The primary diagnostic test and means of making the diagnosis of CPVT is the exercise stress test. An alternative for patients who are unable to exercise is infusion of epinephrine. The protocols for testing and the protocol-specific criteria for the diagnosis of CPVT are as follows: Exercise testing In patients with suspected CPVT (symptomatic patients and asymptomatic family members), we obtain an exercise test to provoke rhythms diagnostic of CPVT. The finding of an increased frequency of nonsustained or sustained VT during exercise or recovery confirms the diagnosis of CPVT ( waveform 1). However, exercise- induced VT is not specific for CPVT, as other ventricular arrhythmias may be induced by exercise, such as idiopathic outflow tract VT. Stress testing is performed in an appropriately monitored setting and typically employs a standard Bruce protocol. The exercise test is terminated upon identification of an increasing frequency of premature ventricular complexes (PVCs) with increasing exercise load or at maximal exertion as defined by the patient. Both nonsustained and sustained VT may also occur during the stress or recovery phase. In our experience, exercise stress testing is more sensitive than other forms of provocative testing. If a standard exercise study does not show exercise-induced ventricular arrhythmias and clinical suspicion for CPVT remains high, an exercise test using a "burst" protocol may reveal arrhythmias diagnostic of CPVT [33]. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 5/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Exercise testing can also be used to risk-stratify patients for arrhythmic events [34-36] or to assess whether chronic beta-blocker therapy suppresses heart rate to levels below those associated with previous arrhythmias. (See 'Initial therapy' below.) Epinephrine infusion Epinephrine infusion is an alternative for patients who are unable to exercise. The test is conducted in the electrophysiology suite with continuous multilead ECG monitoring and resuscitation equipment at the bedside. The initial dose of epinephrine is 0.05 to 0.1 mcg/kg/min, which is increased by 0.05 mcg/kg/min to a maximum of 0.20 mcg/kg/min. CPVT is diagnosed if epinephrine infusion causes nonsustained or sustained polymorphic VT with more than 10 PVCs/minute or new T-wave alternans. Epinephrine appears quite specific for provoking arrhythmia in CPVT patients but is not as sensitive as the exercise test. Ambulatory ECG In children or others unable to perform an exercise stress test and who may have CPVT, we obtain annual ambulatory ECG monitoring. If ambulatory monitoring shows arrhythmias suspicious for CPVT, we pursue exercise testing or epinephrine infusion. Electrophysiology testing We do not use programmed electrical stimulation (electrophysiologic testing) to test for CPVT; exercise testing is a more sensitive test. Studies of CPVT patients suggest that atrial pacing does not readily induce ventricular arrythmias and that exercise provocation is more likely to reveal diagnostic rhythms [5,32,37]. Genetic testing In patients with clinical presentation or pedigree that is suggestive for CPVT, a genetic screening panel may help support the diagnosis. The genetic panel should include the following genes: RYR2, CASQ2, TRDN, TECRL, CALM1, CALM2, and CALM3 [14]. (See 'Genetics' above.) If a patient is found to have a pathogenic variant for CPVT, we perform genetic screening in all of their first-degree relatives. TREATMENT Treatment goals The goals of treatment are to: Stop an acute polymorphic VT episode Prevent cardiac arrest and sustained VT with implantable cardioverter-defibrillator (ICD) plus antiadrenergic medications https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 6/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Minimize VT recurrence Acute management Acute initial management focuses on rapid termination of polymorphic VT. Treatment decisions are often made in the absence of a detailed knowledge of underlying cardiac disease, thus our recommendations do not make clear distinctions based upon the presence of coronary heart disease or primary electrical disease. Patients with polymorphic VT who are hemodynamically unstable or become pulseless require prompt treatment with electrical cardioversion/defibrillation. (See "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.) We use propranolol (40 mg oral doses [or appropriate weight-based dosing in children] every six hours for the first 48 hours, with additional intravenous doses as needed for recurrent breakthrough ventricular arrhythmias) for acute suppression of recurrent polymorphic VT. For long-term preventive therapy, nadolol (1 to 2 mg/kg) is preferred (because of its long duration of action) [3,5]. (See "Electrical storm and incessant ventricular tachycardia", section on 'Initial management' and 'Beta blockers' below.) This guidance agrees with the suggested acute treatment of CPVT as provided in the 2013 HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes (endorsed by the American College of Cardiology and the American Heart Association) [38]. Avoidance of strenuous exercise Participation in competitive athletics and strenuous exercise increases the risk of ventricular arrhythmias in patients with CPVT due to the rise in catecholamines associated with exertion. Thus, we counsel all patients with CPVT to avoid competitive sports. However, some patients may reasonably choose to continue to participate with appropriate cautionary measures, including an emergency action plan with an automated external defibrillator immediately available. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Inherited arrhythmia syndromes'.) Despite our recommendation, limited data suggest that sports participation may be safe for selected patients with CPVT. In a cohort study of 63 patients with CPVT, including 21 active competitive athletes, continuing participation in sports did not elevate rates of life-threatening arrhythmias or death [39]. We await additional data replicating the findings from this small, nonrandomized observational study prior to changing our recommendation against competitive sports for patients with CPVT. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 7/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate High-risk patients High-risk patients are survivors of cardiac arrest (SCA), syncope, sustained VT or ventricular fibrillation (VF), as well as those who have recurrent arrhythmia despite treatment with beta blockers. Initial therapy Implantable cardioverter-defibrillators For patients with CPVT who have survived sudden cardiac arrest (SCA) or who experience syncope due to sustained VT or VF despite therapy with beta blockers, we recommend ICD implantation in addition to beta blocker therapy. Several unique considerations in ICD implantation for CPVT are outlined below: ICDs should not be used alone without pharmacologic therapy [40]. Patients with CPVT who have survived SCA due to sustained VT or VF usually receive an ICD in addition to beta blocker therapy [41]. (See 'Beta blockers' below.) The younger average age of patients with CPVT referred for ICD necessitates a thorough discussion emphasizing the impact of potential complications and repeated procedures on quality of life. In particular, ICD shocks in patients with CPVT can trigger electrical storm, which lowers quality of life. (See "Electrical storm and incessant ventricular tachycardia" and "Cardiac implantable electronic devices: Long-term complications", section on 'Quality of life'.) When ICDs are implanted, they should be programmed with long detection times and high detection rates to minimize the chance of shocks for nonsustained VT or other arrhythmias not requiring such therapy. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Our approach'.) Data from a recent meta-analysis of 53 studies of CPVT emphasizes the efficacy of ICDs in preventing life-threatening arrhythmias but also the high prevalence of device complications and shocks [40]. Among 503 patients with CPVT (median age 15 years) treated with an ICD plus anti-adrenergic therapy (medication and/or sympathetic denervation), 40 percent of patients had at least one appropriate shock, and 21 percent had at least one inappropriate shock. A device-related complication occurred in nearly one-third of ICD recipients during the available follow-up. (See "Cardiac implantable electronic devices: Long-term complications" and "Cardiac implantable electronic devices: Periprocedural complications".) Beta blockers We recommend beta blocker treatment for all patients with spontaneous or documented stress-induced ventricular arrhythmias. We suggest the following treatment approaches: https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 8/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Use of long-acting, nonselective beta blockers (we use nadolol 1 to 2 mg/kg). The long duration of action aides with compliance. Given that most affected individuals are young, repeated education regarding the importance of medication compliance is warranted (see "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Beta blockers'). In some families, beta blocker therapy completely prevents recurrent arrhythmias [4,9]. Thus, it is important to advise patients on the need to be compulsive (not to miss any doses) when taking pharmacologic therapy for CPVT. A systematic review and meta-analysis of 11 observational studies including 403 patients with CPVT revealed that 88 percent of patients were prescribed a beta blocker at some point [42]. There were no control groups for comparison. However, the event rates at four and eight years were as follows: Arrhythmic events (syncope, aborted cardiac arrest, sudden cardiac death [SCD]) 18.6 and 37.2 percent at four and eight years, respectively Near fatal events (aborted cardiac arrest, SCD) 7.7 and 15.3 percent Fatal events (SCD) 3.2 and 6.4 percent Some studies suggest that nonselective beta blockers (eg, nadolol, propranolol) are more effective than beta-1 selective beta blockers at preventing exercise-induced arrhythmias. In a study of 34 patients with CPVT who underwent three exercise stress tests, the maximum heart rate achieved during exercise was significantly lower following nadolol treatment (122 versus 139 beats per minute [bpm]), with a significant reduction in exercise-induced arrhythmias with nadolol compared with beta-1 selective beta blockers and no treatment [43]. Severity of arrhythmias was scored as 1 point for no arrhythmias or only single ventricular extrasystoles, 2 points for >10 ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4 points for nonsustained ventricular tachycardia or sustained ventricular tachycardia. Arrhythmias during exercise stress testing were less severe during treatment with nadolol compared with beta-1 selective beta blockers (arrhythmic score 1.6 0.9 versus 2.5 0.8) and before the initiation of beta blocker treatment (arrhythmic score 1.6 0.9 versus 2.7 0.9); however, no differences were observed during additional treatment with beta-1 selective beta blockers (arrhythmic score 2.5 0.8 versus 2.7 0.9). Monitoring for recurrent ventricular arrythmias After initiating therapy, it is important to regularly monitor for significant spontaneous and stress-induced VT: Regular ICD device checks that can capture a history of ventricular arrythmias. (See "Cardiac implantable electronic devices: Patient follow-up".) https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 9/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate At least annual follow-up exercise test and/or Holter monitor testing while on beta blocker/antiarrhythmic CPVT therapy to confirm that heart rate response to exercise is sufficiently and persistently blunted. The persistence of ventricular premature beats on a Holter monitor is not necessarily an indication of treatment failure. However, recurrent VT despite compliant therapy with beta- adrenergic blocking agents is an indication to add other therapy. Second-line therapy Flecainide For patients with an ICD who continue to have stress-induced ventricular arrhythmias despite beta blocker therapy, we suggest the addition of flecainide for further arrhythmia suppression. For patients who cannot tolerate beta blockers, flecainide may be used as monotherapy. If a patient has a contraindication to flecainide such as coronary disease or a medication intolerance, then verapamil can also be used in its place. Flecainide blocks cardiac sodium channels and inhibits the cardiac ryanodine receptor (RyR2). These combined effects make it an attractive potential therapy for CPVT. Data from animal models have shown the potent inhibitor effect of flecainide on RyR2 channels and suppression of catecholamine-induced polymorphic VT [44]. (See 'Genetics' above.) When added to baseline therapy with a beta blocker, calcium channel blocker, or both, flecainide has been shown to significantly reduce ventricular arrhythmias during exercise [44-49]. Supporting evidence is somewhat limited by studies with small sample sizes: Flecainide as a second agent is efficacious. In one study, flecainide (median daily dose of 150 mg), in addition to either a beta blocker or calcium channel blocker, suppressed exercise-induced ventricular arrhythmias in 76 percent of patients given this regimen [45]. All patients had recognized mutations associated with CPVT. Flecainide may also be effective as a third agent along with both a beta blocker and a calcium channel blocker [44,46-48]. In a series of 10 patients with CPVT who had recurrent VT in spite of therapy with beta-adrenergic blocking agents (all patients) and calcium channel blockers (in 6 of 10 cases), flecainide was effective in suppressing exercise-induced ventricular tachyarrhythmia when given in addition to beta blockers [48]. Flecainide monotherapy may be an option for patients who are unable to tolerate beta blockers due to side effects. In one nonrandomized study of eight patients with CPVT, including seven who were intolerant of beta blockers, no instances of arrhythmic presyncope, syncope, or SCA were seen during the median follow-up of 37 months [50]. In a separate crossover study, 13 patients with CPVT randomized to flecainide versus placebo https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 10/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate for three months had a reduction in exercise-induced arrhythmias and complete suppression of induced arrhythmias in 85 percent of patients [49]. Calcium channel blockers We suggest that verapamil be used as an adjunctive therapy for CPVT patients with ongoing ventricular arrhythmias despite beta blockers and/or flecainide. The addition of a calcium channel blocker, specifically verapamil, appears to provide some additional benefit in patients with ongoing symptomatic arrhythmias. Two small nonrandomized studies have shown a reduction in the amount of ventricular arrhythmias following the addition of verapamil to beta blocker therapy [51,52]. In a crossover study of exercise testing in six CPVT patients on beta blocker therapy, verapamil reduced the number of isolated and successive premature ventricular complexes (PVCs) during exercise by an average of 76 percent [51]. PVCs appeared later and at higher heart rate during verapamil than at baseline (119 versus 127 bpm). In a study of five patients with CPVT and one with hypertrophic cardiomyopathy/exercise- induced ventricular ectopy, verapamil in addition to beta blocker therapy was studied on exercise stress testing. The number of average ventricular ectopic beats decreased from 78 to 6 beats [52]. Sympathetic denervation For patients with CPVT who remain symptomatic after maximal tolerated medical therapy, we suggest left cardiac sympathetic denervation (LCSD). Side effects from sympathetic denervation are common, although overall patient satisfaction following surgery is high. The rationale for and description of LCSD are described separately. (See "Congenital long QT syndrome: Treatment", section on 'Left cardiac sympathetic denervation'.) Data from several observational studies suggest a role for PCSD in patients with refractory CPVT [12,53-55]. Among 63 patients with CPVT who had LCSD for either secondary or primary prevention, the one- and two-year cumulative event-free survival rates were 87 and 81 percent [55]. Additional findings included: The nine primary prevention patients remained free of major cardiac events. Of the 54 secondary prevention patients, 13 had at least one recurrence, no patients had aborted cardiac arrest, two patients had syncope, 10 patients had 1 appropriate ICD discharges, and one patient died suddenly. The percentage of patients with major cardiac events despite optimal medical therapy was reduced from 100 to 32. Among 29 patients with an ICD, the rate of shocks dropped from 3.6 to 0.6 shocks per person per year. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 11/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Patients with an incomplete LCSD were more likely to experience major cardiac events after LCSD (71 versus 17 percent) compared with those with a complete LCSD. While sympathetic denervation can successfully treat CPVT, side effects following the procedure are common. Among 44 patients who underwent LCSD (including patients with CPVT and long QT syndrome), 42 (95 percent) reported postoperative side effects including left-sided dryness, unilateral facial flushing, contralateral hyperhidrosis, and differential hand temperatures [56]. In spite of the side effects, the vast majority of patients were satisfied and felt safer following the procedure. Low-risk patients For CPVT patients who have not had a cardiac arrest, syncope, or sustained VT or VF, we recommend starting beta blocker therapy. (See 'Beta blockers' above.) After starting a beta blocker, patients must be closely followed for any recurrent spontaneous or stress-induced ventricular arrythmias after several weeks of therapy. If there are no recurrent ventricular arrythmias, we recommend continuing medical therapy and periodic outpatient follow-up. (See 'Monitoring for recurrent ventricular arrythmias' above.) If there is any recurrent ventricular arrythmia in low-risk patients once beta blockers have been started, we believe this now places them in a high-risk category, and thus we recommend ICD placement and initiation of flecainide. Specific subsequent treatment steps are outlined above (see 'High-risk patients' above) and in the algorithm ( algorithm 1). Management considerations in patients with COVID-19 Patients with severe COVID-19 disease may require circulatory support with catecholamines. Such therapy may provoke arrhythmias in patients with CPVT or among previously undiagnosed patients. In this situation, use of agents with alpha- and beta-stimulating properties, including epinephrine, should be avoided or used only when the potential benefits outweigh the risks [57]. (See "COVID-19: Arrhythmias and conduction system disease" and "COVID-19: Management of the intubated adult".) Management of genotype positive, phenotype negative patients For patients without clinical manifestations who are diagnosed in childhood based upon genetic analysis, we suggest the use of beta blockers. There are minimal data available to guide the long-term management of genotype-positive, phenotype-negative patients who are diagnosed solely based upon genetic screening. Expert opinion differs slightly on the long-term role of beta blocker therapy, based upon the age at diagnosis: https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 12/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Expert opinion supports the use of beta blockers in patients without clinical manifestations who are diagnosed in childhood based upon genetic analysis [38]. The usefulness and/or efficacy of beta blockers is less well established in patients without clinical evidence of arrhythmias who are diagnosed in adulthood based upon genetic analysis [38]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Definition Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder that presents as familial as well as sporadic cases. Genetics Pathogenic variants in the ryanodine receptor and calsequestrin 2 protein are found in 70 percent of people with CPVT. Other pathogenic variants can cause CPVT, but they are less common. (See 'Genetics' above.) Clinical presentation and risk factors CPVT occurs in the absence of structural heart disease and typically presents in adolescence. The clinical presentation of CPVT is variable; some patients are asymptomatic and identified as part of family screening. Symptomatic patients typically present with syncope or cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) precipitated by emotional or physical stress. (See 'Clinical presentation' above.) Risk factors for sudden death include documented VF, a family history of sudden death, and onset of symptoms in childhood. (See 'Epidemiology' above.) Diagnosis CPVT is diagnosed by an exercise stress test that shows increased frequency of nonsustained or sustained VT during exercise or recovery. In patients with a suspicious clinical presentation or pedigree, appropriate genetic testing can provide additional diagnostic support. (See 'Diagnostic testing and diagnosis' above.) https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 13/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Acute management The acute management of patients with CPVT (or suspected CPVT) includes: Patients with polymorphic VT who are hemodynamically unstable or become pulseless require prompt treatment with electrical cardioversion/defibrillation. (See "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.) Propranolol is used for acute suppression of recurrent polymorphic VT. Propranolol is given as 40 mg oral doses (or appropriate weight-based dosing in children) every six hours for the first 48 hours, with additional intravenous doses as needed for recurrent breakthrough ventricular arrhythmias. (See "Electrical storm and incessant ventricular tachycardia", section on 'Initial management' and 'Beta blockers' above.) Subsequent management Management of CPVT is summarized in the algorithm ( algorithm 1). All patients - For all patients with CPVT (high and low risk), we recommend initiation of beta blocker therapy (Grade 1B). We suggest the use of long-acting nonselective beta blockers (such as nadolol) rather than short-acting or beta-1 selective beta blockers (Grade 2B). (See 'Beta blockers' above.) We advise that patients avoid strenuous exercise; however, some patients may reasonably choose to continue to participate. Appropriate cautionary measures include an emergency action plan with an automated external defibrillator immediately available. (See 'Avoidance of strenuous exercise' above and "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Inherited arrhythmia syndromes'.) Monitoring for recurrent ventricular arrythmias is done by regular device checks, exercise testing, and 24-hour Holter monitoring to confirm suppression of exercise- induced heart rate. High-risk patients are survivors of cardiac arrest (SCA), syncope, or sustained VT or VF. Others are low risk unless they have recurrent arrhythmia despite treatment with beta blockers. High-risk patients require an implantable cardioverter-defibrillator (ICD) in addition to beta blocker therapy. ICDs should not be used alone without pharmacologic therapy. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 14/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate (See 'Implantable cardioverter-defibrillators' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) For patients with continued arrythmia despite beta blocker therapy, we suggest the addition of flecainide (Grade 2C). (See 'Flecainide' above.) Therapy for refractory arrythmia or spontaneous cardiac arrest Additional treatment options for patients with refractory arrhythmias include verapamil and left sympathetic denervation. Side effects from sympathetic denervation are common, although overall patient satisfaction following surgery is high. (See 'Sympathetic denervation' above.) Genotype-positive, phenotype-negative patients For patients without clinical manifestations who are diagnosed in childhood based upon genetic analysis, we suggest the use of beta blockers (Grade 2C). (See 'Management of genotype positive, phenotype negative patients' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Nguyen PT, Scheinman MM, Seger J. Polymorphous ventricular tachycardia: clinical characterization, therapy, and the QT interval. Circulation 1986; 74:340. 2. Wren C, Rowland E, Burn J, Campbell RW. Familial ventricular tachycardia: a report of four families. Br Heart J 1990; 63:169. 3. Leenhardt A, Lucet V, Denjoy I, et al. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 1995; 91:1512. 4. Fisher JD, Krikler D, Hallidie-Smith KA. Familial polymorphic ventricular arrhythmias: a quarter century of successful medical treatment based on serial exercise-pharmacologic testing. J Am Coll Cardiol 1999; 34:2015. 5. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 6. Swan H, Piippo K, Viitasalo M, et al. Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J Am Coll Cardiol 1999; 34:2035. 7. Priori SG, Napolitano C, Tiso N, et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 2001; https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 15/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate 103:196. 8. Laitinen PJ, Brown KM, Piippo K, et al. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 2001; 103:485. 9. Lahat H, Eldar M, Levy-Nissenbaum E, et al. Autosomal recessive catecholamine- or exercise- induced polymorphic ventricular tachycardia: clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation 2001; 103:2822. |
the use of beta blockers. There are minimal data available to guide the long-term management of genotype-positive, phenotype-negative patients who are diagnosed solely based upon genetic screening. Expert opinion differs slightly on the long-term role of beta blocker therapy, based upon the age at diagnosis: https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 12/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Expert opinion supports the use of beta blockers in patients without clinical manifestations who are diagnosed in childhood based upon genetic analysis [38]. The usefulness and/or efficacy of beta blockers is less well established in patients without clinical evidence of arrhythmias who are diagnosed in adulthood based upon genetic analysis [38]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Definition Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder that presents as familial as well as sporadic cases. Genetics Pathogenic variants in the ryanodine receptor and calsequestrin 2 protein are found in 70 percent of people with CPVT. Other pathogenic variants can cause CPVT, but they are less common. (See 'Genetics' above.) Clinical presentation and risk factors CPVT occurs in the absence of structural heart disease and typically presents in adolescence. The clinical presentation of CPVT is variable; some patients are asymptomatic and identified as part of family screening. Symptomatic patients typically present with syncope or cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) precipitated by emotional or physical stress. (See 'Clinical presentation' above.) Risk factors for sudden death include documented VF, a family history of sudden death, and onset of symptoms in childhood. (See 'Epidemiology' above.) Diagnosis CPVT is diagnosed by an exercise stress test that shows increased frequency of nonsustained or sustained VT during exercise or recovery. In patients with a suspicious clinical presentation or pedigree, appropriate genetic testing can provide additional diagnostic support. (See 'Diagnostic testing and diagnosis' above.) https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 13/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Acute management The acute management of patients with CPVT (or suspected CPVT) includes: Patients with polymorphic VT who are hemodynamically unstable or become pulseless require prompt treatment with electrical cardioversion/defibrillation. (See "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.) Propranolol is used for acute suppression of recurrent polymorphic VT. Propranolol is given as 40 mg oral doses (or appropriate weight-based dosing in children) every six hours for the first 48 hours, with additional intravenous doses as needed for recurrent breakthrough ventricular arrhythmias. (See "Electrical storm and incessant ventricular tachycardia", section on 'Initial management' and 'Beta blockers' above.) Subsequent management Management of CPVT is summarized in the algorithm ( algorithm 1). All patients - For all patients with CPVT (high and low risk), we recommend initiation of beta blocker therapy (Grade 1B). We suggest the use of long-acting nonselective beta blockers (such as nadolol) rather than short-acting or beta-1 selective beta blockers (Grade 2B). (See 'Beta blockers' above.) We advise that patients avoid strenuous exercise; however, some patients may reasonably choose to continue to participate. Appropriate cautionary measures include an emergency action plan with an automated external defibrillator immediately available. (See 'Avoidance of strenuous exercise' above and "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Inherited arrhythmia syndromes'.) Monitoring for recurrent ventricular arrythmias is done by regular device checks, exercise testing, and 24-hour Holter monitoring to confirm suppression of exercise- induced heart rate. High-risk patients are survivors of cardiac arrest (SCA), syncope, or sustained VT or VF. Others are low risk unless they have recurrent arrhythmia despite treatment with beta blockers. High-risk patients require an implantable cardioverter-defibrillator (ICD) in addition to beta blocker therapy. ICDs should not be used alone without pharmacologic therapy. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 14/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate (See 'Implantable cardioverter-defibrillators' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) For patients with continued arrythmia despite beta blocker therapy, we suggest the addition of flecainide (Grade 2C). (See 'Flecainide' above.) Therapy for refractory arrythmia or spontaneous cardiac arrest Additional treatment options for patients with refractory arrhythmias include verapamil and left sympathetic denervation. Side effects from sympathetic denervation are common, although overall patient satisfaction following surgery is high. (See 'Sympathetic denervation' above.) Genotype-positive, phenotype-negative patients For patients without clinical manifestations who are diagnosed in childhood based upon genetic analysis, we suggest the use of beta blockers (Grade 2C). (See 'Management of genotype positive, phenotype negative patients' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Nguyen PT, Scheinman MM, Seger J. Polymorphous ventricular tachycardia: clinical characterization, therapy, and the QT interval. Circulation 1986; 74:340. 2. Wren C, Rowland E, Burn J, Campbell RW. Familial ventricular tachycardia: a report of four families. Br Heart J 1990; 63:169. 3. Leenhardt A, Lucet V, Denjoy I, et al. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 1995; 91:1512. 4. Fisher JD, Krikler D, Hallidie-Smith KA. Familial polymorphic ventricular arrhythmias: a quarter century of successful medical treatment based on serial exercise-pharmacologic testing. J Am Coll Cardiol 1999; 34:2015. 5. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 6. Swan H, Piippo K, Viitasalo M, et al. Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J Am Coll Cardiol 1999; 34:2035. 7. Priori SG, Napolitano C, Tiso N, et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 2001; https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 15/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate 103:196. 8. Laitinen PJ, Brown KM, Piippo K, et al. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 2001; 103:485. 9. Lahat H, Eldar M, Levy-Nissenbaum E, et al. Autosomal recessive catecholamine- or exercise- induced polymorphic ventricular tachycardia: clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation 2001; 103:2822. 10. Nof E, Lahat H, Constantini N, et al. A novel form of familial bidirectional ventricular tachycardia. Am J Cardiol 2004; 93:231. 11. Roston TM, Vinocur JM, Maginot KR, et al. Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry. Circ Arrhythm Electrophysiol 2015; 8:633. 12. Wilde AA, Bhuiyan ZA, Crotti L, et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N Engl J Med 2008; 358:2024. 13. Priori SG, Mazzanti A, Santiago DJ, et al. Precision Medicine in Catecholaminergic Polymorphic Ventricular Tachycardia: JACC Focus Seminar 5/5. J Am Coll Cardiol 2021; 77:2592. 14. Walsh R, Adler A, Amin AS, et al. Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death. Eur Heart J 2022; 43:1500. 15. Wehrens XH, Lehnart SE, Huang F, et al. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 2003; 113:829. 16. Suetomi T, Yano M, Uchinoumi H, et al. Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca release leading to catecholaminergic polymorphic ventricular tachycardia. Circulation 2011; 124:682. 17. Tester DJ, Spoon DB, Valdivia HH, et al. Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner/coroner's cases. Mayo Clin Proc 2004; 79:1380. 18. George CH, Higgs GV, Lai FA. Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ Res 2003; 93:531. 19. Paavola J, Viitasalo M, Laitinen-Forsblom PJ, et al. Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves. Eur Heart J 2007; 28:1135. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 16/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate 20. Bhuiyan ZA, van den Berg MP, van Tintelen JP, et al. Expanding spectrum of human RYR2- related disease: new electrocardiographic, structural, and genetic features. Circulation 2007; 116:1569. 21. Bauce B, Nava A, Rampazzo A, et al. Familial effort polymorphic ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy map to chromosome 1q42-43. Am J Cardiol 2000; 85:573. 22. Tiso N, Stephan DA, Nava A, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 2001; 10:189. 23. Tiso N, Salamon M, Bagattin A, et al. The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochem Biophys Res Commun 2002; 299:594. 24. Yano K, Zarain-Herzberg A. Sarcoplasmic reticulum calsequestrins: structural and functional properties. Mol Cell Biochem 1994; 135:61. 25. Lahat H, Pras E, Olender T, et al. A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Genet 2001; 69:1378. 26. di Barletta MR, Viatchenko-Karpinski S, Nori A, et al. Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation 2006; 114:1012. 27. Hayashi M, Denjoy I, Extramiana F, et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 2009; 119:2426. 28. Lieve KVV, Verhagen JMA, Wei J, et al. Linking the heart and the brain: Neurodevelopmental disorders in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2019; 16:220. 29. Kallas D, Roston TM, Franciosi S, et al. Evaluation of age at symptom onset, proband status, and sex as predictors of disease severity in pediatric catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2021; 18:1825. 30. Richter S, Gebauer R, Hindricks G, Brugada P. A classic electrocardiographic manifestation of catecholaminergic polymorphic ventricular tachycardia. J Cardiovasc Electrophysiol 2012; 23:560. 31. Glukhov AV, Kalyanasundaram A, Lou Q, et al. Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1. Eur Heart J 2015; 36:686. https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 17/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate 32. Sumitomo N, Sakurada H, Taniguchi K, et al. Association of atrial arrhythmia and sinus node dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia. Circ J 2007; 71:1606. 33. Roston TM, Kallas D, Davies B, et al. Burst Exercise Testing Can Unmask Arrhythmias in Patients With Incompletely Penetrant Catecholaminergic Polymorphic Ventricular Tachycardia. JACC Clin Electrophysiol 2021; 7:437. 34. Lieve KVV, Dusi V, van der Werf C, et al. Heart Rate Recovery After Exercise Is Associated With Arrhythmic Events in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia. Circ Arrhythm Electrophysiol 2020; 13:e007471. 35. Krahn AD, Healey JS, Chauhan VS, et al. Epinephrine infusion in the evaluation of unexplained cardiac arrest and familial sudden death: from the cardiac arrest survivors with preserved Ejection Fraction Registry. Circ Arrhythm Electrophysiol 2012; 5:933. 36. Marjamaa A, Hiippala A, Arrhenius B, et al. Intravenous epinephrine infusion test in diagnosis of catecholaminergic polymorphic ventricular tachycardia. J Cardiovasc Electrophysiol 2012; 23:194. 37. Danielsen TK, Manotheepan R, Sadredini M, et al. Arrhythmia initiation in catecholaminergic polymorphic ventricular tachycardia type 1 depends on both heart rate and sympathetic stimulation. PLoS One 2018; 13:e0207100. 38. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 39. Ostby SA, Bos JM, Owen HJ, et al. Competitive Sports Participation in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia: A Single Center's Early Experience. JACC Clin Electrophysiol 2016; 2:253. 40. Roston TM, Jones K, Hawkins NM, et al. Implantable cardioverter-defibrillator use in catecholaminergic polymorphic ventricular tachycardia: A systematic review. Heart Rhythm 2018; 15:1791. 41. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 42. van der Werf C, Zwinderman AH, Wilde AA. Therapeutic approach for patients with catecholaminergic polymorphic ventricular tachycardia: state of the art and future https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 18/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate developments. Europace 2012; 14:175. 43. Leren IS, Saberniak J, Majid E, et al. Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with 1-selective - blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2016; 13:433. 44. Watanabe H, Chopra N, Laver D, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med 2009; 15:380. 45. van der Werf C, Kannankeril PJ, Sacher F, et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol 2011; 57:2244. 46. Watanabe H, van der Werf C, Roses-Noguer F, et al. Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2013; 10:542. 47. Hong RA, Rivera KK, Jittirat A, Choi JJ. Flecainide suppresses defibrillator-induced storming in catecholaminergic polymorphic ventricular tachycardia. Pacing Clin Electrophysiol 2012; 35:794. 48. Khoury A, Marai I, Suleiman M, et al. Flecainide therapy suppresses exercise-induced ventricular arrhythmias in patients with CASQ2-associated catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2013; 10:1671. 49. Kannankeril PJ, Moore JP, Cerrone M, et al. Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial. JAMA Cardiol 2017; 2:759. 50. Padfield GJ, AlAhmari L, Lieve KV, et al. Flecainide monotherapy is an option for selected patients with catecholaminergic polymorphic ventricular tachycardia intolerant of - blockade. Heart Rhythm 2016; 13:609. 51. Swan H, Laitinen P, Kontula K, Toivonen L. 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Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm 2009; 6:752. 55. De Ferrari GM, Dusi V, Spazzolini C, et al. Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation. Circulation 2015; 131:2185. 56. Waddell-Smith KE, Ertresvaag KN, Li J, et al. Physical and Psychological Consequences of Left Cardiac Sympathetic Denervation in Long-QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia. Circ Arrhythm Electrophysiol 2015; 8:1151. 57. Wu CI, Postema PG, Arbelo E, et al. SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes. Heart Rhythm 2020; 17:1456. Topic 916 Version 38.0 https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 20/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate GRAPHICS Catecholaminergic polymorphic ventricular tachycardia and nonsustained ventricular tachycardia Ambulatory ECG recordings from a 28-year-old man with exercise-related palpitations. The figure shows two episodes of exercise-related (note sinus tachycardia prior to VT onset) polymorphic VT (arrows). The first episode of VT begins with a VPD on the downstroke of the T wave. The second, briefer episode appears to begin with a later-onset VPD. This patient's arrhythmias were suppressed in response to exercise restriction and nadolol. Genetic testing did not reveal a recognized RYR2 or CASQ2 mutation. Note that the QT interval appears normal for rate. ECG: electrocardiogram; VT: ventricular tachycardia; VPD: ventricular premature depolarization. Courtesy of Alfred Buxton, MD. Graphic 133240 Version 1.0 https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 21/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Algorithm for the long- term management of catecholaminergic polymorphic ventricular tachycardia CPVT: catecholaminergic polymorphic ventricular tachycardia; ICD: implantable cardioverter-defibrillator; AV: atrioventricular. We counsel patients with CPVT to avoid competitive sports and strenuous exercise. Long-acting, nonselective beta blockers (such as nadolol) are preferred over short-acting or B1 selective agents. Flecainide is contraindicated in patients with known structural heart disease (eg, coronary artery disease) o patients with high grade AV block or bifascicular block. Patients who have a high burden of arrhythmias or are intolerant of beta blockers should generally underg sympathetic denervation. Graphic 118659 Version 2.0 https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 22/23 7/6/23, 3:39 PM Catecholaminergic polymorphic ventricular tachycardia - UpToDate Contributor Disclosures Alfred Buxton, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/catecholaminergic-polymorphic-ventricular-tachycardia/print 23/23 |
7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk : Martin S Maron, MD : Samuel L vy, MD, William J McKenna, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 24, 2020. INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease caused by mutations in one of several sarcomere genes that encode components of the contractile apparatus of the heart. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) HCM is characterized by left ventricular (LV) hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities ( figure 1). Depending in part upon the site and extent of cardiac hypertrophy, patients with HCM can develop one or more of the following abnormalities: LV outflow obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".) Diastolic and systolic dysfunction. Myocardial ischemia. Mitral regurgitation. These structural and functional abnormalities can produce a variety of symptoms, including: Fatigue Dyspnea Chest pain Palpitations https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 1/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Presyncope or syncope In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias. Patients with HCM are prone to both atrial and ventricular arrhythmias. Many of these arrhythmias are asymptomatic, but some can precipitate hemodynamic collapse and sudden cardiac death (SCD). SCD is a catastrophic and unpredictable complication of HCM and in some patients may be the first presentation of the disease. The management of patients following risk assessment and following a documented ventricular arrhythmia will be reviewed here. The assessment of risk for arrhythmic SCD is a critical component of the clinical evaluation of nearly all patients with HCM and is reviewed separately. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Other issues related to ventricular arrhythmias and SCD, as well as other clinical manifestations, natural history, diagnosis and evaluation, and treatment of patients with HCM, are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) MANAGEMENT The management of the risk for SCD and ventricular arrhythmias in patients with HCM is centered around minimizing risk associated with physical activity and targeted interventions, primarily implantation of an ICD when indicated. There are limited roles for other nonpharmacologic therapies (eg, septal reduction therapy and catheter ablation) and medical therapy in the management of ventricular arrhythmias and risk of SCD. The overall role of nonpharmacologic therapies and medical therapy in patients with HCM is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction".) Implantable cardioverter-defibrillators (ICDs) The ICD is the best available therapy for patients with HCM who have survived SCD or who are at high risk of ventricular arrhythmias and SCD. Randomized trials of ICD therapy have not been performed in patients with HCM; as a result, the indications for an ICD are derived from largely retrospective observational data that define strength of the noninvasive risk factors in identifying high-risk patients. In addition, efficacy of ICDs in patients with HCM is also derived from the incidence of appropriate ICD https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 2/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate therapies in patients who have had an ICD implanted [1-3]. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Recommendations for ICD therapy For patients who survive an episode of sustained ventricular tachycardia (VT) or SCD, we recommend implantation of an ICD for the secondary prevention of SCD. (See 'Secondary prevention ICD' below.) In patients with HCM with 1 of the major noninvasive risk markers ( table 1), it is reasonable to offer an ICD for primary prevention of SCD, taking into account the individual patient's age, clinical profile, and values/preferences regarding device therapy. (See 'Primary prevention ICD' below.) In patients with 1 major risk marker, but who remain ambivalent or uncertain regarding ICD implantation, magnitude of LV outflow tract gradient, abnormal blood pressure response to exercise, and the results of contrast-enhanced cardiovascular magnetic resonance imaging are important arbitrators in resolving high-risk status and the need for primary prevention ICD therapy. Age is also an important factor in considering patients at risk. Patients with HCM who have achieved an advanced age of 60 years are at very low risk for disease-related adverse events, including SCD, even in the presence of conventional risk factors. Therefore, a high threshold is necessary to consider older patients with HCM at high risk and candidates for ICD therapy for primary prevention of SCD. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) If a patient with HCM develops a clinical indication for permanent pacing, and is otherwise low risk for SCD based on risk stratification strategy, there would be no indication for upgrading the pacemaker to include ICD functionality. Certain other subsets of patients with HCM, namely patients with end-stage HCM with LV ejection fraction <50 percent and patients with HCM and an LV apical aneurysm, are at high risk for SCD [4]. Patients with HCM and an LV apical aneurysm have a fivefold higher risk of life-threatening ventricular arrhythmias and SCD compared with patients with HCM who do not have an LV apical aneurysm. For this reason, many HCM patients with apical aneurysms have sufficiently increased risk of SCD to warrant implantation of an ICD for primary prevention of SCD. As is the case in similar management scenarios where prospective randomized trials are not possible, decisions regarding high-risk status should be made on an individual basis, taking into consideration the entire clinical profile of the patient. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 3/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Secondary prevention ICD Patients with HCM who have survived cardiac arrest due to VT or ventricular fibrillation (VF) are at an increased risk for recurrent events and should undergo ICD implantation for secondary prevention [1,5-12]. This risk was illustrated in a series of 33 patients successfully resuscitated from a cardiac arrest prior to the widespread use of ICDs [8]. They were treated with a variety of strategies, including septal myotomy and medical therapy. Despite treatment, recurrent arrhythmias were common. The survival rates free of recurrent cardiac arrest or death after 1, 5, and 10 years were 83, 65, and 53 percent, respectively. A high rate of recurrent ventricular arrhythmias in patients with HCM and a history of cardiac arrest or sustained VT are further supported by the frequency of appropriate shocks in patients who received an ICD for secondary prevention of SCD [10]. In a study of 160 selected high-risk patients with HCM and an ICD, including 94 patients with 24- or 48-hour ambulatory electrocardiogram (ECG) monitoring pre-ICD implant, nonsustained VT (NSVT) was detected in 86 patients (54 percent) during an average follow-up of four years [13]. Patients with documented NSVT were significantly more likely to develop sustained VT/VF requiring ICD therapy (21 versus 8 percent; adjusted hazard ratio [HR] 3.6, 95% CI 1.3-10.2). Factors associated with a significantly higher likelihood of requiring ICD therapy include NSVT duration >7 beats, rate >200 beats per minute, or more than one NSVT run. Primary prevention ICD In HCM patients with 1 major risk marker, an ICD can be beneficial for primary prevention of SCD. ( algorithm 1) [5,6,12]. The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of ventricular arrhythmias and the prevention of SCD note that an ICD is reasonable in patients with one or more major risk factors [12]. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Impact of number of risk factors' and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.) In a multicenter registry of 506 patients with HCM and an ICD (24 percent for secondary prevention) who were followed for an average of 3.7 years, 20 percent of patients received appropriate ICD interventions [2]. The rate of appropriate device activation was 10.6 percent per year when used for secondary prevention of SCD, and 3.6 percent per year when used for primary prevention. Similar rates of ICD intervention have been reported using registry data in a pediatric population; among 224 children and adolescents with HCM and an ICD (including 188 patients [84 percent] placed for primary prevention) who were followed for an average of 4.3 years, 43 patients (19 percent; 4.5 percent per year) received an appropriate ICD intervention [14]. Choice of device Traditionally, most patients with HCM who underwent ICD implantation received a transvenous ICD system, with the vast majority of long-term safety and efficacy of ICD https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 4/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate therapy in HCM patients being derived from studies with transvenous ICDs. Some patients with HCM may also be candidates for a subcutaneous ICD (S-ICD) rather than the standard ICD with transvenous leads [15]. The S-ICD provides patients the opportunity to avoid intravascular complications from long-term lead placement, a particular relevant point for patients with HCM who are young and often have many decades of risk and the need for primary prevention ICDs. In addition, the S-ICD can be extracted with minimal risk if an indication for device removal emerges at any point in patients' clinical course. However, prior to implantation, the surface ECG must be rigorously scrutinized to determine eligibility for the S- ICD in order to avoid inappropriate shocks related to T-wave oversensing [16]. (See "Subcutaneous implantable cardioverter defibrillators".) Early data from small cohort studies of S-ICD use in patients with HCM are promising: In a cohort of 872 patients (99 with HCM), similar implantation success and one-year complication rates following S-ICD implantation were seen for patients with and without HCM; additionally, 3 of the 99 patients with HCM had VT that was successfully terminated following the initial shock [17]. In a multicenter cohort of 88 patients with HCM who received an S-ICD and were followed for an average of 2.7 years, two patients received appropriate shocks terminating VT, while inappropriate shocks occurred in five patients (due to T-wave oversensing or supraventricular tachycardias with rates in the shock range) [18]. Among 122 consecutive patients with HCM who met criteria for ICD implantation (3 for secondary prevention, 119 for primary prevention based on one or more major risk markers) and were eligible for either S-ICD or transvenous ICD, 47 patients chose S-ICD while 75 chose transvenous ICD [19]. Rate of appropriate shocks was not different between S-ICD and transvenous ICD. Five patients (11 percent) with S-ICD received a total of 10 appropriate shocks, while 15 patients (20 percent) with a transvenous ICD received appropriate therapies (shocks in three patients, antitachycardia pacing in 12 patients). Inappropriate shocks were more common in S-ICD recipients (eight patients [17 percent) versus two patients [3 percent]). Although preliminary, this study demonstrates that despite the absence of antitachycardia pacing with the S-ICD, appropriate shock rates were not greater with the S-ICD compared to transvenous ICD. Our approach to device selection in high-risk HCM patients In patients with an indication for bradycardia pacing, or in whom monomorphic VT is most likely the initiating ventricular arrhythmia (ie, patients with HCM with LV apical aneurysm), https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 5/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate we place a transvenous ICD given the ability to provide bradycardia pacing and antitachycardia pacing. In patients with massive LV hypertrophy (LVH), defined as LV wall thickness 30 mm anywhere in the LV wall, we favor the transvenous ICD given that patients with HCM and massive LVH have not yet been well-represented in prospective S-ICD studies and the theoretical concern regarding long-term efficacy of the S-ICD in aborting life-threatening arrhythmias, particularly in patients with extreme disease expression. In patients with apical aneurysm, monomorphic VT is the most common initiating ventricular tachyarrhythmia, and for this reason we favor transvenous ICD, given the opportunity this device provides for anti-tachycardia pacing treatment to abort VT. For younger, active HCM patients without massive LVH in whom device therapy will be required over many decades of life, we employ a shared decision-making strategy in which patients are fully informed about the strengths and limitations of both devices to enable a transparent and reliable choice regarding selection of ICD. In middle-aged or older high-risk patients with HCM, the overall benefit of S-ICD is generally less compared with the transvenous device and for this reason we generally favor transvenous ICD for this subgroup, although it is reasonable to evaluate for S-ICD placement, incorporating similar shared decision-making strategy as discussed with younger patients. Complications of device therapy Long-term complications following ICD placement include the following [20-22]: Approximately 25 percent of patients experience inappropriate ICD discharge 6 to 13 percent experience lead complications (eg, fracture, dislodgment, oversensing) 4 to 5 percent develop device-related infection 2 to 3 percent experience bleeding or thrombosis By contrast to the experience among ICD recipients with other nonischemic and ischemic etiologies for cardiomyopathy, patients with HCM implanted for primary prevention ICDs do not appear to have a significant increase in all-cause or cardiac mortality following appropriate ICD shocks. Among a cohort of 486 patients with HCM felt to be at high risk for SCD and who received primary prevention ICDs, 94 patients (19 percent) received an appropriate ICD intervention (shock or antitachycardia pacing) over an average follow-up of 6.4 years (3.7 percent per year risk of appropriate ICD intervention) [23]. Freedom from HCM-related mortality at 1, 5, and 10 years was 100, 97, and 92 percent, respectively. The favorable outcome after https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 6/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate appropriate ICD shocks in HCM is likely related to the otherwise preserved myocardial substrate in HCM, in which systolic function is normal and risk of developing advanced HF is low. The rate of inappropriate shocks and lead fractures appears to be higher in children than in adults, largely because their activity level and body growth place continual strain on the leads, which are the weakest link in the system [22]. This issue is of particular concern, given the long periods that young patients will have prophylactically implanted devices. (See "Cardiac implantable electronic devices: Long-term complications".) Nonpharmacologic treatment of LV outflow tract obstruction Nonpharmacologic therapies for LV outflow tract obstruction are discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) Medical treatment Medical therapy for ventricular arrhythmias in patients with HCM has an important role in select clinical scenarios, including: Patients with symptomatic arrhythmias Patients with an ICD who have frequent arrhythmias or antitachyarrhythmia therapies Patients at high risk of ventricular arrhythmias who are not candidates for, or choose not to have, an ICD There is no evidence that pharmacologic therapy provides absolute protection against sudden death due to malignant ventricular arrhythmias in patients with HCM [24]. Thus, for patients with asymptomatic ventricular premature beats (VPBs) or NSVT, we recommend that pharmacologic therapy not be given for the purpose of arrhythmia suppression. However, for patients with symptoms due to VPBs or NSVT, we suggest pharmacologic treatment for symptom control, typically with a beta blocker or an antiarrhythmic drug. Patients with frequent sustained ventricular arrhythmias resulting in ICD shocks should be treated with adjunctive antiarrhythmic therapy, most often sotalol or amiodarone. Our general approach is as follows: For patients with symptomatic VPBs, we use beta blockers. (See "Premature ventricular complexes: Treatment and prognosis".) Patients with symptomatic NSVT can be treated with beta blockers, or in selected patients, sotalol or amiodarone, for the purpose of symptom control [25,26]. If antiarrhythmic therapy is required, we generally prefer sotalol in younger patients (<50 years of age) due to the potential toxicities associated with the long-term use (ie, years to decades) of amiodarone. There is a small risk of proarrhythmia with sotalol due to the potential for QT prolongation, although our experts feel the risks of sotalol in younger patients are https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 7/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate generally lower than the potential long-term toxicities of amiodarone. As such, sotalol remains an option, even in the absence of an ICD, although clinical experience and published data are limited. Because NSVT is associated with an increased risk of SCD, its presence should be taken into account when considering an individual's risk for SCD and the need for ICD therapy. Pharmacologic therapies directed at symptomatic NSVT do not reduce the risk of SCD and should not be used alone as an alternative to ICD therapy. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk stratification'.) Sustained VT in the absence of an identifiable provoking factor is generally regarded as a major risk factor for SCD. Nearly all such patients receive an ICD for secondary prevention. For patients with frequent arrhythmia recurrences who experience multiple shocks, adjunctive antiarrhythmic therapy is indicated, with sotalol or amiodarone and/or a beta blocker as therapeutic options [6,12,26]. Electrical storm and/or incessant VT are highly unusual in patients with HCM, and given the diffusely abnormal myocardial substrate in this disease, the efficacy of radiofrequency ablation is uncertain. One exception is those patients with HCM and LV apical aneurysms, in whom the focus of incessant ventricular tachyarrhythmias can often be reliably identified with mapping techniques (junction of the aneurysm rim with myocardium) and successfully treated with radiofrequency ablation [27,28]. (See "Electrical storm and incessant ventricular tachycardia", section on 'Catheter ablation'.) Catheter ablation Radiofrequency catheter ablation for recurrent VT in patients with HCM has largely been reserved for the subgroup of patients with LV apical aneurysm [28]. Among 13 patients with LV apical aneurysm and recurrent VT, seven underwent catheter ablation for VT, with six of the seven remaining free of subsequent VT at an average of 1.9 years of follow-up [29]. The success of catheter ablation in this subgroup of patients is due to the fact that the structural nidus for VT is commonly at the junction of the aneurysm rim and LV myocardium, providing an identifiable target for ablation. On the other hand, in the remainder of the HCM population, the diffuse abnormal myocardial substrate results in multiple foci for VT and therefore little evidence that catheter ablation would be successful [28]. The use of catheter ablation for ventricular arrhythmias is largely focused in other populations (eg, post-myocardial infarction) and is discussed in detail separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Radiofrequency catheter ablation'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 8/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Restriction of physical activity Due to the potential risk of SCD associated with exercise in patients with HCM, activity restriction is an important component of patient management. Competitive athletes with a probable or unequivocal clinical diagnosis of HCM should not participate in most competitive sports, with the possible exception of those that are low intensity ( figure 2). Activity restriction in competitive athletes with HCM is discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Hypertrophic cardiomyopathy'.) Among patients with HCM who are not competitive athletes, there is frequently a desire to exercise for both recreation and personal fitness. Additionally, exercise may be an important mechanism to prevent cardiometabolic heart disease as most patients with HCM have an expected longevity that is similar to the general population. Historically, patients with HCM have been instructed to confine themselves to mild to moderate recreational level activities, always engaging in a noncompetitive manner. To provide a more concrete guide to the appropriate limits of exercise in HCM patients, some experts have suggested that at peak exertion, HCM patients should still be able to complete full sentences without straining to complete words. Several studies have suggested that exercise, either moderate- or high-intensity, is safe in carefully selected patients with HCM [30-34]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Catheter ablation of arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 9/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)") Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients with hypertrophic cardiomyopathy (HCM) are prone to ventricular arrhythmias. Ventricular arrhythmias can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation (VF). While the frequency of ventricular arrhythmias is highly variable, the annual incidence of sudden cardiac death (SCD) in the clinically identified general HCM patient population is approximately 1 percent. (See 'Introduction' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Epidemiology'.) SCD is the most-feared complication of HCM. The implantable cardioverter-defibrillator (ICD) is the best available therapy for patients with HCM who have survived SCD or who are at high risk of life-threatening ventricular arrhythmias. Persons with a probable or unequivocal clinical diagnosis of HCM should not participate in most competitive sports, with the possible exception of those that are low intensity ( figure 2). (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Hypertrophic cardiomyopathy'.) For patients who survive an episode of sustained VT or sudden cardiac arrest, we recommend implantation of an ICD for secondary prevention of SCD (Grade 1B). (See 'Implantable cardioverter-defibrillators (ICDs)' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) In patients with HCM with 1 of the major noninvasive risk markers, we suggest implantation of an ICD for primary prevention of SCD (Grade 2C). ICD decision making in HCM should almost always take into account the individual patient's age, clinical profile, and values/preferences regarding device therapy. (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Established major risk markers'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 10/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate In patients with one major risk marker, but who remain ambivalent or uncertain regarding ICD implantation, magnitude of LV outflow tract gradient, abnormal blood pressure response to exercise, and the results of contrast-enhanced cardiovascular magnetic resonance imaging are important arbitrators in resolving high-risk status and the need for primary prevention ICD therapy. Age is also an important factor in considering patients at risk. (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.) Certain other subsets of patients with HCM, namely patients with end-stage HCM with LV ejection fraction <50 percent and patients with HCM and an LV apical aneurysm, are at high risk for SCD and therefore are also candidates for ICD therapy [4]. In patients with HCM and an LV apical aneurysm, we suggest implantation of an ICD for primary prevention of SCD (Grade 2C). (See 'Recommendations for ICD therapy' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Established major risk markers'.) Our approach to the selection of a particular type of ICD is presented in the text. (See 'Our approach to device selection in high-risk HCM patients' above.) There is no evidence that pharmacologic therapy provides absolute protection against SCD due to malignant ventricular arrhythmias in patients with HCM. However, medical therapy for ventricular arrhythmias in patients with HCM has an important role in select clinical scenarios: For patients with asymptomatic VPBs or NSVT, we recommend that pharmacologic therapy not be given for the purpose of arrhythmia suppression (Grade 1B). However, because NSVT is associated with an increased risk of SCD, its presence should be taken into account when considering the need for ICD therapy for primary prevention of sudden death. (See 'Medical treatment' above.) For patients with symptoms due to VPBs or NSVT, we suggest pharmacologic treatment for symptom control (Grade 2C). Beta blockers are the preferred initial therapy, and in refractory cases, we suggest sotalol or amiodarone. The purpose of medical therapy is the control of symptoms; it should not be considered an alternative to an ICD in patients at high risk of SCD. (See 'Medical treatment' above.) Patients with frequent sustained ventricular arrhythmias resulting in ICD shocks should be treated with adjunctive antiarrhythmic therapy, most often sotalol or amiodarone. Radiofrequency ablation is an option to abolish or mitigate recurrent ventricular https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 11/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate arrhythmias in patients with HCM and an apical aneurysm, although the efficacy of VT ablation in patients without an apical aneurysm is uncertain. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Perry Elliott, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999; 33:1596. 2. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298:405. 3. Begley DA, Mohiddin SA, Tripodi D, et al. Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003; 26:1887. 4. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006; 332:1251. 5. 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Maurizi N, Olivotto I, Olde Nordkamp LR, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:457. 17. Lambiase PD, Gold MR, Hood M, et al. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts. Heart Rhythm 2016; 13:1066. 18. Nazer B, Dale Z, Carrassa G, et al. Appropriate and inappropriate shocks in hypertrophic cardiomyopathy patients with subcutaneous implantable cardioverter-defibrillators: An international multicenter study. Heart Rhythm 2020; 17:1107. 19. Maron MS, Steiger N, Burrows A, et al. Evidence That Subcutaneous Implantable Cardioverter-Defibrillators Are Effective and Reliable in Hypertrophic Cardiomyopathy. JACC Clin Electrophysiol 2020; 6:1019. 20. Schinkel AF, Vriesendorp PA, Sijbrands EJ, et al. Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 13/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate review and meta-analysis. Circ Heart Fail 2012; 5:552. 21. Vriesendorp PA, Schinkel AF, Van Cleemput J, et al. Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient outcomes, rate of appropriate and inappropriate interventions, and complications. Am Heart J 2013; 166:496. 22. Berul CI, Van Hare GF, Kertesz NJ, et al. Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients. J Am Coll Cardiol 2008; 51:1685. 23. Maron BJ, Casey SA, Olivotto I, et al. Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators. Circ Arrhythm Electrophysiol 2018; 11:e005820. 24. Maron BJ, Maron MS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:1155. 25. McKenna WJ, Oakley CM, Krikler DM, Goodwin JF. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 26. McKenna WJ, Harris L, Rowland E, et al. Amiodarone for long-term management of patients with hypertrophic cardiomyopathy. Am J Cardiol 1984; 54:802. 27. Mantica M, Della Bella P, Arena V. Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical therapy of sustained monomorphic ventricular tachycardia. Heart 1997; 77:481. 28. Rodriguez LM, Smeets JL, Timmermans C, et al. Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia in hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 1997; 8:803. 29. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 30. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 2017; 317:1349. 31. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol 2015; 22:13. 32. Sheikh N, Papadakis M, Schnell F, et al. Clinical Profile of Athletes With Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 14/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Cardiomyopathy. Circ Cardiovasc Imaging 2015; 8:e003454. |
ablation in patients without an apical aneurysm is uncertain. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Perry Elliott, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1999; 33:1596. 2. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298:405. 3. Begley DA, Mohiddin SA, Tripodi D, et al. Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 2003; 26:1887. 4. Spirito P, Autore C. Management of hypertrophic cardiomyopathy. BMJ 2006; 332:1251. 5. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; 124:e783. 6. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733. 7. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000; 342:365. 8. Cecchi F, Maron BJ, Epstein SE. Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest. J Am Coll Cardiol 1989; 13:1283. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 12/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate 9. Primo J, Geelen P, Brugada J, et al. Hypertrophic cardiomyopathy: role of the implantable cardioverter-defibrillator. J Am Coll Cardiol 1998; 31:1081. 10. Magnusson P, Gadler F, Liv P, M rner S. Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. Pacing Clin Electrophysiol 2016; 39:291. 11. Thavikulwat AC, Tomson TT, Knight BP, et al. Appropriate Implantable Defibrillator Therapy in Adults With Hypertrophic Cardiomyopathy. J Cardiovasc Electrophysiol 2016; 27:953. 12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 13. Wang W, Lian Z, Rowin EJ, et al. Prognostic Implications of Nonsustained Ventricular Tachycardia in High-Risk Patients With Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10. 14. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death with implantable cardioverter-defibrillators in children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 2013; 61:1527. 15. Weinstock J, Bader YH, Maron MS, et al. Subcutaneous Implantable Cardioverter Defibrillator in Patients With Hypertrophic Cardiomyopathy: An Initial Experience. J Am Heart Assoc 2016; 5. 16. Maurizi N, Olivotto I, Olde Nordkamp LR, et al. Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:457. 17. Lambiase PD, Gold MR, Hood M, et al. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts. Heart Rhythm 2016; 13:1066. 18. Nazer B, Dale Z, Carrassa G, et al. Appropriate and inappropriate shocks in hypertrophic cardiomyopathy patients with subcutaneous implantable cardioverter-defibrillators: An international multicenter study. Heart Rhythm 2020; 17:1107. 19. Maron MS, Steiger N, Burrows A, et al. Evidence That Subcutaneous Implantable Cardioverter-Defibrillators Are Effective and Reliable in Hypertrophic Cardiomyopathy. JACC Clin Electrophysiol 2020; 6:1019. 20. Schinkel AF, Vriesendorp PA, Sijbrands EJ, et al. Outcome and complications after implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: systematic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 13/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate review and meta-analysis. Circ Heart Fail 2012; 5:552. 21. Vriesendorp PA, Schinkel AF, Van Cleemput J, et al. Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient outcomes, rate of appropriate and inappropriate interventions, and complications. Am Heart J 2013; 166:496. 22. Berul CI, Van Hare GF, Kertesz NJ, et al. Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients. J Am Coll Cardiol 2008; 51:1685. 23. Maron BJ, Casey SA, Olivotto I, et al. Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators. Circ Arrhythm Electrophysiol 2018; 11:e005820. 24. Maron BJ, Maron MS. Contemporary strategies for risk stratification and prevention of sudden death with the implantable defibrillator in hypertrophic cardiomyopathy. Heart Rhythm 2016; 13:1155. 25. McKenna WJ, Oakley CM, Krikler DM, Goodwin JF. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 26. McKenna WJ, Harris L, Rowland E, et al. Amiodarone for long-term management of patients with hypertrophic cardiomyopathy. Am J Cardiol 1984; 54:802. 27. Mantica M, Della Bella P, Arena V. Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical therapy of sustained monomorphic ventricular tachycardia. Heart 1997; 77:481. 28. Rodriguez LM, Smeets JL, Timmermans C, et al. Radiofrequency catheter ablation of sustained monomorphic ventricular tachycardia in hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 1997; 8:803. 29. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 30. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 2017; 317:1349. 31. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol 2015; 22:13. 32. Sheikh N, Papadakis M, Schnell F, et al. Clinical Profile of Athletes With Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 14/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Cardiomyopathy. Circ Cardiovasc Imaging 2015; 8:e003454. 33. Dejgaard LA, Haland TF, Lie OH, et al. Vigorous exercise in patients with hypertrophic cardiomyopathy. Int J Cardiol 2018; 250:157. 34. Pelliccia A, Solberg EE, Papadakis M, et al. Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40:19. Topic 119625 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 15/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 16/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 17/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Established major risk markers and risk modifiers associated with increased risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) Risk factor Comment Major risk factors Family history of HCM- related SCD SCD due to HCM in a close relative, particularly if <40 years of age, should be considered evidence for increased risk of SCD in other related family members. Syncope Unexplained syncope that, based on clinical history, appears to be due to arrhythmia (and not neurally mediated) is associated with increased SCD risk, particularly in young patients and when the event occurred close to the time of evaluation (<6 months). Massive LV hypertrophy An increased risk of SCD in patients with HCM is seen in patients with echocardiographic evidence of 30 mm wall thickness anywhere in the LV chamber. If maximal wall thickness is not clearly defined using echocardiography, additional evaluation with CMR to clarify the extent of LV wall thickening may be warranted. LV apical aneurysm Uncommon subgroup with thin-walled dyskinetic LV apex with regional scarring. LV apical aneurysm is associated with increased risk for sustained monomorphic VT and warrants consideration for ICD. End-stage HCM (LVEF <50 percent) Higher incidence of life-threatening VT associated with this uncommon phase of HCM. These patients often develop advanced heart failure at a young age and therefore are often considered for ICD as a bridge to definitive therapy with heart transplant. Risk Modifiers Extensive LGE (ie, myocardial fibrosis) occupying 15 percent of LV mass is associated with markers of disease severity and adverse Extensive LGE by contrast-enhanced CMR outcomes including increased risk for SCD and should be considered an important arbitrator to resolving ICD decision-making when uncertain following assessment with established major risk markers. Age at time of SCD risk assessment Risk of SCD is greatest in young patients <30 years old and lessens through mid-life. In patients who have achieved advanced age ( 60 years), risk of SCD is low, even in the presence of other risk factors. Defined as 3 consecutive ventricular beats at >120 beats per minute, lasting less than 30 seconds. Multiple bursts identified on ambulatory monitoring are associated with increased risk, particularly in younger patients. Although the data relating characteristics of NSVT to SCD risk NSVT on ambulatory monitoring remain poorly defined, it would be reasonable to give greater weight to increased SCD risk in those patients with HCM with NSVT that is https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 18/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate frequent (>1 burst), of long duration (>7 beats), or particularly fast (>200 beats per minute). LVEF: left ventricular ejection fraction; CMR: cardiovascular magnetic resonance; NSVT: nonsustained ventricular tachycardia; BP: blood pressure; ICD: implantable cardioverter-defibrillator; LGE: late gadolinium enhancement; LVOT: left ventricular outflow tract obstruction. Graphic 102357 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 19/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Algorithm showing the indications for implantable cardioverter-defibrillator (ICD) placement in patients with hypertrophic cardiomyopathy (HCM) Regardless of the level of recommendation put forth in these guidelines, the decision for placement of an ICD must involve prudent application of individual clinical judgment, thorough discussions of the strength of evidence, the benefits, and the risks (including but not limited to inappropriate discharges, lead and procedural complications) to allow active participation of the fully informed patient in ultimate decision making. ICD: implantable cardioverter-defibrillator; HCM: hypertrophic cardiomyopathy; VT: ventricular tachycardia; SD: sudden death; LV: left ventricular; BP: blood pressure; SCD: sudden cardiac death. SCD risk modifiers include established risk factors and emerging risk modifiers. Reproduced from: Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 20/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Coll Cardiol 2011; 58:e212. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 102271 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 21/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Classification of sports based on peak static and dynamic components during competition This classification is based on peak static and dynamic components achieved during competition; however, higher values may be reached during training. The increasing dynamic component is defined in terms of the estimated percentage of maximal oxygen uptake (VO max) achieved and results in an increasing cardiac output. The increasing static component is related to the estimated percentage of maximal voluntary contraction reached and results in an increasing blood pressure load. The lowest total cardiovascular demands (cardiac output and blood pressure) are shown 2 in the palest color, with increasing dynamic load depicted by increasing blue intensity and increasing static load by increasing red intensity. Note the graded transition between categories, which should be individualized on the basis of player position and style of play. Danger of bodily collision (refer to UpToDate content regarding sports according to risk of impact and educational background). https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 22/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Increased risk if syncope occurs. Reproduced from: Levine BD, Baggish AL, Kovacs RJ. Eligibility and disquali cation recommendations for competitive athletes with cardiovascular abnormalities: Task force 1: Classi cation of sports: Dynamic, static, and impact: A scienti c statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2350. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 105651 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 23/24 7/6/23, 3:39 PM Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk - UpToDate Contributor Disclosures Martin S Maron, MD Grant/Research/Clinical Trial Support: iRhythm [Hypertrophic cardiomyopathy]. Consultant/Advisory Boards: Cytokinetics [Steering committee, REDWOOD-HCM]; Edgewise Pharmaceuticals [Myosin inhibitor for treatment of symptomatic hypertrophic cardiomyopathy]; Imbria Pharmaceuticals [Hypertrophic cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. William J McKenna, MD Consultant/Advisory Boards: Bristol Meyers Squibb [Novel pharmacological treatments for HCM]; Cytokinetics [Novel pharmacological treatments for HCM]; Health in Code [Genetic testing in inherited cardiac disease]; Tenaya Therapeutics [Gene therapy in cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-management-of-ventricular-arrhythmias-and-sudden-cardiac-death-risk/print 24/24 |
7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death : Martin S Maron, MD : Samuel L vy, MD, William J McKenna, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 26, 2020. INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease caused by mutations in one of several sarcomere genes that encode components of the contractile apparatus of the heart. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) HCM is characterized by left ventricular (LV) hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities ( figure 1). Depending in part upon the site and extent of cardiac hypertrophy, patients with HCM can develop one or more of the following abnormalities: LV outflow obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction".) Diastolic and systolic dysfunction. Myocardial ischemia. Mitral regurgitation. These structural and functional abnormalities can produce a variety of symptoms, including: Fatigue Dyspnea Chest pain Palpitations https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 1/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Presyncope or syncope In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias. Patients with HCM are prone to both atrial and ventricular arrhythmias. Many of these arrhythmias are asymptomatic, but some can precipitate hemodynamic collapse and sudden cardiac death (SCD). SCD is a catastrophic and unpredictable complication of HCM and in some patients may be the first presentation of the disease. The assessment of risk for arrhythmic SCD is a critical component of the clinical evaluation of nearly all patients with HCM and will be reviewed here. The management of patients following risk assessment and following a documented ventricular arrhythmia is discussed separately. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".) Other issues related to ventricular arrhythmias and SCD, as well as other clinical manifestations, natural history, diagnosis and evaluation, and treatment of patients with HCM, are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction" and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".) EPIDEMIOLOGY Ventricular arrhythmias are common in patients with HCM and can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation. While the frequency of ventricular arrhythmias is highly variable, clinically documented sustained VT is relatively rare, with the annual incidence of sudden cardiac arrest (SCA) in clinically identified HCM referral populations being approximately 1 percent, with even lower reported rate in HCM patients in the general community [1-5]. The frequency of ventricular tachyarrhythmias detected by ambulatory monitoring in patients with HCM has been evaluated in a variety of studies [1,6-12]. As an example, in a study of 178 patients who underwent 24-hour ambulatory monitoring, VPBs were highly prevalent (seen in 88 percent; 12 percent had 500 VPBs) and NSVT was present in 31 percent [1]. However, there is no evidence to suggest that frequent VPBs are, by themselves, indicative of an increased risk of sustained ventricular arrhythmia. This is similar to other forms of heart disease in which treatment of VPBs alone is warranted only in symptomatic patients. (See "Premature ventricular complexes: Treatment and prognosis".) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 2/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Other studies have shown lower rates of NSVT (typically asymptomatic), with ranges of 15 to 31 percent of patients with HCM [1,6-8]. NSVT is more likely in older patients and is associated with greater LV wall thickening and New York Heart Association (NYHA) class III or IV symptoms ( table 1). Episodes are most frequent during sleep and other periods of heightened vagal tone. The prevalence of NSVT is less common in young patients (<40 years old) with HCM, and therefore when present is of greater predictive value for SCD than when it occurs in older patients. Among one cohort of 428 patients 60 years of age with HCM, the risk of arrhythmic SCD was 0.2 percent per year, lower than the younger HCM population and significantly lower than the risk of non-HCM-related death [13]. PATHOGENESIS OF ARRHYTHMIAS An abnormal myocardial substrate comprised of myocyte disarray ( picture 1), interstitial fibrosis, and replacement fibrosis provides the likely structural nidus for the generation of ventricular arrhythmias in patients with HCM. This substrate can be acted upon by potential triggers and/or modifiers, including myocardial ischemia, LV outflow tract obstruction, and abnormal vascular response with inappropriate vasodilatation, as well as the impact of high adrenergic states (eg, during competitive sports, etc) that can lower the threshold for initiating VT/ventricular fibrillation. CLINICAL MANIFESTATIONS The presentation of ventricular arrhythmias in patients with HCM is highly variable, ranging from an absence of symptoms to palpitations to SCA, but in general the presentation of ventricular arrhythmias is similar to their presentation in other types of patients without HCM. Most patients with ventricular premature beats (VPBs) or nonsustained VT (NSVT) will be asymptomatic or have intermittent palpitations. Sustained VT most often results in palpitations, presyncope, or syncope. SCA, although rare, can be the initial presentation of sustained VT or ventricular fibrillation (VF). More detailed discussions of the presenting symptoms of VPBs, NSVT, sustained VT, and VF are discussed elsewhere. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation", section on 'Symptoms' and "Nonsustained ventricular tachycardia: https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 3/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Clinical manifestations, evaluation, and management", section on 'History and associated symptoms' and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'History and associated symptoms'.) EVALUATION Since the underlying abnormal myocardial substrate in HCM can evolve over time, nearly all patients with known or suspected HCM should undergo serial evaluations assessing SCD risk every 12 to 24 months, particularly young and middle-aged HCM patients who were previously considered low or intermediate risk, but who still remain eligible for primary prevention implantable cardioverter-defibrillator (ICD) therapy [14]. Such evaluations should include the following (see "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Diagnostic evaluation'): History and physical examination. Interim family history, with emphasis on any relatives with SCD, syncope, or ICD placement, as well as any new diagnoses of HCM. Echocardiography. 24- to 48-hour ambulatory electrocardiographic (ECG) monitoring. Although the benefit of performing longer-term ambulatory monitoring initially to identify nonsustained ventricular tachycardia (NSVT) can be considered, this strategy has not been systematically evaluated. Exercise (stress) echocardiography testing at initial evaluation to assess for symptoms, provoked LV outflow tract (LVOT) obstruction, arrhythmias, myocardial ischemia, and blood pressure (BP) response. Exercise testing is not generally repeated on an annual basis, unless warranted by the presence of new limiting symptoms, for the purpose of evaluating for a provoked LVOT gradient. Cardiac magnetic resonance (CMR) imaging. Our experts have differing approaches to utilizing CMR in HCM, with currently no clear consensus on how to best apply this advanced imaging technique for HCM diagnosis. Some experts proceed with CMR only when diagnosis of HCM remains uncertain following echocardiography while other experts perform CMR in all patients with suspected or diagnosed HCM to most reliably assess LV morphology, including maximal LV wall thickness, as well as to further inform risk https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 4/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate stratification with assessment of extent of late gadolinium enhancement. (See 'Risk stratification' below.) In a patient who has an ICD, tests for the purpose of risk stratification of sudden death (eg, ambulatory monitoring for NSVT and exercise testing to assess BP response) are not typically repeated. RISK STRATIFICATION Patients with HCM have an increased risk of death from several causes, including SCD, HF, and stroke. Established major risk factors and risk modifiers for SCD include: Prior cardiac arrest or sustained ventricular arrhythmias Family history of first-degree or close relative <50 years of age with SCD judged definitely or likely due to HCM Recent syncope suspected to be arrhythmic in origin Massive LV hypertrophy (LVH) 30 mm anywhere in LV wall LV apical aneurysm of any size End-stage HCM with LV ejection fraction (LVEF) <50 percent Risk modifiers include: Late gadolinium enhancement on cardiac magnetic resonance imaging Patient Age Multiple bursts of NSVT on ambulatory monitoring These established risk factors have greatest weight in young and middle age patients, but risk stratification for SCD should still be performed in all patients with HCM, independent of symptoms or hemodynamic status. The risk factors associated with SCD have also been evaluated for their more general association with overall mortality and outcomes. Several society guidelines for HCM as well as ventricular arrhythmias and SCD have outlined the risk factors for SCD in patients with HCM ( figure 2) [3,6,14-18]. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) Prior arrhythmic events Patients with HCM who are at the highest risk of SCD are those with prior SCA or sustained ventricular tachyarrhythmias [14]. In the absence of a clearly identifiable and reversible cause for SCD, such patients do not require additional risk stratification and should undergo implantation of an ICD for secondary prevention of SCD. (See "Hypertrophic https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 5/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter-defibrillators (ICDs)'.) Established major risk markers Because ventricular arrhythmias can be life-threatening, the ability to identify patients at high risk for SCD due to ventricular arrhythmias is critical among patients with HCM. Retrospective observational cohort studies have demonstrated that the presence of 1 of the major risk factors is associated with an elevated SCD risk, and it is reasonable to consider primary prevention ICD therapy ( table 2) after taking into account the overall clinical profile of the individual patient, including age and the benefits and risks of long- term device therapy. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter-defibrillators (ICDs)'.) The major risk factors for SCD that are most commonly cited include the following ( table 3) [3,14-16,19]: Family history of SCD A family history of HCM-related SCD is associated with an increased risk of SCD in other affected family members [20,21]. This risk is particularly high if there are multiple SCD events in one family, and if the events occurred in younger patients [20,21]. In a report of 41 relatives from eight families, 31 (75 percent) died from their heart disease, including 18 before 25 years of age, 23 with SCD, and in 15 of these 23 patients, SCD was the initial manifestation of the disease [21]. Families with multiple sudden deaths under the age of 40 years, however, are uncommon (approximately 5 percent), whereas a single sudden death is seen in up to 25 percent of families, but is of low positive predictive accuracy (<15 percent) [6,22]. Syncope Syncope, if it is not clearly attributable to another cause (eg, neurocardiogenic syncope), is a risk factor for SCD in patients with HCM [6,23]. The predictive power for syncope is greatest when it occurs in relatively close proximity to the clinical evaluation (<6 months) and in young patients. Its predictive strength is significantly less when the event has occurred remote to the time of visit and/or it has occurred in older patients [23]. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".) Massive LVH LV wall thickness 30 mm is seen in approximately 10 percent of patients with HCM and is associated in the majority of studies with an increased risk of SCD, particularly in patients less than 30 years of age [24-28]. The positive predictive value of massive LVH, however, is relatively low [24,25], although expert opinion would support strong consideration for ICD if massive LVH is confirmed, particularly in young patients [26]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 6/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Both echocardiography and cardiac magnetic resonance (CMR) imaging are used in clinical practice to determine maximal wall thickness [29]. One report from a large HCM referral center suggested a discrepancy between echocardiography and CMR imaging in the classification of massive LVH in 70 percent of patients (44 of 63 patients), with massive LVH identified more commonly on CMR (83 versus 48 percent) [30]. However, the data pertaining to increased sudden death risk in patients with HCM and massive LVH are derived from echocardiographic studies. For this reason, we recommend that if massive LVH ( 30 mm) is identified by echocardiography, using reliable measurements, the patients should be considered high risk with consideration of primary prevention ICD therapy. In patients with echo-derived measurements that are <30 mm but in whom CMR demonstrates massive LVH (echocardiography underestimated wall thickness), it would be reasonable to consider an increased risk for SCD as well, with consideration given to placement of an ICD for primary prevention. The relation of massive LVH and sudden death has been highlighted in a number of studies: In a single-center referral population of 1766 patients with HCM, including 92 with massive LVH, who were initially seen between 2004 and 2015 and followed for an average of 5.3 years, SCD events were significantly more common in patients with massive LVH (3 versus 0.8 percent per year) [31]. In a study of 480 patients, including 43 with massive LVH, who were followed for a mean of 6.5 years, the risk of SCD was zero for a wall thickness 15 mm, compared with 1.8 percent per year for a wall thickness 30 mm; the incidence of SCD almost doubled for each 5 mm increase in wall thickness ( figure 3) [24]. The cumulative risk 20 years after the initial diagnosis was close to 0 for those with a thickness 19 mm, compared with 40 percent for a wall thickness 30 mm. In a similar study of 630 patients, maximal wall thickness 30 mm was associated with sudden death, but only in the cohort who had an additional risk factor (ie, adverse family history, NSVT on Holter, syncope, or abnormal BP response on exercise) [25]. LV apical aneurysm Patients with HCM who have an LV apical aneurysm include a cohort in whom the risk of life-threatening arrhythmia appears increased [29,32,33]. Patients with HCM and LV apical aneurysm constitute a small number of patients, with outcome data supported by a small number of observational studies. Therefore, decisions regarding high-risk status should be considered on an individual basis, taking into consideration the entire clinical profile of the patient. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 7/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Thin-walled apical aneurysms are almost always associated with transmural scar (ie, apical late gadolinium enhancement [LGE]), which represent a structural nidus for the generation of sustained monomorphic VT. Apical aneurysms most notably occur in association with midventricular hypertrophy, which often produces mid-cavitary obstruction resulting in high apical systolic pressures, which likely promotes the adverse LV remodeling that ultimately develops into a thin-walled scarred akinetic apex. Patients with apical aneurysms often come to medical attention because of the dramatically abnormal ECG with precordial ST segment elevation and giant T wave inversions, most notably in leads V3 and V4, a similar ECG pattern to HCM patients with only hypertrophy at the apex (without aneurysm). This phenotype is distinct from HCM patients with increased wall thickness confined to the apex, without associated wall thinning (ie, apical HCM). (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Apical HCM'.) Among a cohort of 1940 consecutive patients with HCM seen at one of two high-volume referral centers and who underwent echocardiography with LV opacification and/or CMR, 93 patients (4.8 percent) were found to have an LV apical aneurysm [33]. Of the 54 patients who received an ICD for primary prevention, 18 patients (33 percent) experienced a life- threatening ventricular arrhythmia requiring ICD intervention, resulting in an arrhythmic event rate of 4.7 percent per year (compared with 0.9 percent per year in the patients without an LV apical aneurysm), with no difference in the risk of SCD based on the size of the aneurysm. In contrast to the general population of patients with HCM without an apical aneurysm, risk of SCD persists into the seventh decade of life (and beyond) among patients with HCM and LV apical aneurysm. In one cohort of 118 such patients, 36 percent of SCD (and aborted SCD) events occurred in patients 60 years of age [34]. In addition, patients with HCM with apical aneurysm represent the only subgroup of patients with HCM in whom radiofrequency ablation appears successful at treating life- threatening recurrent VT. In this series, recurrent VT requiring 2 ICD shocks occurred in 13 patients, of which six underwent radiofrequency ablation with no recurrence of VT. Of note, the high-risk phenotype of HCM with apical aneurysm stands in contrast to apical HCM patients who, in the absence of any of the conventional sudden death risk factors, are in fact at low risk for experiencing life-threatening VT/VF. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Apical HCM' and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Implantable cardioverter- defibrillators (ICDs)' and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Catheter ablation'.) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 8/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate End-stage with LVEF <50 percent A small proportion of patients with HCM (<5 percent) eventually progress to a stage of disease associated with adverse LV remodeling with reduced systolic performance (LVEF <50 percent). This phase has been termed "end-stage" or "burned out" HCM. Once end-stage HCM develops, further deterioration is progressive in a subset of patients, with death from progressive HF, SCD, or the need for heart transplantation. With conventional cardiovascular therapies, some end-stage patients can experience a relatively benign course in which HF symptoms can remain stable over many years. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'HCM with LV systolic dysfunction (ejection fraction <50 percent)'.) Risk modifiers Several other factors contribute to the overall SCD risk profile of patients with HCM: LGE on CMR imaging LGE on CMR imaging is common in HCM and appears to represent the structural nidus for ventricular tachyarrhythmias in patients with HCM with myocardial fibrosis [35,36]. The presence and extent of LGE is associated with markers of disease severity, including the magnitude of LVH and the presence of nonsustained ventricular arrhythmias. How best to integrate LGE in HCM management strategies remains controversial, even among HCM experts. However, based on the totality of data evaluating LGE and outcomes in HCM, we suggest considering the results of contrast-enhanced CMR with LGE in assessing risk of SCD to provide a more complete evaluation of patients who may benefit from primary prevention ICD therapy. More data to inform this management issue will also be forthcoming following the completion of a Nation Institutes of Health (NIH)-funded study, Novel Markers of Prognosis in Hypertrophic Cardiomyopathy (HCMR), involving 40 centers and more than 2500 patients, anticipated to be completed over the next seven years [37]. In addition, there are a number of methods that have been used to quantify LGE in HCM, but there is no expert consensus on which technique should be universally employed in clinical practice. The lack of standardization with respect to the preferred strategy for quantification of LGE in HCM represents a challenge. The two most commonly employed methods to identify high-signal intensity LGE pixels in the LV wall include applying a grayscale threshold several standard deviations (five or six) above mean signal intensity within a region of "nulled" myocardium and the full-width at half maximum method. Both of these techniques are highly reproducible and reliably represent total fibrosis burden as demonstrated by histopathologic analysis of ventricular septal tissue removed in HCM patients undergoing surgical myectomy [38]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 9/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In patients without any of the conventional SCD risk markers, the presence of extensive LGE on CMR may identify high-risk status and prompt consideration for primary prevention ICD therapy. In patients with HCM in whom risk assessment remains ambiguous or uncertain after assessment with the conventional risk factors, extensive LGE can be utilized as a potential arbitrator to help resolve difficult ICD decision-making, with extensive LGE swaying decision-making potentially toward ICD, and no (or minimal) LGE swaying decision-making potentially away from an ICD. The absolute amount of LGE is highly predictive of SCD. However, the pattern of LGE is more variable, with the only consistent LGE pattern observed in HCM being LGE confined to the right ventricular insertion point area, where it has been shown not to be associated with increased risk for SCD. Of note, decisions regarding device therapy in both of these clinical scenarios should be made in the context of a fully informed patient, taking into account the desires and wishes of the patient in a shared decision-making manner. In a cohort of 1293 patients with HCM who underwent CMR and were followed for a median of 3.3 years, LGE was present in 548 patients (42 percent), and the primary end point of SCD events (including SCD and appropriate ICD shocks for documented VT or VF) occurred in 37 patients (3 percent) [39]. Risk of SCD events increased with the amount of LGE present (adjusted hazard ratio 1.46 for each 10 percent increase in LGE, 95% CI 1.12-1.92), particularly among patients with apparent low risk based on the traditional clinical features. In addition, the absence of LGE was associated with lower risk and a source of reassurance for patients. In a 2018 cohort study from a single, high-volume referral center, which included 1423 adult patients (age 18 years) who underwent CMR between 2008 and 2015, 706 patients (50 percent) had LGE identified on CMR imaging [40]. LGE involving 15 percent of the myocardium was associated with a significantly greater risk of SCD or appropriate ICD therapy. In a 2016 meta-analysis, which included 2993 patients from five cohorts, the presence of LGE on CMR imaging was associated with significantly greater risk for total mortality (OR 1.8, 95% CI 1.2-2.7), cardiovascular mortality (OR 2.9, 95% CI 1.5-5.6), and SCD (OR 3.4, 95% CI 2.0-5.9) [41]. For every additional 10 percent of the myocardium affected by LGE, there was an incremental increase in total mortality of approximately 30 percent, with an incremental increase of nearly 60 percent in cardiovascular mortality, SCD, and https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 10/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HF death. Patients with LGE have also been shown to be more likely to have SCD or aborted SCD with an ICD shock [42]. Age at time of SCD risk assessment Risk of SCD is greatest in young patients with HCM (<30 years of age), and this risk decreases but is not eliminated through mid-life [20]. Patients with HCM who are >60 years of age are at a very low risk for any HCM-related adverse events, including SCD [13]. Indeed, risk of SCD in older patients is very low (<1 percent), even among those patients with one or more of the conventional risk factors [13,43,44]. Conversely, the presence of the major risk factors is of greater prognostic significance in young and middle-aged patients with HCM. The impact of age at HCM diagnosis on overall mortality risk (ie, in addition to SCD) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Age at diagnosis'.) NSVT The presence of multiple asymptomatic runs of NSVT (most commonly defined as 3 beats at >120 beats per minute) is associated with an increased risk for SCD in patients with HCM, although the effect of a patient's age plays a role in the associated risk [8-11,45]. Multiple bursts of NSVT are associated with increased risk, particularly in young patients and in patients with symptoms of impaired consciousness [1,7-10,46,47]. Although the data for relating characteristics of NSVT to SCD risk are scant, it would be reasonable to give greater weight to increased risk of SCD in patients with HCM with NSVT that is frequent, prolonged, and particularly fast, while a single, slow, short burst of NSVT on ambulatory monitoring is itself not associated with increased risk of future life-threatening VT/ventricular fibrillation (VF), and in the absence of any other conventional risk factors does not form the basis for primary prevention ICD. For patients with HCM and an ICD, NSVT is associated with an increased risk of appropriate ICD therapies for VT/VF [48]. In a study of 178 adult patients with HCM aged 20 to 50 years who underwent 24-hour ambulatory ECG monitoring and were followed for an average of 5.5 years, NSVT was common (31 percent), with a relatively low annual sudden death rate (1.1 percent). In this cohort of older patients, there was a smaller increase in risk with NSVT (1.6 versus 0.9 percent per year in patients with and without NSVT, defined as 3 beats at 120 beats per minute) [1]. In a series of 531 patients with HCM, of whom 104 had NSVT, the presence of NSVT was associated with an increased risk of SCD in patients less than 30 years of age (odds ratio [OR] 4.4 compared with no NSVT, 95% CI 1.5-12.3) [8]. There was, however, no relation among duration, frequency, or rate of NSVT episodes and prognosis at any age. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 11/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Uncertain risk modifiers Several other clinical factors contribute in an uncertain way to the overall SCD risk profile of patients with HCM: Myocardial ischemia There are conflicting data as to whether myocardial ischemia is a risk factor for SCD in patients with HCM. In a series of 23 young patients with HCM (age 6 to 23 years), ischemia was associated with a history of cardiac arrest or syncope [49]. In contrast, there was no relation between the presence of ischemia and outcomes in a larger prospective series of 216 unselected patients with HCM [50]. The relationship between ischemia and outcomes is likely dependent upon both the age of the patient and the etiology of ischemia (eg, severe small vessel-mediated ischemia versus atherosclerotic obstructive coronary artery disease [CAD]). Patients with HCM and coincident CAD have mortality rates that exceed those of CAD patients with normal LV function [51]. The impact of stress-induced ischemia on overall mortality risk (ie, in addition to SCD) is presented separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) Genotype There appear to be high-risk genotypes for SCD, particularly related to troponin T disease and several of the beta myosin-heavy chain mutations [52]. However, the available data are derived from a small number of families and may be skewed on this basis [14,16]. Moreover, most mutations are novel (ie, "private mutations"), and thus a certain genotype may be associated with higher risk in a specific family but would not be associated with the same consequences in other unrelated patients and families. For this reason, clinical decisions about risk for sudden death and need for primary prevention ICD are not made based on the results of genetic testing. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) LV outflow tract (LVOT) gradient The majority of natural history studies involving patients with HCM have failed to show an association between LVOT gradient and adverse prognosis [20,44,46,47,53]. Two large studies, however, have shown a weak association of LVOT gradients with overall disease-related mortality and sudden death [54,55]. The impact of LVOT obstruction on overall morbidity (ie, HF symptoms and risk for atrial fibrillation) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) In a multicenter, multinational study of 1101 patients (273 [25 percent] with resting LVOT gradient 30 mmHg) followed for a mean of six years, the probability of HCM- related death and of SCD was slightly greater in those with LVOT gradient of at least 30 mmHg (relative risk [RR] 2) [55]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 12/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In a single-center study of 917 patients (288 [31 percent] with resting LVOT gradient 30 mmHg) followed for a median of 61 months, survival free from mortality/transplant was significantly lower in patients with LVOT gradients (87 versus 90 percent), as was survival free from sudden death/ICD discharge (91 versus 96 percent) [54]. LVOT obstruction was independently associated with SCD, and there was a significant trend towards lower sudden death/ICD survival in patients with increasing LVOT obstruction. The incidence of SCD in patients with obstruction also varies substantially based upon the number of additional risk factors ( figure 4) [54]. For patients with an outflow gradient 30 mmHg but no additional risk factors, the annual incidence of SCD or ICD discharge was low. There are also a number of practical limitations to using LVOT gradient as a clinical risk factor for sudden death. Gradients are present in large numbers of patients, which would ultimately lead to significant overtreatment with ICDs in this disease. Additionally, gradients can be abolished and/or significantly mitigated with drugs or invasive septal reduction therapy. Nonrandomized retrospective cohort studies suggest that risk of SCD or appropriate ICD shocks is very low following septal myectomy [56,57]. However, surgical myectomy in asymptomatic or mildly symptomatic patients is not indicated solely as a therapy to decrease sudden death risk. In contrast, septal ablation has not been demonstrated to reduce SCD or ICD discharge rates. However, for those patients in whom risk remains ambiguous after assessment with the conventional sudden death risk factors, the presence of a high LVOT gradient can be used as a potential arbitrator to help resolve difficult ICD decision-making. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Nonpharmacologic treatment of LV outflow tract obstruction'.) Impact of number of risk factors It is reasonable to consider ICD in patients with one major risk factor, since SCD risk is increased. Decisions about high-risk status in patients with one risk factor should be individualized based on the strength of the specific risk factor and the individual patient situation. The presence of two or more risk factors for SCD is associated with even greater SCD risk. In patients in whom sudden death risk remains uncertain after assessment with the major risk markers or who are uncertain about pursuing ICD therapy, the presence of a risk modifier may be associated with additional sudden death risk and therefore may help resolve ICD decision-making. Identification of high-risk patients may be improved by using multiple factors [6,54,58,59]. In a study of 368 patients (mean age 37 years) who were followed for a mean of 3.6 years, estimated https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 13/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate six-year SCD-free survival was associated with the number of risk factors ( figure 5) [6]: Zero risk factors (55 percent of the cohort) 95 percent survival One risk factor (33 percent of the cohort) 93 percent survival Two or three risk factors (12 percent of the cohort) 72 percent survival Data from a multicenter registry of ICDs in patients with HCM published in 2007 suggested that a single risk factor may be sufficient justification for consideration of ICD implantation [60]. Subsequently, in a 2019 single-center study of 2094 consecutive patients evaluated over a 17- year period at a tertiary HCM referral center, 527 patients were implanted with a primary prevention ICD based on clinical evaluation and the presence of one or more high-risk markers [61]. Cumulative five-year likelihood of appropriate ICD intervention was 10.5 percent, with 82 primary prevention ICD recipients (15.6 percent) experiencing VT or VF requiring ICD therapy, whereas only five patients (0.3 percent) without an ICD experienced SCD (including two patients in whom primary prevention ICD was declined by the patient). Data in low-risk patients are limited, but those meeting the following profile probably have an incidence of SCD of <0.5 percent per year [14,16,62]: None of the five major risk factors No or only mild symptoms of HF Left atrium 45 mm LV wall thickness <20 mm LV outflow gradient <50 mmHg Risk prediction model While the risk of SCD in patients with HCM can be estimated from large populations, individualized risk prediction offers the hope of the most accurate risk assessment and appropriate interventions. Given the complexity of SCD risk assessment in patients with HCM and the mixed data on the HCM Risk-SCD calculator, we feel that additional studies are warranted to further validate and refine this risk model in other HCM populations, along with the need for additional comparisons with the current United States guideline-based approach using a number of noninvasive risk markers [63,64]. As with risk prediction in any situation, the ability to discriminate patients with HCM at risk of SCD has been most successful in patients deemed at higher risk. In a retrospective cohort study involving 3675 patients from six European centers (2082 in the development cohort and 1593 in the validation cohort) with a median follow-up of 5.7 years, the primary outcome of SCD or appropriate ICD shock occurred in 198 patients (118 patients with SCD, 27 with aborted SCD, and 53 with appropriate ICD shock) [65]. Using the derived model (which incorporated parameters of age, maximal LV wall thickness, left atrial diameter, LVOT https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 14/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate gradient, family history of SCD, NSVT, and unexplained syncope), which can be accessed online, investigators predicted that for every 16 ICDs implanted, one patient would be saved from SCD every five years. Subsequent studies looking at validation of the HCM Risk-SCD calculator have reported widely varying results in terms of the accuracy of the score for predicting SCD [66-69]. In the largest reported validation cohort (International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy [EVIDENCE-HCM] cohort), which included 2147 patients with |
reason, clinical decisions about risk for sudden death and need for primary prevention ICD are not made based on the results of genetic testing. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".) LV outflow tract (LVOT) gradient The majority of natural history studies involving patients with HCM have failed to show an association between LVOT gradient and adverse prognosis [20,44,46,47,53]. Two large studies, however, have shown a weak association of LVOT gradients with overall disease-related mortality and sudden death [54,55]. The impact of LVOT obstruction on overall morbidity (ie, HF symptoms and risk for atrial fibrillation) is discussed separately. (See "Hypertrophic cardiomyopathy: Natural history and prognosis", section on 'Mortality'.) In a multicenter, multinational study of 1101 patients (273 [25 percent] with resting LVOT gradient 30 mmHg) followed for a mean of six years, the probability of HCM- related death and of SCD was slightly greater in those with LVOT gradient of at least 30 mmHg (relative risk [RR] 2) [55]. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 12/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate In a single-center study of 917 patients (288 [31 percent] with resting LVOT gradient 30 mmHg) followed for a median of 61 months, survival free from mortality/transplant was significantly lower in patients with LVOT gradients (87 versus 90 percent), as was survival free from sudden death/ICD discharge (91 versus 96 percent) [54]. LVOT obstruction was independently associated with SCD, and there was a significant trend towards lower sudden death/ICD survival in patients with increasing LVOT obstruction. The incidence of SCD in patients with obstruction also varies substantially based upon the number of additional risk factors ( figure 4) [54]. For patients with an outflow gradient 30 mmHg but no additional risk factors, the annual incidence of SCD or ICD discharge was low. There are also a number of practical limitations to using LVOT gradient as a clinical risk factor for sudden death. Gradients are present in large numbers of patients, which would ultimately lead to significant overtreatment with ICDs in this disease. Additionally, gradients can be abolished and/or significantly mitigated with drugs or invasive septal reduction therapy. Nonrandomized retrospective cohort studies suggest that risk of SCD or appropriate ICD shocks is very low following septal myectomy [56,57]. However, surgical myectomy in asymptomatic or mildly symptomatic patients is not indicated solely as a therapy to decrease sudden death risk. In contrast, septal ablation has not been demonstrated to reduce SCD or ICD discharge rates. However, for those patients in whom risk remains ambiguous after assessment with the conventional sudden death risk factors, the presence of a high LVOT gradient can be used as a potential arbitrator to help resolve difficult ICD decision-making. (See "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk", section on 'Nonpharmacologic treatment of LV outflow tract obstruction'.) Impact of number of risk factors It is reasonable to consider ICD in patients with one major risk factor, since SCD risk is increased. Decisions about high-risk status in patients with one risk factor should be individualized based on the strength of the specific risk factor and the individual patient situation. The presence of two or more risk factors for SCD is associated with even greater SCD risk. In patients in whom sudden death risk remains uncertain after assessment with the major risk markers or who are uncertain about pursuing ICD therapy, the presence of a risk modifier may be associated with additional sudden death risk and therefore may help resolve ICD decision-making. Identification of high-risk patients may be improved by using multiple factors [6,54,58,59]. In a study of 368 patients (mean age 37 years) who were followed for a mean of 3.6 years, estimated https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 13/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate six-year SCD-free survival was associated with the number of risk factors ( figure 5) [6]: Zero risk factors (55 percent of the cohort) 95 percent survival One risk factor (33 percent of the cohort) 93 percent survival Two or three risk factors (12 percent of the cohort) 72 percent survival Data from a multicenter registry of ICDs in patients with HCM published in 2007 suggested that a single risk factor may be sufficient justification for consideration of ICD implantation [60]. Subsequently, in a 2019 single-center study of 2094 consecutive patients evaluated over a 17- year period at a tertiary HCM referral center, 527 patients were implanted with a primary prevention ICD based on clinical evaluation and the presence of one or more high-risk markers [61]. Cumulative five-year likelihood of appropriate ICD intervention was 10.5 percent, with 82 primary prevention ICD recipients (15.6 percent) experiencing VT or VF requiring ICD therapy, whereas only five patients (0.3 percent) without an ICD experienced SCD (including two patients in whom primary prevention ICD was declined by the patient). Data in low-risk patients are limited, but those meeting the following profile probably have an incidence of SCD of <0.5 percent per year [14,16,62]: None of the five major risk factors No or only mild symptoms of HF Left atrium 45 mm LV wall thickness <20 mm LV outflow gradient <50 mmHg Risk prediction model While the risk of SCD in patients with HCM can be estimated from large populations, individualized risk prediction offers the hope of the most accurate risk assessment and appropriate interventions. Given the complexity of SCD risk assessment in patients with HCM and the mixed data on the HCM Risk-SCD calculator, we feel that additional studies are warranted to further validate and refine this risk model in other HCM populations, along with the need for additional comparisons with the current United States guideline-based approach using a number of noninvasive risk markers [63,64]. As with risk prediction in any situation, the ability to discriminate patients with HCM at risk of SCD has been most successful in patients deemed at higher risk. In a retrospective cohort study involving 3675 patients from six European centers (2082 in the development cohort and 1593 in the validation cohort) with a median follow-up of 5.7 years, the primary outcome of SCD or appropriate ICD shock occurred in 198 patients (118 patients with SCD, 27 with aborted SCD, and 53 with appropriate ICD shock) [65]. Using the derived model (which incorporated parameters of age, maximal LV wall thickness, left atrial diameter, LVOT https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 14/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate gradient, family history of SCD, NSVT, and unexplained syncope), which can be accessed online, investigators predicted that for every 16 ICDs implanted, one patient would be saved from SCD every five years. Subsequent studies looking at validation of the HCM Risk-SCD calculator have reported widely varying results in terms of the accuracy of the score for predicting SCD [66-69]. In the largest reported validation cohort (International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy [EVIDENCE-HCM] cohort), which included 2147 patients with HCM and no prior history of SCD from 14 centers in the United States, Europe, the Middle East, and Asia, 44 patients experienced an SCD event (defined as SCD, successful resuscitation from SCA, or appropriate ICD intervention for VT/VF) over the five-year follow- up (0.5 percent per year) [70]. Among patients with high predicted risk ( 6 percent, n = 297), the five-year incidence of SCD was significantly higher (8.9 percent) compared with patients with intermediate (4 to 6 percent, n = 326) or low (<4 percent, n = 1524) predicted risk (five-year incidence 1.8 and 1.4 percent, respectively). In a cohort of 706 patients with HCM and no prior history of SCD who were seen at two European referral centers, 42 patients (5.9 percent) experienced an SCD event (defined as SCD, successful resuscitation from SCA, or appropriate ICD intervention for VT/VF) over the five-year follow-up (1.2 percent per year) [66]. Patients with an SCD event had significantly greater estimated five-year risk of SCD using the HCM Risk-SCD calculator (4.9 versus 2.8 percent in patients without SCD), with the calculator resulting in improved risk assessment compared with 2003 and 2011 society guidelines. The HCM Risk-SCD calculator has also been retrospectively applied to a cohort of 2094 patients with HCM seen at a large United States referral center [61]. The HCM Risk-SCD calculator accurately predicted patients at low risk without SCD events (92 percent specificity), but the sensitivity of a high-risk classification was only 34 percent for predicting SCD events, suggesting that the majority of patients at risk for SCD would have been missed using only the calculator to quantify risk. In contrast, the enhanced 2011 ACC/AHA guideline criteria had sensitivity and specificity of 87 and 78 percent, respectively, suggesting greater likelihood of preventing SCD with an ICD at the expense of slightly higher use of ICDs in patients without SCD events. The HCM Risk-SCD model and the conventional risk factors from the American College of Cardiology/American Heart Association (ACC/AHA) guidelines were compared in a cohort of 288 patients (mean age 52 years, 66 percent male, 25 percent with LVOT obstruction 30 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 15/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate mmHg) with HCM from a single referral center in the United Kingdom, among whom 14 patients experienced SCD or equivalent (resuscitation from cardiac arrest or appropriate ICD shock for VF or VT >200 beats per minute) over a mean follow-up of 5.6 years [71]. Compared with the conventional ACC/AHA risk factors, the HCM Risk-SCD model more accurately predicted low-risk patients who did not require an ICD (220 of 274 patients [82 percent] compared with 157 of 274 patients [57 percent]) but also failed to identify a significantly greater number of high-risk patients who experienced SCD or equivalent (6 of 14 patients [43 percent] compared with 1 of 14 patients [7 percent]). The presence of LGE identified on CMR may aid in further risk stratifying patients following calculation of the HCM Risk-SCD score. Among 354 patients with HCM and calculated HCM Risk SCD score suggesting low to intermediate five-year risk (<6 percent), patients with LGE extent 10 percent had much higher five-year rates of hard cardiac events including SCD, resuscitated cardiac arrest, appropriate ICD therapies, and sustained VT (23 versus 3 percent) [72]. (See 'Risk modifiers' above.) In a 2019 meta-analysis which included 7291 patients with HCM (including the original HCM Risk- SCD cohort and five subsequent cohorts), 70 percent of patients were identified as low risk, 15 percent as intermediate risk, and 15 percent as high risk [73]. In total, 184 SCD events occurred, with 68 percent occurring in the intermediate and high risk (prevalence of SCD events 1, 2.4, and 8.4 percent in low, intermediate, and high risk groups, respectively). The majority of patients with HCM are stratified as low risk for SCD, but the greatest number of appropriate ICD therapies occur in this low-risk group. Conversely, patients identified as being at high risk of SCD are more likely to receive an appropriate ICD shock, but overall this group receives the lowest number of appropriate ICD therapies. However, proportionally, since the denominator is much larger in low-risk patients, the percentage of patients with ICD shocks is greatest in the high-risk group. This essentially means that, similar to other risk prediction scenarios, the risk score discriminates best those patients with HCM at highest risk for sudden death, but may fail to identify a significant number of patients who have low-risk scores but who are at high risk for sudden death. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 16/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)") Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients with hypertrophic cardiomyopathy (HCM) are prone to ventricular arrhythmias. Ventricular arrhythmias can range from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia (NSVT) to sustained VT and ventricular fibrillation (VF). While the frequency of ventricular arrhythmias is highly variable, the annual incidence of sudden cardiac death (SCD) in the clinically identified general HCM patient population is approximately 1 percent. (See 'Introduction' above and 'Epidemiology' above.) The presentation of ventricular arrhythmias in patients with HCM is highly variable, ranging from an absence of symptoms to palpitations to SCD. Most patients with VPBs or NSVT will be asymptomatic or have intermittent palpitations, while on rare occasions SCD can be the initial presentation of sustained VT or VF. (See 'Clinical manifestations' above.) Since the underlying abnormal myocardial substrate in HCM can evolve over time, all patients with known or suspected HCM should undergo serial evaluations for SCD risk stratification, including history and physical examination, interim family history, echocardiography, ambulatory electrocardiographic (ECG) monitoring, and exercise testing (on a case-by-case basis). With the emerging role of extensive late gadolinium https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 17/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate enhancement (LGE) informing risk assessment, contrast-enhanced cardiac magnetic resonance (CMR) should also be considered. It is reasonable to repeat SCD risk assessment every 12 to 24 months in patients who remain at risk and potentially eligible for an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD. (See 'Evaluation' above.) Major risk factors and risk modifiers associated with an increased risk of SCD in patients with HCM include (see 'Risk stratification' above): Prior or sustained ventricular arrhythmias. Family history of close relative with SCD due to HCM. Syncope suspected to be arrhythmic in origin, particularly when occurring relatively recently to time of evaluation and in younger patients. Multiple bursts of NSVT on ambulatory ECG monitoring. Massive LV hypertrophy 30 mm anywhere in LV wall. LV apical aneurysm. End-stage HCM with LV ejection fraction <50 percent. The results of contrast-enhanced CMR with extensive LGE (ie, myocardial scarring) can be used to help arbitrate ICD decision-making if risk remains ambiguous or uncertain following conventional risk stratification assessment. Age at time of sudden death risk assessment ACKNOWLEDGMENT The editorial staff at UpToDate acknowledges Perry Elliott, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Adabag AS, Casey SA, Kuskowski MA, et al. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy. 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Maron MS, Finley JJ, Bos JM, et al. Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation 2008; 118:1541. 33. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69:761. 34. Rowin EJ, Maron BJ, Chokshi A, Maron MS. Left ventricular apical aneurysm in hypertrophic cardiomyopathy as a risk factor for sudden death at any age. Pacing Clin Electrophysiol 2018. 35. Maron BJ, Maron MS, Lesser JR, et al. Sudden cardiac arrest in hypertrophic cardiomyopathy in the absence of conventional criteria for high risk status. Am J Cardiol 2008; 101:544. 36. Weissler-Snir A, Hindieh W, Spears DA, et al. The relationship between the quantitative extent of late gadolinium enhancement and burden of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy: A delayed contrast-enhanced magnetic resonance study. J Cardiovasc Electrophysiol 2019; 30:651. 37. Kramer CM, Neubauer S. Further Refining Risk in Hypertrophic Cardiomyopathy With Late Gadolinium Enhancement by CMR. J Am Coll Cardiol 2018; 72:871. 38. Moravsky G, Ofek E, Rakowski H, et al. Myocardial fibrosis in hypertrophic cardiomyopathy: accurate reflection of histopathological findings by CMR. JACC Cardiovasc Imaging 2013; 6:587. 39. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 2014; 130:484. 40. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Preserved Systolic Function. J Am Coll Cardiol 2018; 72:857. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 21/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 41. Weng Z, Yao J, Chan RH, et al. Prognostic Value of LGE-CMR in HCM: A Meta-Analysis. JACC Cardiovasc Imaging 2016; 9:1392. 42. Briasoulis A, Mallikethi-Reddy S, Palla M, et al. Myocardial fibrosis on cardiac magnetic resonance and cardiac outcomes in hypertrophic cardiomyopathy: a meta-analysis. Heart 2015; 101:1406. 43. Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005; 45:1340. 44. McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomyopathy. Assessment of patients at high risk. Circulation 1989; 80:1489. 45. Yetman AT, Hamilton RM, Benson LN, McCrindle BW. Long-term outcome and prognostic determinants in children with hypertrophic cardiomyopathy. J Am Coll Cardiol 1998; 32:1943. 46. Cecchi F, Olivotto I, Montereggi A, et al. Hypertrophic cardiomyopathy in Tuscany: clinical course and outcome in an unselected regional population. J Am Coll Cardiol 1995; 26:1529. 47. Spirito P, Chiarella F, Carratino L, et al. Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 1989; 320:749. 48. Wang W, Lian Z, Rowin EJ, et al. Prognostic Implications of Nonsustained Ventricular Tachycardia in High-Risk Patients With Hypertrophic Cardiomyopathy. Circ Arrhythm Electrophysiol 2017; 10. 49. Dilsizian V, Bonow RO, Epstein SE, Fananapazir L. Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1993; 22:796. 50. Yamada M, Elliott PM, Kaski JC, et al. Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome. Eur Heart J 1998; 19:500. 51. Sorajja P, Ommen SR, Nishimura RA, et al. Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease. Circulation 2003; 108:2342. 52. Fananapazir L. Advances in molecular genetics and management of hypertrophic cardiomyopathy. JAMA 1999; 281:1746. 53. Maron BJ, Bonow RO, Cannon RO 3rd, et al. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med 1987; 316:780. 54. Elliott PM, Gimeno JR, Tom MT, et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. 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The management of hypertrophic cardiomyopathy. N Engl J Med 1997; 336:775. 63. Grace A. Prophylactic implantable defibrillators for hypertrophic cardiomyopathy: disarray in the era of precision medicine. Circ Arrhythm Electrophysiol 2015; 8:763. 64. Weissler-Snir A, Adler A, Williams L, et al. Prevention of sudden death in hypertrophic cardiomyopathy: bridging the gaps in knowledge. Eur Heart J 2017; 38:1728. 65. O'Mahony C, Jichi F, Pavlou M, et al. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J 2014; 35:2010. 66. Vriesendorp PA, Schinkel AF, Liebregts M, et al. Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol 2015; 8:829. 67. Maron BJ, Casey SA, Chan RH, et al. 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Topic 4952 Version 37.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 24/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 25/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 26/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 27/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 28/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Myocyte disarray in hypertrophic cardiomyopathy Microscopic appearance of the myocardium in hypertrophic cardiomyopathy, stained with hematoxylin and eosin, shows myocyte disarray with an irregular arrangement of abnormal shaped myocytes that contain bizarre nuclei and surrounding areas of increased connective tissue. Courtesy of Professor Michael Davies, St. George's Hospital, London. Graphic 55914 Version 2.0 Normal endomyocardial biopsy Normal endomyocardial biopsy in longitudinal section. Courtesy of Helmut Rennke, MD. Graphic 61625 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 29/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Pyramid profile of risk stratification model currently used to identify patients a sudden cardiac death (SCD) risk who may be candidates for an implantable card defibrillator (ICD) Major and minor risk markers appear in boxes at the left. At the right are the results of ICD therapy in 730 ch adolescents, and adults assembled from two registry studies. |
model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator. Europace 2016; 18:773. 69. Fern ndez A, Quiroga A, Ochoa JP, et al. Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America. Am J Cardiol 2016; 118:121. 70. O'Mahony C, Jichi F, Ommen SR, et al. International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM). Circulation 2018; 137:1015. 71. Leong KMW, Chow JJ, Ng FS, et al. Comparison of the Prognostic Usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation Risk Stratification Systems for Patients With Hypertrophic Cardiomyopathy. Am J Cardiol 2018; 121:349. 72. Todiere G, Nugara C, Gentile G, et al. Prognostic Role of Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and Low-to-Intermediate Sudden Cardiac Death Risk Score. Am J Cardiol 2019; 124:1286. 73. O'Mahony C, Akhtar MM, Anastasiou Z, et al. Effectiveness of the 2014 European Society of Cardiology guideline on sudden cardiac death in hypertrophic cardiomyopathy: a systematic review and meta-analysis. Heart 2019; 105:623. Topic 4952 Version 37.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 24/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate GRAPHICS Morphologic variants of hypertrophic cardiomyopathy HCM typically presents with asymmetric or localized areas of LV hypertrophy, which are diagrammed in B to J. (A) Normal LV wall thickness. (B) ASH. (C) Sigmoid septum, which is more common in older adults. (D) Midcavity hypertrophy associated with midcavity obstruction. (E) Predominantly free wall hypertrophy, an unusual pattern in HCM. (F) LV wall thinning (associated with low LV ejection fraction) and biatrial enlargement. (G) Predominantly apical LV hypertrophy. (H) Severe concentric hypertrophy with cavity obliteration. (I) Biventricular hypertrophy. (J) Mild to moderate symmetric hypertrophy. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 25/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate HCM: hypertrophic cardiomyopathy; LV: left ventricular; ASH: asymmetrical septal hypertrophy. Graphic 58156 Version 6.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 26/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 27/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 28/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Myocyte disarray in hypertrophic cardiomyopathy Microscopic appearance of the myocardium in hypertrophic cardiomyopathy, stained with hematoxylin and eosin, shows myocyte disarray with an irregular arrangement of abnormal shaped myocytes that contain bizarre nuclei and surrounding areas of increased connective tissue. Courtesy of Professor Michael Davies, St. George's Hospital, London. Graphic 55914 Version 2.0 Normal endomyocardial biopsy Normal endomyocardial biopsy in longitudinal section. Courtesy of Helmut Rennke, MD. Graphic 61625 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 29/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Pyramid profile of risk stratification model currently used to identify patients a sudden cardiac death (SCD) risk who may be candidates for an implantable card defibrillator (ICD) Major and minor risk markers appear in boxes at the left. At the right are the results of ICD therapy in 730 ch adolescents, and adults assembled from two registry studies. BP: blood pressure; CAD: coronary artery disease; EF: ejection fraction; ICD: implantable cardioverter-defibril ventricular; LGE: late gadolinium enhancement; LVH: left ventricular hypertrophy; NSVT: nonsustained ventri tachycardia; SD: sudden death; VT/VF: ventricular tachycardia/ventricular fibrillation. Extensive LGE is a novel primary risk marker that can also be used as an arbitrator when conventional risk a ambiguous. SD events are uncommon after 60 years of age, even with conventional risk factors. Reproduced from: Maron B, Ommen S, Semsarian C. Hypertrophic cardiomyopathy: Present and future, with translation into contempo medicine. J Am Coll Cardiol 2014; 64:83. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 99534 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 30/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate The recognized markers of risk in HCM and their sensitivity, specificity, and positive and negative predictive accuracy (PPA and NPA) Sensitivity, Specificity, PPA, NPA, Risk factor percent percent percent percent Abnormal blood pressure [1] response: <40 years old 75 66 15 97 [2] NSVT: adult <45 years old 69 80 22 97 [3] NSVT: 21 years old <10 89 <10 85 Inducible VT/VF: high risk [4] population 82 68 17 98 [5] Syncope: <45 years old* 35 82 25 86 Family history: at least one unexplained sudden death HCM* 42 79 28 88 [5] [6] LVH 3 cm 26 88 13 95 [7] Two or more risk factors 45 90 23 96 HCM: hypertrophic cardiomyopathy; LVH: left ventricular hypertrophy; ICD: implantable cardioverter- defibrillator; NPA: negative predictive accuracy; NSVT: nonsustained ventricular tachycardia; PPA: positive predictive accuracy; VF: ventricular fibrillation; VT: ventricular tachycardia. Figures provided are for the risk of death from all causes rather than sudden death only. Figures provided are for risk of sudden death and/or appropriate ICD discharge. In this data set from Elliott and colleagues, family history and syncope were combined in order to achieve statistical significance of relative risk. 1. McKenna WJ, Franklin RC, Nihoyannopoulos P, et al. Arrhythmia and prognosis in infants, children and adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol 1988; 11:147. 2. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic signi cance of 24 hour ambulatory electrocardiographic monitoring in patients with hypertrophic cardiomyopathy: a prospective study. Am J Cardiol 1981; 48:252. 3. McKenna WJ, Oakley CM, Krikler DM, et al. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Br Heart J 1985; 53:412. 4. Fananapazir L, Chang AC, Epstein SE, McAreavey D. Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological ndings. Circulation 1992; 86:730. 5. McKenna W, Dean eld J, Faruqui A, et al. Prognosis in hypertrophic cardiomyopathy: role of age and clinical, electrocardiographic and hemodynamic features. Am J Cardiol 1981; 47:532. 6. Elliott PM, Gimeno BJ, Mahon NG, et al. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001; 357:420. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 31/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate 7. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identi cation of high risk patients. J Am Coll Cardiol 2000; 36:2212. Reproduced with permission from: McKenna, WJ, Behr, ER. Hypertrophic cardiomyopathy: management, risk strati cation, and prevention of sudden death. Heart 2002; 87:169. Copyright 2002 BMJ Publishing Group, Ltd. Graphic 80617 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 32/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Established major risk markers and risk modifiers associated with increased risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) Risk factor Comment Major risk factors Family history of HCM- SCD due to HCM in a close relative, particularly if <40 years of age, related SCD should be considered evidence for increased risk of SCD in other related family members. Syncope Unexplained syncope that, based on clinical history, appears to be due to arrhythmia (and not neurally mediated) is associated with increased SCD risk, particularly in young patients and when the event occurred close to the time of evaluation (<6 months). Massive LV hypertrophy An increased risk of SCD in patients with HCM is seen in patients with echocardiographic evidence of 30 mm wall thickness anywhere in the LV chamber. If maximal wall thickness is not clearly defined using echocardiography, additional evaluation with CMR to clarify the extent of LV wall thickening may be warranted. LV apical aneurysm Uncommon subgroup with thin-walled dyskinetic LV apex with regional scarring. LV apical aneurysm is associated with increased risk for sustained monomorphic VT and warrants consideration for ICD. End-stage HCM (LVEF <50 percent) Higher incidence of life-threatening VT associated with this uncommon phase of HCM. These patients often develop advanced heart failure at a young age and therefore are often considered for ICD as a bridge to definitive therapy with heart transplant. Risk Modifiers Extensive LGE (ie, myocardial fibrosis) occupying 15 percent of LV mass is associated with markers of disease severity and adverse outcomes including increased risk for SCD and should be considered Extensive LGE by contrast-enhanced CMR an important arbitrator to resolving ICD decision-making when uncertain following assessment with established major risk markers. Age at time of SCD risk assessment Risk of SCD is greatest in young patients <30 years old and lessens through mid-life. In patients who have achieved advanced age ( 60 years), risk of SCD is low, even in the presence of other risk factors. Defined as 3 consecutive ventricular beats at >120 beats per minute, lasting less than 30 seconds. Multiple bursts identified on ambulatory NSVT on ambulatory monitoring monitoring are associated with increased risk, particularly in younger patients. Although the data relating characteristics of NSVT to SCD risk remain poorly defined, it would be reasonable to give greater weight to increased SCD risk in those patients with HCM with NSVT that is https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 33/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate frequent (>1 burst), of long duration (>7 beats), or particularly fast (>200 beats per minute). LVEF: left ventricular ejection fraction; CMR: cardiovascular magnetic resonance; NSVT: nonsustained ventricular tachycardia; BP: blood pressure; ICD: implantable cardioverter-defibrillator; LGE: late gadolinium enhancement; LVOT: left ventricular outflow tract obstruction. Graphic 102357 Version 9.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 34/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Left ventricular wall thickness predicts sudden death in HCM In a study of 480 patients with an HCM, the incidence of sudden death during a 6.5-year follow-up was directly related to maximal wall thickness. The incidence of sudden death almost doubled for each 5 mm increase in wall thickness. HCM: hypertrophic cardiomyopathy. Data from Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000; 342:1778. Graphic 75913 Version 4.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 35/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Sudden cardiac death and risk factors in hypertrophic cardiomyopathy Kaplan-Meier estimates of the proportions of patients surviving from sudden cardiac death, appropriate ICD discharge, or resuscitated ventricular fibrillation in relation to number of risk factors in patients with obstruction. ICD: implantable cardioverter-defibrillator. Reproduced with permission from: Elliott PM, Gimeno JR, Tome MT, et al. Left ventricular out ow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 2006; 27:1933. Copyright 2006 Oxford University Press. Graphic 65115 Version 2.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 36/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Risk of sudden death in HCM A set of four predictors of sudden death were analyzed to develop a risk stratification algorithm in a study of 368 patients with HCM. The predictors included a history of syncope and/or a family history of sudden death, a left ventricular wall thickness 30 mm, nonsustained ventricular tachycardia on ambulatory monitoring, and an abnormal blood pressure response to exercise (refer to text). This bar graph shows the percentage of each risk factor group (zero, one, two, and three risk factors) in which patients died during follow-up (black bars = sudden death; hatched bars = congestive cardiac failure or transplant; white = all deaths). The majority of deaths were sudden, and the greatest proportion occurred in patients with multiple risk factors. HCM: hypertrophic cardiomyopathy. Data from Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identi cation of high risk patients. J Am Coll Cardiol 2000; 36:2212. Graphic 75731 Version 3.0 https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 37/38 7/6/23, 3:40 PM Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death - UpToDate Contributor Disclosures Martin S Maron, MD Grant/Research/Clinical Trial Support: iRhythm [Hypertrophic cardiomyopathy]. Consultant/Advisory Boards: Cytokinetics [Steering committee, REDWOOD-HCM]; Edgewise Pharmaceuticals [Myosin inhibitor for treatment of symptomatic hypertrophic cardiomyopathy]; Imbria Pharmaceuticals [Hypertrophic cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. William J McKenna, MD Consultant/Advisory Boards: Bristol Meyers Squibb [Novel pharmacological treatments for HCM]; Cytokinetics [Novel pharmacological treatments for HCM]; Health in Code [Genetic testing in inherited cardiac disease]; Tenaya Therapeutics [Gene therapy in cardiomyopathy]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-risk-stratification-for-sudden-cardiac-death/print 38/38 |
7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management : Peter J Zimetbaum, MD, John V Wylie, MD, FACC : Samuel L vy, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 26, 2022. INTRODUCTION Nonsustained ventricular tachycardia (NSVT) is a common but poorly understood arrhythmia. It is usually asymptomatic and most often diagnosed during cardiac monitoring (eg, continuous ambulatory electrocardiography or inpatient telemetry) or on an exercise test performed for other reasons. The presence of NSVT has long been recognized as a potential marker for the development of sustained ventricular arrhythmias and sudden death. However, while NSVT predicts overall mortality, it doesn t specifically predict sudden cardiac death (SCD). Unfortunately, our understanding of which patients with NSVT are at greatest risk for lethal arrhythmias or how the NSVT relates to the lethal arrhythmias is still quite rudimentary. One clearly established premise is that NSVT in the presence of structural heart disease carries a more serious prognosis than NSVT in the absence of a cardiac abnormality. Since NSVT doesn t specifically predict SCD, the nature of the underlying structural heart disease is the primary determinant of mortality. (See "Nonsustained VT in the absence of apparent structural heart disease".) There are two general goals in the management of NSVT: Identification of patients at risk for malignant, sustained arrhythmias and SCD Treatment to suppress symptoms caused by NSVT, when present and clinically significant https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 1/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate This topic will review the diagnosis and management of NSVT. Detailed discussions of risk stratification for arrhythmic death after a myocardial infarction, and the roles of implantable cardioverter-defibrillators and antiarrhythmic drugs in such patients, are presented separately. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction" and "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment".) DEFINITION OF NSVT A variety of definitions of NSVT have been published, but the most commonly used definition is [1]: Three or more consecutive ventricular beats Rate of >100 beats per minute Duration of less than 30 seconds The variable published definitions of NSVT have included: Rates ranging from as low as 100 beats per minute to as high as 140 beats per minute Between three and five consecutive ventricular complexes Durations as short as 15 seconds to as high as one minute Beat limits as low as 15 beats or as high as 99 beats, beyond which the arrhythmia is considered sustained The approach to distinguishing VT from other causes of wide QRS complex tachycardias (ie, supraventricular tachycardia [SVT] with aberrant conduction, SVT with preexcitation, pacemaker- associated tachycardia, or artifact) is discussed separately. (See 'Differential diagnosis' below and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Differential diagnosis'.) CLINICAL MANIFESTATIONS The history, physical examination, and 12-lead electrocardiogram (ECG) can all provide information helping to confirm the diagnosis of NSVT. History and associated symptoms Patients with NSVT are usually asymptomatic, although some patients may notice symptoms associated with episodes of NSVT. Most patients with NSVT will have a history of underlying structural heart disease (eg, coronary heart disease, heart failure, hypertrophic cardiomyopathy, congenital heart disease, etc), although NSVT can also be https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 2/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate seen in patients without known structural heart disease. (See "Nonsustained VT in the absence of apparent structural heart disease".) The type and intensity of symptoms, if present, will vary depending upon the rate and duration of the NSVT along with the presence or absence of significant comorbid conditions. Patients with NSVT who notice symptoms typically present with one or more of the following symptoms: Palpitations Chest pain Shortness of breath Syncope or presyncope Most commonly, symptomatic patients will report palpitations that may or may not be associated with chest pain and/or shortness of breath. If the duration of the episode approaches 20 to 30 seconds with an associated rate of NSVT that is rapid enough to result in hemodynamic compromise, patients may experience presyncope or even syncope. Physical examination Few physical examination findings in patients with NSVT are unique and specific. By definition, patients will have a pulse exceeding 100 beats per minute during the episode. In addition, if the physical examination coincides with an episode of NSVT, this can reveal evidence of atrioventricular (AV) dissociation, which is present in up to 75 percent of patients with VT, although it is not always easy to detect [2-4]. During AV dissociation, the normal coordination of atrial and ventricular contraction is lost, which may produce characteristic physical examination findings including (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'AV dissociation'): Marked fluctuations in the blood pressure because of the variability in the degree of left atrial contribution to left ventricular filling, stroke volume, and cardiac output. Variability in the occurrence and intensity of heart sounds (especially S1) ("cacophony of heart sounds"), which is heard more frequently when the rate of the tachycardia is slower. Cannon "A" waves Cannon A waves are intermittent and irregular jugular venous pulsations of greater amplitude than normal waves. They reflect simultaneous atrial and ventricular activation, resulting in contraction of the right atrium against a closed tricuspid valve. Prominent A waves can also be seen during some SVTs. Such prominent waves result from simultaneous atrial and ventricular contraction occurring with every beat. (See "Examination of the jugular venous pulse".) Electrocardiogram All patients with suspected NSVT should have a 12-lead electrocardiogram, although NSVT is frequently identified on continuous telemetric monitoring, https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 3/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate in which case only one or two leads may be available for review. As with the interpretation of any ECG, the standard initial approach to diagnosis of NSVT includes an assessment of rate, regularity, axis, QRS duration, and QRS morphology. NSVT typically generates a wide QRS complex, usually with a QRS width >0.12 seconds. A full discussion of the ECG features of VT is presented separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Electrocardiogram' and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) Diagnostic evaluation Once NSVT has been identified, reversible causes of arrhythmia should be sought, including electrolyte imbalances, myocardial ischemia, hypoxia, adverse drug effects, anemia, hypotension, and heart failure. For patients who have only a single asymptomatic episode of NSVT, often no further investigation is required. However, for patients with multiple episodes or for those with symptoms felt to be related to NSVT, a thorough diagnostic evaluation to exclude structural heart disease is warranted, including cardiac imaging and ambulatory ECG monitoring for most patients and invasive electrophysiology studies (EPS) only on rare occasions. For patients with recurrent episodes or those who are highly symptomatic, even young, otherwise healthy patients need a thorough cardiac imaging evaluation to exclude entities such as undiagnosed dilated cardiomyopathy, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. Typically, the evaluation for structural heart disease includes an imaging study of the heart, most commonly echocardiography, although cardiac magnetic resonance (CMR) imaging is also reasonable (if locally available) as it provides the most detailed structural information. Continuous ambulatory ECG monitoring is indicated in many patients with NSVT with vague symptoms to establish a correlation between symptoms and arrhythmia and to quantify the frequency of the arrhythmia. Ambulatory monitoring is also useful to exclude the presence of sustained VT. Exercise treadmill testing is indicated in patients with exercise-related symptoms or NSVT and in patients with suspected coronary ischemia. In patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), a signal-averaged ECG can be useful. Invasive EPS are rarely required in the initial evaluation of NSVT. In patients with syncope, near-syncope, or sustained palpitations, EPS should be considered to evaluate for the presence of sustained VT. In addition, in patients with ischemic cardiomyopathy, ejection https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 4/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate fraction 35 to 40 percent, and NSVT, invasive EPS may be used to risk stratify patients for implantable cardioverter-defibrillator implantation [5,6]. An in-depth discussion of the diagnostic evaluation of patients with VT is presented separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Additional diagnostic evaluation'.) DIFFERENTIAL DIAGNOSIS The differential diagnosis for a wide QRS complex tachycardia (WCT) includes NSVT, supraventricular tachycardia with aberrant conduction (either preexistent or rate-related), supraventricular tachycardia with preexcitation, supraventricular tachycardia in a pacemaker- dependent patient, and electrocardiogram (ECG) artifact. Differentiating VT from other causes of WCT may be difficult, particularly if a high-quality 12-lead ECG is not available during the time of the arrhythmia. In general, however, a WCT, particularly when poorly tolerated, should be considered to be VT until proven otherwise. The approach to the differential diagnosis of VT from other causes of WCT is discussed separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Differential diagnosis'.) TREATMENT Symptomatic patients Patients with symptomatic NSVT should usually be treated with beta blockers as the initial therapy. Many patients with NSVT will have coexisting cardiac conditions in which beta blockers are also indicated (eg, coronary heart disease, heart failure), in which case the patient may derive multiple benefits from the use of beta blockers. For patients with NSVT who remain symptomatic in spite of beta blockers, or who are unable to tolerate beta blockers due to side effects, nondihydropyridine calcium channel blockers (ie, verapamil and diltiazem) can be added to the medical regimen, although these agents should only be used in patients with structurally normal hearts and should not be used in patients with uncontrolled heart failure. Antiarrhythmic medications are generally reserved for patients with severely symptomatic NSVT despite therapy with beta blockers and nondihydropyridine calcium channel blockers who are not candidates for catheter ablation of the VT. NSVT is most often asymptomatic, but some patients experience palpitations, chest pain, shortness of breath, presyncope, or syncope. Because many of the symptoms that may be https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 5/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate attributed to NSVT are vague and nonspecific, it is important to try to correlate symptoms to episodes of NSVT before initiating therapy specifically to treat NSVT. Beta blockers For the initial treatment of patients with symptomatic NSVT, we suggest beta blockers. This preference is based on significant indirect evidence of the efficacy of beta blockers for reducing ventricular ectopy and tachyarrhythmias in other cardiac conditions, as well as coadministration of beta blockers for other cardiac conditions and the fact that beta blockers are generally safe and well tolerated [5]. Metoprolol (usual effective dose 50 to 200 mg daily) and carvedilol (usual effective dose 12.5 to 50 mg daily) are the most commonly prescribed beta blockers for the suppression of NSVT. Nondihydropyridine calcium channel blockers For patients with NSVT who remain symptomatic in spite of beta blockers, or who are unable to tolerate beta blockers due to side effects, we suggest adding a nondihydropyridine calcium channel blockers (ie, verapamil [usual effective dose 360 to 480 mg daily] or diltiazem [usual effective dose 240 to 360 mg daily]) rather than an antiarrhythmic medication. For most patients, nondihydropyridine calcium channel blockers are better tolerated and associated with less toxicity than antiarrhythmic drugs. However, nondihydropyridine calcium channel blockers should not be used in patients with structural heart disease or uncontrolled heart failure. (See "Calcium channel blockers in the treatment of cardiac arrhythmias", section on 'Ventricular arrhythmia'.) Antiarrhythmic drugs For some patients who have frequent, highly symptomatic NSVT not adequately suppressed by beta blockers or calcium channel blockers, the addition of antiarrhythmic medications ( table 1) may be helpful. We suggest amiodarone as the initial choice, rather than other antiarrhythmic drugs, based on its efficacy. However, due to potential toxicities of antiarrhythmic drugs, we use them sparingly and only in the most symptomatic patients who have failed other medical therapy and who are not candidates, decline, or fail ablation therapy. Amiodarone may be given at a dose of 200 mg three times daily for two weeks, then 200 mg two times daily for two weeks, and then 200 mg daily. The dose can be further reduced to 100 mg daily if there is concern over toxicity, and follow-up monitoring should be performed. Mexiletine is usually given as 150 to 200 mg every eight hours. These two drugs require careful monitoring, particularly in patients with structural heart disease. In selected cases, other agents such as sotalol or procainamide can be used for suppression of NSVT, but these medications are rarely used and must be used with caution. Amiodarone Amiodarone is the most effective antiarrhythmic agent for suppressing VT, an effect that has clearly been demonstrated in multiple trials of amiodarone in post-myocardial https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 6/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate infarction (MI) and congestive heart failure patients in whom baseline and follow-up 24-hour ambulatory ECGs were performed [7-9]. In the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) pilot study, which compared amiodarone with placebo in patients with frequent or repetitive asymptomatic ventricular premature beats (VPBs), patients receiving amiodarone had significantly fewer VPBs and episodes of NSVT [7]. In the CHF-STAT trial, which compared amiodarone with placebo in patients with heart failure, left ventricular ejection fraction (LVEF) of 40 percent or less, and frequent ventricular premature beats (more than 10 per hour), significantly fewer patients on amiodarone had ventricular tachycardia on Holter monitor (33 versus 76 percent) after two weeks of therapy [10]. Similar results have been seen in patients treated with both amiodarone and a beta blocker [11,12]. In an analysis of eight trials that included over 5000 patients with a prior MI and frequent VPBs (median frequency 18 per hour), amiodarone therapy was associated with a significant 35 percent reduction in arrhythmic/sudden death, and a nonsignificant 8 percent reduction in total mortality [12]. While amiodarone has never been shown to reduce overall mortality, its use is not associated with an increase in mortality due to proarrhythmia (as is the case with class IC antiarrhythmic drugs). However, its well-described, potentially toxic side effects need to be considered before prescribing, and routine monitoring of liver, thyroid, and lung function should be performed in patients on amiodarone. (See "Amiodarone: Clinical uses" and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Class I agents In selected cases, Class IA drugs (eg, procainamide) and class IB drugs (eg, mexiletine) can be used for suppression of NSVT, but these medications must be used with caution. Class IC drugs are generally not used in patients with structural heart disease because of safety concerns. (See "Nonsustained VT in the absence of apparent structural heart disease".) The Cardiac Arrhythmia Suppression Trial (CAST) evaluated the efficacy of flecainide, encainide, and moricizine in suppressing ventricular ectopy in almost 1500 post-MI patients, many of whom had depressed LV function [13,14]. Additionally, only 20 percent of patients had NSVT and only 10 percent had more than one run in 24 hours. The findings were dramatic, showing an increase in arrhythmic sudden death and total cardiovascular mortality in the treated patients even though the original ventricular ectopy was suppressed ( figure 1). Thus, class IC agents are not used in the treatment of NSVT in coronary heart disease. https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 7/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Radiofrequency catheter ablation In patients who have very frequent, symptomatic monomorphic NSVT not controlled by medications or who are unable or unwilling to take medications, catheter ablation can be effective for reducing or eliminating NSVT and associated symptoms [1]. It would be appropriate to consider catheter ablation as a primary alternative to antiarrhythmic drugs. This strategy is most commonly used in patients with idiopathic, triggered arrhythmias, which often originate in the outflow tracts, septum, or papillary muscles. In such patients, catheter ablation can be a highly successful procedure to eliminate the symptoms of arrhythmia [15]. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Implantable cardioverter-defibrillators Implantable cardioverter-defibrillators (ICDs) are not indicated for the treatment of NSVT as NSVT is self-limited and self-terminating. However, some patients with NSVT who are found to have a cardiomyopathy may be a candidate for ICD placement for primary prevention of sudden cardiac death related to sustained ventricular tachyarrhythmias. The use of an ICD for primary prevention is discussed in detail separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Asymptomatic patients Patients with NSVT and no identified symptoms do not require any specific therapy directed toward the NSVT. However, patients with NSVT and associated underlying cardiac comorbidities (eg, coronary heart disease, heart failure) should be treated with optimal medical therapy as indicated for the relevant associated condition. (See "Chronic coronary syndrome: Overview of care".) The Multicenter Unsustained Tachycardia Trial (MUSTT trial), which was not primarily designed as a randomized ICD clinical trial but rather to study the management of high-risk patients using the results of electrophysiology study (EPS), enrolled 704 patients with a prior MI (less than one month to more than three years previously), asymptomatic NSVT, an LVEF 40 percent, and inducible sustained ventricular tachycardia [6,16]. Patients were randomly assigned to no therapy or EP-guided antiarrhythmic therapy, which included either an antiarrhythmic agent (class IA with or without mexiletine, propafenone, sotalol, or amiodarone) or an ICD if at least one antiarrhythmic agent was ineffective; the primary end point was arrhythmic death or resuscitated cardiac arrest, with a secondary endpoint of total mortality. The reduction in the primary and secondary end points in the electrophysiologically guided group was largely attributable to ICD therapy; at five years the primary end point occurred in 9 percent of those receiving an ICD, compared with 37 percent of those receiving an antiarrhythmic drug, and the secondary end point occurred in 24 and 55 percent, respectively. There was no difference in outcome between patients receiving no therapy and those treated with an antiarrhythmic drug ( figure 2) [17]. https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 8/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Patients with asymptomatic NSVT may also be considered for an ICD in the presence of structural heart disease with LVEF <40 percent. Many patients will meet other criteria for primary prevention with an ICD. For post-MI patients with moderate LV dysfunction (ie, LVEF 35 to 40 percent), who do not otherwise meet current criteria for ICD implantation, NSVT remains an indication for EPS and possible ICD implantation. A full discussion of the role of ICDs in primary and secondary prevention of sudden cardiac death is presented separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Definition The most common definition is three or more consecutive ventricular beats, a heart rate of >100 beats per minute, and a duration of arrhythmia of less than 30 seconds. https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 9/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate (See 'Definition of NSVT' above.) Symptoms Patients with nonsustained ventricular tachycardia (NSVT) are usually asymptomatic, although some patients may notice symptoms associated with episodes of NSVT. Symptoms may include palpitations, chest pain, shortness of breath, syncope, or presyncope. Symptoms may vary depending upon the rate and duration of the NSVT along with the presence or absence of significant comorbid conditions. (See 'History and associated symptoms' above.) Physical examination By definition, the pulse rate is >100 beats per minute. Few physical examination findings are unique and specific for NSVT. If the physical examination coincides with an episode of NSVT, this can reveal evidence of atrioventricular (AV) dissociation, including marked fluctuations in blood pressure, variability in the occurrence and intensity of heart sounds (especially S1), and cannon A waves. (See 'Physical examination' above.) Evaluation All patients with suspected NSVT should have a 12-lead electrocardiogram (ECG), although NSVT is frequently identified on continuous telemetry monitoring, in which case only one or two leads may be available for review. (See 'Electrocardiogram' above.) Reversible causes Once identified, reversible causes of NSVT should be sought, including electrolyte imbalances, myocardial ischemia, hypoxia, adverse drug effects, anemia, hypotension, and heart failure. Single asymptomatic episode Often, for these patients, no further investigation is required. Multiple or symptomatic episodes For patients with multiple episodes or with symptoms felt to be related to NSVT, a thorough diagnostic evaluation to exclude structural heart disease is warranted, including cardiac imaging and ambulatory ECG monitoring for most patients and invasive electrophysiology studies (EPS) only on rare occasions. (See 'Diagnostic evaluation' above.) Treatment Asymptomatic patients In general, asymptomatic patients do not require any specific therapy directed toward the NSVT. However, some asymptomatic patients with NSVT who are found to have infarct-related cardiomyopathy with significantly reduced left ventricular systolic function may be https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 10/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate evaluated for implantable cardioverter-defibrillator placement for primary prevention of sudden cardiac death related to sustained ventricular tachyarrhythmias. (See 'Asymptomatic patients' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Symptomatic patients Initial therapy For the initial treatment of patients with symptomatic NSVT, we suggest beta blockers rather than calcium channel blockers or antiarrhythmic medications (Grade 2C). (See 'Beta blockers' above.) For patients with NSVT who remain symptomatic in spite of beta blockers, or who are unable to tolerate beta blockers due to side effects, we suggest adding a nondihydropyridine calcium channel blocker (ie, verapamil or diltiazem) rather than an antiarrhythmic medication (Grade 2C). (See 'Nondihydropyridine calcium channel blockers' above.) Alternative therapy For some patients who have frequent, highly symptomatic NSVT not adequately suppressed by beta blockers or calcium channel blockers, the addition of antiarrhythmic medications ( table 1) may be helpful. We suggest amiodarone as the initial choice, rather than other antiarrhythmic drugs, based on its efficacy (Grade 2C). (See 'Antiarrhythmic drugs' above.) In patients with very frequent symptomatic monomorphic NSVT not controlled by medications or who are unable or unwilling to take medications, catheter ablation can be effective for reducing or eliminating NSVT and associated symptoms. (See 'Radiofrequency catheter ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges the late Mark E. Josephson, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 11/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 2. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245. 3. Tchou P, Young P, Mahmud R, et al. Useful clinical criteria for the diagnosis of ventricular tachycardia. Am J Med 1988; 84:53. 4. Wellens HJ, B r FW, Lie KI. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med 1978; 64:27. 5. Pedersen CT, Kay GN, Kalman J, et al. EHRA/HRS/APHRS expert consensus on ventricular arrhythmias. Europace 2014; 16:1257. 6. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. 7. Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349:675. 8. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta- blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165. 9. Julian DG, Camm AJ, Frangin G, et al. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997; 349:667. 10. Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995; 333:77. 11. Boutitie F, Boissel JP, Connolly SJ, et al. Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators. Circulation 1999; 99:2268. 12. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators. Lancet 1997; 350:1417. 13. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 12/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate 1991; 324:781. 14. Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992; 327:227. 15. Coggins DL, Lee RJ, Sweeney J, et al. Radiofrequency catheter ablation as a cure for idiopathic tachycardia of both left and right ventricular origin. J Am Coll Cardiol 1994; 23:1333. 16. Buxton AE, Fisher JD, Josephson ME, et al. Prevention of sudden death in patients with coronary artery disease: the Multicenter Unsustained Tachycardia Trial (MUSTT). Prog Cardiovasc Dis 1993; 36:215. 17. Wyse DG, Talajic M, Hafley GE, et al. Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis. J Am Coll Cardiol 2001; 38:344. Topic 917 Version 33.0 https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 13/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate GRAPHICS Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 14/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 15/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Encainide and flecainide increase cardiac mortality Results of the Cardiac Arrhythmia Suppression Trial (CAST) in patients with ventricular premature beats after myocardial infarction. Patients receiving encainide or flecainide had, when compared with those receiving placebo, a significantly lower rate of avoiding a cardiac event (death or resuscitated cardiac arrest) (left panel, p = 0.001) and a lower overall survival (right panel, p = 0.0006). The cause of death was arrhythmia or cardiac arrest. Data from Echt DS, Liebson PR, Mitchell B, et al. N Engl J Med 1991; 324:781. Graphic 59975 Version 5.0 https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 16/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate ICD reduces sudden death in MUSTT The MUSTT trial enrolled 704 patients with coronary artery disease, nonsustained ventricular tachycardia (VT), and a left ventricular ejection fraction 40 percent who had sustained VT induced during electrophysiologic (EP) study. Kaplan-Meier estimates show that the incidence of cardiac arrest or death from arrhythmia is significantly lower in those receiving an implantable cardioverter-defibrillator (ICD) compared with those receiving no therapy or those with EP-guided (EPG) antiarrhythmic drug (AAD) therapy. Data from: Buxton AE, Lee KL, Fisher JD, et al. N Engl J Med 1999; 341:1882. Graphic 68247 Version 4.0 https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 17/18 7/6/23, 3:39 PM Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management - UpToDate Contributor Disclosures Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. John V Wylie, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/nonsustained-ventricular-tachycardia-clinical-manifestations-evaluation-and-management/print 18/18 |
7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Nonsustained VT in the absence of apparent structural heart disease : Robert Phang, MD, FACC, FHRS : Samuel L vy, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 25, 2022. INTRODUCTION Nonsustained ventricular tachycardia (NSVT), defined as three or more consecutive ventricular beats at a rate of greater than 100 beats/min with a duration of less than 30 seconds ( waveform 1), is a relatively common clinical problem [1]. It is often asymptomatic and typically diagnosed during cardiac monitoring (eg, ambulatory monitoring or inpatient telemetry) or an exercise test performed for other reasons. It may also be incidentally recorded on a patient's cardiac implantable electronic device. If the patient is asymptomatic, the major clinical challenge is to determine if the NSVT is relatively benign or indicative of an increased risk of sudden cardiac death. A major determinant of prognosis in patients with NSVT is the presence or absence of underlying structural heart disease as diagnosed using other modalities (eg, echocardiography, myocardial perfusion imaging, cardiac computed tomography, or magnetic resonance imaging). The 12 lead electrocardiogram should also be assessed in conjunction with imaging and is particularly important in screening for inherited channelopathies, as those conditions often have no apparent structural heart disease. This topic will discuss NSVT in patients without apparent structural heart disease. NSVT occurring in patients with different forms of heart disease, as well as sustained VT in patients without apparent structural heart disease, are discussed separately. (See "Ventricular tachycardia in the absence of apparent structural heart disease" and "Catecholaminergic polymorphic ventricular tachycardia".) https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 1/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate INCIDENCE OF NSVT NSVT, with an incidence ranging from 0 to 4 percent in the general population, is more common with increasing age and more often occurs in men [2]. These incidence figures are drawn from studies using prolonged recordings in relatively small numbers of normal subjects. It is likely, however, that a single 24-hour recording significantly underestimates the true frequency of this often asymptomatic and intermittent arrhythmia. IDENTIFYING THE ORIGIN OF THE WCT The initial challenge may be determining if the wide complex tachycardia (WCT) is truly of ventricular origin versus aberrantly conducted supraventricular beats. Aberrancy involves the premature activation of the bundle branches where one bundle conducts normally and the other is still refractory and therefore exhibits a typical bundle branch pattern, usually the right bundle branch block (RBBB). Various morphologic clues favor aberrancy, including: Visualization of a premature atrial complex (PAC; also referred to an atrial premature beat,) immediately preceding the WCT Typical RBBB or left bundle branch block (LBBB) morphology of the wide complex beats An incomplete pause (lack of compensatory pause) following the WCT Deceleration of the tachycardia with associated loss of wide complex beats ("peeling back of refractoriness" where the bundle branch block recovers conduction) "Ashman phenomenon" or so-called "long-short" initiation of the WCT where a long R-R cycle is followed by the PAC that initiates the WCT These clues, however, are not absolute rules for aberrancy. In the absence of these findings, the WCT is more likely to represent NSVT. Differentiating VT from SVT with aberrancy is discussed in greater detail separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Basic features'.) SYNDROMES WITH FREQUENT NSVT There are several syndromes associated with frequent episodes of NSVT in the absence of structural heart disease, including repetitive monomorphic VT, idiopathic left VT, and nonsustained polymorphic VT. These conditions are discussed in detail elsewhere but will be https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 2/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate briefly reviewed here. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Repetitive monomorphic ventricular tachycardia Some patients have frequent and repetitive episodes of nonsustained and occasionally sustained VT. The arrhythmias are usually monomorphic, most arise from the right ventricular outflow tract (RVOT), and their frequency and duration can be affected by both exercise and autonomic manipulation. Sixty to 80 percent of patients with idiopathic VT have VT originating from the RVOT, with 30 percent or fewer originating from the left ventricular outflow tract (LVOT) [3]. The prognosis of repetitive monomorphic VT is almost uniformly good, although sudden death can rarely occur. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Repetitive monomorphic VT'.) Idiopathic left ventricular tachycardia Patients who have VT with a typical right bundle branch and left anterior fascicular block morphology are said to have idiopathic left VT originating from the LV posterior septum (also known as Belhassen VT or verapamil-responsive VT). This VT is less frequently associated with exercise and also rarely results in sudden cardiac death, although tachycardia-induced cardiomyopathy has been reported in persons with frequent or sustained episodes of VT. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Idiopathic left ventricular tachycardia'.) Nonsustained polymorphic ventricular tachycardia Polymorphic VT in the absence of structural heart disease occurs in a few settings which involve inherited channelopathies and associated abnormalities on the 12 lead electrocardiogram (ECG) may be apparent. These include the acquired or inherited long QT syndromes, catecholaminergic polymorphic VT, and Brugada syndrome [4]. In comparison with the generally good prognosis associated with idiopathic monomorphic VT, polymorphic VT is associated with an increased risk of sudden death. (See "Congenital long QT syndrome: Treatment" and "Catecholaminergic polymorphic ventricular tachycardia".) Arrhythmogenic right ventricular cardiomyopathy Ventricular arrhythmias, including NSVT, are common in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). While many patients with ARVC have structural cardiac abnormalities that are evident on cardiac imaging, as well as ECG abnormalities, it is also possible to diagnose ARVC by means of genetic testing or endomyocardial biopsy. The clinical manifestations and approach to diagnosing ARVC are discussed in detail separately. (See "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".) https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 3/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate CLINICAL MANIFESTATIONS Symptoms related to NSVT, as with any tachyarrhythmia, are dependent on the ventricular rate and duration of the arrhythmia as well as the presence or absence of other comorbid conditions (ie, heart failure, obstructive coronary heart disease, cerebrovascular disease). By definition, NSVT is self-limiting, lasting less than 30 seconds. As such, patients with NSVT are less likely to develop symptoms than those with sustained VT, and most patients with NSVT are asymptomatic. However, patients with NSVT can develop symptoms of palpitations and/or lightheadedness. On rare occasions, syncope may occur if NSVT is very rapid and results in a significant drop in cardiac output. Because of its self-limited duration of less than 30 seconds, NSVT does not usually result in angina or dyspnea, as can sometimes be seen with sustained VT. (See "Evaluation of palpitations in adults".) EVALUATION NSVT is typically diagnosed during cardiac monitoring (eg, ambulatory monitoring, inpatient telemetry, or recorded on cardiac implantable electronic device) or an exercise test performed for other reasons. Once NSVT has been identified, it is important to determine the presence or absence of any associated structural heart disease. In asymptomatic patients, the evaluation for prognostically significant structural heart disease should include the following: Thorough history, including pertinent family history, and physical examination 12-lead electrocardiogram Transthoracic echocardiography Exercise stress testing In patients who present with syncope felt to be related to ventricular arrhythmia, or those with a strongly positive family history suggesting an inherited cardiomyopathy (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) or inherited channelopathy, there may be a role for additional testing. This testing may include genetic testing for specific mutations as well as advanced non-invasive imaging with cardiac computed tomography or magnetic resonance imaging. The diagnostic approach in such patients is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Clinical utility of cardiovascular magnetic resonance imaging".) https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 4/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate Prolonged palpitations, syncope, or presyncope suggest that there may be a coexistent sustained ventricular arrhythmia. Ambulatory event recorders are valuable in this setting. In addition, electrophysiologic studies can be used to provoke sustained arrhythmias that may produce symptoms mimicking the spontaneous arrhythmia. (See "Ambulatory ECG monitoring" and "Invasive diagnostic cardiac electrophysiology studies".) TREATMENT For patients with NSVT who are asymptomatic and have no evidence of structural heart disease, we suggest no specific medical therapy. However, drug therapy may be required in patients with disabling symptoms. We generally begin with a beta-blocker unless there is a contraindication (eg, uncontrolled asthma), in which case we will try a calcium channel blocker, usually verapamil or diltiazem. If the arrhythmia persists despite treatment with these drugs, the therapeutic options include more potent antiarrhythmic medications or to perform catheter-based ablative therapy. The management of NSVT, including antiarrhythmic drugs and catheter ablation, is discussed in detail separately. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management".) Patients with nonsustained polymorphic VT may have a worse prognosis, and management can be quite complex. Such patients should be referred to an electrophysiologist. (See "Catecholaminergic polymorphic ventricular tachycardia".) PROGNOSIS The prognosis of NSVT is dependent upon the presence or absence of structural heart disease, with a generally benign prognosis in those without apparent structural heart disease. The prognostic significance of NSVT in the absence of apparent heart disease has been studied by many investigators [5-8]. The results obtained have varied with the rigor with which underlying heart disease was excluded. The large, long-term Busselton and Framingham community studies suggested that complex ventricular ectopy and NSVT were associated with an approximately threefold increase in risk of subsequently developing heart disease including angina pectoris, myocardial infarction, and congestive heart failure, but neither study used exercise stress testing to evaluate for coronary artery disease [7,8]. A similar limitation was present in the large Multiple Risk Factor Intervention Trial (MRFIT) [9]. https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 5/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate The results were different in two smaller studies in which exercise testing, echocardiography and, when indicated, coronary arteriography were used to exclude significant structural heart disease [6,10]. These studies followed 118 patients for an average of four years. Only two (1.7 percent) cardiac events were observed, an event rate lower than that in an age-matched population in the United States. The Baltimore Longitudinal Study of Aging, in which patients aged 60 to 85 were screened for cardiovascular disease and followed for 10 years, found that NSVT did not predict a coronary event in this population [11]. Studies of persons with pacemakers who have incidentally recorded NSVT have not shown worse outcomes [12,13]. A study of 119 pacemaker patients with preserved LVEF and incidentally recorded NSVT had no increased mortality [12]. A large prospective study of 565 pacemaker patients with a mean follow-up of four years found that NSVT was not a predictor of adverse outcomes [13]. These findings suggest that a thorough search for organic heart disease is important and that NSVT in the absence of structural heart disease is generally benign. The prognosis of NSVT in persons with underlying structural heart disease is discussed separately. (See "Incidence of and risk stratification for sudden cardiac death after myocardial infarction".) Exercise-induced NSVT Approximately 1 to 4 percent of subjects without obvious evidence of heart disease develop NSVT during exercise [14-17]. The prognostic significance of this is discussed separately. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Ventricular arrhythmias'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Catheter ablation of arrhythmias".) SUMMARY AND RECOMMENDATIONS Background Nonsustained ventricular tachycardia (NSVT), defined as three or more consecutive ventricular beats at a rate of greater than 100 beats/min with a duration of less https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 6/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate than 30 seconds ( waveform 1), is a relatively common clinical problem that occurs in up to 4 percent of the population. (See 'Introduction' above and 'Incidence of NSVT' above.) Diagnosis NSVT is typically diagnosed during cardiac monitoring (eg, ambulatory monitoring, inpatient telemetry, via cardiac implantable electronic devices) or during exercise stress testing. The initial challenge may be determining if the wide complex tachycardia is truly of ventricular origin versus aberrantly conducted supraventricular beats, with several clues from the electrocardiogram that can aid in the distinction. (See 'Identifying the origin of the WCT' above.) Evaluation for cardiac structural disease Once NSVT has been diagnosed, it is important to determine the presence or absence of any associated structural heart disease. A thorough history and physical examination, 12-lead electrocardiogram, transthoracic echocardiography, and exercise stress testing is generally sufficient to exclude prognostically significant structural heart disease in asymptomatic patients. (See 'Evaluation' above.) NSVT with syncope In patients who present with syncope felt to be related to NSVT, or those with a strongly positive family history suggesting an inherited cardiomyopathy (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) or inherited channelopathy, there may be a role for additional testing. This includes genetic testing for specific mutations and advanced noninvasive imaging with cardiac computed tomography or magnetic resonance imaging. (See 'Evaluation' above.) Treatment For patients with NSVT who are asymptomatic and have no evidence of structural heart disease, we suggest no specific medical therapy (Grade 2C). For patients with bothersome symptoms, we use a beta blocker unless there is a contraindication (eg, uncontrolled asthma). In this case, we use a calcium channel blocker, usually verapamil or diltiazem. If NSVT persists despite treatment with these drugs, therapeutic options include more potent antiarrhythmic medications or catheter-based ablation therapy. (See 'Treatment' above and "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management", section on 'Summary and recommendations'.) Prognosis The prognosis of NSVT is generally benign in those without apparent structural heart disease. (See 'Prognosis' above.) The prognosis of NSVT occurring in exercise is discussed separately. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 7/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate 'Nonsustained ventricular tachycardia'.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology), Buxton AE, Calkins H, et al. ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on Electrophysiology). Circulation 2006; 114:2534. 2. Marine JE, Shetty V, Chow GV, et al. Prevalence and prognostic significance of exercise- induced nonsustained ventricular tachycardia in asymptomatic volunteers: BLSA (Baltimore Longitudinal Study of Aging). J Am Coll Cardiol 2013; 62:595. 3. Lerman B, Stein, K, et al. Ventricular tachycardia in patients with structurally normal hearts. In: Cardiac Electrophysiology: From Cell to Beside, 4th ed, 2004. p.668. 4. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111:659. 5. Kinder C, Tamburro P, Kopp D, et al. The clinical significance of nonsustained ventricular tachycardia: current perspectives. Pacing Clin Electrophysiol 1994; 17:637. 6. Kennedy HL, Whitlock JA, Sprague MK, et al. Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy. N Engl J Med 1985; 312:193. 7. Cullen K, Stenhouse NS, Wearne KL, Cumpston GN. Electrocardiograms and 13 year cardiovascular mortality in Busselton study. Br Heart J 1982; 47:209. 8. Bikkina M, Larson MG, Levy D. Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study. Ann Intern Med 1992; 117:990. 9. Abdalla IS, Prineas RJ, Neaton JD, et al. Relation between ventricular premature complexes and sudden cardiac death in apparently healthy men. Am J Cardiol 1987; 60:1036. 10. Montague TJ, McPherson DD, MacKenzie BR, et al. Frequent ventricular ectopic activity without underlying cardiac disease: analysis of 45 subjects. Am J Cardiol 1983; 52:980. 11. Fleg JL, Kennedy HL. Long-term prognostic significance of ambulatory electrocardiographic findings in apparently healthy subjects greater than or equal to 60 years of age. Am J https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 8/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate Cardiol 1992; 70:748. 12. Gabriels J, Wu M, Rosen L, et al. Clinical Significance of Nonsustained Ventricular Tachycardia on Stored Electrograms in Permanent Pacemaker Patients. Pacing Clin Electrophysiol 2016; 39:1335. 13. Jamil HA, Mohammed SA, Gierula J, et al. Prognostic Significance of Incidental Nonsustained Ventricular Tachycardia Detected on Pacemaker Interrogation. Am J Cardiol 2019; 123:409. 14. McHenry PL, Fisch C, Jordan JW, Corya BR. Cardiac arrhythmias observed during maximal treadmill exercise testing in clinically normal men. Am J Cardiol 1972; 29:331. 15. Fleg JL, Lakatta EG. Prevalence and prognosis of exercise-induced nonsustained ventricular tachycardia in apparently healthy volunteers. Am J Cardiol 1984; 54:762. 16. Froelicher VF Jr, Thomas MM, Pillow C, Lancaster MC. Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am J Cardiol 1974; 34:770. 17. Yang JC, Wesley RC Jr, Froelicher VF. Ventricular tachycardia during routine treadmill testing. Risk and prognosis. Arch Intern Med 1991; 151:349. Topic 933 Version 28.0 https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 9/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate GRAPHICS Nonsustained ventricular tachycardia Nonsustained ventricular tachycardia in a patient with underlying atrial fibrillation. The ventricular arrhythmia consists of nine beats at an approximate rate of 170 beats/minute. Courtesy of Ary Goldberger, MD. Graphic 73299 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 10/11 7/6/23, 3:41 PM Nonsustained VT in the absence of apparent structural heart disease - UpToDate Contributor Disclosures Robert Phang, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/nonsustained-vt-in-the-absence-of-apparent-structural-heart-disease/print 11/11 |
7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of the acute management of tachyarrhythmias : Jordan M Prutkin, MD, MHS, FHRS : James Hoekstra, MD, Hugh Calkins, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute, are frequently symptomatic and often result in patients seeking care at their provider's office or the emergency department. Signs and symptoms related to the tachyarrhythmia may include shock, hypotension, heart failure, shortness of breath, chest pain, acute myocardial infarction, palpitations, and/or decreased level of consciousness. An overview of the management of these various arrhythmias will be presented here. More complete reviews of the individual arrhythmias are discussed separately. INITIAL DIAGNOSTIC AND TREATMENT DECISIONS In patients who present with a symptomatic tachyarrhythmia, a 12-lead electrocardiogram (ECG) should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient. Is the patient clinically (or hemodynamically) unstable? The most important clinical determination in a patient presenting with a tachyarrhythmia is whether or not the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 1/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Determining whether a patient's symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease. Hemodynamically unstable and not sinus rhythm If a patient has clinically significant hemodynamic instability potentially due to the tachyarrhythmia, an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia ( algorithm 1). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Similar to sinus rhythm' and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'.) Hemodynamically stable If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient's rhythm can be undertaken [1-3]. A close examination of the 12-lead ECG should permit the correct identification of the arrhythmia in 80 percent of cases [4]. (See 'Is the QRS complex narrow or wide? Regular or irregular?' below and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Evaluation' and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) Is the QRS complex narrow or wide? Regular or irregular? Treatment of any tachyarrhythmia depends on a variety of clinical factors. However, most treatment decisions are made based on the width, morphology, and regularity of the QRS complex ( algorithm 2). In most patients, the differentiation between narrow and wide QRS complex tachyarrhythmias requires only a surface ECG. Narrow QRS complex tachyarrhythmias have a QRS complex <120 milliseconds in duration Wide QRS complex tachyarrhythmias have a QRS complex 120 milliseconds in duration The various types of narrow and wide QRS complex tachyarrhythmias are discussed below. (See 'Narrow QRS complex tachyarrhythmias' below and 'Wide QRS complex tachyarrhythmias' below.) NARROW QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of narrow QRS complex tachycardias will be divided into those with a regular ventricular response and those with an irregular ventricular response ( algorithm 3 and algorithm 1). https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 2/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Regular narrow QRS complex tachyarrhythmias The regular narrow QRS complex tachycardias include ( algorithm 2) [3]: Sinus tachycardia (see "Sinus tachycardia: Evaluation and management") Inappropriate sinus tachycardia (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") Atrioventricular nodal reentrant tachycardia (AVNRT) (see "Atrioventricular nodal reentrant tachycardia") Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) (see "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway") Atrial tachycardia (AT) (see "Focal atrial tachycardia") Atrial flutter (see "Overview of atrial flutter") Intraatrial reentrant tachycardia (IART) (see "Intraatrial reentrant tachycardia") Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia Because the vast majority of regular narrow QRS complex tachycardias are due to sinus tachycardia, AVNRT, AVRT, AT, and atrial flutter, these conditions will be presented here. Discussions regarding the treatment of the other less common types of regular narrow QRS complex tachycardias are presented separately. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia' and "Sinoatrial nodal reentrant tachycardia (SANRT)", section on 'Treatment' and "Intraatrial reentrant tachycardia", section on 'Treatment' and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Permanent junctional reciprocating tachycardia'.) Sinus tachycardia The most common tachycardia is sinus tachycardia. If it is certain that the patient's rhythm is sinus tachycardia and clinically significant cardiac symptoms are present, management should be focused on the underlying disorder and on treating any contributing cause of the rapid heart rate (eg, coronary ischemia, pulmonary embolism, respiratory or cardiac failure, hypovolemia, anemia, hyperthyroidism, fever, pain, or anxiety). This may include volume replacement or diuresis, antibiotics, anti-pyretics, oxygen, pain control, or other treatments as appropriate. In patients with sinus tachycardia and certain forms of heart disease, such as coronary disease or aortic stenosis, treatment may need to be directed at the heart rate itself. In such cases, cautious use of an intravenous beta blocker is appropriate. (See "Sinus tachycardia: Evaluation and management" and "Acute myocardial infarction: Role of beta blocker therapy" and "Medical management of symptomatic aortic stenosis".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 3/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrioventricular nodal reentrant tachycardia (AVNRT) Patients with AVNRT associated with hemodynamic compromise or severe symptoms due to the tachycardia (eg, angina, hypotension, or heart failure) require rapid termination of the arrhythmia. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.) For patients with AVNRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers (Valsalva maneuver or carotid sinus massage) is also reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with AVNRT associated with severe symptoms due to the tachycardia (eg, angina, hypotension, heart failure, or mental status changes) in whom intravenous access is available, we suggest an initial attempt at termination with adenosine ( algorithm 4) rather than cardioversion. If adenosine cannot be administered or is ineffective, patients should undergo immediate DC cardioversion. For patients with AVNRT that is not associated with severe symptoms or hemodynamic collapse, including patients without symptoms, we suggest the following sequential approach to acute termination: Vagal maneuvers (see "Vagal maneuvers") IV adenosine ( algorithm 4) IV non-dihydropyridine calcium channel blocker or an IV beta blocker Atrioventricular reentrant tachycardia (AVRT) Patients with any arrhythmia (ie, orthodromic AVRT, antidromic AVRT, atrial fibrillation/flutter) involving an accessory pathway should have a prompt initial assessment of hemodynamic status. AVRT may result in either a narrow QRS complex tachycardia or a wide QRS complex tachycardia depending on the direction of conduction across the accessory pathway and also the presence of aberrant conduction. (See 'Antidromic AVRT' below and "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome", section on 'Acute treatment of symptomatic arrhythmias'.) For patients with AVRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers is reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with acute symptomatic orthodromic AVRT (usually narrow QRS complex in the absence of an underlying conduction delay) who are hemodynamically stable, our approach is as follows ( table 1): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 4/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate We recommend initial treatment with one or more vagal maneuvers rather than pharmacologic therapy. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted. We suggest intravenous adenosine ( algorithm 4) rather than intravenous verapamil as the initial choice based on its high efficacy and short half-life. If adenosine is ineffective, we proceed with intravenous verapamil as the second-line agent. If orthodromic AVRT persists, intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) are additional therapeutic options. Amiodarone may also be considered. Because most patients with acute symptomatic antidromic AVRT have a wide QRS complex, the approach to this arrhythmia is discussed below. (See 'Antidromic AVRT' below.) Atrial tachycardia Focal atrial tachycardias (AT), usually paroxysmal and self-limited, arise from a single site or area of microreentry or enhanced automaticity outside of the sinus node. (See "Focal atrial tachycardia", section on 'Acute treatment'.) For patients with AT who are felt to be hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. For a hemodynamically stable patient with symptomatic AT, we suggest acute treatment with an oral or intravenous beta blocker or non-dihydropyridine calcium channel blocker (ie, diltiazem or verapamil). Such treatment may slow the ventricular response and/or terminate the arrhythmia. Intravenous amiodarone is an acceptable alternative that may be preferred in a patient with borderline hypotension as amiodarone may slow the rate or convert the rhythm back to normal sinus. Atrial flutter Atrial flutter usually presents as a regular narrow complex tachycardia, though it occasionally may have an irregular ventricular response. Atrial flutter should always be considered high on the differential diagnosis when a patient presents with a regular narrow complex tachycardia with a ventricular response of approximately 150 beats per minute. As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' below.) Irregular narrow QRS complex tachyarrhythmias The irregular narrow QRS complex tachycardias include ( algorithm 2): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 5/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrial fibrillation (AF) (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation") Atrial flutter with variable conduction (see "Overview of atrial flutter") Focal atrial tachycardia with variable conduction (see "Focal atrial tachycardia") Multifocal atrial tachycardia (MAT) (see "Multifocal atrial tachycardia") Atrial fibrillation Most patients with new onset (ie, first detected or diagnosed) AF with a rapid rate present with symptoms related to the arrhythmia. Except for embolization, the symptoms associated with new onset AF are primarily due to a rapid and/or irregular ventricular response. The early steps in the management of a patient with new onset rapid AF involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Urgent or emergent cardioversion should be considered for patients with active ischemia, significant hypotension, severe heart failure, or the presence of a preexcitation syndrome associated with rapid conduction using the accessory pathway. (See 'Atrioventricular reentrant tachycardia (AVRT)' above.) For all patients who do not require urgent or emergent cardioversion, we recommend rate control to improve symptoms and to reduce the risk of tachycardia-mediated cardiomyopathy. We believe a goal of less than 110 beats per minute is reasonable for an asymptomatic patient with a normal ejection fraction. Beta blockers and non- dihydropyridine calcium channel blockers are preferred as first-line agents in most patients, and digoxin should only rarely be used. Intravenous preparations are preferred to oral preparations when rapid control of rate is necessary. For patients with AF less than 48 hours in duration in whom cardioversion is planned, the use of antithrombotic therapy pre-cardioversion to reduce the risk of embolization can be considered. For patients with AF longer than 48 hours in duration (or of unknown duration), we recommend four weeks of therapeutic oral anticoagulation prior to cardioversion, as opposed to immediate cardioversion. Transesophageal echocardiography-based (TEE) screening for the presence of atrial thrombi is recommended if cardioversion is desired earlier than four weeks. Anticoagulation must be continued for a minimum of four weeks after cardioversion. Whether long-term anticoagulation is indicated depends on assessment of the patient's thromboembolic risk profile. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 6/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Atrial flutter As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' above.) Multifocal atrial tachycardia Multifocal atrial tachycardia (MAT) is an arrhythmia with organized atrial activity yielding P waves with three or more different morphologies. MAT is commonly associated with significant underlying pulmonary or cardiac illness. (See "Multifocal atrial tachycardia", section on 'Treatment'.) Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include non-dihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers. Conversely, for patients with severe bronchospasm, we suggest initial therapy with a non-dihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker. Beta blockers may be used cautiously in patients with stable heart failure. Rate control therapy is typically unsuccessful, however, without treating the underlying disorder. WIDE QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of wide QRS complex tachycardias, similar to narrow QRS complex tachycardias, can be divided into those with a regular or irregular ventricular rate. Regular wide QRS complex tachyarrhythmias The regular wide QRS complex tachycardias include ( algorithm 2): Monomorphic ventricular tachycardia (VT). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 7/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Supraventricular tachycardia with aberrant conduction, underlying conduction delay, conduction over an accessory pathway (eg, AVNRT with right bundle branch block), or a paced ventricular response. Supraventricular tachycardia in a patient on certain antiarrhythmic medications or with significant electrolyte abnormalities. Antidromic AVRT. The most concerning potential cause of a wide QRS complex tachycardia is VT, and, in the majority of patients, the arrhythmia should be assumed to be VT until proven otherwise. Immediate assessment of patient stability takes precedence over any further diagnostic evaluation. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'.) A patient who is unresponsive or pulseless should be treated according to standard advance cardiac life support (ACLS) algorithms ( algorithm 5). In a patient who is unstable but conscious, we recommend immediate synchronized cardioversion with appropriate sedation when possible. In a stable patient, a focused diagnostic evaluation may proceed to determine the etiology of the arrhythmia and guide specific therapy. Ventricular tachycardia In stable patients with known or presumed VT, we recommend the following approach (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'): We recommend synchronized external cardioversion, following appropriate sedation, as the initial therapy for most patients with stable VT. If the patient has an implantable cardioverter-defibrillator, it may be possible to terminate the arrhythmia by antitachycardia pacing prior to an attempted cardioversion. In patients with refractory or recurrent wide complex tachycardia (WCT), we suggest an intravenous class I or III antiarrhythmic drug ( table 2), such as amiodarone, lidocaine, or procainamide. In selected patients known to have one of the syndromes of VT in the setting of a structurally normal heart, we suggest calcium channel blockers or beta blockers be used for arrhythmia termination or suppression. However, the decision to use these drugs in this https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 8/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate setting should be made in consultation with a cardiologist experienced in arrhythmia management. Supraventricular tachycardia with aberrant conduction The narrow complex supraventricular tachycardia (SVT) rhythms may present with a wide complex in the setting of aberrant conduction or conduction over an accessory pathway (not including AVRT). In stable patients with a WCT that is known to be an SVT, initial management is similar to that of an SVT with a narrow QRS complex. A continuous rhythm strip should be obtained during any intervention that is intended to slow or terminate the arrhythmia. (See 'Regular narrow QRS complex tachyarrhythmias' above.) For AVNRT or AVRT, or an SVT in which the specific arrhythmia is unknown, we suggest the following sequence of interventions in order to terminate the arrhythmia or to slow ventricular response and facilitate diagnosis in stable patients: Vagotonic maneuvers (eg, valsalva or carotid sinus pressure) Intravenous adenosine ( algorithm 4) Intravenous calcium channel blockers or beta blockers Cardioversion in selected persistent cases, or if the patient is unstable Supraventricular tachycardia with a pacemaker Regular wide QRS complex tachycardias in patients with a pacemaker may be due to tracking of one of the typical supraventricular tachycardias (eg, sinus tachycardia, atrial flutter, etc) or may be due to endless loop tachycardia (ELT, also referred to as pacemaker-mediated tachycardia [PMT]). (See "Unexpected rhythms with normally functioning dual-chamber pacing systems", section on 'Pacemaker-mediated tachycardia'.) In patients with tracking of a native supraventricular tachyarrhythmia, the pacemaker usually should automatically mode switch to a non-tracking mode. If it does not, placing a magnet on the pacemaker will lead to asynchronous pacing at a fixed and lower rate, and the pacemaker settings can be adjusted to prevent rapid pacing. If the rhythm is due to ELT, retrograde conduction from the ventricle to the atrium is sensed by the pacemaker and serves as a trigger to pace the ventricle, which again conducts back to the atrium and perpetuates the tachycardia. Placing a magnet on the pacemaker leads to asynchronous pacing and will stop the tachycardia. Most pacemakers have algorithms to prevent or treat ELT, but pacemaker settings can usually be reprogrammed if they are ineffective. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 9/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Antidromic AVRT For patients with acute symptomatic antidromic AVRT (regular and wide QRS complex) who are hemodynamically stable, our approach is as follows (see "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Antidromic AVRT'): We treat with intravenous procainamide in an effort to terminate the tachycardia or, if the tachycardia persists, slow the ventricular response. This is because it is often difficult to correctly determine that the rhythm is due to antidromic AVRT and not ventricular tachycardia. If the rhythm is definitely known to be antidromic AVRT, then adenosine ( algorithm 4), verapamil, or IV beta blockers may be considered, but monitoring should be continued to ensure that there is not a rapid ventricular rate if atrial fibrillation (AF) subsequently develops after SVT termination. Irregular wide QRS complex tachyarrhythmias The irregular wide QRS complex tachycardias include ( algorithm 2): Polymorphic VT, including torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Irregular narrow complex tachycardias with aberrant conduction, antegrade conduction over an accessory pathway (eg, preexcited AF), or underlying conduction delay (eg, AF with right bundle branch block). Ventricular fibrillation. Polymorphic ventricular tachycardia Polymorphic (or polymorphous) ventricular tachycardia (VT) is defined as an unstable rhythm with a continuously varying QRS complex morphology in any recorded electrocardiographic (ECG) lead. Polymorphic VT is generally a rapid and hemodynamically unstable rhythm, and urgent defibrillation is usually necessary. In addition to immediate defibrillation, further therapy is intended to treat underlying disorders and to prevent recurrences. The specific approach depends upon whether or not the QT interval on the baseline ECG is prolonged. Polymorphic VT that occurs in the setting of QT prolongation in sinus rhythm is considered as a distinct arrhythmia, called torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Prompt defibrillation is indicated in patients with hemodynamically unstable torsades de pointes. In the conscious patient with recurrent episodes of torsades de pointes: https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 10/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Intravenous magnesium sulfate (initial dose of 1 to 2 grams IV over 15 minutes, may be followed by an infusion) is first-line therapy, as it is highly effective for both treatment and prevention of recurrence of long QT-related ventricular ectopic beats that trigger torsades de pointes. The benefit is seen even in patients with normal serum magnesium concentrations at baseline. Temporary transvenous overdrive pacing (atrial or ventricular) at about 100 beats per minute is generally reserved for patients who do not respond to intravenous magnesium. In those with congenital long QT syndrome, beta blockers may be used to reduce the frequency of premature ventricular contractions and shorten the QT interval. For patients with polymorphic VT triggered by pauses or bradycardia, isoproterenol (initial dose 0.05 to 0.1 mcg/kg per minute in children and 2 mcg/minute in adults, then titrated to achieve a heart rate of 100 beats per minute) can be used as a temporizing measure to achieve a heart rate of 100 beats per minute prior to pacing. For patients with polymorphic VT and a normal baseline QT interval, the most likely cause is myocardial ischemia. Treatments may include: Prompt defibrillation in the hemodynamically unstable patient. Beta-blockers if blood pressure tolerates. Metoprolol 5 mg intravenously every five minutes, to a total of 15 mg, may be given. IV amiodarone may prevent a recurrent episode. Urgent coronary angiography and possible revascularization. Short-term mechanical circulatory support. Magnesium is less likely to be effective for polymorphic VT if the baseline QT interval is normal. If the polymorphic VT is due to catecholaminergic polymorphic ventricular tachycardia (CPVT), beta blockers should be used. If it is due to Brugada syndrome, isoproterenol should be initiated. (See "Catecholaminergic polymorphic ventricular tachycardia", section on 'Acute management' and "Brugada syndrome or pattern: Management and approach to screening of relatives".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 11/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Preexcited atrial fibrillation For patients with acute symptomatic preexcited AF who are hemodynamically stable, our approach is as follows: We suggest initial medical therapy with rhythm control versus rate control. While there is no clear first-line medication for rhythm control, options include ibutilide and procainamide. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Atrial fibrillation with preexcitation'.) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability and development of ventricular fibrillation. While preexcited AF conducts down a bypass pathway, in contrast to AVRT, the rhythm is irregularly irregular and wide complex. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Basic and advanced cardiac life support in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 12/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Tachycardia (The Basics)" and "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Initial diagnostic and treatment decisions In patients who present with a symptomatic tachyarrhythmia, a 12-lead ECG should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or |
crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone Antidromic AV reentrant tachycardia Acute termination* Unstable patients: Adenosine, verapamil, diltiazem, Synchronized cardioversion beta blockers, digoxin should all be avoided if NOT certain of diagnosis Stable patients (if CERTAIN of the diagnosis): Same progression of therapies as acute termination of orthodromic AVRT Stable patients (if NOT certain of the diagnosis): IV procainamide, synchronized cardioversion if procainamide is ineffective or not available https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 20/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Chronic prevention First line: Catheter ablation of the accessory pathway Digoxin Beta blockers Second line: Oral flecainide or propafenone in the absence of Verapamil, diltiazem structural or ischemic heart disease Other therapies: Oral IA antiarrhythmic agent OR oral amiodarone Pre-excited atrial fibrillation Acute termination* Unstable patients: Amiodarone Synchronized cardioversion Stable patients: Digoxin Beta blockers First line: IV ibutilide or IV procainamide Adenosine Other therapies: IC antiarrhythmic agent or dofetilide; synchronized cardioversion if other therapies are ineffective or not available Verapamil, diltiazem Chronic prevention First line: Catheter ablation or the accessory pathway Oral digoxin Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone AVRT: atrioventricular reciprocating tachycardia; IV: intravenous; class IC: flecainide, propafenone; class IA: quinidine, procainamide, disopyramide. Cardioversion is indicated if hemodynamically unstable or drugs are ineffective. Ablation of the accessory pathway is generally preferred to cure the arrhythmia. Procainamide is the intravenous drug of choice for acute termination of suspected antidromic AVRT. If the tachycardia is definitely known to be antidromic AVRT, and it has been verified that the AV node (rather than a second accessory pathway) is acting as the retrograde limb of the circuit, one could consider treatment with an agent such as adenosine similar to therapy for orthodromic AVRT, https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 21/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate but it is rare to have all of the necessary data in the acute setting to justify use of AV nodal blocking agents. Graphic 62762 Version 7.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 22/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 23/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 24/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 25/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 26/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 27/28 7/6/23, 3:40 PM Overview of the acute management of tachyarrhythmias - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 28/28 |
7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis : Alfred Buxton, MD : Peter J Zimetbaum, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 24, 2022. INTRODUCTION Sustained monomorphic ventricular tachycardia (SMVT) is defined by the following characteristics: A regular wide QRS complex ( 120 milliseconds) tachycardia at a rate greater than 100 beats per minute The consecutive beats have a uniform and stable QRS morphology The arrhythmia lasts 30 seconds or causes hemodynamic collapse in <30 seconds In patients with significant coronary heart disease (CHD) or other structural heart disease, a wide QRS complex tachycardia should be considered to be VT until proven otherwise [1]. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) This topic will focus on the treatment of SMVT in patients with structural heart disease. The diagnostic approach to SMVT and the treatment of SMVT during an acute myocardial infarction, as well as the management of nonsustained VT, are discussed separately. The approach to patients with idiopathic VT is also discussed separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 1/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate management" and "Ventricular tachycardia in the absence of apparent structural heart disease".) TREATMENT The initial management of a patient with SMVT depends on the hemodynamic stability of the patient ( algorithm 1). Emergency management is required in unstable patients, while additional time may be spent determining the etiology and treating any underlying precipitating factors in patients who are hemodynamically stable (although treatment for such patients should usually be promptly administered). Following initial management and stabilization of the patient, subsequent management of the patient will be guided by the initial presentation (ie, hemodynamically stable or unstable) and the initial approach to treatment. Initial management All patients with SMVT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable ( algorithm 1). While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should: Attach the patient to a continuous cardiac monitor Establish intravenous access Obtain a 12-lead electrocardiogram (ECG) Administer supplemental oxygen Send blood for appropriate initial studies (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Ancillary testing') Differentiation between a hemodynamically stable versus unstable patient is as follows; hemodynamic stability does not necessarily imply SVT with aberrancy, and hemodynamic instability does not always imply VT (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'): An unstable patient will have evidence of hemodynamic compromise (eg, hypotension, altered mental status, chest pain, or heart failure [HF]) and may remain awake with a discernible pulse, but may also be unresponsive and pulseless. Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms ( algorithm 2). (See 'Unstable patients' below.) A stable patient shows no evidence of hemodynamic compromise despite a sustained rapid heart rate, but should have continuous monitoring and frequent reevaluations due to the https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 2/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate potential for rapid deterioration as long as the SMVT persists. (See 'Stable patients' below.) Patients with SMVT who are initially stable may rapidly become unstable, particularly in the setting of extremely rapid heart rates (greater than 200 beats per minute) or significant underlying cardiac comorbidities. Unstable patients Patients with SMVT who are felt to be hemodynamically unstable, severely symptomatic, or become pulseless require prompt treatment with electrical cardioversion/defibrillation ( algorithm 1). Initial treatment with antiarrhythmic medications is not indicated for hemodynamically unstable or pulseless patients. Patients with SMVT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy countershock and cardiopulmonary resuscitation (CPR) ( algorithm 2). Patients should initially be treated with a synchronized shock at maximal energy (ie, 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator) [2]. Subsequent shocks, if required, should be at the highest output available on the defibrillator. (See "Advanced cardiac life support (ACLS) in adults", section on 'Pulseless ventricular tachycardia and ventricular fibrillation' and "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.) For patients with SMVT who are hemodynamically unstable but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (following administration of sedation). Patients should initially be treated with a synchronized 200 joule shock with subsequent shocks that use escalating energy levels. (See "Cardioversion for specific arrhythmias", section on 'Ventricular tachycardia'.) Subsequent antiarrhythmic therapy (intravenous amiodarone, procainamide, lidocaine, or oral agents such as sotalol or amiodarone) is generally indicated only if SMVT recurs. For repetitive episodes of SMVT, consideration should be given to catheter ablation. (See 'Stable patients' below and 'Radiofrequency catheter ablation' below.) Stable patients Patients with SMVT who are hemodynamically stable on presentation may remain stable or may become unstable rapidly and without warning. As such, therapy should be promptly provided to most patients. The choice of initial treatments for hemodynamically stable SMVT includes electrical or pharmacologic cardioversion ( algorithm 1). We generally prefer to begin with an intravenous antiarrhythmic agent and reserve electrical cardioversion for refractory patients or for those who become unstable. If SMVT is not terminated with the initial antiarrhythmic drug, external cardioversion may be https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 3/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate performed or additional antiarrhythmic therapy may be administered (eg, second bolus of amiodarone, adding lidocaine to amiodarone, etc). Rarely, electrical cardioversion may be chosen as the initial therapy for patients with SMVT who are hemodynamically stable, but only if adequate procedural sedation can be administered prior to delivery of the shock. Pharmacologic cardioversion For pharmacologic cardioversion, we administer one of the following antiarrhythmic drugs: Intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours) Intravenous lidocaine (1 to 1.5 mg/kg [typically 75 to 100 mg] at a rate of 25 to 50 mg/minute; lower doses of 0.5 to 0.75 mg/kg can be repeated every 5 to 10 minutes as needed), which may be more effective in the setting of acute myocardial ischemia or infarction Intravenous procainamide (20 to 50 mg/minute until arrhythmia terminates or a maximum dose of 15 to 17 mg/kg is administered) There is no consensus on the choice of initial antiarrhythmic medication for patients with stable monomorphic VT. Some of our experts give lidocaine first, given its ease of rapid administration and because it does not cause hypotension. Other experts choose to give amiodarone or procainamide as the first antiarrhythmic drug for stable monomorphic VT, even though the time to administer is longer than lidocaine. Lidocaine does not usually cause hypotension, while amiodarone and procainamide often reduce the blood pressure, which may hasten the need for electrical cardioversion. Intravenous pharmacologic therapy with amiodarone, procainamide, lidocaine, or sotalol (not available in all countries) may be attempted prior to electrical cardioversion [2-8]. For patients in whom VT terminates during drug infusion, the intravenous drug can usually be discontinued at that point, unless the patient has been experiencing recurrent episodes. For patients with frequent recurrent episodes, the infusion should be continued, and consideration should be given to initiating oral antiarrhythmic drug therapy or referring for catheter ablation. Regardless of the choice of antiarrhythmic drug, the patient should be reevaluated daily (or more frequently if unstable) to determine the optimal approach to antiarrhythmic therapy. Intravenous amiodarone is slower in action than procainamide or lidocaine, but it improves the reversion rate of refractory SMVT and decreases its recurrence after reversion [3,6-8]. Procainamide has the advantage of slowing VT even when it fails to terminate, usually resulting in greater hemodynamic stability, whereas lidocaine usually does not slow SMVT. Procainamide https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 4/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate terminates over 50 percent of episodes of SMVT, while lidocaine usually terminates only 10 to 20 percent. Electrical cardioversion If electrical cardioversion with appropriate procedural sedation is the chosen approach, intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. If the QRS complex and T wave can be distinguished, an attempt at synchronized cardioversion can be performed with a synchronized shock of at least 100 joules using either a biphasic or monophasic defibrillator. If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. If the initial shock is unsuccessful, subsequent shocks should be delivered at escalating energy levels. Initial dosing of antiarrhythmic drugs When an antiarrhythmic drug is prescribed, the following regimens can be used: Lidocaine Intravenous lidocaine can be given in an initial dose of 1 to 1.5 mg/kg (typically 75 to 100 mg at a rate of 25 to 50 mg/minute); lower doses of 0.5 to 0.75 mg/kg can be repeated every 5 to 10 minutes as needed. If VT terminates, then we usually do not begin a continuous infusion. If VT recurs (ie, becomes incessant), a continuous intravenous infusion of 1 to 4 mg/minute may be begun. The maximum total dose is 3 mg/kg (300 mg) over one hour. It is rarely necessary to continue the infusion for more than 24 hours, and the incidence of neurotoxicity increases greatly after 24 hours of infusion. Procainamide Intravenous procainamide can be administered in a number of ways. The standard method is an infusion of 20 to 50 mg/minute while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 15 to 17 mg/kg (1050 to 1200 mg for a 70 kg patient) has been given. Once VT terminates, it is usually not necessary to continue a maintenance infusion, although procainamide can be resumed or continued if VT recurs. Amiodarone Intravenous amiodarone is administered with a 150 mg bolus over 10 minutes, followed by a continuous intravenous infusion of 1 mg/minute for six hours and 0.5 mg/minute, generally for an additional 18 hours or longer. Repeated boluses can be given over 10 minutes every 10 to 15 minutes to a maximum total dose of 2.2 g in 24 hours. The blood pressure must be carefully monitored because the diluent can cause hypotension when the administration of amiodarone occurs too rapidly. (See "Amiodarone: Clinical uses" and "Amiodarone: Clinical uses", section on 'Side effects with IV administration'.) https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 5/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Commonly, oral amiodarone in doses up to 400 mg orally every eight hours is initiated overlapping with intravenous amiodarone for 24 to 48 hours. The high-dose oral amiodarone loading can be continued up to 7 to 10 days before decreasing to maintenance dosing of 200 mg daily. The duration of intravenous and oral amiodarone loading is dependent on the clinical response and the tolerance of the drug. Sotalol In countries in which intravenous sotalol is available, the dose is 1 to 1.5 mg/kg (or 100 mg) at a rate of 10 to 20 mg/minute, watching for bradycardia, hypotension, or the development of other arrhythmias that can be caused by the proarrhythmic effect of sotalol, such as torsades de pointes. This dose may be repeated after six hours if necessary. (See "Clinical uses of sotalol".) Treatment of associated conditions Treatment of underlying conditions associated with VT, such as myocardial ischemia, electrolyte disturbances, drug proarrhythmia, and HF, as well as decreasing the sympathetic facilitation of SMVT, are important components of the acute management of VT. However, most episodes of SMVT do not have identifiable precipitating factors, and SMVT is rarely precipitated by acute myocardial ischemia or electrolyte imbalance, although it most commonly occurs in patients with prior myocardial infarction (MI). The presence of hypokalemia or hypomagnesemia should prompt correction of these electrolyte disturbances, but electrolyte abnormalities alone should not be accepted as the cause for SMVT. Some of the standard pharmacologic therapies for cardiomyopathy/HF have been shown to improve survival, in some cases by reducing the incidence of SCD, but have not necessarily been proven to prevent recurrent VT in patients previously manifesting ventricular arrhythmias. (See "Overview of the management of heart failure with reduced ejection fraction in adults".) Adjunctive use of beta blockers, in combination with antiarrhythmic agents other than sotalol, is an effective approach for reducing sympathetic facilitation of SMVT, especially in patients with frequent recurrences of VT within a short time period (eg, VT "storm") [9,10]. (See "Electrical storm and incessant ventricular tachycardia", section on 'Initial management'.) Electrolyte disturbances, particularly hypokalemia and hypomagnesemia, should be promptly treated when present. (See "Clinical manifestations and treatment of hypokalemia in adults" and "Hypomagnesemia: Evaluation and treatment".) Drug-induced proarrhythmia most commonly results in polymorphic VT in association with marked QT prolongation (QTc 500 milliseconds) and rarely results in SMVT, but should be considered in patients taking potentially proarrhythmic medications. A less common manifestation of drug-related proarrhythmia is incessant slower (usually <150 beats per https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 6/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate minute) monomorphic VT. This can occur when high doses of amiodarone or any other drug capable of slowing intraventricular conduction is given. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) SMVT in patients with ICDs If a patient with an ICD presents with SMVT, one of several possibilities has occurred: The device is malfunctioning and is not effectively detecting VT. The device has been ineffective in terminating VT, and all programmed therapies have been exhausted. The device has effectively terminated the VT, but SMVT has recurred repeatedly and therapies have been exhausted. The rate of the VT is below the programmed VT detection rate of the device. For any of these possibilities, the initial response is the same as in patients without implanted ICDs. If the patient is hemodynamically stable and a programmer is immediately available, the implanted device can be used to attempt termination of SMVT by antitachycardia pacing. An external defibrillator should be immediately available, because there is a possibility that SMVT can be accelerated to VF. Recurrent or refractory SMVT If SMVT recurs following initial therapies, including in patients who already have an implantable cardioverter-defibrillator (ICD), suppression of the arrhythmia by pharmacologic means should be attempted, and further evaluation should focus upon the presence of arrhythmia triggers (eg, ischemia, electrolyte abnormalities, and drug toxicity). Patients who have multiple episodes of SMVT within a relatively short period of time (generally three or more episodes of SMVT within 24 hours or SMVT recurring soon after [ie, within five minutes] termination of another SMVT episode) are considered to have electrical (VT) storm. Patients with hemodynamically unstable VT storm should initially undergo electrical cardioversion/defibrillation according to advanced cardiac life support protocol, while antiarrhythmic drug therapy is generally indicated for treatment of VT storm in patients who are hemodynamically stable. Among antiarrhythmic medications, amiodarone is the most effective for preventing recurrent SMVT, although sotalol and dofetilide are also efficacious for reducing recurrent SMVT [2]. We prefer empiric therapy with amiodarone for patients with recurrent SMVT as well as for those who have refused (or are not candidates for) ablation or ICD placement [11]. Following stabilization of the patient, if there are concerns about potential toxicity https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 7/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate related to amiodarone, particularly for anticipated long-term use, sotalol or dofetilide may be considered. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) If active myocardial ischemia is felt to be a contributing factor, urgent coronary revascularization should be pursued. However, it should not be expected that myocardial revascularization will "cure" SMVT. Ibutilide has been reported as an effective option in patients with VT/VF refractory to both amiodarone and lidocaine in the setting of incomplete revascularization requiring mechanical support [12]. (See "Electrical storm and incessant ventricular tachycardia".) A full discussion of the management of VT storm is presented separately. (See "Electrical storm and incessant ventricular tachycardia".) Chronic therapy Chronic therapy of patients with SMVT usually requires utilization of multiple therapeutic modalities, including the ICD, antiarrhythmic drugs, catheter ablation, and/or arrhythmia surgery. In the absence of a clearly identifiable and reversible cause for SMVT occurring in the setting of cardiomyopathy (ischemic or nonischemic), nearly all patients with a history of SMVT will be candidates for ICD insertion to treat recurrent VT, as well as to reduce the risk of sudden cardiac death (SCD), unless the patient refuses or the risks of ICD insertion are felt to outweigh the potential benefits. Patients with multiple recurrent episodes of SMVT resulting in painful ICD shocks should be evaluated for antiarrhythmic drugs or an ablation strategy (either via catheter-based or surgical approaches) to reduce or eliminate the likelihood of additional shocks. Beta blockers Nearly all patients who experience SMVT have an indication for therapy with a beta blocker, including patients with a prior MI, patients with HF and reduced LV systolic function, etc. Beta blockers provide some level of protection against recurrent SMVT, probably by blocking sympathetic input to the heart. The role of beta blocker therapy in patients with HF and/or a prior MI is discussed in detail separately. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Long-term therapy' and "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.) ICD therapy Patients who survive an episode of SMVT in the setting of structural heart disease (post-MI or nonischemic cardiomyopathy) are typically candidates for implantation of an ICD to treat recurrent VT as well as to reduce the risk of SCD. Although some patients are treated with other therapies, such as antiarrhythmic drugs, radiofrequency ablation (RFA), or surgery, an ICD is the most common initial treatment for SMVT, although survival benefit and superiority of the ICD over other therapies have not been established for any particular therapy since these https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 8/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate patients were excluded from ICD trials. These other therapies are used either as an adjunct to an ICD or as an alternative in patients who are not candidates for or who refuse ICD therapy. Three large, prospective randomized clinical trials (AVID, CASH, and CIDS) and several subsequent meta-analyses have evaluated ICD therapy compared with amiodarone or other antiarrhythmic drugs in survivors of cardiac arrest or life-threatening ventricular tachyarrhythmias, including hemodynamically unstable SMVT [13-18]. Although the AVID trial was the only one to demonstrate a statistically significant survival benefit, the meta-analyses have all shown a significant improvement in overall mortality with ICD therapy. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) There remains some debate regarding the optimal management of sustained, hemodynamically stable VT in persons with a prior MI but normal or near normal left ventricular (LV) systolic function, in whom there is increasing consensus that VT ablation should be considered for primary or initial therapy [19]. Antiarrhythmic drugs No antiarrhythmic medication has been demonstrated to reduce the mortality of patients with SMVT, except beta-adrenergic blocking agents. With that in mind, the use of antiarrhythmic drugs in patients with SMVT is typically limited to two settings: As an adjunct to an ICD in patients with frequent arrhythmia recurrences and ICD shocks. In a 2016 systematic review that included 2268 patients from eight trials, patients taking an antiarrhythmic drug had significantly lower likelihood of appropriate ICD interventions (odds ratio [OR] 0.66, 95% CI 0.44-0.97) [20]. As primary therapy or as adjunctive therapy to catheter ablation in patients who do not want or are not candidates for an ICD. Antiarrhythmic drugs may also be used to improve quality of life in patients with frequent SMVT leading to ICD shocks, or in those patients who are not candidates for or who decline ICD implantation. In the presence of HF and/or structural heart disease, antiarrhythmic drug therapy is limited to a small number of choices (primarily amiodarone, sotalol, and mexiletine) [1,21]. Mexiletine is rarely helpful unless combined with other antiarrhythmic agents, usually amiodarone. Several clinical trials and systematic reviews have evaluated the efficacy of antiarrhythmic drugs as adjuvant therapy in ICD patients [22-27]. There were significant differences in trial methodologies, which limit direct comparisons. Amiodarone has generally been the most effective antiarrhythmic drug for preventing ventricular arrhythmias (and associated ICD shocks). This is based upon a greater efficacy and a lower risk of proarrhythmia compared with other antiarrhythmic drugs [28-33]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Antiarrhythmic drugs' and https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosis 9/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate "Pharmacologic therapy in survivors of sudden cardiac arrest", section on 'Antiarrhythmic drugs'.) The long-term efficacy of other class III drugs, such as dofetilide and dronedarone (neither of which is approved in the United States or many other countries for the treatment of VT), has not been adequately evaluated, although a comparative study in 135 patients found that dofetilide was as effective as sotalol for preventing the induction of SMVT with electrophysiologic testing (36 versus 34 percent) and was better tolerated and more effective during long-term therapy [34,35]. Combination therapy using different classes of antiarrhythmic drugs is rarely used [36]. (See "Clinical use of dofetilide", section on 'Ventricular tachyarrhythmias'.) The class IC drugs are contraindicated in patients with coronary artery disease, while the class IA drugs are used rarely because of concerns about proarrhythmia. (See "Ventricular arrhythmias during acute myocardial infarction: Prevention and treatment".) Dosing The dosing of amiodarone and sotalol for chronic maintenance therapy in patients with recurrent SMVT is as follows: Amiodarone The initial dosing of amiodarone will vary depending on the route (intravenous [IV] or oral) as well as the clinical situation ( table 1). Most patients are started on IV amiodarone and transitioned to oral dosing once clinically stable. For patients who have been on IV therapy for one week or less, or were never given IV amiodarone, we usually start with a full oral amiodarone loading dose of 400 to 1200 mg/day (typically in two or three divided doses and usually with meals to minimize associated GI side effects). This should be continued until a total loading dose of up to 10 grams has been received, and then the dose should be reduced to the usual maintenance dose of 200 mg/day after three to four days. For patients who have been on IV therapy for one to two weeks, we start an intermediate maintenance oral amiodarone dose of 400 to 800 mg/day. This should be continued until a total loading dose of 10 grams has been received, and then the dose should be reduced to the usual maintenance dose of 200 mg/day. As oral amiodarone is only approximately 50 percent bioavailable, a total of 20 to 30 grams needs to be administered. For patients who have been on IV therapy for more than two weeks, we start maintenance oral amiodarone at a dose of 200 mg/day. (See "Amiodarone: Clinical uses", section on 'Amiodarone for ventricular arrhythmias'.) Patients receiving amiodarone chronically for SMVT (and other indications) should have baseline evaluations and regular follow-up of lung, liver, thyroid, skin and eyes. While https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 10/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate historically 400 mg per day was considered an appropriate dose for VT and 200 mg per day an appropriate dose for atrial fibrillation, we strive to find the lowest effective dose to reduce the risk of adverse effects and toxicity. In contemporary practice, amiodarone is rarely used at a dose of 400 mg/day. Patients stable on 400 mg/day initially are generally reduced to 200 mg/day. If a patient is stable on 200 mg daily, we generally propose 200 mg alternating with 100 mg daily, and then eventually 100 mg daily. The risk of recurrent VT on a lower dose, with the possibility of an ICD shock, must be balanced against the desire to reduce the risk of adverse effects in follow-up, which often require discontinuation of the drug. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Sotalol In contrast to amiodarone, sotalol is not universally available in intravenous form. Bradycardic and proarrhythmic events can occur after the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment. We start sotalol at a dose of 80 mg twice daily, with dose adjustments at three-day intervals once steady-state plasma concentrations have been achieved and the QT interval has been reviewed on a surface ECG. Patients with renal insufficiency require a modification of the dosing interval. (See "Clinical uses of sotalol", section on 'Dosing'.) ICD management with chronic antiarrhythmic drug therapy In ICD patients treated with oral antiarrhythmic drugs, several issues require consideration. If SMVT recurs in the setting of antiarrhythmic drug therapy, the rate of the tachycardia is generally slower. Detection parameters should therefore be modified. Antiarrhythmic drug therapy may also render SMVT more susceptible to pace termination; increasing the number of ATP sequences may therefore be reasonable. Finally, some antiarrhythmic drugs, particularly amiodarone, can increase the defibrillation energy requirement. It may therefore be reasonable in some patients to verify the defibrillation safety margin after amiodarone is added. Radiofrequency catheter ablation For patients with recurrent SMVT resulting in ICD shocks despite treatment with an antiarrhythmic drug, we suggest catheter-based RFA rather than the addition of a second antiarrhythmic agent. RFA is also an alternative to antiarrhythmic drugs as the initial therapy for SMVT [21,37,38]. In addition, RFA, with or without antiarrhythmic drug therapy, is an option for patients with SMVT who are not candidates for or who refuse ICD implantation. SMVT in patients with a prior MI is usually due to reentry in a circuit created by the heterogeneous electrical properties of residual myocardium in the region of the scar from the infarct. However, other mechanisms such as abnormal automaticity or triggered activity may https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosi 11/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate occasionally occur. RFA can alter or eliminate such circuits or foci and prevent VT recurrence in selected patients. (See "Reentry and the development of cardiac arrhythmias".) Our suggested approach to utilizing RFA in the treatment of ventricular arrhythmias is generally consistent with the recommendations of professional society guidelines [1,19,37]: For patients with structural heart disease (such as prior MI, dilated cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy), catheter ablation is recommended for any of the following conditions: Symptomatic SMVT, including VT terminated by an ICD, that recurs despite antiarrhythmic drug therapy or when antiarrhythmic drugs are not tolerated or not desired Incessant SMVT or VT storm not due to a transient reversible cause Recurrent SMVT and ventricular fibrillation (VF) that is refractory to antiarrhythmic therapy when there is a suspected trigger that can be targeted for ablation For patients with structural heart disease, catheter ablation should be considered for patients with any of the following: One or more episodes of SMVT despite therapy with one or more class I or III antiarrhythmic drugs Recurrent SMVT due to prior MI and expectation for at least one year of survival as an acceptable alternative to amiodarone therapy Hemodynamically tolerated SMVT due to prior MI who have reasonably preserved left ventricular ejection fraction (LVEF >35 percent) even if they have not failed antiarrhythmic drug therapy Catheter ablation techniques A variety of VT ablation techniques have evolved over the years, including ablation focused on abolition of inducible VT based upon the results of activation and entrainment mapping ( waveform 1) versus more extensive ablation of myocardium displaying abnormal electrogram characteristics ("substrate-based ablation"). The technical aspects of catheter ablation for VT are presented separately. (See "Overview of catheter ablation of cardiac arrhythmias".) While no technique has proven to be universally effective or clearly superior, smaller nonrandomized studies have suggested lower rates of VT recurrence following more extensive ablation [39-43]. Subsequently, in a multicenter trial of 118 patients with hemodynamically https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 12/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate tolerated VT and ischemic cardiomyopathy, in which patients were randomized to clinical ablation of inducible VT (60 patients) or substrate-based ablation targeting all "abnormal" electrograms seen on mapping (58 patients) and followed for 12 months, patients in the substrate-based ablation group had significantly fewer VT recurrences (16 versus 48 percent), less need for antiarrhythmic drugs (12 versus 58 percent), and fewer hospitalizations (12 versus 32 percent) compared with patients in the clinical VT ablation group [44]. There was no difference in periprocedural complications between the two approaches; however, 22 patients in the substrate-based ablation group also underwent EP study and induction of VT, raising some concerns that this may have improved the efficacy of the ablation procedure in the substrate- based group. While these data are encouraging, additional data in larger numbers of patients and additional populations are required prior to recommending widespread implementation of the substrate-based ablation technique, even in patients with hemodynamically-tolerated VT. Additionally, a systematic review and meta-analysis of non-randomized trials suggests significantly lower rates of recurrent VT following a combined endocardial/epicardial ablation compared with endocardial ablation alone, in particular among patients with ischemic cardiomyopathy [45]. (See 'Long-term efficacy' below.) Ablation performed via an epicardial approach is another option for select patients with ventricular tachyarrhythmias. Among a cohort of 444 consecutive patients with VT and prior MI who were referred for catheter ablation, 27 patients (6 percent) had successful epicardial ablation of at least one VT after endocardial ablation failed [46]. Some advocate epicardial in addition to endocardial ablation when performing substrate-based ablation. Cardiac magnetic resonance (CMR) imaging with contrast enhancement is also being investigated as a means of identifying critical sites for reentrant ventricular tachyarrhythmias [47]. In one study of 20 patients (mixed nonischemic and ischemic cardiomyopathy) with prior failed endocardial catheter ablation, CMR with late gadolinium enhancement (LGE) imaging was performed, and subsequently ablation strategies were modified based on LGE findings (nine patients underwent epicardial ablation, while 11 underwent repeat endocardial ablation) [48]. At mean follow-up of 17 months, 18 of 22 patients remained free of recurrent VT. Acute procedural success Depending upon a number of factors, acute success rates (defined as lack of inducible VT or termination of incessant VT) for RFA of VT vary from 70 to 90 percent, with a procedure-related mortality of 0.5 percent [19]. Catheter ablation of VT has been applied most often in patients with frequent episodes. Two- thirds of these patients have experienced at least a 75 percent reduction in frequency of VT [19]. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 13/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Long-term efficacy Catheter ablation has been evaluated as a therapy to prevent recurrent SMVT with good results in several individual trials [19,49-54]. Depending on the clinical presentation of VT (cardiac arrest versus relative hemodynamic stability), ICDs are usually considered in conjunction with ablation, except in patients with fairly normal LV function who present with stable VT. In the VANISH trial, VT ablation was shown to lower VT storm and appropriate ICD shocks. In this a multicenter, non-blinded study, 259 patients with prior MI and a previously implanted ICD who had at least one episode of VT within the preceding six months while on antiarrhythmic drug therapy were randomly assigned to catheter ablation (132 patients) or escalated antiarrhythmic therapy. Antiarrhythmic therapy was defined as initiating or increasing the dose of amiodarone if the prior dose was less than 300 mg daily, or addition of mexiletine to amiodarone if the prior dose was 300 mg daily or greater (127 patients) [52]. Over a mean follow-up of 28 months, patients in the ablation group had a significantly lower rate of the composite primary outcome |
despite treatment with an antiarrhythmic drug, we suggest catheter-based RFA rather than the addition of a second antiarrhythmic agent. RFA is also an alternative to antiarrhythmic drugs as the initial therapy for SMVT [21,37,38]. In addition, RFA, with or without antiarrhythmic drug therapy, is an option for patients with SMVT who are not candidates for or who refuse ICD implantation. SMVT in patients with a prior MI is usually due to reentry in a circuit created by the heterogeneous electrical properties of residual myocardium in the region of the scar from the infarct. However, other mechanisms such as abnormal automaticity or triggered activity may https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognosi 11/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate occasionally occur. RFA can alter or eliminate such circuits or foci and prevent VT recurrence in selected patients. (See "Reentry and the development of cardiac arrhythmias".) Our suggested approach to utilizing RFA in the treatment of ventricular arrhythmias is generally consistent with the recommendations of professional society guidelines [1,19,37]: For patients with structural heart disease (such as prior MI, dilated cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy), catheter ablation is recommended for any of the following conditions: Symptomatic SMVT, including VT terminated by an ICD, that recurs despite antiarrhythmic drug therapy or when antiarrhythmic drugs are not tolerated or not desired Incessant SMVT or VT storm not due to a transient reversible cause Recurrent SMVT and ventricular fibrillation (VF) that is refractory to antiarrhythmic therapy when there is a suspected trigger that can be targeted for ablation For patients with structural heart disease, catheter ablation should be considered for patients with any of the following: One or more episodes of SMVT despite therapy with one or more class I or III antiarrhythmic drugs Recurrent SMVT due to prior MI and expectation for at least one year of survival as an acceptable alternative to amiodarone therapy Hemodynamically tolerated SMVT due to prior MI who have reasonably preserved left ventricular ejection fraction (LVEF >35 percent) even if they have not failed antiarrhythmic drug therapy Catheter ablation techniques A variety of VT ablation techniques have evolved over the years, including ablation focused on abolition of inducible VT based upon the results of activation and entrainment mapping ( waveform 1) versus more extensive ablation of myocardium displaying abnormal electrogram characteristics ("substrate-based ablation"). The technical aspects of catheter ablation for VT are presented separately. (See "Overview of catheter ablation of cardiac arrhythmias".) While no technique has proven to be universally effective or clearly superior, smaller nonrandomized studies have suggested lower rates of VT recurrence following more extensive ablation [39-43]. Subsequently, in a multicenter trial of 118 patients with hemodynamically https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 12/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate tolerated VT and ischemic cardiomyopathy, in which patients were randomized to clinical ablation of inducible VT (60 patients) or substrate-based ablation targeting all "abnormal" electrograms seen on mapping (58 patients) and followed for 12 months, patients in the substrate-based ablation group had significantly fewer VT recurrences (16 versus 48 percent), less need for antiarrhythmic drugs (12 versus 58 percent), and fewer hospitalizations (12 versus 32 percent) compared with patients in the clinical VT ablation group [44]. There was no difference in periprocedural complications between the two approaches; however, 22 patients in the substrate-based ablation group also underwent EP study and induction of VT, raising some concerns that this may have improved the efficacy of the ablation procedure in the substrate- based group. While these data are encouraging, additional data in larger numbers of patients and additional populations are required prior to recommending widespread implementation of the substrate-based ablation technique, even in patients with hemodynamically-tolerated VT. Additionally, a systematic review and meta-analysis of non-randomized trials suggests significantly lower rates of recurrent VT following a combined endocardial/epicardial ablation compared with endocardial ablation alone, in particular among patients with ischemic cardiomyopathy [45]. (See 'Long-term efficacy' below.) Ablation performed via an epicardial approach is another option for select patients with ventricular tachyarrhythmias. Among a cohort of 444 consecutive patients with VT and prior MI who were referred for catheter ablation, 27 patients (6 percent) had successful epicardial ablation of at least one VT after endocardial ablation failed [46]. Some advocate epicardial in addition to endocardial ablation when performing substrate-based ablation. Cardiac magnetic resonance (CMR) imaging with contrast enhancement is also being investigated as a means of identifying critical sites for reentrant ventricular tachyarrhythmias [47]. In one study of 20 patients (mixed nonischemic and ischemic cardiomyopathy) with prior failed endocardial catheter ablation, CMR with late gadolinium enhancement (LGE) imaging was performed, and subsequently ablation strategies were modified based on LGE findings (nine patients underwent epicardial ablation, while 11 underwent repeat endocardial ablation) [48]. At mean follow-up of 17 months, 18 of 22 patients remained free of recurrent VT. Acute procedural success Depending upon a number of factors, acute success rates (defined as lack of inducible VT or termination of incessant VT) for RFA of VT vary from 70 to 90 percent, with a procedure-related mortality of 0.5 percent [19]. Catheter ablation of VT has been applied most often in patients with frequent episodes. Two- thirds of these patients have experienced at least a 75 percent reduction in frequency of VT [19]. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 13/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Long-term efficacy Catheter ablation has been evaluated as a therapy to prevent recurrent SMVT with good results in several individual trials [19,49-54]. Depending on the clinical presentation of VT (cardiac arrest versus relative hemodynamic stability), ICDs are usually considered in conjunction with ablation, except in patients with fairly normal LV function who present with stable VT. In the VANISH trial, VT ablation was shown to lower VT storm and appropriate ICD shocks. In this a multicenter, non-blinded study, 259 patients with prior MI and a previously implanted ICD who had at least one episode of VT within the preceding six months while on antiarrhythmic drug therapy were randomly assigned to catheter ablation (132 patients) or escalated antiarrhythmic therapy. Antiarrhythmic therapy was defined as initiating or increasing the dose of amiodarone if the prior dose was less than 300 mg daily, or addition of mexiletine to amiodarone if the prior dose was 300 mg daily or greater (127 patients) [52]. Over a mean follow-up of 28 months, patients in the ablation group had a significantly lower rate of the composite primary outcome of death, VT storm, or appropriate ICD shock (59 versus 69 percent; hazard ratio [HR] 0.72, 95% CI 0.53-0.98). The difference in outcomes was driven by reductions in VT storm and ICD shocks in the ablation group, as there was no significant difference in total mortality between the two groups. There is continuing concern over evidence that ICD shocks, both "appropriate" and "inappropriate," have adverse effects on survival [55]. As a result, earlier use of VT ablation has been proposed as a way to potentially reduce shocks and thereby improve survival. Two trials have suggested that early VT ablation among patients with cardiomyopathy may reduce cardiovascular events, including VT recurrence and ICD shocks [56,57]. One of these trials evaluated VT ablation at the time of ICD placement [56] and the other evaluated VT ablation shortly after a first ICD shock [57]. PAUSE-SCD Among patients with cardiomyopathy (ischemic, nonischemic, or arrythmia- related), early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death [56]. This trial included 121 patients with cardiomyopathy, SMVT, and an indication for ICD implantation. Participants were randomly assigned to either early VT ablation plus ICD, or medical therapy plus ICD, and were followed for a composite of VT recurrence, cardiovascular hospitalization, or death. Participants assigned to early VT ablation were observed to have fewer primary adverse events compared with the control group (49.3 versus 65.5 percent, HR 0.58 95% CI 0.35-0.96). The observed difference was driven by a reduction in VT recurrence (31.7 versus 50.8 percent), ICD shocks (10 versus 24.6 percent), and antitachycardia pacing (16.2 versus 32.8 percent) in the VT ablation compared with https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 14/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate control group. However, no differences in cardiovascular hospitalization (32 versus. 33.7) or mortality (8.9 versus 8.8 percent) were observed. Complications occurred in 8.3 percent of patients. PARTITA This small trial provides support for performing VT ablation in patients with either ischemic or nonischemic cardiomyopathy after their first ICD shock [57]. The study randomly assigned 47 such patients to either a VT ablation prior to ICD or standard therapy and followed them for the development of death or heart failure (HF) hospitalization. Over a median follow-up of 2.4 years, patients assigned to ablation were less likely to experience death or HF hospitalization (4 versus 42 percent, HR 0.11, 95% CI 0.01-0.85) compared with the control group. The trial was stopped early because it showed early benefit. The ablation group was observed to have fewer deaths (0 versus 33 percent), fewer ICD shocks (9 versus 42 percent), and statistically similar but numerically less HF hospitalizations (4 versus 17 percent). These findings were consistent with two earlier trials of ablation after an initial episode of VT (SMASH-VT and VTACH) [49,53] but differed from the BERLIN VT trial, which did not find benefit for an early VT ablation strategy among patients with ischemic cardiomyopathy [38]. In this study, patients with ischemic cardiomyopathy (left ventricular ejection fraction from 30 to 50 percent) and documented VT were randomly assigned ICD and preventive ablation (76 patients) at the time of enrollment or deferred ablation (83 patients) after three or more appropriate ICD shocks [38]. After a mean follow-up of 13 months, there was no significant difference in the composite primary outcome of death or unplanned hospitalization for VT or HF (33 percent in the early ablation group versus 28 percent in the deferred ablation group), at which point the study was also terminated early for futility. Fewer patients in the early ablation group received appropriate ICD therapy (34 versus 47 percent) or experienced sustained VT (40 versus 48 percent). BERLIN-VT may have had null findings because this study included only patients with ischemic cardiomyopathy (whereas PAUSE-SCD [56]and PARTITA [57] included patients with nonischemic cardiomyopathy). However, because PARTITA was stopped early for benefit, the observed HR may overestimate the efficacy. Consistent with the findings of most individual trials, earlier systematic reviews and meta- analyses have shown that, compared with medical therapy alone, VT ablation generally does not improve mortality but leads to significantly fewer episodes of recurrent VT and VT storm, as well as lower likelihood of an appropriate ICD intervention [20,45,58,59]. As an example, in a 2020 meta-analysis of five randomized trials (635 patients) comparing ablation with medical therapy alone, patients treated with ablation had the following outcomes: https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 15/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Lower likelihood of appropriate ICD therapies (odds ratio [OR] 0.49; 95% CI 0.28-0.87) and appropriate ICD shocks (OR 0.52; 95% CI 0.28-0.96) Lower likelihood of future VT storm (OR 0.64; 95% CI 0.43-0.95) Lower likelihood of cardiac hospitalization (OR 0.67; 95% CI 0.46-0.97) No significant improvement in all-cause mortality (OR 0.89; 95% CI 0.60-1.34) Complications The potential risks and benefits of the ablation procedure include those risks associated with any invasive electrophysiology (EP) study alone ( table 2), although the overall incidence of complications is higher with ablation, which is a lengthier procedure typically performed in higher-risk patients. In a nationwide sample of 4653 patients who underwent ablation in the United States between 2002 and 2011 for post-MI VT, the overall in-hospital complication rate was 11 percent with in-hospital mortality of 1.6 percent [60]. Generally, risks are lower in experienced operators and centers that perform larger numbers of procedures. These risks are discussed in greater detail separately. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Complications of invasive cardiac electrophysiology studies'.) As experience with catheter-based RFA accumulates among patients with VT, rates of early mortality and procedural complications appear to be declining. In a registry of 2061 patients with structural heart disease (mean age 62 years, mean LVEF 34 percent; 53 percent ischemic cardiomyopathy) who underwent RFA for VT (including 35 percent with VT storm), procedure- related complications occurred in 127 patients (7 percent), although in-hospital procedure- related mortality occurred in only 12 patients (0.6 percent) [61]. Early all-cause mortality at 31 days occurred in 100 patients (5 percent), with a greater likelihood of early mortality associated with lower LVEF, worse renal function, and pre-ablation VT storm. Among patients for whom data were available on mode of death, the cause was more frequently deemed advancing HF rather than to worsening arrhythmias (39 versus 22 percent). In a different study of 1251 patients who underwent RFA for VT between 2002 and 2013 and were enrolled in the international VT registry, LVEF <30 percent, previous ablation attempt, and presentation with electrical storm were the factors most associated with higher mortality [62]. Patients undergoing catheter ablation are also at risk of hemodynamic decompensation during or after the procedure. Among a single-center cohort of 193 consecutive patients undergoing catheter ablation for scar-related VT, acute hemodynamic decompensation (defined as persistent hypotension in spite of vasopressors requiring mechanical support or discontinuation of the procedure) occurred in 22 patients (11 percent) [63]. Patients with acute hemodynamic decompensation were more likely to be older, have diabetes or chronic obstructive pulmonary disease, have more severe HF, and more often received general anesthesia. In a separate multicenter cohort of 1365 patients (mean age 64 years, mean LVEF 30 percent) with HF https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 16/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate undergoing VT ablation, including 111 patients with NYHA class 4 symptoms, there was no significant difference in the rate of acute complications between patients with NYHA class 2/3 symptoms (7 percent) and those with NYHA class 4 symptoms (10 percent), suggesting that VT ablation is safe for patients with the most severe HF symptoms [64]. In select cases, percutaneous hemodynamic support can be used during catheter ablation for patients at high risk of complications [65]. Other therapies Not all patients will have their VT controlled with antiarrhythmic medications or RFA. In such cases, surgical therapy for VT remains effective in some patients, while energy sources other than radiofrequency are being investigated. Surgical therapy For most patients, because of the proven efficacy of catheter-based RFA and the development of ICDs, surgical treatment of ventricular arrhythmias is infrequently performed. However, surgical treatment of ventricular arrhythmias may be considered in certain subsets of patients with VT/VF: Patients with VT/VF that is refractory to antiarrhythmic therapy, resulting in frequent ICD shocks Patients with VT/VF that is refractory to antiarrhythmic therapy who have failed prior ablation of VT/VF Patients who are unable to tolerate antiarrhythmic therapy Patients requiring surgery for myocardial revascularization Patients with refractory HF and LV aneurysms that may benefit from aneurysm resection and LV reconstruction Although surgical therapies for SMVT are rarely performed today, they do remain a viable therapeutic option for selected patients with SMVT. Arrhythmia surgery is particularly useful when surgical revascularization (coronary artery bypass grafting [CABG]) is also planned, since it offers added hemodynamic benefits, including improvement in LVEF and alleviation of symptoms of HF, especially those requiring CABG and/or LV aneurysmectomy. Surgical ablation using endocardial resection was the mainstay of therapy for recurrent SMVT following MI unresponsive to pharmacologic therapy until the early 1990s, when RF catheter ablation for VT became feasible. A variety of surgical approaches with inconsistent efficacy have been performed, including LV aneurysmectomy, bilateral sympathectomy, encircling endocardial ventriculotomy, and subendocardial resection. Using LV aneurysmectomy as an example, the association of VT with LV aneurysms has been noted since the early 1900s, but aneurysmectomy alone has shown to have limited success in curing VT, presumably due to the fact that VTs may arise from the border of the aneurysm which is rarely excised during conventional https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 17/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate aneurysmectomy [66]. By contrast, long-term control of VT/VF has been excellent when LV aneurysmectomy is combined with LV reconstruction and subendocardial resection guided by VT mapping, with or without cryoablation [67,68]. Cardiac sympathetic denervation (ie, sympathectomy) can be effective as a temporizing strategy in patients with refractory VT and prior failed catheter ablation [69,70]. Stereotactic radiation therapy Stereotactic radiation therapy, in which high doses of radiation are precisely targeted, has been effective and well-tolerated as part of the treatment of some malignancies and has been investigated for VT in some preclinical studies and case reports [71-74]. In a single-center case series of five patients with structural heart disease (three with nonischemic cardiomyopathy, two with ischemic cardiomyopathy) with failed prior radiofrequency ablation (or who were not candidates for ablation) and ongoing VT in spite of two or more antiarrhythmic drugs, episodes of VT decreased following stereotactic radiation therapy [71]. The procedure was generally well-tolerated, with no apparent deterioration of systolic function, HF exacerbations, or other toxicities. Subsequently, in a prospective nonrandomized single arm study of 19 patients (17 for VT, two for premature ventricular complex/contraction [PVC; also referred to a premature ventricular beats or premature ventricular depolarizations]) who underwent stereotactic radiation therapy, median VT (or PVC) burden was markedly reduced, and the procedure was generally safe and well-tolerated (two patients developed radiation pneumonitis, six developed pericardial effusions [five of which were asymptomatic]) [72]. In another series of 10 patients who underwent stereotactic radiation therapy after failed catheter ablation and were followed for a median of 28 months, 8 of 10 patients experienced recurrent VT during follow-up, although the overall VT burden was reduced by 88 percent [73]. Of note, two patients in this series experienced an increased frequency of VT after radiation therapy. Prior to offering this therapy to patients outside of a clinical trial, stereotactic radiation therapy requires additional efficacy and safety evaluation in larger studies. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ventricular arrhythmias" https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 18/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Catheter ablation of arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Sustained monomorphic ventricular tachycardia (SMVT) is defined as a regular, wide ( 120 milliseconds) QRS complex tachycardia with uniform and stable QRS morphology at a rate of more than 100 beats per minute that lasts for 30 seconds or longer or causes hemodynamic collapse within 30 seconds. (See 'Introduction' above.) All patients with SMVT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. Differentiation between a hemodynamically unstable versus stable patient depends upon hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure (HF). (See 'Initial management' above.) Patients with SMVT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy countershock and cardiopulmonary resuscitation (CPR) ( algorithm 2). Patients should initially be treated with a synchronized 120 to 200 joule shock from a https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 19/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. (See 'Unstable patients' above.) For patients with wide complex tachycardia (WCT) who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (following administration of sedation) (Grade 1B). (See 'Unstable patients' above.) For patients with SMVT who are hemodynamically stable on presentation, after recording a 12-lead ECG we generally prefer to begin with an intravenous antiarrhythmic agent and reserve electrical cardioversion for refractory patients or for those who become unstable ( algorithm 1). (See 'Stable patients' above.) If pharmacologic cardioversion is the chosen approach, we administer intravenous amiodarone, procainamide, or lidocaine. If electrical cardioversion with appropriate procedural sedation is the chosen approach, intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. If the QRS complex and T wave can be distinguished, an attempt at synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator. Treatment of underlying conditions associated with VT, such as myocardial ischemia, electrolyte disturbances, drug proarrhythmia, and HF, as well as decreasing the sympathetic facilitation of SMVT, are important components of the acute management of VT. (See 'Treatment of associated conditions' above.) Chronic therapy of patients with SMVT usually requires utilization of multiple therapeutic modalities, including the implantable cardioverter-defibrillator (ICD), antiarrhythmic drugs, radiofrequency catheter ablation, and/or arrhythmia surgery. In the absence of a clearly identifiable and reversible cause for SMVT, nearly all patients with a history of SMVT will be candidates for ICD insertion for secondary prevention of sudden cardiac death, unless the patient refuses or the risks of ICD insertion are felt to outweigh the potential benefits. (See 'ICD therapy' above.) Nearly all patients who experience SMVT have an indication for therapy with a beta blocker, including patients with a prior myocardial infarction, patients with HF and reduced LV systolic function, etc. Beta blockers provide some level of protection against recurrent SMVT, primarily by reducing myocardial oxygen demand and blocking sympathetic input to the heart. (See 'Beta blockers' above.) https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 20/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Antiarrhythmic drugs may also be used to improve quality of life in patients with frequent SMVT leading to ICD shocks, or in those patients who are not candidates for, or who decline, ICD implantation. Amiodarone has generally been the most effective antiarrhythmic drug for preventing ventricular arrhythmias (and associated ICD shocks). (See 'Antiarrhythmic drugs' above.) For patients with recurrent SMVT resulting in ICD shocks despite treatment with an antiarrhythmic drug, we suggest radiofrequency ablation (RFA) rather than the addition of a second antiarrhythmic agent (Grade 2C). RFA is also an alternative to antiarrhythmic drugs as the initial therapy for SMVT. In addition, RFA, with or without antiarrhythmic drug therapy, is an option for patients with SMVT who are not candidates for or who refuse ICD implantation. (See 'Radiofrequency catheter ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 2. Link MS, Atkins DL, Passman RS, et al. 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Canadian Implantable Defibrillator Study. Eur Heart J 2000; 21:2071. 14. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337:1576. 15. Kuck KH, Cappato R, Siebels J, R ppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH). Circulation 2000; 102:748. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 22/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 16. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000; 101:1297. 17. Lee DS, Green LD, Liu PP, et al. Effectiveness of implantable defibrillators for preventing arrhythmic events and death: a meta-analysis. J Am Coll Cardiol 2003; 41:1573. 18. Betts TR, Sadarmin PP, Tomlinson DR, et al. Absolute risk reduction in total mortality with implantable cardioverter defibrillators: analysis of primary and secondary prevention trial data to aid risk/benefit analysis. Europace 2013; 15:813. 19. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009; 6:886. 20. Santangeli P, Muser D, Maeda S, et al. Comparative effectiveness of antiarrhythmic drugs and catheter ablation for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators: A systematic review and meta-analysis of randomized controlled trials. Heart Rhythm 2016; 13:1552. 21. Santangeli P, Rame JE, Birati EY, Marchlinski FE. Management of Ventricular Arrhythmias in Patients With Advanced Heart Failure. J Am Coll Cardiol 2017; 69:1842. 22. Pacifico A, Hohnloser SH, Williams JH, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 1999; 340:1855. 23. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta- blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165. 24. Dorian P, Borggrefe M, Al-Khalidi HR, et al. Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Circulation 2004; 110:3646. 25. Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 2004; 43:39. 26. K hlkamp V, Mewis C, Mermi J, et al. Suppression of sustained ventricular tachyarrhythmias: a comparison of d,l-sotalol with no antiarrhythmic drug treatment. J Am Coll Cardiol 1999; 33:46. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 23/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 27. Ferreira-Gonz lez I, Dos-Subir L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: a systematic review. Eur Heart J 2007; 28:469. 28. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The CASCADE Investigators. Am J Cardiol 1993; 72:280. 29. Sim I, McDonald KM, Lavori PW, et al. Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Circulation 1997; 96:2823. 30. Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:452. 31. Haverkamp W, Martinez-Rubio A, Hief C, et al. Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and in survivors of cardiac arrest. J Am Coll Cardiol 1997; 30:487. 32. Kovoor P, Eipper V, Byth K, et al. Comparison of sotalol with amiodarone for long-term treatment of spontaneous sustained ventricular tachyarrhythmia based on coronary artery disease. Eur Heart J 1999; 20:364. 33. Man KC, Williamson BD, Niebauer M, et al. Electrophysiologic effects of sotalol and amiodarone in patients with sustained monomorphic ventricular tachycardia. Am J Cardiol 1994; 74:1119. 34. Boriani G, Lubinski A, Capucci A, et al. A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease. Eur Heart J 2001; 22:2180. 35. Baquero GA, Banchs JE, Depalma S, et al. Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies. J Cardiovasc Electrophysiol 2012; 23:296. 36. Greenspan AM, Spielman SR, Horowitz LN. Combination antiarrhythmic drug therapy for ventricular tachyarrhythmias. Pacing Clin Electrophysiol 1986; 9:565. 37. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17:e2. 38. Willems S, Tilz RR, Steven D, et al. Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT): A Multicenter Randomized Trial. Circulation 2020; 141:1057. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 24/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 39. Di Biase L, Santangeli P, Burkhardt DJ, et al. Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol 2012; 60:132. 40. Ja s P, Maury P, Khairy P, et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation 2012; 125:2184. 41. Vergara P, Trevisi N, Ricco A, et al. Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation. J Cardiovasc Electrophysiol 2012; 23:621. 42. Tanawuttiwat T, Nazarian S, Calkins H. The role of catheter ablation in the management of ventricular tachycardia. Eur Heart J 2016; 37:594. 43. Stevenson WG, Tedrow UB, Reddy V, et al. Infusion Needle Radiofrequency Ablation for |
amiodarone. Am Heart J 1993; 125:109. 12. Sendra-Ferrer M, Gonzalez MD. Ibutilide for the control of refractory ventricular tachycardia and ventricular fibrillation in patients with myocardial ischemia and hemodynamic instability. J Cardiovasc Electrophysiol 2019; 30:503. 13. Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg . Canadian Implantable Defibrillator Study. Eur Heart J 2000; 21:2071. 14. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337:1576. 15. Kuck KH, Cappato R, Siebels J, R ppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH). Circulation 2000; 102:748. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 22/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 16. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000; 101:1297. 17. Lee DS, Green LD, Liu PP, et al. Effectiveness of implantable defibrillators for preventing arrhythmic events and death: a meta-analysis. J Am Coll Cardiol 2003; 41:1573. 18. Betts TR, Sadarmin PP, Tomlinson DR, et al. Absolute risk reduction in total mortality with implantable cardioverter defibrillators: analysis of primary and secondary prevention trial data to aid risk/benefit analysis. Europace 2013; 15:813. 19. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009; 6:886. 20. Santangeli P, Muser D, Maeda S, et al. Comparative effectiveness of antiarrhythmic drugs and catheter ablation for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators: A systematic review and meta-analysis of randomized controlled trials. Heart Rhythm 2016; 13:1552. 21. Santangeli P, Rame JE, Birati EY, Marchlinski FE. Management of Ventricular Arrhythmias in Patients With Advanced Heart Failure. J Am Coll Cardiol 2017; 69:1842. 22. Pacifico A, Hohnloser SH, Williams JH, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 1999; 340:1855. 23. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta- blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165. 24. Dorian P, Borggrefe M, Al-Khalidi HR, et al. Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Circulation 2004; 110:3646. 25. Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 2004; 43:39. 26. K hlkamp V, Mewis C, Mermi J, et al. Suppression of sustained ventricular tachyarrhythmias: a comparison of d,l-sotalol with no antiarrhythmic drug treatment. J Am Coll Cardiol 1999; 33:46. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 23/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 27. Ferreira-Gonz lez I, Dos-Subir L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: a systematic review. Eur Heart J 2007; 28:469. 28. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). The CASCADE Investigators. Am J Cardiol 1993; 72:280. 29. Sim I, McDonald KM, Lavori PW, et al. Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Circulation 1997; 96:2823. 30. Mason JW. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N Engl J Med 1993; 329:452. 31. Haverkamp W, Martinez-Rubio A, Hief C, et al. Efficacy and safety of d,l-sotalol in patients with ventricular tachycardia and in survivors of cardiac arrest. J Am Coll Cardiol 1997; 30:487. 32. Kovoor P, Eipper V, Byth K, et al. Comparison of sotalol with amiodarone for long-term treatment of spontaneous sustained ventricular tachyarrhythmia based on coronary artery disease. Eur Heart J 1999; 20:364. 33. Man KC, Williamson BD, Niebauer M, et al. Electrophysiologic effects of sotalol and amiodarone in patients with sustained monomorphic ventricular tachycardia. Am J Cardiol 1994; 74:1119. 34. Boriani G, Lubinski A, Capucci A, et al. A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease. Eur Heart J 2001; 22:2180. 35. Baquero GA, Banchs JE, Depalma S, et al. Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies. J Cardiovasc Electrophysiol 2012; 23:296. 36. Greenspan AM, Spielman SR, Horowitz LN. Combination antiarrhythmic drug therapy for ventricular tachyarrhythmias. Pacing Clin Electrophysiol 1986; 9:565. 37. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17:e2. 38. Willems S, Tilz RR, Steven D, et al. Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT): A Multicenter Randomized Trial. Circulation 2020; 141:1057. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 24/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate 39. Di Biase L, Santangeli P, Burkhardt DJ, et al. Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol 2012; 60:132. 40. Ja s P, Maury P, Khairy P, et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation 2012; 125:2184. 41. Vergara P, Trevisi N, Ricco A, et al. Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation. J Cardiovasc Electrophysiol 2012; 23:621. 42. Tanawuttiwat T, Nazarian S, Calkins H. The role of catheter ablation in the management of ventricular tachycardia. Eur Heart J 2016; 37:594. 43. Stevenson WG, Tedrow UB, Reddy V, et al. Infusion Needle Radiofrequency Ablation for Treatment of Refractory Ventricular Arrhythmias. J Am Coll Cardiol 2019; 73:1413. 44. Di Biase L, Burkhardt JD, Lakkireddy D, et al. Ablation of Stable VTs Versus Substrate Ablation in Ischemic Cardiomyopathy: The VISTA Randomized Multicenter Trial. J Am Coll Cardiol 2015; 66:2872. 45. Romero J, Cerrud-Rodriguez RC, Di Biase L, et al. Combined Endocardial-Epicardial Versus Endocardial Catheter Ablation Alone for Ventricular Tachycardia in Structural Heart Disease: A Systematic Review and Meta-Analysis. JACC Clin Electrophysiol 2019; 5:13. 46. Sarkozy A, Tokuda M, Tedrow UB, et al. Epicardial ablation of ventricular tachycardia in ischemic heart disease. Circ Arrhythm Electrophysiol 2013; 6:1115. 47. Piers SR, Tao Q, de Riva Silva M, et al. CMR-based identification of critical isthmus sites of ischemic and nonischemic ventricular tachycardia. JACC Cardiovasc Imaging 2014; 7:774. 48. Njeim M, Yokokawa M, Frank L, et al. Value of Cardiac Magnetic Resonance Imaging in Patients With Failed Ablation Procedures for Ventricular Tachycardia. J Cardiovasc Electrophysiol 2016; 27:183. 49. Reddy VY, Reynolds MR, Neuzil P, et al. Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med 2007; 357:2657. 50. Stevenson WG, Wilber DJ, Natale A, et al. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation 2008; 118:2773. 51. Al-Khatib SM, Daubert JP, Anstrom KJ, et al. Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial. J Cardiovasc https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 25/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Electrophysiol 2015; 26:151. 52. Sapp JL, Wells GA, Parkash R, et al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med 2016; 375:111. 53. Kuck KH, Schaumann A, Eckardt L, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. Lancet 2010; 375:31. 54. Kuck KH, Tilz RR, Deneke T, et al. Impact of Substrate Modification by Catheter Ablation on Implantable Cardioverter-Defibrillator Interventions in Patients With Unstable Ventricular Arrhythmias and Coronary Artery Disease: Results From the Multicenter Randomized Controlled SMS (Substrate Modification Study). Circ Arrhythm Electrophysiol 2017; 10. 55. Ha AH, Ham I, Nair GM, et al. Implantable cardioverter-defibrillator shock prevention does not reduce mortality: a systemic review. Heart Rhythm 2012; 9:2068. 56. Tung R, Xue Y, Chen M, et al. First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial. Circulation 2022; 145:1839. 57. Della Bella P, Baratto F, Vergara P, et al. Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial. Circulation 2022; 145:1829. 58. Anderson RD, Ariyarathna N, Lee G, et al. Catheter ablation versus medical therapy for treatment of ventricular tachycardia associated with structural heart disease: Systematic review and meta-analysis of randomized controlled trials and comparison with observational studies. Heart Rhythm 2019; 16:1484. 59. Martinez BK, Baker WL, Konopka A, et al. Systematic review and meta-analysis of catheter ablation of ventricular tachycardia in ischemic heart disease. Heart Rhythm 2020; 17:e206. 60. Palaniswamy C, Kolte D, Harikrishnan P, et al. Catheter ablation of postinfarction ventricular tachycardia: ten-year trends in utilization, in-hospital complications, and in-hospital mortality in the United States. Heart Rhythm 2014; 11:2056. 61. Santangeli P, Frankel DS, Tung R, et al. Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients With Structural Heart Disease. J Am Coll Cardiol 2017; 69:2105. 62. Vergara P, Tzou WS, Tung R, et al. Predictive Score for Identifying Survival and Recurrence Risk Profiles in Patients Undergoing Ventricular Tachycardia Ablation: The I-VT Score. Circ Arrhythm Electrophysiol 2018; 11:e006730. 63. Santangeli P, Muser D, Zado ES, et al. Acute hemodynamic decompensation during catheter ablation of scar-related ventricular tachycardia: incidence, predictors, and impact on https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 26/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate mortality. Circ Arrhythm Electrophysiol 2015; 8:68. 64. Tzou WS, Tung R, Frankel DS, et al. Ventricular Tachycardia Ablation in Severe Heart Failure: An International Ventricular Tachycardia Ablation Center Collaboration Analysis. Circ Arrhythm Electrophysiol 2017; 10. 65. Turagam MK, Vuddanda V, Atkins D, et al. Hemodynamic Support in Ventricular Tachycardia Ablation: An International VT Ablation Center Collaborative Group Study. JACC Clin Electrophysiol 2017; 3:1534. 66. Josephson ME, Horowitz LN, Farshidi A, et al. Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 1978; 57:440. 67. Dor V, Sabatier M, Montiglio F, et al. Results of nonguided subtotal endocardiectomy associated with left ventricular reconstruction in patients with ischemic ventricular arrhythmias. J Thorac Cardiovasc Surg 1994; 107:1301. 68. Sosa E, Jatene A, Kaeriyama JV, et al. Recurrent ventricular tachycardia associated with postinfarction aneurysm. Results of left ventricular reconstruction. J Thorac Cardiovasc Surg 1992; 103:855. 69. Richardson T, Lugo R, Saavedra P, et al. Cardiac sympathectomy for the management of ventricular arrhythmias refractory to catheter ablation. Heart Rhythm 2018; 15:56. 70. Murtaza G, Sharma SP, Akella K, et al. Role of cardiac sympathetic denervation in ventricular tachycardia: A meta-analysis. Pacing Clin Electrophysiol 2020; 43:828. 71. Cuculich PS, Schill MR, Kashani R, et al. Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia. N Engl J Med 2017; 377:2325. 72. Robinson CG, Samson PP, Moore KMS, et al. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation 2019; 139:313. 73. Neuwirth R, Cvek J, Knybel L, et al. Stereotactic radiosurgery for ablation of ventricular tachycardia. Europace 2019; 21:1088. 74. Lloyd MS, Wight J, Schneider F, et al. Clinical experience of stereotactic body radiation for refractory ventricular tachycardia in advanced heart failure patients. Heart Rhythm 2020; 17:415. Topic 1040 Version 52.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 27/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate GRAPHICS Algorithm for initial treatment of SMVT in responsive patients with a pulse SMVT: sustained monomorphic ventricular tachycardia; CV: cardioversion. Hemodynamically unstable patients have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure. Hemodynamically stable patients should have none of these findings. Initial choice of pharmacologic agents includes: Intravenous lidocaine (1 to 1.5 mg/kg [typically 75 to 100 mg] at a rate of 25 to 50 mg/minute; lower doses of 0.5 to 0.75 mg/kg can be repeated every 5 to 10 minutes as needed), which may be more effective in the setting of acute myocardial ischemia or infarction Intravenous procainamide (20 to 50 mg/minute until arrhythmia terminates or a maximum dose of 17 mg/kg is administered) Intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours; bolus can be repeated if VT recurs) Electrical cardioversion should be synchronized if possible, using 100-joule biphasic shock or 200- joule monophasic shock. If first shock is unsuccessful, energy level should be escalated on subsequent shocks. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 28/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Conditions associated with SMVT include myocardial ischemia, electrolyte disturbances (eg, hypokalemia, hypomagnesemia), drug-related proarrhythmia, and heart failure. Graphic 108831 Version 1.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 29/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 30/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 31/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 32/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Amiodarone dosing in adults by indication Indications Loading dose Maintenance dose Atrial arrhythmias Prevention of recurrent PAF Total loading dose: 6 to 10 grams Lowest effective dose, usually 100 to 200 mg orally once per day Pharmacologic Outpatient: Given as 400 to cardioversion of PAF 600 mg orally per day in divided doses with meals Maximum 200 mg orally per day Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals Pretreatment before elective cardioversion or catheter ablation of AF Total loading dose: 6 to 10 grams orally over 2 to 6 weeks Lowest effective dose, usually 100 to 200 mg orally once per day Given as 400 to 1200 mg orally per day in divided Maximum 400 mg orally per day in most circumstances doses Restoration and maintenance of NSR in critically ill patients with AF Total IV loading dose: 1050 mg Given as 150 mg IV bolus over 10 to 30 minutes, followed by continuous IV Ventricular rate control in critically ill patients with AF and rapid ventricular response infusion at 1 mg per minute for 6 hours, then 0.5 mg per minute for 18 hours* IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy If amiodarone will be used chronically: Following IV infusion, give 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams; consider overlapping IV and oral amiodarone for 24 to 48 hours Ventricular arrhythmias https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 33/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Primary and secondary Total oral loading dose: 6 to Maximum 400 mg orally per prevention of SCD in patients with LV 10 grams day in most circumstances Outpatient: 400 to 600 mg orally per day in divided Lowest effective dose, ideally 200 mg or less orally once dysfunction who are not candidates for or refuse ICD implantation doses with meal per day or in divided doses Inpatient: 400 to 1200 mg orally per day in divided doses with meals for 1 to 2 weeks Prevention of ventricular Total loading dose: 6 to 10 Maximum 400 mg orally per arrhythmias in patients with ICDs to decrease risk grams day in most circumstances Outpatient: Given as 400 to 600 mg orally per day in Lowest effective dose, ideally 200 mg or less orally per day of shocks divided doses with meals Inpatient: Given as 400 to 1200 mg orally per day in divided doses with meals until desired dose is achieved Cardiac arrest associated with VF or pulseless VT 300 mg IV or IO rapid bolus with a repeat dose of 150 mg as indicated Upon return of spontaneous circulation follow with an infusion of 1 mg per minute for 6 hours and then 0.5 mg per minute for 18 hours* Electrical (VT) storm and incessant VT in hemodynamically stable Total IV loading dose: 1050 mg If amiodarone is used chronically: Lowest effective dose, ideally 200 mg or less 150 mg IV bolus over 10 minutes, followed by patients orally per day; maximum 400 mg orally per day in most continuous IV infusion at 1 circumstances mg per minute for 6 hours, then 0.5 mg per minute for 18 hours IV infusion (0.5 mg per minute) may need to be extended past 24 hours if unable to transition to oral therapy Additional 150 mg boluses may be given if VT storm recurs https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 34/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate If amiodarone will be used chronically: Following IV infusion 400 to 1200 mg orally per day in divided doses to complete a total (IV plus oral) loading dose of 10 grams. Consider overlapping IV and oral amiodarone for 24-48 hours PAF: paroxysmal atrial fibrillation; AF: atrial fibrillation; NSR: normal sinus rhythm; IV: intravenous; SCD: sudden cardiac death; LV: left ventricular; ICD: implantable cardioverter-defibrillator; VF: ventricular fibrillation; VT: ventricular tachycardia; IO: intraosseous. When administered to critically ill patients with atrial fibrillation and rapid ventricular response, repeated 150 mg boluses can be given over 10 to 30 minutes if needed, but no more than six to eight additional boluses should be administered in any 24-hour period. Typically, patients are given 1 or 2 doses of oral amiodarone prior to discontinuation of the IV infusion. Graphic 117524 Version 5.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 35/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Electrophysiology study (EPS) tracings showing concealed entrainment (A) Pacing from the distal electrode pair of the mapping/ablation catheter during mapping of sustained ventr tachycardia. On the left side of the figure are the last three stimuli during a train of pacing at a cycle length o milliseconds. Following pacing, the tachycardia (cycle length 430 milliseconds) resumes. The interval from the paced beat to resumption of tachycardia, measured in the distal ablation catheter (Abl d), is just 10 millisecon greater than the tachycardia cycle length. Note that the interval from the pacing stimulus to onset of the QRS is the same as the interval from the local electrogram to the QRS onset when VT resumes after pacing. Note a the paced VT morphology replicates the morphology of the spontaneous tachycardia. This is an example of "concealed entrainment" and implies the catheter is within a critical part of a reentrant circuit. (B) Same site on the ablation catheter (Abl d) during sinus rhythm as shown during VT in figure A. During sinu rhythm, a late potential is present. The vertical line denotes the end of the QRS complex. Delivery of radiofreq energy at this site resulted in termination of VT. The tachycardia was no longer inducible after ablation. Sites this displaying late potentials may be targeted during "substrate-guided ablation." VT: ventricular tachycardia. Graphic 107237 Version 2.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 36/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Complications of invasive cardiac electrophysiology studies Associated with percutaneous catheterization of veins and arteries Pain Adverse drug reaction Infection/abscess at the catheterization site, sepsis Excessive bleeding, hematoma formation Thrombophlebitis Pulmonary thromboembolism Arterial damage, aortic dissection Systemic thromboembolism Transient ischemic attack/stroke Associated with intracardiac catheters and programmed cardiac stimulation Cardiac chamber or coronary sinus perforation Hemopericardium, cardiac tamponade Atrial fibrillation Ventricular tachycardia/ventricular fibrillation Myocardial infarction Right or left bundle branch block Associated with transcatheter ablation Complete heart block Thromboembolism Vascular access problems (bleeding, infection, hematoma, vascular injury) Cardiac trauma (myocardial perforation, tamponade, valvular damage) Coronary artery thrombosis/myocardial infarction Cardiac arrhythmias Pericarditis Pulmonary vein stenosis Phrenic nerve paralysis Radiation skin burns Possible late malignancy Atrioesophageal fistula https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 37/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Death resulting from one of the above complications Graphic 63157 Version 4.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 38/39 7/6/23, 3:39 PM Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis - UpToDate Contributor Disclosures Alfred Buxton, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-in-patients-with-structural-heart-disease-treatment-and-prognos 39/39 |
7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Ventricular tachycardia in the absence of apparent structural heart disease : David J Callans, MD : N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 06, 2022. INTRODUCTION The evaluation and management of ventricular tachyarrhythmias are uniquely challenging due to the unpredictable and potentially lethal nature of the events. When evaluating patients with ventricular tachycardia (VT) and ventricular fibrillation (VF), several initial distinctions should be made. These include: Arrhythmia duration Sustained or nonsustained Arrhythmia morphology Monomorphic VT, polymorphic VT, or VF Associated symptoms Ranging from none to hemodynamic collapse and sudden cardiac arrest Associated cardiac disease Malignant arrhythmias usually occur in the presence of significant structural heart disease (eg, coronary heart disease with prior myocardial infarction, dilated cardiomyopathy, or hypertrophic cardiomyopathy). In this setting, ventricular arrhythmias carry a high risk of sudden cardiac death (SCD). Less commonly, VT and VF occur in hearts that appear normal. In many such cases, however, the heart is in fact not normal, but rather has less visible abnormalities including derangements of cardiac ion channels or structural proteins. In these patients, ventricular arrhythmias also carry a high risk of SCD. Thus, a significant majority of patients with VT or VF have some form of underlying cardiac disease, are at increased risk for SCD, and require a thorough cardiac https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 1/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate evaluation to exclude structural abnormalities and nonstructural disorders. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".) There are, however, some VT syndromes which occur in normal hearts that have a more benign prognosis [1,2]. These arrhythmias are sometimes referred to as idiopathic VT. Terminology and classifications vary, but three commonly cited syndromes are: Repetitive monomorphic VT, which is also referred to as right ventricular outflow tract (RVOT) VT. This arrhythmia is due to triggered activity and is sensitive to adenosine. An arrhythmia with similar characteristics that originates from the left ventricular outflow tract has also been described. Paroxysmal sustained VT, which is sometimes considered a variant of RVOT VT. Idiopathic left ventricular tachycardia, which originates from the posterior septum, is due to reentry, and is sensitive to verapamil. These arrhythmias have substrate and mechanisms that are different from the malignant arrhythmias that occur in both abnormal and apparently normal hearts. Thus, they should be considered distinct syndromes rather than well-tolerated forms of other ventricular arrhythmia syndromes. The diagnosis, characterization, and management of these monomorphic VTs will be reviewed here. Sustained and nonsustained ventricular arrhythmias in patients with heart disease, and malignant ventricular arrhythmias in the absence of apparent structural heart disease are discussed in detail separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Nonsustained VT in the absence of apparent structural heart disease".) IDIOPATHIC VENTRICULAR ARRHYTHMIAS Although the term idiopathic VT is widely used for the monomorphic VT syndromes described here, use of "idiopathic" can be misleading. Historically, both VT and VF that occur in the absence of apparent heart disease have been referred to as idiopathic. However, with continual improvements in both the understanding of arrhythmia mechanisms and diagnostic methods, an increasing percentage of patients are now given a diagnosis (eg, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy [ARVC], and catecholaminergic polymorphic VT). In contrast to the syndromes discussed here, these disorders have an increased risk of https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 2/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate sudden cardiac death (SCD). (See "Catecholaminergic polymorphic ventricular tachycardia" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations", section on 'Ventricular arrhythmias' and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) Previously reported series of idiopathic VT and VF are likely to include a heterogeneous group of patients with various diagnoses and prognoses. Currently, idiopathic VT generally refers to one of the three benign syndromes described here and excludes patients with other diagnoses. Sites of origin Idiopathic VT, or VT not associated with structural organic heart disease, can arise in several locations: Right ventricular outflow tract (also called repetitive monomorphic VT) Tricuspid annulus Right ventricle Left ventricle Inferoapical septum Left ventricular outflow tract Aortic cusps These arrhythmias, not as rare as previously thought, are susceptible to radiofrequency ablation [3]. (See 'Radiofrequency ablation' below.) Classification Multiple classification schemata for idiopathic VT appear in the literature. Investigations of idiopathic VT syndromes have focused for the most part on individual aspects of the syndrome (eg, clinical presentation, electrocardiographic appearance, electrophysiologic mechanism, response to antiarrhythmic agents); this approach has yielded a bewildering amount of often conflicting information. Despite this confusion, most investigators acknowledge the existence of at least three syndromes of idiopathic monomorphic VT: Repetitive monomorphic VT, also called right ventricular outflow tract (RVOT) VT, is a triggered arrhythmia that is characterized by frequent short "salvos" of nonsustained VT. Less commonly, arrhythmias with similar characteristics and mechanisms originate from the LVOT, and these are considered a variant of RVOT VT. Paroxysmal sustained VT, which also arises from the RV, and is sometimes considered a sustained variant of repetitive monomorphic VT. Idiopathic left ventricular tachycardia, which differs from the LVOT variant of RVOT VT in both the mechanism (reentry) and site of origin (inferoapex or midseptum). https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 3/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate These three syndromes effectively characterize the majority of patients with idiopathic monomorphic VT and often unite clinical presentation, ECG morphology, and anatomic location into recognizable syndromes ( table 1) [1,2]. In fact, however, idiopathic VT can arise from virtually any area of the heart, and other typical locations include the RV and LV inflow areas and the papillary muscles. The syndromes discussed in this section are by far the most frequently observed. Bundle branch reentrant VT is a special form of monomorphic VT that typically occurs in patients with structural heart disease. Patients with BBRVT often have a baseline nonspecific conduction delay or left bundle branch block, and most have a prolonged His-to-ventricle time (ie, HV interval). (See "Bundle branch reentrant ventricular tachycardia".) Idiopathic VT Idiopathic VT has accounted for approximately 10 percent all patients referred for evaluation of VT [1]. The mean age of patients with idiopathic VT is less than that of patients with VT secondary to underlying heart disease. It is important to recognize that not all VT that occurs in the apparent absence of structural heart disease is idiopathic VT. Distinguishing idiopathic VT from other monomorphic VT syndromes is important for several reasons: Idiopathic VT is generally considered to have an excellent prognosis in terms of freedom from both the development of structural heart disease and arrhythmic death [4-10]. There are several exceptions to this generalization, however, and episodes of SCD can occur [7]. Idiopathic VT often responds to antiarrhythmic drugs that would be unhelpful or even contraindicated in VT occurring in the setting of coronary heart disease. Most idiopathic VT syndromes are now amenable to cure with catheter ablation techniques. Other ventricular tachyarrhythmias In addition to monomorphic VT, both polymorphic VT and VF can occur in the absence of structural heart disease. In contrast to the generally good prognosis associated with idiopathic monomorphic VT, these syndromes are associated with an increased risk of SCD. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease".) Polymorphic VT in the absence of structural heart disease occurs in two settings: with a prolonged QT interval in acquired or inherited long QT syndrome; and with a normal QT interval in usually familial disease, which is also called catecholaminergic polymorphic VT. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Catecholaminergic polymorphic ventricular tachycardia".) https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 4/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate VF in the absence of structural heart disease or other reversible arrhythmic triggers (eg, ischemia or metabolic derangements) is also referred to as idiopathic. The diagnosis of idiopathic VF is considered only after all other causes of VF have been rigorously excluded. The rationale for this approach comes from autopsy studies of SCD in previously healthy individuals. These studies found an appreciable incidence of coronary heart disease (most without a previous history of chest pain), hypertrophic cardiomyopathy, myocarditis, and ARVC. Brugada syndrome is a specific cause of lethal ventricular arrhythmias in patients without structural heart disease; it is characterized by ST elevation in the anterior precordial leads on the resting surface electrocardiogram. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) DIAGNOSTIC EVALUATION By definition, patients with idiopathic monomorphic VT have no detectable structural heart disease [1,2,4-9]. Thus, the assessment of these patients focuses upon establishing the presence of a normal heart. The evaluation of the patient with sustained ventricular arrhythmias and sudden death is reviewed in detail separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Additional diagnostic evaluation' and "Cardiac evaluation of the survivor of sudden cardiac arrest".) General approach For the purposes of this review, the following summarizes findings that may be seen in patients with idiopathic monomorphic VT: The resting ECG is typically normal between arrhythmia episodes, although some patients have temporary ECG repolarization abnormalities immediately after VT termination. The signal averaged ECG recorded during sinus rhythm is usually normal, although abnormalities may be seen during VT [6,11]. Functional studies of left ventricular (LV) and right ventricular (RV) performance during sinus rhythm are normal, although segmental wall motion abnormalities may be seen immediately after VT termination. In patients who have not had a recent episode of VT, abnormalities in ventricular function should suggest an alternative diagnosis. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Echocardiography'.) However, in rare cases, LV dysfunction can occur as a consequence of idiopathic VT, due to a tachycardia-induced cardiomyopathy. Such a myopathy can develop without persistent tachycardia if there are very frequent PVCs (ie, >20,000 per day) [12]. This is a very https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 5/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate important condition to recognize, as the LV dysfunction is reversible with treatment of the arrhythmia. (See "Arrhythmia-induced cardiomyopathy", section on 'Frequent ventricular ectopy'.) The exercise stress test should be normal. Coronary angiography, which is considered in patients with minimally symptomatic arrhythmias only if the stress test suggests ischemia, should also be normal. Cardiovascular magnetic resonance imaging (CMR) may reveal mild structural abnormalities of the RV in patients with RMVT, primarily involving the free wall (focal thinning, fatty infiltration, and wall motion abnormalities) [13-15]. The significance of these changes is unclear, since there is a poor correlation between the origin of the RMVT and the site of the CMR abnormalities unless they are also present in the RVOT. Limited data suggest that RV radionuclide myocardial perfusion imaging can distinguish between idiopathic monomorphic VT and VT due to an organic cause such as dilated cardiomyopathy, myocarditis, or ARVC [16]. RV biopsy, which is rarely performed, is usually normal, although a number of studies have reported abnormalities that are nonspecific and of no significant value [17-19]. Distinction from ARVC RMVT can be particularly difficult to distinguish from the more serious disorder, ARVC. Although ARVC is unlikely in patients who have a normal signal averaged electrocardiogram and normal imaging studies of RV size and function, the "development" of ARVC in patients thought to have idiopathic VT at presentation has been reported [9,20]. Thus, the clinical boundaries between idiopathic RV tachycardia and ARVC may be difficult to establish in atypical cases. The findings on the ECG, signal averaged ECG, and electrophysiology (EP) studies may be helpful in making this distinction: The resting ECG can be normal at presentation in approximately 40 percent of patients with ARVC. However, characteristic abnormalities of ARVC develop in almost all patients within six years of presentation [21]. In a cohort of 59 patients (17 with ARVC, 42 with RMVT), ECG features suggestive of ARVC included longer mean QRS duration in lead I (150 versus 123 msec in RMVT), precordial transition in lead V6 (18 versus 0 percent in RMVT), and at least one lead with QRS notching (65 versus 21 percent in RMVT) [22]. The signal averaged ECG in the time domain is typically abnormal in ARVC, but usually normal in idiopathic RV tachycardia [11]. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 6/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate On EP study, four findings are seen in most patients with ARVC but are rare in idiopathic RV tachycardia: inducible VT by programmed stimulation; multiple VT morphologies; fractionated diastolic electrograms during VT or sinus rhythm at the VT site of origin or other RV sites; and regions of low amplitude and prolonged duration on intracardiac electrograms [23-25]. (See 'Electrophysiologic features' below.) REPETITIVE MONOMORPHIC VT Repetitive monomorphic VT (RMVT) is characterized by frequent short "salvos" of monomorphic nonsustained VT ( waveform 1). It was first described by Gallavardin in 1922 and is variously described in the literature as RMVT, RV tachycardia, RVOT tachycardia, catecholamine-sensitive VT, adenosine-sensitive VT, and exercise-induced VT. Approximately 10 to 15 percent of cases arise from the left ventricular outflow tract [26-28]. Although RMVT is considered to occur in "normal" hearts, static and cine-magnetic resonance imaging often reveal mild structural abnormalities of the RV, primarily involving the free wall (focal thinning, fatty infiltration, and wall motion abnormalities) [13-15]. The functional significance of these changes is uncertain. In the few cases studied, DNA from myocardial biopsies of ventricular muscle has been normal [29]. Epidemiology and clinical features RMVT occurs almost exclusively in young to middle-aged patients without structural heart disease [1,2,4-9]. There has generally been no predilection on the basis of sex, although a 2:1 female predominance was observed in one report [26]. A surprising number of competitive athletes (particularly cyclists) are identified in many series of RMVT. The most common associated symptoms are palpitations and lightheadedness during episodes [5,6]. In one illustrative report of 18 patients, twelve had symptomatic arrhythmia, two of whom had syncope, and six were completely asymptomatic. Most arrhythmias are nonsustained (usually 3 to 15 beats), but up to one-half of patients have some sustained episodes, and some patients have only sustained VT [6,9,13,30]. (See 'Paroxysmal sustained VT' below.) Bursts of nonsustained VT are typically provoked by emotional stress or exercise, often occurring during the "warm-down" period after exercise, a time when circulating catecholamines are at peak levels [5,6,8]. There may also be a circadian pattern, with prominent peaks between 7 and 11 AM and 4 and 8 PM, correlating with periods of increased sympathetic activity [31]. In some https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 7/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate patients, a critical "window" of heart rates (upper and lower thresholds) that result in occurrence of the arrhythmia can be defined [27]. The inducibility of RMVT by stress or catecholamine infusion is suggestive of an abnormality in cardiac sympathetic function. Consistent with this hypothesis is evidence of regional cardiac sympathetic denervation in some patients with RMVT and structurally normal hearts (five of nine compared with zero of nine controls in one report) [32]. Patients with RMVT may also have regions of impaired neuronal reuptake of norepinephrine, leading to increased local synaptic catecholamine concentrations and downregulation of myocardial beta adrenergic receptors [33]. There may also be sex-specific triggers. In a report of 47 men and women with RMVT, states of hormonal flux (premenstrual, gestational, perimenopausal, administration of birth control pills) were the most common trigger for RMVT in 59 percent of women and were the only recognizable triggers in 41 percent [34]. Men were more likely than women to identify exercise, stress, or caffeine as a trigger (92 versus 41 percent). Site of origin RV tachycardias usually originate from the septal aspect of the RVOT [6,26,28,35-38]. A nine site mapping schema of the septal RVOT has proven useful in localizing RVOT tachycardias on the basis of their 12 lead ECG morphology ( figure 1) [39]. RV tachycardias typically arise from a very narrow area just inferior to the pulmonary valve in the anterior aspect of the RVOT [37]. Endocardial mapping in such patients shows that the earliest site of endocardial activation occurs in this region [6,9]. Less commonly, sites of origin have been mapped to the RV inflow tract, the free wall of the RVOT, the root of the pulmonary artery, the left and right aortic sinus of Valsalva, the left ventricle, the mitral annulus, and the papillary muscles [26,36,38,40-49]. Electrocardiographic features The typical rate of RMVT ranges from 140 to 180 beats/min, and may fluctuate based upon catecholamine levels. The VT cycle length often prolongs prior to termination. RV outflow tract The majority of RMVT episodes have a characteristic ECG appearance with two main features [1,2,4-9,39]: Left bundle branch block Inferior axis This morphology is consistent with the RVOT origin seen by catheter ablation and endocardial mapping [6,37]. This ECG "signature" accounts for at least 70 percent of all idiopathic VTs [1]. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 8/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate The ECG pattern of RV tachycardia initiation may provide information about the site of origin and the arrhythmogenic mechanism as illustrated by the following observations: In a series of 32 patients with exercise-induced RMVT, VT usually began without a change in cycle length. Arrhythmias that initiated in this manner had an inferior axis, and appeared to be related to triggered activity due to delayed afterpotentials [50]. By comparison, VT initiated with a long-short sequence was more often nonsustained and often had a superior axis, suggesting an origin in the body or septal region of the ventricle; the mechanism for this VT is probably early afterpotentials. In a report of 14 patients, those with septal compared with free wall sites were significantly less likely to have notching of the QRS complex (29 versus 95 percent) and more likely to show early precordial transition by lead V4 (79 versus 5 percent) [51]. In addition, a positive R wave in lead I distinguished posterior from anterior septal and free wall sites. The degree of similarity of 12-lead ECG waveforms between VT and a pace map can be used to estimate the likelihood of successful ablation at that site. (See 'Radiofrequency ablation' below.) The majority of patients with RV tachycardia have a single ECG morphology [23]. However, occasional patients present with multiple tachycardia morphologies arising from discrete sites in the RVOT [52]. The presence of multiple left bundle VT morphologies, particularly during EP study, should suggest the possibility of ARVC [23,53,54]. (See 'Distinction from ARVC' above.) LV outflow tract Electrocardiographic criteria have also been described for RMVT originating in the LVOT [26,27]. In a series of 33 patients with RMVT, four (12 percent) had LV sites of origin that could be predicted by two patterns [26]: A right bundle, inferior axis morphology with a monophasic R wave in V1 that arose from the left fibrous trigone ( waveform 2). A pattern similar to typical RMVT from the RVOT (left bundle, inferior axis) except that the precordial transition was earlier (at V2 for the LVOT as compared with V3 or later for the RVOT). Other reports have characterized unique QRS morphologies for idiopathic VT arising from the sinuses of Valsalva [9,43,44]. Although there is some interindividual variability, premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) arising from the left aortic sinus tend to be negative in lead I and have a "w" pattern in V1, while PVC with a broad R wave in V1 is characteristic of a right aortic cusp origin. The precordial R wave transition is much earlier when VT originates from https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 9/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate either aortic sinus of Valsalva compared with the RVOT, since the LVOT is posterior to the RVOT [44]. Electrophysiologic features RMVT can be induced in the EP laboratory, although usually not with programmed stimulation [5,6,23,27,55]. In most patients, sustained or nonsustained episodes occur in response to burst atrial or ventricular pacing, and are greatly facilitated by isoproterenol or epinephrine infusion [5,6,27,30,55]. These electrophysiologic observations suggest that triggered activity due to delayed afterpotentials, rather than reentry, is the mechanism of RMVT. The response to "pharmacologic probes" further strengthens this hypothesis. RMVT has been terminated with adenosine, verapamil, and beta blockers, all of which interfere with the cAMP-mediated slow inward calcium current [29,40,56-58]. These observations are consistent with the hypothesis that RMVT results from triggered activity induced by cAMP-mediated delayed after depolarizations (DADs) [30,59]. The increase in cAMP activity may, at least in some patients, result from an acquired somatic cell mutation in the inhibitory G protein G-alpha-i2 at the site of the arrhythmogenic focus [59,60]. However, the lack of specificity of these probes and the absence of a uniform response supports the general consensus that the mechanism of RMVT is incompletely characterized and may vary among individuals. Additional support for other mechanisms is based upon the observation that the tachycardia may, in some patients, terminate with overdrive pacing, ventricular extrastimulation, or autonomic modulation using Valsalva maneuver or carotid sinus pressure [9]. EP studies may also help distinguish RMVT occurring in the absence of structural heart disease from that in ARVC [23,24]. (See 'Distinction from ARVC' above.) Prognosis The prognosis of RMVT is almost uniformly good [4-9,55]. The following observations from early studies illustrate the range of findings: Two initial series evaluated 30 and 18 patients [5,6]. The arrhythmia responded to a variety of antiarrhythmic drugs, including type I drugs and propranolol. At a mean of 30 months in one study and a range of 0.5 to 8 years in the other, there were no deaths or episodes of cardiac arrest [5,6]. A third report consisted of 24 young patients, most of whom had RV tachycardia and two- thirds of whom were symptomatic [7]. At a mean follow-up of 7.5 years, three patients died suddenly; none was taking antiarrhythmic drugs at the time. The SCD events may have been due to RMVT itself, although patients with other syndromes now known to be https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 10/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate malignant may have been included (eg, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy). Alternatively, a tachycardia-induced cardiomyopathy may have predisposed patients to additional arrhythmias. (See "Arrhythmia-induced cardiomyopathy".) Malignant variant More recent studies in which these other syndromes were unlikely have identified a malignant variant of RMVT. Polymorphic VT and VF, which are malignant arrhythmias, have been demonstrated in patients with RMVT [61,62]. In one series, three patients with RMVT later developed VF. In these patients, PVCs were more closely coupled to prior beats than is usual for RMVT [61]. It was postulated that relatively early triggered beats occurred in a vulnerable period during repolarization, resulting in VF. In a subsequent report, 16 patients with frequent PVCs from the RVOT were noted to have polymorphic VT or VF that was initiated by one of the PVCs [62]. In contrast to the first study, the coupling interval of the PVCs in patients who developed malignant arrhythmias was not different from that in 85 other patients with RMVT who did not have malignant arrhythmias. Radiofrequency (RF) ablation successfully eliminated the RVOT PVCs in 13 patients and modified the PVCs in the other three. Over a mean follow-up of 54 months, none had recurrent VF or syncope. (See 'Radiofrequency ablation' below.) The prevalence of this malignant variant, and whether it represents a distinct disorder from RMVT, is unclear. The high frequency in the above study (16 of 101 patients) is probably a substantial overestimate due to referral bias. In addition, it is possible that some cases categorized as polymorphic VT were simply the common form of RVOT VT in which QRS morphology varied during the tachycardia due to fluctuations in loading conditions. An editorial accompanying this report addressed the issue of whether RF ablation should now be considered in all patients with RMVT [63]. Due to the relatively high prevalence of RVOT PVCs, the rarity of malignant RVOT VT/VF, it is reasonable to focus concern on patients with the following higher risk characteristics: A history of syncope Very fast VT (>230 beats/min) Very frequent ectopy (>20,000 PVCs/day) PVCs with a short coupling interval Treatment of RMVT Therapeutic decisions for RMVT should consider that many patients are young and otherwise healthy. As a result, ablative therapy may be preferable to chronic administration of antiarrhythmic drugs. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 11/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Medical therapy Medical therapy serves two roles in RMVT: termination of the arrhythmia; and prevention of recurrence. RMVT can be terminated with adenosine and beta blockers, all of which interfere with the cAMP-mediated slow inward calcium current [29,40,56-58]. For prevention of recurrence, beta blockers are often used as first-line agents. These drugs are attractive since their side effect profiles are mild in comparison with antiarrhythmic agents [64]. Propranolol has prevented recurrence in as many as 14 of 22 patients with a typical RVOT origin of RMVT [6,65]. However, other studies have found that these agents were much less likely to prevent recurrent RMVT, although the combination of a beta blocker with a class I drug may be useful [9,55]. Class I antiarrhythmic agents ( table 2) alone are helpful in some patients. However, class III drugs (sotalol and amiodarone) may be preferred, especially in patients with arrhythmia that is refractory to other drugs [9]. Radiofrequency ablation Due to the limited efficacy and potential side effects of antiarrhythmic drugs, there has been increasing use of radiofrequency (RF) ablation in patients with symptomatic RMVT. Professional society guidelines for the management of ventricular arrhythmias and the prevention of SCD indicate that there is evidence and/or general agreement supporting RF ablation in patients with symptomatic idiopathic VT that is drug-refractory, or in such patients who are intolerant of drugs or do not desire long-term drug therapy [64]. The 2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias recommended catheter ablation in the following patients with idiopathic VT and without structural heart disease [66,67]: Severely symptomatic patients with monomorphic VT. Monomorphic VT in patients in whom antiarrhythmic drugs are not effective, not tolerated, or not desired. Patients with recurrent sustained polymorphic VT and VF (electrical storm) that is refractory to antiarrhythmic therapy when there is a suspected trigger that can be targeted for ablation. Success rates for RF catheter ablation range from 80 to 100 percent [28,35,36,40,41,68]. The success rate depends in part upon the location of the focus; the success of catheter ablation for idiopathic VTs in atypical positions is generally not as high as for RVOT locations [36]. The degree of similarity of 12-lead ECG waveforms between VT and a pace map can be used to estimate the https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 12/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate likelihood of successful ablation at that site [69]. A mean absolute deviation >12 percent suggests sufficient dissimilarity to dissuade ablation at that site. Although successful ablation of LVOT tachycardia has been performed using an endocardial approach, coronary venous mapping and percutaneous approaches to the pericardial space have shown that some of these VTs arise from the LV epicardium [28,45,46,68,70]. There have also been several reports of successful ablation of RMVT from the left and right sinuses of Valsalva [43]. Radiofrequency ablation is generally associated with a low rate of procedural complications [28,35-38,40]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Long term follow-up of patients successfully treated with radiofrequency catheter ablation is limited. In two reports of 42 patients in whom all tachycardias were successfully ablated, only five (12 percent) had a detected recurrence during a 2 to 50 month follow-up [68,71]. The likelihood of successful ablation may be less when the site of origin is not endocardial or not definitively identified during mapping [68]. In a review of 75 patients with presumed RVOT VT, the inability to identify a focus, and therefore the success rate, correlated with the QRS duration in lead V2 [72]. The success rate was 95 percent when the QRS duration in V2 during pace mapping was 160 ms in duration compared with only 54 percent when the QRS duration was <160 ms. Left-sided and epicardial ablation strategies were not pursued in this experience. Epicardial ablation A possible explanation for failed radiofrequency ablation is that the arrhythmia arises from an epicardial rather than an endocardial focus. In one report of failed ablation (either acute failure of the procedure or late recurrence of arrhythmia) in 30 patients with VT (15 with apparently normal hearts), subxiphoid instrumentation of the pericardial space was used for both epicardial mapping and ablation [70]. Twenty-four of the VTs appeared to originate from the epicardium; 17 were successfully ablated, while the other seven had sites that were inaccessible primarily due to interference from the left atrial appendage. Six of these seven patients could be ablated from the left coronary cusp. PAROXYSMAL SUSTAINED VT Paroxysmal sustained VT is another clinical syndrome of idiopathic right ventricular tachycardia that resembles RMVT in many ways [6,9,13,73]. The most frequent QRS morphology is a left bundle branch block with an inferior axis, and the typical site of origin is the superior septal aspect of the RVOT. Furthermore, patients with paroxysmal sustained VT appear to respond to https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 13/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate antiarrhythmic agents, particularly adenosine, in a manner similar to patients with RMVT, although data are limited [73]. Because of these similarities, it is not clear if paroxysmal sustained VT is a distinct clinical syndrome. Compared with nonsustained RMVT, this disorder is more often symptomatic and less often exercise-provoked. It is also more frequently induced by programmed stimulation, although isoproterenol may facilitate induction in some cases. On the other hand, some investigators dispute the existence of paroxysmal sustained VT as a syndrome distinct from RMVT. One study, for example, found that 58 percent of patients with RMVT had at least one episode of sustained VT [9]. In addition, electrophysiologic studies may reproduce sustained VT in patients who present with only nonsustained VT (particularly during isoproterenol infusion) or vice versa. It has also been suggested that the incidence of sudden cardiac death in RMVT is actually due to overlap with paroxysmal sustained VT. For these reasons, the two syndromes are occasionally considered together as idiopathic right ventricular tachycardia, or simply as RMVT. IDIOPATHIC LEFT VENTRICULAR TACHYCARDIA Idiopathic left ventricular tachycardia (ILVT) was first described in 1979 [74]. Belhassen was the first to report the characteristic termination of this VT with intravenous verapamil [75], accounting for its two descriptive eponyms: Belhassen VT and verapamil-responsive VT. Clinical features The typical patient with ILVT presents at age 20 to 40, but often reports symptomatic episodes dating back to adolescence. The clinical characteristics of ILVT appear to be more uniform than those of the idiopathic RV tachycardias [10,75-80]. It has a more variable association with physical activity, and is not usually provoked by exercise. It frequently produces symptoms such as palpitations and presyncope; syncope is uncommon. Cardiac arrest is rare, but isolated cases have been reported [78]. Tachycardia-related cardiomyopathy has been reported, but is unusual since episodes are typically infrequent. Site of origin Endocardial mapping during the VT demonstrates that the site of earliest activation is the inferoseptal region of the left ventricle in patients with a left frontal axis [10]. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 14/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Mapping for catheter ablation also consistently localizes this VT to the inferior aspect of the midseptal region [81]. By comparison, the anterosuperior left ventricle is the initial site in those patients with VT that has a right frontal axis [10,78,82]. Electrocardiographic features Corresponding to its left ventricular origin, ILVT has a right bundle branch block morphology with a left superior frontal plane axis and a relatively narrow QRS duration (typically 0.12 to 0.14 sec) ( waveform 3). A small subset of patients with ILVT has a right frontal plane (2 of 16 in one report) [10]. ILVT is often confused with supraventricular tachycardia because of its characteristic ECG morphology, and the response to verapamil (see below). The signal averaged ECG in the time domain is usually normal during sinus rhythm. However, frequency analysis using fast Fourier transform has shown an abnormal high-frequency component of the initial portion of the QRS complex that may distinguish these patients from normals [83]. Electrophysiologic features ILVT is typically reproduced in the electrophysiology laboratory using programmed stimulation employing extrastimuli and, on occasion, with rapid atrial or ventricular pacing [10,38,74-80]. In contrast to RMVT, ILVT is not usually provoked by isoproterenol infusion. These observations, coupled with the response of ILVT to pacing (entrainment), support a reentrant mechanism [82]. Further support for a reentrant mechanism comes from several mapping studies: One report identified a mid-diastolic potential and a single fused presystolic Purkinje potential at the VT exit site during VT [84]. This observation suggests a macroreentry circuit involving the normal Purkinje system and abnormal Purkinje tissue that manifests |
ablation. Success rates for RF catheter ablation range from 80 to 100 percent [28,35,36,40,41,68]. The success rate depends in part upon the location of the focus; the success of catheter ablation for idiopathic VTs in atypical positions is generally not as high as for RVOT locations [36]. The degree of similarity of 12-lead ECG waveforms between VT and a pace map can be used to estimate the https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 12/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate likelihood of successful ablation at that site [69]. A mean absolute deviation >12 percent suggests sufficient dissimilarity to dissuade ablation at that site. Although successful ablation of LVOT tachycardia has been performed using an endocardial approach, coronary venous mapping and percutaneous approaches to the pericardial space have shown that some of these VTs arise from the LV epicardium [28,45,46,68,70]. There have also been several reports of successful ablation of RMVT from the left and right sinuses of Valsalva [43]. Radiofrequency ablation is generally associated with a low rate of procedural complications [28,35-38,40]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Long term follow-up of patients successfully treated with radiofrequency catheter ablation is limited. In two reports of 42 patients in whom all tachycardias were successfully ablated, only five (12 percent) had a detected recurrence during a 2 to 50 month follow-up [68,71]. The likelihood of successful ablation may be less when the site of origin is not endocardial or not definitively identified during mapping [68]. In a review of 75 patients with presumed RVOT VT, the inability to identify a focus, and therefore the success rate, correlated with the QRS duration in lead V2 [72]. The success rate was 95 percent when the QRS duration in V2 during pace mapping was 160 ms in duration compared with only 54 percent when the QRS duration was <160 ms. Left-sided and epicardial ablation strategies were not pursued in this experience. Epicardial ablation A possible explanation for failed radiofrequency ablation is that the arrhythmia arises from an epicardial rather than an endocardial focus. In one report of failed ablation (either acute failure of the procedure or late recurrence of arrhythmia) in 30 patients with VT (15 with apparently normal hearts), subxiphoid instrumentation of the pericardial space was used for both epicardial mapping and ablation [70]. Twenty-four of the VTs appeared to originate from the epicardium; 17 were successfully ablated, while the other seven had sites that were inaccessible primarily due to interference from the left atrial appendage. Six of these seven patients could be ablated from the left coronary cusp. PAROXYSMAL SUSTAINED VT Paroxysmal sustained VT is another clinical syndrome of idiopathic right ventricular tachycardia that resembles RMVT in many ways [6,9,13,73]. The most frequent QRS morphology is a left bundle branch block with an inferior axis, and the typical site of origin is the superior septal aspect of the RVOT. Furthermore, patients with paroxysmal sustained VT appear to respond to https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 13/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate antiarrhythmic agents, particularly adenosine, in a manner similar to patients with RMVT, although data are limited [73]. Because of these similarities, it is not clear if paroxysmal sustained VT is a distinct clinical syndrome. Compared with nonsustained RMVT, this disorder is more often symptomatic and less often exercise-provoked. It is also more frequently induced by programmed stimulation, although isoproterenol may facilitate induction in some cases. On the other hand, some investigators dispute the existence of paroxysmal sustained VT as a syndrome distinct from RMVT. One study, for example, found that 58 percent of patients with RMVT had at least one episode of sustained VT [9]. In addition, electrophysiologic studies may reproduce sustained VT in patients who present with only nonsustained VT (particularly during isoproterenol infusion) or vice versa. It has also been suggested that the incidence of sudden cardiac death in RMVT is actually due to overlap with paroxysmal sustained VT. For these reasons, the two syndromes are occasionally considered together as idiopathic right ventricular tachycardia, or simply as RMVT. IDIOPATHIC LEFT VENTRICULAR TACHYCARDIA Idiopathic left ventricular tachycardia (ILVT) was first described in 1979 [74]. Belhassen was the first to report the characteristic termination of this VT with intravenous verapamil [75], accounting for its two descriptive eponyms: Belhassen VT and verapamil-responsive VT. Clinical features The typical patient with ILVT presents at age 20 to 40, but often reports symptomatic episodes dating back to adolescence. The clinical characteristics of ILVT appear to be more uniform than those of the idiopathic RV tachycardias [10,75-80]. It has a more variable association with physical activity, and is not usually provoked by exercise. It frequently produces symptoms such as palpitations and presyncope; syncope is uncommon. Cardiac arrest is rare, but isolated cases have been reported [78]. Tachycardia-related cardiomyopathy has been reported, but is unusual since episodes are typically infrequent. Site of origin Endocardial mapping during the VT demonstrates that the site of earliest activation is the inferoseptal region of the left ventricle in patients with a left frontal axis [10]. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 14/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Mapping for catheter ablation also consistently localizes this VT to the inferior aspect of the midseptal region [81]. By comparison, the anterosuperior left ventricle is the initial site in those patients with VT that has a right frontal axis [10,78,82]. Electrocardiographic features Corresponding to its left ventricular origin, ILVT has a right bundle branch block morphology with a left superior frontal plane axis and a relatively narrow QRS duration (typically 0.12 to 0.14 sec) ( waveform 3). A small subset of patients with ILVT has a right frontal plane (2 of 16 in one report) [10]. ILVT is often confused with supraventricular tachycardia because of its characteristic ECG morphology, and the response to verapamil (see below). The signal averaged ECG in the time domain is usually normal during sinus rhythm. However, frequency analysis using fast Fourier transform has shown an abnormal high-frequency component of the initial portion of the QRS complex that may distinguish these patients from normals [83]. Electrophysiologic features ILVT is typically reproduced in the electrophysiology laboratory using programmed stimulation employing extrastimuli and, on occasion, with rapid atrial or ventricular pacing [10,38,74-80]. In contrast to RMVT, ILVT is not usually provoked by isoproterenol infusion. These observations, coupled with the response of ILVT to pacing (entrainment), support a reentrant mechanism [82]. Further support for a reentrant mechanism comes from several mapping studies: One report identified a mid-diastolic potential and a single fused presystolic Purkinje potential at the VT exit site during VT [84]. This observation suggests a macroreentry circuit involving the normal Purkinje system and abnormal Purkinje tissue that manifests decremental properties and verapamil sensitivity. A second study using electroanatomic mapping found that, during sinus rhythm, only patients with ILVT had a retrograde potential originating from the left posterior Purkinje fiber; diastolic potentials during ILVT coincided with the earliest retrograde Purkinje potential during sinus rhythm [81]. The His bundle is commonly activated early in a retrograde fashion during ILVT, and a distinct Purkinje spike typically precedes the onset of the QRS ( image 1) [76]. However, the retrograde His bundle deflection can be dissociated from the QRS complex by premature stimulation in the ventricle, atrium, or His region, implying that the reentrant circuit does not require the His bundle [78,80]. These findings also suggest that the posterior fascicle of the left bundle branch https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 15/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate may be a part of, or at least in close proximity to the VT circuit ( figure 2A-B). The terms fascicular ventricular tachycardia and fascicular tachycardia been used to describe this arrhythmia [80,85,86]. Treatment of ILVT Verapamil is usually effective in the treatment of ILVT, both for the termination of acute episodes and the prevention of recurrence [10,78-80,85]. Verapamil can be given 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. In one report, for example, intravenous verapamil terminated the arrhythmia in 13 of 14 patients and was effective in all five patients who required long-term oral therapy for symptom control [10]. By comparison, vagal maneuvers, beta blockers, and lidocaine are often ineffective. There is little reported experience with the use of other antiarrhythmic drugs; the class III agents are the most effective among those tested, while class I drugs are rarely of benefit [9]. Catheter ablation has been performed with efficacy rates of 85 to 100 percent in patients with resistant or incessant ILVT or those intolerant of medications [28,38,76,77,84,87]. Selection of ablation target sites focuses on pace mapping techniques and/or activation mapping, with particular attention to the mid-diastolic potential and/or presystolic Purkinje activation [76,84]. Electroanatomic mapping and identification of the earliest retrograde Purkinje potential can also be used for guiding ablation [81]. Reported series of catheter ablation for ILVT, although small, have demonstrated a high rate of chronic arrhythmia control and relative freedom from procedural complications [76,77,87]. In one report, for example, 17 successfully ablated patients were followed for a mean of seven months [77]. No patient had a recurrent symptomatic tachyarrhythmia, and in the six who were and underwent repeat electrophysiology study, the tachycardia could not be induced. SPORADIC POLYMORPHIC VT IN THE STRUCTURALLY NORMAL HEART Polymorphic VT may present in patients with no significant structural heart disease and no family history who do not have catecholaminergic polymorphic VT (CPVT). One study evaluated 15 such patients who presented with syncope, presyncope, or cardiac arrest [88]. The arrhythmia was induced by exercise in four and by coronary vasospasm in two. Electrophysiologic similarities may exist between rapid polymorphic VT in the normal heart and idiopathic ventricular fibrillation (VF). As an example, idiopathic VF is often initiated by a PVC with a very short coupling interval; polymorphic VT may also be preceded by a short-long-short https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 16/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate cardiac cycle. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) Prior to making this diagnosis, cardiac catheterization with coronary angiography is necessary to exclude the presence of obstructive coronary artery disease. Some individuals with sporadic disease have undergone genetic testing; some but not all of these patients have de novo mutations similar to mutations observed in patients with familial disease, and have therefore been classified as having CPVT [89-91]. Chronic therapy There are presently no consensus treatment guidelines for the management of sporadic polymorphic VT in an otherwise normal heart. Therapy may be directed by the following observations: Chronic beta blocker administration may be effective in some patients whose polymorphic VT is reproducibly initiated by an infusion of isoproterenol or by exercise, a characteristic also seen with familial disease [88]. The use of pacing, beta blockers, and calcium channel blockers alone or in combination may be effective if the arrhythmia is pause-dependent. Occasional patients with frequent uniform PVC triggering recurrent polymorphic VT or VF may be treated by catheter ablation of the PVCs when other methods fail. However, an implantable cardioverter-defibrillator (ICD) is often the treatment of choice because patients with polymorphic VT and minimal or no structural heart disease are at risk for sudden death, and respond erratically to antiarrhythmic drugs [88,92]. Similar recommendations apply to patients with idiopathic VF. Pharmacologic or ablative therapy remains necessary in addition to the ICD for suppression of frequent arrhythmias (that result in ICD shocks). (See "Early repolarization".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Catheter ablation of arrhythmias".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 17/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Catheter ablation for the heart (The Basics)") Beyond the Basics topic (see "Patient education: Catheter ablation for abnormal heartbeats (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Malignant ventricular arrhythmias usually occur in the presence of significant structural heart disease. Less commonly, ventricular tachycardia (VT) and ventricular fibrillation (VF) occur in hearts that appear normal but in fact, contain less visible abnormalities including derangements of cardiac ion channels or structural proteins. Idiopathic VT syndromes, including repetitive monomorphic VT, paroxysmal sustained VT, and idiopathic left ventricular tachycardia, occur in structurally normal hearts and have a more benign prognosis. (See 'Introduction' above.) Idiopathic VT syndromes account for approximately 10 percent all patients referred for evaluation of VT, with the mean age of patients with an idiopathic VT being less than that of patients with VT secondary to underlying heart disease. Distinguishing an idiopathic VT syndrome from other monomorphic VT syndromes is important given the far better prognosis, greater array of antiarrhythmic drug options, and amenability to cure with ablation. (See 'Idiopathic VT' above.) The diagnostic evaluation to establish the presence and type of heart disease in patients with sustained VT generally includes various invasive and noninvasive techniques, depending in part upon the clinical history and presentation. These include electrocardiography (ECG), echocardiography, exercise treadmill testing, signal averaged https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 18/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate ECG, coronary angiography, endomyocardial biopsy, or magnetic resonance imaging. (See 'General approach' above and "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation", section on 'Additional diagnostic evaluation'.) Repetitive monomorphic VT (RMVT), also called right ventricular outflow tract (RVOT) VT, is a triggered arrhythmia that is characterized by frequent short "salvos" of nonsustained VT. The most common symptoms associated with RMVT are palpitations and lightheadedness, typically occurring during or immediately after exercise or emotional stress, although a significant proportion of patients are asymptomatic. Most RMVT episodes have a characteristic ECG appearance with left bundle branch block appearance and an inferior axis. (See 'Repetitive monomorphic VT' above.) Treatment decisions for RMVT should consider that many patients are young and otherwise healthy, and as a result, ablative therapy may be preferable to chronic administration of antiarrhythmic drugs. RMVT can be terminated with adenosine, verapamil, and beta blockers, with beta blockers also often used as first-line agents to prevent recurrence. While class I and III antiarrhythmic drugs are effective in many patients, catheter ablation is frequently preferred given its high success rate and low rate of associated complications. (See 'Treatment of RMVT' above.) Paroxysmal sustained VT is another clinical syndrome of idiopathic VT that resembles RMVT in many ways. The QRS morphology on ECG is frequently a left bundle branch block pattern with an inferior axis, and patients typically respond to antiarrhythmic agents, particularly adenosine, in a manner similar to patients with RMVT. However, paroxysmal sustained VT is more often symptomatic and less often exercise-provoked than RMVT. (See 'Paroxysmal sustained VT' above.) Idiopathic left ventricular tachycardia (ILVT), also called Belhassen VT or verapamil- responsive VT, is not usually provoked by exercise and, while frequently associated with symptoms of palpitations and presyncope, is rarely associated with syncope of cardiac arrest. ILVT has a right bundle branch block morphology with a left superior frontal plane axis and a relatively narrow QRS duration (typically 0.12 to 0.14 sec). Verapamil is usually effective in the treatment of ILVT, both for the termination of acute episodes and the prevention of recurrence. Additionally, catheter ablation is highly successful in curing ILVT. (See 'Idiopathic left ventricular tachycardia' above.) ACKNOWLEDGMENT https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 19/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Brooks R, Burgess JH. Idiopathic ventricular tachycardia. A review. Medicine (Baltimore) 1988; 67:271. 2. Belhassen B, Viskin S. 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Repetitive monomorphic tachycardia from the left ventricular outflow tract: electrocardiographic patterns consistent with a left ventricular site of origin. J Am Coll Cardiol 1997; 29:1023. 27. Coumel P, LeClerq JP, Slama R. monomorphic idiopathic ventricular tachycardia. In: Cardiac E lectrophysiology and Arrhythmias, Zipes DP, Jalife J (Eds), Grune and Stratton, Orlando 1985. p.455. 28. Coggins DL, Lee RJ, Sweeney J, et al. Radiofrequency catheter ablation as a cure for idiopathic tachycardia of both left and right ventricular origin. J Am Coll Cardiol 1994; 23:1333. 29. Lerman BB, Stein K, Engelstein ED, et al. Mechanism of repetitive monomorphic ventricular tachycardia. Circulation 1995; 92:421. 30. Kim RJ, Iwai S, Markowitz SM, et al. Clinical and electrophysiological spectrum of idiopathic ventricular outflow tract arrhythmias. J Am Coll Cardiol 2007; 49:2035. 31. Hayashi H, Fujiki A, Tani M, et al. Circadian variation of idiopathic ventricular tachycardia originating from right ventricular outflow tract. Am J Cardiol 1999; 84:99. 32. Mitrani RD, Klein LS, Miles WM, et al. Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease. J Am Coll Cardiol 1993; 22:1344. 33. Sch fers M, Lerch H, Wichter T, et al. Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia. J Am Coll Cardiol 1998; 32:181. 34. Marchlinski FE, Deely MP, Zado ES. Sex-specific triggers for right ventricular outflow tract tachycardia. Am Heart J 2000; 139:1009. 35. Klein LS, Shih HT, Hackett FK, et al. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease. Circulation 1992; 85:1666. 36. Calkins H, Kalbfleisch SJ, el-Atassi R, et al. Relation between efficacy of radiofrequency catheter ablation and site of origin of idiopathic ventricular tachycardia. Am J Cardiol 1993; 71:827. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 22/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 37. Movsowitz C, Schwartzman D, Callans DJ, et al. Idiopathic right ventricular outflow tract tachycardia: narrowing the anatomic location for successful ablation. Am Heart J 1996; 131:930. 38. Klein LS, Miles WM. Ablative therapy for ventricular arrhythmias. Prog Cardiovasc Dis 1995; 37:225. 39. Jadonath RL, Schwartzman DS, Preminger MW, et al. Utility of the 12-lead electrocardiogram in localizing the origin of right ventricular outflow tract tachycardia. Am Heart J 1995; 130:1107. 40. Wilber DJ, Baerman J, Olshansky B, et al. Adenosine-sensitive ventricular tachycardia. Clinical characteristics and response to catheter ablation. Circulation 1993; 87:126. 41. Timmermans C, Rodriguez LM, Crijns HJ, et al. Idiopathic left bundle-branch block-shaped ventricular tachycardia may originate above the pulmonary valve. Circulation 2003; 108:1960. 42. Sekiguchi Y, Aonuma K, Takahashi A, et al. Electrocardiographic and electrophysiologic characteristics of ventricular tachycardia originating within the pulmonary artery. J Am Coll Cardiol 2005; 45:887. 43. Kanagaratnam L, Tomassoni G, Schweikert R, et al. Ventricular tachycardias arising from the aortic sinus of valsalva: an under-recognized variant of left outflow tract ventricular tachycardia. J Am Coll Cardiol 2001; 37:1408. 44. Ouyang F, Fotuhi P, Ho SY, et al. Repetitive monomorphic ventricular tachycardia originating from the aortic sinus cusp: electrocardiographic characterization for guiding catheter ablation. J Am Coll Cardiol 2002; 39:500. 45. Frey B, Kreiner G, Fritsch S, et al. Successful treatment of idiopathic left ventricular outflow tract tachycardia by catheter ablation or minimally invasive surgical cryoablation. Pacing Clin Electrophysiol 2000; 23:870. 46. Stellbrink C, Diem B, Schauerte P, et al. Transcoronary venous radiofrequency catheter ablation of ventricular tachycardia. J Cardiovasc Electrophysiol 1997; 8:916. 47. Tada H, Ito S, Naito S, et al. Idiopathic ventricular arrhythmia arising from the mitral annulus: a distinct subgroup of idiopathic ventricular arrhythmias. J Am Coll Cardiol 2005; 45:877. 48. Yamada T, Murakami Y, Yoshida N, et al. Preferential conduction across the ventricular outflow septum in ventricular arrhythmias originating from the aortic sinus cusp. J Am Coll Cardiol 2007; 50:884. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 23/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 49. Yokokawa M, Good E, Desjardins B, et al. Predictors of successful catheter ablation of ventricular arrhythmias arising from the papillary muscles. Heart Rhythm 2010; 7:1654. 50. Gill JS, Prasad K, Blaszyk K, et al. Initiating sequences in exercise induced idiopathic ventricular tachycardia of left bundle branch-like morphology. Pacing Clin Electrophysiol 1998; 21:1873. 51. Dixit S, Gerstenfeld EP, Callans DJ, Marchlinski FE. Electrocardiographic patterns of superior right ventricular outflow tract tachycardias: distinguishing septal and free-wall sites of origin. J Cardiovasc Electrophysiol 2003; 14:1. 52. Callans DJ, Schwartzman D, Gottlieb CD, Marchlinski FE. Insights into the electrophysiology of ventricular tachycardia gained by the catheter ablation experience: "learning while burning". J Cardiovasc Electrophysiol 1994; 5:877. 53. Marcus FI, Fontaine GH, Guiraudon G, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation 1982; 65:384. 54. Blomstr m-Lundqvist C, Sabel KG, Olsson SB. A long term follow up of 15 patients with arrhythmogenic right ventricular dysplasia. Br Heart J 1987; 58:477. 55. Ritchie AH, Kerr CR, Qi A, Yeung-Lai-Wah JA. Nonsustained ventricular tachycardia arising from the right ventricular outflow tract. Am J Cardiol 1989; 64:594. 56. Lerman BB, Belardinelli L, West GA, et al. Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity. Circulation 1986; 74:270. 57. Sung RJ, Shapiro WA, Shen EN, et al. Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity. J Clin Invest 1983; 72:350. 58. Sung RJ, Keung EC, Nguyen NX, Huycke EC. Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias. J Clin Invest 1988; 81:688. 59. Farzaneh-Far A, Lerman BB. Idiopathic ventricular outflow tract tachycardia. Heart 2005; 91:136. 60. Lerman BB, Dong B, Stein KM, et al. Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2. J Clin Invest 1998; 101:2862. 61. Viskin S, Rosso R, Rogowski O, Belhassen B. The "short-coupled" variant of right ventricular outflow ventricular tachycardia: a not-so-benign form of benign ventricular tachycardia? J Cardiovasc Electrophysiol 2005; 16:912. 62. Noda T, Shimizu W, Taguchi A, et al. Malignant entity of idiopathic ventricular fibrillation and polymorphic ventricular tachycardia initiated by premature extrasystoles originating from the right ventricular outflow tract. J Am Coll Cardiol 2005; 46:1288. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 24/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 63. Viskin S, Antzelevitch C. The cardiologists' worst nightmare sudden death from "benign" ventricular arrhythmias. J Am Coll Cardiol 2005; 46:1295. 64. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 65. Gill JS, Blaszyk K, Ward DE, Camm AJ. Verapamil for the suppression of idiopathic ventricular tachycardia of left bundle branch block-like morphology. Am Heart J 1993; 126:1126. 66. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace 2009; 11:771. 67. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17:e2. 68. Rodriguez LM, Smeets JL, Timmermans C, Wellens HJ. Predictors for successful ablation of right- and left-sided idiopathic ventricular tachycardia. Am J Cardiol 1997; 79:309. 69. Gerstenfeld EP, Dixit S, Callans DJ, et al. Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia. J Am Coll Cardiol 2003; 41:2046. 70. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation 2003; 108:1329. 71. Chinushi M, Aizawa Y, Takahashi K, et al. Radiofrequency catheter ablation for idiopathic right ventricular tachycardia with special reference to morphological variation and long- term outcome. Heart 1997; 78:255. 72. Flemming MA, Oral H, Kim MH, et al. Electrocardiographic predictors of successful ablation of tachycardia or bigeminy arising in the right ventricular outflow tract. Am J Cardiol 1999; 84:1266. 73. Lerman BB, Stein KM, Markowitz SM. Idiopathic right ventricular outflow tract tachycardia: a clinical approach. Pacing Clin Electrophysiol 1996; 19:2120. 74. Zipes DP, Foster PR, Troup PJ, Pedersen DH. Atrial induction of ventricular tachycardia: reentry versus triggered automaticity. Am J Cardiol 1979; 44:1. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 25/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 75. Belhassen B, Rotmensch HH, Laniado S. Response of recurrent sustained ventricular tachycardia to verapamil. Br Heart J 1981; 46:679. 76. Nakagawa H, Beckman KJ, McClelland JH, et al. Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential. Circulation 1993; 88:2607. 77. Wen MS, Yeh SJ, Wang CC, et al. Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease. Circulation 1994; 89:1690. 78. German LD, Packer DL, Bardy GH, Gallagher JJ. Ventricular tachycardia induced by atrial stimulation in patients without symptomatic cardiac disease. Am J Cardiol 1983; 52:1202. 79. Klein GJ, Millman PJ, Yee R. Recurrent ventricular tachycardia responsive to verapamil. Pacing Clin Electrophysiol 1984; 7:938. 80. Ward DE, Nathan AW, Camm AJ. Fascicular tachycardia sensitive to calcium antagonists. Eur Heart J 1984; 5:896. 81. Ouyang F, Cappato R, Ernst S, et al. Electroanatomic substrate of idiopathic left ventricular tachycardia: unidirectional block and macroreentry within the purkinje network. Circulation 2002; 105:462. 82. Okumura K, Matsuyama K, Miyagi H, et al. Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for reentry with an area of slow conduction and effect of verapamil. Am J Cardiol 1988; 62:727. 83. Kinoshita O, Kamakura S, Ohe T, et al. Spectral analysis of signal-averaged electrocardiograms in patients with idiopathic ventricular tachycardia of left ventricular origin. Circulation 1992; 85:2054. 84. Nogami A, Naito S, Tada H, et al. Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia. J Am Coll Cardiol 2000; 36:811. 85. Nogami A, Naito S, Tada H, et al. Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients. J Cardiovasc Electrophysiol 1998; 9:1269. 86. Francis J, Venugopal K, Khadar SA, et al. Idiopathic fascicular ventricular tachycardia. Indian Pacing Electrophysiol J 2004; 4:98. 87. Gupta AK, Kumar AV, Lokhandwala YY, et al. Primary radiofrequency ablation for incessant idiopathic ventricular tachycardia. Pacing Clin Electrophysiol 2002; 25:1555. 88. Eisenberg SJ, Scheinman MM, Dullet NK, et al. Sudden cardiac death and polymorphous ventricular tachycardia in patients with normal QT intervals and normal systolic cardiac https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 26/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate function. Am J Cardiol 1995; 75:687. 89. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 90. Wilde AA, Bhuiyan ZA, Crotti L, et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N Engl J Med 2008; 358:2024. 91. Tan JH, Scheinman MM. Exercise-induced polymorphic ventricular tachycardia in adults without structural heart disease. Am J Cardiol 2008; 101:1142. 92. Meissner MD, Lehmann MH, Steinman RT, et al. Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter- defibrillator therapy. J Am Coll Cardiol 1993; 21:1406. Topic 965 Version 31.0 |
evidence suggesting cyclic AMP-mediated triggered activity. Circulation 1986; 74:270. 57. Sung RJ, Shapiro WA, Shen EN, et al. Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity. J Clin Invest 1983; 72:350. 58. Sung RJ, Keung EC, Nguyen NX, Huycke EC. Effects of beta-adrenergic blockade on verapamil-responsive and verapamil-irresponsive sustained ventricular tachycardias. J Clin Invest 1988; 81:688. 59. Farzaneh-Far A, Lerman BB. Idiopathic ventricular outflow tract tachycardia. Heart 2005; 91:136. 60. Lerman BB, Dong B, Stein KM, et al. Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2. J Clin Invest 1998; 101:2862. 61. Viskin S, Rosso R, Rogowski O, Belhassen B. The "short-coupled" variant of right ventricular outflow ventricular tachycardia: a not-so-benign form of benign ventricular tachycardia? J Cardiovasc Electrophysiol 2005; 16:912. 62. Noda T, Shimizu W, Taguchi A, et al. Malignant entity of idiopathic ventricular fibrillation and polymorphic ventricular tachycardia initiated by premature extrasystoles originating from the right ventricular outflow tract. J Am Coll Cardiol 2005; 46:1288. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 24/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 63. Viskin S, Antzelevitch C. The cardiologists' worst nightmare sudden death from "benign" ventricular arrhythmias. J Am Coll Cardiol 2005; 46:1295. 64. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 65. Gill JS, Blaszyk K, Ward DE, Camm AJ. Verapamil for the suppression of idiopathic ventricular tachycardia of left bundle branch block-like morphology. Am Heart J 1993; 126:1126. 66. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Europace 2009; 11:771. 67. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020; 17:e2. 68. Rodriguez LM, Smeets JL, Timmermans C, Wellens HJ. Predictors for successful ablation of right- and left-sided idiopathic ventricular tachycardia. Am J Cardiol 1997; 79:309. 69. Gerstenfeld EP, Dixit S, Callans DJ, et al. Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia. J Am Coll Cardiol 2003; 41:2046. 70. Schweikert RA, Saliba WI, Tomassoni G, et al. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation 2003; 108:1329. 71. Chinushi M, Aizawa Y, Takahashi K, et al. Radiofrequency catheter ablation for idiopathic right ventricular tachycardia with special reference to morphological variation and long- term outcome. Heart 1997; 78:255. 72. Flemming MA, Oral H, Kim MH, et al. Electrocardiographic predictors of successful ablation of tachycardia or bigeminy arising in the right ventricular outflow tract. Am J Cardiol 1999; 84:1266. 73. Lerman BB, Stein KM, Markowitz SM. Idiopathic right ventricular outflow tract tachycardia: a clinical approach. Pacing Clin Electrophysiol 1996; 19:2120. 74. Zipes DP, Foster PR, Troup PJ, Pedersen DH. Atrial induction of ventricular tachycardia: reentry versus triggered automaticity. Am J Cardiol 1979; 44:1. https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 25/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 75. Belhassen B, Rotmensch HH, Laniado S. Response of recurrent sustained ventricular tachycardia to verapamil. Br Heart J 1981; 46:679. 76. Nakagawa H, Beckman KJ, McClelland JH, et al. Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential. Circulation 1993; 88:2607. 77. Wen MS, Yeh SJ, Wang CC, et al. Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease. Circulation 1994; 89:1690. 78. German LD, Packer DL, Bardy GH, Gallagher JJ. Ventricular tachycardia induced by atrial stimulation in patients without symptomatic cardiac disease. Am J Cardiol 1983; 52:1202. 79. Klein GJ, Millman PJ, Yee R. Recurrent ventricular tachycardia responsive to verapamil. Pacing Clin Electrophysiol 1984; 7:938. 80. Ward DE, Nathan AW, Camm AJ. Fascicular tachycardia sensitive to calcium antagonists. Eur Heart J 1984; 5:896. 81. Ouyang F, Cappato R, Ernst S, et al. Electroanatomic substrate of idiopathic left ventricular tachycardia: unidirectional block and macroreentry within the purkinje network. Circulation 2002; 105:462. 82. Okumura K, Matsuyama K, Miyagi H, et al. Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for reentry with an area of slow conduction and effect of verapamil. Am J Cardiol 1988; 62:727. 83. Kinoshita O, Kamakura S, Ohe T, et al. Spectral analysis of signal-averaged electrocardiograms in patients with idiopathic ventricular tachycardia of left ventricular origin. Circulation 1992; 85:2054. 84. Nogami A, Naito S, Tada H, et al. Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia. J Am Coll Cardiol 2000; 36:811. 85. Nogami A, Naito S, Tada H, et al. Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients. J Cardiovasc Electrophysiol 1998; 9:1269. 86. Francis J, Venugopal K, Khadar SA, et al. Idiopathic fascicular ventricular tachycardia. Indian Pacing Electrophysiol J 2004; 4:98. 87. Gupta AK, Kumar AV, Lokhandwala YY, et al. Primary radiofrequency ablation for incessant idiopathic ventricular tachycardia. Pacing Clin Electrophysiol 2002; 25:1555. 88. Eisenberg SJ, Scheinman MM, Dullet NK, et al. Sudden cardiac death and polymorphous ventricular tachycardia in patients with normal QT intervals and normal systolic cardiac https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 26/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate function. Am J Cardiol 1995; 75:687. 89. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69. 90. Wilde AA, Bhuiyan ZA, Crotti L, et al. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N Engl J Med 2008; 358:2024. 91. Tan JH, Scheinman MM. Exercise-induced polymorphic ventricular tachycardia in adults without structural heart disease. Am J Cardiol 2008; 101:1142. 92. Meissner MD, Lehmann MH, Steinman RT, et al. Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter- defibrillator therapy. J Am Coll Cardiol 1993; 21:1406. Topic 965 Version 31.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 27/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate GRAPHICS Criteria for the diagnosis of arrhythmogenic right ventricular dysplasia Family history Major Familial disease confirmed at necropsy or surgery Minor Family history of premature sudden death (<35 years) caused by suspected ARVD Family history (clinical diagnosis based on present criteria) ECG depolarization/conduction abnormalities Major Epsilon waves or localized prolongation (>110 ms) of the QRS complex in the right precordial leads (V1 to V3) Minor Late potentials seen on signal averaged ECG Repolarization abnormalities Minor Inverted T waves in right precordial leads (V2 and V3) in people >12 years and in the absence of right bundle branch block Tissue characterisation of walls Major Fibrofatty replacement of myocardium on endomyocardial biopsy Global and/or regional dysfunction and structural alterations (detected by echocardiography, angiography, magnetic resonance imaging, or radionuclide scintigraphy) Major Severe dilatation and reduction of right ventricular ejection fraction with no (or only mild) left ventricular impairment Localized right ventricular aneurysms (akinetic or dyskinetic areas with diastolic bulging) Severe segmental dilatation of the right ventricle Minor https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 28/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Mild global right ventricular dilatation and/or ejection fraction reduction with normal left ventricle Mild segmental dilatation of the right ventricle Regional right ventricular hypokinesia Arrhythmias Minor Left bundle branch block type ventricular tachycardia (sustained or nonsustained) documented on ECG, Holter monitoring, or during exercise testing Frequent ventricular extrasystoles (more than 1000/24 h) on Holter monitoring ARVD: arrhythmogenic right ventricular dysplasia; ECG: electrocardiogram. Data from: McKenna WJ, Thiene G, Nava A, et al. Br Heart J 1994; 71:215. Graphic 54842 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 29/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Telemetry recording (lead II) from a patient with RMVT Repetitive monomorphic ventricular tachycardia (RMVT) is characterized by frequent short "salvos" or bursts of monomorphic nonsustained VT. The bursts may vary in duration, but all demonstrate the same QRS morphology. Graphic 66679 Version 2.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 30/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Nine site mapping schema for RVOT tachycardia The septal aspect of the right ventricular outflow tract (RVOT) is depicted as seen in the 30 RAO view, divided into posterior (1, 4, and 7), intermediate (2, 5, and 8), and anterior (3, 6, and 9) sites. Pacing from posterior sites (1 and 7) results in a dominant R wave in lead I, and frequently in a small R wave before a dominant S wave in lead aVL. Pacing from anterior sites (3 and 9) always produces an initial Q wave (QS, Qr, or qR) in lead I, and a QS complex in a VL. Early precordial R wave transition (R/S >1 in V1, V2, or V3) is observed during pacing from posterior and superior sites. Moving diagonally from superior-posterior to inferior-anterior results in progressive delay in the precordial R wave transition. Redrawn with permission from: Callans DJ. J Cardiovasc Electrophysiol 1994; 5:880. Futura Publishing Company. Graphic 72301 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 31/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 12-lead electrocardiogram (ECG) recorded in a patient with repetitive monomorphic ventricular tachycardia (RMVT) arising from the left ventricular outflow tract (LVOT) This electrocardiogram (ECG) illustrates repetitive monomorphic ventricular tachycardia (RMVT) with a right bundle, inferior axis morphology signifying its left ventricular site of origin. This VT was localized to the area of the aorto-mitral continuity in the left ventricular outflow tract (LVOT). Graphic 81690 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 32/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 33/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 34/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate 12-lead electrocardiogram (ECG) showing idiopathic left ventricular tachycardia The typical ECG features of an idiopathic left ventricular tachycardia are QRS complexes that are relatively narrow (0.12 sec) and have a right bundle branch morphology (tall R waves in V1 and V2 and a terminal S wave in V5 and V6); the frontal plane axis is extremely leftward (negative QRS complexes in leads II, III, and aVF), suggesting a left anterior fascicular block. The tachycardia was localized to the inferior apical left ventricular septum, accounting for the extreme leftward axis. Graphic 64279 Version 4.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 35/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Electrophysiology study (EPS) tracing of idiopathic left ventricular tachycardia Idiopathic LV tachycardia originates from the inferior portion of the ventricular septum. Surface leads (I, II, III, V1, and V6), and intracardiac recordings from the high right atrium (HRA), His bundle region (HBE), right ventricular apex (RVA), right ventricular outflow tract (RVOT), and several recordings from the left ventricle at the site of successful ablation (LV fixed, LV var, LV bipol, LV uni) are shown. The presence of a sharp potential in the LV recordings (arrow) is consistent with local activation of the Purkinje system. This potential precedes the onset of the QRS during ventricular tachycardia (VT) by 40 msec. Reprinted with permission of Futura Publishing Company. Graphic 51420 Version 4.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 36/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Noncontact endocardial map during sinus rhythm The sequence of isopotential maps of the left ventricular endocardium (purple) is modeled to the ventricular chamber dimensions. The location of the multielectrode array is represented by the orange ellipsoid. Surface ECG lead I and selected virtual electrograms from a line following fascicular activation are shown beneath each map. Initial activation (arrow, panel A) occurs in the upper part of the fascicles and then progresses toward the apex (arrow, panel B). At the apex, fascicular activation initiates ventricular activation (white area, panel C). Data from: Peters NS, Jackman WM, Schilling RJ, et al. Circulation 1997; 95:1658. Graphic 68778 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 37/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Noncontact endocardial map of fascicular tachycardia During tachycardia, the fascicular activation sequence is altered; panel A shows that activation begins near the left ventricular apex (red arrow) and panel B shows that activation (red arrow) propagates toward His bundle (white arrow). This rapid retrograde fascicular activation is closely followed by ventricular activation, seen as a white area in panel C. The relative delay in right ventricular activation produces a QRS complex with right bundle branch block pattern in ECG lead I. With permission from: Peters NS, Jackman WM, Schilling RJ, et al. Circulation 1997; 95:1658. Graphic 76252 Version 3.0 https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 38/39 7/6/23, 3:40 PM Ventricular tachycardia in the absence of apparent structural heart disease - UpToDate Contributor Disclosures David J Callans, MD Consultant/Advisory Boards: Abbott [Catheter ablation, leadless pacing, clinical events committee member for Nanosense trial]; Biosense Webster [Catheter ablation]; Boston Scientific [Catheter ablation, directing fellows programs]; Medtronic [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/ventricular-tachycardia-in-the-absence-of-apparent-structural-heart-disease/print 39/39 |
7/6/23, 3:39 PM Wearable cardioverter-defibrillator - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wearable cardioverter-defibrillator : Mina K Chung, MD : Richard L Page, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 22, 2023. INTRODUCTION The implantable cardioverter-defibrillator (ICD) has been shown to improve survival from sudden cardiac arrest and to improve overall survival in several populations at high risk for sudden cardiac death (SCD). However, there remain situations in which implantation of an ICD is immediately not feasible (eg, patients with an active infection), may be of uncertain benefit, may not be covered by third-party payers (eg, early post-myocardial infarction, patients with limited life expectancy or new onset systolic heart failure), or when an ICD must be removed (eg, infection). In cases where ICD implantation must be deferred, a wearable cardioverter-defibrillator (WCD) offers an alternative approach for the prevention of SCD. The WCD (LifeVest [Zoll Medical Corporation] or Assure [Kestra Medical Technologies, Inc]) is an external device capable of automatic detection and defibrillation of ventricular tachycardia and ventricular fibrillation ( picture 1 and figure 1). While the WCD can be worn for years, typically the device is used for several months as temporary protection against SCD. The indications, efficacy, and limitations of the wearable cardioverter-defibrillator will be discussed here. Detailed discussions of the roles of the ICD are presented separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 1/28 7/6/23, 3:39 PM Wearable cardioverter-defibrillator - UpToDate DESCRIPTION AND FUNCTIONS OF THE WCD The WCD is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) [1]. The approved devices do not have pacing capabilities and therefore are unable to provide therapy for bradycardic events or antitachycardic pacing. Wearing the WCD The WCD is composed of dry, nonadhesive monitoring electrodes, defibrillation electrodes incorporated into a chest strap or vest assembly, and a defibrillation battery and monitor unit ( picture 1). The Assure WCD garment has two styles designed for female and male body habitus and different sizes. The monitoring electrodes are positioned circumferentially around the chest and provide two to four surface electrocardiogram (ECG) leads. The defibrillation electrodes are positioned in a vest assembly for apex-posterior defibrillation. Proper fitting is required to achieve adequate skin contact to avoid noise and frequent alarms. Detection and delivery of shocks Arrhythmia detection by the WCD is programmed using ECG rate and morphology criteria. The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline electrocardiographic template. Typical programming is reflected in default device settings: VT detection 150 beats per minute (LifeVest) or 170 beats per minute (Assure). Programmable ranges for LifeVest are 120 to 250 beats per minute, not to exceed the VF detection rate; for Assure they are, 130 to the programmed VF threshold minus 10 beats per minute. VF detection 200 beats per minute. Programmable ranges are 120 to 250 beats per minute (LifeVest) or 180 to 220 beats per minute (Assure). Treatment with 150 joules (LifeVest) or 170 joules (Assure) shocks for up to five shocks. For the Zoll LifeVest WCD, the tachycardia detection rate is programmable for VF between 120 and 250 beats per minute, and the VF shock delay can be programmed from 25 to 55 seconds. The VT detection rate is programmable between 120 bpm to the VF setting with a VT shock delay https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 2/28 7/6/23, 3:39 PM Wearable cardioverter-defibrillator - UpToDate of 60 to 180 seconds. VT signals can allow synchronized shock delivery on the R wave, but if the R wave cannot be identified, unsynchronized shocks will be delivered. For the Kestra Assure WCD, the tachycardia detection rate is programmable for VF between 180 and 220 beats per minute, and for VT detection programmable from 130 beats per minute up to the programmed VF rate: 10 beats per minute. Detection utilizes a segment-based analysis of 4.8-second segments that continuously overlap by 2.4 seconds. VF confirmation requires two out of two segments (approximately 5 seconds), and VT confirmation requires 15 out of 19 segments (approximately 45 seconds). The first and last segments must be in the programmed treatment zone. If an arrhythmia is detected, vibration and audible alarms are initiated. A flashing red light and shock icon are activated on the Assure monitor. Although shocks may be transmitted to bystanders in physical contact with the patient being shocked by a WCD, a voice cautions the patient and bystanders to the impending shock. Patients are trained to hold a pair of response buttons on the LifeVest device or press the alert button on the Assure device during these alarms to avoid receiving a shock while awake. A patient's response serves as a test of consciousness; if no response occurs and a shock is indicated, the device charges, extrudes gel from the defibrillation electrodes, and delivers up to five biphasic shocks at preprogrammed energy levels (ranging from 75 to 150 joules for the LifeVest device and 170 joules for the Assure device). The LifeVest device includes a default sleep time from 11 PM to 6 AM, programmable in one-hour increments, which allows additional time for deep sleepers, if they awaken, to abort shocks. Efficacy in terminating VT/VF Shock efficacy with the WCD appears to be similar to that reported with implantable cardioverter-defibrillators (ICDs). However, sudden cardiac death may still occur in those not wearing the device, those with improper positioning of the device, due to bystander interference, due to the inability of the WCD to detect the ECG signal, or due to bradyarrhythmias. These results highlight the importance of patient education and promotion of compliance while using the WCD. The efficacy of the WCD has been tested for induced ventricular tachyarrhythmias as well as for spontaneous events during clinical trials and postmarket studies. When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in up to 100 percent of cases [1-7]. In a study of induced VT/VF in the electrophysiology laboratory, the WCD successfully detected and terminated VT/VF with 100 percent first-shock success [2]. The following large registry studies of patients with WCDs showed high shock success rates: https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 3/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In a US postmarket study of 8453 patients who wore a WCD after myocardial infarction, 146 VT/VF events occurred in 133 patients, and the overall shock success rate for terminating VT/VF was 82 percent, with 91 percent immediate survival [6]. In this study, shock success resulting in survival was 95 percent in revascularized and 84 percent in non-revascularized patients, suggesting that lower efficacy rates may be related to ischemic events. In the WEARIT-II registry of 2000 patients who wore a WCD for a median of 90 days, 120 episodes of sustained VT/VF were seen in 41 patients [7]. For 90 of the episodes, patients pressed the response buttons to abort shock delivery, with the majority of sustained VT episodes terminating spontaneously following use of the response button. All of the remaining 30 VT/VF episodes in 22 different patients were successfully terminated with a single shock. Among 6043 German patients who wore the device between April 2010 and October 2013, 94 patients were shocked for sustained VT/VF, with the WCD successfully terminating VT/VF in 88 patients (94 percent) [8]. The WCD appears equally efficacious among patients with and without myocardial ischemia immediately prior to VT/VF detection and shock (as defined by 0.1 mV ST-segment changes on ECG), with first shock termination rates of 96 percent in both groups [9]. Avoiding inappropriate shocks When electronic noise occurs, which may potentially be interpreted at VT or VF, the WCD emits a noise alarm. This electronic noise can often be minimized or eliminated by changing body position or tightening of the electrode belt, and shocks can be avoided by pushing the response buttons. While a dual-chamber ICD with an atrial lead would seemingly have greater ability to discriminate between supraventricular tachycardia (SVT) and VT, the incidence of inappropriate shocks due to atrial fibrillation, sinus tachycardia, or other supraventricular arrhythmias in clinical studies of WCDs has been low. The LifeVest WCD uses a two-channel proprietary vectorcardiogram morphology matching algorithm to prevent shocks during SVT if the QRS is unchanged, and inappropriate shocks can also be averted when the patient presses the response buttons. The Assure WCD uses a four-channel ECG with a single noise-free channel required for analysis and an algorithm that excludes noisy and low amplitude channels ( figure 2). (See 'Inappropriate shocks' below.) In a small study of the 60 patients with a permanent pacemaker, in which a variety of pacing modes (AAI, VVI, DDD) and configurations (unipolar, bipolar) were tested, unipolar DDD pacing triggered VT/VF detection in six patients (10 percent), while no other pacing modes or configurations triggered arrhythmia detection [10]. As such, patients whose pacemaker is https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 4/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate programmed to unipolar DDD pacing should be evaluated for pacemaker reprogramming to a bipolar mode prior to WCD usage. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, of 163 WCD-detected episodes, four were VT/VF and 159 were non-VT/VF with three false-positive shock alarm markers recorded, corresponding to a very low rate of inappropriate detection [11]. No ICD-recorded VT/VF episodes meeting WCD programmed criteria were missed. Median daily use was high at 23 hours. Bradycardia/asystole Neither of the approved WCDs deliver antibradycardic pacing, but they do record the ventricular rate when the heart rate decreases or asystole occurs: For the LifeVest device, asystole recordings are triggered when ventricular heart rates drop below 10 beats per minute or 16 seconds of asystole, and the device automatically records the event with 120 seconds preceding the onset. If using the secure website in conjunction with the WCD, alerts can be configured to prompt the healthcare provider that a patient is experiencing bradycardia or an asystole. For the Assure device, asystole is detected when there is no detected heart rate for >20 seconds (five of seven segments with heart rate 0 beats per minute or amplitude <100 uV); prolonged heart rates below 30 beats per minute may be detected as bradycardia. When asystole or bradycardia is detected, a loud alarm is triggered to attract bystanders and instruct them to call 911 and begin CPR if the patient is unconscious. The alert can be silenced by pressing the alert button or it resolves when a heart rate >30 bpm is detected for >30 seconds. Storage of ECGs and compliance data In addition to delivering therapeutic shocks for life- threatening ventricular arrhythmias, the WCD stores data regarding tachyarrhythmias, bradycardia/asystole (see 'Bradycardia/asystole' above), patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted via a modem to the manufacturer's network. Treatments, patient compliance, ECG records, and system performance can be viewed using a secure website. The WCD stores ECGs from arrhythmia detections, usage, and compliance trends: For the LifeVest system: The system is programmed to define ventricular arrhythmias when the ventricular heart rate exceeds a preprogrammed rate threshold with an ECG morphology that does not match a baseline ECG template. The monitoring software captures 30 seconds of ECG https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 5/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate signal prior to the determination of VT or VF and continuously records until 15 seconds after the alarms stop. Patients can perform manual recordings by pressing response buttons for three seconds, which records the prior 30 seconds plus the next 15 seconds. Data on patient compliance, ECG signal quality, alarm history, and noise occurrence are recorded, including time/date stamps for device on/off switching, monitor connection to the electrodes, and electrode-to-skin contact. Compliance may be determined by assessing the time that the user had the device turned on, the belt connected, and at least one monitoring electrode contacting the skin. For the Assure system: Up to 120 seconds of data are recorded prior to arrhythmia onset detection, confirmation, and therapy are detected, and up to 60 seconds are detected after rate recovery or conversion. Patient activity is also stored, utilizing an accelerometer located in the hub component in the middle of the patient's back. Daily usage is recorded in one-minute increments when the sensors are in contact with the patient's skin. INDICATIONS The WCD is indicated as temporary therapy for patients with a high risk for sudden cardiac death (SCD) [1,12-16]. Our recommended approach is consistent with that of the 2016 science advisory from the American Heart Association (also endorsed by the Heart Rhythm Society) and the 2017 AHA/ACC/HRS guideline [16,17]. Examples of persons who may benefit from the temporary use of a WCD include: Patients with a permanent implantable cardioverter-defibrillator (ICD) that must be explanted, or those with a delay in implanting a newly indicated ICD (eg, due to systemic infection). (See 'Bridge to indicated or interrupted ICD therapy' below.) Patients with reduced left ventricular (LV) systolic function (LVEF 35 percent) who have had a myocardial infarction (MI) within the past 40 days. (See 'Early post-MI patients with LV dysfunction' below.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 6/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Patients with reduced LV systolic function (LVEF 35 percent) who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months. (See 'Patients with LV dysfunction early after coronary revascularization' below.) Patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function (LVEF 35 percent) that is potentially reversible. (See 'Newly diagnosed nonischemic cardiomyopathy' below.) Patients with severe heart failure who are awaiting heart transplantation. (See 'Bridge to heart transplant' below.) A 2019 systematic review and meta-analysis, which included 33,242 WCD users from 28 studies (the randomized VEST trial and 27 nonrandomized studies), assessed the likelihood of WCD therapy in a broad range of patient populations, including both primary/secondary prevention and ischemic/nonischemic cardiomyopathy patients. The incidence of appropriate shocks was 5 per 100 persons over three months (1.67 percent per month) with mortality while wearing the device noted to be 0.7 per 100 persons over three months [18]. Bridge to indicated or interrupted ICD therapy In some patients with an indication for ICD placement, implantation of the device may be delayed due to comorbid conditions, including [16,17]: Infection Recovery from surgery Lack of vascular access In addition, patients with a preexisting ICD who develop device infection or endocarditis usually require system extraction to effectively treat the infection. Unless the patient is pacemaker dependent, reimplantation in many patients is deferred until the infection is completely cleared after an appropriate course of antibiotics. The WCD may provide protection against ventricular tachyarrhythmias during these periods until an ICD can be implanted [4,5,16]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".) In a review of 8058 patients who were prescribed the WCD after ICD removal because of infection, median time to reimplantation was 50 days, and 334 (4 percent) experienced 406 ventricular tachycardia/ventricular fibrillation (VT/VF) events, with 348 events treated by the WCD and 54 treatments averted by conscious patients [19]. The one-year cumulative event rate was 10 percent. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 7/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Early post-MI patients with LV dysfunction Among patients with LV ejection fraction (LVEF) 35 percent who are less than 40 days post-MI, there are conflicting data on the benefits of a WCD for primary prevention against SCD. Following discussion of the potential benefits and risks, use of the WCD within this 40-day window could be considered among motivated patients who have LVEF 35 percent and in New York Heart Association (NYHA) functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD implantation after 40 days [16,17]. Patients should be reminded of the importance of compliance with the WCD in order to optimize any potential benefits on prevention of arrhythmic death. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, while the patient is taking appropriate medical therapy, ICD implantation is indicated [16]. After ICD implantation, use of the WCD would be discontinued. Despite advances in the treatment of acute coronary syndromes with early revascularization and effective medical therapies that have reduced mortality, some residual risk of SCD remains in the early period following an MI, especially in the setting of severely reduced LVEF (2.3 percent/month for patients with LVEF 30 percent) [4,20]. However, there are conflicting data on the utility of an ICD in the early post-MI period. In an analysis of 712 patients with a history of MI who were enrolled in the SCD-HeFT trial, there was no evidence of differential mortality benefit with ICDs as a function of time after MI, indicating that the potential benefit of ICD therapy is not restricted only to remote MIs [21]. In the DINAMIT (674 patients) and IRIS (898 patients) trials, which randomized patients with LVEF 35 percent to either early ICD implantation 6 to 40 days after acute MI or medical therapy alone, there was no significant improvement in overall mortality [22,23]. Despite a reduction in arrhythmic deaths among patients with an ICD, there was a higher risk of nonarrhythmic deaths during this early period, resulting in similar overall mortality rates. Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within 40 days of acute MI [16]. However, due to the risk of SCD in some patients early post- MI, the WCD has been studied in this patient population. In the VEST trial, 2302 patients with an acute MI and LVEF 35 percent were randomly assigned (within seven days of hospital discharge) in a 2:1 ratio to wear the WCD in addition to usual medical treatment (1524 patients) or to receive standard medical treatment alone (778 patients) [24]. Over an average follow-up of 84 days, patients in the https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 8/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate WCD group had no significant improvement in the primary outcome of arrhythmic death (25 patients [1.6 percent] versus 19 patients [2.4 percent] with medical therapy alone; relative risk [RR] 0.67; 95% CI 0.37-1.21). Compliance with medical therapy was excellent in both groups, likely contributing to fewer than expected events and the trial possibly being underpowered. However, compliance with WCD usage was markedly lower than expected (median and mean daily wear times of 18 and 14 hours, respectively), with over half of patients assigned to the WCD not wearing it by the end of the 90-day study. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. Asystolic events not treated by the WCD likely also contributed to the nonsignificant primary outcome results of the trial. A subsequent as-treated and per- protocol analysis of VEST (censoring participants at the time they stopped wearing the WCD) reported a significant reduction in total and arrhythmic mortality among participants wearing the WCD compared with control participants (total mortality hazard ratio 0.25; CI 0.13-0.43; arrhythmic death hazard ratio 0.09; CI 0.02-0.39) [25]. The VEST study also demonstrates the challenges in trying to improve mortality in the post- MI population. Not all patients will survive despite initial appropriate and successful shocks for VT or VF. Of nine patients wearing the WCD with arrhythmic death in the VEST trial, four had been initially successfully treated but subsequently died. Of six patients who had an appropriate shock from the WCD but died during the study, two developed post-VT/VF asystole. Similar WCD shock rates (between 1.5 and 2 percent within 90 days post-MI) have been reported in observational studies [3,5,6]. In registry data from two large registries (involving 3569 and 8453 patients, respectively), similar rates of WCD shocks have been seen (1.7 and 1.6 percent of patients, respectively) [5,6]. Patients with LV dysfunction early after coronary revascularization Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD [16]. LVEF should be reassessed three months following CABG or PCI. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG or PCI, implantation of an ICD is usually indicated [16]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) While professional society guidelines do not specifically exclude ICD implantation for patients with LV dysfunction within three months of revascularization, reimbursement in some countries https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 9/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate may be denied. As an example, in the United States the national coverage decision for the Centers for Medicare & Medicaid Service (CMS) excludes coverage for primary prevention ICDs if patients have had CABG surgery or PCI within the past three months. This is based upon the clinical profile of subjects included in the major ICD trials for primary prevention of SCD in ischemic cardiomyopathy [12,13,26,27]. Despite this exclusion period, patients with LV dysfunction (eg, LVEF 30 percent) have been shown to have significantly higher rates of mortality early after PCI or CABG based on large National Cardiovascular Data Registry (NCDR) and Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database studies, respectively [28,29]. Patients with significant LV dysfunction have higher 30-day mortality rates after coronary artery bypass graft (CABG) surgery than patients with normal LV function. While these persons have an increased risk of SCD due to ventricular arrhythmias, they are also at risk for nonarrhythmic causes of death. There are limited data on the utility of an ICD in the early post-CABG period, as several ICD studies of primary prevention have excluded patients within one to three months after coronary revascularization [12-14]. However, the CABG Patch trial did not report a survival benefit from epicardial ICD implantation at the time of CABG in patients with LVEF 35 percent [27]. (See "Early cardiac complications of coronary artery bypass graft surgery" and "Early noncardiac complications of coronary artery bypass graft surgery".) Professional society guidelines do not recommend ICD implantation for primary prevention of SCD within three months of CABG [16]. However, due to the risk of SCD in some patients early post-CABG, the WCD has been studied in this patient population, in whom wearing the WCD may provide protection from SCD during healing and potential recovery of LV function [3,16,17]. The potential utility for a WCD in this setting is illustrated by the following studies: In a nonrandomized comparison of nearly 5000 patients with LVEF 35 percent from two separate cohorts who underwent revascularization with CABG or percutaneous coronary intervention (PCI) (809 patients discharged with a WCD from a national registry and 4149 patients discharged without WCD from Cleveland Clinic CABG and PCI registries), patients discharged with the WCD had significantly lower 90-day mortality rates (3 versus 7 percent) [30]. While patients using a WCD appear to have improved outcomes, only 1.3 percent of the WCD group received an appropriate therapy while wearing the device, thereby indicating that the majority of the mortality benefit was not attributable to life-saving therapies from the WCD. In a German cohort of 354 patients who wore the WCD, including approximately 90 patients in the early post-CABG period, 7 percent received a shock for a ventricular tachyarrhythmia during the three months of WCD use [4]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 10/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In a study of 3569 patients in the United States using the WCD, among which 9 percent of WCD use was early post-CABG, appropriate shocks for a ventricular tachyarrhythmia occurred in 0.8 percent of these patients over a mean follow-up of 47 days [5,31]. Newly diagnosed nonischemic cardiomyopathy In selected patients with newly diagnosed nonischemic cardiomyopathy with severely reduced LV systolic function that is potentially reversible, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function [16,17]. While a benefit from ICD implantation has long been recognized in patients with significant LV systolic dysfunction related to underlying ischemic heart disease, an increase in SCD risk and potential benefit from an ICD has also been demonstrated in patients with a nonischemic cardiomyopathy in several studies [14,32]: In SCD-HeFT, which compared ICD implantation with amiodarone treatment alone or placebo for primary prevention of SCD in patients with ischemic or nonischemic heart failure and LVEF 35 percent, patients who received an ICD had significantly improved survival [14]. However, patients within three months of their initial heart failure diagnosis were excluded from this study. In DEFINITE, which compared ICD implantation with standard medical therapy to standard medical therapy alone for primary prevention of SCD in patients with a nonischemic cardiomyopathy, nonsustained VT, and LVEF 35 percent, there was a trend toward improved mortality in patients who received an ICD, regardless of duration since diagnosis [32]. Following DEFINITE, another study reported similar occurrences of lethal arrhythmias irrespective of diagnosis duration in patients with a nonischemic cardiomyopathy and LVEF 35 percent [33]. Major society guidelines recommend implantation of an ICD for nonischemic cardiomyopathy with LVEF 35 percent, provided that a reversible cause of transient LV dysfunction has been excluded and that response to optimal medical therapy has been assessed [16]. The guidelines do not specify a waiting period prior to reassessing LVEF. In the United States, however, the Center for Medicare Services (CMS) requires a three-month period of optimal medical therapy prior to reimbursement for ICD placement for primary prevention (if repeat LVEF assessment continues to show LVEF 35 percent). (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Nonischemic dilated cardiomyopathy'.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 11/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In patients felt to be at high risk of SCD while undergoing a trial of optimal medical therapy, the WCD may provide protection against SCD while awaiting improvement in LV function, although the event rates in this population appear to be lower than patients with ischemic cardiomyopathy [16]. In a post-approval study of the WCD, 0.7 percent of patients prescribed a WCD for recently diagnosed nonischemic cardiomyopathy required shocks for a ventricular tachyarrhythmia over a mean follow-up period of 57 days [5,31]. Among a single-center cohort of 254 patients with newly diagnosed nonischemic cardiomyopathy treated with the WCD between 2004 and 2015 (median duration of treatment 61 days, total follow-up 56.7 patient-years) who were highly compliant with using the WCD (median wear time 22 hours per day), no patients received an appropriate shock, and only three patients (1.2 percent) received an inappropriate shock [34]. This was compared with 6 of 271 patients (2.2 percent) with newly diagnosed ischemic cardiomyopathy who received an appropriate shock; in this group, two (0.7 percent) received inappropriate shocks. Of interest, 39 percent of nonischemic and 32 percent of ischemic cardiomyopathy patients experienced improvement in LVEF to >35 percent, obviating the need for an ICD. In a prospective study of the WCD in advanced heart failure patients (SWIFT), 75 patients hospitalized with heart failure (66 percent nonischemic cardiomyopathy) were prescribed a WCD for three months. Among the nonischemic cardiomyopathy patients, one had recurrent supraventricular tachycardia and another had multiple ventricular premature beats detected, but no WCD therapies were delivered [35]. In the WEARIT II registry, which included 927 patients with nonischemic cardiomyopathy, over a median wear time of 90 days, the treated event rate was 1 percent, compared with 3 percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. |
percent for the 805 patients with ischemic cardiomyopathy [7]. Special populations include those with alcoholic cardiomyopathy, postpartum cardiomyopathy, or myocarditis, all of which may or may not be associated with improvement in ventricular function with optimal medical therapy and reversal or treatment of causative factors. In a study of 127 patients with alcoholic cardiomyopathy wearing the WCD a median of 51 days, 5.5 percent had appropriate shocks for VT/VF [36]. Improved LVEF occurred in 33 percent, and 23.6 percent received an ICD. In the PROLONG study of 156 patients (111 with nonischemic cardiomyopathy) with newly diagnosed LVEF 35 percent wearing a WCD for an average of 101 days, WCD shocks for VT/VF were experienced by 7.2 percent, compared with 6.7 percent in the 45 patients with https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 12/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate ischemic cardiomyopathy [37]. The event rates were 21.1 percent in the 19 patients with postpartum cardiomyopathy, 0 percent in the six patients with myocarditis, and 4.7 percent in patients with other forms of nonischemic cardiomyopathy. In a separate study of 107 women with peripartum cardiomyopathy, who were matched to 159 nonpregnant women with nonischemic dilated cardiomyopathy, the event rate was 0 in the peripartum cardiomyopathy over an average WCD use of 124 days, compared with two shocks in one patient with nonperipartum nonischemic cardiomyopathy [38]. With such low event rates, the utility of the WCD for newly-diagnosed nonischemic cardiomyopathy has been debated. However, from the WEARIT II registry, the number of VT/VF events per 100 patient-years was 1.5 for treated events versus 12 for untreated events [7]. Presumably, some of the untreated events led to earlier ICD implantation and may represent a nontreatment yield from the WCD monitoring functions. As data remain limited for such patients, the decision on whether to use a WCD remains based on clinical judgment for patients assessed to have high-risk severe newly diagnosed nonischemic cardiomyopathy while undergoing optimization of medical therapy, awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Therapy for arrhythmias'.) Bridge to heart transplant Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD [17]. ICD implantation is often recommended for such patients, particularly those discharged to home while awaiting transplantation. The WCD may be a reasonable noninvasive alternative approach, though data on its use in patients awaiting heart transplantation are limited: In one study of 91 cardiac transplant candidates discharged to home (UNOS Status 1B patients receiving home inotrope infusion), among whom 25 had an ICD and 13 used a WCD, two patients died suddenly at home, one who was not wearing his WCD and another who declined use of a WCD [39]. In the 13 patients wearing the WCD, three asymptomatic events occurred with one shock delivered for rapid atrial fibrillation. In a German study of 354 WCD patients, 6 percent wore the WCD while awaiting heart transplantation, with an incidence of ventricular arrhythmias of 11 percent [4]. In the WEARIT study of WCD use in 177 patients with NYHA functional class III or IV heart failure (not listed for heart transplant but with similar functional status to patients who might be listed for heart transplant), one patient received two successful defibrillations [3]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 13/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In a registry of 121 patients prescribed a WCD as a bridge to heart transplantation, seven patients (6 percent) received appropriate shocks over an average use of 127 days (median 39 days) [40]. The International Society for Heart and Lung Transplantation Guidelines state as a class I recommendation that an ICD or WCD should be provided for status 1B patients who are discharged home given that the wait for transplantation remains significant [41]. The WCD may also be appropriate in patients whose anticipated waiting time to transplant is short (ie, blood types A and B) if an ICD is not already present [41]. WCD in patients with VADs The role for ICD and WCD therapy remains unclear in patients with ventricular assist devices (VADs). With VADs, circulatory support is often adequate even in the event of a ventricular tachyarrhythmia. However, one study reported the presence of an ICD was associated with improved survival in patients undergoing VAD support [42]. Whether the WCD could impart similar survival benefits in patients awaiting transplantation with VAD support has yet to be studied. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) WCD use in hemodialysis patients Patients with end-stage kidney disease on hemodialysis are at high risk for SCD, but they are also at higher risk for infection, bleeding, and other complications of implantable device therapies, which may lead to underutilization of ICDs. Although the arrhythmia event rates for patients on hemodialysis wearing a WCD are not published, a study of 75 hemodialysis patients who experienced sudden cardiac arrest events while wearing a WCD reported that 78.6 percent of events were due to VT/VF and 21.4 percent were due to asystole [43]. Survival was 71, 51, and 31 percent at 24 hours, 30 days, and one year, respectively, which was reported to be improved compared with historical controls. LIMITATIONS AND PRECAUTIONS In spite of its overall efficacy for terminating life-threatening ventricular arrhythmias, the WCD does have some limitations. The device must be fitted to each patient, and some patients may not have a good fit due to body habitus. Its external nature does not allow for pacemaker functionality and introduces a component of patient interaction and compliance as well as the potential for external noise leading to inappropriate shocks. The device must be removed for bathing, but no protection is afforded while the device is off. Therefore, it is advisable that caregivers or other persons be nearby during these periods when the WCD is not worn. Comfort may also be an issue for some patients due to the size and weight of the device. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 14/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Patient size The WCD can only be fitted on patients with a chest circumference less than 57 inches (144 cm); therefore, it may not be an option for morbidly obese patients. However, among 574 patients from the WCD registry, which included normal weight (body mass index [BMI] between 18 and 24.9; n = 157), overweight (BMI between 25 and 29.9; n = 186), and obese (BMI 30; n = 231, including 55 with BMI 40) patients who experienced 623 ventricular tachycardia/ventricular fibrillation (VT/VF) events while wearing the WCD, the median daily wear time (21 hours), first shock success rate (93 to 94 percent), and 24-hour post-shock survival (92 to 94 percent) were similar across all BMI groups [44]. There are also limited data on WCD use in children, in whom the device may not fit properly if the child is small. (See 'Use of the WCD in children' below.) Lack of pacemaker functionality Because of its external nature, the WCD is not able to function as a pacemaker, which limits the possible therapies it can deliver in two ways: The WCD cannot deliver pacing therapies to treat bradycardia or asystole. In the German study, two patients developed asystole while wearing the WCD, and both patients died [4]. In the US post-approval registry study, 23 of 3569 patients (0.6 percent) experienced asystole, with an associated mortality of 74 percent [5]. In the post-myocardial infarction (MI) registry of 8453 patients, 34 died (0.4 percent) with bradycardia-asystole events [6]. In the WEARIT-II registry, 6 of 2000 patients (0.3 percent) had asystole, and all three of the deaths that occurred while wearing the WCD during the study (0.2 percent) occurred following an asystole event [7]. The WCD cannot provide antitachycardia pacing for VT, which can reduce patient shocks, when effective. When considering these limitations, an implantable cardioverter-defibrillator (ICD) would be preferred, if indicated, in a patient who is pacemaker-dependent or in whom antitachycardia pacing is desired as the initial therapy for VT. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Use in patients with a preexisting permanent pacemaker With certain precautions, the WCD can be used in patients with a preexisting permanent pacemaker. The manufacturer recommends that the device not be worn if the pacemaker stimulus artifact exceeds 0.5 millivolts, as this may mask underlying ventricular fibrillation and prevent appropriate device therapy. Conversely, the VT threshold of the WCD should be set higher than the maximal pacing rate to avoid an inappropriate WCD shock due to oversensing paced beats. Following any WCD shock, the patient's pacemaker should be interrogated to ensure that there has been no damage to the pacemaker or any changes in the pacemaker setting. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 15/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Inappropriate shocks Both the WCD and the ICD may inappropriately deliver shocks due to electronic noise, device malfunction, or detection of supraventricular tachycardia above the preprogrammed rate criteria. Studies of ICDs have reported an incidence of inappropriate shock of 0.2 to 2.3 percent of patients per month [32,45-51]. Comparable rates of inappropriate shocks have been reported among users of the WCD, with rates ranging from 0.5 to 1.4 percent per month [3-7]. In a systematic review and meta-analysis which included 33,242 patients from 28 studies (the randomized VEST trial and 27 nonrandomized studies), inappropriate shocks occurred at a rate of 2 per 100 persons over three months (0.67 percent per month) [18]. Inappropriate shocks with a WCD can be potentially reduced due to the ability to abort shocks while awake by pressing response buttons. (See 'Avoiding inappropriate shocks' above.) Patient compliance and complaints Patients may not comply with wearing the WCD for a variety of reasons, chief among them device size and weight, skin rash, itching, and problems sleeping. However, efficacy of the WCD in the prevention of sudden cardiac death is highly dependent on patient compliance and appropriate use of the device [3-5,7]. In the WEARIT/BIROAD study, 23 percent of the 289 subjects withdrew before reaching a study endpoint, with size and weight of the monitor being the most frequent reason for withdrawal [3]. Skin rash and/or itching were also reported by 6 percent of patients. In the US postmarket study, median and mean daily use were 21.7 hours and 19.9 hours, respectively [5]. Daily use was >90 percent (>21.6 hours) in 52 percent of patients and >80 percent (>19.2 hours) in 71 percent of patients. Longer duration of monitoring correlated with higher compliance rates. WCD use was stopped prematurely in 14 percent, primarily because of comfort issues related to the size and weight of the WCD. In the WEARIT-II registry, median daily use was 22.5 hours [7]. Similar to the US postmarket study, longer duration of monitoring (15 or more days) was associated with higher rates of compliance. In the nationwide German cohort, median daily use among 6043 patients was 23.1 hours for a median of 59 days [8]. Lower rates of compliance were reported in a study of 147 patients from two academic medical centers in Boston, in which median daily use was 21 hours for a median of 50 days [52]. In an international registry of 708 patients, appropriate WCD shock was documented in 2.2 percent, inappropriate shock in 0.5 percent, and mean wear time was 21.2 4.3 hours/day (and was lower in younger patients) [53]. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 16/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate In the WEARIT-France cohort study of 1157 patients, median daily wear time was 23.4 hours, with younger age associated with lower compliance [54]. In the VEST randomized trial after MI, median and mean daily wear times were only 18 and 14 hours, respectively, with over half of patients assigned to the WCD not wearing it by the end of the 90-day study [24]. Among 48 total deaths in the WCD group, only 12 patients (25 percent) were wearing the WCD at the time of death. In the as-treated and per-protocol analysis of VEST [25], better WCD compliance was predicted by cardiac arrest during index MI, higher creatinine, diabetes, prior heart failure, ejection fraction 25 percent, Polish enrolling center, and number of WCD alarms. Worse compliance was associated with being divorced, Asian race, higher body mass index, prior PCI, or any WCD shock. In a study of 130 patients with an ICD and fitted with an ASSURE WCD programmed for detection only and followed for 30 days, median daily use was high at 23 hours [11]. Rates of WCD discontinuation appear similar to reported rates of compliance with other prescribed therapies. One study reported that 15 percent of patients stop using aspirin, ACE inhibitors and beta-blockers within 30 days of a MI [55]. Improved compliance and acceptance of the WCD may be seen with newer devices, which are 40 percent smaller in size and weight or which offer multiple sizes and gender-specific fitting. USE OF THE WCD IN CHILDREN In December 2015, the US Food and Drug Administration (FDA) approved the WCD for use in children, although the WCD was used off-label prior to FDA approval [56]. As such, there are relatively few peer-reviewed publications documenting experience with the WCD in children [57- 59]. In a retrospective review of all patients <18 years of age who were prescribed the WCD between 2009 and 2016 (n = 455 patients), median duration of use was 33 days and wear time 20.6 hours [59]. Eight patients received at least one shock (seven episodes of ventricular tachycardia/ventricular fibrillation [VT/VF] in six patients, two inappropriate shocks due to oversensing), with four of the seven episodes of VT/VF terminated with a single shock and all seven episodes successfully terminated by the WCD. There were seven deaths (1.5 percent); none were wearing the WCD at the time of death. Children require special attention to assure compliance and correct fitting for optimal use. A variety of device harness sizes are available, but the smallest option may still be too large for https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 17/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate smaller children. Additional data on clinical efficacy, compliance, and complications should be collected in children as WCD use increases. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Introduction The wearable cardioverter-defibrillator (WCD) is an external device capable of automatic detection and defibrillation of ventricular tachycardia (VT) or ventricular fibrillation (VF) ( picture 1). In cases where the need for an implantable cardioverter- defibrillator (ICD) is felt to be temporary or implantation of the ICD must be deferred, a WCD may be an acceptable alternative approach for the prevention of sudden cardiac death (SCD). (See 'Description and functions of the WCD' above.) Device functions In addition to delivering therapeutic shocks for life-threatening ventricular arrhythmias, the WCD stores data regarding arrhythmias, patient compliance with the device, and noise or interference with its proper functioning. Arrhythmia recordings from the WCD are available for clinician review once stored data are transmitted to the manufacturer's network. (See 'Storage of ECGs and compliance data' above.) Efficacy When worn properly, the WCD appears to be as effective as an ICD for the termination of VT and VF, with successful shocks occurring in nearly 100 percent of cases. In addition, inappropriate shock rates from the WCD appear to be comparable to and in some studies lower than those reported for ICDs. (See 'Efficacy in terminating VT/VF' above and 'Inappropriate shocks' above.) Indications The WCD is an option as temporary therapy for select patients with a high risk for SCD: Among patients with left ventricular ejection fraction (LVEF) 35 percent who are less than 40 days post-myocardial infarction (MI), we discuss the potential benefits and risks of WCD use and offer it to highly motivated patients with NYHA functional class II or III, or LVEF <30 percent and in NYHA class I, as these patients would be candidates for ICD https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 18/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate implantation after 40 days. Reevaluation of LVEF should occur one to three months after the MI. If LVEF remains 35 percent on follow-up assessment, despite appropriate medical therapy, ICD implantation is indicated and should be considered. (See 'Early post-MI patients with LV dysfunction' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) Among patients with LVEF 35 percent who have undergone coronary revascularization with coronary artery bypass graft (CABG) surgery in the past three months, we offer a WCD to highly motivated patients for primary prevention against SCD. LVEF should be reassessed three months following CABG. If a sustained ventricular tachyarrhythmia has occurred, or if the LVEF remains 35 percent three months after CABG, implantation of an ICD is usually indicated. (See 'Patients with LV dysfunction early after coronary revascularization' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) In selected patients with severe but potentially reversible cardiomyopathy, such as tachycardia- or myocarditis-associated cardiomyopathy, the WCD may be useful for the prevention of SCD due to ventricular arrhythmias while awaiting improvement in LV function, ICD implantation, or if needed, cardiac transplantation. (See 'Newly diagnosed nonischemic cardiomyopathy' above.) Patients with severe heart failure awaiting heart transplantation represent a group at particularly high risk for SCD in whom ICD implantation is often recommended. The WCD may be a reasonable noninvasive alternative approach, particularly for patients whose anticipated waiting time to transplant is short if an ICD is not already present. (See 'Bridge to heart transplant' above.) Some patients with an indication for an ICD may require a delay in ICD implantation due to comorbid conditions (ie, infection, recovery from surgery, lack of vascular access). Additionally, some patients who have an ICD need it removed due to infection. In such patients, the WCD may provide protection against ventricular tachyarrhythmias until an ICD can be implanted or reimplanted. (See 'Bridge to indicated or interrupted ICD therapy' above.) Device limitations Limitations of the WCD (compared with a traditional ICD) include the lack of pacemaker functionality, the requirement for patient interaction and compliance, and potential discomfort due to the size and weight of the device. (See 'Limitations and precautions' above.) https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 19/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Sharma PS, Bordachar P, Ellenbogen KA. Indications and use of the wearable cardiac defibrillator. Eur Heart J 2016. 2. Reek S, Geller JC, Meltendorf U, et al. Clinical efficacy of a wearable defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks. Pacing Clin Electrophysiol 2003; 26:2016. 3. Feldman AM, Klein H, Tchou P, et al. Use of a wearable defibrillator in terminating tachyarrhythmias in patients at high risk for sudden death: results of the WEARIT/BIROAD. Pacing Clin Electrophysiol 2004; 27:4. 4. Klein HU, Meltendorf U, Reek S, et al. Bridging a temporary high risk of sudden arrhythmic death. Experience with the wearable cardioverter defibrillator (WCD). Pacing Clin Electrophysiol 2010; 33:353. 5. Chung MK, Szymkiewicz SJ, Shao M, et al. Aggregate national experience with the wearable cardioverter-defibrillator: event rates, compliance, and survival. J Am Coll Cardiol 2010; 56:194. 6. Epstein AE, Abraham WT, Bianco NR, et al. Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction. J Am Coll Cardiol 2013; 62:2000. 7. Kutyifa V, Moss AJ, Klein H, et al. Use of the wearable cardioverter defibrillator in high-risk cardiac patients: data from the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry). Circulation 2015; 132:1613. 8. W nig NK, G nther M, Quick S, et al. Experience With the Wearable Cardioverter- Defibrillator in Patients at High Risk for Sudden Cardiac Death. Circulation 2016; 134:635. 9. Kandzari DE, Perumal R, Bhatt DL. Frequency and Implications of Ischemia Prior to Ventricular Tachyarrhythmia in Patients Treated With a Wearable Cardioverter Defibrillator Following Myocardial Infarction. Clin Cardiol 2016; 39:399. 10. Schmitt J, Abaci G, Johnson V, et al. Safety of the Wearable Cardioverter Defibrillator (WCD) in Patients with Implanted Pacemakers. Pacing Clin Electrophysiol 2017; 40:271. 11. Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter defibrillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. 12. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 20/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933. 13. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877. 14. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225. 15. Al-Khatib SM, Friedman P, Ellenbogen KA. Defibrillators: Selecting the Right Device for the Right Patient. Circulation 2016; 134:1390. 16. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 17. Piccini JP Sr, Allen LA, Kudenchuk PJ, et al. Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death: A Science Advisory From the American Heart Association. Circulation 2016; 133:1715. 18. Masri A, Altibi AM, Erqou S, et al. Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death: A Systematic Review and Meta-Analysis. JACC Clin Electrophysiol 2019; 5:152. 19. Ellenbogen KA, Koneru JN, Sharma PS, et al. Benefit of the Wearable Cardioverter- Defibrillator in Protecting Patients After Implantable-Cardioverter Defibrillator Explant: Results From the National Registry. JACC Clin Electrophysiol 2017; 3:243. 20. Solomon SD, Zelenkofske S, McMurray JJ, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005; 352:2581. 21. Piccini JP, Al-Khatib SM, Hellkamp AS, et al. Mortality benefits from implantable cardioverter- defibrillator therapy are not restricted to patients with remote myocardial infarction: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Heart Rhythm 2011; 8:393. 22. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter- defibrillator after acute myocardial infarction. N Engl J Med 2004; 351:2481. 23. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009; 361:1427. 24. Olgin JE, Pletcher MJ, Vittinghoff E, et al. Wearable Cardioverter-Defibrillator after Myocardial Infarction. N Engl J Med 2018; 379:1205. https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 21/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate 25. Olgin JE, Lee BK, Vittinghoff E, et al. Impact of wearable cardioverter-defibrillator compliance on outcomes in the VEST trial: As-treated and per-protocol analyses. J Cardiovasc Electrophysiol 2020; 31:1009. 26. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. 27. Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997; 337:1569. 28. Weintraub WS, Grau-Sepulveda MV, Weiss JM, et al. Prediction of long-term mortality after percutaneous coronary intervention in older adults: results from the National Cardiovascular Data Registry. Circulation 2012; 125:1501. 29. Shahian DM, O'Brien SM, Sheng S, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation 2012; 125:1491. 30. Zishiri ET, Williams S, Cronin EM, et al. Early risk of mortality after coronary artery revascularization in patients with left ventricular dysfunction and potential role of the wearable cardioverter defibrillator. Circ Arrhythm Electrophysiol 2013; 6:117. 31. Verdino RJ. The wearable cardioverter-defibrillator: lifesaving attire or "fashion faux pas?". J Am Coll Cardiol 2010; 56:204. 32. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350:2151. 33. Makati KJ, Fish AE, England HH, et al. Equivalent arrhythmic risk in patients recently diagnosed with dilated cardiomyopathy compared with patients diagnosed for 9 months or more. Heart Rhythm 2006; 3:397. 34. Singh M, Wang NC, Jain S, et al. Utility of the Wearable Cardioverter-Defibrillator in Patients With Newly Diagnosed Cardiomyopathy: A Decade-Long Single-Center Experience. J Am Coll Cardiol 2015; 66:2607. 35. Barsheshet A, Kutyifa V, Vamvouris T, et al. Study of the wearable cardioverter defibrillator in advanced heart-failure patients (SWIFT). J Cardiovasc Electrophysiol 2017; 28:778. 36. Salehi N, Nasiri M, Bianco NR, et al. The Wearable Cardioverter Defibrillator in Nonischemic Cardiomyopathy: A US National Database Analysis. Can J Cardiol 2016; 32:1247.e1. 37. Duncker D, K nig T, Hohmann S, et al. Avoiding Untimely Implantable Cardioverter/Defibrillator Implantation by Intensified Heart Failure Therapy Optimization https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 22/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Supported by the Wearable Cardioverter/Defibrillator-The PROLONG Study. J Am Heart Assoc 2017; 6. 38. Saltzberg MT, Szymkiewicz S, Bianco NR. Characteristics and outcomes of peripartum versus nonperipartum cardiomyopathy in women using a wearable cardiac defibrillator. J Card Fail 2012; 18:21. 39. Lang CC, Hankins S, Hauff H, et al. Morbidity and mortality of UNOS status 1B cardiac transplant candidates at home. J Heart Lung Transplant 2003; 22:419. 40. Opreanu M, Wan C, Singh V, et al. Wearable cardioverter-defibrillator as a bridge to cardiac transplantation: A national database analysis. J Heart Lung Transplant 2015; 34:1305. 41. Gronda E, Bourge RC, Costanzo MR, et al. Heart rhythm considerations in heart transplant candidates and considerations for ventricular assist devices: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates 2006. J Heart Lung Transplant 2006; 25:1043. 42. Cantillon DJ, Tarakji KG, Kumbhani DJ, et al. Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator. Heart Rhythm 2010; 7:466. 43. Wan C, Herzog CA, Zareba W, Szymkiewicz SJ. Sudden cardiac arrest in hemodialysis patients with wearable cardioverter defibrillator. Ann Noninvasive Electrocardiol 2014; 19:247. 44. Wan C, Szymkiewicz SJ, Klein HU. The impact of body mass index on the wearable cardioverter defibrillator shock efficacy and patient wear time. Am Heart J 2017; 186:111. 45. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation 2005; 111:2898. 46. Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008; 359:1009. 47. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008; 51:1357. 48. Klein RC, Raitt MH, Wilkoff BL, et al. Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. J Cardiovasc Electrophysiol 2003; 14:940. 49. Wilkoff BL, Ousdigian KT, Sterns LD, et al. A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 23/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate randomized multicenter EMPIRIC trial. J Am Coll Cardiol 2006; 48:330. 50. Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 2008; 52:541. 51. Wilkoff BL, Hess M, Young J, Abraham WT. Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 2004; 15:1002. 52. Leyton-Mange JS, Hucker WJ, Mihatov N, et al. Experience With Wearable Cardioverter- Defibrillators at 2 Academic Medical Centers. JACC Clin Electrophysiol 2018; 4:231. 53. El-Battrawy I, Kovacs B, Dreher TC, et al. Real life experience with the wearable cardioverter- defibrillator in an international multicenter Registry. Sci Rep 2022; 12:3203. 54. Garcia R, Combes N, Defaye P, et al. Wearable cardioverter-defibrillator in patients with a transient risk of sudden cardiac death: the WEARIT-France cohort study. Europace 2021; 23:73. 55. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006; 166:1842. 56. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm466852.htm (Access ed on December 21, 2015). 57. Everitt MD, Saarel EV. Use of the wearable external cardiac defibrillator in children. Pacing Clin Electrophysiol 2010; 33:742. 58. Collins KK, Silva JN, Rhee EK, Schaffer MS. Use of a wearable automated defibrillator in children compared to young adults. Pacing Clin Electrophysiol 2010; 33:1119. 59. Spar DS, Bianco NR, Knilans TK, et al. The US Experience of the Wearable Cardioverter- Defibrillator in Pediatric Patients. Circ Arrhythm Electrophysiol 2018; 11:e006163. Topic 15824 Version 35.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 24/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate GRAPHICS Wearable cardioverter-defibrillator The wearable cardioverter-defibrillator consists of a vest incorporating two defibrillation electrodes and four sensing electrocardiographic electrodes connected to a waist unit containing the monitoring and defibrillation electronics. Reproduced with permission from: ZOLL Medical Corporation. Copyright 2012. All rights reserved. Graphic 60103 Version 3.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 25/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Electrocardiogram sensing (A) Five ECG electrodes are positioned circumferentially around the torso at the level of the subxiphoid process, labelled left front (LF), right front (RF), left back (LB), right back (RB), and right leg drive (RLD). Red dashed arrows represent the four differential ECG vectors derived using RLD as a ground reference. (B) Garment interior depicting five embedded, cushioned ECG electrodes and defibrillation pads (two posterior and one anterior). ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140856 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 26/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate ASSURE WCD System noise management The A WCD employs three levels of protection to achieve a low false alarm rate due to noise. Level 1 (blue) minimize noise. Level 2 (red) detect and remove noise that does occur. Level 3 (yellow) allow time for remaining noise to subside before alarming. A-WCD: ASSURE WCD System; VT: ventricular tachycardia; VF: ventricular fibrillation; ECG: electrocardiogram. From: Poole JE, Gleva MJ, Birgersdotter-Green U, et al. A wearable cardioverter de brillator with a low false alarm rate. J Cardiovasc Electrophysiol 2022; 33:831. https://onlinelibrary.wiley.com/doi/10.1111/jce.15417. Copyright 2022 Wiley Periodicals, LLC. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/). Graphic 140843 Version 1.0 https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 27/28 7/6/23, 3:40 PM Wearable cardioverter-defibrillator - UpToDate Contributor Disclosures Mina K Chung, MD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wearable-cardioverter-defibrillator/print 28/28 |
7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology Anatomy of the Heart Cardiac Anatomy S. Yen Ho, PhD FRCPath FESC FHEA Royal Brompton Hospital Traditionally, the heart is described as having left heart and right heart chambers. Current imaging techniques can show in exquisite detail the heart in its anatomical position inside the living patient s chest and demonstrate the convoluted arrangement of right heart chambers relative to left heart chambers and the fact that right heart chambers are not strictly right-sided nor are left heart chambers left-sided. These important relationships of the chambers can be replicated with an endocast (Figure 1). In cardiac anatomy, knowledge of the relative disposition of the cardiac chambers is as relevant as the intrinsic chamber morphology. This review considers the cardiac chambers, coronary arteries and the conduction system. Figure 1. The endocast is viewed from 5 different perspectives to demonstrate the spatial relationship between right (coloured blue) and left (coloured red) heart chambers and between atria and ventricles. The blue and white arrows represent the right and left ventricular outflow tracts respectively. Contents Position of the heart The morphologically right atrium The morphologically left atrium The morphologically right ventricle The morphologically left ventricle The aorta The pulmonary arteries The coronary circulation The cardiac conduction system The sinus node The atrioventricular conduction system References Position of the heart The cardiac silhouette is generally taken to be trapezoidal in shape. The rib cage provides good markers for charting the cardiac silhouette. The normal position of the cardiac apex is generally taken to be in the fifth intercostal space in the mid-clavicular line. The lower border is a nearly horizontal line in the area of the left sixth rib to the right sixth costal cartilage (Figure 2). The upper border is hidden behind the https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 1/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology sternum at level the second and third the of Figure 2. The long axis of the heart is at an angle to the long axis of the body. Approximately a third of the heart is to the right of the midline of the sternum and the remainder is to the left of the midline. Figure 4. A. This frontal view shows the right and left surfaces of the heart. The left anterior descending coronary artery buried in epicardial fat marks the plane of the ventricular septum. B. The obtuse and acute margins of the ventricles are demonstrated in this apical view. cartilages. The right margin of the heart peeps out behind the right border of the sternum between the right third and sixth cartilages. In the infant, the upper part of the cardiac shadow is broad owing to the prominence of the overlying thymus gland. Inferior to the thymus, a fibrous pericardial sac encloses the mass of the heart. The sac has cuff-like attachments around the adventitia of the great arteries and veins as they enter or emerge from the heart. The pericardial cavity is contained between the double-layered serous pericardium. The parietal pericardium is adherent to the fibrous pericardium while the visceral layer is densely adherent to the cardiac surface forming the epicardium. Due to the contours of the heart and great arteries there exist two recesses within the pericardial cavity. These are the transverse and oblique sinuses. The transverse sinus occupies the inner heart curvature and lies between the Figure 3. A. Viewed from the front, the right atrium and right ventricle overlaps the left atrium and left ventricle. The atrial chambers are to the right of their respective ventricular chambers. B. The four cardiac valves are at different levels and different planes with the pulmonary(P) valve situated the most cephalad. The aortic(A) valve is wedged between the tricuspid(T) and mitral(M) valves. https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 2/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology posterior surface of the great arteries and the anterior surface of the atrial chambers. The reflection of the serous pericardium around the four pulmonary veins and the inferior caval vein forms the oblique sinus. When the pericardium is removed, the major part of the heart visible from the front is the ventricular mass. Here, the morphologically right ventricle occupies the greater part (Figure 3). The left ventricle appears only as a narrow slip along the left cardiac border. The shape of the heart is generally likened to a pyramid. The apex points downwards, forwards and to the left while the base faces posteriorly and to the right. While the cardiac apex is usually represented by the vortex of the left ventricle, the cardiac base is less well defined owing to differences in definition. The anatomical base is formed mainly by the left atrium receiving the pulmonary veins and to a small extent by the posterior part of the right atrium. The base in clinical practice, however, refers to the portion of the heart near the parasternal parts of the second intercostal spaces. The cardiac long axis, therefore, lies in a line drawn from the left hypochondrium towards the right shoulder. This orientation deviates considerably from the long axis of the body. Furthermore, the position of the cardiac septum at about 45 to the median brings the right heart structures anterior to the left heart structures (Figure 3A). The ventricles are situated inferior and leftward relative to their corresponding atria. This results in the right atrioventricular junction being in a nearly vertical plane. The left atrium is the most posterior cardiac chamber being directly anterior to the oesophagus at the bifurcation of the trachea. In frontal projection, only its appendage is visible. The aorta has a deep-seated origin and only becomes part of the cardiac silhouette as it arches upwards and backwards, forming a spiral with the pulmonary trunk. The cardiac valves are offset from one another, in keeping with the disposition of the cardiac chambers and great arteries. When viewed in frontal projection, the pulmonary valve, being the most superior valve, is horizontally situated behind the third costal cartilage. The aortic valve lies posterior and to the right, above the nearly vertically orientated tricuspid valve (Figure 3B). The mitral valve is further posterior, overlapped by the more anterior but inferior tricuspid valve. The aortic valve therefore occupies a central position in the heart, wedged between the two atrioventricular valves. The cardiac surfaces are described as the sternocostal, diaphragmatic, left and right (Figure 4). The sternocostal surface is covered anteriorly by the sternum and pleurae. The diaphragmatic surface is horizontally orientated. The sharp angle formed mainly by the right ventricle and occupying the lower heart border is the acute margin of the heart. The rounded obtuse margin of the heart is formed mainly by the left ventricle to the left of the sternocostal surface. The morphologically right atrium The right atrium is composed of an anterior appendage, a posterior venous sinus, a septal portion and a vestibule. The junction between the appendage and the venous sinus is marked epicardially by an atrial groove the terminal groove, in which lies the sinus node. Inside the chamber, the terminal groove is represented by a muscle bundle, the terminal crest (crista terminalis), from which pectinate muscles radiate into the appendage (Figure 5). The appendage has a characteristic triangular shape and a wide communication with the venous sinus. The smooth-walled venous sinus receives the superior and inferior caval veins in its cephalic and caudal extremities respectively. The coronary sinus opens close to the septal portion and near the opening of the inferior caval vein. The outlet portion of the atrium, the vestibule leading to the tricuspid valve orifice, is also smooth walled. The obliquely orientated atrial septum extends from right posterior to left anterior position. When viewed from the right atrial aspect, the atrial septum is characterised by a muscular rim the limbus - which surrounds the flap valve of the oval fossa (Figure 5). The extent of the true septum, however, is limited to the flap valve and the immediate part of its surrounding muscular rim. On the epicardial side much of the rim is filled by the https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 3/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology interatrial groove which separates the right atrium from the right pulmonary veins posteriorly and superiorly. In its anterior part, the continuation of the interatrial groove and its musculature extends to the anterior wall of the right atrium, directly related to the transverse pericardial sinus. Only a small portion of the inferior rim is part of the true atrial septum. Its major portion is the continuation of the right atrial wall, the vestibule, overlying the crest of the ventricular septum (Figure 5). In fetal life, the flap valve of the oval fossa allows venous return mostly from the inferior caval vein to enter the left atrium. After birth the valve is normally large enough to close the interatrial communication as higher left atrial pressure pushes the valve against the muscular rim forming a complete seal. A probe patency (a probe could be passed from right to left atrium through an unsealed antero-superior part of the rim) exists in about a quarter of the normal population and is generally referred to as a PFO. the infolded rim contains Figure 5. A. This right lateral view shows the right atrium dominated by its large, triangluar shaped appendage. The dots mark the terminal groove. The arrow indicates the crest of the appendage. B. The lateral wall of the appendage incised and flipped backward to show the pectinate muscles and the thin, membrane-like atrial wall between the muscle bundles. The terminal crest (dots) marks the border between the pectinated appendage and the smooth-walled venous sinus. The oval fossa is surrounded by its muscular rim. The smooth-walled vestibule leads to the tricuspid valve orifice. The morphologically left atrium The left atrium also has a venous component, a characteristic appendage, a septal component and a vestibule that leads to the mitral orifice. Other than the appendage, the main chamber of the left atrium is relatively smooth-walled. The appendage is hook- shaped with a crenelated external appearance and a narrow junction with the venous component (Figure 6). The junction is not marked by any structure comparable to the terminal crest although in many hearts there is a prominent infolding of the atrial wall between the orifice of the atrial appendage and the orifices of the left pulmonary veins. The venous portion is anchored by the pulmonary veins which drain directly into its superior and posterior parts. There are usually four pulmonary venous orifices but variations are not uncommon. The coronary sinus runs inferiorly behind the posterior wall to open into the right atrium. The flap valve of the oval fossa on the septal aspect has a small crescent marking the free edge of the valve at the fossa opening (the site of the PFO) whereas the rest of the valve blends into the atrial wall (Figure 6). The morphologically right ventricle Description of the ventricular chambers is facilitated by considering them in terms of three components - inlet, apical trabecular and outlet. The inlet contains the atrioventricular valve and its tension apparatus; the outlet supports the arterial valve. The apical trabecular portion is the most distinctive in each ventricle being characteristically coarse in the right ventricle (Figure 7A) and fine in the left ventricle. In a similar way, the muscular ventricular septum can be considered in terms of inlet, apical trabecular and outlet portions. A small fibrous area, the membranous septum, is located at this tripartite junction. The attachment of the septal tricuspid valve leaflet divides the membranous septum into atrioventricular and interventricular components (Figure 7B). It is important to appreciate that the entire ventricular septum is not on one plane. Owing to the 'wrap-around' relationship of the right ventricle to the left ventricle, the various portions are arranged at angles to each other. The inlet septum (between the ventricular inlet portions) is more or less at the sagittal plane of the body. Extending out https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 4/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology apically and curving between the and outlet inlet Figure 7. A. The right ventricle is opened to show the septum and the muscular crest separating tricuspid from pulmonary valves. The moderator band (open arrow) extends from the foot of the septomarginal trabeculation to the free wall of the right ventricle. Coarse trabeculations fill the apical component. B. This close-up view of the tricuspid valve at the commissure between septal and antero-septal leaflets shows the annulus (broken line) crossing the membranous septum (dots) dividing it into atrioventricular(av) and interventricular(iv) components. lateral components projection, the right ventricle is seen to sweep from beneath to above the left ventricle. When viewed in frontal projection the right ventricle passes in front of the left ventricle (Figure 1). A prominent Y-shaped muscle band, the septomarginal trabeculation, is adherent onto the septal surface. Clasped in between the limbs of the septomarginal trabeculation is the supraventricular crest, a distinctive feature of the right ventricle. The tricuspid valve is separated from the pulmonary valve by this crest (Figure 7A). Much of the crest is simply the infolded inner heart curvature with fatty tissue containing the right coronary artery on its epicardial aspect. The body of the septomarginaI trabeculation gives origin to the moderator band that crosses the ventricular cavity to insert to the anterior wall. The right ventricular inlet component extends from the tricuspid valve orifice to the attachment of the papillary muscle but a discrete demarcation is not seen. The tricuspid valve lacks a well-formed fibrous annulus. Its three leaflets are not always easy to identify owing to clefts within its major leaflets. The commissural chords will identify the divisions between the three leafets - the antero-superior, the septal and the postero-inferior. The direct attachment of the septal leaflet to the septum is a distinguishing feature of the tricuspid valve. is the trabecular septum. In Figure 6. A. This view from the left-lateral aspect shows the finger-like left atrial appendage with the left atrium situated posteriorly. The left ventricle tapers to a rounded apex. B. This section through the aortic root and mitral valve displays the left atrial aspect of the septum enface. The crescentic edge (arrow) of the fossa valve has not sealed completely resulting in a PFO. The asterisk marks the location of the transverse pericardial sinus. The morphologically left ventricle https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 5/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology In contrast to the right ventricle, the left ventricle is a conical structure with thick tubular walls tapering to a rounded apex (Figure 6A) where the apical wall becomes as thin as 1-2 mm. Very little of the left ventricle is visible from the front of the heart (Figures 1 and 3A) although in the infant a relatively greater portion may be seen. As with the right ventricle, the left ventricle comprises inlet, trabecular and outlet portions. The acute angle between inlet and outlet portions brings the aortic valve in adjacency and in fibrous continuity with the mitral valve. There is no structure comparable to the supraventricular crest in the left ventricle. There is also no structure corresponding to the septomarginal trabeculation on the smooth septal surface (Figure 8A). Figure 8. A. The left ventricle is opened through its outflow tract into the aortic valve. The aortic valve leaflets are in fibrous continuity with the anterior leaflet of the mitral valve. The fibrous continuity is expanded at the right and left fibrous trigones. The right trigone(asterisk) is the landmark for the atrioventricular conduction bundle. Note how the thickness of the left ventricular wall diminishes remarkably at the apex (open arrow). B. This dissection shows the central location of the aortic valve. L, N and R are the left-coronary, non-coronary and right-coronary aortic sinuses respectively. The inlet component surrounds and contains the mitral valve and its tension apparatus. The outlet component supports the aortic valve but only half its circumference is muscular while the other half is an area of fibrous continuity between aortic and mitral valves. The aortic (antero-superior) leaflet of the mitral valve is suspended like a curtain between the inlet and outlet components. The deeply wedged posterior position of the aortic outflow tract displaces the mitral valve leaflets away from the septum as contrasted with the septal attachment of the tricuspid valve. The trabecular component has characteristically fine trabeculations (Figure 8A). The mitral valve annulus is thickened at each commissure to form the left and right fibrous trigones. The annular attachment of the aortic (or anterior) leaflet is related to the membranous septum and right fibrous trigone (together making the central fibrous body). The other leaflet of the mitral valve - the mural (or posterior) leaflet - usually has three scallops. The mitral valve is supported by two groups of papillary muscles in antero-lateral and postero-medial positions. Although textbook pictures tend to portray the papillary muscles as arranged far apart, they are in reality situated close to one another. Each papillary muscle supports the adjacent part of both leaflets and the commissures are marked by fan- shaped commissural chords. The outlet component supports the aortic valve. The semilunar leaflets are attached within the expanded aortic sinuses (of Valsalva). The sinuses are not strictly in right and left position although they are so designated in consideration of the origins of the coronary arteries. The central position of the aorta places it in close relation to each of the cardiac chambers and valves (Figure 8B). The commissure between right and left coronary cusps is usually positioned opposite a commissure of the pulmonary valve. The commissure between the left and non-coronary leaflets points towards the left atrium. The commissure between right coronary and non-coronary leaflets lies above the membranous septum and is closely related to the right atrium and right ventricle and the atrioventricular conduction bundle (Figure 8B). The aorta https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 6/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology The ascending aorta arises in right posterior position relative to the pulmonary trunk (Figure 1, upper panel). It ascends superiorly, obliquely to the right and slightly anterior toward the sternum. On the right is the medial wall of the right atrium. Anteriorly are the right atrial appendage, the right ventricular outflow tract and the pulmonary trunk. The transverse pericardial sinus separates the back of the aorta from the left atrium and right pulmonary artery. The arch of the aorta begins just above the cuff of pericardial reflection, proximal to the origin of the brachiocephalic artery. The arch passes superiorly for a short distance before passing posteriorly to the left and finally terminating on the lateral aspect of the vertebral column. In its course, the arch gives origin to the neck and arm arteries. The arterial duct, a patent channel in fetal life, connects the left pulmonary artery to the aorta just distal to the origin of the left subclavian artery. In the adult, the duct is represented by a fibrous ligament. The pulmonary arteries The pulmonary trunk is also covered with a cuff of serous pericardium at its origin. It arises from the anterior aspect of the heart, just behind the left lateral edge of the sternum. It swings diagonally to the left side of the ascending aorta (Figure 1, upper panel). Being a short vessel, it soon bifurcates into the left and right pulmonary arteries. The left pulmonary artery passes in front of the descending aorta and superior to the left main bronchus before branching in the lung hilum. The longer right pulmonary artery traverses the mediastinum under the aortic arch before passing behind the superior caval vein to reach the right lung hilum. The coronary circulation As mentioned previously, the left and right coronary arteries emerge from the left and right coronary sinuses respectively. Usually the arteries arise from within the sinus just beneath or at the level of the aortic bar (sinutubular junction). In the left sinus there is usually a single orifice but in the right sinus it is usual to find multiple orifices where the early branches of the right coronary artery take direct origin. The main coronary arteries pass within the the atrioventricular and interventricular grooves. The left coronary has a short main stem that branches into the anterior descending and circumflex arteries (Figure 9). The circumflex runs in the left atrioventricular groove in the right and the right coronary artery runs atrioventricular groove to variable lengths. From the atrioventricular groove, the encircling arteries give origin to ventricular and atrial branches. An early atrial branch is the sinus node artery which arises slightly more frequently from the right than the left coronary artery. It usually ascends the interatrial musculature to reach the terminal groove but recent evidence has shown a more variable course. In the majority of hearts the posterior descending artery, which the posterior interventricular groove, is a branch from the right coronary artery and this is termed 'right dominance'. In a little under 10% of hearts the posterior descending is a branch of the circumflex giving 'left dominance'. fatty tissues of Figure 9. Diagram showing the right (RCA) and left (LCA) coronary arteries and their main ventricular branches. The left anterior descending (LAD) and posterior descending (PDA) coronary arteries mark the anterior and posterior margins of the ventricular septum. runs in https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 7/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology A 'balanced' circulation is seen when both right and left coronary arteries give rise to parallel posterior descending branches. The artery to the atrioventricular node arises from the dominant artery at the cardiac crux. After passing through the capillary network, coronary arterial blood is collected by venules which drain to the cardiac veins. The veins drain either to the coronary sinus or directly to the cardiac chambers. The great cardiac vein ascends along the anterior descending coronary and turns into the left atrioventricular groove. In the posterior atrioventricular groove it becomes the coronary sinus. It is joined near its entrance to the right atrium by the middle cardiac vein which ascends in the posterior interventricular groove and the small cardiac vein. The latter ascends along the marginal coronary artery before entering the posterior atrioventricular groove. Atrial veins also empty into the coronary sinus. A further group of veins, the anterior cardiac veins, run across the anterior aspect of the heart to drain directly into the right atrium. In addition to the coronary arteries and veins, the heart also has an extensive lymphatic network. These are divided into the deep, middle and superficial plexuses which drain into collecting channels accompanying the major arterial stems and finally into primary lymph nodes situated in the anterior mediastinum. The cardiac conduction system The full complement of the histologically specialised tissues making the conduction system of the heart comprises the sinus node and the atrioventricular system (Figure 10). The latter is made up of the atrioventricular node, the penetrating atrioventricular bundle and the ventricular bundle branches. The geometry of the right atrium is such that it is made up of bands of muscle which separate the orifices of the great veins and the oval fossa. The spread of excitation from the sinus to the atrioventricular node has been shown to spread preferentially along these broad bands of ordinary atrial myocardium. The sinus node The 'ultimum moriens', the last part of the heart to stop beating when the organ is isolated from the body, first prompted Wenckebach to believe that this may also be the seat of the heart beat.[1] The discovery of the sinus node in the heart of a mole culminated in a paper in 1907 'a remarkable in which Keith and Flack described the remnant of primitive sino auricular junction in all mammalian hearts. These fibres are in close connection with the vagus and sympathetic nerves, and have a special arterial blood supply; in them the dominating rhythm of the heart is believed to normally arise'.[2] The subsequent elegant combined anatomico-physiological studies of Lewis and the Oppenheimers in 1910 confirmed the pacemaking role of the sinus node.[3] The sinus node predominantly occupies an antero-lateral location of the superior cavo-atrial junction within the terminal groove (Figure 11A). Only occasionally it is horseshoe-shaped draping over the right atrial summit. In most adult hearts it is shaped like a tadpole measuring about 3mm in diameter at its widest Figure 10. The cardiac conduction system. Normally, the insulating fibro-fatty tissue plane at the atrioventricular junction prevents atrial myocardium from contacting ventricular myocardium. The penetrating bundle is the only muscular bridge. fibres persisting at https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 8/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology part and 15 to 20mm in length. A tapering 'tail' of the node may be traced from the epicardium to pass intramyocardially toward the inferior part of the terminal crest. The sinus node is easily recognised by the light microscope at low magnification. It is made up of small cells grouped together in interconnecting fascicles set in a fibrous tissue matrix (Figure 11B). The fibrous matrix becomes more prominent with increasing age. At the margins of the node is a short transitional area where nodal cells merge into atrial myocardium. In places, discrete tongues of transitional cells are found which extend into the terminal crest and toward the myocardial sleeve of the superior caval vein. The blood supply to the node shows considerable variation. A main artery penetrating the length of the node is seen in some hearts. In others, the nodal substance is penetrated by ramifications of an artery approaching the node through one or both ends, there being variations in nodal approaches. Even the origin of the sinus node artery is diverse, arising from the right or left coronary artery at different locations. Collections of ganglion cells are usually observed in the epicardium and also in the environs of the sinus node. Figure 11. A. The sinus node (dotted shape) is superimposed onto the terminal groove in this picture of the right atrium viewed from the right side. The arrows indicate the sectioning plane of the histological section shown in B. B. This section from an infant heart is stained in Masson s trichrome stain that colours myocardium red and fibrous tissue blue. The sinus node is readily identifiable by its composition of small myocytes in a fibrous matrix. The atrioventricular conduction system Occasional reference to this as the system of His-Tawara gives credit to two of the pioneering investigators in this field. The myocardial bridge that connects atrial myocardium to ventricular myocardium across the insulating fibro-fatty tissues of the atrioventricular junction was found by His in 1893 and given the appellation penetrating bundle of His .[4] Tawara's monograph[5] accompanied by colour plates in 1906 gave a detailed description of the atrioventricular node and how it was a continuum with the bundle described by His and the ventricular fibres previously described by Purkinje.[6] This firmly estabIished the presence of an atrioventricular conduction system (Figure 10) and was subsequently confirmed by Keith and Flack in the same year.[7] Gross anatomical landmarks to the location of the atrioventricular system are invaluable guides to cardiac surgeons and interventionists who have to perform intracardiac procedures since trauma to any part of the system can produce dire complications. The atrioventricular node is located at the apex of an angle formed by the tendinous continuation of the Eustachian valve (tendon of Todaro) and the annular insertion of the septal leaflet of the tricuspid valve (Figure 12). The coronary sinus completes the base of the triangular shape which bears the name 'triangle of Koch' in recognition of Koch's elegant descriptions.[8] The tendon of Todaro inserts into the central fibrous body. In the adult the atrioventricular node measures about 4 mm in width and 8 mm in length. In histological sections the compact part of the node is easily recognisable being composed of interconnecting fascicles of small cells, closely adherent to the central fibrous body. In cross section the node appears like a haIf-oval lying against the fibrous body (Figure 12D). A transitional zone of attenuated myocardial cells extends into the atrial myocardium. The node becomes the penetrating bundle as the conduction system passes through the central fibrous body (Figure 12C). https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 9/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology The Figure 13. This picture from Tawara s monograph (1906) shows the tree-fascicular arrangement of the left bundle branch in man. (Tawara S 1906 Das Reizleitungssystem des S ugetierherzens. Eine Anatomisch-Histologische Studie ber das Atrioventrikularb ndel und die Purkinjeschen F den. Gustav Fischer, Jena.) Figure 12. A. This view of the right atrium and right ventricle shows the anterior and posterior borders of the triangle of Koch (broken lines) that mark location of the atrioventricular node and bundle (orange shapes). The arrows B, C, D indicate the cuts made through the conduction system as shown on the histologic sections. B, C and D are step sections stained with Masson s trichrome technique and displayed in similar orientation tracing the atrioventicular conduction system from the AV node (AVN) that adjoins the central fibrous body (cfb), to the penetrating His bundle (H), and the branching bundle (BB) dividing into the left (LBB) and right (RBB) bundle branches. penetrating bundle veers to the left as it continues into the branching bundle to emerge in the left ventricle beneath the commissure that separates the right- coronary and non-coronary aortic valve leaflets. The bifurcation into left and right bundle branches marks the beginning of the branching bundle (Figure 12B). The right bundle branch is cord-like and frequently is the turns continuation of downwards and passes the substance of the septomarginal trabeculation directly beneath the medial papillary muscle complex. It then passes subendocardially towards the right ventricular apex and crosses the ventricular cavity within the moderator band before ramifying. The left bundle branch is morphologically different from the right bundle branch. It descends from the nodal- bundle axis as a sheet of cells within the subendocardial tissues of the aortic outflow tract. Tawara's original reconstructions show the bundle radiating in fan-like fashion into three major divisions which are interconnected distally by a subendocardial network that ramifies into the ventricular myocardium (Figure 13).[5] Later investigations using careful serial reconstructive techniques support the trifascicular concept seemingly in conflict with the 'hemiblock' theory which promotes a bifascicular morphology.[9] the nodal-bundle axis. intramyocardially It into References 1. Wenckebach KF. Beitr ge zur Kenntnis der menschlichen Herzt tigkeit. Arch Anat Physiol l907; 2:1. https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 10/11 7/3/23, 11:56 PM Anatomy of the Heart - Textbook of Cardiology 3. Lewis T. Oppenheimer BS, Oppenheimer A. Site of origin of the mammalian heart beat: the pacemaker in the dog. Heart 1910;2:147 4. His W Jr. Die Thatigkeit des embryonalen Herzens und deren Bedeutung f r die Lehre von Herzbewegung beim Erwachsenen. Ar Med Klin Leip 1893:14. 5. Tawara S. Das Reizleitungssystem des Saugetierherzen. Gustav Fischer, Jena. 1906 6. Purkinje JE. Mikroskopisch neurologische Beobachtungen. Archiv Anat Physiol u Wiss Med I845;12:28I. 8. Koch W. Der funktionelle Bau des menschlichen Herzens. Berlin: Urban v Schwarzenburg,1922:92. 9. Rosenbaum MB, Elizari MV, Lazzari JO. The hemiblocks. In: Tampa Tracings. Oldsmar, Fla. 1970. 10. Keith A and Flack M. The Form and Nature of the Muscular Connections between the Primary Divisions of the Vertebrate Heart. J Anat Physiol. 1907 Apr;41(Pt 3):172-89. 11. Keith A and Flack MW. The auriculo-ventricular bundle of the human heart. 1906. Ann Noninvasive Electrocardiol. 2004 Oct;9(4):400-9. DOI:10.1111/j.1542-474X.2004.94003.x | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Anatomy_of_the_Heart&oldid=2568" This page was last edited on 11 January 2021, at 22:28. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Anatomy_of_the_Heart 11/11 |
7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Atherosclerosis Ronak Delewi, MD; Hayang Yang, MsC; John Kastelein, MD, PhD A 53 years old man, without medical history or medication visits the family physician and makes an anxious impression. His friend has recently suffered from a myocardial infarction (MI) and he is worried that he might also soon face the same situation. As for family medical history, he has a father with hypertension and an uncle with diabetes mellitus. He does not seem to have any symptoms or complaints at this moment, but he has been smoking for 25 years and is overweight. Because of these characteristics he is worried that he will suffer from a MI. Upon physical examination, his BMI was 29 kg/m2, RR was 152/90 mmHg and heart rate was 75 bpm. The family physician orders a blood test for lipid profile and glucose. Both turn out to be in the normal range. The family physician gives the patient advice concerning primary prevention for atherosclerosis; quit smoking, try to achieve weight reduction, do regular physical activity, restrict alcohol consumption to less than 3 drinks a day and follow a varied and balanced diet. Regarding hypertension, the advice is to keep his RR under 140/90 mmHg. Antihypertensive medication is not indicated at this moment, because his 10-years risk of death due to cardiovascular disease (Systematic Coronary Risk Evaluation) is lower than 20%. He is advised to undergo regular checkups of cardiovascular risk profile or report to the doctor s office in case of chest pain. Contents Introduction Arterial vessel in homeostasis Three layers of arterial vessel Cellular components involved in atherosclerosis Endothelial cells Vascular smooth muscle cells Extracellular matrix 1.2 Arterial vessel with atherosclerosis Three pathologic stages of atherogenesis Initiation and formation of atherosclerotic plaque Endothelial dysfunction Lipoprotein entry and modification Leukocyte recruitment Foam cell formation Plaque progression Smooth muscle cell migration Extracellular matrix metabolism Plaque rupture https://www.textbookofcardiology.org/wiki/Atherosclerosis 1/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Integrity of plaque Thrombogenic potential after rupture Complications of atherosclerosis Risk factors of atherosclerosis Common risk factors Dyslipidemia Lipid-Altering therapy Tobacco smoking Lack of physical activity Obesity Diet Alcohol consumption Psychosocial factors Estrogen Status Biomarkers Homocysteine Lipoprotein A C-Reactive Protein and other markers of inflammation Infection Co-morbidity groups Hypertension Antihypertensive therapy Diabetes Mellitus References Introduction Since the 20th century, cardiovascular disease (CVD s) has grown to be the leading cause of death and disability in the world, illustrated by 17.3 million deaths per year in 2008. Amongst cardiovascular disease, coronary heart disease (46% among males, 38% among females) and cerebrovascular disease (34% among males, 37% among females) account for the largest proportion of CVD. In 2008, heart attack and stroke were responsible for 7.3 million deaths and 6.2 million deaths, respectively. Obstructive coronary and cerebrovascular diseases are caused, in the vast majority of cases, by atherosclerosis. Atherosclerotis vascular disease begins early in life and over time can eventually lead to obstructive arterial disease. Once atherosclerotic lesions become clinically significant, serious acute complications such as ischemic heart disease, MI and stroke may occur. This chapter deals with the complex pathological process of atherosclerosis, possible consequences of atherosclerosis and the most recent treatment for atherosclerosis in order to prevent CVD s. Arterial vessel in homeostasis https://www.textbookofcardiology.org/wiki/Atherosclerosis 2/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Figure 2. World map CVD mortality rates in females orld map CVD es in males Figure 3. Distribution of CVD death among males in 2008 stribution of CVD g females in 2008 The core of the pathogenesis of atherosclerosis is a disease state of the arterial wall. In order to understand the pathogenesis of atherosclerosis, it is thus necessary to know about the function and normal morphology of non-pathological arteries. Three layers of arterial vessel The normal arterial vessel consists of 3 layers, namely intima, media and outer adventitia. The intima is located closest to the arterial lumen and is therefore most intimate with the blood. This layer is composed of a single layer of endothelial cells (endothelium), connective tissue, and several smooth muscle cells. The endothelium functions as an active metabolic barrier as well as a carrier between blood and the arterial wall. It plays a crucial role in atherosclerosis. Connective tissue consists of a matrix of collagen, proteoglycans and elastin. Lymphocytes, macrophages and other types of inflammatory cells may occasionally reside in the intima. The media is the middle layer and its inner and outer boundaries are formed by the internal and external elastic laminae. The media consists of layers of smooth muscle cells with contractile and synthetic function. As for the contractile function, smooth muscle cells enable vasoconstriction and vasodilatation. As for the synthetic function, they are responsible for the growth of the vascular extracellular matrix. The most external vessel wall layer is called the adventitia and contains fibroblasts, connective tissue, nerves, lymphatics and vasa vasorum. Inflammatory cells may also occasionally reside in the adventitia. https://www.textbookofcardiology.org/wiki/Atherosclerosis 3/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology There is a constant dynamic interchange between the arterial wall and its cellular components and the surrounding extracellular matrix. By understanding the physiology of this dynamic interchange and the function of each cellular component, the dysfunction of these cellular components leading to atherogenesis can be better understood. Cellular components involved in atherosclerosis Endothelial cells The normal artery wall contains endothelial cells that manage the homeostasis of the wall by structural, metabolic, and signaling functions. The endothelium plays a role as a barrier to elements contained in the blood, but is also an active biologic interface between the blood and other tissues, regulating cellular and nutrient trafficking. It has several important functions such as keeping certain elements in blood separated from the vessel and maintaining a balance between pro-coagulant and anticoagulant activity, pro- and anti-inflammatory response, and contracted and relaxed vasomotor tone. The endothelium produces antithrombotic molecules in order to prevent blood from clotting. Certain molecules such as heparin sulfate, thrombomodulin, and plasminogen rest on the endothelial surface whereas molecules such as prostacyclin and nitric oxide (NO) enter the blood. Endothelium can produce prothrombotic molecules when it encounters stressors; however, it normally maintains a balanced anticoagulant state, maintaining blood fluidity. Endothelial cells also have an important function as a regulator of the immune response. In a normal situation without pathologic stimuli, endothelial cells are not capable to attract and bind patrolling leukocytes, thus maintaining an anti-inflammatory state. When local injury or infection initiates pathologic stimulation, endothelial cells respond by secreting chemokines that attract white blood cells to the injured area. Additionally, endothelium produces cell surface adhesion molecules, which recruit mononuclear cells to the endothelium and therefore promote their migration to the injury site. This response is important for the development of atherosclerosis. Another function of endothelium is to modulate contraction of smooth muscle cells in the media by releasing substances such as vasodilators and vasoconstrictors. Vasodilators (e.g. NO, prostacyclin) and vasoconstrictors (e.g. endothelin) fine-tune the resistance of the vessel and subsequently alter the arterial blood flow. Endothelium normally maintains a state of net relaxed vasomotor tone with a predominance of vasodilators. Endothelium can also respond to various physical stimuli such as shear stress and can additionally dilate the blood vessel. The endothelium principally regulates such response through release of NO. This endothelial-dependent response is called flow-mediated vasodilation (FMD), which can be measured for clinical evaluation of endothelial function. For example, impairment of FMD is observed in the early stages of atherosclerosis. However, endothelial function tests are currently not recommended to be used for surrogate markers in clinical practice since the tests are technically challenging and the validation of clinical benefits in the evaluation of cardiovascular risk requires more evidence. As mentioned earlier, endothelial cells can respond to or in other words get activated due to changes in the local extracellular milieu. Examples of such changes are common stresses (e.g. shear stress and mild changes in temperature), transient infections and minor trauma. The term endothelial cell activation (EC activation) refers to a change from the normal state, illustrated by loss of barrier function, pro- adhesive (leukocyte adhesion), vasoconstriction, and procoagulant properties. EC activation is not necessarily linked to disease and can be temporary and mild or permanent and severe. https://www.textbookofcardiology.org/wiki/Atherosclerosis 4/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology In conclusion, the normal arterial endothelium consists of a dynamic interface with net anticoagulant properties, net relaxation of smooth muscle cells and anti-inflammatory characteristics. Endothelial cells may react to various changes in homeostasis and become activated endothelial cells . Vascular smooth muscle cells As mentioned earlier, smooth muscle cells have two functions, namely contractile and synthetic. Vasoconstriction and vasodilatation are regulated by various vasoactive substances such as angiotensin II, acetylcholine, NO and endothelin, which are released by endothelium. Another element of contractile function is the elasticity of the vessel, which is regulated by the lamina elastica. They are situated between the smooth muscle cells and are responsible for the stretching of the vessel during systole and diastole. This function is crucial in the pathogenesis of atherosclerosis, because it prevents the weakening of the vessel wall that can prevail as a complication of atherosclerosis. For example, aneurysm due to weakening of the vessel wall is a serious complication of atherosclerosis. It is important to understand the synthetic function of smooth muscle cells since the dysfunction of it is thought to contribute to the pathogenesis of atherosclerosis. Normally the smooth muscle cells synthesize collagen, elastin and proteoglycans that form the connective tissue matrix of the vessel wall. Smooth muscle cells can also synthesize vasoactive and inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor- (TNF- ). These mediators stimulate leukocyte migration and induce the endothelial cells to express leukocyte adhesion molecules as mentioned earlier. This synthetic function is found to be more dominant in case of an atherosclerotic plaque, which is illustrated in the next section (1.2). Although smooth muscle cells rarely divide in normal circumstances, it can proliferate in response to injury, which is an important sign of atherosclerotic plaque formation. Extracellular matrix Vascular extracellular matrix in the media consists of elastin, proteoglycans and fibrillar collagen, which are principally synthesized by smooth muscle cells as mentioned earlier. With the provision of flexibility by elastin and biomechanical strength by fibrillar collagen, the arterial vessel is able to maintain the structural integrity despite high pressure within the lumen. 1.2 Arterial vessel with atherosclerosis Three pathologic stages of atherogenesis Atherogenesis can be divided into five key steps, which are 1) endothelial dysfunction, 2) formation of lipid layer or fatty streak within the intima, 3) migration of leukocytes and smooth muscle cells into the vessel wall, 4) foam cell formation and 5) degradation of extracellular matrix. Via these consecutive steps, an atherosclerotic plaque is formed. The formation of the plaque can also be divided into three major stages namely 1) the fatty streak, which represents the initiation 2) plaque progression, Atheroclerotic plaque in a coronary artery https://www.textbookofcardiology.org/wiki/Atherosclerosis 5/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology which represents adaption and 3) plaque disruption, which represents the clinical complication of atherosclerosis. Initiation and formation of atherosclerotic plaque The earliest visible signs of atherogenesis are the fatty streak and pre-existing lesions of adaptive intimal thickening. Fatty streak is a yellow discoloration on the surface of the artery lumen, which is flat or slightly elevated in the intima and contains accumulations of intracellular and extracellular lipid. At this stage of initiation, the fatty streak doesn t protrude substantially into the artery wall nor impedes blood flow. This process is already visible in most people by the age of 20. At this stage, there are no symptoms and this lesion may even diminish over time. Initiation of fatty streak development is most likely caused by endothelial dysfunction, since it involves entry and modification of lipids within the subintima. This modified layer of lipids creates a proinflammatory environment and initiates the migration of leukocytes and formation of foam cells (Figure 5). Intimal thickening mainly contains smooth muscle cells and proteoglycan-collagen matrix with a few or no infiltrating inflammatory cells. Figure 5. Fatty streak formation Endothelial dysfunction Table 6. Factors correlated with endothelial dysfunction Endothelial dysfunction is a primary event in atherogenesis, which can be caused by various agents, such as physical stress and chemical irritants. Endothelial dysfunction is also observed in other pathological conditions, which are often related as hypercholesterolemia, diabetes, hypertension, heart failure, cigarette smoking and aging. Increased age Male sex Family history of coronary heart disease Tobacco smoking Elevated cholesterol Low HDL-cholesterol Diabetes mellitus Hypertension Obesity High fat consumption to atherosclerosis such Endothelial cells can display different reactions according to various levels of physical stress. There are two atheroprotective endothelial functions from physical stress. When endothelial cells are exposed to laminar flow, which display minimal physical stress, they secrete NO. NO functions as an anti- atherosclerotic substance through vasodilation, inhibition of platelet aggregation and anti-inflammatory effects. The second function is executed, when exposed to laminar flow by an expression of the antioxidant enzyme superoxide dismutase. This enzyme performs anti-atherosclerotic role by acting against reactive oxygen species, which are produced by chemical irritants or transient ischemia in the vessel. https://www.textbookofcardiology.org/wiki/Atherosclerosis 6/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Unfortunately, atheroprotective endothelial functions can be impaired by several factors. The first factor is disturbed flow (low shear stress with rapid fluctuations), which is typically located at arterial branch points and bifurcations and can impair the protective functions. This is well in prevalence of illustrated by the difference atherosclerosis between branched arteries and bifurcated vessels. Bifurcation areas such as the common carotid and left coronary arteries are common deposition sites for atherosclerosis than arteries with few branches such as the internal mammary artery. Thus, many observations show that the distribution of atherosclerotic lesions is common in large vessels and they vary in location and frequency among different vascular beds. These findings encourage a belief that hemodynamic factors play an important role in atherogenesis. Furthermore, the fact that hypertension intensifies the severity of atherosclerotic lesions additionally supports this hypothesis. these two Table 7. Interventions that enhance endothelial function L-arginine Estrogen Antioxidants Quit smoking Reducing cholesterol Exercise the Another major atheroprotective endothelial chemical irritants such as cigarette smoking, abnormally high circulating lipid levels and high glucose level (diabetes mellitus). They can contribute to endothelial dysfunction and are all well- known risk factors for atherosclerosis. Exposure to chemical irritants promotes endothelial dysfunction by increasing endothelial production of reactive oxygen species, which alter the metabolic and synthetic functions of endothelial cells. As a result, the endothelium become inclined to exhibit proinflammatory processes, such as secreting inflammatory cytokines. factor that can function impair is Figure 8. Endothelial dysfunction: Leukocyte adhesion and migration into the deep layer of the intima. In conclusion, hemodynamic and chemical stressors contribute to disturbance of endothelial homeostasis and promote endothelial dysfunction. This in impairment of permeability barrier function, secretion of stimulation of adhesion inflammatory molecules on the cell surface that promote leukocyte recruitment, and altered antithrombotic properties and release of vasoactive molecules (Figure 8). Consequently, these effects establish the groundwork for further advancement of atherosclerosis. results cytokines, Lipoprotein entry and modification Disruption of the integrity of endothelial barrier due to endothelial dysfunction allows the passage of circulating lipoproteins (low-density lipoprotein, LDL) into the intima. By binding to proteoglycans, LDL particles start to accumulate. This accumulation is a critical process in atherogenesis since LDL may undergo chemical modifications while residing longer in the intima. It is needless to say that an elevated circulating LDL concentration strongly contributes to this accumulating process. Another major risk https://www.textbookofcardiology.org/wiki/Atherosclerosis 7/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology factor for this process is hypertension since it causes augmented vessel wall stress. Elevated vessel wall stress influences smooth muscle cells to synthesize proteoglycans in the intima, promoting LDL-binding with proteoglycans and therefore contributing to trapping of lipoproteins and lipid accumulation within the intima. At this point, macrophages adhere to dysfunctional endothelial cells and transmigrate into the intima. These macrophages are called foam cells after they have taken up lipids. As mentioned earlier, chemical modification occurs with LDL when chronic accumulation takes place inside the intima. There are several types of chemical modification that may occur. One is called oxidation and it results from the chemical reaction of reactive oxygen species and pro-oxidant enzymes produced by endothelial or smooth muscle cells, or macrophages penetrating the intima. This type of oxidative stress leads to cellular dysfunction and damage in endothelial cells and macrophages. Furthermore chronic hyperglycemia can stimulate glycation of LDL that may ultimately alter LDL into an antigenic and proinflammatory molecule. This explains why diabetes mellitus is a major risk factor for atherosclerosis. The biochemical modification of LDL into a proinflammatory molecule contributes to the inflammation process established by endothelial dysfunction. Furthermore, the oxidized LDL molecule induces tissue damage, which can initiate angiogenesis, forming new vasa vasorum in the plaque. It also induces leukocyte recruitment and foam cell formation in the fatty streak throughout the plaque development. Leukocyte recruitment Leukocyte recruitment to the arterial wall is another key step in atherogenesis, which is dependent on two important factors; expression of leukocyte adhesion molecules (LAM) on the endothelial wall and chemoattractant signals that direct diapedesis (intruding of molecules through the intact vessel wall). These two factors mainly direct monocytes to the atherosclerotic lesion. T lymphocytes that play a central role in the immune system reside within plaques at all stages of atherogenesis, mainly producing cytokines. As mentioned earlier, modified LDL can maintain leukocyte recruitment by inducing LAM and chemokine expression. It can also stimulate endothelial and smooth muscle cells to produce proinflammatory cytokines. These proinflammatory cytokines can also induce LAM and chemoattractant cytokine expression, equivalent to the working of modified LDL. In conclusion, modified LDL can directly or indirectly promote leukocyte recruitment and atherogenesis. Foam cell formation When monocytes enter the intima, they differentiate into phagocytic macrophages. These phagocytic macrophages may become foam cells when they absorb lipoproteins. They don t phagocyte LDL with a classic cell surface LDL-receptor, since it does not recognize modified LDL, but with a family of scavenger receptors that do bind and internalize modified LDL. Uptake by scavenger receptors avoids negative feedback inhibition from the high cholesterol content unlike the classic LDL-receptors, and allows the macrophages to imbibe cholesterol-rich lipid that results into the formation of foam cells. This uptake seems to be beneficial at first sight, since it absorbs the inflammatory modified-LDL, however since these foam cells have impaired trafficking, they will be locally accumulated in the plaque and encourage the plaque progression by serving as a source of proinflammatory cytokines. Plaque progression https://www.textbookofcardiology.org/wiki/Atherosclerosis 8/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology The atherosclerotic plaque at this stage is called fibrous cap atheroma featuring two characteristics, which are lipid-rich necrotic core and encapsulation by a fibrous cap (Figure 9). The fibrous cap is an area between the vessel lumen and the core of the plaque, which contains dead foam cells, macrophages, smooth muscle cells, lymphocytes and extracellular matrix. A distinctive hallmark of this phase is necrosis with macrophage infiltration around a lipid pool and loss of proteoglycans or collagen. At this point, the deposition of free cholesterol is not easily visible and the plaque does not always cause luminal restriction of blood flow due to a compensatory outward remodeling of the plaque wall. This remodeling preserves the diameter of the vessel lumen and thus may evade detection by angiography. Continuous plaque growth at a later stage contains cellular debris, higher free cholesterol and results into complete depletion of extracellular matrix. From this stage, the fibrous cap atheroma may go through episodes of hemorrhage with or without calcification and even fibrous cap disruption. Progressive vessel narrowing may result in ischemia and can cause ischemic symptoms such as angina pectoris or intermittent claudication. Figure 9. Fibrous cap formation and the necrotic core. Smooth muscle cell migration Smooth muscle cells play a central role at the phase of transition from fatty streak to plaque formation. During this phase, smooth muscle cells migrate from the media to the intima. After migration, smooth muscle cells proliferate within the intima and secrete extracellular matrix macromolecules. Additionally, foam cells, activated platelets and endothelium stimulate substances that induce the migration and accumulation of smooth muscle cells. For example, foam cells release platelet derived growth factor (PDGF), cytokines and growth factors that directly contribute to the migration and proliferation process, and they also activate smooth muscle cells and leukocytes to reinforce inflammation in the atherosclerotic lesion. Although plaque progression is traditionally known as a gradual and continuous process, recent evidence claims that this process can be strongly accentuated by bursts of smooth muscle replication. The observation of small ruptures within the plaque occurring without any clinical symptoms or signs supports this suggestion. These small ruptures expose tissue factor secreted by foam cells that stimulates coagulation and microthrombus formation in the lesion. Such microthrombi contain activated platelets that release additional factors such as PDGF and heparinase that can further stimulate local smooth muscle cell migration and proliferation. Heparinase stimulates smooth muscle cell migration and proliferation by degrading heparan sulfate, which normally counteracts this process. Extracellular matrix metabolism Metabolic processes in extracellular matrix play a central role in bridging the plaque progression to plaque rupture. Ultimately, this process weakens the fibrous cap, predisposing it to rupture. This process is influenced by the balance of matrix deposition synthesis by smooth muscle cells and degradation by matrix metalloproteinases (MMP), a class of proteolytic enzymes. For example, PDGF and TGF- stimulate interstitial collagen production, while inflammatory cytokines such as IFN- inhibits collagen synthesis. TGF- also induces formation of fibronectin and proteoglycans. It is an important regulator https://www.textbookofcardiology.org/wiki/Atherosclerosis 9/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology since it enhances the expression of protease inhibitors, leading to the inhibition of proteolytic enzymes that promote matrix degradation. On the other hand, inflammatory cytokines weaken the fibrous cap by stimulating local foam cells to secrete MMP that degrades collagen and elastin of the fibrous cap. Furthermore, the deeper parts of the thickened intima undergo necrosis due to poor nourishment. Plaque rupture Integrity of plaque Chronic shifting of the balance towards extracellular matrix metabolism leads to serious consequences for the plaque integrity. As mentioned earlier, it accelerates inflammatory stimulation or activation of apoptosis pathways and therefore leads to death of smooth muscle and foam cells. Cell death leads to release of cellular contents, whereby more lipids and cellular debris is absorbed to the dynamic lipid core. Due to this process, the size of the lipid core grows and as a result alters biomechanical environment and hence the stability of the plaque. One example of this is a plaque border adjacent to the normal tissue, called shoulder region, which is the main location where the hemodynamic stress is focused. As the size and the protrusion of the plaque in the vessel increase, the hemodynamic stress will also increase around local accumulation of foam cells and lymphocytes at this site makes the plaque more susceptible to rupture by accelerating degradation of extracellular matrix. However, although shoulder area is considered as the weakest point where the fibrous cap would mostly likely rupture, there have been autopsy studies that showed an equal number of ruptures occurring at the midportion of the fibrous cap. When the fibrous cap is very thick and contains small lipid core, the plaque is called stable and it may reinforce the narrowing of the artery, but on the other hand diminishes the susceptibility to rupture. Plaques with thinner fibrous caps are called vulnerable plaques. They are identified by a large necrotic core, rich with lipid, taking about 25% of the plaque area, and a thin fibrous cap of less than 65 M thickness, which separates the necrotic core from the vessel lumen. Vulnerable plaque is infiltrated by a large amount of macrophages and a smaller amount of T-lymphocytes. It typically lacks smooth muscle cells due to apoptosis. This type of lesion causes less obstruction in the artery, but is more fragile and has higher susceptibility to rupture and trigger thrombosis than a thick fibrous cap. At this stage, plaque hemorrhage can occur due to rupture of vasa vasorum within a plaque. Vasa vasorum is a newly formed vascularization in the plaque due to tissue damage. Due to its fragility it may rupture easily, increasing the risk to form intraplaque hemorrhage. Intraplaque hemorrhage may lead to subsequent rupture of the fibrous cap (Figure 10) or occlusion of the vessel through intramural hematoma. Plaque calcification is another factor that contributes to plaque rupture. It usually occurs in areas of necrosis and elsewhere in the plaque and can eventually lead to higher rigidity of the vessel wall. Calcification is dependent on mineral deposition and resorption by osteoblast-like and osteoclast-like cells in the vessel wall. In conclusion, there are seven important factors associated with plaque ruptures; range of inflammation area, considerable size of lipid core, fibrous cap thinner than 65 M, apoptosis leading to fewer smooth muscle cells, disrupted balance of proteolytic enzymes and their inhibitors, Figure 10. The ruptured plaque. the shoulder region. Furthermore, https://www.textbookofcardiology.org/wiki/Atherosclerosis 10/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology plaque calcification, and hemorrhage in the plaque. Although it remains difficult to foresee the clinical consequences, progression to a complicated plaque can lead to major cardiovascular disease, mostly affecting individuals in their 60s and 70s, although it may also occur among people at an earlier age. Thrombogenic potential after rupture When the fibrous cap is ruptured, the highly thrombogenic components of the necrotic core, including tissue factor, gets in direct contact with the circulating monocytes in the blood. It is believed that these circulating monocytes in the blood play a stronger role as a source of tissue factor than the necrotic core. Tissue factor stimulates platelet activation and thus can initiate and propagate thrombus. The thrombus formed at the rupture site is called white thrombus due to its grossly white appearance of rich platelet. At the proximal and distal ends near the site of white thrombosis there is another type of thrombus composed of layers of red blood cells and fibrin and is therefore called red thrombus. Thrombosis can be healed through several processes such as penetration of smooth muscle cells, neovascularization via vasa vasorum, proliferation of extracellular matrix, inflammation and re-endothelialization on the luminal surface. Thus clinically, ruptures can be silent and heal, without major clinical complications such as MI and stroke. For example, small non-occlusive thrombi may be reabsorbed into the plaque, continuing the process of smooth cell growth and fibrous deposition. The extent of how occlusive and transient the thrombus will be is largely dependent on the thrombogenic potential of the plaque. The counter-balancing of coagulation and fibrinolysis also determines the probability of a major clinical event due to occlusive thrombosis. Inflammatory stimuli in the plaque environment incite smooth muscle cells, endothelial cells, and foam cells to release tissue factor that initiates the extrinsic coagulation pathway. Inflammatory stimuli also stimulate expression of antifibrinolytics such as plasminogen activator inhibitor-1 and consequently enhance thrombosis. As mentioned earlier, the activated endothelial cells also contribute to thrombosis and coagulation by depositing fibrin at the vascular wall. Thus, the inflammatory and dysfunctional condition of the plaque environment decreases the counterbalancing of coagulation and fibrinolysis, increasing the probability of major clinical complications of atherosclerosis. The concept of vulnerable plaque has developed into a new concept of vulnerable patient as the concept of pathogenesis of atherosclerosis was linked to a person s susceptibility to coagulation and thus vascular events, which can be influenced by many personal factors such as genetics (e.g. procoagulant prothombin gene mutation), coexisting condition (e.g. diabetes), and lifestyle factors (e.g. smoking, obesity). https://www.textbookofcardiology.org/wiki/Atherosclerosis 11/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Progression of coronary atherosclerosis can be gradual (bottom) or can lead to plaque rupture with acute occlusion of a coronary vessel due to clot formation Complications of atherosclerosis The clinical complications of atherosclerosis are highly dependent on the location and size of affected vessels, the duration of the chronic process, and the type of plaque, since the severity of impairment of atherosclerosis differs throughout the vasculature. For example, stable plaque can easily result into angina pectoris due to its thick fibrous cap that directly affects the diameter of the relatively small coronary vessels. On the other hand, vulnerable plaque is non- Figure 11. Most common locations of atherosclerosis Dorsal section of the abdominal aorta Proximal coronary arteries Popliteal arteries Descending thoracic aorta Internal carotid arteries Renal arteries stenotic, but can easily cause acute therefore myocardial thrombosis and infarction due to its fragility towards rupture when located at physically stressed areas such as bifurcations. Often with vulnerable plaques there are relatively few symptoms, however they are more numerous and dispersed throughout the arteries compared to stable plaque . Thus, you can either have an occlusion due to the growing plaque or due to the embolization of the ruptured fragments of the original plaque. Due to the difficult detection of vulnerable plaques while they are widely dispersed, it is highly important to tackle the risk factors prior to plaque rupture. Thus in the following paragraph, we will highlight the clinical risk factors associated four major with atherosclerosis. The clinical consequences of atherosclerosis are listed and explained below. Figure 12. Complications of atherosclerosis 1. Acute narrowing of the vessel lumen: When the plaque ruptures, it will release its pro-coagulants in the bloodstream and that will lead to the formation of thrombus at the rupture site. The rupture often occurs at sites of erosion and fissuring on the fibrous cap surface. This thrombus may cause a complete occlusion of a particular vessel and result in ischemic necrosis (infarction) of the tissue that this particular vessel is supplying to. Clinically this is manifested as stroke, MI, gangrene of several possible organs such as intestine, spleen or lower extremities. These occlusions may also dissolve spontaneously due to pro-fibrinolytic enzymes such as streptokinase and tissue plasminogen activator (TPA). 2. Chronic occlusion: When the occlusion is gradual and incomplete, it may chronically disturb the blood supply to tissues in the distribution of the affected vessel. This can result in chronic ischemia of those tissues that can additionally lead to complaints of angina pectoris or intermittent claudication or to organ atrophy (e.g. atrophy of kidney, intestines and skin due to impairment of blood flow in renal artery, mesenteric artery, peripheral vasculature among diabetics.). https://www.textbookofcardiology.org/wiki/Atherosclerosis 12/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 3. Embolism: Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. For example, fragments of thrombi in abdominal aorta may transfer to the popliteal artery subsequently resulting in gangrene of the leg. Ulceration of atheroma may also produce cholesterol crystal emboli . This type of emboli is visualized as needle- shaped areas in affected tissues, mostly detected in the kidney. 4. Aneurysm: After a chronic period, atherosclerotic lesion may extend into the medial layer, resulting into atrophy and loss of elastic tissue. This can subsequently cause dilatation and weakness of the artery, forming aneurysm. Over time, aneurysms may suddenly rupture and result in a life- threatening situation for the patients. Risk factors of atherosclerosis Recent studies have shown that atherosclerosis is not just the inevitable process of aging, but also a process with many modifiable components. A worldwide INTERHEART study has established the importance of nine potentially modifiable risk factors for atherosclerosis, which account for over 90% of the population-attributable risk of a first MI (figure 12). A variety of non-modifiable risk factors such as advanced age, gender and hereditary coronary heart disease are important to recognize in patients with atherosclerosis. Recently the role of several biological markers associated with the development of cardiovascular events is accentuated since one out of five cardiovascular events occurs in patients lacking the earlier mentioned risk factors. Figure 13. Nine modifiable risk factors for atherosclerosis according to INTERHEART study Dyslipidemia Tabacco smoking Lack of physical activity Abdominal obesity Psychosocial factors Daily consumption of fruits and vegetables Regular alcohol consumption Hypertension Diabetes Mellitus Common risk factors Dyslipidemia One of the major modifiable risk factors for atherosclerosis is hypercholesterolemia. Studies show that dyslipidemia (defined as an elevated apo B to apo A-1 ratio) was responsible for 49% of the population- attributable risk of a first MI. In countries with high consumption of saturated fat and high cholesterol levels (e.g. the United States), observational studies have shown that the mortality rates from coronary disease are higher compared with countries with traditionally low consumption of saturated fat and cholesterol levels (e.g. Japan). Several trials have shown that the risk of ischemic heart disease positively correlates with higher total serum cholesterol levels. For example, the impact of hypercholesterolemia can be illustrated by an observational result from the Framingham Heart Study, which shows that a person with a total cholesterol level of 240 mg/dl has twice the coronary risk a person would have with a cholesterol level of 200 mg/dl. However, it is a mistake to think that all lipoproteins consisting of cholesterol are harmful since cholesterol can provide critical functions to all cells that need to form membranes and to synthesize products such as steroid hormones and bile salts. Incidence of atherosclerosis and coronary artery disease increases with higher levels of LDL particles. As mentioned earlier, LDL can accumulate in the intima of the artery in excess and undergo chemical modifications that activate endothelial cells to proceed to atherosclerosis. When people generally refer to https://www.textbookofcardiology.org/wiki/Atherosclerosis 13/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Figure 14. Recommendations regarding dyslipidemia General recommendations: |
The concept of vulnerable plaque has developed into a new concept of vulnerable patient as the concept of pathogenesis of atherosclerosis was linked to a person s susceptibility to coagulation and thus vascular events, which can be influenced by many personal factors such as genetics (e.g. procoagulant prothombin gene mutation), coexisting condition (e.g. diabetes), and lifestyle factors (e.g. smoking, obesity). https://www.textbookofcardiology.org/wiki/Atherosclerosis 11/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Progression of coronary atherosclerosis can be gradual (bottom) or can lead to plaque rupture with acute occlusion of a coronary vessel due to clot formation Complications of atherosclerosis The clinical complications of atherosclerosis are highly dependent on the location and size of affected vessels, the duration of the chronic process, and the type of plaque, since the severity of impairment of atherosclerosis differs throughout the vasculature. For example, stable plaque can easily result into angina pectoris due to its thick fibrous cap that directly affects the diameter of the relatively small coronary vessels. On the other hand, vulnerable plaque is non- Figure 11. Most common locations of atherosclerosis Dorsal section of the abdominal aorta Proximal coronary arteries Popliteal arteries Descending thoracic aorta Internal carotid arteries Renal arteries stenotic, but can easily cause acute therefore myocardial thrombosis and infarction due to its fragility towards rupture when located at physically stressed areas such as bifurcations. Often with vulnerable plaques there are relatively few symptoms, however they are more numerous and dispersed throughout the arteries compared to stable plaque . Thus, you can either have an occlusion due to the growing plaque or due to the embolization of the ruptured fragments of the original plaque. Due to the difficult detection of vulnerable plaques while they are widely dispersed, it is highly important to tackle the risk factors prior to plaque rupture. Thus in the following paragraph, we will highlight the clinical risk factors associated four major with atherosclerosis. The clinical consequences of atherosclerosis are listed and explained below. Figure 12. Complications of atherosclerosis 1. Acute narrowing of the vessel lumen: When the plaque ruptures, it will release its pro-coagulants in the bloodstream and that will lead to the formation of thrombus at the rupture site. The rupture often occurs at sites of erosion and fissuring on the fibrous cap surface. This thrombus may cause a complete occlusion of a particular vessel and result in ischemic necrosis (infarction) of the tissue that this particular vessel is supplying to. Clinically this is manifested as stroke, MI, gangrene of several possible organs such as intestine, spleen or lower extremities. These occlusions may also dissolve spontaneously due to pro-fibrinolytic enzymes such as streptokinase and tissue plasminogen activator (TPA). 2. Chronic occlusion: When the occlusion is gradual and incomplete, it may chronically disturb the blood supply to tissues in the distribution of the affected vessel. This can result in chronic ischemia of those tissues that can additionally lead to complaints of angina pectoris or intermittent claudication or to organ atrophy (e.g. atrophy of kidney, intestines and skin due to impairment of blood flow in renal artery, mesenteric artery, peripheral vasculature among diabetics.). https://www.textbookofcardiology.org/wiki/Atherosclerosis 12/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 3. Embolism: Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. For example, fragments of thrombi in abdominal aorta may transfer to the popliteal artery subsequently resulting in gangrene of the leg. Ulceration of atheroma may also produce cholesterol crystal emboli . This type of emboli is visualized as needle- shaped areas in affected tissues, mostly detected in the kidney. 4. Aneurysm: After a chronic period, atherosclerotic lesion may extend into the medial layer, resulting into atrophy and loss of elastic tissue. This can subsequently cause dilatation and weakness of the artery, forming aneurysm. Over time, aneurysms may suddenly rupture and result in a life- threatening situation for the patients. Risk factors of atherosclerosis Recent studies have shown that atherosclerosis is not just the inevitable process of aging, but also a process with many modifiable components. A worldwide INTERHEART study has established the importance of nine potentially modifiable risk factors for atherosclerosis, which account for over 90% of the population-attributable risk of a first MI (figure 12). A variety of non-modifiable risk factors such as advanced age, gender and hereditary coronary heart disease are important to recognize in patients with atherosclerosis. Recently the role of several biological markers associated with the development of cardiovascular events is accentuated since one out of five cardiovascular events occurs in patients lacking the earlier mentioned risk factors. Figure 13. Nine modifiable risk factors for atherosclerosis according to INTERHEART study Dyslipidemia Tabacco smoking Lack of physical activity Abdominal obesity Psychosocial factors Daily consumption of fruits and vegetables Regular alcohol consumption Hypertension Diabetes Mellitus Common risk factors Dyslipidemia One of the major modifiable risk factors for atherosclerosis is hypercholesterolemia. Studies show that dyslipidemia (defined as an elevated apo B to apo A-1 ratio) was responsible for 49% of the population- attributable risk of a first MI. In countries with high consumption of saturated fat and high cholesterol levels (e.g. the United States), observational studies have shown that the mortality rates from coronary disease are higher compared with countries with traditionally low consumption of saturated fat and cholesterol levels (e.g. Japan). Several trials have shown that the risk of ischemic heart disease positively correlates with higher total serum cholesterol levels. For example, the impact of hypercholesterolemia can be illustrated by an observational result from the Framingham Heart Study, which shows that a person with a total cholesterol level of 240 mg/dl has twice the coronary risk a person would have with a cholesterol level of 200 mg/dl. However, it is a mistake to think that all lipoproteins consisting of cholesterol are harmful since cholesterol can provide critical functions to all cells that need to form membranes and to synthesize products such as steroid hormones and bile salts. Incidence of atherosclerosis and coronary artery disease increases with higher levels of LDL particles. As mentioned earlier, LDL can accumulate in the intima of the artery in excess and undergo chemical modifications that activate endothelial cells to proceed to atherosclerosis. When people generally refer to https://www.textbookofcardiology.org/wiki/Atherosclerosis 13/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology Figure 14. Recommendations regarding dyslipidemia General recommendations: A varied and balanced diet Regular fish intake (n 3 fatty acids) Fruits and vegetables, 3-5 portions per day, cereals and grain products, skimmed dairy products, and low-fat meat Restriction of fatty products and products with a high caloric density. The total fat intake should not be higher than 30% of calory intake. The saturated fat intake should not be higher than 30% of total lipids The cholesterol intake should be under 300 mg per day Specific diet recommendations: Avoid hard margarines and products of animal origin (meat, dairy products) Increase intake of omega-3 fatty acids from fish oils and certain vegetal oils Increase intake of polyunsaturated fatty acids, soluble fibres, and phytosterols Exercise and body weight reduction within obese group Normalization of glycaemia in diabetic patients Reduce the intake of refined sugars and replace them with complex sugars from fruits, vegetables, and grain products bad cholesterol , they are referring to LDL particles. On the other hand, high levels of high-density lipoprotein (HDL) constitute good cholesterol since it protects against atherosclerosis by reversing the cholesterol transport from peripheral tissues to the liver for disposal and functions as an antioxidant. In order to give additional explanation to what is bad cholesterol, all lipid and lipoprotein abnormalities that are associated with higher coronary risk will be named subsequently: increased total cholesterol, increased LDL-cholesterol, ratio, hypertriglyceridemia, increased non-HDL-cholesterol, elevated lipoprotein A, elevated apolipoprotein B (apo B is primarily found in LDL), decreased apolipoprotein A-I (apo A-1 is found in HDL), small and dense LDL particles. low HDL-cholesterol, elevated total-to-HDL-cholesterol There are several causes for persistent elevated levels of LDL, such as high fat consumption or genetic abnormalities (e.g. familial hypercholesterolemia). Familial hypercholesterolemia is a condition with deficient LDL receptors that cannot efficiently dispose LDL from the circulation. There are two types of this disease with different manifestations. Patients with the heterozygote type have only one defective gene for the receptor and suffer from high serum level of LDL, easily developing atherosclerosis. Homozygotes have a complete lack of normal LDL receptors and thus may experience cardiovascular events already in the first decade of life. In the absence of genetic abnormalities, the quantity of cholesterol in serum is strongly related to saturated fat consumption. Lipid-Altering therapy Controlling serum lipids is a key step to limit the consequences of atherosclerosis. Major clinical trials have shown that coronary events and mortality significantly decreased when total and LDL-cholesterol levels were reduced for the primary and secondary prevention of CAD events. One of the most important strategies to reduce the complications of atherosclerosis is diet and exercise. In order to decrease cholesterol, Mediterranean diet is often recommended. Mediterranean diet consists of low animal fat, high olive oil, moderate energy consumption, nuts, vegetables, regular and moderate https://www.textbookofcardiology.org/wiki/Atherosclerosis 14/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology wine, lots of whole grains and beans. A meta-analysis of six randomized trials showed that Mediterranean diet low fat diets among led to greater reduction in total cholesterol than overweight/obese population. Mediterranean-styled diet in this context means replacement of saturated fats with polyunsaturated fats such as omega-3 fatty acid and -linolenic acid. Polyunsaturated fats are potential anti-atherogenic due to their inhibiting action on cytokine-induced expression of leukocyte adhesion molecules at endothelial cells. Exercise and loss of excessive weight also contributes to improve abnormal lipid levels by reducing triglycerides and increasing HDL. In primary prevention, pharmacologic agents are the second option when lifestyle modifications fail to achieve targeted lipid profile. There are several groups of lipid-altering medicines such as HMG-CoA reductase inhibitors (statins), niacin, fibric acid derivatives, cholesterol intestinal absorption inhibitors, and bile acid-binding agents. In the clinical setting, statins are widely used, being the most cost-effective LDL-lowering drugs. They reduce intracellular cholesterol concentration by inhibiting HMG-CoA reductase, which is an enzyme that synthesizes cholesterol. This results into increased LDL-receptor expression and therefore leads to higher clearance of LDL molecules from blood. They also affect the liver and thereby lower the rate of VLDL synthesis, which results into lower levels of serum triglyceride. Statins also raise HDL, but this mechanism is not fully understood yet. Large studies, which have evaluated the effects of statin therapy, showed that ischemic cardiac events, the occurrence of MI and mortality rates were significantly reduced by implementing statin therapy. This significant improvement did not only apply to people with known preexisting atherosclerotic disease, but also to people within lower ranges of LDL and without preexisting atherosclerotic disease. For example, West of Scotland Coronary Prevention Study (WOSCPS trial) evaluated the effect of pravastatin on rates of nonfatal MI or CHD death, nonfatal MI, all cardiovascular deaths and total mortality among patients with hypercholesterolemia without preexisting CVD for five years. Use of pravastatin resulted in 31% risk reduction (p<0.001) in nonfatal MI or CHD death, and a 32% risk reduction (p=0.033) in all cardiovascular deaths as compared to the control group. Inhibiting HMG-CoA reductase results in several mechanisms that explain the beneficial effect of using statins. One beneficial mechanism is via lowering LDL and raising HDL. This results into less lipid content in atherosclerotic plaques and improve their biologic activity. Furthermore, the anti-thrombotic and anti-inflammatory profile is enhanced by other mechanisms such as increased NO synthesis and fibrinolytic activity, inhibition of smooth muscle proliferation and monocyte recruitment, and reduced production of matrix-degrading enzymes by macrophages. Several studies suggest that other mechanisms also contribute to the anti-inflammatory profile. For example, statins reduce endothelial expression of leukocyte adhesion molecules and macrophage tissue factor production by inhibiting the macrophage cytokines or by activating PPAR- . Another anti-inflammatory action of statins, supported by clinical trials is reducing the serum level of C-reactive protein, which is a marker of inflammation. Although statin therapy can reduce the risk of atherosclerotic cardiovascular disease by about one third, there is still a need for additional risk-reducing therapies. Thus, a new idea was developed to raise HDL cholesterol as a treatment for atherosclerosis. With the finding of the high-HDL phenotype of a human genetic deficiency of cholesteryl ester transfer protein (CETP), a new class of drugs was developed, which inhibits CETP. CETP functions as a mediator for transfer of cholesteryl ester from HDL to VLDL/LDL, which is then cleared by LDL receptors in liver. Thus when CETP is inhibited, this transfer process is inhibited and the direct hepatic HDL clearance pathway takes over. This leads to less fractional clearance https://www.textbookofcardiology.org/wiki/Atherosclerosis 15/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology of HDL from plasma, which is beneficial for atherosclerosis. Although the absolute clearance rate of HDL remains the same, the key step for atherosclerosis, which is the removal of cholesterol from macrophage foam cells in artery wall by HDL, is reduced. The most recently investigated CETP inhibitors are torcetrapib, anacetrapib, and dalcetrapib. In the Investigation of Lipid Level Management to Understand Its Impact in Atherosclerotic Events (ILLUMINATE) trial, involving 15,000 patients at high risk for coronary heart disease, torcetrapib was clinically investigated. Unfortunately this trial was prematurely stopped due to the finding of an increase in cardiovascular events associated with an undiscovered off-target effect. Anacetrapib and dalcetrapib are still under active clinical investigation, since they lack the off-target effects of torcetrapib. Tobacco smoking Tobacco use, including environmental smoking exposure, is known to increase the risk of atherosclerosis and ischemic heart disease based on numerous studies. For example, INTERHEART study shows that smoking is responsible for 36% of the population-attributable risk of a first MI. Other studies showed that smoking is an independent major risk factor for coronary heart disease, cerebrovascular disease and total atherosclerotic cardiovascular disease. The Atherosclerosis Risk in Communities Study measured the direct effect of smoking on the development of atherosclerosis. They measured intima-medial thickness of the carotid artery of 10,914 patients for three years with ultrasound. Their result showed that current smokers had a 50% increased progression of atherosclerosis in comparison to nonsmokers during the study period. Also patients with environmental tobacco smoke exposure (passive smokers) had 20% higher rate of atherosclerotic progress versus patients without environmental smoke exposure. Tobacco smoking can lead to many mechanisms that contribute to atherosclerosis. Smoking also leads to increased LDL levels, decreased HDL levels in blood and elevated insulin resistance. In addition it enhances oxidative modification of LDL by releasing free radicals and reduces generation of nitric oxide. This can promote endothelial dysfunction and thus lead to impairment of vasodilatation of coronary arteries and reduction of coronary flow reserve even in passive smokers. Tobacco smoking inappropriately stimulates sympathetic nervous system, increasing heart rate, blood pressure and perhaps coronary vasoconstriction. Smoking promotes a prothrombotic environment through inhibition of endothelial release of tissue plasminogen activator, elevation of fibrinogen concentration in blood, enhancement of platelet activity (possibility related to sympathetic activation) and enhanced expression of tissue factor. Smoking can even damage the vessel wall and ultimately cause a decrease in the elasticity of the artery, enhancing the stiffness of vessel wall. Smoking has been associated with increased C-reactive protein and fibrinogen, suggesting a correlation with inflammatory response, which is an important part of atherogenesis. There have also been findings that show higher expression of leukocyte adhesion molecules among smokers than nonsmokers. Smoking may additionally induce tissue hypoxia through displacement of oxygen with carbon monoxide in hemoglobin. To stop smoking is known as one of the most effective preventive measures of CVD and their complications. Soon after cessation, cardiac risks due to smoking decreases in a short period, and continues to diminish when cessation is permanently preserved. The risk for cardiovascular disease among patients with coronary heart disease decreases 7-47%. Not only does cessation of smoking reduce risk of CVD, but also substantially reduce the risk of all-cause mortality. Lack of physical activity https://www.textbookofcardiology.org/wiki/Atherosclerosis 16/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology INTERHEART study showed that lack of exercise accounted for 12% of the population- attributable risk of a first MI. Recent evidence shows that physical activity of even a moderate degree can protect against coronary heart disease and all-cause mortality .The beneficial effects of physical exercise are a decrease of triglyceride levels and blood pressure, elevation of HDL, enhancement of insulin sensitivity and production of NO by the endothelial cells, and of course weight loss. Although large scale randomized primary prevention trials are lacking, physical activity should be promoted to anyone with risk of developing atherosclerosis. Physical Activity Obesity The American Heart Association has published an article, identifying obesity as an independent risk factor for coronary heart disease. Obesity is for several correlated with atherosclerosis such as hypertension, insulin resistance, glucose intolerance, decreased HDL serum level and hypertriglyceridemia. Weight loss is an important treatment to prevent many obesity-related risk factors for atherosclerosis that has just been mentioned. risk factors Diet A healthy diet reduces CVD risk. In general, when following the rules for a healthy diet, no dietary needed. N-3 polyunsaturated fatty acid (PUFA) consumption mainly from oily sh, is potentially associated with bene cial effects on cardiac risk factors, notably reduction in triglycerides but not all trials have shown randomized, controlled reductions current recommendations are to increase PUFA intake through sh consumption, rather than from supplements. Recently, the largest study ever conducted with a so-called Mediterranean diet, supplemented with extra-virgin olive oil or supplements are in CV events Thus https://www.textbookofcardiology.org/wiki/Atherosclerosis 17/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology nuts, incidence of major cardiovascular events in patients at high risk of CV events but without prior CV disease.[1] reduced the The following activities have similar benefits to health: Activity Duration Washing and waxing a car 45-60 minutes Washing windows or floors 45-60 minutes Alcohol consumption Playing volleyball 45 minutes Alcohol is harmful when used chronic or excessive and can lead to various complications such as liver and heart failure, increased cancer risk, neurological complications and injuries. However despite effects, these moderate drinking (US parameters; women: <2 drinks per day, men: <3 drinks per day) may to have protective benefits with regards coronary heart disease according to several prospective cohort studies. These studies showed that moderate drinking resulted in a reduction of risk in coronary heart disease by 40-70% compared to no or heavy drinkers. This beneficial effect was seen in various groups without or with known risk for coronary heart disease and adults older than 65 years old. In a meta-analysis study, alcohol drinkers had lower relative risk for CVD mortality (0.75, 95% CI 0.70-0.80), coronary heart disease mortality (0.75, 0.68-0.81) and incidence of coronary heart disease (0.71, 0.66-0.77) than nondrinkers. Wheeling self in wheelchair 30-40 minutes Bicycling - 8 km 30 minutes Pushing a pushchair - 2.5 km 30 minutes adverse Walking - 3 km 30 minutes Swimming laps 20 minutes Playing basketball 15-20 minutes Psychosocial factors Mentioned by INTERHEART study, psychosocial factors may directly contribute to the early development of atherosclerosis. Psychological stress may directly damage endothelium and indirectly aggravate other common risk factors such as smoking, dyslipidemia and hypertension. Due to the difficulty in quantifying the extent of atherosclerosis, studies showing the relationship between stress and atherosclerosis have been limited. Epidemiologic studies have shown stronger link between psychosocial factors (loss of job, depression and bereavement) and MI and sudden death. Estrogen Status Women and men have different risk for cardiovascular diseases throughout life. For example, at young age, men have an estimated four- to fivefold higher risk than women. However this difference diminishes and the age point of no difference is strongly related to the moment of menopause. From this observation, it has been suggested that estrogen may play athero-protective roles, since the levels of estrogen declines after menopause. In premenopausal women, estrogen raises HDL levels and reduces LDL levels in blood. Estrogen can even exhibit antioxidant and antithrombotic properties and can improve endothelium-dependent vasodilatation. In the past, hormone replacement therapy has been suggested by several studies due to the findings of potential athero-protective roles of estrogen. However, these findings were not confirmed in the randomized primary prevention study of the Women s Health Initiative not in the HERS trial of secondary prevention. These studies showed that hormone replacement therapy (estrogen-progestin https://www.textbookofcardiology.org/wiki/Atherosclerosis 18/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology replacement) may increase cardiovascular risk in women and have no cardioprotective effect. Thus hormone replacement therapy is currently not recommended for reducing cardiovascular risk, due to its possible harmfulness consequences according to current clinical trials. Biomarkers Biomarkers can serve to identify patients with subclinical atherosclerotic disease that are at risk of developing cardiovascular events. Homocysteine Homocysteine is an intermediary amino acid produced during the conversion of methionine to cysteine. A significant positive correlation was found between the serum levels of homocysteine and the incidence of cardiovascular diseases. Although the clear mechanism of this correlation is undetermined, the overall result of the most current evidence suggests that homocysteine can modestly contribute to cardiovascular risk by inducing vascular injury. Homocysteine promotes oxidative stress, intimal thickening, disruption of elastic lamina, hypertrophy of smooth muscle cells, vascular inflammation platelet accumulation and production of occlusive thrombi when elevated in blood. Several conditions can cause hyperhomocystinemia, such as genetic defects in methionine metabolism or insufficient consumption of folic acid, which is involved in the methionine pathway. Such disorders cause premature and severe atherosclerosis. Despite this observational relationship, there is no data yet that proves reducing high serum level of homocysteine will lead to a decrease in atherosclerosis or its complications. Lipoprotein A Some studies have concluded that lipoprotein (a) is an independent risk factor for coronary artery disease. As lipoprotein (a) contains apo (a), which structurally resembles plasminogen, lipoprotein (a) interferes with fibrinolysis by competing with plasminogen binding with molecules. This leads to impairment of plasminogen activation, plasmin generation and lysis of fibrin clots. In addition, lipoprotein (a) binds with macrophages through a high-affinity receptor, promoting foam cell production and deposition of cholesterol in atherosclerotic plaques. As with homocysteine, not all studies support this theory of correlation, although increased risk of cardiovascular events appear to correlate with people with highest lipoprotein (a) serum level. C-Reactive Protein and other markers of inflammation Since the participation of inflammatory cells and mediators in atherosclerosis is well established, markers of inflammation have received a lot of attention. Several markers of inflammation such as C- reactive protein (CRP), fibrinogen and amyloid A are produced by hepatocytes in an acute phase under the influence of cytokines such as IL-6 when they mobilize from intima to the liver during the fatty streak stage. From these markers, CRP has shown the greatest association with atherosclerosis as a marker of low-grade systemic inflammation. A significant association between elevated CRP level in blood and prevalence of atherosclerosis has been shown in more than 30 epidemiologic studies. Different studies showed that higher basal CRP levels (four-fold higher) were found in patients with MI as compared to controls. Several studies have proposed that elevated plasma CRP can be an independent predictor for many cardiovascular diseases based on the result that CRP plasma value was able to predict the long-term risk of first MI, ischemic stroke or peripheral vascular disease among the male group. In addition, recent studies have shown that CRP also has a role as a mediator in atherogenesis. By inducing https://www.textbookofcardiology.org/wiki/Atherosclerosis 19/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology adhesion molecule expression and release of IL-6 and monocyte chemoattractant protein-1 via endothelial cells, CRP sustains the inflammatory state of atherosclerosis by recruiting monocytes and lymphocytes. Infection A variety of infectious agents such as Chlamydia pneumonia, cytomegalovirus and Helicobacter pylori were identified in the lesions of atherosclerosis and this observation raised the suggestion that these infectious agents may contribute to atherogenesis. However, to date, the definite proof of this theory is lacking and also there haven t been any clinical studies that showed significant relationship between the antibiotic treatment against these infectious agents and the risk of cardiac events of the survivors of acute coronary syndromes. Chlamydia is a strong candidate among other infectious agents, since they produce heat shock protein 60 (HSP-60) that activates macrophages and stimulates the production of matrix metalloproteinases. Furthermore, HDP-60 can also stimulate foam cell formation, lipoprotein oxidation, and increased pro-coagulant activity, which are the major attributing components of atherosclerosis. Although there is no evidence to date, some researchers believe that exogenous pathogens can cause endothelial injury and inflammation that can lead to initiation or exacerbation of atherosclerosis. Co-morbidity groups Hypertension Hypertension is defined as a systolic blood pressure (SBP) 140mmHg and/or a diastolic blood pressure (DBP) 90mmHg. Elevated blood pressure is a well established risk factor for atherosclerosis, including mortality from coronary heart disease and stroke. For example, cardiovascular disease doubles with every 20 mmHg increase in SBP or every 10 mmHg increase in DBP. One of the mechanisms of hypertension contributing to atherosclerosis is injury of vascular endothelium by elevated hemodynamic stress. Injury of endothelium may increase the permeability of the vessel wall to lipoproteins. Increased blood pressure may also increase the number of scavenger receptors on macrophages, which enhances the development of foam cells. Furthermore, increased cyclic circumferential strain in hypertensive arteries can result into promoting LDL accumulation in the intima and facilitation of their oxidative modification. Finally, hypertension can contribute to atherogenesis due to the presence of Angiotensin II, which not only works as a vasoconstrictor, but also as a pro- inflammatory cytokine. Antihypertensive therapy Figure 16. Lifestyle recommendations for hypertension can Antihypertensive lifestyle consist either or interventions pharmacotherapy. Lifestyle modifications consist of diet, body weight reduction, increased of activity, therapy of Weight reduction in overweight individuals Reduction of salt consumption to < 6g daily Restriction of alcohol intake to < 10-30g/day (men) and < 10-20g/day (women) Regular physical activity Smoking cessation and cessation https://www.textbookofcardiology.org/wiki/Atherosclerosis 20/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology smoking. As for diet, high consumption of fruits, vegetables, dairy products low in fat, fish oils, potassium and reduced consumption of sodium and alcohol are recommended. The indication for pharmacotherapy depends on the severity of hypertension and on the assessment of total CVD risk. Several large trials have shown that pharmacotherapy for hypertension can substantially reduce major cardiovascular events such as MI and stroke. Drug therapy is indicated when chronic SBP 160mmHg and/or DBP 100mmHg, or if target organ damage is present. Diabetes Mellitus With estimated global incidence of 170 million people, diabetes mellitus is a large problem worldwide. Diabetes mellitus increases the risk of acute coronary events by three- to five folds and 80% of diabetic patients will face atherosclerosis-related cardiovascular diseases. Risk for atherosclerosis among diabetics is considered to be as high as in patients with previous MI. Based on this observation, the National Cholesterol Education Program report from the United States and guidelines from Europe considers type 2 diabetes to be a CHD equivalent, categorizing it to the highest risk for MI. There are several possible mechanisms that make this group particularly vulnerable to atherosclerosis. An example of mechanism is non-enzymatic glycation of lipoproteins, which promotes uptake of cholesterol by scavenger macrophages. Furthermore, pro-thrombotic and anti-fibrinolytic properties of diabetes can also contribute to this vulnerability. The high prevalence of endothelial dysfunction among diabetes group leads to reduced bioavailability of NO and enhanced leukocyte adhesion. The most effective prevention of atherosclerosis among diabetes group is tight regulation of serum glucose levels. This intervention significantly reduces the risk of microvascular complications such as retinopathy and nephropathy. Furthermore, intense anti-diabetic regime also reduced macrovascular outcomes such as MI and stroke among a group of diabetes type 1. Additionally managing hypertension and dyslipidemia among diabetic groups also significantly reduces the risk of cardiovascular diseases. References 1. Estruch R, Ros E, and Mart nez-Gonz lez MA. Mediterranean diet for primary prevention of cardiovascular disease. N Engl J Med. 2013 Aug 15;369(7):676-7. DOI:10.1056/NEJMc1306659 | 2. Anderson J.L., Carlquist J.F., Muhlestein J.B., et al. Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. J Am Coll Cardiol 1998; 32:35. 3. Barua R.S., Ambrose J.A., Eales-Reynolds L.J., et al. Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation. Circulation 2001; 104:1905. 4. Barter P.J., Caulfield M., Eriksson M., et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357:2109. 5. Bazzano L.A., He J., Muntner P., et al. Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann Intern Med 2003; 138:891. https://www.textbookofcardiology.org/wiki/Atherosclerosis 21/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 6. Bennet A., Di Angelantonio E., Erqou S., et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch Intern Med 2008; 168:598. 7. Blood Pressure Lowering Treatment Trialists' Collaboration, Turnbull F., Neal B., et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336:1121. 8. Burke A.P., Farb A., Malcom G.T., Liang Y., Smialek J.E., Virmani R. "Plaque rupture and sudden death related to exertion in men with coronary artery disease." JAMA. 1999;281(10):921. 9. Camm A.J., F scher T.F., Serruys P.W., eds. (2010). The ESC Textbook of Cardiovascular Medicine Online Second Edition. Oxford: Oxford University Press. 10. Celermajer D.S., Sorensen K.E., Georgakopoulos D., et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993; 88:2149. 11. Dauchet L., Amouyel P., Dallongeville J. Fruit and vegetable consumption and risk of stroke: a meta- analysis of cohort studies. Neurology 2005; 65:1193. 12. De Backer G., Ambrosioni E., Borch-Johnsen K., et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2003; 10:S1. 13. Downs J.R., Clearfield M., Weis S., Whitney E., Shapiro D.R., Beere P.A., Langendorfer A., Stein EA, Kruyer W, Gotto AM Jr. "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study." JAMA. 1998;279(20):1615. 14. Eckel R.H., York D.A., R ssner S., et al. Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: executive summary. Circulation 2004; 110:2968. 15. Emerging Risk Factors Collaboration, Erqou S., Kaptoge S., et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009; 302:412. 16. Fuchs C.S., Stampfer M.J., Colditz G.A., et al. Alcohol consumption and mortality among women. N Engl J Med 1995; 332:1245. https://www.textbookofcardiology.org/wiki/Atherosclerosis 22/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 17. Grady D., Herrington D., Bittner V., et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:49. 18. Harker L.A., Ross R., Slichter S.J., Scott C.R. Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 58:731. 19. Haffner S.M., Lehto S., R nnemaa T., et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339:229. 20. Howard G., Wagenknecht L.E., Burke G.L., Diez-Roux A., Evans G.W., McGovern P., Nieto F.J., Tell in G.S. "Cigarette smoking and progression of atherosclerosis: The Atherosclerosis Risk Communities (ARIC) Study." JAMA. 1998;279(2):119. 21. Jackson R., Scragg R., Beaglehole R. Alcohol consumption and risk of coronary heart disease. BMJ 1991; 303:211. 22. Jee S.H., Suh I., Kim I.S., Appel L.J. "Smoking and atherosclerotic cardiovascular disease in men with low levels of serum cholesterol: the Korea Medical Insurance Corporation Study." JAMA. 1999;282(22):2149. 23. Kannel W.B., D'Agostino R.B., Belanger A.J. Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Framingham Study. Am Heart J 1987; 113:1006. 24. Klein S., Burke L.E., Bray G.A., et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2004; 110:2952. 25. Knoops K.T., de Groot L.C., Kromhout D., et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 2004; 292:1433. 26. Kwaliteitsinstituut voor de gezondheidszorg CBO and Nederlandse Huisartsen Genootschap. (2006). Multidisciplinaire richtlijn cardiovasculair risicomanagement 2006. Alphen aan den Rijn: Van Zuiden Communications. 27. Lilly L.S. (ed.). (2007). Pathophysiology of Heart Disease. Baltimore: Lippincott Williams & Wilkins, p. 118 140. https://www.textbookofcardiology.org/wiki/Atherosclerosis 23/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 28. Lilly L.S. (ed.). (2007). Pathophysiology of Heart Disease. Baltimore: Lippincott Williams & Wilkins, p. 118 140. 29. Nordmann A.J., Suter-Zimmermann K., Bucher H.C., et al. Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors. Am J Med 2011; 124:841. 30. Mancia G., Messerli F., Bakris G., et al. Blood pressure control and improved cardiovascular outcomes in the International Verapamil SR-Trandolapril Study. Hypertension 2007; 50:299. 31. McCully K.S. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56:111. 32. Mendis S., Puska P., Norrving B. (eds.). (2011). Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization. |
There are several possible mechanisms that make this group particularly vulnerable to atherosclerosis. An example of mechanism is non-enzymatic glycation of lipoproteins, which promotes uptake of cholesterol by scavenger macrophages. Furthermore, pro-thrombotic and anti-fibrinolytic properties of diabetes can also contribute to this vulnerability. The high prevalence of endothelial dysfunction among diabetes group leads to reduced bioavailability of NO and enhanced leukocyte adhesion. The most effective prevention of atherosclerosis among diabetes group is tight regulation of serum glucose levels. This intervention significantly reduces the risk of microvascular complications such as retinopathy and nephropathy. Furthermore, intense anti-diabetic regime also reduced macrovascular outcomes such as MI and stroke among a group of diabetes type 1. Additionally managing hypertension and dyslipidemia among diabetic groups also significantly reduces the risk of cardiovascular diseases. References 1. Estruch R, Ros E, and Mart nez-Gonz lez MA. Mediterranean diet for primary prevention of cardiovascular disease. N Engl J Med. 2013 Aug 15;369(7):676-7. DOI:10.1056/NEJMc1306659 | 2. Anderson J.L., Carlquist J.F., Muhlestein J.B., et al. Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. J Am Coll Cardiol 1998; 32:35. 3. Barua R.S., Ambrose J.A., Eales-Reynolds L.J., et al. Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation. Circulation 2001; 104:1905. 4. Barter P.J., Caulfield M., Eriksson M., et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357:2109. 5. Bazzano L.A., He J., Muntner P., et al. Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann Intern Med 2003; 138:891. https://www.textbookofcardiology.org/wiki/Atherosclerosis 21/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 6. Bennet A., Di Angelantonio E., Erqou S., et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch Intern Med 2008; 168:598. 7. Blood Pressure Lowering Treatment Trialists' Collaboration, Turnbull F., Neal B., et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 2008; 336:1121. 8. Burke A.P., Farb A., Malcom G.T., Liang Y., Smialek J.E., Virmani R. "Plaque rupture and sudden death related to exertion in men with coronary artery disease." JAMA. 1999;281(10):921. 9. Camm A.J., F scher T.F., Serruys P.W., eds. (2010). The ESC Textbook of Cardiovascular Medicine Online Second Edition. Oxford: Oxford University Press. 10. Celermajer D.S., Sorensen K.E., Georgakopoulos D., et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993; 88:2149. 11. Dauchet L., Amouyel P., Dallongeville J. Fruit and vegetable consumption and risk of stroke: a meta- analysis of cohort studies. Neurology 2005; 65:1193. 12. De Backer G., Ambrosioni E., Borch-Johnsen K., et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2003; 10:S1. 13. Downs J.R., Clearfield M., Weis S., Whitney E., Shapiro D.R., Beere P.A., Langendorfer A., Stein EA, Kruyer W, Gotto AM Jr. "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study." JAMA. 1998;279(20):1615. 14. Eckel R.H., York D.A., R ssner S., et al. Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: executive summary. Circulation 2004; 110:2968. 15. Emerging Risk Factors Collaboration, Erqou S., Kaptoge S., et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009; 302:412. 16. Fuchs C.S., Stampfer M.J., Colditz G.A., et al. Alcohol consumption and mortality among women. N Engl J Med 1995; 332:1245. https://www.textbookofcardiology.org/wiki/Atherosclerosis 22/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 17. Grady D., Herrington D., Bittner V., et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:49. 18. Harker L.A., Ross R., Slichter S.J., Scott C.R. Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 58:731. 19. Haffner S.M., Lehto S., R nnemaa T., et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339:229. 20. Howard G., Wagenknecht L.E., Burke G.L., Diez-Roux A., Evans G.W., McGovern P., Nieto F.J., Tell in G.S. "Cigarette smoking and progression of atherosclerosis: The Atherosclerosis Risk Communities (ARIC) Study." JAMA. 1998;279(2):119. 21. Jackson R., Scragg R., Beaglehole R. Alcohol consumption and risk of coronary heart disease. BMJ 1991; 303:211. 22. Jee S.H., Suh I., Kim I.S., Appel L.J. "Smoking and atherosclerotic cardiovascular disease in men with low levels of serum cholesterol: the Korea Medical Insurance Corporation Study." JAMA. 1999;282(22):2149. 23. Kannel W.B., D'Agostino R.B., Belanger A.J. Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Framingham Study. Am Heart J 1987; 113:1006. 24. Klein S., Burke L.E., Bray G.A., et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2004; 110:2952. 25. Knoops K.T., de Groot L.C., Kromhout D., et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 2004; 292:1433. 26. Kwaliteitsinstituut voor de gezondheidszorg CBO and Nederlandse Huisartsen Genootschap. (2006). Multidisciplinaire richtlijn cardiovasculair risicomanagement 2006. Alphen aan den Rijn: Van Zuiden Communications. 27. Lilly L.S. (ed.). (2007). Pathophysiology of Heart Disease. Baltimore: Lippincott Williams & Wilkins, p. 118 140. https://www.textbookofcardiology.org/wiki/Atherosclerosis 23/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 28. Lilly L.S. (ed.). (2007). Pathophysiology of Heart Disease. Baltimore: Lippincott Williams & Wilkins, p. 118 140. 29. Nordmann A.J., Suter-Zimmermann K., Bucher H.C., et al. Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors. Am J Med 2011; 124:841. 30. Mancia G., Messerli F., Bakris G., et al. Blood pressure control and improved cardiovascular outcomes in the International Verapamil SR-Trandolapril Study. Hypertension 2007; 50:299. 31. McCully K.S. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56:111. 32. Mendis S., Puska P., Norrving B. (eds.). (2011). Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization. 33. Mukamal K.J., Chung H., Jenny N.S., et al. Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study. J Am Geriatr Soc 2006; 54:30. 34. Newby D.E., Wright R.A., Labinjoh C., et al. Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. Circulation 1999; 99:1411. 35. 'Keefe O'Keefe J.H., Bybee K.A., Lavie C.J. Alcohol and cardiovascular health: the razor-sharp double-edged sword. J Am Coll Cardiol 2007; 50:1009. 36. Paffenbarger R.S. Jr, Hyde R.T., Wing A.L., et al. The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993; 328:538. 37. Pasceri V., Cheng J.S., Willerson J.T., et al. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001; 103:2531. 38. Pasceri V., Willerson J.T., Yeh E.T. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102:2165. 39. Pearson T.A., Mensah G.A., Alexander R.W., et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107:499. https://www.textbookofcardiology.org/wiki/Atherosclerosis 24/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 40. Poirier P., Giles T.D., Bray G.A., et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2006; 113:898. 41. Powell K.E., Thompson P.D., Caspersen C.J., Kendrick J.S. Physical activity and the incidence of coronary heart disease. Annu Rev Public Health 1987; 8:253. 42. Reaven G., Tsao P.S. Insulin resistance and compensatory hyperinsulinemia: the key player between cigarette smoking and cardiovascular disease? J Am Coll Cardiol 2003; 41:1044. 43. Ridker P.M., Cushman M., Stampfer M.J., et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336:973. 44. Ridker P.M., Glynn R.J., Hennekens C.H. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998; 97:2007. 45. Rimm E.B., Ascherio A., Giovannucci E., et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996; 275:447. 46. Rolland P.H., Friggi A., Barlatier A., et al. Hyperhomocysteinemia-induced vascular damage in the minipig. Captopril-hydrochlorothiazide combination prevents elastic alterations. Circulation 1995; 91:1161. 47. Ronksley P.E., Brien S.E., Turner B.J., et al. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011; 342:d671. 48. Rose G., Hamilton P.J., Colwell L., Shipley M.J. A randomised controlled trial of anti-smoking advice: 10-year results. J Epidemiol Community Health 1982; 36:102. 49. Rossouw J.E., Anderson G.L., Prentice R.L., et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321. 50. Rozanski A., Blumenthal J.A., Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99:2192. 51. Rubin R., Strayer D.S., Rubin E. (ed.). (2008). Rubin's Pathology: Clinicopathologic Foundations of Medicine Fifth Edition. Baltimore: Lippincott Williams & Wilkins, p387-408 https://www.textbookofcardiology.org/wiki/Atherosclerosis 25/26 7/4/23, 12:20 AM Atherosclerosis - Textbook of Cardiology 52. Sacks F.M., Pfeffer M.A., Moye L.A., Rouleau J.L., Rutherford J.D., Cole T.G., Brown L., Warnica J.W., Arnold J.M., Wun C.C., Davis B.R., Braunwald E. "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators." N Engl J Med. 1996;335(14):1001. 53. Shepherd J., Cobbe S.M., Ford I., Isles C.G., Lorimer A.R., MacFarlane P.W., McKillop J.H., Packard C.J. "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group." N Engl J Med. 1995;333(20):1301. 54. Stefanadis C., Tsiamis E., Vlachopoulos C., et al. Unfavorable effect of smoking on the elastic properties of the human aorta. Circulation 1997; 95:31. 55. Tall, A. R. "CETP inhibitors to increase HDL cholesterol levels." N.Engl.J.Med. 356.13 (2007): 1364- 66. 56. The health benefits of smoking cessation. A report of the Surgeon General. DHHS Publication (CDC) 90-8416; U.S. Department of Health and Human Services, Washington, DC, 1990. 57. Theorell, T., Lind, E., Floderus, B. The relationship of disturbing life-changes and emotions to the development of myocardial infarction and other serious diseases. Int J Epidemiol 1975; 4:281. 58. Vita J.A., Keaney J.F. Jr. Endothelial function: a barometer for cardiovascular risk? Circulation 2002; 106:640. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Atherosclerosis&oldid=2501" This page was last edited on 8 December 2013, at 20:56. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Atherosclerosis 26/26 |
7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology Bradycardia S bastien Krul, MD Contents Introduction Disorders of Conduction and Impulse Formation Sinus Node Dysfunction Sinus Bradycardia Sinus Node Exit Block Sinus Arrest Asystole Sick Sinus Syndrome AV-Block First Degree AV Block Second Degree AV Block Third Degree AV Block Paroxysmal AV block Ventricular Conduction Block Right bundel branch block (RBBB) Left anterior fascicular block (LAFB) Left posterior fascicular block (LPFB) Left bundel branch block (LBBB) Functional conduction disorders: Aberrant Conduction Phase 3 aberration Phase 4 abberation or deceleration dependant Acceleration dependant Diagnosis Signs & Symptoms Investigations Treatment Drug Therapy Temporary pacing Device Therapy References Introduction Abbreviations https://www.textbookofcardiology.org/wiki/Bradycardia 1/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology Bradycardias are symptomatic heart rhythm disorders resulting from an inappropriately low heart rhythm due to inappropriate slow impulse formation or conduction delay of the cardiac impulse in the myocardium or conduction system during physiologic conditions. These two problems can lead to a slow heart rate, a bradycardia. Generally the definition of bradycardia is a heart rate of <60 beats per minute. However, a normal variation of heart rate exists[1]. For instance, during sleep and in athletes the heart rate can be as low as 40 beats per minute.[2] AV: Atrio Ventricular bpm: beats per minute LBBB: Left Bundle Branch Block LAFB: Left Anterior Fascicular Block LPFB: Left Posterior Fascicular Block RBBB: Right Bundle Branch Block Bradycardia can be caused by a variety of intrinsic and extrinsic causes. The most common intrinsic cause is ageing, but ischemic heart disease, infiltrative diseases or surgery can also result in conduction disorders.[3, 4, 5] Medication that modifies the excitability of the heart is the most frequent extrinsic cause. However, electrolyte and metabolic disorders may influence the heart rate directly or indirect. Complaints from bradycardia result from an insufficient capacity of the heart to supply the body with blood. Complaints of palpitations, syncope or heart failure may result from bradyarrhythmias, but often vague symptoms like dizziness, exercise intolerance or fatigue may be more prominent[6]. A causal relation between complaints and the bradycardia should be established and reversible causes should be identified (for instance use of certain drugs). Disorders of Conduction and Impulse Formation Sinus Node Dysfunction Sinus Bradycardia Sinus bradycardia is a slow sinus rhythm of <60 beats per minute[1]. Sinus bradycardia can be physiological, as in athletes or during sleep[7]. Commonly sinus bradycardia is caused by medication, ischemia or neuro-mediated bradycardia, such as in a vasovagal reaction[5]. Furthermore metabolic diseases can cause bradycardia, e.g. hypothermia or hypothyroidism. Sinus Node Exit Block In the case of sinus node exit block, an impulse generated from the sinus node is blocked at one of the exit sides of the sinus node. However impulse formation is not affected, therefore the interval between subsequent beats should be similar to n=x times the P-P interval. On the surface electrocardiogram this is expressed as a pause. Like AV-nodal conduction disorders (see below) multiple subtypes can be distinguished: Second degree Type I (Wenkebach) SA exit block: the P-P interval progressively shortens prior to the pause https://www.textbookofcardiology.org/wiki/Bradycardia 2/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology Second degree Type II SA exit block: the pause equals approximately 2-4 times the preceding PP interval Third degree SA exit block: absence of P waves, but still impulse formation at the level of the sinus node (can only be diagnosed with an sinus node electrode, during electrophysiological evaluation) Sinus node dysfunction. Sinus Arrest If the sinus node has a problem with impulse formation it is defined as a sinus arrest. There can be the appearance of an irregular rhythm, however sinus P-waves are clearly present, between intervals of no rhythm or an escape rhythm. In comparison with the sinus node exit block, there is no relation with a previous P-P interval. Often an ectopic pacemaker takes over lower in the conduction system, but the new rate varies slightly from the old one. Asystole Asystole is the lack of cardiac activity eventually leading to immediate death. Sick Sinus Syndrome Sick sinus syndrome is a denoter of diseases of inappropriate sinus node responses [3]. These encompass for instance: An inappropriate response after tachycardia due to overdrive suppression (which can result in long pauses) An inadequate response to exercise. Bradycardia-tachycardia syndrome; where alternating bradycardia and tachycardia arise. AV-Block First Degree AV Block https://www.textbookofcardiology.org/wiki/Bradycardia 3/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology Technically an AV-delay and not an AV block, 1st degree AV block is defined as a prolonged interval between atrial ventricular activation (>200ms). This delay results from disease in the AV-node or His-Purkinje system. An AV block is not the cause of bradycardia, because every atrial impulse results in conduction to the ventricles. and Second Degree AV Block The second degree AV block can be divided two separate entities depending on the clinical characteristics of the conduction disorder. If conduction to the ventricle is conducted in a 2:1 fashion; that is if after every second P-wave there is no conduction to the ventricle, it is not possible to distinguish between the two types and a severe kind of conduction block should be assumed. If two sequential P-wave are not followed by a QRS-complex the term malignant block is used, as this could lead to or be an indication of a total block. in The three different types of AV nodal block. Mobitz I (Wenkebach): The Mobitz type I block is characterized by a progressively increased P-Q interval until atrial activation is blocked in the AV-node. Thereafter conduction is restored and this cycle repeats itself. A common finding in the Mobitz I block is that the first prolongation of the PR interval is associated with the largest increase in interval. After this first prolongation of the interval, the interval gradually increases. Usually Mobitz type II block is located at the atrioventricular node and rarely deteriorates to a more severe conduction block.[8, 9] Mobitz II: When atrial activation is blocked, without progressively increasing P-Q interval a Mobitz Type II AV block is present. This sudden failure of AV conduction is an omen of severe conduction disease in usually infra-Hision part of the atrioventricular conduction system.[8, 10, 11] Third Degree AV Block Third degree AV block is complete block of conduction between atria en ventricle. Atrial and ventricular rhythms are complete dissociated.[12] Paroxysmal AV block Paroxysmal atrioventricular block (PAVB), is characterized by a sudden and unexpected block of the atrial impulse. Due to the delayed emerge of an escape rhythm, these patients often present with syncope. However, if a escape rhythm is established patients may present themselves without symptoms. Two different variations of the PAVB are commonly distinguished; https://www.textbookofcardiology.org/wiki/Bradycardia 4/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology 1. Pause-dependent PAVB The PD-PAVB occurs after the onset of a pause. This pause can be compensatory after a premature beat, overdrive suppression of sinus rhythm or other disorders of impulse formation. There are several hypothesis to explain this phenomenon, amongst them phase 4 depolarization (see Phase 4 abberation). 2. Tachycardia-dependent PAVB The TD-PAVB occurs more frequently in patients due to the increased rate of the atria. TD-PAVB is associated with 2nd degree Mobitz block and Adam-Stokes Syndrome. However, some occurrences of TD-PAVB occur without a noticeable increase in atrial rate, due to minor electrophysiological changes due to changes in autonomic tone or coronary perfusion. The mechanism responsibly for the occurrence of TD-PAVB is probably repetitive concealed conduction.[13] Ventricular Conduction Block Ventricular conduction blocks predominantly prolong the QRS-complex, but are rarely the result of bradycardias. However, the occurrence of ventricular block on the surface ECG inform the clinician about the health of the underlying conduction system and might occur simultaneously with other types of conduction disorders. Right bundel branch block (RBBB) The right bundle branch is composed of one fascicle. Right bundle branch block is a unifascicular block of the right bundle and can be found in healthy people and is represented by a broad QRS complex (>120ms). However, a new RBBB in a patient with a history of normal ventricular conduction warrens further cardiological investigation. The last activity is to the right and results in a RSR pattern in V1 where R > R. This results from the delayed activation of the right ventricle. In V6 a slurred S wave can be seen at the end of the QRS complex[5, 14, 15, 16] Left anterior fascicular block (LAFB) The left bundle branch is composed of two fascicles. One of the fascicle has an anterior location and activates the interventricular septum and the anterior of the ventricle. Clinically a LAFB is represented by a left axis deviation and an absent or very small S and normal q in lead I and a S>R in lead II and III. QRS duration should be <120ms[5, 14, 15, 16]. Left posterior fascicular block (LPFB) The second fascicle of the left bundle branch is the posterior fascicle. This fascicle has a posterior location and activates the posterior and lateral part of the ventricle. A left posterior fascicular block results in a right axis deviation and is represented by a deep S in I and small q in III with a QRS duration of <120ms[5, 14, 15, 16]. Left bundel branch block (LBBB) https://www.textbookofcardiology.org/wiki/Bradycardia 5/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology If the two fascicles of the left bundle branch show conduction block there is a left bundle branch block. This bifascicular block is uncommon in healthy patients and further cardiologic investigations need to be performed to screen for underlying disease. Left bundle branch block causes the left ventricle to activate later then the right ventricle. This results in typical ECG characteristics, most importantly a broad QRS of >120ms. In V1 a broad monomorphic S wave can be seen (sometimes with a small r wave) representing slow left ventricular activation. In the lead V6 a broad monomorphic R wave is seen with no Q waves[5, 14, 15, 16]. [Afbeelding samenvatting alle Ventriculaire geleidingsstoornissen] Function conducti disorder Aberrant Conducti Traces of right bundle branch block and the different types of left bundle branch conduction disorders. In certain physiological conditions a ventricular conduction disorder can arise on the ECG. This functional conduction disorder is called aberrant conduction and can mimic any form of interventricular conduction disorder. In most cases a right bundle branch block pattern can be seen on the surface ECG https://www.textbookofcardiology.org/wiki/Bradycardia 6/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology because the right bundle has a longer refractory period. There are a few mechanisms which can cause aberrant conduction[15, 16]. Phase 3 aberration Phase 3 aberration is a situation that occurs when the bundle branches receive a new impulse, before they are repolarized. The bundles are still in their refractory period. This is also called Ashman phenomenon. As a result of the refractionary state of the bundle, conduction can not proceed along the refractory bundle and a conduction block is visible on the surface ECG. Thus for instance short coupled atrial activity can procedure phase 3 aberrant conduction[15, 16]. Phase 4 abberation or deceleration dependant During a prolonged interval between cardiac activity, the Purkinje fibers can depolarize spontaneously. This depolarisation results in the conduction slowing and can even produce a conduction block. This is usually a pathological response, resulting from an increased activity in the Purkinje fibers, but can be normal at very low heart rates. Phase 4 aberration thus only occurs after prolonged pause [15, 16]. Acceleration dependant This kind of aberrant conduction resembles phase 3 aberrant conduction; however appearance of the conduction disorders is the result of a small increase in rhythm. The ventricular conduction disorder is a result of an abnormal response of tissue that has diminished excitability and fails to excite the corresponding bundle[15, 16]. Diagnosis In the diagnosis of bradyarrhythmias the identification of reversible causes is important to prevent unnecessary treatment. After a detailed history and physical examination there are additional investigations which can give information about the location of the nature of the bradyarrhythmia.[4]. While not all investigations are necessary, a thorough work-up has to be performed to prevent serious clinical events or pacemaker implantation. Especially the differentiation between bradyarrhtyhmias and vasovagal syncope can be difficult, but is very important for the management of symptoms [6]. Signs & Symptoms A patient with a bradyarrhythmia can be completely asymptomatic. Otherwise, patients with bradycardia may present with a diversity of signs and symptoms. A pause in ventricular contraction > 6 seconds often resuls in syncope or near syncope [6]. More often symptoms are nonspecific and chronic and are a result of the chronotopic incompetence and reduced cardiac output. Symptoms like dizziness, light-headedness or confusional states, episodes of fatigue or muscular weakness, exercise intolerance, heart failure or palpitations can be experienced by the patient.[5] Investigations There are a number of additional investigations which can uncover the cause of bradyarrhythmias. https://www.textbookofcardiology.org/wiki/Bradycardia 7/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology ECG: A surface ECG can demonstrate the conduction disorder and relate complaints to electrocardiographic findings. A Valsalva manoeuvre or carotid sinus massage whilst performing an ECG can give information about function of the autonomous nervous system and its possible role in the occurrence of the bradyarrrhythmia. X-ECG: An exercise test can give information about the chronotropic competence of the cardiac conduction system [17]. Long-term ECG recording: Holter recording can identify causes of paroxysmal or intermittent bradyarrhythmias. Importantly a correlation with symptoms can be made and pathological causes of bradyarrhythmias or long pause (>3sec) during the night can be identified. If 24h or 48h Holter recordings cannot identify the cause of symptoms longer duration of monitoring may be required[18]. Transient event recorders can record up to 30seconds of ECG when a patient activates the device. This device can be especially useful when non-invasive monitoring is required due to the low occurrence of the bradyarrhythmia[19]. For longer monitoring an implantable loop recorder can be used. This small device can be implanted and observe rhythm over an extensive period [20]. Electrophysiological testing: If non-invasive testing does not discover the arrhythmia underlying the symptoms, an electrophysiologic study may be undertaken to assess sinus nodal function and atrioventricular conduction. The measurement of conduction intervals and reaction to standard electrophysiological pacing protocols can elucidate the cause of bradyarrhtyhmia. Treatment Fortunately the human heart has a couple of backup mechanisms that can sustain a heart rate in case of severe bradycardia. These escape mechanisms can occur in every part of the heart (i.e. atrium, AV, node, ventricle). In general, the rate of the escape mechanism is faster when the escape rhythm is located higher in the conduction system, for instance an escape rhythm of the atrium has a higher frequency than an escape rhythm from the ventricles. If no reversible cause for the bradyarrhythmia can be found and the bradyarrhythmia persist, further therapy is required if the patients remains symptomatic. Drug Therapy There are no options for chronic drug therapy in bradyarrhthmias. In the acute setting atropine or isoprenaline may be used to increase heart rate or AV-nodal conduction [21]. Patients with severe bradyarrhythmias (Type 2 AV nodal Mobitz II block, Type 3 AV nodal block, sinus arrest >3 seconds) should be considered for permanent or temporary pacing therapy. Temporary pacing Temporary pacing can be used to bridge the time to pacemaker implantation or until the bradyarrhythmia is resolved. Transvenous pacing is the most accepted method and can be used to pace the right atrium or the right ventricle after insertion of a temporary pacemaker wire through venous access. Pacing through the oesophagus can only capture the atrium, due to the anatomical position of the heart in relation with the oesophagus. Transcutanous pacing is a painful and emergency option in which muscle and heart are stimulated with large electrodes. Finally epicardal pacing is usually performed after cardiac surgery and requires surgical implantation of the electrodes on the epicardium. Device Therapy https://www.textbookofcardiology.org/wiki/Bradycardia 8/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology Implantable pacemakers activate cardiac myocardium with electrical stimulation, leading to muscle contraction. Due to the nature of a pacemaker, the activation is different from the physiological conduction system, there are electrical and mechanical consequences. It is therefore important to adjust pacemaker setting to the individual patient. The type of pacemakers and their settings are extensively covered in the device chapter of cardiac arrhythmias. The indications for pacemaker implantation in patients with bradyarrhythmias are mentioned below. Sinus node disease: Pacemaker implantation should be strongly considered in patients with sinus node disease which manifests as symptomatic bradycardia in which the symptom-rhythm correlation must have been 1) spontaneously occurring or 2) drug-induced where alternative drug therapy is lacking.[22, 23] Other reasonable eligible candidates for permanent pacing are patients with syncope with sinus node disease, spontaneously occurring or induced at electrophysiological study or patients with symptoms clearly associated to bradycardia but without documentation of this bradycardia. Patients with sinus node disease without symptoms including use of bradycardia-provoking drugs, patients with symptoms of sinus node dysfunction occurring in the absence of the bradycardia or patients with symptomatic sinus node dysfunction where symptoms can reliably be attributed to non-essential medication do not have an indication for permanent pacemaker therapy.[23] Atrioventricular Block: The following patients with AV conduction block have an strong indication for pacemaker therapy; 1) chronic symptomatic third or second degree (Mobitz I or II) atrioventricular block including induced third or second degree atrioventricular block by required medication[23, 24, 25] 2) asymptomatic patients with third or second degree (Mobitz I or II) atrioventricular block and documented asystole greater than 3.0 seconds in SR or 5.0 seconds in AF, an escape rhythm less than 40 bpm (or >40 bpm with left ventricular dysfunction) or infranodal escape rhythm [23, 26, 27]3) neuromuscular diseases (e.g. myotonic muscular dystrophy, Kearns Sayre syndrome, etc.) with third-degree or second-degree atrioventricular Block[28, 29] or 4) third or second degree (Mobitz I or II) atrioventricular block after catheter ablation of the atrioventricular junction or after valve surgery when the block is not expected to resolve[23, 30, 31, 32] and 5) patient with third or second degree AV block during exercise with no myocardial ischemia[23, 33]. Patients with asymptomatic first degree atrioventricular block, asymptomatic second degree Mobitz I with supra-Hisian conduction block or atrioventricular block expected to resolve do not require a pacemaker implantation.[9, 23, 34] Intraventricular conduction Block: Patient which show a intermittent third-degree atrioventricular block, advanced second-degree or Mobitz II atrioventricular block have an strong indication for pacemaker therapy[23, 35, 36, 37, 38]. Patients with a bundle branch block without atrioventricular block or symptoms and bundle branch block with first-degree atrioventricular block without symptoms should not have a pacemaker implanted.[23, 39] References <biblio> 1. Epstein pmid=23255456 2. Ferrer pmid=5695590 3. Talan pmid=7083929 4. Mangrum pmid=10706901 5. Strasberg pmid 7471363 6. Donoso pmid 14118480 https://www.textbookofcardiology.org/wiki/Bradycardia 9/10 7/4/23, 12:17 AM Bradycardia - Textbook of Cardiology 7. Zipes pmid 378457 8. Levine pmid=13356435 9. Kay pmid=6461235 10. Kastor pmid=1089890 11. Dreifus pmid=6826942 12. Ector pmid=6191291 13. Langberg pmid 2598419 14. Kim pmid=11230857 15. Glikson pmid=9388104 16. Shaw pmid=4005079 17. Choksk pmid=2360528 18. Mymin pmid=3762641 19. Stevenson pmid=2299071 20. James pmid=14451031 21. Friedberg pmid=14206803 22. Dhingra pmid=4817704 23. McAnulty1 pmid=7088050 24. McAnulty2 pmid=619828 25. Spodick pmid=1529897 26. Ector2 pmid=6147639 27. Mova pmid=19713422 28. Simons pmid=9894656 29. Wiens pmid=6741841 30. Lichstein pmid=6176956 31. Kinley pmid=7503472 32. Krahn pmid=15125724 33. Hoffman pmid=3536438 34. ESC isbn=9780199566990 35. ECGpedia http://en.ecgpedia.org 36. Robles isbn=9789031313983 37. Wellens isbn=9781416002598 38. Elsherrif PMCID: PMC2877697 Retrieved from "http://www.textbookofcardiology.org/index.php?title=Bradycardia&oldid=2527" This page was last edited on 7 January 2014, at 07:10. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Bradycardia 10/10 |
7/4/23, 12:19 AM Brugada Syndrome - Textbook of Cardiology Brugada Syndrome By: Louise R.A. Olde Nordkamp, Arthur A.M. Wilde Brugada syndrome refers to a hereditary disease that is associated with a risk of sudden cardiac death. It is characterized by typical ECG abnormalities: ST segment elevation in the precordial leads (V1 - V3).[2] The Brugada brothers were the first to describe the characteristic ECG findings and link them to sudden death. Before that, the characteristic ECG findings, were often mistaken for a right ventricle myocardial infarction and already in 1953, a publication mentions that the ECG findings were not associated with ischemia as people often expected. Contents General features Clinical diagnosis Physical examination Typical ECG abnormalities in Brugada syndrome: ST elevation in V1-V3, without ischemia.[1] ECG tests Genetic diagnosis Risk Stratification Treatment Lifestyle modification Medication/Other therapies: References General features The diagnosis is based on ECG findings. It is an inheritable cardiac arrhythmia [3] syndrome with an autosomal dominant inheritance. Males are often more symptomatic than females, probably by the influence of sex hormones on cardiac arrhythmias and/or ion channels. The arrhythmias typically occur in patients between 30-40 years of age and often during rest or while sleeping. The right ventricle is most affected in Brugada syndrome, and particularly (but not specifically) the right ventricular outflow tract. The prevalence varies between 5-50:10.000, largely depending on the geographic location (especially in some Southeast Asian countries the disease is more prevalent). https://www.textbookofcardiology.org/wiki/Brugada_Syndrome 1/5 7/4/23, 12:19 AM Brugada Syndrome - Textbook of Cardiology Clinical diagnosis The clinical diagnosis of Brugada syndrome is confirmed in an individual with the following: Findings ECG Type 1 ECG with coved type ST-elevation And at least one of the following Documented ventricular fibrillation Self-terminating polymorphic ventricular tachycardia Syncope Clinical history A family history of sudden cardiac death <45yrs Coved-type ECGs in family members Inducibility of VT/VF during programmed electrical stimulation Noctural agonal respiration Physical examination Patients can present with symptoms of arrhythmias: Out-of-hospital-cardiac-arrest Syncope, pre-syncope (weakness, lightheadedness, dizziness) Chest pain Shortness of breath Paleness Sweating Other clinical presentations of Brugada syndrome may include sudden infant death syndrome (SIDS) and sudden unexpected nocturnal death syndrome (SUDS), which is seen in southeast Asia in which young persons die from cardiac arrest with no identifiable cause (also known as bangungut in the Philippines, lai tai in Thailand, pokkuri in Japan and dab tsog in Laos. However, most patients with Brugada syndrome are asymptomatic and are under medical attention because of family screening for sudden cardiac death/Brugada syndrome or because a Brugada ECG was found coincidentally. ECG tests The ECG in Brugada syndrome is characterized by ST-segment elevations directly followed by a negative T-wave in the right precordial leads (V1-V3) and in leads positioned one or two intercostal space higher. It is referred to as a coved type Brugada ECG, or type 1 ECG, and cannot be explained by electrolyte disturbances, ischemia or structural heart disease. This specific ECG hallmark typically fluctuates over time, and can also be presented as a type 2 or type 3 ECG or even a normal ECG. The type 2 ST-segment https://www.textbookofcardiology.org/wiki/Brugada_Syndrome 2/5 7/4/23, 12:19 AM Brugada Syndrome - Textbook of Cardiology elevation has a saddleback appearance with a high takeoff ST-segment elevation of 2mm, a trough displaying 1mm, and then either a positive or a biphasic T wave. Type 3 has either a saddleback or coved appearance with a ST-segment elevation of <1mm (figure 1). Type 2 and 3 are not diagnostic of the BrS. In some patients a type 1 ECG may only be unmasked or modulated by sodium channel blockers (such as ajmaline or flecainide) a febrile state, vagotonic agents, -adrenergic agonists, -adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hyperkalemia, hypokalemia, hypercalcemia, and alcohol or cocaine toxicity. [3] Genetic diagnosis In only ~30% genetic variants can be detected in the SCN5A[4] gene, which results in a loss of function of the cardiac sodium channel function. This impairs the fast upstroke in phase 0 of the action potential and leads to conduction slowing in the heart. In the remaining patients sometimes cardiac calcium channel genes (CACNxxx) or potassium channel genes (KCNxx) are involved, but in most of the Brugada syndrome patients no genetic defects are found.[5] An example of a Brugada type I ECG Risk Stratification Brugada with symptoms (a history of VT/VF or cardiac syncope) and spontaneous coved-type ECG are at risk for future arrhythmic events. However, in asymptomatic Brugada syndrome patients is still ill-defined. Family history of sudden cardiac death, male gender and inducibility of VT/VF during programmed electrical stimulation[8] is not consistently shown to syndrome patients risk stratification[7] Risk stratification scheme according to clinical variables in Brugada syndrome [6] https://www.textbookofcardiology.org/wiki/Brugada_Syndrome 3/5 7/4/23, 12:19 AM Brugada Syndrome - Textbook of Cardiology be a risk factor. Therefore, risk stratification is best done by an expert cardio-genetics cardiologist.[6] Treatment Lifestyle modification All Brugada syndrome patients should avoid drugs that could manifest a type 1 ECG and VF. These drugs are listed on www.BrugadaDrugs.org (http://www.brugadadrugs.org). Fever may also provoke type 1 ECG and VF. Patients with fever are advised to go to the hospital to make an ECG. When ECG changes are present, monitoring is warranted and antipyretics are needed. Medication/Other therapies: ICD implantation is first line therapy in Brugada patients with a previous cardiac arrest, ventricular tachycardia or cardiac syncope. ICD implantation in asymptomatic patients is not advised and needs careful judgement regarding the low annual rate of arrhythmic events and high incidence rate of complications (7.5 per 100 patient-years). In Brugada patients with recurrent VF events or ICD shocks, isoproterenol or quinidine are known to be effective for VF suppression in both children and adults. Ablation of a fractionated electrogram in the epicardial right ventricular outflow tract is a promising option for VF suppression in Brugada patients in a small study, but still has to be proven in larger cohorts of Brugada patients. References 1. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, and Wilde A. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005 Apr;2(4):429-40. DOI:10.1016/j.hrthm.2005.01.005 | 2. Brugada P and Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992 Nov 15;20(6):1391-6. DOI:10.1016/0735-1097(92)90253-j | 3. Mizusawa Y and Wilde AA. Brugada syndrome. Circ Arrhythm Electrophysiol. 2012 Jun 1;5(3):606- 16. DOI:10.1161/CIRCEP.111.964577 | 4. Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, Mansourati J, Le Scouarnec S, Kyndt F, Le Caignec C, Guicheney P, Gouas L, Albuisson J, Meregalli PG, Le Marec H, Tan HL, and Schott JJ. SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet. 2009 Dec;2(6):552-7. DOI:10.1161/CIRCGENETICS.109.853374 | 5. Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, Babuty D, Sacher F, Giustetto C, Schulze-Bahr E, Borggrefe M, Haissaguerre M, Mabo P, Le Marec H, Wolpert C, and Wilde AA. Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation. 2010 Feb 9;121(5):635-43. DOI:10.1161/CIRCULATIONAHA.109.887026 | 6. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, and Nastoli J. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002 Mar 19;105(11):1342-7. DOI:10.1161/hc1102.105288 | https://www.textbookofcardiology.org/wiki/Brugada_Syndrome 4/5 7/4/23, 12:19 AM Brugada Syndrome - Textbook of Cardiology 7. Gehi AK, Duong TD, Metz LD, Gomes JA, and Mehta D. Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis. J Cardiovasc Electrophysiol. 2006 Jun;17(6):577-83. DOI:10.1111/j.1540-8167.2006.00455.x | 8. Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, Giordano U, Pappone C, Mascioli G, Rossetti G, De Nardis R, and Colombo M. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol. 2012 Jan 3;59(1):37-45. DOI:10.1016/j.jacc.2011.08.064 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Brugada_Syndrome&oldid=2261" This page was last edited on 25 March 2013, at 01:59. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Brugada_Syndrome 5/5 |
7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology Cardiac Arrest S bastien Krul, MD, Jonas de Jong, MD Contents Introduction Basic Life Support (BLS) Foreign body airway obstruction Basic life support in children Automatic external defibrillator (AED) Preventing in Hosptial Cardiac Arrest Advanced Life Support (ALS) Patient assessment Shock protocol No-shock protocol Post-cardiac arrest treatment Prognosis after cardiac arrest Special circumstances References Introduction Survival of cardiac arrest continues to be very poor. In-hospital cardiac arrest has a survival to hospital discharge of 17,6% all rhythms[1]. Out-of-hospital cardiac arrest has a worse survival with 10,7% survival to hospital discharge for all rhythms.[2] Survival is dependent on the characteristics of the cardiac arrest (rhythm), on the patient s medical history, and the time between the cardiac arrest en start of resuscitation. [3, 4, 5] The introduction of the automated external defibrillator (AED) has dramatically increased survival of out-of-hospital cardiac arrest victims.[6, 7] In this chapter we give an overview of basic life support (BLS) and advanced life support (ALS) based on the recommendation of the European Resuscitation Council Guidelines for Resuscitation 2010. Basic Life Support (BLS) To increase survival after cardiac arrest it is vital to decrease the time to resuscitation.[3] The training of persons in BLS can increase bystander participation in performing cardiopulmonary resuscitation (CPR). [8] When non-arrest victims inadvertently receive CPR it is extremely rare to inflict serious harm (2% chance of a fracture)[9]. Furthermore the risk of disease transmission is extremely low, especially without high-risk activities as intravenous canulation.[10, 11] A straightforward protocol has been created to execute BLS (Figure 1).[12] https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 1/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology Figure 1. The basic life support algorithm. https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 2/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology If at any stage the patient is conscious, has normal ventilation or recovers consciousness a care provider should find out what is wrong with the person and get help if needed. Repeated reassessment is necessary to detected deterioration of the patient s condition. Foreign body airway obstruction An obstruction of the airway is uncommon, but reversible and adequate recognition can prevent cardiac arrest.[13] Airway obstruction is usually related to eating. In a mild obstruction patients can cough and speak and only frequent reassessment is advised. Patients that have a severe obstruction are unable to speak and have problems breathing and coughing. If a patient is still conscious five back blows can be applied between the shoulder blades whilst the patient leans forward. Otherwise five abdominal thrusts can be applied by clenching a fist and grasping it with the other hand. Place the hands it between the rib-cage and the umbilicus and pull sharply inward and upward whilst standing behind the patients.[14, 15] If the patient loses consciousness start BLS.[12] Basic life support in children In general the BLS algorithm is similar in children. However, due to the differences in underlying pathology of cardiac arrest and the size of children, small changes must be incorporated. Firstly, as pulmonary causes for cardiac arrest are more frequent, the BLS can be started with 5 initial rescue breaths before starting with the chest compression. The chest compression should compress the chest at least one third of the depth. The chest compression can be performed with one or two hands for a child over 1 year and with 2 fingers for an infant under 1 year.[12] Automatic external defibrillator (AED) The AED is a complex device that analyses the rhythm of patients and delivers a shock to defibrillate patients. It detect whether a patient has ventricular fibrillation or a different arrhythmia. When it detects a shockable rhythm it advises the user to deliver the shock, all settings are automatically adjusted. It also remembers the course of events so that the tracing can be recovered and analysed after the resuscitation. When the AED is attached during BLS let the AED assess the rhythm. Do not manipulate the person while the AED assesses the rhythm to prevent motion artefact disturbing the detection algorithm. Follow the instructions of the AED; this can be either a shock or no shock. After shock or non-shock immediately continue with chest compressions and rescue breaths. Continue the CPR until the AED rechecks the rhythm. Standard AED are usable for children older than 8 years, special paediatric pads and an AED paediatric mode should be used in younger children.[16] Preventing in Hosptial Cardiac Arrest The best way to prevent sudden death is to early detect deterioration of a patient and to act on early warning signs.[18] Cardiac arrest is rarely unpredictable and is precipitated by a slow deterioration. An early warning score (Figure 2) helps to create consensus among care providers about the sickness of a patient.[19, 20] If the summed score reached a certain threshold, a doctor should be notified. The notified doctor should https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 3/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology assess the patient within 30 minutes a treatment plan. If the patient does not improve within 60 minutes a reassessment should follow with possible inclusion of team a medical emergency care intensive or (MET) specialist.[21] and discuss Advanced Life Support (ALS) BLS the cornerstone to the treatment of cardiac arrest. Early and high quality CPR is the to survival. critical hospital setting trained experts and technical equipment can facilitate arrest management. In case of a witnessed cardiac arrest caused by VT/VF in a monitored setting, three successive shocks followed by immediate CPR may be considered. If no defibrillation options are available and a precordial thump can be given in the first few seconds after the cardiac arrest.[22] It can not cause delay of the resuscitation attempt. The only intervention besides proper BLS and early defibrillation to increase survival is the administration of adrenaline.[23] The ALS protocol deviates into two strategies encountered in the setting of cardiac arrest; a shock protocol and no-shock protocol (Figure 3). During both protocols it is important to establish intravascular access as soon as possible, as an alternative intraosseous injection of drugs can be performed.[24] Furthermore assessment of airway management and ventilation is essential. Oxygen should be administered as soon as possible and be titrated to the arterial blood oxygen saturation. Tracheal intubation is the optimal method of providing and maintaining a clear and secure airway. Intubation should be performed by experienced personnel to reduce complications and delay between intubation and chest compressions. When there is return of spontaneous circulation the resuscitation team should stabilize the patient to prevent recurrence of cardiac arrest.[25, 26] In Figure 2. An example of a MEWS. Adapted from: [17]. cardiac Patient assessment During a cardiac arrest a structured assessment of the patient is required to detect the effects of the resuscitation, return of spontaneous circulation, reversible causes. To facilitate this assessment, an ABCDE approach can be used.[27, 28] Airway: During the first step it is important to assess if the airway is clear. Airway obstruction can occur at any level. It can be caused by obstruction from the soft palate and epiglottis, blood, vomit and foreign bodies or airway oedema. It is important to look, listen and feel for airway obstruction. Look for chest and abdominal movements, listen and feel for airflow at the mouth and nose. In partial airway obstruction, the inspiration or expiration is usually noisy by an inspiratory stridor or expiratory wheeze. Breathing: Hypoxaemia is a reversible cause and after assessment and securing the airway, ventilation of the patient should be optimized. The airway can be secured using a variety of devices and ventilation methods. Arterial blood oxygen saturation can be monitored to assess hypoxaemia. If necessary tracheal intubation, sedation and controllered ventilation should be instituted. Circulation: Myocardial ischemia or infarction is a common cause of cardiac arrest. Furthermore before or after the cardiac arrest tachycardias or bradycardias may occur and acute management is indicated. https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 4/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology Figure 3. The advanced life support algorithm. https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 5/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology Disability: This step consist of determining the Glasgow Coma Scale of the patients and look for neurologic symptoms that might cause cardiac arrest. Furthermore it is important monitor glucose and temperature. Environment: In an out of hospital cardiac arrest setting it is important to secure the environment of the cardiac arrest. There should be a safe environment for both the caregiver and the patient. The patient and environment itself might show the cause of the cardiac arrest e.g. chemical or electrical burns, drowning, anaphylactic shock, illicit drugs. Shock protocol When a shockable rhythm is detected, it is important to minimize the time between chest compressions and defibrillation.[29, 30] When the shock is delivered immediately resume with the chest compressions to minimize delay. Even after a successful shock the heart can be stunned and effective circulation can only be maintained through chest compressions. After the first round of shock and compressions reassess rhythm and act according to the protocol. After the third shock has been given, adrenaline 1mg and amiodarone 300mg can be administered intravenously.[23, 31] Further adrenaline 1mg can be administered every 3-5 minutes, there is no further indication for anti-arrhythmic drugs during resuscitation. Continuous monitoring is required for return of spontaneous circulation or for asystole and initiation of the no-shock protocol. No-shock protocol When asystole or pulseless electrical activity is detected CPR should be started immediately simultaneously with 1mg intravenous adrenaline. Assess the rhythm after 2 minutes of chest compressions and continue according to the rhythm. Continue with adrenaline injections intravenously every 3-5 minutes if no return of spontaneous circulation has been achieved. There is no place for further medical intervention. Post-cardiac arrest treatment After cardiac arrest and return of spontaneous circulation the whole body ischemia/reperfusion affects all organ systems. Multiple organ failure, increased risk of infection, neurocognitive dysfunction and myocardial dysfunction are common problems encountered after a cardiac arrest which resembles the problems encountered with sepsis.[26] After resuscitation strict control of oxygenation, cardiac output and glucose metabolism can improve outcome after cardiac arrest.[26, 32, 33] Treatment of the underlying cause of the cardiac resuscitation, for instance a myocardial infarction should be considered. Studies have indicated that therapeutic hypothermia (32-34oC) during 12-24h after cardiac arrest can increase neurological outcome.[34] This can be achieved by internal infusion or external cooling. Therapeutic hypothermia should be initiated in comatose patients quickly after return of circulation. When cooled the temperature should be maintained without to much fluctuations.[35] Warming of the patient should occur very slowly (0.25oC to 0.5oC per hour) to prevent rapid plasma electrolyte concentration changes, intravascular volume and metabolic rate changes.[36] Prognosis after cardiac arrest Prognosis after cardiac arrest is difficult and cannot be fully predicted. Survival after cardiac arrest is poor, mainly due to neurological damage, and two out of three patients admitted to the ICU following cardiac arrest die from neurological injury.[37] Most prognostic markers have been studied in the era before therapeutic hypothermia. Therefore their value in patients that are actively cooled is incompletely understood. It is not possible to predict outcome reliable within 24 hours after cardiac arrest. Clinical examination of the patient can give information on the prognosis of the patient 24 hours after cardiac https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 6/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology arrest. After 72 hours the absence of both pupillary light and corneal reflex predict poor outcome.[38] In patients that are not treated with therapeutic hypothermia absence of vestibulo-ocular reflexes at >24h and a Glasgow coma scale motor score of 2 or less >72 hours after return of spontaneous circulation are possible prognostic markers of a worse outcome.[38, 39] Furthermore myoclonal status is associated with poor outcome, but recovery can occur, and is therefore not useful in determining the prognosis.[40] Electrophysiological studies measuring somatosensory evoked potentials (SSEP) after 24 hours, absence of bilateral N20 cortical response to median nerve stimulation predicts a poor outcome.[41] Special circumstances In all circumstances the normal protocol for BLS and ALS is the cornerstone in the treatment of cardiac arrest. However some conditions encountered during resuscitation or as a cause of cardiac arrest, can affect the procedure.[42] Anaphylaxis: Anaphylaxis is a life-threatening hypersensitivity reaction and can be accompanied by airway/breathing/circulation problems due to swelling of the mucosa.[43] The cause of the anaphylaxis should be identified and can be a broad range of triggers (food, insects, drugs etc.).[44] Anaphylaxis rapidly develops after exposure to the trigger, usually within minutes. Patients should receive intramuscular adrenaline before an intravenous route is established and anti-inflammatory drugs (steroids, anti-histamines) should be initiated.[44, 45, 46, 47] Oxygen en fluids should be administered as swelling of the airway can result impair breathing and due to fluid loss is out of the circulation hypovolaemia can develop. Asthma: Patients with asthma who experience a cardiac arrest usually have a long period of hypoxaemia, however cardiac arrest is not necessarily related to asthma severity.[48] Patients with acute severe asthma require oxygen, aggressive medical therapy and should be admitted to the critical care area. The main troubles encountered in the resuscitation of patients with asthma relates to the underlying lung disease. In general increased lung resistance makes ventilation of these patients difficult and can increase the risk of gastric inflation.[49] Early intubation is indicated in these patients during the ALS setting. Due to the hyperinflation of the lungs more energy might be required in defibrillating these patients, as the heart is isolated by air.[50] Cardiac arrest after cardiac surgery: Cardiac arrest after cardiac surgery is usually caused by specific causes related as a consequence of the cardiac surgery, such as tamponade, hypovolaemia, myocardial ischaemia, tension pneumothorax, or pacing failure.[51] Early resternotomy can be the key to survival, especially after repeated defibrillation has failed or if asystole is observed.[52, 53, 54] When the sternum is opened internal cardioversion (output of 5-20J) and cardiac compression can be applied across the ventricles. Drowning: Drowning is a common cause of accidental death.[55] There are no differences between victims of salt water and fresh water drowning. Correction of hypoxia is critical in the outcome of these victims as cardiac arrest is a consequence of the hypoxia. Care should be taken to start immediate resuscitation and restore oxygenation, ventilation and perfusion. During BLS it is recommended to start the BLS with 5 rescue breaths.[56] Rescue breathing is difficult after drowning due tot the presence of fluid in the airway and the high inflation pressure required after drowning. Furthermore regurgitation is common and removal of the regurgitated material during resuscitation is required.[57] It is common for hypothermia to be present in victims of drowning, complicating the resuscitation attempt. After return of spontaneous circulation, pneumonia is common and patients are prone to develop acute respiratory distress syndrome (ARDS).[58, 59] Electrocution: Electrocution can result in multi-system injury and usually occur in the workspace in adult or at home in children. The direct effects of an electric shock on tissues, for instance paralysis of the respiratory system or muscles, VF in the myocardium, ischemia due to coronary artery spasm or asystole can result in a cardiac arrest.[60] Electrical burns can complicate the resuscitation and care should be taken to avoid further complications resulting from these burns. Adequate fluid therapy is required if there is significant tissue destruction. Due to electrical burns around the neck and muscular paralysis early intubation and prolonged ventilatory support may be required.[61] https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 7/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology Electrolyte disorder: Electrolyte abnormalities are among the most common causes of cardiac arrhythmias. Potassium disorders are commonly seen, especially hyperkalaemia has a high risk of malignant arrhythmias.[62] During cardiac arrest treatment of these abnormalities is no different than in the normal clinical setting, and aggressive treatment of the electrolyte disorder should be initiated.[63, 64] Hyperthermia: Exogenous or endogenous hyperthermia can result in heat stress, progressing to heat exhaustion and results in heat stroke.[65] Heat stress can provoke edema, syncope and cramps and is treated with rest, cooling and oral rehydration and salt replacement. Heat exhaustion is a systemic reaction to prolonged heat exposure and is accompanied by headaches, dizziness, nausea, vomiting, tachycardia, hypotension, muscle pain, weakness and cramps. Treatment is similar as in a heat stroke, but active cooling might be required in severe cases with ice packs or cold intravenous fluids. Heat stroke is a systemic inflammatory response with a core temperature above 40,6oC. It can lead to varying levels of organ dysfunction accompanied by mental changes.[66] It can occur during high environmental temperatures or during strenuous physical exercise in high environmental temperatures. Rapid cooling of the victim should occur as soon as possible.[67] Patients with heat-stroke usually have electrolyte abnormalities and hypovolaemia. Hypothermia: In hypothermia (<35oC) it is difficult to detect signs of life. Therefore resuscitation should proceed according to standard protocols until the patient has reached normothermia. Second to resuscitation, warming of the body temperature by passive or active external and internal methods should be started. Examples of passive rewarming are drying and insulation of the body, whilst examples of active rewarming are infusion of warmed intravenous fluids or forced air rewarming.[68, 69, 70] As a result of rewarming vasodilatation occurs and fluid administration may be required. Resuscitation during hypothermia is difficult, the thorax is stiff and the heart is less responsive to medication and defibrillation. Furthermore drug metabolism is slowed, resulting in increased plasma levels of medication.[71] Medication should be administered at double intervals in patients <35oC and withheld in patient <30oC. Rhythm disturbances usually seen at rewarming after hypothermia are bradycardia, atrial fibrillation, VF and asystole. Bradycardia and atrial fibrillation revert to normal sinus rhythm as the core body temperature increases.[72] Poisoning: Accidental poisoning in children or by therapeutic or recreational drugs in adults are the main causes of poisoning, however rarely causes cardiac arrest.[73] It is important to identify the poison to start antidote treatment or decontamination.[74] During the BLS and ALS care should be taken when performing mount-to-mouth ventilation in the presence of certain chemical types of poisoning. Respiratory arrest and airway depression is more common after poisoning.[75] Early intubation can prevent cardiac arrest and pulmonary aspiration. When confronted with a poisoning in an ALS setting, temperature should be monitored as hypo- or hyperthermia my occur after drug overdose. Furthermore, due to the slow metabolization or excretion of certain poisons the resuscitation can continue for a long period. Pregnancy: If a cardiac arrest occurs during pregnancy the safety of the fetus should always be considered. Due to the growth of the uterus compression of the inferior vena cava can occur and as a result venous return and cardiac output is compromised. During CPR displace the uterus to the left or apply a left lateral tilt of the surface the patient is lying upon to minimize compression from the uterus. [76] Furthermore the increased abdominal pressure can increase the risk of pulmonary aspiration and can hamper proper ventilation; therefore early intubation can lower risks and ease cardiopulmonary resuscitation. During ALS normal defibrillator shock energies can be used.[77] An emergency hysterotomy or cesarean section needs to be considered, if gestational age is after 20 weeks.[78] After 20 weeks the size of the uterus is large enough to compromise cardiac output, however fetal viability begins at approximately 24-25 weeks.[79] Traumatic Cardiorespiratory Arrest: Cardiac arrest caused by trauma has low chance of survival.[80] Blunt trauma can cause commotio cordis if there is an impact to the chest wall over the heart.[81] This impact can cause arrhythmias (usually ventricular fibrillation) and occurs often during sports.[82] Penetrating trauma can be cause for an emergency thoracotomy. Emergency thoracotomy has to be performed early after onset of CPR.[83] It is important to manage the resuscitation according to protocol and treat reversible causes. https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 8/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology References <biblio> 1. ESC isbn=9780199566990 2. Nolan1 pmid=20956052 3. Koster2 pmid=20956051 4. Deakin3 pmid=20956050 5. Deakin4 pmid=20956049 6. Soar8 pmid=20956045 7. Atwood pmid=16199289 8. Meaney pmid=19770741 9. Waalewijn pmid=11719156 10. Holmberg1 pmid=11320981 11. Holmberg2 pmid=9547841 12. SOSKANTO pmid=17368153 13. White pmid=20026780 14. Peberdy pmid=16784998 15. Mejicano pmid=9841588 16. Fingerhut pmid=10662354 17. Guildner pmid=1018395 18. Ruben pmid=740619 19. Niemann pmid=10381988 20. Alfonzo pmid=16600469 21. Mahoney pmid=15846652 22. Bronstein pmid=20028214 23. Zimmerman pmid=14668617 24. Yanagawa pmid=17870477 25. Yeon pmid=19443097 26. Manolios pmid=3340043 27. Gregorakos pmid=19132444 28. Berkel pmid=8857116 29. Paal pmid=16508739 30. Mattu pmid=12098179 31. Kornberger pmid=10488932 32. Reuler pmid=358883 33. Zell pmid=3985447 34. Pease pmid=12075060 35. Bouchama pmid=19404610 36. Bouchama2 pmid=17498312 37. Romagnoli pmid=17430352 38. Bowman pmid= 7618786 39. Deakin5 pmid=9667332 40. Soar3 pmid=18358585 41. Lieberman pmid=17165265 https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 9/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology 42. Simpson pmid=20413204 43. Kemp pmid=18691308 44. Choo pmid=22513951 45. Sheikh pmid=17620060 46. Anthi pmid=9440561 47. Pottle pmid=11886732 48. elBanayosy pmid=9713724 49. Dunning pmid=19297185 50. Rosemurgy pmid=8371308 51. Maron pmid=20220186 52. Maron2 pmid=19221222 53. JACS pmid=11548801 54. Bamber pmid=12818977 55. Nanson pmid=11493495 56. Katz pmid=15970850 57. Allen pmid=8179651 58. Geddes pmid=3543629 59. Cooper pmid=8570929 60. Smith pmid=15071378 61. Hodgetts pmid=12161291 62. Bellomo pmid=20598425 63. Hillman pmid=15964445 64. Pellis pmid=19010581 65. Glaeser pmid=8517560 66. Olasveengen pmid=19934423 67. Nolan5 pmid=18963350 68. Thim pmid=22319249 69. Guly pmid=12835350 70. Balan pmid=17068310 71. Padkin pmid=19460604 72. Froehler pmid=17559883 73. Polderman pmid=19237924 74. Arrich pmid=17334257 75. Laver pmid=15365608 76. Zandbergen pmid=16401847 77. Edgren pmid=3621954 78. English pmid=19604197 79. Wijdicks pmid=16864809 80. Edelson pmid=16982127 81. Eftestol pmid=12010909 82. Dorian pmid=11907287 83. IHI http://www.ihi.org/knowledge/Pages/ImprovementStories/HospitalatNightProgram.aspx Retrieved from "http://www.textbookofcardiology.org/index.php?title=Cardiac_Arrest&oldid=2163" https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 10/11 7/4/23, 12:18 AM Cardiac Arrest - Textbook of Cardiology This page was last edited on 20 February 2013, at 19:38. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Cardiac_Arrest 11/11 |
7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology Cardiac Arrhythmias S bastien Krul, MD Contents Introduction Cardiac Action Potential Phase 0: Rapid Depolarization Phase 1: Early Rapid Repolarization Phase 2: Plateau Phase 3: Final Rapid Repolarization Phase 4: Resting membrane potential Cardiac conduction Sinus node Atrium AV node Bundle of His Bundle Branches Ventricle Mechanisms of Arrhythmia Abnormal Impulse Formation Abnormal Automaticity Triggered Activity Disorders of Impulse Conduction Conduction block Re-entry References Introduction A basic knowledge of the cardiac action potential and cardiac conduction system facilitates understanding of cardiac arrhythmias. The effects and side-effects of anti-arrhythmic drugs are depended on the influence on ion channels involved in the generation and/or perpetuation of the cardiac action potential. Cardiac Action Potential The cardiac action potential is a result of ions flowing through different ion channels. Ion channels are passages for ions (mainly Na+, K+, Ca2+ and Cl-) that facilitate movement through the cell membrane. Changes in the structure of these channels can open, inactivate or close these channels and thereby https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 1/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology control the flow of ions into and out of the myocytes. Due to differences in the type and structure of ion channels, the various parts of the heart have slightly different action potential characteristics. Ion channels are mostly a passive passageway, where movement of ions is caused by the electrochemical gradient. In addition to these passive ion channels a few active trigger-dependent channels exist that open or close in response to certain stimuli (for instance acetylcholine or ATP). The changes in the membrane potential due to the movement of ions produce an action potential which lasts only a few hundreds of milliseconds. Disorders in single channels can lead to arrhythmias, as seen in the section primary arrhythmias. The action potential is propagated throughout the myocardium by the depolarization of the immediate environment of the cells and through intracellular coupling with gap- junctions.[1] In summary during the depolarization, sodium ions (Na+) stream into the cytoplasm of the cell followed by a influx of calcium (Ca2+) ions (both from the inside (sarcoplasmatic reticulum) and outside of the cell). These Ca2+ ions cause the actual muscular contraction by coupling with the muscle fibers. During repolarization the cell returns to the resting membrane potential, due to the passive efflux of K+(Figure 1). In detail the (ventricular) action potential can be divided in five phases: [2, 3] Phase 0: Rapid Depolarization is Rapid started once the membrane potential reaches a certain threshold (about -70 to -60 produces mV). activation sodium channels and a rapid influx of Na+ and a corresponding rapid upstroke of the action potential. higher potentials (-40 to -30) Ca2+ in the influx participates upstroke. In the sinus node and AV node a slower upstroke can be observed (Figure 2). This is because the rapid depolarization in is mainly these cells slower the mediated by acting Ca2+ ion channels. The slower activation produces a slower upstroke. depolarization This of At Figure 1. The cardiac ventricular action potential and relevant ion channels. Phase 1: Early Rapid Repolarization https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 2/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology Immediately following rapid depolarization, the inactivation of the Na+ channel (INa) and subsequent activation of the outward K+ channel (Ito) and the Na+/Ca2+ exchanger (INa,Ca), which exchanges 3 Na+ for 1 Ca2+, produces a early rapid repolarization. Due to the limited role of the Na+ channel in the upstroke of sinus node and AV node cells and the subsequent slower depolarization, this rapid repolarization is not visible in their action potentials (Figure 2). Phase 2: Plateau The plateau phase represents an equal influx and efflux of ions in or out of the cell producing a stable membrane potential. This plateau phase is predominantly observed in the ventricular action potential. The inward movement of Ca2+ through the open L-type Ca2+ channels (ICa-L) and the exchange of Na+ for internal Ca2+ by the Na+/Ca2+ exchanger (INa,Ca) are responsible for the influx of ions during the plateau phase. The efflux of ions is the result of outward current carried by K+ (IKur and Ks). Phase 3: Final Rapid Repolarization Final repolarization is mainly caused by inactivation of Ca2+ channels, reducing the influx of positive ions. Furthermore repolarizing K+ currents (delayed rectifier current IKs and IKr and inwardly rectifying current IK1 and IK,Ach) are activated which increase efflux of positive K+ ions. This results in an repolarization to the resting membrane potential. Phase 4: Resting membrane potential During phase 4 of the action potential intracelullar and extracellular concentrations of ions are restored. Depending on cell type the resting membrane potential is between -50 to -95 mV. Sinus node and AV nodal cells have a higher resting membrane potential (-50 to -60 mV and -60 to -70 respectively) in comparison with atrial and ventricular cardiomyocytes (-80 to -90 mV). Sinus node cells and AV nodal cells (and to a lesser degree Purkinje fibers cells) have a special voltage dependent channel If, the funny current. Furthermore they lack IK1, a K+ ion channel that maintains the resting membrane potential in atrial and ventricular tissue. The If channel causes a slow depolarization in diastole, called the phase 4 diastolic depolarization, which results in normal automaticity. The frequency of the sinus node discharges are regulated by the autonomous nerve system and due to the relative high firing frequency (60-80 beats per minute) the sinus node dominates other potential pacemaker sites. Cardiac conduction The cardiac conduction system (Figure 2) consist of specialized fast conducting tissue though which the electric activity of the heart spreads from the atria to the ventricles. The characteristics of the different parts of the conduction system are a result of the different characteristics of the individual myocytes. On a larger level, function is controlled predominantly by the autonomic nervous system (both vagal and sympathetic nerve system). Especially the sinus node and atrioventricular node are responsive to the autonomic nerve system. The ganglionic plexus, a conglomeration of both vagal and sympathetic nerves, form the intrinsic cardiac nerve system and innervate through a network of nerve fibers the atria and ventricles. The vagal and sympathetic nerve system are both continually active in the heart, but vagal activity dominates the tonic background stimulation of the autonomic nerve system. Moreover the heart https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 3/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology is more susceptible to vagal stimulation. Vagal stimulation provokes a rapid response and the effect dissipates swiftly in contrast to sympathetic stimulation which has a slow onset and offset. Vagal stimulation results in a reduction in sinus node activation frequency and prolongs AV nodal conduction. These effects can occur simultaneously or independent of each other. Sympathetic stimulation exerts reverse effects, accelerating the sinus node firing frequency and improving AV nodal conduction. The autonomic nerve system has a small effect on cardiomyocytes. Vagal stimulation tends to prolong the refractory period and decrease the myocardial contractility. Sympathetic stimulation has the opposite effect on the cardiac tissue. The physiological modulation of cardiac conduction is vital to adaptation of the heart to rest and exercise. However the autonomic nervous system can contribute as a modifier is certain to facilitate the occurrence of certain arrhythmias.[3] Sinus node The sinus node is a densely innervated area located in the right atrium which is right supplied (55%-60%) or circumflex (40%-45%) coronary artery. It is a small structure of 10- 20mm long and 2-3mm wide and contains a diversity of cells. include These pacemaker cells which are discharged synchronously due to mutual entrainment. This results in an activation wave front activating the rest of the atrium. by the Figure 2. The different shapes of the cardiac action potential in the heart. Atrium The impulse formed in the sinus node is conducted through the atrium to the AV-node. Evidence indicates three preferential conduction pathways. The pathways show preferential conduction due to their anatomical structure and rather than specialized conduction properties. The three pathways are: the anterior internodal pathway, the middle internodal tract the posterior internodal pathway. The anterior internodal pathway connect to the anterior interatrial band, also known as the Bachmann bundle. This bundle of muscular tissue conducts the sinus wave front from the right to the left atrium. AV node https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 4/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology The connection between atria and ventricles is facilitated through the AV node, lying in the right atrial myocardium and a penetrating part, the bundle of His. The AV node acts as a gatekeeper, regulating impulse conduction from the atrium to the ventricle. Additionally, due to the phase 4 diastolic depolarization it can exhibit impulse formation. The AV node is supplied in most cases (85%-90%) by the right coronary artery or in the remaining cases the circumflex artery. Bundle of His Connecting the distal AV node and the proximal bundle branches, the bundle of His is supplied by both the posterior and anterior descending coronary arteries. It is enclosed by the central fibrous body and membranous septum between the atria and the ventricles. The location and blood supply protect the bundle of His from external influences. Bundle Branches From the bundle of His the right bundle branch continues to the right ventricular apex. The left bundle branch splits of and divides in two fascicular branches. Commonly the left bundle branch consist of an anterior fascicle, which activates the anterosuperior portion of the left ventricle. and the thicker and more protected posterior fascicle which activates the inferoposterior part of the left ventricle. Ventricle The ventricle is activated through the dense network of Purkinje fibers originating from the bundle branches. They penetrate the myocardium and are the starting point of the ventricular activation. The left ventricular areas first excited are the anterior and posterior paraseptal wall and the central left surface of the interventricular septum. The last part of the left ventricle to be activated is the posterobasal area. Septal activation starts in the middle third of the left side of the interventricular septum, and at the lower third at the junction of the septum and posterior wall. Activation of the right ventricle starts near the anterior papillary muscle 5 to 10 milliseconds after onset of the left ventricle.[4] Mechanisms of Arrhythmia Structural abnormalities or electric changes in the cardiomyocytes can impede impulse formation or change cardiac propagation, therefore facilitating arrhythmias. Arrhythmogenic mechanisms can arise in single cells (automaticity, triggered activity), but other mechanisms require multiple cells for arrhythmica induction (re-entry). We briefly discuss the pathophysiological mechanisms of the main causes of arrhythmia. [5] Abnormal Impulse Formation Abnormal Automaticity The mechanism of abnormal automaticity is similar to the normal automaticity of sinus node cells. Abnormal automaticity can be caused by changes in the cell ion channel characteristics due to drugs (digoxine) or changes in the electrotonic environment (myocardial infarction). Abnormal automaticity can result from an increase of normal automaticity in non-sinus node cells or a truly abnormal https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 5/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology automaticity in cells that don't exhibit a phase 4 diastolic depolarization. An important phenomenon in (both normal and abnormal) automaticity is overdrive suppression. In overdrive suppression the automaticity of cells is reduced after a period of high frequency excitation. The cellular mechanism responsible for this effect is an increased activity of the Na+, K+ pump (INa, K) which results in an increased efflux of Na+, thereby inducing a hyperpolarization.[2] Triggered Activity Triggered activity is depolarization of a cell triggered by a preceding activation. Due to early or delayed afterdepolarizations the membrane potential depolarizes and, when reaching a threshold potential, activates the cell. These afterdepolarizations are depolarizations of the membrane potential initiated by the preceding action potential. Depending on the phase of the action potential in which they arise, they are defined as early or late afterdepolarizations (figure 3). Figure 3. The different mechanisms of arrhythmia. A disturbance of the balance in influx and efflux of ions during the plateau phase (phase 2 or 3) of the action potential is responsible for the early afterdepolarizations. Multiple ion currents can be involved in the formation of early after depolarizations depending on the triggering mechanism. Early afterdepolarizations can develop in cells with an increased duration of the repolarization phase of the action potential, as the plateau phase is prolonged. The prolonged repolarization might reactivate the Ca2+ channels that have recovered from activation at the beginning of the repolarization. Otherwise disparity in action potential duration of surrounding myocytes can destabilize the plateau phase through adjacent depolarizing currents. Delayed afterdepolarizations occur after the cell has recovered after completion of repolarization. In delayed afterdepolarization an abnormal Ca2+ handling of the cell is responsible for the afterdepolarizations due to release of Ca2+ from the storage of Ca2+ in the sarcoplasmatic reticulum. The accumulation of Ca2+ increases membrane potential and depolarizes the cell until it reaches a certain threshold, thereby creating an action potential. A high heart rate can result in the accumulation of intracellular Ca2+ and induce delayed afterdepolarizations. Disorders of Impulse Conduction Conduction block https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 6/7 7/3/23, 11:59 PM Cardiac Arrhythmias - Textbook of Cardiology Conduction block or conduction delay is a frequent cause of bradyarrhythmias, especially if the conduction block is located in the cardiac conduction system. However tachyarrhythmias can also result from conduction block when this block produces a re-entrant circuit (see below). Conduction block can develop in different (pathophysiological) conditions or can be iatrogenic (medication, surgery). Re-entry Re-entry or circus movement is a multicellular mechanism of arrhythmia. Important criteria for the development of re-entry are a circular pathway with an area in this circle of unidirectional block and a trigger to induce the re-entry movement. Re-entry can arise when an impulse enters the circuit, follows the circular pathway and is conducted through an unidirectional (slow conducting) pathway. Whilst the signal is in this pathway the surrounding myocardium repolarizes. If the surrounding myocardium has recovered from the refractory state, the impulse that exits the area of unidirectional block can reactivate this recovered myocardium. This process can repeat itself and thus form the basis of a re-entry tachycardia. Slow conduction and/or a short refractory period facilitate re-entry. The reason of unidirectional block can be anatomical (atrial flutter, AVNRT, AVRT) or functional (myocardial ischemia) or a combination of both.[6, 7] References <Biblio> 1. Durrer pmid=5482907 2. deBakker pmid=8353918 3. Coronel isbn=9031348295 4. Braunwald isbn=1437703984 5. Kleber pmid=15044680 6. Janse pmid=2678165 7. Berne isbn=0815109520 Cardiodrugstemplate Retrieved from "http://www.textbookofcardiology.org/index.php?title=Cardiac_Arrhythmias&oldid=2366" This page was last edited on 9 May 2013, at 13:03. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Cardiac_Arrhythmias 7/7 |
7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Cardiac Pharmacology Heather Melrose, Jonas de Jong Contents Renin-Angiotensin-Aldosterone System Neural Control of the Cardiovascular System Sympathetic (Adrenergic) Nervous System Vasculature Heart Parasympathetic Nervous System Vasculature Heart Platelet/Clotting System Anti-coagulants Pharmacokinetics Common Drug-Drug Interactions References Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease. Renin-Angiotensin-Aldosterone System The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood is activated by pressure. The system decreases in blood volume or pressure detected in two ways: a drop in blood pressure baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; aldosterone. renin, angiotensin Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. detected by and RAAS schematic Angiotensin II causes increases in blood pressure by actions at various sites: https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 1/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Adrenal Glands: Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance. Kidneys: Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow. Cardiovascular System: Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy. Central Nervous System: In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased thirst, encouraging water intake. Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease. Neural Control of the Cardiovascular System Sympathetic (Adrenergic) Nervous System The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. Vasculature The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately contraction, vasoconstriction and consequent increases in systemic blood pressure. results in myocyte Interaction between the sympathic and parasympathic nervous system and the heart Heart Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the -receptor subfamily and include 1 and 3 receptors. Catecholamine binding to 1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However 3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart. https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 2/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias. Parasympathetic Nervous System The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. Vasculature Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation. Heart Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions. Platelet/Clotting System Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or clot , helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. Platelet activation and inhibition operates through surface receptors on platelets. Feedback loops enhance platelet activation (e.g. ADP released by platelets increases platelet activation, through the ADP receptor) There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process. ischaemia or stroke; Anti-coagulants Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia. As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A2 reduces platelet aggregation and thus prevents clot formation. https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 3/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology P2Y12 inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y12 subtype of the platelet ADP receptor. By blocking P2Y12, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation. Pharmacokinetics When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated: Standard units (Abbreviation) Property Description Formula Dose Amount of active drug given to patient mg (D) Drug Specific (From clinical studies) Concentration Amount of drug in a given plasma volume g/ml (C) = D / Vd The concentration of drug needed to elicit a response halfway between zero and maximal responses. y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient) EC50 g/ml (EC50) The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. Volume of Distribution L (Vd) D / C Elimination Constant (Rate) The rate at which the drug is removed from the body. h-1 (Ke) ln(2) / t1/2 or CL / Vd 100 (AUC (po) D (iv))/(AUC (iv) D (po)) no units as expressing a fraction (f) AUC = Area under curve po = oral intravenous administration administration How much of the administered dose is available for actual use by the body. Bioavailability iv = The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration g/ml (Cmax or Cmin) Identified via direct measurement of plasma C Cmax or Cmin The time it takes for a drug to reach Cmax following administration Identified via direct measurement of plasma C over time tmax h (tmax) The time it takes for a drug to reach half its original concentration Half-life h (t1/2) ln(2) / Ke The volume of plasma cleared of the drug over a set time Drug Clearance l/h (CL) Vd x Ke or D / Area under curve Common Drug-Drug Interactions It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug drug interactions related to cardiovascular drugs are listed below: https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 4/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Drugs that drug action Drugs that drug action Drug Diuretics Antiarrhythmics Macrolide antibiotics Cholestyramine Neomycin Keto- and intraconazole Calcium antagonists Cyclosporine, indomethacin HMG CoA reductase inhibitors Benzodiazepines Amiodarone Verapamil Rifampicin Antacids (liquid) Digoxin Furosemide Amiodarone Sulfa Macrolide and quinolone antibiotics NSAIDs Azathioprine Phenobarbitone Carbamazepine Dexamethasone Prednisolone Rifampicin Vitamin K Raloxifene Warfarin Rifampicin Caffeine Methylxanthines Phosphodiesterase inhibitors Statins Calcium channel blockers Warfarin Proton pump inhibitors Clopidogrel NSAIDs Phenytoin Colesevelam Furosemide NSAIDs Probenecid Calcium channel blockers Indomethacin Antacids ACE Inhibitors Amiodarone Calcium channel blockers Diltiazem Phenoxybenzamine Phenobarbital Rifampicin Cimetidine Antacids (liquid) NSAIDs -blockers Amiodarone Verapamil Fibrates Amprenavir Diltiazem Nevirapine Rifampicin Statins There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by- product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 5/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: Enzyme Substrates (e.g.) Inhibitors (e.g.) Inducers (e.g.) Clopidogrel Propranolol Warfarin Moclobemide Chloramphenicol Many anti-convulsants (Valproate) Proton pump inhibitors (Omeprazole) Rifampicin Carbamazepine Prednisone CYP2C19 Donepezil Statins (Atorvastatin) Ca-channel blockers (Nifedipine) Amiodarone Dronedarone Quinidine PDE5 Inhibitors (Sildenafil) Kinins Caffeine Eplerenone Propranolol Salmeterol Warfarin Clopidogrel Protease inhibitors (Ritonavir) Macrolides (Clarithromycin) Chloramphenicol Nefazodone Some Ca-channel blockers (Verapamil) Cimetidine Some azole anti-fungals (Ketaconazole) Grapefruit juice Some anti-convulsants (Carbamazepine) Baribiturates (Phenobarbital) St. John s Wort Some reverse transcriptase inhibitors (Efavirenz) Some Hypoglycaemics (Pioglitazone) Glucocorticoids Modafinil CYP3A4 Fluvastatin Angiotensin receptor II agonists (losartan) Warfarin Torasemide Some azole anti-fungals (Fluconazole) Amiodarone Antihistamines (Cyclizine) Chloramphenicol Fluvastatin Fluvoxamine Probenecid Sertraline Rifampicin Secobarbital CYP2C9 -blockers (Propranolol) Class I anti-arrythmics (Flecainide) Donepezil SSRIs (Fluoxetine) Quinidine Sertraline Terbinafine Amiodarone Cinacalcet Ritonavir Antipsychotics (Haloperidol) Antihistamines (Promethazine) Metoclopramide Ranitidine Mibefradil Rifampicin Dexamethasone Glutethimide CYP2D6 In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: General Use of Medicine (http://w ww.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicin e/GeneralUseofMedicine/UCM229033.pdf) https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 6/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Cardiovascular Drugs Examples (generic name) Typical Dosage Guidelines / Class of Indication Drug Type Indications Side Effects (Prevalence %) :Anti-hypertensives Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus). Furosemide: 20-40mg once daily Oedema Diuretics Furosemide Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC [1] Furosemide: 40-80mg once daily Resistant Hypertension Hypertension: Class IA [2] Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory- tract symptoms (2-10%), gastro- intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity. Hypertension symptomatic class LVD: Class IA [1] in (NYHA II-IV) HF and Captopril: 12.5mg twice daily Hypertension Hypertension in diabetics: Class IA [3] Post STEMI: Class IA [4] Diabetic Class IC [2] patients: ACE Inhibitors Captopril, Monopril Captopril: 12.5mg 3 times daily Heart Failure Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA [1] Captopril: 6.25mg once daily Prophylaxis Following MI Captopril: 75- 100mg once daily Diabetic nephropathy Hypertension: Class IA [2] Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash; Losartan: 50mg once daily in Hypertension diabetics: Class IA [3] Hypertension Angiotensin Receptor Blockers Losartan, Candesartan Losartan: 12.5-150mg daily Left ventricular hypertrophy LVH: Class IB [4] Diabetic nephropathy Losartan: 50mg daily Alpha Blockers Prazosin, Doxazosin Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8- 18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris Prazosin: 1- 10mg 2-3 times daily Hypertension Congestive Heart Failure Prazosin: 4- 20mg daily https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 7/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema. Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes. Raynaud s Syndrome Prazosin: 1- 2mg daily Beta Blockers Atenolol, Propranolol Atenolol: 25- 50mg daily Hypertension ACS: Class IIaB [2] Angina symptomatic class LVD: Class IA [1] in (NYHA II-IV) HF and Atenolol: 100mg once/twice daily Angina Arrhythmias Atenolol: 50- 100mg daily Atrial fibrillation: Class IA; Polymorphic VT: Class IB [4] Symptomatic (NYHA class II-IV) HF, LVD IA; and AF: Class Management of VA in HF: Class IA [1] SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class Sinus IIIC; tachycardia: Class IC; tolerated Poorly AVNRT with haemodynamic Class intolerance: IIaC; Recurrent symptomatic AVNRT: IC; Class Documented PSVT with only dual AV- nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; well Infrequent, AVNRT: tolerated Focal Class IB; tachycardia: junction Class IIaC; Nonparoxysmal junctional tachycardia: IIaC; WPW Class Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; infrequent Since or episode(s): AVRT https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 8/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology IIaB; Acute Class treatment of Focal Tachycardia: Atrial Class IIaC; therapy Prophylactic for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB [5] Atenolol: 50- 200mg daily Migraine Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis; Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA [1] Nifedipine: 20-30mg once daily Hypertension Calcium Channel Blockers Nifedipine, Verapamil, Diltiazem Nifedipine: 5- 20mg 3 times daily Raynaud s Syndrome Nifedipine: 5- 20mg 3 times daily Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA [1] Angina (prophylaxis) Anti-Arrhythmics Class I (sodium channel blockers) Flecainide, Lidocaine, Procainamide Ventricular Arrhythmias Flecainide: 50-100mg twice daily Sustained VT and VF: Class IIbC [4] Oedema, pro-arrhythmic effects (1- 13%); dyspnoea; nervous-system side- effects including dizziness, asthenia, fatigue, fever; visual disturbances (13- 28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating. Pre-excited SVT/AF: Class IB; Wide QRS- complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS- complex tachycardia of unknown origin with LVD: Class IB; Focal tachycardia: junction IIaC; WPW Class IIaC; Syndrome: poorly AVRT, tolerated: IIaC; Single infrequent AVRT or episode(s): Class IIbC; Acute treatment Atrial of Focal Class Tachycardia: https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 9/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology Prophylactic IIaC; therapy for AT: Class (Stable IIaC; AF flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB [5] Class II (Beta blockers) (See above) (See above) (See above) (See above) Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC [4] Management of VA in IA; Class HF: Prevention of VA in HF: Class IIbB [1] SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class QRS- IB; Wide complex tachycardia of unknown origin with LVD: IB; AVNRT Recurrent unresponsive to beta blocker or calcium- channel blocker and patient not desiring RF ablation: Class junction IIbC; Focal Class tachycardia: WPW IIaC; IIaC; Syndrome: AVRT, poorly tolerated: Class IIaC; infrequent Since or episode(s): AVRT Class IIbB; Acute treatment of Focal Tachycardia: Atrial IIaC; Class Prophylactic therapy for AT: Class IIaC; AF tolerated): (Poorly Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT pregnancy: during Class IIIC [5] Gastro-intestinal disturbances (2- 20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9- 59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate- grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10- 30%), respiratory distress syndrome, sweating, and hot flushes Class Class III (Potassium channel blockers) Amiodarone: 200mg 2-3 times daily Amiodarone, Sotalol Ventricular, Arrhythmias Class IV (Calcium (See above) (See above) (See above) (See above) https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 10/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology channel blockers) SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC [5] Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia. Acute: 0.75- 1.5mg over 24 hours; Maintenance: 125-150 g daily Supra-ventricular Arrhythmias Symptomatic (NYHA class II-IV) HF: Class IIbB Digoxin (NYHA Symptomatic class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC [1] 62.5-125 g daily Heart Failure Anti-platelet Drugs Prevention in AF: Class IC; Prevention in diabetic patients: IIaB [2] Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%). Prevention Symptomatic class AF: Class IIA [1] in (NYHA II-IV) HF and Prevention of thrombotic cerebro- or cardio-vascular disease in Prevention hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but renal with reduced function/high risk: Class IIbA [3] 75mg once/day Aspirin Post-MI: Class Ia [3] 300-600mg every 4-6 hours as necessary Pain / pyrexia Clopidogrel Prevention of thrombotic events (esp. when warfarin not tolerated) 75mg once/day Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB [2] Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, Prevention Symptomatic class AF: Class IIA [1] in (NYHA II-IV) HF and of Acute coronary artery syndrome: Class IB; phase https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 11/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus. Non-cardioembolic cerebral events: Class IA [3] ischaemic 300mg daily initially then 75mg once/day Acute myocardial infarction Post STEMI: Class IA [4] 300mg daily initially then 75mg once/day Acute coronary syndrome ACS: Class IIaC [2] Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura. Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA [1] Prevention of thrombotic events. 60mg bolus then 5-10mg once daily Acute coronary syndrome: Class [3] phase of artery IB Prasugrel Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo. Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA [1] Prevention of thrombotic events. 180mg bolus then 90mg twice daily Acute coronary syndrome: Class [3] phase of artery IB Ticragelor Vitamin K Antagonists 5-10mg initially then tailored to individual (usually 3- 9mg once daily at the same time) Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, purple toes , skin necrosis (increased risk in patients with protein C or protein S deficiency) Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) Warfarin Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, purple toes , skin necrosis (increased risk in patients with protein C or protein S deficiency) Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) 4mg initially, followed by 1-8mg daily Acenocoumarol Lipid-Lowering Drugs Statins Simvastatin, Atorvastatin Primary hyper- cholesterolaemia, combined hyperlipidaemia Simvastatin: 10-20mg once daily Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 12/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology IIaB; PAD: Class IA; HIV patients: IIaC [2] eczema (4.5%), urinary tract infection (3.2%) Hypertension diabetics: Class ACS: Class IA [3] in IA; Simvastatin: 40mg once daily Familial hyper- cholesterolaemia HeFH: Class IC [2] Prevention of cardiovascular events 20-40mg once daily Class IA [2] Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC [6] Hyperlipidaemias of types IIa, IIb, III, IV and V Gemfibrozil: 0.9-1.2mg daily Gemfibrozil Fibrates Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis Primary and familial hyper- cholesterolaemia 10mg once daily Transplant patients (with high LDL-C): Class IIbC [6] Ezetimibe References 1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, B hm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, K ber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, R nnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, and ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-847. DOI:10.1093/eurheartj/ehs104 | 2. Ryd n L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, Cosentino F, J nsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba-Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Py r l K, Raz I, Schernthaner G, Volpe M, Wood D, Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC), and European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007 Jan;28(1):88-136. DOI:10.1093/eurheartj/ehl260 | https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 13/14 7/4/23, 12:41 AM Cardiac Pharmacology - Textbook of Cardiology 3. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syv nne M, Scholte op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F, European Association for Cardiovascular Prevention & Rehabilitation (EACPR), and ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012 Jul;33(13):1635-701. DOI:10.1093/eurheartj/ehs092 | 4. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK, Atar D, Badano LP, Bl mstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, and Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619. DOI:10.1093/eurheartj/ehs215 | 5. Blomstr m-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW Jr, Stevenson WG, Tomaselli GF, Antman EM, Smith SC Jr, Alpert JS, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO Jr, Priori SG, Blanc JJ, Budaj A, Burgos EF, Cowie M, Deckers JW, Garcia MA, Klein WW, Lekakis J, Lindahl B, Mazzotta G, Morais JC, Oto A, Smiseth O, Trappe HJ, American College of Cardiology, American Heart Association Task Force on Practice Guidelines, and European Society of Cardiology Committee for Practice Guidelines. Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias). Circulation. 2003 Oct 14;108(15):1871-909. DOI:10.1161/01.CIR.0000091380.04100.84 | 6. European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D, and ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011 Jul;32(14):1769-818. DOI:10.1093/eurheartj/ehr158 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&oldid=2554" This page was last edited on 28 May 2015, at 08:41. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Cardiac_Pharmacology 14/14 |
7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology Chest Pain / Angina Pectoris Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary by are lumen of the atherosclerosis and the coronary arteries progressively narrow, a dysbalance between myocardial oxygen oxygen supply consumption may causing myocardial ischemia. In stable angina this imbalance mainly occurs when oxygen exercise, demand increased heart rate, contractility or wall stress. arteries affected and myocardial occur, An epicardial coronary artery with a atherosclerotic narrowing increases due to A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. [1] In addition, laboratory tests and specific cardiac investigations are often necessary. Contents History Physical Examination Electrocardiogram (ECG) Laboratory Testing Stress Testing in Combination with Imaging Coronoary Angiography Treatment Medical Therapy https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 1/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology PCI CABG References History Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. [2] Some patients only complain about abdominal pain so the presentation can be aspecific. [3], [4] Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. [5] Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. [6] The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. [7] Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back. Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non- cardiac chest pain, see Table 1. Table 1. Clinical classification of chest pain [8] Typical angina (definite) Meets three of the following characteristics: Substernal chest discomfort of characteristic quality and duration Provoked by exertion or emotional stress Relieved by rest and/or nitroglycerine Atypical angina (probable) Meets two of these characteristics Non-cardiac chest pain Meets one or none of the characteristics The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 2/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology Table 2. Clinical pre-test probabilities a in patients with stable chest pain symptoms. [9] Typical angina Atypical angina Non-anginal pain Age Men Women Men Women Men Women 30-39 59 28 29 10 18 5 40-49 69 37 38 14 25 8 50-59 77 47 49 20 34 12 60-69 84 58 59 28 44 17 70-79 89 68 69 37 54 24 >80 93 76 78 47 65 32 ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease. a Probabilities of obstructive coronary disease shown re ect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years. Groups in white boxes have a PTP <15% and hence can be managed without further testing. Groups in blue boxes have a PTP of 15 65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered. Groups in light pink boxes have PTPs between 66 85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD. In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk strati cation only. The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3 Table 3. Classification of angina severity according to the Canadian Cardiovascular Society Class Level of Symptoms Class I 'Ordinary activity does not cause angina' Angina with strenuous or rapid or prolonged exertion only Class II 'Slight limitation of ordinary activity' Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening Class III 'Marked limitation of ordinary physical activity' Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions Class IV 'Inability to carry out physical activity without discomfort' or 'angina at rest' https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 3/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology During angina pectoris vegetative symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. [10] Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter. Physical Examination There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension, valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease. Electrocardiogram (ECG) The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. [11] Exercise ECG testing is performed with gradually increasing intensity on a treadmill or a bicycle ergo- meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. [12] Laboratory Testing Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile. Stress Testing in Combination with Imaging Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 4/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. [9] Diagnosis of CAD Sensitivity (%) Specificity (%) Exercise ECG a, 91, 94, 95 45 50 85 90 Exercise stress echocardiography 96 80 85 80 88 Exercise stress SPECT 96-99 73 92 63 87 Dobutamine stress echocardiography 96 79 83 82 86 Dobutamine stress MRI b,100 79 88 81 91 Vasodilator stress echocardiography 96 72 79 92 95 Vasodilator stress SPECT 96, 99 90 91 75 84 Vasodilator stress MRI b,98, 100-102 67 94 61 85 Coronary CTA c,103-105 95 99 64 83 Vasodilator stress PET 97, 99, 106 81 97 74 91 CAD = coronary artery disease; CTA = computed tomography angiography; ECG = electrocardiogram; MRI = magnetic resonance imaging; PET = positron emission tomography; SPECT = single photon emission computed tomography. a Results without/with minimal referral bias. b Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias. c Results obtained in populations with low-to-medium prevalence of disease. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. 1. Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. [13] An alternative is pharmacological stress testing using dobutamine. 2. Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . [14] 3. Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. [15] https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 5/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology The stress testing can be used to determine the choice therapy between medical only or medical therapy and invasive assessment of the in coronary patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, ischemic likelihood of disease, and risk of the subsequent for patient including complications risk mortality based on For scores. the [16] initial the for algorithm evaluation of patients with clinical symptoms of angina see Figure 1. findings on anatomy Coronoary Angiography angiography Coronary the in (CAG) can assist diagnosis and the selection treatment options of for pectoris. angina stable During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina Treatment Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. [17] Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 6/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. Medical Therapy Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. blockers lower heart rate and blood pressure. [8] Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. [18] Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. [19] Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. PCI The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. CABG With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart ( off-pump surgery) References 1. Sampson JJ and Cheitlin MD. Pathophysiology and differential diagnosis of cardiac pain. Prog Cardiovasc Dis. 1971 May;13(6):507-31. DOI:10.1016/s0033-0620(71)80001-4 | 2. Foreman RD. Mechanisms of cardiac pain. Annu Rev Physiol. 1999;61:143-67. DOI:10.1146/annurev.physiol.61.1.143 | 3. Canto JG, Shlipak MG, Rogers WJ, Malmgren JA, Frederick PD, Lambrew CT, Ornato JP, Barron HV, and Kiefe CI. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA. 2000 Jun 28;283(24):3223-9. DOI:10.1001/jama.283.24.3223 | 4. Pope JH, Ruthazer R, Beshansky JR, Griffith JL, and Selker HP. Clinical Features of Emergency Department Patients Presenting with Symptoms Suggestive of Acute Cardiac Ischemia: A Multicenter Study. J Thromb Thrombolysis. 1998 Jul;6(1):63-74. DOI:10.1023/A:1008876322599 | 5. Constant J. The clinical diagnosis of nonanginal chest pain: the differentiation of angina from nonanginal chest pain by history. Clin Cardiol. 1983 Jan;6(1):11-6. DOI:10.1002/clc.4960060102 | 6. Abrams J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J. 1985 Jul;110(1 Pt 2):216-24. 7. Henrikson CA, Howell EE, Bush DE, Miles JS, Meininger GR, Friedlander T, Bushnell AC, and Chandra-Strobos N. Chest pain relief by nitroglycerin does not predict active coronary artery disease. Ann Intern Med. 2003 Dec 16;139(12):979-86. DOI:10.7326/0003-4819-139-12-200312160- 00007 | https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 7/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology 8. 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Guidelines for cardiac exercise testing. ESC Working Group on Exercise Physiology, Physiopathology and Electrocardiography. Eur Heart J. 1993 Jul;14(7):969-88. 12. Fox K, Garc a MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, de Backer G, Hjemdahl P, L pez-Send n J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, and Grupo de trabajo de la sociedad europea de cardiologia sobre el manejo de la angina estable. [Guidelines on the management of stable angina pectoris. Executive summary]. Rev Esp Cardiol. 2006 Sep;59(9):919- 70. DOI:10.1157/13092800 | 13. Amanullah AM and Lindvall K. Predischarge exercise echocardiography in patients with unstable angina who respond to medical treatment. Clin Cardiol. 1992 Jun;15(6):417-23. DOI:10.1002/clc.4960150605 | 14. Brown KA. Prognostic value of thallium-201 myocardial perfusion imaging in patients with unstable angina who respond to medical treatment. J Am Coll Cardiol. 1991 Apr;17(5):1053-7. DOI:10.1016/0735-1097(91)90829-x | 15. Kwong RY, Schussheim AE, Rekhraj S, Aletras AH, Geller N, Davis J, Christian TF, Balaban RS, and Arai AE. Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging. Circulation. 2003 Feb 4;107(4):531-7. DOI:10.1161/01.cir.0000047527.11221.29 | 16. Fraker TD Jr, Fihn SD, 2002 Chronic Stable Angina Writing Committee, American College of Cardiology, American Heart Association, Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Gardin JM, O'Rourke RA, Williams SV, Smith SC Jr, Jacobs AK, https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 8/9 7/4/23, 12:20 AM Chest Pain / Angina Pectoris - Textbook of Cardiology Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, and Yancy CW. 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 guidelines for the management of patients with chronic stable angina. J Am Coll Cardiol. 2007 Dec 4;50(23):2264-74. DOI:10.1016/j.jacc.2007.08.002 | 17. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Association for Percutaneous Cardiovascular Interventions (EAPCI), Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, and Taggart D. Guidelines on myocardial revascularization. Eur Heart J. 2010 Oct;31(20):2501-55. DOI:10.1093/eurheartj/ehq277 | 18. Abrams J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J. 1985 Jul;110(1 Pt 2):216-24. 19. Hennekens CH, Dyken ML, and Fuster V. Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1997 Oct 21;96(8):2751-3. DOI:10.1161/01.cir.96.8.2751 | 20. Davies SW. Clinical presentation and diagnosis of coronary artery disease: stable angina. Br Med Bull. 2001;59:17-27. DOI:10.1093/bmb/59.1.17 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&oldid=2449" This page was last edited on 16 September 2013, at 12:50. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Chest_Pain_/_Angina_Pectoris 9/9 |
7/4/23, 12:20 AM Chronic Coronary Disease - Textbook of Cardiology Chronic Coronary Disease Even though coronary disease mortality rates have declined since 1970, it is still the leading cause of death in many western countries and in an increasing number of non western countries. [1] The reduction in mortality rates is the result of improved acute care and improved primary and secondary prevention. [2], [3] Contents Cigarette smoking Hypertension Cholesterol Exercise Obesity Healthy food choices Screening References The following risk factors for chronic coronary disease are modifiable and should be dealt with. [4] Cigarette smoking Damages the endothelium of the blood vessels potentially facilitating cholesterol adherence. Smoking is a reversible and therefore a leading preventable cause of coronary disease. All patients who smoke should be counselled to give up smoking. Nicotine replacement therapy and behavioural therapy can assist. [ OR 2.87 for current vs never, PAR 35.7% for current and former vs never.] [4] Hypertension Is defined as a systolic pressure >140 mmHg and/or diastolic pressure >90 mmHg. Patients with hypertension should be first treated with non pharmacologic therapies, including salt restriction, weight reduction in overweight/obese patients, and avoidance of excess alcohol intake. Antihypertensive drugs are indicated in patients with persistent hypertension despite non pharmacologic therapy. Most patients will require multiple antihypertensive drug therapies. [ OR 1.91, PAR 17.9%] [4] Cholesterol Is the felon in the atherosclerosis tale and therefore cholesterol levels in the blood should be optimal, meaning low LDL levels and high HDL levels. Secondary causes of dyslipidemia should be excluded. The target level of LDL is 2,5 mmol/L in stable patients and 1.8 mmol/L in high risk patients, including post https://www.textbookofcardiology.org/wiki/Chronic_Coronary_Disease 1/4 7/4/23, 12:20 AM Chronic Coronary Disease - Textbook of Cardiology ACS patient. This can be achieved by the use of lipid lowering therapy particularly statins. [ OR 3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile] [4] Exercise Lowers morbidity and mortality from coronary disease. [ OR 0.86, PAR 12.2%] [4] Patients should be encouraged to exercise 5 times a week during 30 minutes. Referral to fitness program may be useful. Obesity Is associated with several risk factors for coronary heart disease, including hypertension, high cholesterol and insulin resistance as well as diabetes. Data show a relationship of higher body weight with morbidity and mortality from coronary disease. All patients who are willing to lose weight should receive information about behaviour modification, diet, and increased physical activity. [OR 1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile] [4] Healthy food choices Potentially result in a lower risk of coronary disease. A healthy diet consists of high intake of fruit and vegetables, high fiber intake, a low glycemic index and load, unsaturated fat rather than saturated fat, a limited intake of red or processed meat and intake of omega 3 fatty acids. [OR 0.70, PAR 13.7% for lack of daily consumption of fruits and vegetables] [4] Several studies have shown that people who have a high intake of fruit and vegetables have reduced risk coronary disease. It is possible that this is due to specific compounds in vegetables and fruits, or because people who eat more vegetables and fruits tend to eat less meat and saturated fat. In diabetes mellitus tight glycemic control is important to protect against many vascular complications, including coronary disease. [OR 2.37, PAR 9.9%] [4] https://www.textbookofcardiology.org/wiki/Chronic_Coronary_Disease 2/4 7/4/23, 12:20 AM Chronic Coronary Disease - Textbook of Cardiology A small amount of alcohol results in a lower risk of morbidity and mortality from coronary disease. Max. 3 units/day for men and 2 units/day for women. [OR 0.91, PAR 6.7%] [4] Screening Because extensive coronary disease can exist with minimal or no symptoms, screening for coronary disease has been suggested. Although screening results in indentifying patients at increased risk there is no evidence that screening actually improves outcome. [5] References 1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J, and American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics 2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):948-54. DOI:10.1161/CIRCULATIONAHA.109.192666 | https://www.textbookofcardiology.org/wiki/Chronic_Coronary_Disease 3/4 7/4/23, 12:20 AM Chronic Coronary Disease - Textbook of Cardiology 2. Capewell S, Beaglehole R, Seddon M, and McMurray J. Explanation for the decline in coronary heart disease mortality rates in Auckland, New Zealand, between 1982 and 1993. Circulation. 2000 Sep 26;102(13):1511-6. DOI:10.1161/01.cir.102.13.1511 | 3. Heidenreich PA and McClellan M. Trends in treatment and outcomes for acute myocardial infarction: 1975-1995. Am J Med. 2001 Feb 15;110(3):165-74. DOI:10.1016/s0002-9343(00)00712-9 | 4. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, and INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. DOI:10.1016/S0140-6736(04)17018-9 | 5. Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, and American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee to Update the 1997 Exercise Testing Guidelines. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol. 2002 Oct 16;40(8):1531-40. DOI:10.1016/s0735-1097(02)02164-2 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Chronic_Coronary_Disease&oldid=1596" This page was last edited on 5 December 2012, at 14:35. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Chronic_Coronary_Disease 4/4 |
7/4/23, 12:19 AM CPVT - Textbook of Cardiology CPVT Auteur: Louise R.A. Olde Nordkamp Supervisor: Arthur A.M. Wilde Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) refers to a hereditary disease that is associated with exercise (or adrenergic) induced ventricular arrhythmias and/or cardiac syncope and carries an increased risk of sudden cardiac death. Contents General features Clinical diagnosis Physical examination ECG tests Genetic diagnosis Risk Stratification and Treatment "Lifestyle modification": Medication/Other therapies: References General features The diagnosis is based on adrenergic-induced bidirectional and polymorphic ventricular tachycardia. The resting ECG is normal and the heart is structurally normal. It is an inheritable cardiac arrhythmia syndrome[1] with an autosomal dominant (RyR2)[2] or recessive (CASQ2) inheritance. The arrhythmias typically occur in children[3] and adolescents. The mortality rate is approximately 31% by the age of 30 years, if untreated. The prevalence is estimated to be 1:10.000 in Europe. Clinical diagnosis The clinical diagnosis of CPVT is confirmed in an individual with polymorphic VT reproducibly induced during exercise tests, isoproterenol infusion or emotion and exercise. Patients present themselves most often with syncope or even an out-of-hospital cardiac arrest, usually during the first or second decade of life. The symptoms are always triggered by exercise or emotional stress. A family history of exercise-related syncope, seizure or sudden death is reported in 30% of the patients. https://www.textbookofcardiology.org/wiki/CPVT 1/4 7/4/23, 12:19 AM CPVT - Textbook of Cardiology Family members of patients with CPVT who also carry a mutation in a CPVT-associated gene are often asymptomatic. Physical examination Patients can present with symptoms of arrhythmias during exercise: Out-of-hospital-cardiac-arrest Syncope, pre-syncope (weakness, lightheadedness, dizziness) ECG tests The resting ECG in CPVT is normal. However, there is a progressive ventricular ectopy as heart rate increases during exercise or isoproterenol infusion. Both the frequency and the complexity of the ventricular ectopy increase with the work load. It generally starts with monomorphic premature ventricular complexes (PVCs) and is followed bigemini and subsequently more complex arrhythmias, including doublets triplets, bidirectional ventricular to polymorphic ventricular tachycardia. Most of the times, the arrhythmia is self- limiting. However, in some patients, especially if exercise is continued, repeated polymorphic VTs can deteriorate in ventricular fibrillation and sudden cardiac death. tachycardia Genetic diagnosis CPVT is caused by mutations in genes involved in the calcium homeostasis of cardiac cells. Four disease-causing genes have been identified: the ryanodine[5] receptor 2 gene (RyR2) (60%), the cardiac calsequestrin 2 gene (CASQ2) (1-2%), the calmodulin gene (CALM1) (<1%) and the TRDM gene (<1%). Mutant RyR2 channels have a gain- of-function effect, resulting in excessive calcium release during sympathetic activation. Mutant CASQ2 causes loss of buffering capacity for calcium of the sarcoplasmatic reticulum. The mutations cause Intraluminal calcium as a primary regulator of endoplasmic reticulum function 2005[4] https://www.textbookofcardiology.org/wiki/CPVT 2/4 7/4/23, 12:19 AM CPVT - Textbook of Cardiology excessive calcium in the myocyte cytosol generating depolarizing membrane currents, which in turn lead to delayed afterdepolarizations and cardiac arrhythmias. Risk Stratification and Treatment Risk stratification and treatment is best provided by an expert cardio-genetics cardiologist. "Lifestyle modification": All CPVT patients should avoid competitive and other strenuous exercise Medication/Other therapies: -blockers are first line therapy in CPVT because of their sympatholytical effect. However, -blockers are not fully protective in all CPVT patients. Flecainide[6] can be given to CPVT patients with refractory ventricular ectopy despite -blocker therapy. Flecainide directly blocks RyR2 channels.[7] Left cardiac sympathetic denervation[8] can be done in selected patients and largely prevents norepinephrine release in the heart and may therefore reduce adrenergically mediated arrhythmias. The need for ICD therapy needs careful judgement since ICDs might not offer the ultimate protection in CPVT because of the fact that both appropriate and inappropriate shocks can trigger catecholamine release, resulting in arrhythmic ICD storms and death. References 1. Leenhardt A, Denjoy I, and Guicheney P. Catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2012 Oct;5(5):1044-52. DOI:10.1161/CIRCEP.111.962027 | 2. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, DeSimone L, Coltorti F, Bloise R, Keegan R, Cruz Filho FE, Vignati G, Benatar A, and DeLogu A. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 Jul 2;106(1):69-74. DOI:10.1161/01.cir.0000020013.73106.d8 | 3. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, and Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation. 1995 Mar 1;91(5):1512-9. DOI:10.1161/01.cir.91.5.1512 | 4. From Denis Burdakova, Ole H. Petersenb, Alexei Verkhratskya Intraluminal calcium as a primary regulator of endoplasmic reticulum function 2005 Cell Calcium 5. van der Werf C, Nederend I, Hofman N, van Geloven N, Ebink C, Frohn-Mulder IM, Alings AM, Bosker HA, Bracke FA, van den Heuvel F, Waalewijn RA, Bikker H, van Tintelen JP, Bhuiyan ZA, van den Berg MP, and Wilde AA. Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives. Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):748-56. DOI:10.1161/CIRCEP.112.970517 | 6. van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Ha ssaguerre M, Knollmann BC, and Wilde AA. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011 May 31;57(22):2244-54. DOI:10.1016/j.jacc.2011.01.026 | https://www.textbookofcardiology.org/wiki/CPVT 3/4 7/4/23, 12:19 AM CPVT - Textbook of Cardiology 7. van der Werf C and Wilde AA. Catecholaminergic polymorphic ventricular tachycardia: important messages from case reports. Europace. 2011 Jan;13(1):11-3. DOI:10.1093/europace/euq330 | 8. Wilde AA, Bhuiyan ZA, Crotti L, Facchini M, De Ferrari GM, Paul T, Ferrandi C, Koolbergen DR, Odero A, and Schwartz PJ. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N Engl J Med. 2008 May 8;358(19):2024-9. DOI:10.1056/NEJMoa0708006 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=CPVT&oldid=2522" This page was last edited on 29 December 2013, at 22:13. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/CPVT 4/4 |
7/4/23, 12:18 AM Devices - Textbook of Cardiology Devices Contents Pacemakers Patients Implantation Device measurements Stimulation threshold (in mV@ms): Sensitivity (in mV): Impedance (in ): Battery: Programming Pacemaker codes Explanations of table: III: Triggered: Inhibited: Dual: IV: Rate modulation: Commonly used pacemakers AAI: VVI: VDD: DDD: Uni- and bipolar sensing and stimulation Unipolar: Bipolar: Follow up Complications Undersensing: Oversensing: Non-capture: Changes in impedance: Pacemaker syndrome: Operative failures: Long term complications: Implantable cardioverter defibrillators (ICD) Patients Secondary prevention Primary prevention Implantation Device measurements Heart signal: Sensing and pacing thresholds: Lead impedance: Battery status: https://www.textbookofcardiology.org/wiki/Devices 1/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology Programming Arrhythmia detection zones Numbers of intervals to detect / Time to detect Therapy Follow up Complications and inappropriate shocks Cardiac resynchronisation therapy (CRT) Patients Implantation Programming, follow up and complications References Pacemakers A pacemaker monitors the electrical impulses in the heart. When needed, it sends small electrical impulses to the heart muscle to maintain a normal heart rate. A pacemaker rhythm can easily be recognized on the ECG. It shows pacemaker spikes: vertical signals that represent the electrical activity of the pacemaker. Usually these spikes are more visible in unipolar than in bipolar pacing (see image on the right). Ventricular paced rhythm shows ventricular pacemaker spikes. Patients in patients with a In general, pacemaker documented irreversible bradycardia which causes symptoms. Symptoms associated with bradycardia can be lightheadedness, palpitations, dyspnea, angina and syncope. The causal relation between the abnormal heart rhythm and symptoms is crucial for the decision to implant a pacemaker. implantation is indicated Implantation Schematic display of a pacemaker. Pacemaker implantation is performed under local anaesthesia in a sterile operating room or catheterization laboratory. Implantation starts with inserting the pacemaker lead(s), most often into the left or right cephalic vein. Fluoroscopy is used to ensure the appropriate location in the atrium or ventricle. Leads are often positioned in the auricle of the right atrium and/or the right ventricular apex. Device measurements Ohm s law: U = I x R Determination of stimulation threshold, after the red arrow the stimulus intensify and duration is not sufficient anymore to capture the heart. U = Voltage I = Current R = Impedance Stimulation threshold (in mV@ms): https://www.textbookofcardiology.org/wiki/Devices 2/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology The stimulation threshold is the minimum stimulus intensity (in mV) and duration (in ms) necessary to capture the heart. Sensitivity (in mV): The degree that the pacing system sees or senses signals, controlled by the sensitivity setting which is graduated in mV. Impedance (in ): The total pacing impedance is the sum of all resistance to the flow of the electrical impulses. Battery: Device longevity is estimated based on the remaining battery voltage and battery impedance (and past history of percent pacing in case battery status is checked at follow up visits). If these tests are within limits, the pacemaker leads are properly positioned. Thereafter, the pacemaker pulse generator is implanted subcutaneously or subpectorally under the left or right clavicle. Programming Pacemaker codes Pacemakers can be categorized according to the NASPE coding system that usually consists of 3-5 letters. I II III IV V Chamber(s) paced Chamber(s) sensed Response to sensing Rate modulation Multisite pacing O = none O = none O = none O = none O = none A = atrium A = atrium T = triggered R = rate adaptive A = atrium V = ventricle V = ventricle I = inhibited V = ventricle D = dual (A+V) D = dual (A+V) D = dual (I+T) D = dual (A+V) Explanations of table: III: Triggered: A sensed event triggers a pacemaker output pulse Inhibited: Detection of physiological heart activitity will inhibit an electrical pacemaker impulse Dual: https://www.textbookofcardiology.org/wiki/Devices 3/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology A pacemaker with dual response to sensing will inhibit a pacemaker output pulse if it senses an intrinsic event in that same chamber, but it will trigger a pacemaker output pulse in the ventricle if it senses an intrinsic event in the atrium (after a programmed atrioventricular interval) IV: Rate modulation: In some patients, rate adaptive pacing is programmed on to ensure that when patients exercise increases, the pacemaker ensures that the heart rate increases to provide additional cardiac output. There are many ways to sense physiological exercise, including motion sensors and ventilation sensors. Commonly used pacemakers AAI: The atria are paced, when the intrinsic atrial rhythm falls below the pacemaker's threshold. VVI: The ventricles are paced, when the intrinsic ventricular rhythm falls below the pacemaker's threshold. DDD paced rhythm VDD: The pacemaker senses atrial and ventricular events, but can only pace the ventricle. This type of pacemaker is used in patients with a reliable sinus node, but with an AV-block. DDD: The pacemaker records both atrial and ventricular rates and can pace either chamber when needed. Uni- and bipolar sensing and stimulation Sensing and stimulation of the myocardium demands a closed electrical circuit. A pacemaker can sense and stimulate in a unipolar and bipolar fashion: Unipolar: circuit Pacemaker between 1 electrode at the distal end of lead and the pacemaker pulse generator (large circuit 40-60 cm). Advantage: large pacemaker spikes (easier interpretation pacemaker ECG) Disadvantage: extracardiac stimulation ECG with unipolar stimulation displaying large pacemaker spikes. ECG with bipolar stimulation displaying small pacemaker spikes https://www.textbookofcardiology.org/wiki/Devices 4/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology (pectoral muscle), sensing of extracardiac signals (such as ventricular depolarisations in the atrial sensing channel (far field R waves) or non-physiological noise) Bipolar: Pacemaker circuit between 2 electrodes at the distal end of the lead (small circuit 10-15 mm) Advantage: more reliable sensing Disadvantage: small pacemaker spikes (difficult interpretation pacemaker ECG) Follow up The first 6-8 weeks after implantation, patients are advised not to over-stretch their arm on the same side as the pacemaker (such as golf, swimming etc.) to allow time for the lead to mature. Control visits for pacemakers are usually every 6 months. During this visit several electrical parameters are measured: battery status, stimulation thresholds and impedance. Complications Undersensing: File:Ventricular undersensing.svg An intrinsic depolarization that is present, is not sensed by the pacemaker. This can be due to: Ventricular undersensing. Failure of appropriate ventriculation inhibition Inappropriately programmed sensitivity Lead dislodgement Lead failure, such as lead fracture or insulation failure Lead maturation: the amplitude may abruptly decline during the first week after implantion, but these values return to the implantation values after about 6-8 weeks as the lead matures Oversensing: File:Ventricular oversensing.svg Ventricular oversensing. Failure of appropriate ventricular firing The pacemakers senses signals on the marker channel that do not correspond to the ECG pattern. This can be physiologic (e.g. ventricular pulse or myopotentials) or non-physiologic (e.g. lead fracture or if the lead is loose from the pacemaker pulse generator or outside interference such as TENS therapy or surgical diathermy). Non-capture: The electrical impulse is not followed by the myocardium. This can be due to: Lead dislodgement Cardiac perforation Poor connection between lead and pacemaker Lead maturation: as the lead matures and becomes surrounded by fibrotic tissue, the threshold of stimulation decreases, which may result in non- capture Twiddler s syndrome: a permanent malfunction of a pacemaker due to the patient's manipulation of the pulse generator Electrolyte disturbances: hyperkalemia, acidosis and alkalosis can affect the stimulation threshold Myocardial infarction: if a MI occurs near the tip of the head, an increase in stimulation threshold and/or non-capture can occur Failure of atrial capture in a patient with atrial standstill, no P-waves are seen after the atrial stimuli. https://www.textbookofcardiology.org/wiki/Devices 5/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology Drug therapy: e.g. flecainide can affect the stimulation threshold Battery depletion: if the delivered voltage is significantly reduced, advanced stages of battery depletion may result in non- capture Exit block: occurs when the stimulation threshold exceeds the pacemaker s maximum output Changes in impedance: High lead impedance can be due to an open pacing circuit (e.g. lead is not connected to the pacemaker pulse generator or lead fracture). Low lead impedance can be due to a insulation break, which exposes the wire to body fluids which have a low resistance. Also, fluid/blood in the pacemaker header can decrease the lead impedance. Pacemaker syndrome: Pacemaker syndrome is the presence atrioventricular (AV) dissynchrony occurs after pacemaker implantation, regardless of the pacing mode. It is an iatrogenic disease that causes symptoms of fatigue, lightheadedness and hypotension. Symptoms are caused by the loss of atrial contribution to ventricular filling leading to a combination of backward and forward failure. Also atrial cannon waves can be present. In most cases treatment consists of adding an atrial lead and optimizing AV synchrony. Operative failures: Implantation related complications are: Pneumo/hematothorax (may require drain) Cardiac perforation/tamponade (may require drain) Pericarditis Lead dislodgement Infection: pocket infection or lead- or pacemaker pulse generator infection (may require pacemaker extraction) Bleeding/hematomas (may require drainage) Long term complications: Long term pacemaker related complications are: Erosion of the pulse generator through the skin (requires pacemaker extraction) Venous thrombosis (vena cava superior syndrome, deep vein thrombosis, lung embolism) Implantable cardioverter defibrillators (ICD) An ICD is a device that monitors heart rhythms. If it senses dangerous rhythms, it delivers shocks or anti-tachypacing (ATP) therapy. Many ICDs record the heart's electrical patterns when there is an abnormal heartbeat. Nowadays, transvenous ICDs can also deliver pacing therapy if necessary. If a patient does not have an indication for pace-therapy, the pacemaker in the ICD is programmed at VVI 40 bpm (see above pacemaker programming). Patients Schematic display of an ICD https://www.textbookofcardiology.org/wiki/Devices 6/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology Many ICD trials have been performed to establish the ICD indications, particularly in ischemic and dilated cardiomyopathy. Indications for ICD therapy can be divided into secondary and primary prevention. Basically, the indications are expanding from secondary to primary prevention, depending on the underlying heart disease. Secondary prevention Secondary prevention is therapy for patients who have already suffered a cardiac arrest or syncopal/hypotensive ventricular tachycardia. All patients who are resuscitated from VT/VF or who experienced spontaneous hemodynamic non-tolerated sustained VT in the absence of a reversible cause (e.g. acute myocardial infarction or electrolyte disturbances) have an indication for ICD therapy, regardless of the type of underlying heart disease. A fully subcutaneous ICD (SQICD) has a can and lead that are placed subcutaneous but outside of the thorax. This type of ICD does not have te option to give anti-tachypacing or continuous pacemaker functionality, but can deliver a shock to cardiovert ventricular fibrillation. Primary prevention Primary prevention is therapy that is given in order to prevent sudden death in patients who have not yet suffered a life- threatening sustained ventricular arrhythmia, but who are at high risk of such an arrhythmia. ICD therapy is effective in patients with a low left ventricular ejection fraction (LVEF) =30% more than one month after myocardial infarction that never had shown any ventricular arrhythmia (MADITT II trial). Additionally ICD therapy appeared to be effective in patients with ischemic or dilated cardiomyopathy and a LVEF of =35% and congestive heart failure NYHA class II or III. Patients do not meet the evidence based ICD implantation criteria if they have (1) a myocardial infarction within 40 days before ICD implantation; (2) newly diagnosed heart failure at the time of ICD implantation without prior therapy; (3) NYHA class IV symptoms of congestive heart failure. A seperate chapter deals with a more complete list of ICD indications Implantation ICDs are implanted under local anaesthesia in a sterile operating room or catheterization like pacemaker implantation, with inserting the ICD leads in the left or right cephalic vein. Fluoroscopy is used to ensure the appropriate location in the atrium or ventricle. Leads are often positioned in the auricle of the right atrium and/or the right ventricular apex. laboratory. Transvenous ICD implantation starts, After implantation, defibrillation testing is done by inducing VT/VF to test the ICD system and determine the defibrillation threshold. X-thorax of a patient with an ICD (in posteroanterior and lateral view) Device measurements Also device measurements will be done during and after ICD implantation. These are indicators of device and lead functioning and are comparable to the measurements in pacemaker systems (see above). Heart signal, sensing and pacing thresholds and lead impedance will be measured implantation: Heart signal: Real time intracardial electrocardiograms are measured. During follow up, sudden and significant decrease or disappearance of amplitudes and/or slew rates for P and/or R waves can be a sign of lead- or device problems and are further investigated. Sensing and pacing thresholds: https://www.textbookofcardiology.org/wiki/Devices 7/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology During ICD implantation baseline sensing and pacing thresholds are measured. During follow-up the sensing and pacing thresholds will be compared to the chronic baseline. Significant increases or decreases may be indicative for lead- or device problems and are further investigated. Lead impedance: During ICD implantation baseline lead impedance is measured. During follow-up lead impedance is compared to the chronic baseline. Decreases of pacing impedances may be indicative of insulation failure. Sudden and significant increases in pacing impedance may be indicative of conduction fracture. Battery status: Battery status is determined during implantation and every follow up visit. Programming In order for and ICD to deliver therapy for specific tachyarrhythmias, it needs a reliable method to sort out arrhythmias, group them by categories (e.g. supraventricular tachycardia (SVT) and ventricular tachycardia (VT)) and make a determination as to when therapy delivery is mandated. Different ICD variables can be programmed in different ICDs, depending on the ICD manufacturer. Mainly, these ICD variables can be programmed: Arrhythmia detection zones The ICD diagnoses rhythm disorders by counting intervals on the intracardiac electrogram. This is a rate-based detection scheme that can be adjusted to meet the individual patient s needs by programming. The ICD counts the current interval as one value and then average of the current interval and the preceding intervals. If these intervals fall into the same category, the event is binned in that category. If both events are tachycardia of fibrillation, but not in the same category, the interval is binned in the higher category. SVT discriminators: 1. Waveform morphology (broad vs. small complex or comparison of morphology with template of normal QRS wave) 2. Onset of arrhytmia (sudden vs. slowly) 3. Stability of arrhythmia (regular vs. irregular) 4. Relationship between P- and R-waves (atrial lead required) The arrhythmia detection zone is the category in which a predefined therapy will be given: Monitor zone (e.g. 160-180 bpm): All events in this zone will be recorded in the ICD and can be seen during follow up visits, however no therapy is given. Fast VT zone (e.g. 180-240 bpm): All events in this zone will be recorded in the ICD and can be seen during follow up visits. Therapy is given or not if the arrhythmia satisfies several criteria, which are programmed as well, such as SVT/VT discriminators. VF zone (e.g. >240 bpm): All events in this zone will be recorded in the ICD and can be seen during follow up visits and therapy is given immediately. Numbers of intervals to detect / Time to detect ICD strook met intracardiale electrocardiogram (EGM): VF met shock. De rode pijl geeft het moment van de shock aan. https://www.textbookofcardiology.org/wiki/Devices 8/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology The ICD diagnoses an arrhythmia when a sufficient (and programmable) number of events in an event sequence are binned. This is usually stated in an X out of Y pattern, such as 12 out of 16 intervals. Therapy ATP: ATP refers to the use of pacing stimulation techniques for termination of monomorphic ventricular tachyarrhythmias. Such techniques offer the potential for painless termination of VTs. Shock: High voltage shocks are given to restore VT/VF into sinus rhythm. Different detection schemes and therapies can be programmed for different categories. For example, ATP may be appropriate treatment for slow VTs and shock therapy is an appropriate treatment for VF. After therapy is deliverd, the ICD monitors the next intervals to redetect sinus rate (which means the therapy worked) or redetect the arrhythmia (which results in resumed therapy). Follow up Like pacemaker implantation, the first 6-8 weeks after transvenous ICD implantation, patients are advised not to over-stretch their arm on the same side as the ICD (such as golf, swimming etc.) to allow time for the lead to mature. Control visits for ICD are usually every 6 months. During this visit several electrical parameters are measured: battery status, sensing and pacing thresholds and impedance of all leads (see above). Complications and inappropriate shocks Also in ICDs problems of undersensing, oversensing, non-capture, changes in impedance, operative failures and long-term complications can occur (see above at pacemaker complications). Additionally, a major complication in some patients with ICDs is the occurrence of inappropriate shocks. An inappropriate shock is shock therapy for anything else but ventricular fibrillation or ventricular tachycardia. This can be due to, for example, supraventricular tachycardia with fast ventricle response (including sinus tachycardia and atrial fibrillation), T- wave oversensing, detection of physiological- or other non-cardiac activity and lead- or device failure. Cardiac resynchronisation therapy (CRT) CRT-pacemaker (CRT-P) is a biventricular pacemaker with leads in both ventricles to ensure synchronized contraction. A CRT-defibrillator (CRT-D) is an ICD with biventricular pacing option. It appears that atrio-ventricular and intraventricular conduction delays further aggrevates left ventricular (LV) dysfunction in patients with underlying cardiomyopathies. Notably, left bundle branch block (LBBB) alters the sequence of LV contraction, causing wall segments to contract early or late. Dyssynchrony seems to represent a pathophysiological process function, causing LV that directly depresses ventricular remodelling and congestive heart failure and as a consequence causes a higher risk of morbidity and mortality. Atrio- biventricular pacing (CRT) for patients with symptomatic heart failure and intra- or interventricular conduction disturbances has proved beneficial. Schematic display of an CRT device Patients CRT-P or CRT-D appears to be effective in patients with NYHA function class III/IV for congestive heart failure, LVEF =35%, QRS width = 120 ms (especially LBBB) who are on optimal medical therapy. Patients with NYHA function class IV should be ambulatory (no admissions for heart failure during the last month and a reasonable expectation of survival > 6 months). https://www.textbookofcardiology.org/wiki/Devices 9/10 7/4/23, 12:18 AM Devices - Textbook of Cardiology Also patients with NYHA function class II, LVEF =35%, QRS width = 150 ms (especially LBBB) who are on optimal medical therapy are appropriate patients for CRT-D therapy. Implantation CRT-P or CRT-D implantion requires implantation of three transvenous leads: Chest X-ray of a patient with an CRT device (in posteroanterior and lateral view) The red arrow is the right atrial lead The blue arrow is the right ventricular lead The green arrow is the coronary sinus lead Right atrial lead Right ventricular lead Left ventricular lead. The left ventricular lead is usually positioned in the coronary sinus, alternatively it can be positioned epicardially on the left ventricle (by a surgical procedure) or intracardially in the left ventricle (through a transseptal puncture). Programming, follow up and complications Programming should specifically aim at ensuring atrial-synchronous permanent biventricular pacing, by performing AV- interval optimization (echocardiography guided or using invasive haemodynamic measurments) and performing ventricular- ventricle (VV) interval optimization. Further programming, follow up and complications are similar to pacemakers and ICDs (see above). References 1. Epstein et al. ACC/AHA/HRS Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. Heart Rhythm 2008;5:e1-62 2. Vardas et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: the task force for cardiac pacing and cardiac resynchronization therapy of the European society of cardiology. Developed in collaboration with the European Heart Rhythm Association. Eur Heart J 2007; 28:2256-95 3. ECGpedia (http://en.ecgpedia.org) Retrieved from "http://www.textbookofcardiology.org/index.php?title=Devices&oldid=2367" This page was last edited on 9 May 2013, at 13:04. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Devices 10/10 |
7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Diabetes Jonas de Jong and Alice Li Contents Preamble Case Report Introduction Diabetes and pre-diabetic glucose abnormalities Epidemiology and cardiovascular risk of diabetes Identification of subjects at high risk for CVD Treatments to reduce cardiovascular risk CAD and diabetes Case Report Introduction Evaluation Treatments and outcomes Heart failure and diabetes Case Report Introduction Evaluation Treatments and outcomes Atrial fibrillation and diabetes Introduction Treatments and outcomes Peripheral and cerebrovascular diseases and diabetes Case Report Introduction Evaluation Treatments and outcomes References Preamble Diabetes (diabetes mellitus) is one of the metabolic diseases with higher blood sugar level, either due to the pancreatic beta cells do not produce enough insulin, or the cells do not respond to the insulin that is produced.[1] Its clinical symptoms include three polies: polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). https://www.textbookofcardiology.org/wiki/Diabetes 1/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Diabetes is categorized as three types in the clinic: Type 1 diabetes (T1D, diabetes mellitus 1, DM1) results from pancreatic beta cell destruction and thus fails to produce insulin, and is insulin dependent which relies on insulin injection, it is also named insulin-dependent diabetes mellitus (IDDM). Since T1D happens mostly in juveniles it is also called juvenile-onset diabetes. Type 2 diabetes (T2D, diabetes mellitus 2, DM2) results from the reason that the beta cells do not respond to insulin (insulin resistance), and it may co-exist with the situation of partially or fully insulin-dependent, which is also named non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. In some type 2 diabetes, concomitant insulin therapy may be necessary (IDDM2). The third type is gestational diabetes occurs while pregnancy. Comparison of type 1 and 2 diabetes[2] Feature Type 1 diabetes Type 2 diabetes Onset Sudden Gradual Age at onset Mostly in children Mostly in adults Body habitus Thin or normal[3] Often obese Ketoacidosis Common Rare Autoantibodies Usually present Absent Endogenous insulin Low or absent Normal, decreased or increased Concordance in identical twins 50% 90% Prevalence ~10% ~90% There is no cure for diabetes currently except that most of the gestational diabetes disappears when the pregnancy is ended, but it is treatable. The current therapies are insulin, other non-curing medications, and pancreatic replacement therapies like pancreatic islet transplantations which have been applied to severe T1D cases successfully since 1980s .[4]Since both T1D and T2D are chronic diseases and the progresses of modern medicine, acute complications like hypoglycemia and ketoacidosis are under well controlled, and thus chronic and long-term complications like chronic renal failure, and diabetic retinopathy, especially cardiovascular diseases (CVD), are drawing attentions. https://www.textbookofcardiology.org/wiki/Diabetes 2/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Basic treatment steps of diabetes: Educate the patient Treat concomittant hyperlipidemia) risk factors (e.g. hypertension, obesity, start met metformine (500 mg 1 dd, max. 1000 mg 3 dd) Step 1 start cholesterol lowering drug (e.g. simvastatine 40mg once daily) start ACE inhibitor if no hypertension but with microalbuminuria (e.g. enalapril 10-20mg once daily) BMI <27: add sulfonylureumderivate (eg. tolbutamide 500 mg once daily, max. 1000 mg twice daily) BMI =27: add sulfonylureumderivaat if no CVD or heart failure Step 2 If CVD but no increased risk of heart failure add (pioglitazon 15 mg once daily, max. 45 mg once daily) Step 3 Add long acting insulin to oral treatment (stop pioglitazon if present) Step 4a NPH-insuline or mix-insuline twice daily Step 4b Insulin four times daily Case Report Rick is a 56-year-old plumber of a local firm, and his friends called him stocky since he is 7 8 and 260 lbs. He is married and was diagnosed with type 2 diabetes 14 months ago. He used to smoke 10 cigarettes a day and is currently not smoking, but he continued to eat fatty fast food seven to ten times per week due to his flow of work. He had followed lifestyle advice and lost some weight and was doing more exercises, but had now been diagnosed with hypertension (163/95 mmHg). His physician decided to offer Rick some treatments for his hypertension, and Rick attended for a further check-up 18 months after the diabetic diagnosis. It was found that Rick now has chest pain, and he had to start taking aspirin and a beta blocker. Introduction As per the World Health Organization (WHO), an estimated 347 million people world-wide have diabetes in 2012.[5] The number of deaths attributed to diabetes was previously estimated at just over 800,000. However, it has long been known that the number of deaths related to diabetes is considerably underestimated. With regarding the causes of death of diabetes, one important factor contributing the increased morbidity and mortality in diabetic individuals is the development of cardiovascular disease, one of the chronic complications of diabetes. Several studies have demonstrated that diabetic patients have a risk of death that is two to three times higher than that among people without diabetes.[2] https://www.textbookofcardiology.org/wiki/Diabetes 3/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology The following is a comprehensive list of other causes of diabetes:[6] Genetic defects of -cell function Endocrinopathies Maturity onset diabetes of the young Mitochondrial DNA mutations Growth hormone excess (acromegaly) Cushing syndrome Hyperthyroidism Pheochromocytoma Glucagonoma Genetic defects in insulin processing or insulin action Defects in proinsulin conversion Insulin gene mutations Insulin receptor mutations Infections Cytomegalovirus infection Coxsackie B4 virus Exocrine pancreatic defects Chronic pancreatitis Pancreatectomy Pancreatic neoplasia Cystic fibrosis Hemochromatosis Fibrocalculous pancreatopathy Drugs Glucocorticoids Thyroid hormone -adrenergic agonists Statins[7] Multiple epidemiologic studies have established diabetes as a major risk factor for the development of all manifestations of cardiovascular disease, including myocardial infarction, stroke, peripheral vascular disease, and heart failure,[3][8][9][10] and recent data suggest that the proportion of cardiovascular disease attributable to diabetes is increasing.[8] It is estimated that cardiovascular disease accounts for 65% of all deaths in persons with diabetes.[11] In a recent meta-analysis of nearly 700,000 people from 102 prospective studies, diabetes conferred an approximate two fold risk for coronary heart disease and stroke, independently from other conventional risk factors.[10] Thus, in order to reduce the health burden of diabetes, it is considered necessary to aggressively prevent and treat cardiovascular disease in these patients. Diabetes and pre-diabetic glucose abnormalities Type 1 diabetes is caused by the gradually decreasing of endogenous insulin production by pancreatic beta cells and thus loss of the control of blood glucose, whereas type 2 diabetes is caused by the rising blood glucose resulted from a combination of genetic predisposition, unhealthy diet, physical inactivity, and body weight-gain.[12] The higher than normal blood glucose level in both type 1 and type 2 diabetes results in pathophysiological processes, which are associated with the development of microvascular disease and atherosclerosis. Patients with diabetes are thus at a particularly high risk for cardiovascular, cerebrovascular, and peripheral artery disease. Diabetes is characterized by recurrent or persistent hyperglycemia (high blood glucose), and is diagnosed by demonstrating any one of the following:[13] Fasting blood glucose level = 126 mg/dl (= 7.0 mmol/L) 2 hours glucose tolerance test: Plasma glucose = 200 mg/dL (= 11.1 mmol/L) HbA1C IFCC = 48 mmol/mol (6.5%) https://www.textbookofcardiology.org/wiki/Diabetes 4/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology A positive result should be confirmed by a repeat on a different day. People with fasting glucose levels from 110 to 125 mg/dl (6.1 to 7.0 mmol/L) are considered to have impaired fasting glucose.[14] People with blood glucose at 140 mg/dL ~ 200 mg/dL (7.8 ~ 11.1 mmol/L) as glucose tolerance test result are considered to have impaired glucose tolerance, which in particular is a major risk for progression to diabetes, as well as cardiovascular disease.[15] HbA1C (glycated hemoglobin), which is an indicator of average blood glucose level, is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[16] Measuring HbA1C assesses the effectiveness of therapy by monitoring long-term serum glucose regulation, and patients with diabetes who manage to keep their HbA1C level below 53 mmol/mol (7%) are considered to have good glycemic control. Epidemiology and cardiovascular risk of diabetes The age-specific prevalence of diabetes rises with age up to the seventh to eighth decades in both men and women.[17] The prevalence is less than 10% in subjects below the age of 60, and 10 20% between 60 ~ 69 years; 15 20% in the oldest groups have previously known diabetes; and a similar proportion have screen-detected asymptomatic diabetes. This suggests that the lifetime risk of diabetes in European people is 30 40%. The prevalence of impaired glucose tolerance increases linearly with age, but the prevalence of impaired fasting glycaemia does not. In middle aged people, the prevalence of impaired glucose homeostasis is about 15%, whereas it is 35 40% in the elderly. The prevalence of diabetes and impaired glucose tolerance defined by isolated post-load hyperglycemia is higher in women than in men, but the prevalence of diabetes and impaired fasting glucose diagnosed by isolated fasting hyperglycemia is higher in men than in women. Several prospective studies have unequivocally confirmed that post-load hyperglycemia increases cardiovascular diseases morbidity and mortality, however, it remains to be demonstrated that lowering a high 2-hours post-load blood glucose will reduce the risk. Studies are underway but thus far data are scarce. A secondary endpoint analysis of the STOP-NIDDM (Study to Prevent Non-Insulin-Dependent Diabetes Mellitus) revealed statistically significant reductions in cardiovascular diseases event rates in impaired glucose tolerance subjects receiving acarbose compared with placebo.[6] Since acarbose specifically reduces post-prandial glucose excursions, this is the first demonstration that lowering post- prandial glucose and may lead to a reduction in cardiovascular diseases events, but it should be noted that the power in this analysis is low due to a small number of cases. Identification of subjects at high risk for CVD Predicting risk of cardiovascular disease in diabetics can be done with the risk score of the DECODE study. The Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) group developed a cardiovascular diseases risk score, which is presently the only one of its kind including impaired glucose tolerance or impaired fasting glucose in the risk function determination.[7] The large European DECODE study is a collaborative prospective study of 22 cohorts in Europe with baseline glucose measurements for 29714 subjects aged 30-89 years who were followed-up for 11 years, indicated that either fasting or 2-hours post-load blood glucose is an independent risk factor for all- cause and cardiovascular morbidity and mortality even in people without diagnosed diabetes.[18] Predicting risk to develop diabetes is possible with the Finnish Diabetes Risk Score.[19] The Finnish Diabetes Risk Score predicts the 10 year risk for developing type 2 diabetes with 85% accuracy. It also detects asymptomatic diabetes and abnormal glucose tolerance with high reliability in other populations, which can be used as a self-administered test to screen subjects at high risk for type 2 diabetes, and can also be used in the general population and clinical practice to identify undetected type 2 diabetes, and https://www.textbookofcardiology.org/wiki/Diabetes 5/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology the abnormal glucose tolerance. In addition, Finnish Diabetes Risk Score is a good predictor that can be used to predict coronary artery disease, stroke and total mortality.[20] Such a simple scoring system can be used to identify high-risk individuals. If under proper management, it can be applied to not only diabetes prevention, but also to cardiovascular diseases prevention. Treatments to reduce cardiovascular risk Treatment to reduce cardiovascular risk [21] Lifestyle and comprehensive management Classa Levelb Recommendation Structured patient education improves metabolic and blood pressure control I A Non-pharmacological life style therapy improves metabolic control I A Self-monitoring improves glycaemic control I A Near normoglycaemic control (HbA1c 6.5%c) reduces microvascular complications I A reduces macrovascular complications Intensi ed insulin therapy in type 1 diabetes reduces morbidity and mortality I A Early escalation of therapy towards prede ned treatment targets improves a composite of morbidity and mortality in type 2 diabetes IIa B Early initiation of insulin should be considered in patients with type 2 diabetes failing glucose target IIb C Metformin is recommended as rst line drug in overweight type 2 diabetes IIa B aClass of recommendation. bLevel of evidence. cDiabetes Control and Complication Trial-standardized. To reduce the risk of cardiovascular disease, the followings are needed to be considered: a) the prevention of the progression of diabetes; b) the prevention of cardiovascular disease by physical activity; and c) the treatments to reduce cardiovascular risk. With regarding the first treatment the prevention of the progression of diabetes, clinical studies have demonstrated that effective lifestyle intervention strategies and drug treatments can prevent or at least delay the progression to type 2 diabetes in high-risk individuals. For instance, the Finnish Diabetes Prevention Study found that a 5% reduction in bodyweight, achieved through an intensive diet and exercise program was associated with a 58% reduction in the risk of developing type 2 diabetes in https://www.textbookofcardiology.org/wiki/Diabetes 6/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology overweight subjects with impaired glucose tolerance;[22] and the US Diabetes Prevention Program found that lifestyle modification reduced the incidence of type 2 diabetes by 58% in overweight adults with impaired glucose tolerance.[23] As the second treatment, the prevention of cardiovascular disease by physical activity, The International Diabetes Federation (European Region) have recommended physical activity for the prevention of cardiovascular disease complications among diabetic patients,[24] since studies found that physical activity was associated with reduced risk of cardiovascular disease, cardiovascular death, and total mortality in men with type 2 diabetes. People physically active at their work had a 40% lower cardiovascular mortality compared with people with lower physical activity at work. A high level of leisure-time physical activity like walking and walking pace was associated with a 33% drop in cardiovascular mortality, and moderate physical activity was linked to a 17% drop in cardiovascular mortality compared with the most sedentary group.[25] To reduce cardiovascular risk in both type 1 and type 2 diabetes long-term hyperglycemia should be treated aggressively. These patients often have a combination of the major vascular risk factors known as the metablolic syndrome.[26][27] The additional treatment of metabolic syndrome is strongly based on non-pharmacological therapy including lifestyle changes, self-monitoring, and requires structured patient education including a heavy emphasis on smoking cessation, etc.[28][29][30] Specific recommendations include 30 min of physical activity for at least five times weekly, increase of fiber uptake to 30g daily, restriction of calorie intake to 1500 calorie daily, restriction of fat intake to 30 35% of total daily uptake, avoidance of trans-fats, and avoidance of liquid mono- and disaccharides. And the most importance of them, a tight glycemic control which will be described in the CAD treatment section. CAD and diabetes Case Report Max is a 53 year old male administrator who had had high blood glucose for 12 months, and a random reading exceeds 342 mg/dL (18.9 mmol/L), blood glucose HBA1C 83.6 mmol/L (9.8%), normal blood pressure 136/92 mmHg on an office visit with a body mass index of 29. He started feeling a little tired recently and was getting up at night to urinate two to three times weekly. Max was eating as usual with no diabetes meal plan at this time, and had limited activities and rare exercise monthly. A few months ago, he got a myocardial infarction and was taking some cardiovascular and hypertensive medications. Max was trying to communicate with his physician and to search the internet to find out some effective solutions to reduce his risks of progression of his coronary artery disease and other cardiovascular complications. Introduction The most common cause of death in European diabetic adults is coronary artery disease (CAD). Studies have demonstrated that the risk is two to three times higher than that among people without diabetes. [31] The prevalence of coronary artery disease in patients with type 1 or 2 diabetes are widely different. [32][33] In the EURODIAB IDDM Complication Study which involved 3250 type 1 diabetic patients from 16 countries, the prevalence of cardiovascular disease was 9% in men and 10% in women; and it is increasing with age that it is 6% in the age group of 15 29 years and 25% in the age group of 45 59 years. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more https://www.textbookofcardiology.org/wiki/Diabetes 7/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology common in patients with cardiovascular disease, while in women, a greater body mass index was associated with increased prevalence of cardiovascular disease. The risk of coronary artery disease in type 1 diabetic patients increases dramatically when they have the onset of diabetic nephropathy. Diabetic men and women had comparable mortality rates, whereas coronary mortality among men was significantly higher.[35] Further evidences of the important relations between diabetes and myocardial infarction were obtained from the INTERHEART study in Canada. Diabetes increased the risk of myocardial infarction by more than two times in men and women, and independent of ethnicity. And thus a history of diabetes increased cardiovascular disease and mortality markedly. Diabetes or hyperglycemia itself and its complications are very important for the increased risk for coronary artery disease and related mortality. and myocardial infarction Coronary Artery Diseases[34] Evaluation Diabetes is commonly considered as a coronary artery disease risk equivalent. High-risk factors for coronary artery disease include: [21][36][37] Typical or atypical symptoms 55 years of age or older Peripheral or carotid vascular disease And plus 2 or more of the following factors: hyperlipidemia, hypertension, smoking, family history of premature coronary artery disease, microalbuminuria, and progressive retinopathy. Coronary artery disease is associated with smoking, diabetes, and hypertension. Limitation of blood flow to the heart by the artery may cause angina (chest pain) that occurs regularly with activity, after heavy meals, or at other predictable times due to microvascular dysfunction. Detection of coronary artery disease involves the usual diagnostic methods which include baseline electrocardiography (ECG), https://www.textbookofcardiology.org/wiki/Diabetes 8/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology exercise stress testing ischemic ECG, myocardial perfusion scintigraphy, stress echocardiography, exercise radioisotope test (myocardial scintigraphy), coronary angiography, intravascular ultrasound and magnetic resonance imaging (MRI). Treatments and outcomes Treatment options based on accumulated evidence [21] Revascularization Anti-ischaemic medication Anti-platelet agents Anti-thrombin agents Secondary prevention by means of Lifestyle habits including food and physical activity Smoking cessation Blocking the renin angiotensin system Blood pressure control (target < 140/85 mmHg)[38] Lipid-lowering medication (target LDL < 1.8 mmol/L or < 70 mg/dL)[38] Blood glucose control (target HbA1c < 53 mmol/mol or < 7%) The preventive modalities include doctors counsel exercise, the diabetes with CAD meal plan aiming at long-term weight loss, aspirin in doses of 75 to 81 mg/d,[39] (in patients who do not tolerate or have a contra-indication to aspirin, clopidogrel can be used as an alternative antiplatelet agent [40]), antihypertensive therapy and glycemic control. The optimization of glycemic control is important for prevention and control of any diabetes related cardiovascular diseases.[10] In addition to controlling cardiovascular risk factors, patients with diabetes should aim for good glycemic control (HbA1C < 53 mmol/mol or < 7% for all patients and, for the individual patient, an HbA1C as close as to normal (< 42 mmol/mol or < 6%) as possible) soon after the diagnosis of diabetes to prevent macrovascular as well as microvascular complications. Glycemic targets should be individualized according to the diabetes progression, comorbidities development, and the avoidance of the side effects of therapy (hypoglycemia and weight gain). There is no simple and effective treatment for coronary artery disease currently. Therapeutic options are based on three principles:[41] 1) Medical treatment medications like cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.; 2) Coronary interventions as angioplasty and coronary stent-implantation; 3) Coronary artery bypass grafting (CABG - coronary artery bypass surgery). Recent research progress focuses on new angiogenic treatment modalities (angiogenesis) and various stem cell therapies. Heart failure and diabetes Case Report The 56-year-old plumber Rick was taking medications from his physician to protect his heart and brain, and he felt fluid retention, breathlessness and fatigue most recently. His clinical checkup data were: random blood glucose 388 mg/dL (21.5 mmol/L), fasting glucose 334 mg/dL (18.5 mmol/L), HbA1C 121.8 mmol/L (13.3%, his HbA1C had steadily increased over the past 8 months), total cholesterol 147 https://www.textbookofcardiology.org/wiki/Diabetes 9/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology mg/dL (8.2mmol/L), HDL 78 mg/dL (4.3 mmol/L), LDL 82 mg/dL (4.6 mmol/L), Trigs 75 mg/dL (4.1 mmol/L), blood pressure 168/98. His physician recommended a diet plan but he refused since he had fast food daily due to his job and he loved chocolates. Three months ago while Rick was on anti-hypertension medications, had a fall when he was in hospital for severe flu . Further tests in hospital diagnosed that he had a severely reduced left ventricular ejection fraction and diabetic nephropathy. Introduction Prevalence of diabetes and heart failure are increasing exponentially worldwide [42]. Diabetes is well-known to increase the risk of heart failure independent of other traditional risk factors and ischemia. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.[43] Little the prevalence of the combination of diabetes and heart failure. The most recent and extensive data on the prevalence of diabetes and heart failure are from the Reykjavi k Study, showing that the prevalence of the combination of heart failure and diabetes is 0.5% in men and 0.4% in women, increasing with increasing age. Heart failure was found in 12% of those with diabetes compared with only 3% in individuals without diabetes. [44] Thus, there was a strong association between diabetes and heart failure. In the Framingham study, the incidence of heart failure was double among males and five times higher in females with diabetes during 18 years of follow-up, compared with patients free from diabetes, is known about The major signs and symptoms of heart failure. Several clinical and experimental studies have shown that diabetes mellitus leads to functional, biochemical, and morphological abnormalities of the heart, independent of promoting myocardial ischemia, and some of these changes happen earlier in the natural history of diabetes.[42] Diabetes is an independent risk factor for heart failure, and promotes myocardial remodeling (a precursor of heart failure), and the mechanisms beyond ischemia that lead to the development of heart failure in individuals with varying degrees of impaired glucose homeostasis. The most common abnormality observed in asymptomatic diabetics is left ventricular diastolic dysfunction, likely resulting from greater left ventricular myocardial and vascular stiffness. There is also growing evidence that some, if not all, of these structural and biochemical myocardial abnormalities start at the pre-diabetic stage. Evaluation The diagnosis of heart failure can be difficult, especially in the early stages. Although symptoms bring patients to medical attention, many of the symptoms of heart failure are non-specific and do not, therefore, help discriminate between heart failure and other problems. Symptoms that are more specific (i.e. orthopnea and paroxysmal nocturnal dyspnea) are less common, especially in patients with milder https://www.textbookofcardiology.org/wiki/Diabetes 10/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology symptoms, and are therefore insensitive.[45] The echocardiogram and ECG are the most useful tests in patients with suspected heart failure. The echocardiogram provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, and valve function. The ECG shows the heart rhythm and electrical conduction, i.e. whether there is sinoatrial disease, atrio-ventricular block, or abnormal intra-ventricular conduction. The ECG may also show evidence of left ventricular hypertrophy or Q waves (indicating loss of viable myocardium), giving a possible clue to the etiology of heart failure. Routine biochemical and hematological investigations are also important to determine whether renin angiotensin aldosterone blockade can be initiated safely for renal function and potassium, to exclude anemia which can mimic or aggravate heart failure, and to provide other, useful information. Natriuretic peptide levels and Chest X-ray can be applied as references. Treatments and outcomes Heart failure and diabetes[21] Classa Levelb Recommendation ACE-inhibitors are recommended as rst-line therapy in diabetic patients with reduced left ventricular dysfunction with or without symptoms of heart failure I C Angiotensin-II receptor blockers have similar effects in heart failure as ACE- inhibitors and can be used as an alternative or even as added treatment to ACE-inhibitors I C Beta blockers (metoprolol, bisoprolol, and carvedilol) are recommended as rst-line therapy in diabetic patients with heart failure I C Diuretics, in particular loop diuretics, are important for symptomatic treatment of diabetic patients with uid overload owing to heart failure IIa C Aldosterone antagonists may be added to ACE-inhibitors, BBs, and diuretics in diabetic patients with severe heart failure IIb C aClass of recommendation. bLevel of evidence. According to the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) Guidelines,[32] there are very few clinical trials on heart failure treatment specifically for diabetic patients. Information on treatment efficacy of various drugs is therefore based on diabetic subgroups included in various heart failure trials. A disadvantage of this is that the subgroups are not always well defined as regards the diabetic state and treatment. Most data favor a proportionately similar efficacy in patients with and without diabetes. Traditional treatment of heart failure in diabetic patients is based on diuretics, ACE-inhibitors, and Beta-blockades, as outlined in other guidelines.[46] Moreover, it is assumed that meticulous metabolic control should be beneficial in heart failure patients with diabetes. Diuretics are mandatory for relief of symptoms that are due to fluid overload. These drugs should, however, not be used in excess since they induce neuro-hormonal activation.[46] ACE-inhibitors are beneficial in moderate-to-severe heart failure with and without diabetes, they inhibit angiotensin- converting enzyme, thereby decreasing the tension of blood vessels and blood volume, thus lowering blood pressure. Frequently prescribed ACE inhibitors include perindopril, captopril, enalapril, lisinopril, https://www.textbookofcardiology.org/wiki/Diabetes 11/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology and ramipril. Hypoglycaemia has been reported following the institution of ACE-inhibitors in patients with diabetes on glucose-lowering treatment.[47] It is therefore recommended to monitor blood glucose carefully in the early phase of the institution of an ACE-inhibitor in such patients. Beta-blockade decreases myocardial free fatty acid exposure, thereby changing that metabolic pathway in type 2 diabetes.[48] The addition of eplerenone, a selective aldosterone blocker, to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.[49] Atrial fibrillation and diabetes Introduction Evidences show that, apart from coronary artery disease, diabetic patients are at increased risk of arrhythmias.[50] The underlying risk factors for an arrhythmogenic substrate in patients with diabetes include imbalance in autonomic tone, silent ischemia, slowed conduction, heterogeneities in atrial and ventricular repolarization, and the extent of myocardial damage and scar formation. Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes.[50] This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment. Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors. Atrial fibrillation is commonly observed in diabetic patients with prevalence rates estimated to be at least double than those among people without diabetes, and up to three times higher in patients with coexistent hypertension.[51] Treatments and outcomes Arrhythmias: atrial brillation and sudden cardiac death[21] Classa Levelb Recommendation Aspirin and anticoagulant use as recommended for patients with atrial brillation should be rigorously applied in diabetic patients with atrial brillation to prevent stroke I C Chronic oral anticoagulant therapy in a dose adjusted to achieve a target international normalized ratio (INR) of 2 3 should be considered in all patients with atrial brillation and diabetes, unless contraindicated IIa C Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that predispose to sudden cardiac death I C Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients IIa B aClass of recommendation. bLevel of evidence. https://www.textbookofcardiology.org/wiki/Diabetes 12/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Aspirin and anticoagulant use as recommended for patients with atrial fibrillation should be rigorously applied in diabetic patients with atrial fibrillation to prevent heart stroke. Oral anticoagulation is most beneficial for patients at higher risk for stroke, whereas the risks outweigh the benefit in patients at low risk.[52] Thus, quantifying the risk of stroke is crucial for determining which atrial fibrillation patients would benefit most from anticoagulant therapy. Based on the CHADSVASC risk score, all patient with diabetes and atrial fibrillation have an indication for anti-coagulation.[53] Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. The causes underlying the increased vulnerability of the electrical substrate in these patients are unclear and it is likely to be the consequence of the interplay of several concomitant factors. (i) Atherosclerosis [54] and (ii) microvascular disease [55] are increased in patients with diabetes and they concur to the development of ischemia that pre-disposes to cardiac arrhythmias. (iii) Diabetic autonomic neuropathy [56][57] leads to abnormal reflexes and innervation of the diabetic heart influencing electrical instability. (iv) The electrocardiogram of diabetic patients presents repolarization abnormalities manifesting as prolonged QT interval and altered T waves [57] that may reflect abnormal potassium currents.[58] Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients and should be under well controlled. Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that pre-dispose to sudden cardiac death. Microvascular disease and nephropathy are indications of increased risk of sudden cardiac death in diabetic patients. Peripheral and cerebrovascular diseases and diabetes Case Report Simone is a 72-year old lady. She could not remember when she was diagnosed of type 2 diabetes. In one afternoon, while she was eating her late lunch with her husband, he noticed that she was no longer answering his questions and her lower jaw is slightly misplaced. Her husband tried to put on some cold packs to somehow soften the hardened jaw part but it didn t work. So he drove her to the local hospital for check-up, but her doctor ordered for admission immediately. As the consequence, Simone was diagnosed with an embolic stroke and atrial fibrillation at the time of admission. A few days after admission, Simone was getting worse. She could hardly speak and open her eyes, and was unable to swallow fluids. Her doctor had to order nasogastric tube insertion and oxygen administration. Her vital signs were: body temperature of 37.2 degree Celsius, blood pressure of 142/94 mmHg, pulse rate of 84 beats per minute of irregular rhythm, and respiratory rate of 24 cycles per minute. She looked generally weak and did not respond to questions, and not even to painful stimuli, and she elicited rates and crackling sounds during respiration, and was diagnosed of type 2 diabetes with emblic stroke with hemorrhagic conversion. Introduction https://www.textbookofcardiology.org/wiki/Diabetes 13/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Diabetes and cerebrovascular diseases are peripheral vascular disease and stroke. Peripheral vascular disease (PVD, also known as peripheral artery disease, PAD) is a term used to refer to atherosclerotic blockages found in the lower extremity, and it causes either acute or chronic ischemia (lack of blood supply). It has a two- to four-fold increased in subjects with diabetes, which is present in 15% of diabetic patients. The ankle/brachial index, systolic a peripheral noninvasive measure in vascular disease, epidemiological The symptomatic manifestations of peripheral vascular disease are intermittent claudication and limb ischemia. Impairment of the circulation in the foot owing to diabetic macro- and microvascular diseases is the most common non-traumatic reason for limb amputation. The prevalence of peripheral vascular disease increases with advancing age, duration of diabetes, and peripheral neuropathy. The latter condition may mask the symptoms of limb ischemia and thus disease progression may be advanced before patients and healthcare providers realize that peripheral vascular disease is present. About 20% of patients with mild peripheral vascular disease may be asymptomatic; other symptoms include:[61] related peripheral incidence blood pressure of Defect of the blood-brain barrier after stroke shown in MRI. is widely used studies.[59][60] Claudication like pain, weakness, numbness, or cramping in muscles Sores, wounds, or ulcers that heal slowly or not at all Noticeable change in color or temperature when compared to the other limb, or to both limbs Diminished hair and nail growth on affected limb and digits. Cerebrovascular disease is a group of brain dysfunctions related to problematic blood vessels supplying the brain, and hypertension is the most important cause.[62] The typical cerebrovascular disease in diabetes is brain stroke, which is the second leading cause of death worldwide. A transient ischemic attack (minor stroke) leaves little to no permanent damage in the brain, which symptoms include facial weakness, visual impairment, loss of coordination or balance, sudden headache, and mental confusion with unintelligible speech. And symptoms of a cerebral contralateral (opposite sided) include paralysis of a single body part; paralysis of one side of the body; localized tingling, numbness; hemianopia visual loss; aphasia (loss of speech); even loss of consciousness. Cerebrovascular mortality rates have been shown to be raised in patients with type 2 diabetes and have been reported that it is at least as great a risk factor in type 1 diabetes as in type 2. It is found that cerebrovascular mortality is raised at all ages in these patients.[63] Typical brain strokes can be classified into two categories: ischemic and hemorrhagic strokes.[62] Ischemic strokes are those that are caused by vessel occlusion mostly by embolism, while hemorrhagic strokes (intracerebral hemorrhage) are the ones which result from rupture of a blood vessel due to hypertension. About 80% of strokes are caused by ischemia, and the remainder by hemorrhage. Some hemorrhages develop inside the areas of ischemia, and thus it is unknown how many hemorrhages actually start as ischemic stroke. Evaluation https://www.textbookofcardiology.org/wiki/Diabetes 14/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology |
Treatments and outcomes Arrhythmias: atrial brillation and sudden cardiac death[21] Classa Levelb Recommendation Aspirin and anticoagulant use as recommended for patients with atrial brillation should be rigorously applied in diabetic patients with atrial brillation to prevent stroke I C Chronic oral anticoagulant therapy in a dose adjusted to achieve a target international normalized ratio (INR) of 2 3 should be considered in all patients with atrial brillation and diabetes, unless contraindicated IIa C Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that predispose to sudden cardiac death I C Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients IIa B aClass of recommendation. bLevel of evidence. https://www.textbookofcardiology.org/wiki/Diabetes 12/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Aspirin and anticoagulant use as recommended for patients with atrial fibrillation should be rigorously applied in diabetic patients with atrial fibrillation to prevent heart stroke. Oral anticoagulation is most beneficial for patients at higher risk for stroke, whereas the risks outweigh the benefit in patients at low risk.[52] Thus, quantifying the risk of stroke is crucial for determining which atrial fibrillation patients would benefit most from anticoagulant therapy. Based on the CHADSVASC risk score, all patient with diabetes and atrial fibrillation have an indication for anti-coagulation.[53] Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. The causes underlying the increased vulnerability of the electrical substrate in these patients are unclear and it is likely to be the consequence of the interplay of several concomitant factors. (i) Atherosclerosis [54] and (ii) microvascular disease [55] are increased in patients with diabetes and they concur to the development of ischemia that pre-disposes to cardiac arrhythmias. (iii) Diabetic autonomic neuropathy [56][57] leads to abnormal reflexes and innervation of the diabetic heart influencing electrical instability. (iv) The electrocardiogram of diabetic patients presents repolarization abnormalities manifesting as prolonged QT interval and altered T waves [57] that may reflect abnormal potassium currents.[58] Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients and should be under well controlled. Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that pre-dispose to sudden cardiac death. Microvascular disease and nephropathy are indications of increased risk of sudden cardiac death in diabetic patients. Peripheral and cerebrovascular diseases and diabetes Case Report Simone is a 72-year old lady. She could not remember when she was diagnosed of type 2 diabetes. In one afternoon, while she was eating her late lunch with her husband, he noticed that she was no longer answering his questions and her lower jaw is slightly misplaced. Her husband tried to put on some cold packs to somehow soften the hardened jaw part but it didn t work. So he drove her to the local hospital for check-up, but her doctor ordered for admission immediately. As the consequence, Simone was diagnosed with an embolic stroke and atrial fibrillation at the time of admission. A few days after admission, Simone was getting worse. She could hardly speak and open her eyes, and was unable to swallow fluids. Her doctor had to order nasogastric tube insertion and oxygen administration. Her vital signs were: body temperature of 37.2 degree Celsius, blood pressure of 142/94 mmHg, pulse rate of 84 beats per minute of irregular rhythm, and respiratory rate of 24 cycles per minute. She looked generally weak and did not respond to questions, and not even to painful stimuli, and she elicited rates and crackling sounds during respiration, and was diagnosed of type 2 diabetes with emblic stroke with hemorrhagic conversion. Introduction https://www.textbookofcardiology.org/wiki/Diabetes 13/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Diabetes and cerebrovascular diseases are peripheral vascular disease and stroke. Peripheral vascular disease (PVD, also known as peripheral artery disease, PAD) is a term used to refer to atherosclerotic blockages found in the lower extremity, and it causes either acute or chronic ischemia (lack of blood supply). It has a two- to four-fold increased in subjects with diabetes, which is present in 15% of diabetic patients. The ankle/brachial index, systolic a peripheral noninvasive measure in vascular disease, epidemiological The symptomatic manifestations of peripheral vascular disease are intermittent claudication and limb ischemia. Impairment of the circulation in the foot owing to diabetic macro- and microvascular diseases is the most common non-traumatic reason for limb amputation. The prevalence of peripheral vascular disease increases with advancing age, duration of diabetes, and peripheral neuropathy. The latter condition may mask the symptoms of limb ischemia and thus disease progression may be advanced before patients and healthcare providers realize that peripheral vascular disease is present. About 20% of patients with mild peripheral vascular disease may be asymptomatic; other symptoms include:[61] related peripheral incidence blood pressure of Defect of the blood-brain barrier after stroke shown in MRI. is widely used studies.[59][60] Claudication like pain, weakness, numbness, or cramping in muscles Sores, wounds, or ulcers that heal slowly or not at all Noticeable change in color or temperature when compared to the other limb, or to both limbs Diminished hair and nail growth on affected limb and digits. Cerebrovascular disease is a group of brain dysfunctions related to problematic blood vessels supplying the brain, and hypertension is the most important cause.[62] The typical cerebrovascular disease in diabetes is brain stroke, which is the second leading cause of death worldwide. A transient ischemic attack (minor stroke) leaves little to no permanent damage in the brain, which symptoms include facial weakness, visual impairment, loss of coordination or balance, sudden headache, and mental confusion with unintelligible speech. And symptoms of a cerebral contralateral (opposite sided) include paralysis of a single body part; paralysis of one side of the body; localized tingling, numbness; hemianopia visual loss; aphasia (loss of speech); even loss of consciousness. Cerebrovascular mortality rates have been shown to be raised in patients with type 2 diabetes and have been reported that it is at least as great a risk factor in type 1 diabetes as in type 2. It is found that cerebrovascular mortality is raised at all ages in these patients.[63] Typical brain strokes can be classified into two categories: ischemic and hemorrhagic strokes.[62] Ischemic strokes are those that are caused by vessel occlusion mostly by embolism, while hemorrhagic strokes (intracerebral hemorrhage) are the ones which result from rupture of a blood vessel due to hypertension. About 80% of strokes are caused by ischemia, and the remainder by hemorrhage. Some hemorrhages develop inside the areas of ischemia, and thus it is unknown how many hemorrhages actually start as ischemic stroke. Evaluation https://www.textbookofcardiology.org/wiki/Diabetes 14/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Peripheral vascular diseases: An objective measure of peripheral vascular disease is the ankle brachial blood pressure index, defined as the ratio between the arterial pressure at the ankle level and in the brachial artery with the highest pressure,[59] which means that when the blood pressure reading in the ankles is lower than that in the arms, blockages in the arteries providing blood from the heart to the ankle are suspected. The ankle brachial blood pressure index should normally be 0.9. This measurement is valuable for early detection of peripheral artery disease and also for a better stratification of overall cardiovascular risk. A 0.5 or an ankle pressure as 50 mm Hg indicates severely impaired circulation to the foot, below 0.8 indicates moderate ischemic disease, and below 0.5 implies severe ischemic disease, alternatively a 0.4 is used as a threshold. An index above 1.3 indicates poorly compressible vessels as a result of stiff arterial walls, which in diabetic patients are due to atherosclerosis in the media layer of the arterial wall. Further traditional examinations include a lower limb Doppler ultrasound, an angiography where a catheter is inserted into the common femoral artery and selectively guided to the artery, or an X-ray by injecting a radio dense contrast agent to observe the artery directly. On the other hand, modern and non- invasive technologies like multislice computerized tomography (CT) scanners and magnetic resonance imaging (MRI) provide direct imaging of the aorta and lower limb arteries without the need for an injection of contrast agents and as an alternative to angiography. Cerebrovascular diseases: After transient ischemic attack or minor stroke, the risk of further stroke is substantially higher than previously thought, reaching as high as 30% within the first month in some subgroups.[62] Patients at very high risk (>30%) of recurrence within 7 days can be identified on the basis of their ages, blood sugar levels, blood pressures, and other symptoms. Simple risk scores have been developed on the basis of these factors to predict those patients at greatest risk who might benefit the most from early risk-factor modifications. Both the ischemic and hemorrhagic strokes are diagnosed through the following techniques: a neurological body examination, Doppler ultrasound, arteriography, and CT and MRI scans of the brain. The imaging techniques will assist in determining the subtypes and causes of stroke. And blood tests may be helpful in finding out the causes of stroke. Treatments and outcomes Peripheral vascular disease[21] Classa Levelb Recommendation All patients with type 2 diabetes and CVD are recommended treatment with low-dose aspirin IIa B In diabetic patients with peripheral vascular disease, treatment with clopidogrel or low molecular weight heparin may be considered in certain cases IIa B Patients with critical limb ischaemia should, if possible, undergo revascularization procedures I B An alternative treatment for patients with critical limb ischaemia, not suited for revascularization, is prostacyclin infusion I A aClass of recommendation. bLevel of evidence. https://www.textbookofcardiology.org/wiki/Diabetes 15/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Peripheral vascular diseases: Preventions are most important strategies, such as regular exercises, the optimization of glycemic control, management of hypertension, smoking cessation, antiplatelet and anti- cholesterol medications like aspirin, clopidogrel and statins. For diabetic patients with peripheral vascular disease, general measures to reduce overall cardiovascular risk should be intensive, and treatment of hypertension should be vigorous. But in patients with critical limb ischemia and very low distal perfusion pressures, it may be dangerous to lower blood pressure too much for the foot, and thus blood pressure should be kept at a level permitting adequate arterial inflow to the distal extremity. Platelet inhibition with low-dose aspirin, in the magnitude of 75 250 mg per day, is indicated in all patients with severe peripheral vascular disease; further inhibition of platelet aggregation by clopidogrel or dipyridamole along with anticoagulation with low molecular weight heparin may be the first set of choice.[64][65][66] If anatomically possible, a revascularization procedure should be attempted in all patients with critical limb ischemia,[67] such as an angioplasty or a bypass grafting can be done on solitary lesions in large arteries like the femoral artery, but the revascularization may not have sustained benefits. A synthetic prostacyclin (Ilomedin, Iloprost) is the only pharmacological agent so far convincingly shown to have significant beneficial effects on ulcer healing and pain relief on patients with critical limb ischemia, which is given intravenously daily for a period of 2 4 weeks.[68] Stroke[21] Classa Levelb Recommendation For stroke prevention, blood pressure lowering is more important than the choice of drug. Inhibition of the renin angiotensin aldosterone system may have additional bene ts beyond blood pressure lowering per se IIa B Patients with acute stroke and diabetes should be treated according to the same principles as stroke patients without diabetes IIa C aClass of recommendation. bLevel of evidence. Cerebrovascular diseases: Stroke prevention should be based on a multifactorial strategy aimed at the treatment of hypertension, hyperlipidemia, microalbuminuria, hyperglycemia and the use of antiplatelet medications. Antiplatelet therapy reduces the incidence of stroke in diabetic patients and is indicated for both primary and secondary prevention.[69] Low dose Aspirin (75 250 mg daily) should be the initial choice, but in case of intolerance, clopidogrel 75 mg once daily should be given.[70] In patients with recurrent stroke, a combination of aspirin and dipyridamol should be a better option. After a transient ischemic attack or stroke, since complications are more frequent in diabetic subjects compared with non-diabetic subjects, special attention should be paid to the overall risk for peri- and post-operative morbidity and mortality when making decision on surgical interventions, and a simple risk score that can be used to stratify patients into different risk groups for complications after surgery has been developed.[71] An alternative to endoarterectomy is carotid artery angioplasty and carotid artery stenting, which has been found to be not inferior to endoarterectomy and may prove to be a preferable method in high-risk patients.[72] https://www.textbookofcardiology.org/wiki/Diabetes 16/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology The treatment in the acute phase of stroke in diabetic patients should follow the same principles as in the general population, and patients should be kept in stroke care units as the routine management to close surveillance of vital functions and optimization of circulation and metabolic conditions. [62]Thrombolysis like recombinant tPA is one of the most effective treatments but requires application within 3 4 h of stroke onset, which reduces mortality and disability from stroke, but is associated with a risk of hemorrhage. Because of the substantial effectiveness of tPA, efforts to increase the number of patients who are eligible for thrombolytic therapy, and combination of tPA with modern imaging technologies are underway.[62] Hemispheric decompression in young patients with malignant middle cerebral artery territory infarction and space occupying brain edema is supported by evidence. Mechanical thrombectomy and hemicraniectomy could be other options.[73][74] As reviewed recently, strict blood glucose control with intensive insulin therapy improved mortality and morbidity of adult diabetic stroke patients. Besides saving lives, intensive insulin therapy largely prevented several critical illness-associated complications including critical illness polyneuropathy, blood stream infections, anemia, and acute renal failure.[75] But arguments of the safety of the intensive insulin therapy on diabetic patients are ongoing, and new evidences show that diabetic critical-ill patients react differently to the therapy compared to non-diabetic ones, and a carbohydrate-restrictive strategy could be safer and as efficient as intensive insulin therapy, and thus could be a replacement in the near future.[76][77] References 1. Shoback, edited by David G. Gardner, Dolores (2011). Greenspan's basic & clinical endocrinology (9th ed.). New York: McGraw-Hill Medical. pp. Chapter 17. ISBN 0-07-162243-8 2. Dandona L, Dandona R, Naduvilath TJ, McCarty CA, and Rao GN. Population based assessment of diabetic retinopathy in an urban population in southern India. Br J Ophthalmol. 1999 Aug;83(8):937- 40. DOI:10.1136/bjo.83.8.937 | 3. Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, Fonseca V, Gerstein HC, Grundy S, Nesto RW, Pignone MP, Plutzky J, Porte D, Redberg R, Stitzel KF, Stone NJ, American Heart Association, and American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation. 2007 Jan 2;115(1):114-26. DOI:10.1161/CIRCULATIONAHA.106.179294 | 4. Largiad r F, Kolb E, Binswanger U, and Illig R. [Successful allotransplantation of an island of Langerhans]. Schweiz Med Wochenschr. 1979 Nov 24;109(45):1733-6. 5. World Health Organization (WHO), an estimated 347 million people world-wide have diabetes in 2012 (http://www.who.int/mediacentre/factsheets/fs312/en/index.html) 6. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, and STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003 Jul 23;290(4):486-94. DOI:10.1001/jama.290.4.486 | 7. Balkau B, Hu G, Qiao Q, Tuomilehto J, Borch-Johnsen K, Py r l K, DECODE Study Group, and European Diabetes Epidemiology Group. Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study. Diabetologia. 2004 Dec;47(12):2118-28. DOI:10.1007/s00125-004-1574-5 | 8. Fox CS, Coady S, Sorlie PD, D'Agostino RB Sr, Pencina MJ, Vasan RS, Meigs JB, Levy D, and Savage PJ. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham https://www.textbookofcardiology.org/wiki/Diabetes 17/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Heart Study. Circulation. 2007 Mar 27;115(12):1544-50. DOI:10.1161/CIRCULATIONAHA.106.658948 | 9. Kannel WB and McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8. DOI:10.1001/jama.241.19.2035 | 10. Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, and Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010 Jun 26;375(9733):2215-22. DOI:10.1016/S0140-6736(10)60484-9 | 11. Centers for Disease Control and Prevention: National Diabetes Fact Sheet. 2007. (https://www.cdc.g ov/diabetes/pubs/pdf/ndfs_2007.pdf) 12. DeFronzo RA. International Textbook of Diabetes Mellitus. 3rd ed. Chichester, West Sussex; Hoboken, NJ: John Wiley; 2004. 13. Alberti KG and Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998 Jul;15(7):539-53. DOI:10.1002/(SICI)1096- 9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S | 14. WHO: Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia : report of a WHO/IDF consultation; 2006 (http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf) 15. Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, and Yazdi H. Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. Evid Rep Technol Assess (Summ). 2005 Aug(128):1-11. 16. Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, and Brancati FL. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010 Mar 4;362(9):800-11. DOI:10.1056/NEJMoa0908359 | 17. DECODE Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts. Diabetes Care. 2003 Jan;26(1):61-9. DOI:10.2337/diacare.26.1.61 | 18. DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases?. Diabetes Care. 2003 Mar;26(3):688-96. DOI:10.2337/diacare.26.3.688 | 19. Saaristo T, Peltonen M, Lindstr m J, Saarikoski L, Sundvall J, Eriksson JG, and Tuomilehto J. Cross- sectional evaluation of the Finnish Diabetes Risk Score: a tool to identify undetected type 2 diabetes, abnormal glucose tolerance and metabolic syndrome. Diab Vasc Dis Res. 2005 May;2(2):67-72. DOI:10.3132/dvdr.2005.011 | 20. Silventoinen K, Pankow J, Lindstr m J, Jousilahti P, Hu G, and Tuomilehto J. The validity of the Finnish Diabetes Risk Score for the prediction of the incidence of coronary heart disease and stroke, and total mortality. Eur J Cardiovasc Prev Rehabil. 2005 Oct;12(5):451-8. DOI:10.1097/01.hjr.0000174793.31812.21 | 21. Ryd n L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, Cosentino F, J nsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba- Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Py r l K, Raz I, Schernthaner G, Volpe M, Wood D, Task Force on https://www.textbookofcardiology.org/wiki/Diabetes 18/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC), and European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007 Jan;28(1):88-136. DOI:10.1093/eurheartj/ehl260 | 22. Hu G, Qiao Q, Silventoinen K, Eriksson JG, Jousilahti P, Lindstr m J, Valle TT, Nissinen A, and Tuomilehto J. Occupational, commuting, and leisure-time physical activity in relation to risk for Type 2 diabetes in middle-aged Finnish men and women. Diabetologia. 2003 Mar;46(3):322-9. DOI:10.1007/s00125-003-1031-x | 23. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, and Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. DOI:10.1056/NEJMoa012512 | 24. Working Party of the International Diabetes Federation (European Region). Hypertension in people with Type 2 diabetes: knowledge-based diabetes-specific guidelines. Diabet Med. 2003 Dec;20(12):972-87. DOI:10.1046/j.1464-5491.2003.01021.x | 25. Tanasescu M, Leitzmann MF, Rimm EB, and Hu FB. Physical activity in relation to cardiovascular disease and total mortality among men with type 2 diabetes. Circulation. 2003 May 20;107(19):2435- 9. DOI:10.1161/01.CIR.0000066906.11109.1F | 26. Isomaa B, Almgren P, Tuomi T, Fors n B, Lahti K, Niss n M, Taskinen MR, and Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001 Apr;24(4):683-9. DOI:10.2337/diacare.24.4.683 | 27. Bonora E, Targher G, Formentini G, Calcaterra F, Lombardi S, Marini F, Zenari L, Saggiani F, Poli M, Perbellini S, Raffaelli A, Gemma L, Santi L, Bonadonna RC, and Muggeo M. The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study. Diabet Med. 2004 Jan;21(1):52-8. DOI:10.1046/j.1464-5491.2003.01068.x | 28. Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister LA, Hoogwerf B, Mayer-Davis E, Mooradian AD, Purnell JQ, and Wheeler M. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 2002 Jan;25(1):148-98. DOI:10.2337/diacare.25.1.148 | 29. Pastors JG, Warshaw H, Daly A, Franz M, and Kulkarni K. The evidence for the effectiveness of medical nutrition therapy in diabetes management. Diabetes Care. 2002 Mar;25(3):608-13. DOI:10.2337/diacare.25.3.608 | 30. Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, Temprosa M, and Diabetes Prevention Program Research Group. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005 Apr;28(4):888-94. DOI:10.2337/diacare.28.4.888 | 31. Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes. 1999 May;48(5):937-42. DOI:10.2337/diabetes.48.5.937 | 32. Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, and Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care. 2000 Oct;23(10):1516-26. DOI:10.2337/diacare.23.10.1516 | 33. Koivisto VA, Stevens LK, Mattock M, Ebeling P, Muggeo M, Stephenson J, and Idzior-Walus B. Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group. Diabetes Care. 1996 Jul;19(7):689-97. DOI:10.2337/diacare.19.7.689 | 34. Lanza GA. Cardiac syndrome X: a critical overview and future perspectives. Heart. 2007 Feb;93(2):159-66. DOI:10.1136/hrt.2005.067330 | 35. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, and INTERHEART Study Investigators. Effect of potentially modifiable risk factors https://www.textbookofcardiology.org/wiki/Diabetes 19/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. DOI:10.1016/S0140-6736(04)17018-9 | 36. Haffner SM. Coronary heart disease in patients with diabetes. N Engl J Med. 2000 Apr 6;342(14):1040-2. DOI:10.1056/NEJM200004063421408 | 37. Berry C, Tardif JC, and Bourassa MG. Coronary heart disease in patients with diabetes: part I: recent advances in prevention and noninvasive management. J Am Coll Cardiol. 2007 Feb 13;49(6):631-42. DOI:10.1016/j.jacc.2006.09.046 | 38. Authors/Task Force Members, Ryd n L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL, ESC Committee for Practice Guidelines (CPG), Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Document Reviewers, De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Sch chinger V, Scheen A, Schirmer H, Str mberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, and Xuereb RG. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013 Oct;34(39):3035-87. DOI:10.1093/eurheartj/eht108 | 39. Campbell CL, Smyth S, Montalescot G, and Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007 May 9;297(18):2018-24. DOI:10.1001/jama.297.18.2018 | 40. Cheng JW. Pharmacoeconomic analysis of clopidogrel in secondary prevention of coronary artery disease. J Manag Care Pharm. 2007 May;13(4):326-36. DOI:10.18553/jmcp.2007.13.4.326 | 41. Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. Harrison's Principles of Internal Medicine (16th edition). 2005. New York: McGraw-Hill Medical Publishing. 42. Dhingra R and Vasan RS. Diabetes and the risk of heart failure. Heart Fail Clin. 2012 Jan;8(1):125- 33. DOI:10.1016/j.hfc.2011.08.008 | 43. Avogaro A, Vigili de Kreutzenberg S, Negut C, Tiengo A, and Scognamiglio R. Diabetic cardiomyopathy: a metabolic perspective. Am J Cardiol. 2004 Apr 22;93(8A):13A-16A. DOI:10.1016/j.amjcard.2003.11.003 | 44. Thrainsdottir IS, Aspelund T, Thorgeirsson G, Gudnason V, Hardarson T, Malmberg K, Sigurdsson G, and Ryd n L. The association between glucose abnormalities and heart failure in the population- based Reykjavik study. Diabetes Care. 2005 Mar;28(3):612-6. DOI:10.2337/diacare.28.3.612 | 45. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, B hm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, K ber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, R nnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, and ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure https://www.textbookofcardiology.org/wiki/Diabetes 20/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012 Aug;14(8):803-69. DOI:10.1093/eurjhf/hfs105 | 46. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, L vy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pi rard L, Remme WJ, and Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 2005 Jun;26(11):1115-40. DOI:10.1093/eurheartj/ehi204 | 47. Morris AD, Boyle DI, McMahon AD, Pearce H, Evans JM, Newton RW, Jung RT, and MacDonald TM. ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit. Diabetes Care. 1997 Sep;20(9):1363-7. DOI:10.2337/diacare.20.9.1363 | 48. D vila-Rom n VG, Vedala G, Herrero P, de las Fuentes L, Rogers JG, Kelly DP, and Gropler RJ. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2002 Jul 17;40(2):271-7. DOI:10.1016/s0735-1097(02)01967-8 | 49. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. DOI:10.1056/NEJMoa030207 | 50. Du X, Ninomiya T, de Galan B, Abadir E, Chalmers J, Pillai A, Woodward M, Cooper M, Harrap S, Hamet P, Poulter N, Lip GY, Patel A, and ADVANCE Collaborative Group. Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study. Eur Heart J. 2009 May;30(9):1128-35. DOI:10.1093/eurheartj/ehp055 | 51. Movahed MR, Hashemzadeh M, and Jamal MM. Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol. 2005 Dec 7;105(3):315-8. DOI:10.1016/j.ijcard.2005.02.050 | 52. Hart RG, Benavente O, McBride R, and Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999 Oct 5;131(7):492-501. DOI:10.7326/0003-4819-131-7-199910050-00003 | 53. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P, and ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012 Nov;33(21):2719-47. DOI:10.1093/eurheartj/ehs253 | 54. pmid=A 55. pmid=B 56. pmid=C 57. pmid=D 58. pmid=E https://www.textbookofcardiology.org/wiki/Diabetes 21/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology 59. pmid=F 60. Hiatt WR, Hoag S, and Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation. 1995 Mar 1;91(5):1472-9. DOI:10.1161/01.cir.91.5.1472 | 61. Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, and Grobbee DE. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):185-92. DOI:10.1161/01.atv.18.2.185 | 62. Peripheral Arterial Disease at Merck Manual of Diagnosis and Therapy, retrieved on January 5, 2013. (http://www.merckmanuals.com/professional/cardiovascular_disorders/peripheral_arterial_diso rders/peripheral_arterial_disease.html?qt=&sc=&alt=) 63. Donnan GA, Fisher M, Macleod M, and Davis SM. Stroke. Lancet. 2008 May 10;371(9624):1612-23. DOI:10.1016/S0140-6736(08)60694-7 | 64. Laing SP, Swerdlow AJ, Carpenter LM, Slater SD, Burden AC, Botha JL, Morris AD, Waugh NR, Gatling W, Gale EA, Patterson CC, Qiao Z, and Keen H. Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke. 2003 Feb;34(2):418-21. DOI:10.1161/01.str.0000053843.03997.35 | 65. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. DOI:10.1016/s0140-6736(96)09457-3 | 66. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001 May 24;344(21):1608-21. DOI:10.1056/NEJM200105243442108 | 67. Kalani M, Apelqvist J, Blomb ck M, Brismar K, Eliasson B, Eriksson JW, Fagrell B, Hamsten A, Torffvit O, and J rneskog G. Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo- controlled study. Diabetes Care. 2003 Sep;26(9):2575-80. DOI:10.2337/diacare.26.9.2575 | 68. Dormandy JA and Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296. 69. Loosemore TM, Chalmers TC, and Dormandy JA. A meta-analysis of randomized placebo control trials in Fontaine stages III and IV peripheral occlusive arterial disease. Int Angiol. 1994 Jun;13(2):133-42. 70. Colwell JA. Aspirin therapy in diabetes mellitus. Diabetologia. 1997 Jul;40(7):867. 71. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, and Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13. DOI:10.1016/s0022-510x(96)00308-5 | 72. Tu JV, Wang H, Bowyer B, Green L, Fang J, Kucey D, and Participants in the Ontario Carotid Endarterectomy Registry. Risk factors for death or stroke after carotid endarterectomy: observations from the Ontario Carotid Endarterectomy Registry. Stroke. 2003 Nov;34(11):2568-73. DOI:10.1161/01.STR.0000092491.45227.0F | 73. Goodney PP, Schermerhorn ML, and Powell RJ. Current status of carotid artery stenting. J Vasc Surg. 2006 Feb;43(2):406-11. DOI:10.1016/j.jvs.2005.11.012 | 74. Tenser MS, Amar AP, and Mack WJ. Mechanical thrombectomy for acute ischemic stroke using the MERCI retriever and penumbra aspiration systems. World Neurosurg. 2011 Dec;76(6 Suppl):S16-23. DOI:10.1016/j.wneu.2011.07.003 | 75. Simard JM, Sahuquillo J, Sheth KN, Kahle KT, and Walcott BP. Managing malignant cerebral infarction. Curr Treat Options Neurol. 2011 Apr;13(2):217-29. DOI:10.1007/s11940-010-0110-9 | https://www.textbookofcardiology.org/wiki/Diabetes 22/23 7/4/23, 12:20 AM Diabetes - Textbook of Cardiology 76. Van den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R, and Mesotten D. Clinical review: Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target?. J Clin Endocrinol Metab. 2009 Sep;94(9):3163-70. DOI:10.1210/jc.2009-0663 | 77. Arabi YM, Dehbi M, Rishu AH, Baturcam E, Kahoul SH, Brits RJ, Naidu B, and Bouchama A. sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy. Crit Care. 2011 Aug 26;15(4):R203. DOI:10.1186/cc10420 | 78. WHO Diabetes: the cost of diabetes. (http://www.who.int/mediacentre/factsheets/fs236/en/) 79. de Azevedo JR, de Araujo LO, da Silva WS, and de Azevedo RP. A carbohydrate-restrictive strategy is safer and as efficient as intensive insulin therapy in critically ill patients. J Crit Care. 2010 Mar;25(1):84-9. DOI:10.1016/j.jcrc.2008.10.011 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Diabetes&oldid=2454" This page was last edited on 2 October 2013, at 10:54. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Diabetes 23/23 |
7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology Diagnostic Testing Contents Electrocardiography (ECG) Structured ECG assessment Rhythm Rate Conduction PQ interval QRS duration QR interval Heart axis P wave morphology QRS morphology ST morphology Echocardiography Cardiac stress test Indication Diagnostic value Contraindications Adverse effects Limitations Results Stress echocardiography Nuclear stress test References Electrocardiography (ECG) The electrocardiogram asses the electrical activity of the human heart and translates this into a graphic representation. In Figure 1 the body location for the 10 electrodes of a 12-channel ECG are shown. The exact placement of the electrodes is of utmost in obtaining an interpretable ECG. The ECG is a graphic representation of the difference in voltage between the patches over time. importance Figure 1. A short ECG registration of the normal heart rhythm (sinus rhythm). Source: Ecgpedia.org https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 1/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology An ECG can be used to directly clarify the mechanism of an irregular heart rhythm detected on physical examination or that of an extremely rapid or slow rhythm. In addition the ECG can help in identifying structural heart disease (i.e. cardiac hypertrophy), ischemic heart disease (i.e. myocardial infarction) or other causes of symptoms outside of the heart (i.e. pulmonary embolism). So called Holter monitoring or other continuous-ECG monitoring devices allow assessment of cardiac rate and rhythm on a continuous and ambulatory basis. The most common use of ECG monitoring is the evaluation of symptoms such as syncope, near-syncope, or palpitation for which there is no obvious cause and cardiac rhythm disturbances are suspected. Several examples of the beneficial uses in diagnosis and treatment of cardiac patients are mentioned. However, keep in mind that the current list is only a brief summary and in real life the use of the ECG is broader. First, the ECG is an important tool in diagnosing and managing acute myocardial infarction. In patients with chest pain that is suspect for myocardial ischemia, the characteristic ST-segment changes (elevations or depressions) are one of the important corner stones of diagnosis and subsequent treatment. In addition, rapid resolution of the ECG changes of myocardial infarction after reperfusion therapy has prognostic value and identifies patients with reperfused coronary arteries. In the diagnosis of the cause for severe rhythm disturbances, cardiac shock or after cardiac arrest the ECG is also of great importance for rapidly assessing possible underlying (cardiac) causes. Metabolic disturbances or medication induced arrhythmias can induce characteristic changes of the QT time, QRS and ST morphology. The diagnosis based on the ECG observations can be life-saving in emergency situations with patients in shock or after a cardiac arrest. Another example of the helpful use of the ECG is the characteristic changes on the ECG associated with ventricular or atrial enlargement, which could strengthen the diagnosis of cardiomyopathic or valvular disease based on the physical examination. Lastly, evidence of conduction abnormalities may help explain the mechanism of arrhythmias causing symptoms such as palpitations, syncope or angina Structured ECG assessment In order to be able to completely appreciate the information hidden in the simple graphic representation a structured assessment of the ECG at all time is of utmost importance. The 7+2 steps approach is a very well accepted method to fulfil this requirement: 1. Rhythm 2. Rate 3. Conduction (PQ,QRS,QT) 4. Heart Axis 5. P Wave Morphology 6. QRS Morphology 7. ST Morphology Interpretation: 1. Compare with previous ECG https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 2/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology 2. Conclusion Rhythm The sinus node (SA) is located in the roof of the right atrium. It is the fastest physiological pacemaker. When the sinus node generates an electrical impulse, the surrounding cells of the right atrium depolarize. Then the cells of the left atrium, the AV (atrioventricular)node, follow, and at last the ventricles are stimulated via the His bundle. The presence and assessment of P-wave morphology is necessary to determine the rhythm. Normal sinus node rhythm can be presumed if the following criteria are met: P wave (atrial contraction) precedes every QRS complex; A P wave is followed by a QRS complex; The rhythm is regular, but varies slightly during respirations; The rate ranges between 60 and 100 beats per minute; The P waves maximum height at 2.5 mm in II and/or III; The P wave is positive in I and II, and biphasic in V1. Rate The heart rate represents the number of ventricular beats per minute. In normal conditions the heart rate is between 60 and 100 beats per minute. The heart rate is determined by measuring the time between two QRS complexes. The ECG is normally printed on a paper strip transported through an ECG writer at the speed of 25 mm/second, or digitally represented at a similar taper speed. The ECG has a grid with thick lines 5 mm apart (= 0,20 second) and thin lines 1 mm (0,04 second). The easiest estimation method, easy to use in regular heart beats, to asses the rate is the square counting method . Use the sequence 300-150-100-75-60-50-43-37. Count from the first QRS complex, the first thick line is 300, the next thick line 150 etc. Stop the sequence at the next QRS complex. When the second QRS complex is between two lines, take the mean of the two numbers from the sequence or use the fine- tuning method listed below. Conduction PQ interval The PQ interval starts at the beginning of the atrial contraction and ends at the beginning of the ventricular contraction. The PQ interval (sometimes referred to as the PR interval as a Q wave is not always present) indicates how fast the action potential is transmitted through the AV node (atrioventricular) from the atria to the ventricles. Measurement should start at the beginning of the P wave and end at the beginning of the QRS segment. The normal PQ interval is between 0.12 and 0.20 seconds. https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 3/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology A prolonged PQ interval is a sign of a degradation of the conduction system or increased vagal tone (Bezold- Jarisch reflex), or it can be pharmacologically induced. This is called 1st, 2nd or 3rd degree AV block. A short PQ interval can be seen in the WPW syndrome in which faster-than-normal conduction exists between the atria and the ventricles. QRS duration The QRS duration indicates how fast the ventricles depolarize. The normal QRS is < 0.10 seconds. The ventricles depolarize normally within 0.10 seconds. When this is longer than 110 milliseconds, this is a conduction delay. Possible causes of a QRS duration > 110 milliseconds include: Figure 2. A representation of the several intervals of an ECG. Source: Ecgpedia.org Left bundle branch block; Right bundle branch block; Electrolyte Disorders; Atrioventricular rhythm and paced rhythm. For the diagnosis of LBBB or RBBB QRS duration must be >120 ms. QR interval The normal QTc (corrected) interval The QT interval indicates how fast the ventricles are repolarised, becoming ready for a new cycle. The normal value for QTc is: below 450ms for men and below 460ms for women. If QTc is < 340ms short QT syndrome can be considered. The QT interval comprises the QRS-complex, the ST-segment, and the T-wave. One difficultly of QT interpretation is that the QT interval gets shorter as the heart rate increases. This problem can be solved by correcting the QT time for heart rate using the Bazett formula: Thus at a heart rate of 60 beats per minute, the RR interval is 1 second and the QTc equals QT/1. The QTc calculator can be used to easily calculate QTc from the QT and the heart rate or RR interval. On modern ECG machines, the QTc is given. However, the machines are not always capable of making the correct determination of the end of the T wave. Therefore, it is important to check the QT time manually Conduction (http://en.ecgpedia.org/wiki/Conduction). Most QT experts define the end of the T wave as the intersection of the steepest tangent line from the end of the T-wave with the base line of the ECG. https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 4/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology In a pathological prolonged QT time, it takes longer than the normal amount of time for the myocardial cells to be ready for a new cycle. There is a possibility that some cells are not yet repolarised, but that a new cycle is already initiated. These cells are at risk for uncontrolled depolarization, induction of Torsade de Pointes and subsequent Ventricular Fibrillation. The QT interval is prolonged in congenital long QT syndrome, but QT prolongation can also occur be acquired as results of: Medication (anti-arrhythmics, tricyclic antidepressants, phenothiazedes, for a complete list see Torsades (http://en.ecgpedia.org/wiki/Torsades)); Electrolyte imbalances; Ischemia. Heart axis The electrical heart axis is an average of all depolarisations in the heart. The depolarization wave begins in the right atrium and proceeds to the left and right ventricle. Because the left ventricle wall is thicker than the right wall, the arrow indicating the direction of the depolarization wave is directed to the left. One can easily estimate the heart axis by looking at leads I and AVF: Positive (the average of the QRS surface above the baseline) QRS deflection in lead I: the electrical activity is directed to the left (of the patient); Positive QRS deflection in lead AVF: the electrical activity is directed down. This indicates a normal heart axis. Usually, these two leads are enough to diagnose a normal heart axis! A normal heart axis is between -30 and +90 degrees. Abnormal axis can be: A left heart axis is present when the QRS in lead I is positive and negative in II and AVF. (between -30 and -90 degrees); A right heart axis is present when lead I is negative and AVF positive. (between +90 and -180 degrees); An extreme heart axis is present when both I and AVF are negative. This is a rare finding. (between -90 and -180 degrees). P wave morphology The P-wave morphology can reveal right or left atrial hypertrophy or atrial arrhythmias and is best determined in leads II and V1 during sinus rhythm. Characteristics of a normal P-wave: The maximal height of the P wave is 2.5 mm in leads II and / or III; The p wave is positive in II and AVF, and biphasic in V1; The p wave duration is shorter than 0.12 seconds. Abnormal P-wave morphology could be: https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 5/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology A elevation or depression of the PTa segment (the part between the p wave and the beginning of the QRS complex), resulting from atrial infarction or pericarditis; P-wave enlargement due to atrial enlargement; If the P-wave inversion most likely caused by an ectopic atrial rhythm not originating from the sinus node. QRS morphology The basic questions in judging QRS morphology are: Are there any pathological Q waves as a sign of previous myocardial infarction? Are there signs of left or right ventricular hypertrophy? Does the QRS complex show microvoltage (roughly QRS < 5mm)? Is the conduction normal or prolonged (QRS-interval > 0,12s)? Is the R wave propagation normal? Normally R waves become larger from V1-V5. At V5 it should be maximal. If the R wave in V2 is larger than in V3, this could be a sign of a (previous) posterior myocardial infarction. If all these items are normal you can go on to the next step: ST morphology. ST morphology The ST segment represents ventricular repolarisation. Repolarisation follows upon contraction and depolarization. During repolarisation the cardiomyocytes elongate and prepare for the next heartbeat. This process takes much more time than the depolarization. The elongation that takes place during repolarisation is not passive; it is an active process during which energy is consumed. On the ECG, the repolarisation phase starts at the junction, or j point, and continues until the T wave. The ST segment is normally at or near the baseline. Minor STT changes are not necessarily associated with cardiac ischemia. The T wave is usually concordant with the QRS complex. Thus if the QRS complex is positive in a certain lead (the area under the curve above the baseline is greater than the area under the curve below the baseline) than the T wave usually is positive too in that lead. Accordingly the T wave is normally upright or positive in leads I, II, AVL, AVF and V3-V6. The T wave is negative in V1 and AVR. The T wave flips around V2, but there is likely some genetic influence in this as in Blacks the T wave usually flips around V3. The T wave angle is the result of small differences in the duration of the repolarisation between the endocardial and epicardial layers of the left ventricle. The endocardial myocytes need a little more time to repolarise (about 22 msec). This difference causes an electrical current from the endocardium to the epicardium, which reads as a positive signal on the ECG. ST segment abnormalities include the following: ST segment elevation ST segment depression Flat T wave Negative (or inverted) T wave https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 6/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology A broad spectrum of disease could cause ST segment abnormalities such as (acute) ischemia (ST segment elevation and/or depression and T wave inversion), pulmonary embolism (ST segment elevation), acute neurologic events (ST segment elevation), and pericarditis (ST segment elevation). For a complete list see ST Morphology (http://en.ecgpedia.org/wiki/ST_Morphology) Compare the old and the new ECG An abnormal ECG does not directly and solely prove acute cardiac disease. And a normal ECG does not exclude cardiac disease. It is necessary therefore to compare new ECG with ECGs made in the past on all 7 aspects mentioned above. Interpretation of the ECG Final conclusions should consist of one sentence, which sums up all important aspects of the ECG. It is not necessary to mention all 7 aspects, although one has to look at all of them to find the right conclusion! The normal characteristics of an ECG are shown below (Table 1 and Figure 1). For more elaborate information on the ECG, please visit Echopedia.org (http://en.ecgpedia.org). Characteristics of a normal ECG Rhythm: sinus Rate: 60-100 bpm Conduction: PQ interval 120-200ms QRS width 60-100ms QTc interval 390-450ms (use the QTc calculator for this) Heart axis: between -30 and +90 degrees P wave morphology: The maximal height of the P wave is 2.5 mm in leads II and / or III The p wave is positive in II and AVF, and biphasic in V1 The p wave duration is usually shorter than 0.12 seconds QRS morphology: No pathological Q waves No left or right ventricular hypertrophy No microvoltage Normal R wave propagation. (R waves increase in amplitude from V1-V5) ST morphology: No ST elevation or depression T waves should be concordant with the QRS complex The ECG should not have changed from the previous ECG Echocardiography Echocardiography is based on the use of ultrasound directed at the heart to create images of cardiac anatomy and display them in real time on a digital screen. The transthoracic echocardiography is obtained by placing a transducer in various positions on the anterior chest The processing of the https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 7/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology ultrasound waves creates cross-sectional images of the heart and great vessels in a variety of standard planes. In general, echocardiography is a sensitive and non-invasive tool for detecting anatomic abnormalities of the heart and great vessels. The imaging technique is used to investigate the heart in multiple planes in order to asses the existence of (dys)function and structural abnormalities of cardiac chambers and valves throughout the cardiac cycle. Both the cross sectional and longitudinal views are used to look for the presence of any anatomical or functional abnormalities with most of the structures of the heart. [Figure 4 & 5] two-dimensional echocardiographic Figure 3. Transthoracic echocardiography. Heart normal LPLA left parasternal long axis echocardiography view. Figure 4. Apical four chamber view by two dimensional echocardiography. In addition, in the cross sectional planes ventricular wall motion and left ventricular wall thickening during systole (an important measure of myocardial viability) can be investigated. The systematically assessment of cross sectional segment can also be used to estimate left ventricular volumes and ejection fraction. [Figure 6] Figure 5. Short axis view of left ventricle by two dimensional echocardiography. Although the two-dimensional imaging technique gives superior view of the important structures of the heart, the analog echocardiographic display referred to as M-mode, motion-mode, or time-motion mode, is still in use for the high resolution axial and temporal imaging. The analog technique is preferred to measure the size of structures in its axial direction, and its high sampling rate allows for the resolution of complex cardiac motion patterns. [Figure 7] Doppler ultrasound is a technique of combined with the traditional ultrasound technique. The Doppler technique assesses changes in frequency of the reflected ultrasound compared with the transmitted ultrasound. The difference is used to be translated in a picture of the flow velocity. The continuous-wave Doppler mode is used to quantitate the exact velocity of the flow and estimate the pressure gradient when high velocities are suspected. The technique creates a graphic representation of the flow velocity in https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 8/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology echotransducers beam in a time continuous wave. The technique is hampered by the fact that anatomical structures can make disturb the beam and subsequently the flow velocity measurement. When there is ambiguity about the source of the high velocity, pulsed-wave Doppler could be a more useful tool. This technique is range-gated in order to make it possible to investigate specific areas along the beam (sample volumes). Another technique widely integrated in echocardiography is the colour Doppler. The colour Doppler technique projects in coloured images informative for the direction of flow, the velocity, and the presence or absence of turbulent flow. The flow velocity colour in real-time combined with the two-dimensional structural imaging to investigate blood flow in the heart and great vessels. The colour Doppler image technique is in particular of use in detecting regurgitant blood flows across cardiac valves or to visualise any abnormal communications in the heart. [Figure 8] images are Figure 6. Heart short axis with myocardial segments. The non-invasive echocardiography has now largely replaced cardiac catheterization for calculation of the hemodynamics changes caused by valvular disease. Several examples of methods to examine hemodynamics of the heart and valves by echocardiopgraphy are: Velocities across a valve can be converted to pressure gradients; Velocities at cardiac anatomic sites of known size on the two-dimensional echocardiographic can be converted to cardiac output; Cardiac output and pressure gradients can be used to calculate the stenotic valve area. Figure 7. Echocardiogram in the parasternal long-axis view, showing a measurement of the heart's left ventricle in M-mode. Unfortunately, it is impossible to obtain high-quality images or Doppler signals in as many a small percent of patients. Underlying conditions such as obesity, emphysema or chest wall deformities can limit the use of transthoracic echocardiography. A technique to partly cope with transoesophageal limitations these echocardiography (TEE) [Figure 9]. is With TEE a smaller ultrasound probe is placed on a gastroscopic device for introduction in the oesophagus the heart. Besides overcoming structural behind in general TEE produces much higher problems, resolution images of posterior cardiac structures. With TEE left atrial thrombi, small mitral valve vegetations, and thoracic aortic dissection can be diagnosed a high degree of accuracy. The downside of the techniques is the invasiveness of the procedure; the introduction of a probe into the oesophagus is very often experienced as rather uncomfortable by patients. Figure 8. Apical view with colour Doppler projection showing a ventricular septal defect. https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 9/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology For more information on echocardiography, please visit Echopedia.org (http://en.ecgpedia.org). Cardiac stress test Cardiac stress tests compare the coronary circulation while the patient is at rest with the same patient's circulation observed during maximum physical exertion, showing any abnormal blood flow to the heart's muscle tissue (the myocardium). This test can be used to diagnose for patient ischemic heart disease, and prognosis after a heart attack (myocardial infarction). The level of mechanical stress is progressively increased by adjusting the difficulty (steepness of the slope) and speed. The test administrator or attending physician examines the symptoms and blood pressure response. With use of ECG, the test is most commonly called a cardiac stress test, but is known by other names, such as exercise treadmills, exercise tolerance test, stress test or stress test ECG. Figure 9. Transoesophageal echocardiography ultrasound diagram. testing, stress testing Indication The American Heart Association recommends ECG treadmill testing as the first choice for patients with medium risk of coronary heart disease according to risk factors of smoking, family history of coronary artery stenosis, hypertension, diabetes and high cholesterol. Diagnostic value Figure 10. Cardiac stress test making use of a walking treadmill. Source: Wikimedia public domain. The common approach for stress testing by American College of Cardiology and American Heart Association indicates the following:[1] Treadmill test: sensitivity 73-90%, specificity 50-74% (Modified Bruce Protocol) Nuclear test: sensitivity 81%, specificity 85-95% Stress-ECG of a patient with coronary heart disease: ST-segment depression (arrow) at 100 watts of exercise. A: at rest, B: at 75 watts, C: at 100 watts, D: at 125 watts. (Sensitivity is the percentage of sick people who are correctly identified as having the condition. Specificity indicates the percentage of healthy people who are correctly identified as not having the condition.) The value of stress tests has always been recognized as limited in assessing coronary atherosclerosis. This is because the stress test has a relatively high false- negative and false-positive rate. Other detection methods have higher sensitivity and specificity but this https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 10/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology improved test characteristics often comes at a price, either in the form of radiation (CT), risk of complications in an invasive procedure (coronary angiography), or costs and limited availability (MRI). Contraindications Stress cardiac imaging is not recommended for asymptomatic, low-risk patients as part of their routine care.[2] Some estimates show that such screening accounts for 45% of cardiac stress imaging, and evidence does not show that this results in better outcomes for patients.[2] Unless high-risk markers are present, such as diabetes in patients aged over 40, peripheral arterial disease; or a risk of coronary heart disease greater than 2 percent yearly, most health societies do not recommend the test as a routine procedure.[2][3][4][5] Absolute contraindications to cardiac stress test include: Acute myocardial infarction within 48 hours Unstable angina not yet stabilized with medical therapy Uncontrolled cardiac arrhythmia, which may have significant hemodynamic responses (e.g. ventricular tachycardia) Severe symptomatic aortic stenosis, aortic dissection, pulmonary embolism, and pericarditis Multivessel coronary artery diseases that have a high risk of producing an acute myocardial infarction Decompensated or inadequately controlled congestive heart failure[6] Uncontrolled hypertension (blood pressure>200/110mm Hg)[6] Severe pulmonary hypertension[6] Acute aortic dissection[6] Acutely ill for any reason[6] Adverse effects Side effects from cardiac stress testing may include Palpitations, chest pain, myocardial infarction, shortness of breath, headache, nausea or fatigue. Adenosine and dipyridamole can cause mild hypotension. As the tracers used for this test are carcinogenic, frequent use of these tests carries a small risk of cancer. Limitations The stress test does not detect: Atheroma Vulnerable plaques https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 11/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology The test has relatively high rates of false positives and false negatives compared with other clinical tests. Results Once the stress test is completed, the patient generally is advised to not suddenly stop activity, but to slowly decrease the intensity of the exercise over the course of several minutes. Increased spatial resolution allows a more sensitive detection of ischemia. Stress testing, even if made in time, is not able to guarantee the prevention of symptoms, fainting, or death. Stress testing, although more effective than a resting ECG at detecting heart function, is only able to detect certain cardiac properties. The detection of high-grade coronary artery stenosis by a cardiac stress test was the key to recognizing people who have heart attacks since 1980. From 1960 to 1990, despite the success of stress testing to identify many who were at high risk of heart attack, the inability of this test to correctly identify many others is discussed in medical circles but unexplained. High degrees of coronary artery stenosis, which are detected by stress testing methods are often, though not always, responsible for recurrent symptoms of angina. Unstable atheroma produces vulnerable plaques hidden within the walls of coronary arteries which go undetected by this test. Limitation in blood flow to the left ventricle can lead to recurrent angina pectoris. Stress echocardiography A stress test may be accompanied by echocardiography.[7] The echocardiography is performed both before and after the exercise so that structural differences can be compared. Nuclear stress test The best known example is myocardial perfusion imaging. Typically, a radiotracer (Tc-99 sestamibi, Myoview or Thallous Chloride 201) may be injected during the test. After a suitable waiting period to ensure proper distribution of the radiotracer, photos are taken with a gamma camera to capture images of the blood flow. Photos taken before and after exercise are examined to assess the state of the coronary arteries of the patient. Showing the relative amounts of radioisotope within the heart muscle, the nuclear stress tests more accurately identify regional areas of reduced blood flow. Stress and potential cardiac damage from exercise during the test is a problem in patients with ECG abnormalities at rest or in patients with severe motor disability. Pharmacological stimulation from vasodilators such as dipyridamole or adenosine, or positive chronotropic agents such as dobutamine can be used. Testing personnel can include a cardiac radiologist, a nuclear medicine physician,a nuclear medicine technologist, a cardiology technologist, a cardiologist, and/or a nurse. References https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 12/13 7/3/23, 11:57 PM Diagnostic Testing - Textbook of Cardiology 1. Gibbons, R., Balady, G.; Timothybricker, J., Chaitman, B., Fletcher, G., Froelicher, V., Mark, D., McCallister, B. et al. (2002). ACC / AHA 2002 guideline update for exercise testing: summary article A report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines, Journal of the American College of Cardiology 2. American College of Cardiology, Five Things Physicians and Patients Should Question, Choosing Wisely: an initiative of the ABIM Foundation (American College of Cardiology), retrieved August 17 2012 3. Taylor, A. J.; Cerqueira, M.; Hodgson, J. M ; Mark, D.; Min, J.; O'Gara, P.; Rubin, G. D.; American College of Cardiology Foundation Appropriate Use Criteria Task Force et al. (2010). ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. Journal of the American College of Cardiology 56 (22): 1864 1894. doi:10.1016/j.jacc.2010.07.005. PMID 21087721. edit 4. Douglas, P. S.; Garcia, M. J.; Haines, D. E.; Lai, W. W.; Manning, W. J.; Patel, A. R.; Picard, M. H.; Polk, D. M. et al. (2011). ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography. Journal of the American College of Cardiology 57 (9): 1126 1166. doi:10.1016/j.jacc.2010.11.002. PMID 21349406. edit 5. Hendel, R. C.; Abbott, B. G.; Bateman, T. M.; Blankstein, R.; Calnon, D. A.; Leppo, J. A.; Maddahi, J.; Schumaecker, M. M. et al. (2010). The role of radionuclide myocardial perfusion imaging for asymptomatic individuals. Journal of Nuclear Cardiology 18 (1): 3 15. doi:10.1007/s12350-010- 9320-5. PMID 21181519. edit 6. Henzlova, Milena; Cerqueira, Hansen, Taillefer, Yao (2009). Stress Protocols and Tracers. Journal of Nuclear Cardiology. doi:10.1007/s12350-009-9062-4. 7. Rimmerman, Curtis (2009-05-05). The Cleveland Clinic Guide to Heart Attacks. Kaplan Publishing. pp. 113 . ISBN 978-1-4277-9968-5. Retrieved 25 September 2011. 8. Weissman, Neil J.; Adelmann, Gabriel A. (2004). Cardiac imaging secrets. Elsevier Health Sciences. pp. 126 . ISBN 978-1-56053-515-7. Retrieved 25 September 2011. 9. Nicholls, Stephen J.; Worthley, Stephen (2011-01). Cardiovascular Imaging for Clinical Practice. Jones & Bartlett Learning. pp. 198 . ISBN 978-0-7637-5622-2. Retrieved 25 September 2011. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Diagnostic_Testing&oldid=2542" This page was last edited on 26 May 2015, at 20:24. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Diagnostic_Testing 13/13 |
7/4/23, 12:19 AM DPP6 - Textbook of Cardiology DPP6 Contents DPP6 haplotype causing idiopathic VF General features Clinical diagnosis Physical examination ECG tests Genetic diagnosis Risk Stratification Treatment References DPP6 haplotype causing idiopathic VF Auteur: Louise R.A. Olde Nordkamp Supervisor: Arthur A.M. Wilde The DPP6 haplotype was recently associated with idiopathic ventricular fibrillation in several families in the Netherlands.[1] The DPP6 haplotype is a founder haplotype from the Netherlands, which indicates that the families with the DPP6 haplotype are descendants from the same ancestors. General features The diagnosis is based on the presence of the DPP6 haplotype during genetic screening in familial idiopathic VF. The resting ECG is normal and the heart is structurally normal. It is an inheritable cardiac arrhythmia syndrome with an autosomal dominant inheritance. The arrhythmias typically occur between the age of 20-60 years. The penetrance of idiopathic VF is high: 50% of the male DPP6 haplotype carriers experienced (aborted) sudden cardiac death before the age of 58 years.[2] Clinical diagnosis The diagnosis is based solely on the presence of the DPP6 haplotype. Physical examination Patients can present with symptoms of arrhythmias: https://www.textbookofcardiology.org/wiki/DPP6 1/3 7/4/23, 12:19 AM DPP6 - Textbook of Cardiology Out-of-hospital-cardiac-arrest Syncope, pre-syncope (weakness, lightheadedness, dizziness) ECG tests The resting ECG in patients with the DPP6 haplotype is normal. Also during Holter recordings and exercise tests, no abnormalities are found. However, ICD read-outs of DPP6 patients revealed that VF in these patients is elicited by very short-coupled ventricular extrasystoles from the right ventricular apex. Genetic diagnosis Haplotype-sharing analysis implicated that chromosome 7q36 harboring DPP6 was involved in familial idiopathic VF in several families in the Netherlands. DPP6 is a modifier of the cardiac transient outward current (Ito). It is believed that an increased expression of DPP6 is causal to the proarrhythmic substrate. ECG recording of idiopathic ventricular fibrillation (IVF) in a risk haplotype carrier. The short coupled ventricular extrasystoles from the right ventricular apex/lower free wall (indicated by asterisks) first result in compensatory pauses and then in IVF requiring external defibrillation[3] Risk Stratification At this moment, it is only possible to determine the risk of idiopathic VF in asymptomatic family members by DPP6 carrier status. So far, no clinical characteristics on ECG, Holter monitoring, exercise test or on echocardiography or cardiac MRI are associated with arrhythmic events in patients who already have proven DPP6 carrier status. Future studies have to provide a more advanced risk stratification. Treatment Currently ICD therapy is advised for both secondary nd primary prevention of sudden cardiac death. In DPP6 patients with recurrent VF events or ICD shocks, isoproterenol or quinidine are known to be effective for VF suppression. Also ablation of the triggering ventricular extrasystoles from the right ventricular apex can be effective in these patients. References 1. Postema PG, Christiaans I, Hofman N, Alders M, Koopmann TT, Bezzina CR, Loh P, Zeppenfeld K, Volders PG, and Wilde AA. Founder mutations in the Netherlands: familial idiopathic ventricular fibrillation and DPP6. Neth Heart J. 2011 Jun;19(6):290-6. DOI:10.1007/s12471-011-0102-8 | 2. Alders M, Koopmann TT, Christiaans I, Postema PG, Beekman L, Tanck MW, Zeppenfeld K, Loh P, Koch KT, Demolombe S, Mannens MM, Bezzina CR, and Wilde AA. Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation. Am J Hum Genet. 2009 Apr;84(4):468-76. DOI:10.1016/j.ajhg.2009.02.009 | https://www.textbookofcardiology.org/wiki/DPP6 2/3 7/4/23, 12:19 AM DPP6 - Textbook of Cardiology Retrieved from "http://www.textbookofcardiology.org/index.php?title=DPP6&oldid=2262" This page was last edited on 25 March 2013, at 02:01. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/DPP6 3/3 |
7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Grown-up Congenital Heart Disease (GUCH) Contents Septal defects Atrial septal defect Case Report Introduction Classification Pathophysiology Evaluation and therapy Outcome Ventricular septal defect Case report Introduction Classification Pathophysiology Evaluation Treatment Outcome Atrioventricular septal defect Case report Introduction Pathophysiology Evaluation Treatment and outcome Patent ductus arteriosus Case report Introduction Evaluation Treatment and outcome Coarctation of the aorta Case report Introduction Pathophysiology Evaluation Treatment and outcome Transposition of the great arteries Case report https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 1/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Introduction Pathophysiology Treatment Outcome Congenitally corrected transposition of the great arteries Congenitally corrected transposition of the great arteries Introduction Pathophysiology Evaluation Treatment and outcome Univentricular heart Case report Introduction Pathophysiology Treatment Outcome Tetralogy of Fallot Case report Introduction Anatomy Pathophysiology Treatment Outcome Marfan syndrome Case report Introduction Criteria for diagnosis of Marfan syndrome Pathophysiology Treatment Outcome Ebsteins anomaly Case report Introduction Pathophysiology Treatment Outcome Pulmonary hypertension Case report Introduction Classification Pulmonary arterial hypertension in congenital heart disease Pathophysiology Classification https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 2/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Treatment Outcome References Septal defects Atrial septal defect Case Report Introduction Atrial septal defect (ASD) is common, accounting for approximately 7 percent of congenital heart disease. The ASD s can occur in several different anatomic portions of the atrial septum, and the location of the defect generally reflects the abnormality of embryogenesis that led to the anomaly. The functional consequences of an ASD are determined by its diameter, the anatomic location and the presence or absence of other cardiac anomalies. Classification The various forms of ASD s are differentiated from each other by the structures of the heart involved and the formation during embryological development. The ostium secundum defect is the most frequent form of ASD (70%), localized at the fossa ovalis with a diameter of about 1 2 cm. It commonly arises from an enlarged foramen ovale, inadequate growth of the septum secundum or excessive absorption of the septum primum. The sinus venosus defect (15% of all ASD s) is localized high in the atrial septum, at the inflow of the superior caval vein. Note that in 80-90% of patients this defect is accompanied by an anomalous pulmonary venous drainage of the right pulmonary vein into the right atrium. Inferior sinus venosus defects do exist, but are very exceptional. The ostium primum defect is localized low in the atrial septum at the atrioventricular junction. It forms the atrial component of the category of congenital heart disease referred to as atrioventricular defects, with a common atrioventricular junction and an abnormal atrioventricular valve. The coronary sinus defect, localized at the atrial ostium of the coronary sinus, is rare and usually accompanied by other cardial defects like anomalous drainage of the superior vena cava. Pathophysiology The presence of an ASD will in all cases gradually lead to a left to right shunt across the defect. At birth the volume of blood shunting from systemic to pulmonary circulation is small, because the right ventricle is still relatively thick-walled and noncompliant. In response to a decrease in pulmonary https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 3/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology vascular resistance after birth, the right ventricle remodels and its compliance increases. This leads to a decrease in right atrial pressure and an increase in shunt volume across the defect during the first years of life. The blood shunts during the late systole and early diastole, leading to a diastolic volume overload of the right atrium and right ventricle, but also the pulmonary veins and arteries. This volume overload of the pulmonary circulation will consequently lead to right-sided dilatation. The end diastolic increase in pressure of pulmonary circulation can result in systemic venous stuwing. This stuwing is augmented by another mechanism caused by the right ventricular volume overload; deviation of the ventricular septum to the left and the decrease in left ventricle preload because of the left to right shunt, lead to a decrease in stroke volume of the left ventricle. The renine- angiotensin system is activated, leading to an increase in intravascular volume and signs of venous stuwing. The right-sided volume overload is usually well tolerated for years, but in adulthood hemodynamic factors can influence the shunt size in both directions. If the right ventricle will start failing due to chronic volume overlad, the left to right shunt can decrease. If the left ventricle function will decline due to hypertension or coronary artery disease, the lef to right shunt can increase. In 10-20% of adult patients with an isolated ASD pulmonary hypertension will develop, leading to a decrease in left to right shunt and eventually right to left shunt with cyanosis (Eisenmenger syndrome). Figure 1. Heart from the right side view, showing different locations of atrial septal defects. Figure 2. Schematic drawing showing the location of different types of ASD, the view is into an opened right atrium. VCS, superior caval vein. VCI, inferior caval vein. HV, right ventricle. 1, upper sinus venosus defect. 2, lower sinus venosus defect. 3, secundum defect. 4, defect involving coronary sinus. 5, primum defect. Evaluation and therapy Most ASDs less than 8mm in diameter close spontaneously in infants, however above the age of 4 years spontaneous closure is unusual. During childhood and early adulthood most patients with moderate to large uncorrected ASDs are asymptomatic. Most of them will become symptomatic during adulthood (usually from the age of 40) and require closure of the defect. Indications for closure of an ASD in adulthood are development of symptoms and a high rate of shunt flow. Decreased exercise tolerance, fatigue, dyspnoe, syncope and paradoxal embolization are manifestions of such symptomatic ASDs that warrant closure of the defect. Atrial arrhythmias are usually one of the first presenting symptoms, however these symptoms alone are not an indication for closure, since the incidence after the procedure is not likely to be reduced. When closure of the ASD is indicated, this can be performed with surgery or percutaneous intervention. Surgical closure is usually performed using a patch of pericardium or Dacron. Prior to surgery, a comprehensive noninvasive evaluation is essential to exclude pulmonary hypertension and associated anatomic defects such as anomalous pulmonary and systemic venous connections. In nearly all cases, https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 4/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology echocardiography can resolve these questions, obviating the need for cardiac catheterization.Transcatheter closure avoids cardiopulmonary bypass, thoracotomy, and atriotomy, and is associated with excellent outcomes. As a result, this approach has largely replaced surgery in many centers for patients with a defect that is less than 20 mm in diameter. Outcome The short- and long-term outcomes are generally excellent after either surgical or transcatheter closure of an isolated ASD in children. Several investigations showed that there is almost no increase in long-term mortality or serious morbidity compared to controls, following surgical repair of an ASD under 25 years of age. The perioperative mortality is low (< 1%) and there are few perioperative complications (about 10%). However late in adulthood about 50% of all patients develop sinusknoopdysfunctie and symptomatic supraventricular tachyarrhythmias. Figure 23. Chest radiograph, left lateral view, of a 34-year old female who recently underwent percutaneous closure of her ASD with an Amplatzer device. When the ASD is closed percutaneously the short-term outcomes (less than one year) are excellent, with reported procedure success rates of 88 to 98%. Ventricular septal defect Case report Introduction The ventricular septal defect is the most common in childhood (30%). Most congenital heart defect patients have an isolated VSD, however a VSD also occurs in combination with other defects like Tetralogy of Fallot, which will be discussed elsewhere. About five percent of all patients with a VSD have a chromosomal abnormality, including trisomy 13, 18 and 21. Due to a high rate of spontaneous closure (50%) VSD is less seen in adulthood. Figure 3. Schematic drawing showing three main anatomic components of the interventricular septum: the septum of the atrioventricular canal (1), the muscular septum (2), the parietal band or distal conal septum (3). There are three main anatomic components of the interventricular septum (Figure 3); the septum of the atrioventricular canal (1), the muscular septum (2), the parietal band or distal conal septum (3). VSDs may occur at various locations in any of the three components. The location of the defect is not of particular interest when taking the characteristics of the intracardiac shunt in https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 5/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology account. However it is important in terms of the frequency of involvement of the atrioventricular valves and the rate of spontaneous closure and additionally the relation to the AV pathway when considering surgical correction. Classification The VSD can be classified into four types, related to the anatomic components involved; Type 1 is the infundibular VSD, which results from a defect in the septum below the aortic and pulmonary valves. The loss of support to the adjacent septal leaflets of these valves causes cusp prolapse into the VSD leading to progressive aortic regurgitation, which is the hallmark of this defect. Type 2, the membranous VSD, is the most common type of VSD (around 80%) and results from a deficiency of the membranous septum. This defect borders the septal leaflet of the tricuspid valve and might also extend into the muscular septum when it is referred to as a perimembranous VSD. Figure 4. Heart from the right side view, showing different locations of ventricular septal defects. Type 3 are inlet VSDs, located beneath both mitral and tricuspid valves. Despite proximity to those valves, this type of defect is not associated with mitral or tricuspid regurgitation unless associated with atrioventricular canal defect. This typically large defect is often associated with Down syndrome. Muscular defects (type 4) are located within the trabecular septum and accounts for 5 20% of all VSDs. It is bordered only by muscle, away from the cardiac valves. Muscular defects can be small or large in size and consist of a single or multiple defects. Pathophysiology The severity of the shunt across the VSD is determined by its size and the ratio of pulmonary to systemic vascular resistance. In small or restrictive VSDs the diameter of the defect is 25% of the aortic annulus diameter. These small defects cause small left to right shunts with no left ventricular overload or pulmonary hypertension. Moderate sized VSDs, measuring 25 75% of the aortic annulus diameter, result into mild volume overload of the pulmonary arteries, left atrium and left ventricle with no or only mild pulmonary hypertension. In large defects, defined as those with diameters equal or greater than 75% of the aortic annulus, there is no restriction of blood flow across the septum, leading to equal pressures in both right and left ventricle. The large left to right shunt initially only leads to excessive volume overload in the pulmonary arteries, left atrium and left ventricle. The chronic pressure and volume overload combined with the increase flow https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 6/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology leads to irreversible changes of the pulmonary vasculature, which results in an increase in pulmonary vascular resistance. This increase in resistance leads to a reversal of the shunt through the VSD causing right to left shunt with cyanosis (Eisenmenger syndrome). Evaluation Small defects are usually asymptomatic, however are fairly easy to detect during physical examination. There can be a palpable thrill accompanied by a holosystolic murmur grade 4-6. In some muscular defects the murmur is non holosystolic, due to the contraction and therby closure of the defect during systole. In moderate sized defects, with a large systemic to pulmonary flow of at least 1:2, a middiastolic rumble is audible due to the increased flow across the mitral valve. The pulmonary component of the second heart tone is loud. Only in a large VSD accompanied by the Eisenmenger syndrome and central cyanosis there is barely any shunt murmur audible. However there are murmurs audible caused by the pulmonary hypertension; an earlydiastolic murmur due to the pulmonary valve regurgitation and a holosystolic murmur due to the tricuspid valve regurgitation. Defects with large shunts that cause symptoms like decreased exercise tolerance and dyspnoe are usually detected and closed early in childhood. The ECG and chest X-ray of a patient with a small VSD are usually normal, but can show signs of left atrial and left ventricle overload in moderate sized defects. With echocardiography the localisation, size and hemodynamic influence of the VSD can be investigated. Dilatation of the left atrium and left ventricle might be present and the pressures in the pulmonary artery can be estimated by means of the tricuspid regurgitation. Invasive measurement by means of catheterization is only indicated when there is doubt about the shunt size and the pulmonary vascular resistance. Treatment Treatment and prognosis of a VSD depends on the size en localisation of the defect, the pulmonary vascular resistance and possible concomitant defects. Spontaneous closure occurs mainly in small defects, of which 75 percent closes before age 10. In patients with a small defect no pulmonary hypertension develops, however there is an increased risk of endocarditis. In patients with significant shunts studies have shown that surgical closure reduces pulmonary artery pressure and improves long-term survival. Therefore, repair of VSD should be considered in all adult patients who are symptomatic or have signs of left ventricular volume overload. Medical treatment is reserved for (1) asymptomatic patients without evidence of left ventricular volume overload and (2) patients with symptoms and/or left ventricular volume overload who are not candidates for repair such as those with large defects and Eisenmenger syndrome. Repair of VSD has been historically performed surgically. However, percutaneous VSD repair has been growing given the desire of young adults to avoid surgery. Surgical and percutaneous VSD closure should be performed by surgeons and cardiologists with appropriate training and expertise. Indications for closure of a VSD in an adult are included in the 2008 American College of Cardiology/American Heart Association (ACC/AHA) adult congenital heart disease guidelines as follows. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 7/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Similar recommendations are included in the European Society of Cardiology and the Canadian Society of Cardiology guidelines. Closure of a VSD is indicated when there is a Qp/Qs 2 and clinical evidence of LV volume overload. Closure of a VSD is indicated when the patient has a history of infective endocarditis. Closure of a VSD is reasonable when there is net left to right shunting with a Qp/Qs 1.5 with pulmonary artery pressure less than two thirds of systemic pressure and PVR is less than two thirds of systemic vascular resistance. Closure of a VSD is reasonable when there is net left to right shunting with a Qp/Qs 1.5 in the presence of LV systolic or diastolic dysfunction or failure. Indications for surgical closure of VSD in infants and young children may include: Infants <6 months (<3 months for those with trisomy 21) who have uncontrolled heart failure despite maximal medical and dietary interventions or who have pulmonary hypertension. Children with a persistent significant shunt (Qp:Qs >2:1), should undergo surgical repair even in the absence of elevated PA pressures. Subpulmonic and membranous defects, regardless of size, with aortic regurgitation should be surgically corrected before the aortic valve is permanently damaged. The decision to close small defects with aortic valve prolapse without aortic regurgitation is controversial. Closure of a VSD is not recommended in patients with severe irreversible pulmonary artery hypertension. Transcatheter device VSD closure is a treatment option for isolated uncomplicated muscular VSDs, and for certain membranous VSDs, in selected patients with suitable anatomy. Appropriate anatomy for transcatheter closure includes a VSD location remote from the tricuspid and aortic valves with an adequate rim. Successful transcatheter closure has been accomplished in the presence of multiple muscular or membranous fenestrations. The technical success rate of transcatheter closure of selected muscular and membranous VSDs is high (93-100%) and the mortality rate is low (0 2.7%). Outcome The long-term outcome for children who undergo surgical closure of VSD in childhood is generally excellent. Early surgical repair results in near normal long-term growth in the vast majority of patients. Most survivors are asymptomatic and lead normal lives. Adults with repaired VSD without residua have excellent outcomes and normal survival, with a 25year survival of 83%. However, long-term survival is less favorable when repair is done at older age or in presence of pulmonary hypertension. Although the prognosis after surgical repair of uncomplicated VSD is excellent in the majority of patients, long-term residua and sequelae are not uncommon including conduction disease, cardiac arrhythmias, residual VSD, endocarditis, tricuspid regurgitation, ventricular dysfunction, pulmonary hypertension, and aortic regurgitation. Development of complete atrioventricular block is the most significant of the transcatheter procedural complications. Approximately 6% of patients who underwent transcatheter closure of membranous defects, developed complete heart block necessitating pacemaker implantation. Real-time three- https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 8/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology dimensional transesophageal echocardiography has been increasingly used to guide such procedures. Given the lack of data on long-term outcomes following catheter closure of VSD in adults, patients should be followed every one to two years at an adult congenital heart disease center. Atrioventricular septal defect Case report Introduction The atrioventricular septal defect (AVSD) consist of several different lesions with a common atrioventricular (AV) junction and abnormal AV valves, consisting of five leaflets (Figure 5). The AVSD makes 3 procent of all congenital heart defects in children. When the AVSD is complete it consists of a defect on the atrial and on the ventricular side of the common AV- valve ring. (Figure 5, middle). The complete AVSD is usually associated with Down Syndrome, but also with other cardiac defects like ASD type 2, persisting left inferior caval vein and tetralogy of Fallot. Figure 5. Left: schematic drawing of a normal heart with a normal mitral (M) and tricuspid (T) valve. Middle: a complete AVSD where the mitral and tricuspid valve is replaced by a common valve with a right anterosuperior leaflet (1), a right inferior leaflet (2), a superior bridging leaflet (3), an inferior bridging leaflet (4), and a left mural leaflet (5). Right: showing the anatomic arrangement in an incomplete AVSD. a=aorta, p= pulmonary artery. In an incomplete AVSD the superior and inferior bridging leaflets are connected with each other and with the interventricular septum in the centre. (Figure 5, right) Due to this connection there are two divided AV inlets, leaving no open communication between the ventricles, thus no VSD exists. However there is a rather large defect in the interatrial septum. The incomplete AVSD is often referred to as ostium primum defect or ASD type 1. The left AV-valve consist of three leaflets (there is a cleft in the mitral valve) and is usually incompetent. Due to one common AV junction in both types of AVSD, the aortic valve is not in the usual wedged position between the two separate AV inlets, but located more anterior. Therefore the outflow tract of the left ventricle is elongated and slightly constricted. In angiography this abnormally shaped outflow tract is known as a gooseneck. Pathophysiology The exact pathophysiology depends on the location and severity of the defect. In a complete AVSD there is combined right and left ventricular overload due to the left-to-right shunt at atrial and ventricular level combined with the regurgitation of the right and left AV valve. As a result the elevated pulmonary pressures due to the extremely high flow will rapidly convert to pulmonary hypertension. This will lead to bidirectional shunting across the defect with a preferably right-to-left shunt and cyanosis (Eisenmenger syndrome). https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 9/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In an incomplete AVSD the hemodynamic consequences are comparable to an ASD type 2. However the serious left AV-valve regurgitation can cause an increase in the atrial left-to right shunt. Evaluation The complete AVSD leads to symptoms of heart failure early in childhood and most patients will have been surgically corrected in adulthood. During physical examination signs of a residual shunt or regurgitation of the AV-valves might be present. This defect is rarely diagnosed in adulthood and usually there is Eisenmenger syndrome present, with clinical signs previously described in isolated ASD or VSD. The clinical symptoms of an incomplete AVSD are comparable with those of an ASD type 2. During physical examination a murmur of the regurgitant AV-valve might be audible. The ECG shows a deviation of the heart axis to the left, in contrast to the right axis deviation in atrial septal defects. This is due to the abnormal position of the His bundle which causes a delay in conduction through the left anterior fascicular branch. Treatment and outcome The survival for patients with a complete AVSD without corrective surgery is very limited, most patients will not reach adulthood. Therefore surgical correction at an early age (usually in the first year of life) is advised. Patients with a corrected complete AVSD need lifelong cardiologic follow up, due to frequent residual defects like residual VSD, progressive regurgitation of the left AV-valve, pulmonary hypertension and often rhythm- or conduction disorders. Patients with Down Syndrome and complete AVSD are more likely to develop progressive pulmonary hypertension, even after corrective surgery. The aberrant anatomy of the AV-valves, even after corrective surgery, is important when reviewing echocardiographic images. They can, for example, be easily mistaken for vegetations in endocarditis. The survival for patients with an incomplete AVSD is higher compared to the complete AVSD, but generally worse compared to other ASD types. This is due to the concomitant disorders of the left AV- valve and the conduction system. Left AV-valve regurgitation will lead to an increase in left-to-right shunt and earlier development of pulmonary hypertension compared to ASD type 2. In childhood there is usually already an indication for correction of the defect in which the anatomically abnormal AV-valve can be repaired. However a slight amount of regurgitation will remain present. In some cases the progressive failure of the AV-valve will require a second repair or replacement, but in most patients the insufficiency will remain mild. Besides the AV-valve problems there are frequent rhythm and conduction disorders; atrial fibrillation, supraventricular tachycardia, complete heartblock or sinus dysfunction. Depending on the kind of disorder patients can require medical treatment or a pacemaker. Patent ductus arteriosus Case report Introduction https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 10/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology The ductus arteriosus (DA) is a fetal vascular connection between the main pulmonary artery and the descending aorta that diverts blood away from the pulmonary bed (Figure 6). After birth, the DA undergoes active constriction and eventual obliteration. A patent ductus arteriosus (PDA) occurs when the ductus fails to completely close postnatally. The incidence of PDA has increased dramatically over the last two decades. This is due to the improved survival rate of premature infants, because the incidence of PDA significantly increases in infants born before 30 weeks gestation. Figure 6. Schematic cross-section of the heart showing a patent ductus arteriosus. The reported incidence of an isolated PDA among term infants ranges from 0.03 to 0.08 percent. There is a female predominance for PDA with a 2:1 female to male ratio in most case series of term infants. The incidence of PDA is also greater in infants born at high altitude compared to those born at sea level, and in infants with congenital rubella. PDA may present with other congenital heart lesions, especially those associated with hypoxemia. PDA should be considered when the clinical features of left-to-right shunt seem out of proportion to the particular lesion being considered. Evaluation The clinical manifestations of a PDA are determined by the degree of left-to-right shunting, which is dependent upon the size and length of the PDA, and the difference between pulmonary and systemic vascular resistances. The hemodynamic consequences of the PDAs can be categorized by the degree of left-to-right shunting based upon the pulmonary to systemic flow ratio (Qp:Qs) [21]. Small Qp:Qs <1.5 to 1 Moderate Qp:Qs between 1.5 and 2.2 to 1 Large Qp:Qs >2.2 to 1 Typical findings during physical examination are a continuous murmur and a low diastolic blood pressure. In small shunts the ECG and chest x-ray are normal. In larger left-to-right shunts signs of left atrial and left ventricular overload might be present. Echocardiography is a very sensitive and specific method to identify the left-to-right shunt. Treatment and outcome Patients with an open PDA have an increased risk of infectious endarteritis, heart failure, pulmonary hypertension and most of these patients become symptomatic in adulthood. Patients with a non- restrictive PDA rarely reach adulthood, unless the pulmonary vascular resistance increases leading to a https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 11/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology decrease in left ventricular overload. This hemodynamic state is known as Eisenmenger syndrome in which the shunt is reversed and there is cyanosis present. Patients in who the ductus is closed in childhood have a normal life expectancy. In patients with a PDA, the primary management decision is whether to actively close the PDA, or to conservatively observe and monitor the patient's cardiac status on a regular basis. PDA closure is recommended for patients with a significant left-to-right shunt who are symptomatic, have evidence of left-sided volume overload or have reversible pulmonary arterial hypertension. Closure results in resolution of symptoms and a decrease in the likelihood or severity of PAH, and the development of irreversible pulmonary vascular disease (Eisenmenger syndrome). Figure 7. Echocardiographic image showing a coil in the ductus arteriosus. P=pulmonary artery, A= aorta. PDA closure is not recommended in patients with severe and irreversible PAH because of the procedural risk, the fact that closure does not improve survival, and right to left ductal shunting may be necessary to maintain cardiac output during episodes of increasing pulmonary vascular resistance. Interventions for PDA closure include: pharmacological treatment which is used exclusively in premature infants, surgical ligation or percutaneous catheter occlusion. Surgical closure has a low mortality (<1%) in children and young adults. In adult patients the perioperative risk is increased (around 3%) due to a higher rate of complications like bleeding, heart failure in a compromised left ventricular function and damage to the recurrent laryngeal nerve or phrenic nerve. Percutaneous PDA occlusion was first introduced in 1967 and provides an alternative to surgical ligation. Many different techniques have been developed, however the two techniques most commonly used are coils or occlusion devices. Both techniques lead to a full occlusion of the PDA and normalization of left ventricular hemodynamics. Coarctation of the aorta Case report Introduction Coarctation of the aorta is a narrowing of the thoracic aorta, typically located in the region of the obliterated ductus arteriosum. (Figure 9) The relation to the position of the left subclavian artery differs, in most patients the left subclavian artery is located anterior of the coarctation. Aortic coarctation is frequently associated with diffuse hypoplasia of the aortic arch and isthmus. The incidence of coarctation of the aorta is 4 in 10.000 live births, accounting for 5 9% of the children with congenital heart defects, occurring two to five times more frequently in males than females. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 12/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Coarctation of the aorta can be an isolated congenital heart defect, however usually it coincides with other congenital defects. Associated heart defects are patent ductus arteriosus, ventricular septal defect, mitral valve stenosis and valvular and subvalvular aortic stenosis. Furthermore around 75% of all patients with a coarctation of the aorta have a bicuspid aortic valve. The development of coarctation aorta depends on genetic as well on non-genetic factors. Parents with coarctation aorta have a 2% (male) or 4% (female) chance of passing this defect to their child. Figure 9. Schematic drawing of the anatomy prenatal (left) and postnatal (right) in coarctation of the aorta. In the normal situation (without coarctation) only 10 percent of the fetal cardiac output flows through the descending aorta. Therefore there are no hemodynamic consequences prenatal of coarctation of the aorta. In the postnatal situation, after closure of the ductus arteriosus, around 75% of cardiac output needs to pass the coarctation, leading to obstruction. Pathophysiology Coarctation aorta has no hemodynamic consequences in utero, because only 10% of the total cardiac output crosses from the ascending to the descending aorta. However after birth the ductus arteriosus and foramen ovale close, leading the whole cardiac output through the narrowed aortic segment. This leads to an increase in resistance in the left ventricular outflow tract, resulting in an elevated systolic pressure in the left ventricle and upper extremities. When coping with the elevated pressures, the left ventricle will become hypertrophic. If the coarctation is severe or in the acute phase (after birth when the ductus is closed), systolic dysfunction of the left ventricle and heart failure can occur. Most adult patients are asymptomatic unless severe hypertension is present leading to headache, epistaxis, heart failure, or aortic dissection. In addition, claudication may occur due to reduced flow to the lower extremities. Evaluation Coarctation of the aorta is easily diagnosed without invasive methods, by means of physical examination, echocardiography or MRI. The combination of weak or absent femoral arterial pulses and upper body hypertension in physical examination points into the direction of coarctation of the aorta. Nevertheless, studies have shown that the diagnosis in hypertensive patients is often missed by the referring doctor. As a consequence, a significant number of asymptomatic subjects with aortic coarctation are probably not detected until adult life, so their incidence at birth is likely to be underestimated. Late detection of subjects with aortic coarctation can have detrimental effects on survival. For, without correction, the mean life expectancy of patients with aortic coarctation is 35 years and 90% of those patients die before reaching the age of 50 years. Chest radiograph varies with age and severity of the coarctation. In infants with heart failure, the chest radiograph shows generalized cardiomegaly with increased pulmonary vascular markings due to pulmonary venous congestion. In older children and adults, the heart size may be normal but notching of the posterior one-third of the third to eighth ribs due to erosion by the large collateral arteries might be present. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 13/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transthoracic echocardiography, including suprasternal notch views, is useful for initial imaging and hemodynamic evaluation in suspected aortic coarctation. Echocardiographic evaluation should also include measurement of the dimensions of the aortic annulus, aortic sinuses, sinotubular ridge, and ascending aorta; identification of aortic valve anatomy; determination of left ventricular size and function; and identification of any potential associated lesions such as ventricular septal defect, subvalvular aortic stenosis and mitral valve deformity. Treatment and outcome Figure 11. Schematic drawing showing surgical procedures for repair of a coarctation of the aorta. Left: an interposition graft. Middle: the extended aortic arch repair. Right: the extra-anatomical bypass. Figure 10. Schematic drawing showing surgical procedures for repair of coarctation of the aorta. Left: resection with end-to-end anastomosis. Middle: dilating technique using a patch; this technique is used in coarctations involving a long segment of the aorta. Right: the subclavian flap aortoplasty, using the left subclavian artery. Since surgical repair of aortic coarctation became available in 1944, survival of patients with aortic coarctation has dramatically improved and the number of patients who were operated on and reach adulthood is steadily increasing. However, life expectancy is still not as normal as in unaffected peers. Survival of patients operated at a median age of 16 years was 91% at 10 years, 84% at 20 years and 72% at 30 years after operation. Survival of post-coarctectomy patients is significantly affected by age at operation and nowadays early repair is advocated. Even after early repair before the age of 5 years the estimated survival is still reduced, with 91% of the operated patients alive at 20 years and 80% at 40 to 50 years after surgery. However, repair of aortic coarctation is still recommended in patients at older age when diagnosis is delayed, because it improves blood pressure regulation and is probably associated with a lower risk of cardiovascular events in later years and improved survival. There are several surgical techniques used for correction of the aortic coarctation. (Figure 10 & 11) Resection of the narrowed aortic segment with end-to-end anastomosis is the most commonly used technique. The subclavian flap aortoplasty and dilatation with a patch are not in use anymore due to a decreased blood flow in the left arm and a high rate of aneurysmatic deformation of the vessel respectively. When end-to-end anastomosis is not feasible, an interposition graft might be used instead. Sometimes a complete resection of the stenosis is not possible, for example when the carotid arteries are part of the coarctation, then an extended aortic arch repair or extra-anatomic bypass might be an appropriate choice. (Figure 7) https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 14/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transcatheter interventions for native aortic coarctation have been used for over 20 years. Transcatheter treatment for native aortic coarctation has been shown to be feasible, relatively safe and effective at short term and intermediate follow-up and is rapidly becoming the treatment of choice. Older age, however, seems to be a risk factor for suboptimal outcome after balloon angioplasty possibly due to a more fibrotic and rigid aorta. Especially in the full grown patient, stent placement seems a particularly attractive option, resulting in an almost complete relief of the gradient in 95% of the patients. Another benefit of stent placement is the ability to address longer segment coarctations, which typically have a poorer outcome after balloon angioplasty alone. Long-term results, however, are to be awaited. Concern after surgery or catheter intervention falls chiefly in seven categories: recoarctation, aortic aneurysm formation or aortic dissection, coexisting bicuspid aortic valve, endocarditis, premature coronary atherosclerosis, cerebrovascular accidents and systemic hypertension. Transposition of the great arteries Case report Introduction Figure 13. Schematic drawing of the circulation in transposition of the great arteries. Left: normal position of the great arteries with the pulmonary and systemic circulation serially connected. Right: transposition of the great arteries with a parallel circulation. Transposition of the great arteries (TGA) accounts for 5- 8% of all congenital heart defects and occurs 2-3 times more frequently in males. TGA is best defined as a normal atrioventricular connection with an abnormal ventricular arterial connection; the morphological left atrium is connected through the left ventricle with the pulmonary artery and the morphological right atrium through the right ventricle with the aorta. (Figure Figure 12: Schematic drawing showing transposition of the great arteries. The pulmonary artery is located above the left ventricle (LV) and the aorta is located above the right ventricle (RV). https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 15/38 7/4/23, 12:41 AM |
Pathophysiology Coarctation aorta has no hemodynamic consequences in utero, because only 10% of the total cardiac output crosses from the ascending to the descending aorta. However after birth the ductus arteriosus and foramen ovale close, leading the whole cardiac output through the narrowed aortic segment. This leads to an increase in resistance in the left ventricular outflow tract, resulting in an elevated systolic pressure in the left ventricle and upper extremities. When coping with the elevated pressures, the left ventricle will become hypertrophic. If the coarctation is severe or in the acute phase (after birth when the ductus is closed), systolic dysfunction of the left ventricle and heart failure can occur. Most adult patients are asymptomatic unless severe hypertension is present leading to headache, epistaxis, heart failure, or aortic dissection. In addition, claudication may occur due to reduced flow to the lower extremities. Evaluation Coarctation of the aorta is easily diagnosed without invasive methods, by means of physical examination, echocardiography or MRI. The combination of weak or absent femoral arterial pulses and upper body hypertension in physical examination points into the direction of coarctation of the aorta. Nevertheless, studies have shown that the diagnosis in hypertensive patients is often missed by the referring doctor. As a consequence, a significant number of asymptomatic subjects with aortic coarctation are probably not detected until adult life, so their incidence at birth is likely to be underestimated. Late detection of subjects with aortic coarctation can have detrimental effects on survival. For, without correction, the mean life expectancy of patients with aortic coarctation is 35 years and 90% of those patients die before reaching the age of 50 years. Chest radiograph varies with age and severity of the coarctation. In infants with heart failure, the chest radiograph shows generalized cardiomegaly with increased pulmonary vascular markings due to pulmonary venous congestion. In older children and adults, the heart size may be normal but notching of the posterior one-third of the third to eighth ribs due to erosion by the large collateral arteries might be present. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 13/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transthoracic echocardiography, including suprasternal notch views, is useful for initial imaging and hemodynamic evaluation in suspected aortic coarctation. Echocardiographic evaluation should also include measurement of the dimensions of the aortic annulus, aortic sinuses, sinotubular ridge, and ascending aorta; identification of aortic valve anatomy; determination of left ventricular size and function; and identification of any potential associated lesions such as ventricular septal defect, subvalvular aortic stenosis and mitral valve deformity. Treatment and outcome Figure 11. Schematic drawing showing surgical procedures for repair of a coarctation of the aorta. Left: an interposition graft. Middle: the extended aortic arch repair. Right: the extra-anatomical bypass. Figure 10. Schematic drawing showing surgical procedures for repair of coarctation of the aorta. Left: resection with end-to-end anastomosis. Middle: dilating technique using a patch; this technique is used in coarctations involving a long segment of the aorta. Right: the subclavian flap aortoplasty, using the left subclavian artery. Since surgical repair of aortic coarctation became available in 1944, survival of patients with aortic coarctation has dramatically improved and the number of patients who were operated on and reach adulthood is steadily increasing. However, life expectancy is still not as normal as in unaffected peers. Survival of patients operated at a median age of 16 years was 91% at 10 years, 84% at 20 years and 72% at 30 years after operation. Survival of post-coarctectomy patients is significantly affected by age at operation and nowadays early repair is advocated. Even after early repair before the age of 5 years the estimated survival is still reduced, with 91% of the operated patients alive at 20 years and 80% at 40 to 50 years after surgery. However, repair of aortic coarctation is still recommended in patients at older age when diagnosis is delayed, because it improves blood pressure regulation and is probably associated with a lower risk of cardiovascular events in later years and improved survival. There are several surgical techniques used for correction of the aortic coarctation. (Figure 10 & 11) Resection of the narrowed aortic segment with end-to-end anastomosis is the most commonly used technique. The subclavian flap aortoplasty and dilatation with a patch are not in use anymore due to a decreased blood flow in the left arm and a high rate of aneurysmatic deformation of the vessel respectively. When end-to-end anastomosis is not feasible, an interposition graft might be used instead. Sometimes a complete resection of the stenosis is not possible, for example when the carotid arteries are part of the coarctation, then an extended aortic arch repair or extra-anatomic bypass might be an appropriate choice. (Figure 7) https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 14/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Transcatheter interventions for native aortic coarctation have been used for over 20 years. Transcatheter treatment for native aortic coarctation has been shown to be feasible, relatively safe and effective at short term and intermediate follow-up and is rapidly becoming the treatment of choice. Older age, however, seems to be a risk factor for suboptimal outcome after balloon angioplasty possibly due to a more fibrotic and rigid aorta. Especially in the full grown patient, stent placement seems a particularly attractive option, resulting in an almost complete relief of the gradient in 95% of the patients. Another benefit of stent placement is the ability to address longer segment coarctations, which typically have a poorer outcome after balloon angioplasty alone. Long-term results, however, are to be awaited. Concern after surgery or catheter intervention falls chiefly in seven categories: recoarctation, aortic aneurysm formation or aortic dissection, coexisting bicuspid aortic valve, endocarditis, premature coronary atherosclerosis, cerebrovascular accidents and systemic hypertension. Transposition of the great arteries Case report Introduction Figure 13. Schematic drawing of the circulation in transposition of the great arteries. Left: normal position of the great arteries with the pulmonary and systemic circulation serially connected. Right: transposition of the great arteries with a parallel circulation. Transposition of the great arteries (TGA) accounts for 5- 8% of all congenital heart defects and occurs 2-3 times more frequently in males. TGA is best defined as a normal atrioventricular connection with an abnormal ventricular arterial connection; the morphological left atrium is connected through the left ventricle with the pulmonary artery and the morphological right atrium through the right ventricle with the aorta. (Figure Figure 12: Schematic drawing showing transposition of the great arteries. The pulmonary artery is located above the left ventricle (LV) and the aorta is located above the right ventricle (RV). https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 15/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 12)The aorta is often located on the right side and in front of the pulmonary artery (D-TGA). In 70 percent there is an isolated form of TGA, in 30 percent the TGA is accompanied by other heart defects, like VSD or obstruction of the left ventricle outflow tract. Pathophysiology The circulation in TGA patients is not serial but parallel (Figure 13); the venous blood is returned to the systemic circulation through the right atrium and ventricle, while the arterial oxygenated blood is directed back into the pulmonary artery through the left atrium and ventricle. Due to this abnormal circulation there is severe cyanosis directly after birth, therefore it is critical for the ductus arteriosus and foramen ovale to remain open. Without treatment there is a mortality of 30% within one week, 50% within one month and 90% within one year. When an associated VSD is present the chances of survival are higher due to more shunting thus more oxygenated blood in the systemic circulation. These patients are able to reach early adulthood without corrective surgery or intervention. However the pulmonary hypertension that develops in this situation will eventually lead to severe problems. Treatment Mortality of TGA has dramatically improved from 90 percent for unoperated patients to rates of less than 5 percent following corrective surgery using the arterial switch operation. Most patients are referred for surgical repair during the first three to five days of life. The choice of surgical procedure is dependent on the presence and nature of other cardiac anomalies. In patients without any other cardiac defect (simple D-TGA), arterial switch operation is the recommended procedure. In general, the arterial switch operation has replaced the earlier atrial switch procedures developed by Mustard and Senning. In patients with D-TGA and a ventricular septal defect (VSD), the preferred procedure is arterial switch operation and VSD closure. In patients with D-TGA, large VSD, and significant pulmonary stenosis, the Rastelli procedure, an alternative surgical approach, should be considered. In some cases, arterial switch operation with or without repair of the left ventricular outflow obstruction is used. Both the arterial switch operation and Rastelli procedures are surgical anatomic corrections resulting in a morphologic left ventricle as the systemic ventricle. In comparison to atrial switch procedures, which involved the rerouting of venous return in the atria and are now only rarely performed, the arterial switch operation appears to have similar long-term survival rates with reduced long-term morbidity primarily due to a lower risk of atrial arrhythmias and heart failure. As a result, it is the recommended procedure in most patients with D-TGA. Outcome The long-term survival rates for patients with D-TGA following surgical correction are excellent for both arterial switch operation and atrial switch procedures. The long-term survival 20 years after discharge is about 95 and 80 percent for arterial switch and atrial switch respectively. Progressive congestive heart failure and sudden death are the principal causes of death. Perioperative mortality is greater in patients with complex (additional cardiac anomaly) D-TGA compared to those with simple D-TGA. There are no clinical trials comparing outcomes of arterial switch and atrial switch procedures. Reintervention is common following both approaches. Patients who undergo surgical repair for D-TGA have a reduced exercise capacity primarily due to pulmonary disease. Patients after arterial switch operation appear to have better exercise capacity than those who underwent atrial switch procedures. The decrease in exercise capacity, however, does not limit https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 16/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology ordinary activity as most patients meet the criteria for New York Heart Association functional class I. It appears that patients with D-TGA may have mild long-term neurodevelopmental impairment, most likely due to perioperative factors including hypoxemia, acidosis, cardiopulmonary bypass, and hemodynamic instability. Congenitally corrected transposition of the great arteries Congenitally corrected transposition of the great arteries Introduction The congenitally corrected transposition of the great arteries (ccTGA) is characterized by a normal anatomical position of both atria, with an abnormal connection between the atria and the ventricles. The right atrium is connected with the left ventricle and the left atrium is connected with (Figure 14) Furthermore the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. There are, in conclusion, abnormal atrioventricular connections and abnormal ventricular-arterial connections present in ccTGA. CcTGA is a very rare defect, accounting for about 1% of all congenital heart disease. the right ventricle. Pathophysiology Figure 14. Congenitally corrected transposition of the great arteries. RA, right atrium. LA, left atrium. RV, right ventricle. LV, left ventricle. p, pulmonary artery. ao, aorta. tric, tricuspid valve. The blood corrected because oxygenated blood flows through the systemic circulation and deoxygenated blood is transported to the lungs. In this particular heart defect the right ventricle functions as a systemic ventricle. With the atrioventricular valves following the position of the ventricles, the tricuspid valve is now the systemice AV-valve. flow in ccTGA is Additionally the coronary arteries are a mirror image of the normal anatomic situation. The coronary artery on the right side of the heart runs like a morphological left coronary artery; starting with a main stem which divides into a left anterior descending and circumflex branch. The coronary artery on the left is the morphological right coronary artery, which now runs around the tricuspid valve on the left. Even the conduction system is abnormal in this congenital heart defect. Normally the AV node is positioned at the base of the interatrial septum, from where the His bundle arises into the interventricular septum. Due to misalignment in ccTGA there is no bundle directly from the normal AV node into the interventricular septum. Usually there is an additional AV node located more anterior and laterally from where a long bundle arises which runs beneath the pulmonary valve leaflets into the interventricular septum. Due to the long route this bundle is rather vulnerable. Where in normal hearts the electrical activation of the ventricles in the septum runs from left to right, in ccTGA it is the exact opposite; the septum is activated from right to left, which is visible on the ECG as an abnormal initial activation. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 17/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology There is a VSD present in 60% of all ccTGA patients, who will often become symptomatic at younger age. Pulmonary valve stenosis is seen in 30 50% of patients, usually in those who already have a VSD as well. Abnormal anatomy of the tricuspid valve (M. Ebstein like) is seen in 25-30% of patients, sometimes accompanied by VSD or pulmonary valve stenosis. More than 80 percent of patients have an abnormal function of the tricuspid valve, which often becomes insufficient. Evaluation When only ccTGA is present, without other cardiac defects, the diagnosis is often not recognized until adulthood. However, when there is a VSD and/or pulmonary valve stenosis present, it presents short after birth with cyanosis and heart failure or even a total AV-block. Adult patients are usually recognized due to an abnormal ECG, abnormal chest radiograph, systolic murmur due to the regurgitation of the systemic AV-valve, occurrence of atrial tachycardia or an AV- block. Reduced exercise capacity might be present. The ECG is the most typical for ccTGA; left heart axis deviation, septum activation in mirror image (no Q-wave in I, aVL and V6, no R-top in V1) and a rather deep Q-wave in III and aVF. Echocardiography is a good diagnostic tool to review the exact anatomy. The right ventricle positioned on the left side is identified by the typical morphology of the trabeculae. Furthermore the tricuspid valve has a lower insertion compared to the mitral valve. Treatment and outcome Patients with ccTGA require lifelong follow up due to the risk of arrhythmias and associated sudden death, increase of pulmonary valve stenosis, increase of tricuspid valve regurgitation, supraventricular tachycardia, heart failure or endocarditis. Due to the complex anatomy and the low incidence of this pathology, this is best acquired at a specialised centre of congenital heart disease. Arrhythmias need treatment, preferably not with negative inotropic agents, but digoxin and possibly amiodaron are preferred. When presenting with atrial arrhythmias conversion to sinus rhythm is highly important in these patients, who are in need of their atrial kick . Many patients with ccTGA require pacemaker placement, often already in childhood or early adulthood. Frequent followup in these patients is required due to the high complication rate; dislocation of the lead which is located in the smooth-walled left ventricle and risk of infection or endocarditis. Determining the right time to replace the tricuspid valve is difficult in these patients. Preferably this is done just before the right systemic ventricle starts dilating and fails, but it remains an estimation which should be made for each individual patient. To restore normal blood flow through the ventricles, with the left ventricle functioning as the systemic ventricle, there is an option to perform a double switch operation. During this procedure both atria and both great arteries are switched, meaning a combination of the arterial switch and the atrial switch procedure. From a physiologic point of view this operation is worth considering while the left ventricle will function as systemic ventricle, however it is associated with a high perioperative mortality due to the https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 18/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology extent of surgery. Furthermore the left ventricle requires training prior to surgery, to be able to cope with the high arterial pressure after years of low pulmonary pressure. In conclusion the chance of success of this double switch operation is very low in patients above 16 years of age. Univentricular heart Case report Introduction Around 10 percent of all congenital heart defect patients have just one functioning ventricle. The other ventricle is present, however it is rudimentary or underdeveloped so it can not function normally. In utero this causes rarely any problems, due to the parallel circulation the other ventricle takes over both functions. It is after birth, if the ductus arteriosus closes, when problems arise. Pathophysiology The hypoplastic left heart syndrome (HLHS) is the most common type of univentricular heart. (Figure 15) Not only the left ventricle, but often the aortic valve, ascending aorta and aortic arch are hypoplastic as well. This will redirect blood from the left atrium into the right atrium, where is will be mixed with venous blood and pumped into the right ventricle and pulmonary artery. The whole systemic circulation depends on the shunt from pulmonary artery through the ductus arteriosus into the aorta. When the ductus starts closing the consequences are dramatic, with severe cyanosis and acidosis. Figure 15. Schematic drawing representing the hypoplastic left heart syndrome. When a hypoplastic right ventricle is present with associated atresia of the pulmonary circulation after birth will solely depend on ductus the arteriosus.When the ductus starts closing, progressive cyanosis is the main presenting symptom. the pulmonary artery, left-to-right shunt through the Other cardiac defects associated with only one functional ventricle are: tricuspid valve atresia, mitral valve atresia, severe form of Ebstein anomaly, double inlet left ventricle and unbalanced AVSD. All patients with one functioning ventricle have complete mixing of saturated and desaturated blood leading to Figure 24. Echocardiographic image of a male patient with a univentricular heart. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 19/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology chronic hypoxemia (Figure 24). Furthermore there is a chronic volume overload to the ventricle, serving as both pulmonary and systemic ventricle, leading to an early development of heart failure. Due to the obligatory intracardiac shunting the pulmonary filter is bypassed, which will increase the chance of cardiovascular accidents and brain abscesses. Treatment In case of a ductus-dependent defect initial treatment immediately after birth consists of prevention of ductus closure. At first this can be achieved pharmacologically with prostaglandin, however due to the many side effects this is no long-term solution. When there is a dependent pulmonary circulation an aortopulmonary shunt will be constructed during the first weeks of life to ensure accurate blood flow to the lungs after discontinuation of the prostaglandin. Figure 16. Schematic drawing showing the Fontan procedure. If there is a dependent systemic circulation the surgical treatment usually consists of three different steps. Since the anatomy is by no means normalized, one can not speak of a surgical correction, it is referred to as a definitive palliation. At first a Norwood or Sano procedure is performed in neonates where a neo-aorta is constructed by dividing the pulmonary artery. Second stage is the construction of a cavopulmonary shunt, also known as bidirectional Glenn shunt, which is performed at 4 -6 months of age. The third and final stage is known as Fontan procedure and performed at 18 30 months of age, where a total cavopulmonary connection is created. (Figure 16) All surgical procedures are described in more detail separately. Outcome With an expanding cohort of survivors of surgical palliation through Fontan completion, increasing information is being accumulated on the long-term morbidity of these patients. Active areas of interest include exercise tolerance, neurodevelopmental outcome, and quality of life. When assessed prospectively by formal exercise testing, children with HLHS after surgical repair showed considerable age-related decline in exercise performance. Among patients participating in treadmill or bicycle ergometry, those aged 8 to 12 performed at 70 percent of predicted peak oxygen consumption, whereas older children reached only 60 percent of predicted performance. Several reports have demonstrated significant neurodevelopmental impairment in survivors of HLHS following staged repairs or cardiac transplantation. There is a paucity of data on the quality of life for patients with HLHS. In one report of survivors and their families, parents reported poorer functional health status than patients assessed at 18 years of age. Risk factors that lower survival include noncardiac congenital anomalies and/or genetic disorder, particularly chromosomal defects, prematurity, low birth weight for gestational age, and living in a high poverty neighborhood. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 20/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology With an expanding cohort of survivors of surgical palliation through Fontan completion, increasing information is being accumulated on the long-term morbidity of these patients. Active areas of interest life. When assessed include exercise tolerance, neurodevelopmental outcome, and quality of prospectively by formal exercise testing, children with HLHS after surgical repair showed considerable age-related decline in exercise performance. Among patients participating in treadmill or bicycle ergometry, those aged 8 to 12 performed at 70 percent of predicted peak oxygen consumption, whereas older children reached only 60 percent of predicted performance. Several reports have demonstrated significant neurodevelopmental impairment in survivors of HLHS following staged repairs or cardiac transplantation. There is a paucity of data on the quality of life for patients with HLHS. In one report of survivors and their families, parents reported poorer functional health status than patients assessed at 18 years of age. Risk factors that lower survival include noncardiac congenital anomalies and/or genetic disorder, particularly chromosomal defects, prematurity, low birth weight for gestational age, and living in a high poverty neighborhood. Tetralogy of Fallot Case report Introduction In 1888 Etienne Louis Arthur Fallot described the maladie bleue as a combination of: Stenosis of the pulmonary artery (PS) Ventricular septal defect (VSD) Deviation of the origin of the aorta to the right Hypertrophic right ventricle This constellation of findings has since become known as tetralogy of Fallot (TOF). (Figure 17) The prevalence of TOF is about 3.9 per 10.000 live births. This defect accounts for about 7 to 10 percent of cases of congenital heart disease and is one of the most common congenital heart lesions requiring intervention in the first year of life. Figure 17. Schematic drawing representing the four features of tetralogy of Fallot. Anatomy https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 21/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In fact there is only one anatomic abnormality in TOF; a misalignment of the interventricular septum. As a consequence the muscular part of the interventricular septum is not able to fuse with the cranial part of the septum (leaving a ventricular septal defect) and overriding of the aorta, which causes stenosis of the right ventricular outflow tract. The hypertrophy of the right ventricle is a direct consequence of the elevated pressure in the right ventricle due to the large unrestrictive VSD. Pathophysiology The combination of infundibular PS and a VSD causes the blood flow in utero to flow directly into the aorta, leading to a high chance of underdevelopment of the pulmonary valve and arteries. Therefore pulmonary valve stenosis and hypoplasia of the pulmonary arteries are often found in TOF patients. Stenosis at the origin or more distally of the right or left pulmonary artery are frequently found, so is total absence of (usually the left) pulmonary artery. Furthermore about 33% percent of all TOF patients has a descending aorta on the right side. The physiologic consequences of TOF are largely dependent upon the degree of right ventricular outflow obstruction. Since the VSD is typically large and unrestrictive, the pressure in the right ventricle reflects that of the left ventricle. As a result, the direction of blood flow across the VSD will be determined by the path of least resistance for blood flow, not by the size of the VSD. If the resistance to blood flow across the obstructed right ventricular outflow tract is less than the resistance to flow out of the aorta into the systemic circulation, blood will naturally shunt from the left ventricle to the right ventricle and into the pulmonary bed. In this situation, there is predominately a left-to-right shunt and the patient will be acyanotic. As the degree of right ventricular outflow obstruction increases, the resistance to blood flow into the pulmonary bed also increases. If the right ventricular obstruction is significant enough to increase resistance, it will be easier for blood to cross the VSD from the right ventricle into the left ventricle and go out the aorta, which now becomes the path of least resistance. This right-to-left shunt across the VSD will result in a large volume of desaturated blood entering the systemic circulation and cyanosis and polycythemia will ensue. One of the physiologic characteristics of TOF is that the right ventricular outflow obstruction can fluctuate. An individual with minimal cyanosis can develop a dynamic increase in right ventricular outflow tract obstruction with a subsequent increase in right-to-left shunt and the development of cyanosis. In the most dramatic situation, there can be near occlusion of the right ventricular outflow tract (RVOT) with profound cyanosis. These episodes are often referred to as "hypercyanotic spells". The exact etiology of these episodes is unclear, although there have been a number of proposed mechanisms, infundibular contractility, peripheral vasodilatation, hyperventilation, and including stimulation of right ventricular mechanoreceptors. increased Treatment Patients with TOF can undergo either palliative (shunts) or corrective (intracardiac repair) surgery. Although most children with TOF undergo intracardiac repair as their initial intervention, the principle of shunts remains an important palliative procedure for infants who may not be acceptable candidates for intracardiac repair due to prematurity, hypoplastic pulmonary arteries, or coronary artery anatomy. Shunts are constructed to increase the blood flow to the lungs, to improve the development of the pulmonary arteries. Many patients who underwent intracardiac repair initially had a palliative shunt. Blalock and Taussig first reported successful surgical palliation of TOF in 1945. The procedure, which https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 22/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology has since come to bear their names, used a subclavian artery to create an aorta-to-pulmonary artery connection. The technique has been modified and is now usually performed using a Gortex tube to create the connection. A different type of shunt is the aortopulmonary anastomis, where a direct connection between the descending aorta and left pulmonary artery (Potts) or between the ascending aorta and the right pulmonary artery (Waterston) is constructed. Intracardiac repair of TOF was reported by Lillehi in 1954. It consists of patch closure of the ventricular septal defect and enlargement of the RVOT. The latter is accomplished by relieving pulmonary stenosis, resecting infundibular and subinfundibular muscle bundles and if necessary by a transannular patch, creating unobstructed flow from the RV into the pulmonary arteries. Outcome A few decades ago the perioperative mortality in TOF patients was rather high (until 25 percent) but gradually declined to the current risk of around 3%. The survival in TOF patients after surgery is, although slightly less than the average population, considerably good. The longest follow-up cohort shows a survival rate of 85% after 35 years. However the rate of morbidity is very high in TOF patients due to a wide range of residual defects, that can increase over time. Therefore all patients with TOF require a lifelong, regular cardiologic follow up. The main complications of TOF include pulmonary regurgitation, residual right ventricular outflow tract obstruction, pulmonary hypertension and residual shunt. Intracardiac repair with a transannular RVOT patch can result in chronic severe pulmonary regurgitation. This leads to RV enlargement and patients may develop decreased exercise tolerance, right heart failure, and arrhythmias. A surgical prosthetic pulmonary valve may be necessary to restore the valve competence and improve RV function and functional status in TOF patients. Residual RVOT obstruction can persist after the original intracardiac operation due to hypertrophied subvalvar muscle, annular hypoplasia, pulmonary valve stenosis, supravalvar pulmonary stenosis, or branch pulmonary artery stenosis. Mild obstruction is usually well tolerated, but significant obstruction may require reoperation or catheter-based intervention. Relief of pulmonary artery stenosis by balloon dilation or stenting may be necessary prior to pulmonary valve replacement. Pulmonary hypertension can be present in TOF patients due to: hypoplastic pulmonary arteries with associated high vascular resistance, excessive shunting across the surgically constructed shunts (mainly Potts or Waterston shunts) or presence of multiple pulmonary artery stenosis. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 23/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology A residual VSD shunt is present in about 20 percent of all operated TOF patients, requiring a reoperation in 5 10 percent of them. Residual shunt might be due to detachment of the patch or an additional septal defect which was not recognized during surgery. Marfan syndrome Case report Introduction Figure 19. Magnetic resonance imaging of the aorta, showing aortic root dilatation in Marfan syndrome. Marfan syndrome (MFS) is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals and is one of the most common inherited disorders of connective tissue. While most MFS patients have an affected parent, around 15 30 percent have a de novo mutation. MFS is associated with a broad range of clinical symptoms and associated disorders, ranging from classic ocular, cardiovascular, and musculoskeletal abnormalities to manifestations including involvement of the lung, skin, and central nervous system. Figure 18. Echocardiographic image of aortic root dilatation in Marfan syndrome. Progressive dilatation of the ascending aorta is one of the key features, which causes a high risk of sudden death due to aortic dissection or rupture in young Marfan patients. (Figure 18 & 19) The underlying genetic defect is localised in the fibrillin gene on chromosome 15 (FBN1) in which recently around 600 different mutations are found. However in about 10% of MFS patients there is no mutation identified in the FBN1 gene, furthermore FBN1 mutations also occur across a wide range of milder phenotypes that overlap the classic Marfan phenotype. Therefore it is not possible to diagnose MFS solely with genetic information. Criteria for diagnosis of Marfan syndrome The 2010 revised Ghent criteria puts greater weight on aortic root aneurysm/dissection and ectopia lentis as the cardinal clinical features of MFS and on testing for mutations in FBN1 and other relevant genes. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 24/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In the absence of family history of MFS, the presence of one of any of the following criteria is diagnostic for MFS: Aortic criterion (aortic diameter Z 2 or aortic root dissection) and ectopia lentis* Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a causal FBN1 mutation Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a systemic score 7 Ectopia lentis and a causal FBN1 mutation as defined above that has been identified in an individual with aortic aneurysm In the presence of family history of MFS (as defined by the above criteria), the presence of one of any of the following criteria is diagnostic for MFS: Ectopia lentis Systemic score 7 points* Aortic criterion (aortic diameter Z 2 above 20 years old, Z 3 below 20 years, or aortic root dissection)* For criteria with an asterisk (*), the diagnosis of MFS can be made only in the absence of discriminating features of Shprintzen-Goldberg syndrome (SGS), Loeys-Dietz syndrome (LDS), or vascular Ehlers- Danlos syndrome (vEDS) and after TGFBR1/2, collagen biochemistry, or COL3A1 testing if indicated. The revised Ghent nosology includes the following scoring system for systemic features: Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point) Pectus carinatum deformity: 2 (pectus excavatum or chest asymmetry: 1 point) Hindfoot deformity: 2 points (plain pes planus:1 point) Pneumothorax: 2 points Dural ectasia: 2 points Protrusio acetabuli: 2 points Reduced upper segment/lower segment ratio (US/LS) AND increased arm span/height AND no severe scoliosis: 1 point Scoliosis or thoracolumbar kyphosis: 1 point Reduced elbow extension ( 170 degrees with full extension): 1 point Facial features (at least 3 of the following 5 features: dolichocephaly [reduced cephalic index or head width/length ratio], enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia): 1 point Skin striae: 1 point Myopia >3 diopters: 1 point Mitral valve prolapse (all types): 1 point A systemic score 7 indicates systemic involvement. Pathophysiology Aortic root disease, leading to aneurysmal dilatation, aortic regurgitation, and dissection, is the main cause of morbidity and mortality in the MFS. Dilatation of the aorta is found in approximately 50 percent of children with MFS and progresses with time. Approximately 60 to 80 percent of adult https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 25/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology patients with MFS have dilatation of the aortic root (with normal range adjusted for patient body surface area and age) by echocardiography, often accompanied by aortic regurgitation. Dilatation may also involve other segments of the thoracic aorta, the abdominal aorta, the root of the pulmonary artery or even the carotid and intracranial arteries. Untreated MFS is frequently associated with aortic dissection, which begins just above the coronary ostia and extends the entire length of the aorta; it is a type I dissection in the DeBakey classification or a type A in the Dailey scheme. Approximately 10 percent of dissections begin distal to the left subclavian (type III or type B) but dissection is rarely limited to just the abdominal aorta. Many patients with MFS and aortic dissection have a family history of dissection. Mitral valve prolapse (MVP) is frequently identified in patients with MFS. However, only one point in the systemic score is assigned for MVP since it is a nonspecific feature and most patients with mitral valve prolapse do not have MFS. The frequency of MVP in MFS increases with age and is greater in women. Tricuspid valve prolapse may also occur. Treatment Beta blockers decrease myocardial contractility and may also improve the elastic properties of the aorta, particularly in patients with an aortic root diameter <40 mm thereby decreasing the risk of aortic dissection and delaying the aortic dilatation. Prophylactic treatment with beta blockers is considered the standard of care in adults with MFS. Furthermore patients with MFS are advised to avoid any contact sports, exercise at maximal capacity, and isometric activities. The exact aortic root diameter at which elective surgery should be performed is uncertain. The current guidelines recommend elective operation for patients with MFS at an external diameter of 50 mm to avoid acute dissection or rupture. Indications for repair at an external diameter less than 50 mm include rapid growth (>2 mm/y), family history of aortic dissection at a diameter less than 50 mm, desire of pregnancy or presence of progressive aortic or mitral valve regurgitation. However one must take into account that a predicted aortic root diameter varies with body size and age and may be smaller in women. Smaller patients have dissection at a smaller aortic root size and 15 percent of patients with MFS have dissection at a diameter less than 50 mm. |
Pulmonary hypertension can be present in TOF patients due to: hypoplastic pulmonary arteries with associated high vascular resistance, excessive shunting across the surgically constructed shunts (mainly Potts or Waterston shunts) or presence of multiple pulmonary artery stenosis. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 23/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology A residual VSD shunt is present in about 20 percent of all operated TOF patients, requiring a reoperation in 5 10 percent of them. Residual shunt might be due to detachment of the patch or an additional septal defect which was not recognized during surgery. Marfan syndrome Case report Introduction Figure 19. Magnetic resonance imaging of the aorta, showing aortic root dilatation in Marfan syndrome. Marfan syndrome (MFS) is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals and is one of the most common inherited disorders of connective tissue. While most MFS patients have an affected parent, around 15 30 percent have a de novo mutation. MFS is associated with a broad range of clinical symptoms and associated disorders, ranging from classic ocular, cardiovascular, and musculoskeletal abnormalities to manifestations including involvement of the lung, skin, and central nervous system. Figure 18. Echocardiographic image of aortic root dilatation in Marfan syndrome. Progressive dilatation of the ascending aorta is one of the key features, which causes a high risk of sudden death due to aortic dissection or rupture in young Marfan patients. (Figure 18 & 19) The underlying genetic defect is localised in the fibrillin gene on chromosome 15 (FBN1) in which recently around 600 different mutations are found. However in about 10% of MFS patients there is no mutation identified in the FBN1 gene, furthermore FBN1 mutations also occur across a wide range of milder phenotypes that overlap the classic Marfan phenotype. Therefore it is not possible to diagnose MFS solely with genetic information. Criteria for diagnosis of Marfan syndrome The 2010 revised Ghent criteria puts greater weight on aortic root aneurysm/dissection and ectopia lentis as the cardinal clinical features of MFS and on testing for mutations in FBN1 and other relevant genes. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 24/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology In the absence of family history of MFS, the presence of one of any of the following criteria is diagnostic for MFS: Aortic criterion (aortic diameter Z 2 or aortic root dissection) and ectopia lentis* Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a causal FBN1 mutation Aortic criterion (aortic diameter Z 2 or aortic root dissection) and a systemic score 7 Ectopia lentis and a causal FBN1 mutation as defined above that has been identified in an individual with aortic aneurysm In the presence of family history of MFS (as defined by the above criteria), the presence of one of any of the following criteria is diagnostic for MFS: Ectopia lentis Systemic score 7 points* Aortic criterion (aortic diameter Z 2 above 20 years old, Z 3 below 20 years, or aortic root dissection)* For criteria with an asterisk (*), the diagnosis of MFS can be made only in the absence of discriminating features of Shprintzen-Goldberg syndrome (SGS), Loeys-Dietz syndrome (LDS), or vascular Ehlers- Danlos syndrome (vEDS) and after TGFBR1/2, collagen biochemistry, or COL3A1 testing if indicated. The revised Ghent nosology includes the following scoring system for systemic features: Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point) Pectus carinatum deformity: 2 (pectus excavatum or chest asymmetry: 1 point) Hindfoot deformity: 2 points (plain pes planus:1 point) Pneumothorax: 2 points Dural ectasia: 2 points Protrusio acetabuli: 2 points Reduced upper segment/lower segment ratio (US/LS) AND increased arm span/height AND no severe scoliosis: 1 point Scoliosis or thoracolumbar kyphosis: 1 point Reduced elbow extension ( 170 degrees with full extension): 1 point Facial features (at least 3 of the following 5 features: dolichocephaly [reduced cephalic index or head width/length ratio], enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia): 1 point Skin striae: 1 point Myopia >3 diopters: 1 point Mitral valve prolapse (all types): 1 point A systemic score 7 indicates systemic involvement. Pathophysiology Aortic root disease, leading to aneurysmal dilatation, aortic regurgitation, and dissection, is the main cause of morbidity and mortality in the MFS. Dilatation of the aorta is found in approximately 50 percent of children with MFS and progresses with time. Approximately 60 to 80 percent of adult https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 25/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology patients with MFS have dilatation of the aortic root (with normal range adjusted for patient body surface area and age) by echocardiography, often accompanied by aortic regurgitation. Dilatation may also involve other segments of the thoracic aorta, the abdominal aorta, the root of the pulmonary artery or even the carotid and intracranial arteries. Untreated MFS is frequently associated with aortic dissection, which begins just above the coronary ostia and extends the entire length of the aorta; it is a type I dissection in the DeBakey classification or a type A in the Dailey scheme. Approximately 10 percent of dissections begin distal to the left subclavian (type III or type B) but dissection is rarely limited to just the abdominal aorta. Many patients with MFS and aortic dissection have a family history of dissection. Mitral valve prolapse (MVP) is frequently identified in patients with MFS. However, only one point in the systemic score is assigned for MVP since it is a nonspecific feature and most patients with mitral valve prolapse do not have MFS. The frequency of MVP in MFS increases with age and is greater in women. Tricuspid valve prolapse may also occur. Treatment Beta blockers decrease myocardial contractility and may also improve the elastic properties of the aorta, particularly in patients with an aortic root diameter <40 mm thereby decreasing the risk of aortic dissection and delaying the aortic dilatation. Prophylactic treatment with beta blockers is considered the standard of care in adults with MFS. Furthermore patients with MFS are advised to avoid any contact sports, exercise at maximal capacity, and isometric activities. The exact aortic root diameter at which elective surgery should be performed is uncertain. The current guidelines recommend elective operation for patients with MFS at an external diameter of 50 mm to avoid acute dissection or rupture. Indications for repair at an external diameter less than 50 mm include rapid growth (>2 mm/y), family history of aortic dissection at a diameter less than 50 mm, desire of pregnancy or presence of progressive aortic or mitral valve regurgitation. However one must take into account that a predicted aortic root diameter varies with body size and age and may be smaller in women. Smaller patients have dissection at a smaller aortic root size and 15 percent of patients with MFS have dissection at a diameter less than 50 mm. The classic aortic root surgery is the Bentall procedure in which the ascending aorta is replaced, together with the aortic valve, by a graft with prosthetic valve. In this procedure the coronary arteries need to be reimplanted in the aortic graft. In patients with anatomically normal valves, in whom the insuf ciency is due to the dilated annulus or dissection, valve-sparing operations with root replacement by a Dacron prosthesis and with reimplantation of the coronary arteries into the prosthesis (David s procedure) or remodelling of the aortic root (Yacoub s procedure) have now become the preferred surgical procedures. Aortic regurgitation is, however, a common complication, requiring reoperation in 20% of patients after 10 years. Outcome The reported operative mortality of the Bentall procedure is 1.5% for elective and 11.7% for emergency operations. Five- and 10-year survival rates of 84 and 75%, respectively, have been reported. This relatively limited prognosis is due to late sequelae associated with MFS; 75% require reoperations, 10% mitral valve surgery, 1% develop endocarditis and 1% a CVA. Marfan syndrome has also been associated https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 26/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology with a considerably higher risk of re-dissection and recurrent aneurysm than other aetiologies of aortic disease. Long-term results of valvesparing aortic root replacement in Marfan syndrome are still unknown. Ebsteins anomaly Case report Introduction Figure 21. Schematic drawing showing Ebstein s anomaly of the tricuspid valve. Left: normal heart with openend right ventricle. Right: Ebstein s anomaly with displacement of the septal and posterior tricuspid leaflet, leading to atrialisation of a significant part of the right ventricle. Ebsteins anomaly, named after Wilhelm Ebstein (1836 1912) (Figure 20) is a congenital heart defect of the tricuspid valve. The prevalence of morphological Figure 20. Wilhelm Ebstein (1836 1912). Ebstein's anomaly is about 1 in 50.000 200.000 with a similar incidence in both males and females. As its name clearly indicates, the tricuspid valve consists of three leaflets; anterosuperior, septal and inferior. The Ebstein s anomaly consists of a variety of anatomical and functional abnormalities of the tricuspid valve. Typical features are: displacement of the septal and inferior leaflet downwards from the atrioventricular junction and toward the body of the right ventricle or the apex the anterior leaflet is not displaced, enlarged (sail-like) and can show fenestrations the tricuspid valve inlet is displaced towards the right ventricular outflow tract and often stenotic atrialisation of the right ventricle because of a downward extension of the tricuspid valve, leaving a small right ventricle or only a right ventricular outflow tract Pathophysiology https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 27/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology The Ebstein s anomaly can be isolated or associated with other cardiac defects like ASD or patent foramen ovale, pulmonary outflow tract obstruction, VSD, coarctation of the aorta, ccTGA, one or more accessory conduction pathways or patent ductus arteriosus. The primary hemodynamic consequence of Ebstein s anomaly is tricuspid regurgitation (TR), which varies in severity. Severe TR causes a volume overload and right-sided cardiac chamber dilation and dysfunction, leading to a decrease in cardiac output. In some cases even hepatic congestion and failure can arise. Ebstein's anomaly can be classified as mild, moderate, or severe based upon the extent of apical displacement of the valve leaflets with resultant tricuspid regurgitation, and the degree of right ventricular dysfunction. Symptoms such as cyanosis and heart failure from severe TR may appear soon after birth, because of high pulmonary vascular resistance. However, symptoms often improve as pulmonary vascular resistance decreases. At a later age, symptoms such as exertional dyspnea, fatigue, cyanosis, and palpitations may recur; these symptoms may be insidious in onset. Palpitations due to atrial tachyarrhythmia are present in 20 to 30 percent of cases. Some of these arrhythmias may be due to Wolff-Parkinson-White syndrome, since up to 20 percent of patients have one or more accessory pathways; the majority of these pathways are located around the orifice of the malformed tricuspid valve. Patients with Ebstein's anomaly who have an interatrial communication are at risk for paradoxical embolization, brain abscesses, and sudden death. Treatment Indications for surgical tricuspid valve repair or replacement are: decrease in exercise capacity progressive cyanosis progressive right ventricular dilatation or dysfunction occurrence of paradoxal embolism supraventricular arrhythmias despite pharmacological or ablation therapy progressive cardiomegaly on chest radiograph There are two main surgical techniques used in tricuspid valve repair. The Danielson repair consists of horizontally plicating the atrialized portion of the RV while multiple commissuroplasty stitches are placed. The Carpentier technique consists of detaching the large sail-like anterior leaflet from the valve annulus and translocating it in a clockwise division in order to create what essentially becomes a single leaflet valve. The atrialized portion of the RV is plicated but in a vertical not a horizontal fashion. If repair is not possible and the patient has reached adult size, tricuspid valve replacement becomes necessary. A biologic prosthesis, such as a porcine valve, is usually chosen because of the high incidence of thromboembolism with a mechanical prosthesis placed in the right heart. Outcome The prognosis varies with the severity of the disease. The 1 and 10 year survival rates for all liveborn patients have been estimated 67 percent and 59 percent respectively. The major causes of death are heart failure, perioperative, and sudden death. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 28/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology However, survival is probably increasing as advances in diagnostic and surgical techniques and postoperative care have led to improvements in surgical outcome. Pulmonary hypertension Case report Introduction Pulmonary hypertension (PH) is a progressive life-threatening condition and associated with a high rate of mortality, despite medical intervention. PH is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. The definition of pulmonary hypertension (PH) is based upon right heart catheterization where PH is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest. Classification PH is classified into five groups: 1. Pulmonary arterial hypertension (PAH). This group consists of idiopathic PAH and PAH due to connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn, pulmonary veno-occlusive disease, drug- and toxin-induced PH and pulmonary capillary hemangiomatosis. 2. Pulmonary hypertension owing to left heart disease. PH due to systolic dysfunction, diastolic dysfunction, or valvular heart disease is included in this group. 3. Pulmonary hypertension owing to lung diseases or hypoxemia. This group includes PH due to chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with a mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, and other causes of hypoxemia [4]. 4. Chronic thromboembolic pulmonary hypertension. This group includes patients with PH due to thromboembolic occlusion of the proximal or distal pulmonary vasculature. 5. Pulmonary hypertension with unclear multifactorial mechanisms. These patients have PH caused by hematologic disorders (eg, myeloproliferative disorders), systemic disorders (eg, sarcoidosis), metabolic disorders (eg, glycogen storage disease), or miscellaneous causes Pulmonary arterial hypertension in congenital heart disease In approximately 6% of adults with congenital heart disease PAH develops. In fact congenital heart disease has emerged to be one of the commonest associated causes of PAH. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 29/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology The occurrence of PAH in congenital heart disease is usually the result of systemic-to-pulmonary shunting, leading to a blood volume overload of the pulmonary vasculature. Left to right shunts are most common; VSD, ASD, patent ductus arteriosus or AVSD. Pathophysiology The pathogenesis of PH is complex and just beginning to be elucidated. In patients with congenital heart disease, left-to-right intracardiac shunting increases flow through the pulmonary vasculature, this causes shear forces that disrupt the vascular endothelium and activate cellular mechanisms critical to the pathogenesis and progression of PAH. The mechanism of damage to the pulmonary vasculature differs in patients with ASD compared to VSD. Vascular injury is related to the degree and duration of volume overload alone with an ASD, whereas high pressure shear forces also contribute with a VSD. Figure 22. Photo showing typical features of chronic hypoxemia in Eisenmenger syndrome, with typical digital clubbing with cyanotic nail beds. In patients with an ASD, shunting is delayed until maturation of the pulmonary vasculature occurs. The normal pulmonary vasculature is able to accommodate the increased volume of flow by vasodilating and recruiting previously unperfused vessels; thus, pulmonary artery pressures do not rise significantly in most patients with an ASD until adult life. In contrast to patients with an ASD, clinical sequelae always develop in patients with a large (nonrestrictive) VSD. Severe PAH is present from birth because of the unique hemodynamics. The combined effect of volume overload and shear forces elevates the pulmonary vascular resistance, which becomes fixed during childhood. As a result, shunt reversal (right-to-left flow) is common, with hypoxemia resulting. This is often referred to as the Eisenmenger syndrome. Eisenmenger syndrome forms a small percentage (1%) of CHD patients and is defined as CHD with an initial large systemic-to-pulmonary shunt that induces progressive pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. Eisenmenger syndrome represents the most advanced form of PAH associated with CHD. An important subgroup in this Eisenmenger population is patients with Down syndrome. Classification Pulmonary arterial hypertension in congenital heart disease can be divided into four quite distinct phenotypes, which may be feasible to use in clinical practice. A. Eisenmenger syndrome. This includes all systemic-to-pulmonary shunts resulting from large defects and leading to a severe increase in pulmonary vascular resistance (PVR) and a reversed (pulmonary-to- systemic) or bidirectional shunt; cyanosis, erythrocytosis, and multiple organ involvement are present. B. PAH associated with systemic-to-pulmonary shunts. This includes moderate to large defects; PVR is mildly to moderately increased, systemic-to-pulmonary shunt is still prevalent, and no cyanosis is present at rest. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 30/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology C. PAH associated with small defects. This includes small defects (usually VSD<1 cm and ASD <2 cm of effective diameter assessed by echocardiography). D. PAH after corrective cardiac surgery. In this group of patients the congenital heart disease has been corrected, but PAH is still present immediately after surgery or recurs several months or years after surgery in the absence of significant postoperative residual lesions. Treatment Early treatment of PH is generally suggested because advanced disease may be less responsive to therapy. PAH is characterized by symptoms of dyspnea, fatigue, chest pain, and syncope. Primary therapeutic strategy should be considered in all patients with PAH and consists of diuretic, oxygen, anticoagulant, and digoxin therapy, as well as exercise and lifestyle advices. Injured endothelial cells release factors that are known to contribute to PAH. Inhibition of these factors forms the basis of some of the advanced therapies for PAH. Patients with CHD-PAH who progress to NYHA functional class II, III, or IV, qualify for advanced therapy. This is irrespective of any primary therapy given. Advanced therapy is directed at the PAH itself, rather than the underlying cause of the PAH. For PAH treatments with advanced therapy three main pathways have been detected: prostacyclin, nitric oxide and endothelin-1.This resulted in therapies with prostanoids such as epoprostenol, phosphodiesterase-5 inhibitors such as sildenafil and endothelin-1 receptor antagonists such as bosentan. Outcome The prognosis is generally poor but varies according to the severity of the underlying cause, the functional abnormalities, and the hemodynamic abnormalities. Factors that may indicate a poor prognosis include age at presentation greater than 45 years, NYHA functional class III or IV, failure to improve to a lower NYHA functional class during treatment, pericardial effusion, large right atrial size, elevated right atrial pressure, septal shift during diastole, decreased pulmonary arterial capacitance (ie, the stroke volume divided by the pulmonary arterial pulse pressure) and increased N-terminal brain natriuretic peptide level. Therapy improves exercise capacity and functional class, however the impact on mortality has been less well established. References 1. Basow, D. S. (2012a). Classification and clinical features of isolated atrial septal defects in children. UpToDate. Waltham, MA.: UpToDate. 2. Basow, D. S. (2012b). Management of atrial septal defects in adults. UpToDate. Waltham, MA.: UpToDate. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 31/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 3. Basow, D. S. (2012c). Management and outcome of isolated atrial septal defects in children. UpToDate. Waltham, MA.: UpToDate. 4. Basow, D. S. (2012d). Pathophysiology and clinical features of atrial septal defects in adults. UpToDate. Waltham, MA.: UpToDate. 5. Basow, D. S. (2012e). Identification and assessment of atrial septal defects in adults. UpToDate. Waltham, MA.: UpToDate. 6. Basow, D. S. (2012f). Devices for percutaneous closure of a secundum atrial septal defect. UpToDate. Waltham, MA.: UpToDate. 7. Berger, F., Vogel, M., Alexi-Meskishvili, V., & Lange, P. E. (1999). Comparison of results and complications of surgical and Amplatzer device closure of atrial septal defects. The Journal of Thoracic and Cardiovascular Surgery, 118(4), 674-678; discussion 678-680 8. Engelfriet, P., Boersma, E., Oechslin, E., Tijssen, J., Gatzoulis, M. A., Thil n, U., Kaemmerer, H., e.a. (2005). The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. European Heart Journal, 26(21), 2325-2333. doi:10.1093/eurheartj/ehi396 9. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006a). Atrial Septal Defect. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 10. Roos-Hesselink, J. W., Meijboom, F. J., Spitaels, S. E. C., van Domburg, R., van Rijen, E. H. M., Utens, E. M. W. J., Bogers, A. J. J. C., e.a. (2003). Excellent survival and low incidence of arrhythmias, stroke and heart failure long-term after surgical ASD closure at young age. A prospective follow-up study of 21-33 years. European Heart Journal, 24(2), 190-197. 11. Basow, D. S. (2012h). Pathophysiology and clinical features of isolated ventricular septal defects in infants and children. UpToDate. Waltham, MA.: UpToDate. 12. Basow, D. S. (2012i). Management of isolated ventricular septal defects in infants and children. UpToDate. Waltham, MA.: UpToDate. 13. Baumgartner, H., Bonhoeffer, P., De Groot, N. M. S., de Haan, F., Deanfield, J. E., Galie, N., Gatzoulis, M. A., e.a. (2010). ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). European Heart Journal, 31(23), 2915-2957. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 32/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 14. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006b). Ventricular Septal Defect. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 15. Verheugt, C. L., Uiterwaal, C. S. P. M., Grobbee, D. E., & Mulder, B. J. M. (2008). Long-term prognosis of congenital heart defects: a systematic review. International Journal of Cardiology, 131(1), 25-32. 16. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Patent Ductus Arteriosus. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum 17. Rudolph, A. M. (1970). The changes in the circulation after birth. Their importance in congenital heart disease. Circulation, 41(2), 343-359. 18. Ijland, M. M., & Tanke, R. B. (2009). Aortic coarctation. Circulation, 120(13), 1294-1295. 19. Luijendijk, P, Boekholdt, S. M., Blom, N. A., Groenink, M., Backx, A. P., Bouma, B. J., Mulder, B. J. M., e.a. (2011). Percutaneous treatment of native aortic coarctation in adults. Netherlands Heart Journal: Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 19(10), 436-439. 20. Luijendijk, Paul, Bouma, B. J., Vriend, J. W. J., Vliegen, H. W., Groenink, M., & Mulder, B. J. M. (2011). Usefulness of exercise-induced hypertension as predictor of chronic hypertension in adults after operative therapy for aortic isthmic coarctation in childhood. The American Journal of Cardiology, 108(3), 435-439. 21. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Coarctation of the aorta. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 22. Vriend, J. W. J., & Mulder, B. J. M. (2005). Late complications in patients after repair of aortic coarctation: implications for management. International Journal of Cardiology, 101(3), 399-406. 23. Vriend, J. W. J., Oosterhof, T., & Mulder, B. (2005). Noninvasive imaging for the postoperative assessment of aortic coarctation patients. Chest, 127(6), 2295. 24. Drenthen, W., Pieper, P. G., Ploeg, M., Voors, A. A., Roos-Hesselink, J. W., Mulder, B. J. M., Vliegen, H. W., e.a. (2005). Risk of complications during pregnancy after Senning or Mustard (atrial) repair of complete transposition of the great arteries. European Heart Journal, 26(23), 2588-2595. doi:10.1093/eurheartj/ehi472 https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 33/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 25. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Transposition of the great arteries. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 26. van der Zedde, J., Oosterhof, T., Tulevski, I. I., Vliegen, H. W., & Mulder, B. J. M. (2005). Comparison of segmental and global systemic ventricular function at rest and during dobutamine stress between patients with transposition and congenitally corrected transposition. Cardiology in the Young, 15(2), 148-153. doi:10.1017/S1047951105000326 27. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Congenitally corrected transposition of the great arteries. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 28. Winlaw, D. S., McGuirk, S. P., Balmer, C., Langley, S. M., Griselli, M., St mper, O., De Giovanni, J. V., e.a. (2005). Intention-to-treat analysis of pulmonary artery banding in conditions with a morphological right ventricle in the systemic circulation with a view to anatomic biventricular repair. Circulation, 111(4), 405-411. 29. Winter, M. M., Bouma, B. J., van Dijk, A. P. J., Groenink, M., Nieuwkerk, P. T., van der Plas, M. N., Sieswerda, G. T., e.a. (2008). Relation of physical activity, cardiac function, exercise capacity, and quality of life in patients with a systemic right ventricle. The American Journal of Cardiology, 102(9), 1258-1262. 30. Winter, M. M., van der Bom, T., de Vries, L. C. S., Balducci, A., Bouma, B. J., Pieper, P. G., van Dijk, A. P. J., e.a. (2011). Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial. European Heart Journal. 31. Winter, M. M., van der Plas, M. N., Bouma, B. J., Groenink, M., Bresser, P., & Mulder, B. J. M. (2010). Mechanisms for cardiac output augmentation in patients with a systemic right ventricle. International Journal of Cardiology, 143(2), 141-146. 32. Basow, D. S. (2012). Hypoplastic left heart syndrome. UpToDate. Waltham, MA.: UpToDate. 33. Basow, D. S. (2012). Hypoplastic left heart syndrome. UpToDate. Waltham, MA.: UpToDate. 34. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Univentricular heart and the Fontan circulation. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 35. Schuuring, M. J., Vis, J. C., Bouma, B. J., van Dijk, A. P. J., van Melle, J. P., Pieper, P. G., Vliegen, H. W., e.a. (2011). Rationale and design of a trial on the role of bosentan in Fontan patients: Improvement of exercise capacity? Contemporary Clinical Trials, 32(4), 586-591. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 34/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 35. Schuuring, Mark J, Vis, J. C., Duffels, M. G., Bouma, B. J., & Mulder, B. J. (2010). Adult patients with pulmonary arterial hypertension due to congenital heart disease: a review on advanced medical treatment with bosentan. Therapeutics and Clinical Risk Management, 6, 359-366. 36. van den Bosch, A. E., Roos-Hesselink, J. W., Van Domburg, R., Bogers, A. J. J. C., Simoons, M. L., & Meijboom, F. J. (2004). Long-term outcome and quality of life in adult patients after the Fontan operation. The American Journal of Cardiology, 93(9), 1141-1145. 37. Balci, A., Drenthen, W., Mulder, B. J. M., Roos-Hesselink, J. W., Voors, A. A., Vliegen, H. W., Moons, P., e.a. (2011). Pregnancy in women with corrected tetralogy of Fallot: occurrence and predictors of adverse events. American Heart Journal, 161(2), 307-313. 38. Lillehei, C. W., Cohen, M., Warden, H. E., Read, R. C., Aust, J. B., Dewall, R. A., & Varco, R. L. (1955). Direct vision intracardiac surgical correction of the tetralogy of Fallot, pentalogy of Fallot, and pulmonary atresia defects; report of first ten cases. Annals of Surgery, 142(3), 418-442. 39. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Tetralogy of Fallot. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 40. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Marfan s syndrome. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 40. Mulder, Barbara J M, & van der Wall, E. E. (2009). Tetralogy of Fallot: in good shape? The International Journal of Cardiovascular Imaging, 25(3), 271-275. 41. Oosterhof, T., Mulder, B. J. M., Vliegen, H. W., & de Roos, A. (2006). Cardiovascular magnetic resonance in the follow-up of patients with corrected tetralogy of Fallot: a review. American Heart Journal, 151(2), 265-272. 42. Vliegen, H. W., van Straten, A., de Roos, A., Roest, A. A. W., Schoof, P. H., Zwinderman, A. H., Ottenkamp, J., e.a. (2002). Magnetic resonance imaging to assess the hemodynamic effects of pulmonary valve replacement in adults late after repair of tetralogy of fallot. Circulation, 106(13), 1703-1707. 43. Windhausen, F., Boekholdt, S. M., Bouma, B. J., Groenink, M., Backx, A. P. C. M., de Winter, R. J., Mulder, B. J. M., e.a. (2011). Per-operative stent placement in the right pulmonary artery; a hybrid technique for the management of pulmonary artery branch stenosis at the time of pulmonary valve replacement in adult Fallot patients. Netherlands Heart Journal: Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 19(10), 432-435. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 35/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 44. de Witte, Piet, Aalberts, J. J. J., Radonic, T., Timmermans, J., Scholte, A. J., Zwinderman, A. H., Mulder, B. J. M., e.a. (2011). Intrinsic biventricular dysfunction in Marfan syndrome. Heart (British Cardiac Society), 97(24), 2063-2068. 45. Engelfriet, P., & Mulder, B. (2007). Is there benefit of beta-blocking agents in the treatment of patients with the Marfan syndrome? International Journal of Cardiology, 114(3), 300-302. 46. Radonic, T, de Witte, P., Groenink, M., de Bruin-Bon, R., Timmermans, J., Scholte, A., van den Berg, M., e.a. (2011). Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Clinical Genetics. 47. Basow, D. S. (2012). Ebstein s anomaly of the tricuspid valve. UpToDate. Waltham, MA.: UpToDate. 48. Carpentier, A., Chauvaud, S., Mac , L., Relland, J., Mihaileanu, S., Marino, J. P., Abry, B., e.a. (1988). A new reconstructive operation for Ebstein s anomaly of the tricuspid valve. The Journal of Thoracic and Cardiovascular Surgery, 96(1), 92-101. 49. Celermajer, D. S., Bull, C., Till, J. A., Cullen, S., Vassillikos, V. P., Sullivan, I. D., Allan, L., e.a. (1994). Ebstein s anomaly: presentation and outcome from fetus to adult. Journal of the American College of Cardiology, 23(1), 170-176. 50. Ebstein W. (1866) Ueber einen sehr seltenen Fall von Insufficienz der Valvula tricuspidalis, bedingt durch eine angeborene hochgradige Missbildung. Arch Anat physiol;33:238. 51. Mulder, B. J. M. (2002). Ebstein s anomaly in adults. The International Journal of Cardiovascular Imaging, 18(6), 439-441. 52. Mulder, B. J. M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Ebstein anomaly of the tricuspid valve. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 53. Beghetti, Maurice, & Tissot, C. (2009). Pulmonary arterial hypertension in congenital heart diseases. Seminars in Respiratory and Critical Care Medicine, 30(4), 421-428. 54. Beghetti, Maurice, & Tissot, C. (2010). Pulmonary hypertension in congenital shunts. Revista Espa ola De Cardiolog a, 63(10), 1179-1193. 55. Duffels, M G J, Engelfriet, P. M., Berger, R. M. F., van Loon, R. L. E., Hoendermis, E., Vriend, J. W. J., van der Velde, E. T., e.a. (2007). Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. International Journal of Cardiology, 120(2), 198- https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 36/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology 204. 56. Engelfriet, Peter M, Duffels, M. G. J., M ller, T., Boersma, E., Tijssen, J. G. P., Thaulow, E., Gatzoulis, M. A., e.a. (2007). Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart (British Cardiac Society), 93(6), 682-687. 57. Galie, N., Hoeper, M. M., Humbert, M., Torbicki, A., Vachiery, J.-L., Barbera, J. A., Beghetti, M., e.a. (2009). Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). European Heart Journal, 30, 2493-2537. 58. Gatzoulis, M A, Alonso-Gonzalez, R., & Beghetti, M. (2009). Pulmonary arterial hypertension in paediatric and adult patients with congenital heart disease. European Respiratory Review: An Official Journal of the European Respiratory Society, 18(113), 154-161. 59. Lau, E. M. T., Manes, A., Celermajer, D. S., & Gali , N. (2011). Early detection of pulmonary vascular disease in pulmonary arterial hypertension: time to move forward. European Heart Journal, 32(20), 2489-2498. 60. Mulder, B J M. (2010). Changing demographics of pulmonary arterial hypertension in congenital heart disease. European Respiratory Review: An Official Journal of the European Respiratory Society, 19(118), 308-313. doi:10.1183/09059180.00007910 61. Mulder, B.J.M., Pieper, P. G., Meijboom, F. J., & Hamer, J. P. M. (2006). Eisenmenger syndrome. Adult Congenital Heart Disease (Aangeboren hartafwijkingen bij volwassenen) (Second edition.). Houten: Bohn Stafleu van Loghum. 62. Schuuring, M J, van Riel, A. C. M. J., Bouma, B. J., & Mulder, B. J. M. (2011). Recent progress in treatment of pulmonary arterial hypertension due to congenital heart disease. Netherlands Heart Journal: Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 19(12), 495-497. 63. Simonneau, G., Robbins, I. M., Beghetti, M., Channick, R. N., Delcroix, M., Denton, C. P., Elliott, C. G., e.a. (2009). Updated clinical classification of pulmonary hypertension. Journal of the American College of Cardiology, 54(1 Suppl), S43-54. 64. Vis, J. C., Duffels, M. G., Mulder, P., de Bruin-Bon, R. H. A. C. M., Bouma, B. J., Berger, R. M. F., Hoendermis, E. S., e.a. (2011). Prolonged beneficial effect of bosentan treatment and 4-year survival rates in adult patients with pulmonary arterial hypertension associated with congenital heart disease. International Journal of Cardiology. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 37/38 7/4/23, 12:41 AM Grown-up Congenital Heart Disease (GUCH) - Textbook of Cardiology Retrieved from "http://www.textbookofcardiology.org/index.php?title=Grown- up_Congenital_Heart_Disease_(GUCH)&oldid=927" This page was last edited on 1 February 2012, at 16:52. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Grown-up_Congenital_Heart_Disease_(GUCH) 38/38 |
7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Heart Failure Contents Introduction History Framingham heart study Definition and diagnosis Definition of heart failure Prevalence Acute and chronic heart failure Systolic versus diastolic heart failure Pathophysiology of heart failure Management Clinical aspects History Symptoms and signs Severity of HF Physical examination Additional diagnostic tests Electrocardiogram Chest X-ray Echocardiography Laboratory tests Exercise test Heart catheterization Etiology of heart failure Coronary heart disease Hypertension Heart rhythm disorders Valvular disease Cardiomyopathies Pericardial disease and Tamponade Drugs Toxins Endocrine disorders Nutritional status Infiltrative and storage disorders Infectious disease Management in investigating etiology of heart failure https://www.textbookofcardiology.org/wiki/Heart_Failure 1/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Therapy of heart failure Non-pharmacological treatment Education Fluid and sodium restriction Body weight Alcohol and tobacco Exercise Other Pharmacological treatment Angiotensin-converting enzyme (ACE) inhibitors Beta Blockers Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists) Loop of Henle diuretics Thiazides Aldosterone antagonists Choice and combination of diuretics Angiotensin receptor blockers (ARBs) Digoxin Ivabradine Hydralazine and isosorbide dinitrate (H-ISDN) Other Therapy of acute heart failure Management of HF beyond medication Device treatment Timing of ICD implantation Heart transplantation and Left Ventricular Assist Devices Management of HF patients with preserved LVEF (HFPEF) Prognosis References Ineke Nederend MSc, Peter Damman MD, W.E.M. Kok MD PhD Introduction History In 1628, William Harvey first described the circulation. Before this time, there was very little understanding of the nature of heart failure (HF). There are, however, accounts of a disease that now would be called heart failure, and herbal medicines such as the ancient boiled bulb of squill, or, later on, the broom plant (Cytisus scoparius) and the foxglove (Digitalis purpura) were used as diuretics to treat https://www.textbookofcardiology.org/wiki/Heart_Failure 2/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology heart failure or dropsy (edema). Foxglove was described as a diuretic by William Withering in 1785.[1] The essential glycoside substance digitalis of the leaves of the plant improves contractility of the cardiac muscle and has important parasympathetic effects, particularly on the atrioventricular node. In the 1950s, thiazide diuretics were introduced, and in the 1960s furosemide became available. For a long time, diuretics and digitalis were the main treatment options for HF. Vasodilator therapy for HF was introduced around 1960, and the first randomized trial showing a mortality benefit with nitrates and alphablockers for HF was published in 1986. In 1975, the first ACE inhibitor, captopril, was developed and it was approved for human use in 1981, in 1987. with data from the first randomized trial being published Spironolacton, introduced in 1959, was used (in low dose) for HF only after the introduction of ACE inhibitors. Beta blockers were hardly used in heart failure even though they were shown to beneficial in the 1970s. It was only in 1994 that data from the first randomized trial demonstrated a mortality benefit with beta blocker therapy. Foxglove (digitalis), used as a medicine for heart failure. Framingham heart study In 1948, the Framingham heart study was launched. At its start, 5209 residents of the town Framingham in the USA, aged between 30 and 62 years, were included in the study in an attempt to determine risk factors for cardiac disease. The study is still in progress today and long term data from the lengthy follow up have been published. This study is considered to be the most important longitudinal source of data on the epidemiology of heart failure[2]. Definition and diagnosis Definition of heart failure The term heart failure (HF) (congestive heart failure or cardiac decompensation or decompensatio cordis) describes an acute or chronic situation in which the amount of blood pumped through the circulation by the heart, is insufficient to meet the body s demands at a normal cardiac filling pressure. According to the guidelines of the European Society of Cardiology, HF is defined as a syndrome in which the patient has the following triad of features: (1) symptoms typical of HF; (2) signs typical of HF; and most importantly (3) objective evidence of a structural or functional abnormality of the heart at rest (Table 1). https://www.textbookofcardiology.org/wiki/Heart_Failure 3/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 1. Definition of heart failure Heart failure is a clinical syndrome in which patients have the following features: Symptoms typical of heart failure Breathlessness Orthopnoea Paroxysmal nocturnal dyspnoea Reduced exercise tolerance Fatigue Tiredness Ankle swelling And Signs typical of heart failure Elevated jugular venous pressure Hepatomegaly Third heart sound Pulmonary rales Pleura effusion Peripheral oedema Hepatojugular reflux Cardiomegaly on X-ray of the thorax And Objective evidence of a structural or functional abnormality of the heart at rest Abnormal echocardiogram Abnormal pump function on nuclear imaging or on MRI Prevalence The prevalence of HF in the Western world is estimated to be 1-2%, and the incidence is approximately 5-10 per 1000 persons per year (7,9). Coronary heart disease at a young age is more prevalent in men than women, and so the prevalence of HF is also higher in this group compared to age matched women. In older age groups, the prevalence of HF is equal between the sexes. Acute and chronic heart failure Heart failure may become a chronic condition, in which HF is persistent either with recurrences or with slow progression. A patient may be described as decompensated when chronic stable HF deteriorates. Acute HF has traditionally been used to describe the nature of the clinical presentation, as severe or of recent onset. Different clinical presentations fall under this definition. Systolic versus diastolic heart failure https://www.textbookofcardiology.org/wiki/Heart_Failure 4/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Heart failure patients may be broadly classified into one of two groups, or a combination of both, depending on the left ventricular ejection fraction (LVEF). The LVEF is most often assessed with echocardiography (see Table 3). When the LVEF is less than 45%, systolic pump function is abnormal and it is named systolic HF.[3] If LVEF is preserved (>50%), symptoms are attributed to impaired relaxation of the heart during diastole and therefore this condition is diagnosed as diastolic HF or HF with a preserved LVEF.[3][4] As a result of impaired relaxation, end diastolic pressure and, subsequently, left atrial- and pulmonary pressure will rise; alveolar pulmonary edema develops as a consequence of these changes. LF diastolic dysfunction may be present in asymptomatic patients, and it is considered an important precursor of heart failure.[5] Frequently, patients have both systolic and diastolic heart failure at the same time, but the term for this ailment is still systolic heart failure. The term heart failure is not limited to a failing left ventricle; the right ventricle may also be involved in the process and there may also be isolated right ventricular heart failure. Pathophysiology of heart failure HF is caused by a loss of cardiac pump function, which can be due to a structural abnormality of the heart muscle (e.g. myocardial infarction) or a change in the heart function (and often structure) in response to an abnormal load (e.g. aortic valve stenosis). The relationship between loading the ventricle (by filling it) and its output was described by Frank and Starling in 1918 and has become the cornerstone in understanding heart failure and how to treat it. The relationship states that as a result of loading the heart (increasing its filling or its pressure), the output increases (Figure 1). A heart that has a lower output can be improved by increasing loading its volume and pressure. This is what naturally happens filling (LV dilatation and pressure) when the heart does not pump out enough volume, and, in the first phase of disease, compensates for the loss of contractility. It takes more energy from the heart to work at an increased loading, but the heart has a reasonable energy reserve. In a chronic situation, remodeling of the heart progresses (by hypertrophy of the myocytes and dilatation by increasing myocyte length and matrix changes), which, in the long term, leads to a further loss in function. The result of this dysfunction is further increased loading pressures in the heart and, by communicating the diastolic loading pressures to the left atrium and pulmonary veins, the pulmonary capillaries may become overloaded and leak water into the lungs. This is the practical restriction of further filling the heart as a tool to improve its function; even poor left ventricles may be filled more to increase their output [6] but the patients pulmonary capillaries cannot tolerate these hydrostatic pressures and start to leak water. its Figure 1. Frank-Starling curve increased Hemodynamic explanations (the heart as a pump) use the concept of preload (filling) and afterload (workload of the heart, which is wall tension and arterial pressure or vascular resistance). In this way, the progression of left sided heart failure towards right sided heart failure is explained as follows: prolonged left ventricular failure increases pressures in the left atrium (preload), which in time leads to a https://www.textbookofcardiology.org/wiki/Heart_Failure 5/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology subsequent increased resistance in the pulmonary vascular system (which is the the right ventricle) and afterload of right lead eventually may also ventricular failure. Another relevant issue is afterload of the left ventricle influencing the output of the heart: as the afterload of the aortic pressure also influences the timing of closure of the aortic valve, a high aortic pressure will close the aortic valve early and will, therefore, diminish the output. Decreasing (theoretically diastolic, but more practically systolic) aortic pressure will increase the stroke volume by latter closure of the aortic valves. (Figure 2) to system sympathetic Hormonal/ mechanisms Sympathetic (RAAS/ overstimulation) of heart failure are as hemodynamic important mechanisms of heart failure. as the Figure 2. Effects of decreased afterload. Red arrows indicate aortic valve opening, which occurs later and at higher LV systolic pressure when the diastolic aortic pressure is higher. Blue arrows indicate closing of the aortic valve. Bidirectional arrows represent stroke volume. When aortic pressure is decreased, stroke volume increases as a result of a lower aortic pressure during closure of the aortic valve. A decreased cardiac output to diminished renal perfusion and release of hormones in the RAA-system: renin is released into the circulation by the renal juxtaglomerular which stimulates the cleavage of angiotensinogen into angiotensin I and II during its passage through II stimulates vasoconstriction in the kidneys, and in other vascular systems, increasing blood pressure; the second effect of angiotensin is to stimulate the release of aldosterone from the adrenals into the plasma, which retains sodium from the kidney tubules in the blood and thereby water. The RAA system, which works as a compensatory mechanism for heart failure to increase blood pressure and blood volume, also stimulates hypertrophy of muscle cells and the formation of fibrosis, which in the long term are detrimental to heart failure. leads apparatus, the lungs. Angiotensin Figure 3. Management in heart failure. The other compensatory mechanism for heart the sympathetic nervous system, increases heart rate to increase cardiac output, which is a powerful compensatory mechanism. However, chronic stimulation of the sympathetic nerves to the heart, leading to higher heart rates, is toxic to the heart, because of continuous release of norepinephrine to the failure, stimulation of https://www.textbookofcardiology.org/wiki/Heart_Failure 6/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology myocyte. In addition, as a result of their continued stimulation, the betareceptors for norepinephrine are downregulated in heart failure, which further diminishes the function and functional reserve of the heart. Management When a patient presents with symptoms of heart failure, it is worthwhile to have a dedicated diagnostic and therapeutic plan, in the order as indicated below (Figure 3). Clinical aspects are important for diagnosis, but the final diagnosis is only made after objective evidence of heart dysfunction. Clinical aspects History A careful history of the patient is important for the diagnosis and in order to identify the cause of HF. The history (and physical examination) can be used to differentiate between the abovementioned potential causes of HF (refer to Etiology of heart failure). Family history of HF, smoking status, hyperlipidaemia, hypertension and diabetes mellitus are factors that should be taken into account during the assessment of the patient history in order to draw a risk profile of the patient. Finally, the history should include previous events and the response to therapy. Symptoms and signs HF can manifest with a multitude of different symptoms and signs, but shortness of breath and tiredness are the most characteristic. The Framingham Heart Study defined major and minor diagnostic criteria for HF. Major criteria: Paroxysmal nocturnal dyspnea Neck vein distention Pulmonaty rales Radiographic cardiomegaly (increasing heart size on chest radiography) Acute pulmonary edema S3 gallop Increased central venous pressure (>16 cm H2O at right atrium) Hepatojugular reflux Weight loss >4.5 kg in 5 days in response to treatment Minor criteria: Bilateral ankle edema Nocturnal cough Dyspnea on ordinary exertion Hepatomegaly Pleural effusion https://www.textbookofcardiology.org/wiki/Heart_Failure 7/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Tachycardia (heart rate>120 beats/min.) Minor criteria are acceptable only if they cannot be attributed to another medical condition (such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome). Diagnosis of HF requires the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria. The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure in an outpatient population.[7] Severity of HF In general, correlation between the severity of symptoms and the severity of HF in terms of loss of maximal oxygen consumption is weak.[3] The New York Heart Association functional classification is used most frequently to classify the severity of HF (Table 2). Assessing severity is needed for the proper therapy/ medication to be chosen. Table 2. NYHA functional classification Severity based on symptoms and physical activity No limitation of physical activity. Ordinary physical activity does not cause undue palpitation, or dyspnoea. fatigue, Class I Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnoea. Class II Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitation, or dyspnoea. Class III Unable to carry on any physical activity without discomfort. Symptoms at rest. Class IV If any physical activity is undertaken, discomfort is increased. Physical examination https://www.textbookofcardiology.org/wiki/Heart_Failure 8/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology There are several key features in the clinical examination of a patient presenting with HF. The physical examination should focus on the general appearance of the patient, pulse and blood pressure, signs of fluid overload (increased jugular venous pressure, peripheral edema, ascites and hepatomegaly), the lungs, and the heart (apex, Gallop rhythm, third heart sound, murmurs). Additional diagnostic tests In order to assist in the diagnosis of HF and to differentiate between possible causes of HF, the following tests are available. Electrocardiogram An electrocardiogram (ECG) should be performed on every patient suspected of HF. Several common abnormalities (including possible causes) indicative of HF on the ECG include but are not limited to: sinus tachy- or bradycardia, atrial tachycardia, -flutter, or fibrillation, ventricular arrhythmias, ischemia (including myocardial infarction), abnormal Q waves, left ventricular hypertrophy, micro voltages, and QRS length >120 ms. Although an abnormal ECG (excluding arrhythmias) has a low positive predictive value for HF, a normal ECG is highly indicative of the absence of HF. Chest X-ray A chest X-ray is a part of the standard examination in potential HF patients. Importantly, the X-ray is a tool to detect cardiomegaly (defined as a cardiac: thoracic ratio of > 0,5) or other clues (redistribution, Kerley B-lines and pleural effusion) that indicate HF. It is also important to rule out other causes of dyspnea. Echocardiography Echocardiography is the cornerstone in the diagnosis of HF, and should be performed routinely, because ventricular function can be evaluated accurately with this technique. It can provide objective evidence of a structural or functional abnormality of the heart at rest, besides signs and symptoms that are typical of heart failure. Important parameters that can be assessed include, but are not limited to, wall motion, valve function, left ventricular ejection fraction and diastolic function. Diastolic dysfunction might be an important finding in symptomatic patients with a preserved ejection fraction. Refer to Table 3 for common echocardiographic findings in HF. Transesophageal echocardiography is indicated in patients with an inadequate transthoracic echo window, suspected endocarditis, complicated valvular disease or to exclude a LV thrombus. If echocardiography provides inadequate information or in patients with suspected coronary artery disease, additional imaging includes CT scanning, cardiac magnetic resonance imaging or radionuclide imaging. Laboratory tests A standard blood assessment includes a complete blood count, electrolytes, renal function, glucose and liver function. Furthermore, urinalysis and other tests, depending on the clinical condition of the patient, complete the laboratory assessment. For example, cardiac troponins must be sampled if an ACS is in the differential diagnosis. In patients suspected of HF, values of natriuretic peptides (such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP)) can provide important information https://www.textbookofcardiology.org/wiki/Heart_Failure 9/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology regarding the diagnosis, management and prognosis of HF. Natriuretic peptides are enzymes, secreted by the atria or ventricles in response to myocardial wall stress. The most commonly used tests are BNP and NT-proBNP measurements, which despite their different half-lives in the plasma, do not differ substantially terms of diagnostic ability. Cut-off values are different in acute settings with acute dyspnea compared to chronic settings. Normal values are almost 100% specific, and exclude heart failure in patients >18 year old. Abnormal values do not have a 100% predictive value, and objective evidence for heart failure is still needed. The values for BNP and NTproBNP are also used to evaluate the prognosis in patients with known HF, in whom higher values carry a worse prognosis. in Exercise test Figure 4. Flowchart suspected heart failure [3] An exercise test is not diagnostic for HF, but may be used to identify ischemia as the cause of heart failure, or it can be used to assess the severity of HF, usually in conjunction with maximal oxygen uptake (VO2max) measurement. This test is performed on a treadmill or on a bicycle ergo meter. The patient is asked to give maximal effort while the workload gradually increases. During the test, the ECG is monitored for ischemia. When possible, oxygen consumption should also be measured during the test. Not only is an oxygen consumption test a good tool to discriminate between lung- peripheral- or heart problems, but the obtained value for maximal oxygen uptake (VO2max) has an important prognostic value. Heart catheterization Heart catheterization is not always part of the routine diagnosis and work-up of patients with HF. It should be considered however to exclude coronary heart disease (Class of recommendation IIa, level of evidence C, see Table 4). Coronary angiography is recommended in patients at high risk of coronary artery disease (Class of recommendation I, level of evidence C) and in HF patients with significant valvular disease (Class of recommendation IIa, level of evidence C). https://www.textbookofcardiology.org/wiki/Heart_Failure 10/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 3. Common echocardiographic abnormalities in heart failure Measurement Abnormality Clinical implications Left ventricular ejection fraction (LVEF) Left ventricular global systolic dysfunction Reduced (< 50%) Myocardial infarction/ischaemia, Cardiomyopathy, Left ventricular wall motion Akinesis, hypokinesis, dyskinesis Myocarditis Left ventricular end- diastolic diameter Increased ( 60 mm/>32 mm/m2)) Volume overload HF likely Volume overload Left ventricular end- systolic diameter Increased ( 45 mm/>25 mm/m2,) HF likely Left ventricular fractional shortening Reduced (<25%) Left ventricular systolic dysfunction Increased filling pressures, Left atrial volume index Increased (volume >34 mL/m2) Mitral valve dysfunction Hypertention, Aortic stenosis, Left ventricular thickness Hypertrophy (>11 12 mm) Hypertrophic cardiomyopathy May be primary cause of HF or complicating factor Valvular stenosis or regurgitation (especially aortic stenosis and mitral insufficiency) Asses consequences haemodynamic Valvular structure and function Consider surgery Mitral diastolic flow profile Abnormalities of the early and late diastolic filling patterns Indicates diastolic dysfunction and suggests mechanism Tricuspid regurgitation peak velocity Increased right ventricular systolic pressure Increased (>3.4 m/s) Pericardium Effusion, Consider tamponade, Haemopericardium, Malignancy, Calcification Systemic disease, Acute or chronic pericarditis, https://www.textbookofcardiology.org/wiki/Heart_Failure 11/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Constrictive pericarditis Aortic outflow velocity time integral Reduced (<15 cm) Reduced low stroke volume Right ventricular function (e.g. TAPSE) Reduced (TAPSE < 16 mm) RV systolic dysfunction Increased right atrial pressures, Right ventricular dysfunction, Inferior vena cava Dilated, with no respiratory collapse Volume overload Pulmonary hypertention possible Etiology of heart failure Coronary heart disease The most important cause (50% of the cases) of HF in the Western world is ischemic heart disease, including myocardial infarction. These patients mainly suffer from systolic HF due to wall motion abnormalities of the affected area and re-modeling of the non-affected parts of the myocardium. Hypertension In patients with a high systolic blood pressure (BP), the left ventricle faces an increased afterload (a higher workload pumping the blood against the increased vascular resistance). Over a certain period of time, this will lead to hypertrophy of the cardiac myocardium, and longer term remodeling may lead to pump function disorders (diastolic or systolic). In as many as 60-70% of patients suffering HF, hypertension is the primary or secondary cause of the condition. Heart rhythm disorders Atrial fibrillation is a common rhythm disorder in the elderly. With this condition, the atria do not contract in the coordinated fashion as they would in normal sinus rhythm, and therefore the atria never optimally empty. Normally, the atrial kick contributes approximately 15% of the stroke volume. The absence of the atrial kick during atrial fibrillation can contribute to a reduced LVEF. However, atrial fibrillation is seldom the cause of heart failure, but more often a trigger of heart failure in already existing structural heart disease. Valvular disease https://www.textbookofcardiology.org/wiki/Heart_Failure 12/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Valvular disease, especially mitral- or aortic, can cause volume and pressure overload of the left ventricle of the heart. This overload causes dilation and / or hypertrophy of the left ventricle, which in the long term decreases the pump function. Cardiomyopathies Dilated cardiomyopathy (DCM) is characterized by dilatation of one or both of the ventricles of the heart, with a general decrease in contractility and consequently a decreased pump function. In approximately 30% of the cases, DCM is hereditary. Hypertrophic cardiomyopathy (see also Hypertension) is characterized by hypertrophy, which may be concentric or asymmetric. The asymmetric form is usually hereditary. Restrictive cardiomyopathy is characterized by a primary diastolic dysfunction of one or more of the ventricles, leading to increased filling pressures and hypertrophy, and initially a preserved systolic function. Arrhythmogenic right ventricular cardiomyopathy is characterized by fatty infiltration and fibrosis of the right ventricle or the left ventricle or both and is usually hereditary. Pericardial disease and Tamponade Restriction of ventricular filling by a tight (inflamed or constrictive) pericardium or by pericardial effusion and tamponade can be the cause of diastolic HF. Drugs Drugs that can cause HF are: Cytotoxic agents (chemotherapy, especially doxorubicin) The antipsychotic agent clozapine Drugs that can aggravate HF are: Beta blockers Calcium antagonist Antiarrhythmics Disulfiram Toxins Alcohol Cocaine, Trace elements (mercury, cobalt, arsenic). Endocrine disorders Diabetes mellitus https://www.textbookofcardiology.org/wiki/Heart_Failure 13/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Hypo- or hyperthyroidism Cushing syndrome Adrenal insufficiency Excessive growth hormone in acromegaly Phaeochromocytoma Nutritional status Deficiency of thiamine, selenium, or camitine, in states of severe cachexia. Infiltrative and storage disorders Sarcoidosis Amyloidosis Haemochromatosis Connective tissue disease Infectious disease Chagas disease HIV infection Viral, bacterial or protozoal diseases causing myocarditis. Management in investigating etiology of heart failure 1. Assess globally: are there triggers of heart failure. Hypertension, infection, anemia, rhythm disorders. Perform standard laboratory tests: in addition to hemoglobin, leukocytes, thrombocytes, creatinin, sodium and potassium levels, also liver function, thyroid function (TSH), glucose. 2. Assess ischemia: are there indications of ischemic etiology (ECG: Q s or significant and changing ST segments, laboratory: troponins, and echocardiogram: segmental wall motion abnormality in coronary territory areas) ? If yes, then proceed with further coronary artery or myocardial perfusion imaging. 3. Are there no indications for ischemic etiology? Classify phenotype of cardiomyopathy: dilated, hypertrophic, restrictive, arrhytmogenic right ventricular cardiomyopathy. Then assess with additional laboratory tests, including creatinin kinase, autoimmune markers, eosinophilia, ferritin and iron saturation. In some suspected cases: calcium and albumin. Look for clues of etiologies: history, family history (including maternal inheritage of diabetes in a family) In case of fever look for infectious etiology, MRI confirmation for possible myocarditis, plasma serology. Look for clues on ECG: microvoltage on the ECG, AV block in combination with later atrial fibrillation. Additional lab may be warranted (monoclonal proteins in case of microvoltage in the presence of sufficient amounts of myocardium and the absence of pericardial fluid or pulmonary emphysema) https://www.textbookofcardiology.org/wiki/Heart_Failure 14/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology MRI for further classification of cardiomyopathy and assessment of presence and localization of delayed contrast enhancement Coronary arteriography or coronary CT scan to exclude coronary artery disease Myocardial biopsy in cases where the suspicion of severe underlying disease is high (e.g. fulminant myocarditis, sarcoidosis suspicion on MRI with no other organ involved). Genetic testing after counseling Therapy of heart failure The therapeutic management of HF involves both pharmacological and non-pharmacological treatment. The goal is reduction in mortality and morbidity, prevention of the progression of HF, and the treatment of (non-) cardiovascular co-morbidities. Non-pharmacological treatment Non-pharmacological management is of great importance for HF patients. It can have a significant impact on symptoms, functional capacity, wellbeing, morbidity, and prognosis. The most important non- pharmacological options are described below. Education Education of both the patient and their family about HF and its symptoms is important. The patient and/or the caregiver should be able to undertake appropriate actions such as adjusting the diuretic dose or contact the physician when necessary. (Class I recommendation, level of evidence C; see Table 4) Education on the importance and (side) effects of medication should be provided to the patient in order to increase compliance. (Class I recommendation, level of evidence C) Fluid and sodium restriction In patients with severe symptoms of HF, restriction of fluid intake (to 1500 ml/day) may be considered. (Class IIa recommendation, level of evidence C). Also, patients should be educated about the salt content of food and advised to minimize their salt intake (< 2 gram/ day) in order to prevent fluid retention. (Class I recommendation, level of evidence C) Body weight CHF patients should carefully monitor their body weight. A sudden increase in weight is a potential consequence of fluid retention and deterioration of HF. If patients notice a weight gain of >2kg in 3 days, they should consult their physician. (Class I recommendation, level of evidence C). In obese patients (body mass index >30 kg/m2), weight reduction should be promoted to prevent progression of HF, decrease symptoms and improve the overall wellbeing of the patient. (Class IIa recommendation, level of evidence C). Also, attention should be paid to weight loss due to malnutrition, which is frequently https://www.textbookofcardiology.org/wiki/Heart_Failure 15/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology observed in severe HF. An altered metabolism, inflammatory mechanisms or a decreased food intake may be important factors in the pathophysiology of cardiac cachexia in HF. (Class I recommendation, level of evidence C) Alcohol and tobacco Alcohol intake should be minimized, as it may increase blood pressure and/or have a negative inotropic effect. (Class IIa recommendation, level of evidence C). Smoking cessation should be encouraged. It is recommended that patients with HF receive support and advice on this topic. (Class I recommendation, level of evidence C). A reduction in alcohol and tobacco intake might also improve co-morbidities, including sleep disorders. Exercise Exercise training is recommended to all chronic stable HF patients. Twenty years ago, exercise was strongly discouraged in patients with HF as it was considered to be harmful. Nowadays, numerous studies have demonstrated the opposite. Rehabilitation programs have shown to increase exercise capacity and health related quality of life, and decrease hospitalization rates and symptoms. (Class I recommendation, level of evidence A) Other Other non-pharmacological treatment recommendations include immunization of HF patients (pneumococcal- and influenza vaccination should be considered), the consulting of a physician around pregnancy, the screening for depression and sleep disorders that require additional medical attention. Pharmacological treatment A flowchart for the treatment of patients presenting with systolic HF is depicted in Figure 5. Medications with a class I indication in patients with systolic heart failure are summarized in Table 5. Indications, mode of action, contraindications of the medication, and possible side effects of drugs included in this algorithm are discussed below. https://www.textbookofcardiology.org/wiki/Heart_Failure 16/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Figure 5. Treatment options for patients with chronic systolic HF https://www.textbookofcardiology.org/wiki/Heart_Failure 17/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology NYHA I & EF <40% NYHA II NYHA III NYHA IV Diuretic ACE-inhib AT-II antagonist Alternative Alternative Alternative Post infarction Betablocker Aldosteron antagonist EF < 35% EF < 35% EF < 35% Nitrate / Hydralazine Afro-American Afro-American Afro-American SR>75/min & EF<35% SR>75/min & EF<35% SR>75/min & EF<35% Ivabradine Digoxin Table 5. Medication with a class I indication in patients with systolic heart failure. Note that AT-II antagonists are alternative medicine for ACE inhibitors in case of intolerance (coughing, allergy). Nitrates and Hydralazine are added therapy for patients of Afro-American descent, and alternative therapy for patients that cannot tolerate ACE-inhibitors and AT-II antagonists). Digoxin can also be seen as symptomatic (instead of added preventive) treatment, not always necessary in NYHA III or even IV. Angiotensin-converting enzyme (ACE) inhibitors An ACE inhibitor is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are: History of angioedema Bilateral renal artery stenosis Serum potassium concentration >5.0 mmol/L Serum creatinine >220 mol/L Severe aortic stenosis ACE inhibitors relieve the heart by decreasing the preload and afterload. This is achieved through two mechanisms. Firstly, conversion of angiotensin-I to angiotensin II is inhibited, which reduces vasoconstriction and lowers BP. Secondly, production of aldosterone is decreased, as angiotensin II induces this production. Aldosterone stimulates sodium- and water retention. Possible side effects are symptomatic hypotension (dizziness), hyperkalemia, worsening renal function and cough. In patients with congestive HF, total mortality and hospitalization are significantly reduced by ACE inhibitors.[8] Beta Blockers Beta blockade (in addition to an ACE inhibitor or ARB when ACE inhibitor is not tolerated) is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV) and in asymptomatic patients with a LVEF 40% after a MI. (Class I recommendation, level of evidence A).[9] https://www.textbookofcardiology.org/wiki/Heart_Failure 18/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Contraindications are: Bronchial asthma Second - or third degree heart block, sick sinus syndrome, sinus bradycardia Beta blockers mainly exert their effect by reducing the toxic effects of the sympathetic nervous stimulation on the heart and by deactivating the renin-angiotensin system. Possible side effects include (symptomatic) hypotension, worsening of HF and bradycardia. The recommendation is start low, go slow , i.e. start with a low dose, and titrate every two weeks. In patients with persistent symptoms after treatment with a combination of beta blocker and ACE inhibitor or ARB, a mineralocorticoid/aldosterone receptor antagonist (MRA) is recommended. (Class I recommendation, level of evidence A) Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists) Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart lung vasculature decrease. the and Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnea and edema. Figure 6 depicts the nephron and the sites where different diuretics work. Loop of Henle diuretics Figure 6. Diuretics and site of action in the nephron. Loop of Henle diuretics act on ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorption. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis. the Thiazides Thiazide increases urine production by decreasing reabsorption of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function. Aldosterone antagonists Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to Table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications: https://www.textbookofcardiology.org/wiki/Heart_Failure 19/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Serum potassium concentration > 5.0 mmol/L Serum creatinine > 220 mol/L Concomitant potassium sparing diuretic or potassium supplements Combination of an ACEI and ARB Aldosterone antagonists reduce sodium retention by the kidney, and inhibit fibrosis formation in the heart. Possible side effects include hyperkalemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is an alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality. [10] Choice and combination of diuretics Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic if a suboptimal response occurs. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting that diuretic resistance is due to distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinine clearance < 20 ml/min (creatinine > 220 micromol/L), addition of an aldosterone antagonist should be considered. In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then prescribed as an alternative diuretic. Angiotensin receptor blockers (ARBs) |
Exercise Exercise training is recommended to all chronic stable HF patients. Twenty years ago, exercise was strongly discouraged in patients with HF as it was considered to be harmful. Nowadays, numerous studies have demonstrated the opposite. Rehabilitation programs have shown to increase exercise capacity and health related quality of life, and decrease hospitalization rates and symptoms. (Class I recommendation, level of evidence A) Other Other non-pharmacological treatment recommendations include immunization of HF patients (pneumococcal- and influenza vaccination should be considered), the consulting of a physician around pregnancy, the screening for depression and sleep disorders that require additional medical attention. Pharmacological treatment A flowchart for the treatment of patients presenting with systolic HF is depicted in Figure 5. Medications with a class I indication in patients with systolic heart failure are summarized in Table 5. Indications, mode of action, contraindications of the medication, and possible side effects of drugs included in this algorithm are discussed below. https://www.textbookofcardiology.org/wiki/Heart_Failure 16/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Figure 5. Treatment options for patients with chronic systolic HF https://www.textbookofcardiology.org/wiki/Heart_Failure 17/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology NYHA I & EF <40% NYHA II NYHA III NYHA IV Diuretic ACE-inhib AT-II antagonist Alternative Alternative Alternative Post infarction Betablocker Aldosteron antagonist EF < 35% EF < 35% EF < 35% Nitrate / Hydralazine Afro-American Afro-American Afro-American SR>75/min & EF<35% SR>75/min & EF<35% SR>75/min & EF<35% Ivabradine Digoxin Table 5. Medication with a class I indication in patients with systolic heart failure. Note that AT-II antagonists are alternative medicine for ACE inhibitors in case of intolerance (coughing, allergy). Nitrates and Hydralazine are added therapy for patients of Afro-American descent, and alternative therapy for patients that cannot tolerate ACE-inhibitors and AT-II antagonists). Digoxin can also be seen as symptomatic (instead of added preventive) treatment, not always necessary in NYHA III or even IV. Angiotensin-converting enzyme (ACE) inhibitors An ACE inhibitor is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are: History of angioedema Bilateral renal artery stenosis Serum potassium concentration >5.0 mmol/L Serum creatinine >220 mol/L Severe aortic stenosis ACE inhibitors relieve the heart by decreasing the preload and afterload. This is achieved through two mechanisms. Firstly, conversion of angiotensin-I to angiotensin II is inhibited, which reduces vasoconstriction and lowers BP. Secondly, production of aldosterone is decreased, as angiotensin II induces this production. Aldosterone stimulates sodium- and water retention. Possible side effects are symptomatic hypotension (dizziness), hyperkalemia, worsening renal function and cough. In patients with congestive HF, total mortality and hospitalization are significantly reduced by ACE inhibitors.[8] Beta Blockers Beta blockade (in addition to an ACE inhibitor or ARB when ACE inhibitor is not tolerated) is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV) and in asymptomatic patients with a LVEF 40% after a MI. (Class I recommendation, level of evidence A).[9] https://www.textbookofcardiology.org/wiki/Heart_Failure 18/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Contraindications are: Bronchial asthma Second - or third degree heart block, sick sinus syndrome, sinus bradycardia Beta blockers mainly exert their effect by reducing the toxic effects of the sympathetic nervous stimulation on the heart and by deactivating the renin-angiotensin system. Possible side effects include (symptomatic) hypotension, worsening of HF and bradycardia. The recommendation is start low, go slow , i.e. start with a low dose, and titrate every two weeks. In patients with persistent symptoms after treatment with a combination of beta blocker and ACE inhibitor or ARB, a mineralocorticoid/aldosterone receptor antagonist (MRA) is recommended. (Class I recommendation, level of evidence A) Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists) Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart lung vasculature decrease. the and Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnea and edema. Figure 6 depicts the nephron and the sites where different diuretics work. Loop of Henle diuretics Figure 6. Diuretics and site of action in the nephron. Loop of Henle diuretics act on ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorption. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis. the Thiazides Thiazide increases urine production by decreasing reabsorption of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function. Aldosterone antagonists Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to Table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications: https://www.textbookofcardiology.org/wiki/Heart_Failure 19/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Serum potassium concentration > 5.0 mmol/L Serum creatinine > 220 mol/L Concomitant potassium sparing diuretic or potassium supplements Combination of an ACEI and ARB Aldosterone antagonists reduce sodium retention by the kidney, and inhibit fibrosis formation in the heart. Possible side effects include hyperkalemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is an alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality. [10] Choice and combination of diuretics Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic if a suboptimal response occurs. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting that diuretic resistance is due to distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinine clearance < 20 ml/min (creatinine > 220 micromol/L), addition of an aldosterone antagonist should be considered. In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then prescribed as an alternative diuretic. Angiotensin receptor blockers (ARBs) ARBs are recommended in patients who do not tolerate an ACE inhibitor. Until recently, the addition of ARBs was the first choice recommendation in patients with HF and EF 40% who remained symptomatic despite optimal treatment with ACE inhibitor and beta blocker. As aldosterone antagonists have also proven their effects in NYHA class II patients, aldosterone antagonists have become first choice additional therapy after an ACE inhibitor and beta blocker. Whether ARBs may still be recommended in this patient group as added therapy after the addition of aldosterone antagonist is not known. Contraindications are: Bilateral renal artery stenosis Serum potassium concentration > 5.0 mmol/L Serum creatine > 220 mol/L Severe aortic stenosis Possible side effects include symptomatic hypotension (dizziness), hyperkalemia, and a worsening renal function. Digoxin https://www.textbookofcardiology.org/wiki/Heart_Failure 20/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology In the past, digoxin was the standard treatment in HF. Digoxin inhibits sodium-potassium ATPase in the cell membrane of the myocytes, and, by decreasing the sodium extrusion, also inhibits the exchange of calcium out of the cell for sodium into the cell. More calcium remains in the myocyte and increases the contractility of the heart. In contrast to other inotropics, digoxin does not increase mortality. In patients with symptomatic HF and atrial fibrillation (AF) with a ventricular rate at rest of >80 beats per minute, use of digoxin may be considered to slow the ventricular rate. (Class I recommendation, level of evidence C) Digoxin may be considered to reduce HF hospitalization in patients with symptomatic (NYHA class II- IV) systolic HF in sinus rhythm with an EF 45%. These patients should also use an ACE inhibitor (or ARB) and an MRA (or ARB) and preferably a beta blocker. (Class IIb recommendation, level of evidence B) This may also be considered in patients with an EF 45% and persisting symptoms despite treatment with an ACE inhibitor (or ARB) and an MRA (or ARB). (Class IIb recommendation, level of evidence B) Contraindications for the use of digoxin are: Second- or third degree heart block without a permanent pacemaker, sick sinus syndrome Pre-excitation syndromes Possible side effects include sinoatrial or atrioventricular block, arrhythmias or signs of toxicity (nausea and visual effects as halos). Ivabradine Ivabradine lowers the heart rate through inhibition of the If channel in the sinus node. This drug can be used in patients who are still in NYHA class II-IV after treatment with ACE inhibitor (or ARB), beta blocker and an MRA (or ARB), who have a LVEF 35%, are in sinus rhythm and have a heart rate 75 beats/min. Ivabradine may also be used in patients who do not tolerate, or have contraindications for the use of beta blockers. Hydralazine and isosorbide dinitrate (H-ISDN) H-ISDN can be used as an alternative treatment when both ACEI and ARBs are not tolerated by symptomatic HF patients with a LVEF 45% and dilated LV (or EF 35%). These patients should also receive a beta blocker and MRA. (Class IIb recommendation, level of evidence B). H-ISDN can be used in addition to the standard HF treatments (ACEI, beta blocker and MRA) in patients of Afro-American descent (Class IIb recommendation). H-ISDN may reduce risk of HF hospitalization and risk of premature death in patients with a LVEF 45% and dilated LV (or EF 35%) with persistent symptoms despite treatment with beta blocker, ACEI (or ARB), and an MRA (or ARB). (Class IIb recommendation, level of evidence B) Contraindications for the use of H-ISDN are: Symptomatic hypotension Lupus syndrome Severe renal failure The H-ISDN combination acts by decreasing peripheral vascular resistance. https://www.textbookofcardiology.org/wiki/Heart_Failure 21/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Possible side effects include symptomatic hypotension or drug-induced lupus-like syndrome. Other Anticoagulants Anti platelet agents Statins Anti arrhythmic medication Calcium antagonists Therapy of acute heart failure When severe symptoms of heart failure quickly develop over time, it is termed acute heart failure. In Table 6, common their acute HF medications recommended doses are summarized. In Figure 7, a flowchart for the treatment of acute HF is depicted. The mainstay of acute heart includes inotropics and diuretics, vasodilators, vasopressors. Moreover, oxygen and morphine can be added. and failure therapy Figure 7. Flowchart acute HF. https://www.textbookofcardiology.org/wiki/Heart_Failure 22/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 6. Medication in acute heart failure Medication Condition Dose Diuretics Adequate blood pressure and signs of overfilling 40 mg Furosemide i.v. Renal failure 125 mg max 1000 mg 1 mg Bumetanide i.v. Renal failure 3 mg max 25 mg Vasodilators Adequate blood pressure and signs of severe overfilling 20 g/min max 200 g/min (guided by blood pressure) Nitroglycerine i.v. Hypertensive crisis or in combination with inotropic in case of a cardiogenic shock 0.3 g/kg/min max 5 g/kg/min (guided by blood pressure) Nitroprusside i.v. Inotropes Low blood pressure and/or renal failure with or without overfilling Dobutamine i.v. 2-3 g/kg/min max 20 g/kg/min Low blood pressure and/or renal failure with or without overfilling 2-3 g/kg/min max 20 g/kg/min Dopamine i.v. Signs of peripheral hypoperfusion with or without overfilling, and adequate blood pressure 0.25 0.75 mg/kg in 10 minutes; subsequently 1.25 7.5 g/kg/min Enoximone i.v. 0.1 g/kg/min, If beta-blockade is thought to be contributing to hypoperfusion can be decreased to 0.05 or increased to 0.2 g/kg/min Levosimendan i.v. Vasopressors Restore circulation in cardiogenic shock Adrenalin i.v. Noradrenalin i.v. Septic shock Patient presents at first aid or emergency room with signs of acute HF. https://www.textbookofcardiology.org/wiki/Heart_Failure 23/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 7. Medication in chronic heart failure Medication Condition Dose Adequate blood pressure and signs of overfilling Loop diuretic 40 mg Furosemide Renal failure 80 mg max 1000 mg 1 mg Bumetanide Renal failure 2 mg max 25 mg ACE inhibitors Start 6.25mg Captopril 1st week 6.25mg three times daily. 3-5 weeks 12.5mg three times daily. >7 weeks 25mg three times daily. Start 2.5-5mg Lisinopril 1st week 2.5-5mg twice daily. 3-5 weeks 5-10mg twice daily. >7 weeks 10-20mg twice daily. Beta blockers EF >30-45% and NYHA II-III Start 25mg Metoprolol zoc (succinate) 1st week 50mg once daily. 3-5 weeks 100mg once daily. >7 weeks 100-200mg once daily. EF <30% and NYHA IV Start 12.5mg 1st week 25mg once daily. 3-5 weeks 50mg once daily. https://www.textbookofcardiology.org/wiki/Heart_Failure 24/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology >7 weeks 100-200mg once daily. EF >30-45% and NYHA II-III Start 2.5mg Bisoprolol 1st week 3.75mg once daily. 3-5 weeks 5mg once daily. >7 weeks 7.5-10mg once daily. EF <30% and NYHA IV Start 1.25mg 1st week 2.5mg once daily. 3-5 weeks 3.75mg once daily. >7 weeks 5-7.5-10mg once daily. EF >30-45% and NYHA II-III Start 6.25mg Carvedilol 1st week 6.25mg twice daily. 3-5 weeks 12.5mg twice daily. >7 weeks 25mg twice daily. EF <30% and NYHA IV Start 3.125mg 1st week 3.125mg twice daily. 3-5 weeks 6.25mg twice daily. >7 weeks 12.5-25mg daily. twice EF >30-45% and NYHA II-III Start 1.25mg Nebivolol 1st week 2.5mg once daily. 3-5 weeks 5mg once daily. >7 weeks 10mg once daily. EF <30% and NYHA IV Start 1.25mg 1st week 2.5mg once daily. 3-5 weeks 5mg once daily. https://www.textbookofcardiology.org/wiki/Heart_Failure 25/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology >7 weeks 10mg once daily. Aldosterone antagonist Start 25mg s.i.d. Spironolactone/eplerenone 1st week potassium <5.0: 25mg once daily. potassium 5.0-5.5: 12.5mg once daily. potassium >5.5: stop 3rd week potassium <5.0: 25mg once daily. potassium 5.0-5.5: 12.5mg once daily. potassium >5.5: stop Start 0.5mg, 0.25mg and 0,25 mg, each with 6 hours in between Digoxin Continue with 0.25mg once daily. Half dose with age above 70 or creatinin above 110 or with amiodarone use AT II blockers Start 4mg Candesartan 3-5 weeks 8mg once daily. >7 weeks 16mg once daily. Start 40mg twice daily Valsartan 3-5 weeks 80mg twice daily. >7 weeks 160mg twice daily. Hydralazine and isosorbide dinitrate (H-ISDN) Start 25mg three times daily. Hydralazine 3-5 weeks 50mg three times daily. https://www.textbookofcardiology.org/wiki/Heart_Failure 26/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology >7 weeks 75-100mg times daily. three Start 20mg twice daily ISDN 3-5 weeks 40mg twice daily >7 weeks 80mg twice daily Management of HF beyond medication Device treatment is an Prevention of because important approximately half of the deaths occur suddenly, and many of these are related to ventricular Implantable arrhythmias. cardioverter-defibrillator (ICD) therapy is in survivors of cardiac recommended life arrest I is >1 expectancy recommendation, level of evidence A). sudden death in HF goal , irrespective of EF, when (Class year. In symptomatic HF patients (NYHA class II-III) with an EF 35% after more than 3 months of pharmacological treatment and a life expectancy >1 year, prophylactic ICD implantation is recommended in patients with I recommendation, level of evidence A) and non-ischemic I (Class etiology recommendation, level of evidence B). ischemic etiology (Class Cardiac resynchronization therapy (CRT) is indicated in patients with symptomatic heart failure with one type and severity of ventricular conduction delay (LBBB, QRS 120 msec), and preferably in patients with sinus rhythm. The responder rate (improvement of at least 5% EF) is about 70%. Recommendation for use of this therapy differs according to heart rhythm, NYHA class, QRS duration and morphology, and LVEF. This is depicted in the Figure 8. Figure 8. flowchart CRT Timing of ICD implantation Figure 5 offers recommendations to which patients should receive ICD treatment. In this flowchart, the timing of the placement has not been defined completely. In most patients, it should be safe to wait for their ICD whilst receiving (pharmacological) treatment as events typically occur after 6-12 months.[11] https://www.textbookofcardiology.org/wiki/Heart_Failure 27/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology An exception to this rule is the group of high risk patients (i.e. patients with major myocardial infarction (MI), who have extensive fibrosis on the MRI or NSVT despite optimal pharmacological treatment); an ICD implantation should not be postponed too long in these patients. Early (within 40 days after event) ICD placement after an acute myocardial infarction has not been shown to reduce mortality, because the patients most at risk of sudden death are also the patients most at risk of death due to heart failure.[12] [13][14] For this reason, prophylactic ICD treatment is recommended only after 40 days in post-infarct patients who have an EF < 35%. For non-ischemic heart failure patients, three months is considered a safe waiting time for an ICD. There are, however, also higher risk patients among this group, and a decision should be made for each patient on an individual basis.[15] Heart transplantation and Left Ventricular Assist Devices When a patient has severe and progressive HF, his or her prognosis is grim. Considering the paucity of donor hearts, the waiting list for heart transplantation may be long and early consideration of heart transplantation is part of the treatment strategy in HF. Average 2-year survival rates after cardiac transplantation are approximately 80%. A patient in NYHA class III should be evaluated with an exercise test for maximal oxygen uptake, in order to consider further steps. Indication for heart transplantation includes a VO2max < 14 ml/min/kg.[16] Exclusion pulmonary hypertension (risk of immediate RV donor failure), severe comorbidity, and diabetes mellitus with organ damage. Left Ventricular Assist Devices are more commonly to transplantation, when the patient in on a waiting list. They have evolved from pulsatile to continuous flow pumps, with less complications and a longer durability. Often Left Ventricular Assist Devices become destination therapy. criteria are used as a bridge Management of HF patients with preserved LVEF (HFPEF) Figure 9. Two-year mortality in landmark contemporary clinical heart failure trials (from Cleland et al) To date, no evidence exists of any treatment reducing morbidity or mortality in this patient group. With the aim of controlling water and sodium retention and to decrease breathlessness and edema, diuretics are prescribed to HFPEF patients. Furthermore, ACE-I, Angiotensin II blockers and/or beta blockers may be considered. The CHARM trial including 3023 HF patients with preserved EF, showed angiotensin II blockade (candesartan) to have a moderate effect on hospital admission but showed no effect on the risk of cardiovascular death.[17] Prognosis The life expectancy of a patient with heart failure is determined by age, NYHA class, LVEF, normal level of sodium, systolic blood pressure, use of medication and use of ICD or CRT-D (Seattle Heart failure is score (http://depts.washington.edu/shfm/app.php)). The mean yearly annual mortality https://www.textbookofcardiology.org/wiki/Heart_Failure 28/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology approximately 10%, varying from <6% per year when a normal LVEF is identified, to > 14% per year with an EF of <15%. Trials with medication illustrate that the (short term) benefit of medication is highest when the NYHA class is higher (Figure 9).[18] References 1. Withering W., Keys TE, An account of the foxglove and some of its medical uses, with practical remarks on dropsy, and other diseases, Classics of Cardiology. Volume I. New York, NY: Henry Schuman, Dover Publications; 1941: 231 252. 2. Kannel WB, Silbershatz H, Belanger AJ, Wilson PW, Levy D. Profile for Estimating Risk of Heart Failure, Arch Intern Med. 1999;159:1197-204 3. McMurray JJV et al., ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012, European Heart Journal (2012; 33;1787 1847) 4. McDonagh TA, Morrison CE, Lawrence A, Ford I, Tunstall-Pedoe H, McMurray JJ, Dargie HJ. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet. 1997 Sep 20;350(9081):829-33 5. Wang TJ, Evans JC, Benjamin EJ, Levy D, LeRoy EC, Vasan RS. Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation. 2003 Aug 26;108(8):977-82. Epub 2003 Aug 11. 6. Holubarsch C et al, Existence of the Frank-Starling Mechanism in the Failing Human Heart Investigations on the Organ, Tissue, and Sarcomere Levels. Circulation. 1996 Aug 15;94(4):683-9. 7. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. New England Journal of Medicine. 1971; 23;285(26):1441-6. 8. Garg R, Yusuf S, Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Journal of the American Medical Association. 1995;273:1450-6 9. Foody JM, Farrell MH, Krumholz MH. -Blocker Therapy in Heart Failure. Scientific Review. Journal of the American Medical Association. 2002;287(7):883-889. 10. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. New England Journal of Medicine .1999;341:709-17 https://www.textbookofcardiology.org/wiki/Heart_Failure 29/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology 11. Moss AJ, Zareba W, Hall J, Klein H, Wilbur DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML . Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. New England Journal of Medicine. 2002;346:877 883. 12. Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. New England Journal of Medicine.2004;351:2481 2488 13. Steinbeck G, Andresen D, Seidl K, Brachmann J, Hoffmann E, WojciechowskiD, Kornacewich-Jach Z, Sredniawa B, Lupkovics G, Hofgartner F, Lubinski A, Rosenqvist M, Habets A, Wegscheider K, Senges J. Defibrillator implantation early after myocardial infarction. New England Journal of Medicine. 2009;361:1427 1436 14. Wilber DJ, Zareba W, Hall WJ, Brown MW, Lin AC, Andrews ML, Burke M, MossAJ . Time- dependence of mortality risk and defibrillator benefit after myocardial infarction. Circulation. 2004;109:1082 1084. 15. Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH. Prophylactic defibrillator implantation in patients with non-ischemic dilated cardiomyopathy. England Journal of Medicine. 2004;350:2151 2158 16. Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH, Wilson JR. Value of peak exercise consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991;83:778 786 17. Yusuf S. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. The Lancet. Sept 2003 362;9386:777-781 18. Cleland JGF, Andrew L, Clark AL. Delivering the cumulative benefits of triple therapy to improve outcomes in heart failure. Journal of the American College of Cardiology. 2003;42(7) 19. Mosterd A. Clinical epidemiology in heart failure. Heart 2007;93:1137-1146 20. McMurray JJ. Clinical practice. Systolic heart failure. New England Journal of Medicine. 2010;362: 228-238 Retrieved from "http://www.textbookofcardiology.org/index.php?title=Heart_Failure&oldid=2560" This page was last edited on 11 October 2015, at 16:00. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Heart_Failure 30/30 |
7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology HIV and the Heart Tim P. van de Hoef, MD Contents Case Study Introduction Factors contributing to HIV-associated cardiovascular disease Traditional cardiovascular risk factors Non-modifiable risk factors Modifiable risk factors Antiretroviral therapy effects HIV-infection related factors Inflammation Immune dysfunction and immune activation Virologic Suppression and the Risk of CVD Prevention of CVD in HIV-infected patients Clinical presentation and revascularization References Case Study A 42-year old male patient presents with ongoing fulminant retrosternal chest pain, radiating to the left shoulder and the jaw, with concomitant nausea. The patient awoke with these discerning complaints 21/2 hours ago, and there is no (recent) history of anginal symptoms. His medical history includes human immunodeficiency virus seropositivity since his 24th, for which he since successfully receives chronic combined antiretroviral therapy with Truvada (tenofovir/emtricitabine), ritonavir, and atazanavir, with undetectable viral loads. In the presence of hypercholesterolemia, further medication includes ezetemibe solotherapy, since statins were not tolerated. The electrocardiogram shows ST-segment elevation in the anterior precordial leads, and the patient is diagnosed with anterior wall acute myocardial infarction. Emergency coronary angiography is performed without delay, revealing a thrombotic occlusion of the left anterior descending coronary artery. Manual thrombus aspiration and subsequent stent implantation is performed successfully. In addition to lifelong aspirin treatment, and, despite revascularization guideline recommendation, the patient is post-treated with clopidogrel instead of prasugrel or ticagrelor for the first year following the acute myocardial infarction. Introduction https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 1/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Contemporary antiretroviral therapy (ART) treatment strategies for human immunodeficiency virus (HIV) infection have led to a decrease in acute immunodeficiency syndrome (AIDS)-related (fatal) events [1]. Consequently, life expectancy of HIV-positive patients has improved dramatically, which is now quite comparable to HIV-negative populations [2][3]. Inferably, there has been a shift from opportunistic AIDS-related diseases to non-infectious co-morbidity, including cardiovascular disease (CVD).[4] The World Health Organization recently estimated that both CVD and HIV will be in the top 3 causes for both global mortality as well as global disability-adjusted life-years in the year 2030, indicating that the interrelation between the two diseases will be an important challenge in global public health in the near future.[5] Cardiovascular fatal events comprise 7-15% of total fatal events in HIV-infected patients.[6][1][7] Compared with the non-infected population, HIV-infected patients are at increased risk for CVD[8][9], even in HIV-infected patients treated with antiretroviral drugs.[10] Moreover, the age at which CVD surfaces in HIV-infected patients was found to be substantially lower compared with the general non- infected population, suggesting an accelerated atherosclerotic process.[11] Several recent reports suggest an important association between HIV-infection, ART, and CVD. Most likely, a combination of factors is involved in the relationship between HIV and the heart, which implicates that the HIV-infected population may benefit from a tailored approach to CVD prevention and management. The attributing factors and their relevance in the management of CVD in HIV-positive patients will be discussed in detail in the next paragraphs. Factors contributing to HIV-associated cardiovascular disease The etiology of cardiovascular disease in HIV-positive patients is most likely multifactorial of nature, and includes traditional risk factors for cardiovascular disease, antiretroviral drug effects, as well as factors directly associated with the HIV-infection itself. As such, HIV seropositivity is known to be associated with all stages of atherosclerosis; from the stage of preclinical endothelial dysfunction[12][13], and the early subclinical stage of atherosclerosis [14][15][16], to obstructive (epicardial) coronary artery disease. [17] Traditional cardiovascular risk factors Traditional risk factors for cardiovascular disease, in particular smoking, dyslipidemia, diabetes mellitus or impaired glucose tolerance, and hypertension, have been shown to be more prevalent in HIV-infected populations, and moreover to confer into an increased risk for CVD compared with the general non- infected population of equivalent age[18][19][20][21][22][23]. Although the increased prevalence of traditional CVD risk factors plays an important role in the increased CVD risk in HIV-infected populations, it is unlikely that traditional risk factors are the sole origin of the increased CVD risk in HIV-positive patients. Indeed, in several large cohort studies, statistical risk-adjustment for traditional CVD risk factors was shown to only partly explain the increase in CVD-risk in HIV-positive patients[9] [14], supporting the hypothesis that antiretroviral drug effects and HIV-infection-related factors play an important role in the added risk. https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 2/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology In general, CVD is considered the consequence of a chain of events, initiated by a myriad of risk factors. [24] Intervention anywhere along the chain of events may therefore result in mitigation of the CVD risk, and thereby traditional risk factors constitute an important target for management and prevention of CVD, no less in HIV-infected patients. Non-modifiable risk factors Risk factors that do not constitute a modifiable therapeutic target comprise age, sex, and a family history of CVD. With increasing age, structural and hemodynamic changes in the cardiovascular system, oxidative stress, and endothelial dysfunction progress. Moreover, the duration of exposure to pro- atherogenic risk factors accumulates with advancing age. In general, older people have more atherosclerosis that younger people. Thereby, the risk for CVD increases with advancing age.[25] Importantly, age was shown to be a particularly important determinant of CVD risk in HIV-infected patients. In all age subgroups, HIV-infected patients are at increased risk for in particular AMI in comparison with age- and CVD risk factor-matched non-infected controls. [26][18] The risk for CVD becomes clinically pertinent for men at younger ages than for women: for men, this is in their mid-forties, while this is at the time of menopause for women. The origin of this sex-difference in not yet fully elucidated, but is at least in part explained by an earlier onset of traditional CVD risk factors, such as hypertension and dyslipidemia, in men, and supposed hormonal protective effects in pre-menopausal women.[3] A positive family history is a well-known important risk factor for CVD both in men and women, which risk is independent of other concomitant CVD risk factors.[27] Many risk factors are under genetic control (blood pressure, lipid spectra, obesity), but these do not account for the total aggregated risk observed in families[28], indicating that family history of CVD as a risk factor goes beyond the accumulation of risk from inherited traditional risk factors. It must be noted that while family history is an undisputable risk factor, obviously a large number of modifiable risk factors are found in people with a family history of CVD, adding to the accumulated CVD risk. Although non-modifiable in nature, these risk factors importantly add to the accumulated CVD risk within a specific patient and therefore play an important role in risk stratification and prevention of CVD, in particular in HIV-infected patients. Modifiable risk factors Risk factors that comprise modifiable targets for therapeutic strategies include hypertension, dyslipidemia, diabetes, and smoking. Importantly, the prevalence of these traditional risk factors is increased in HIV-positive populations.[11] Compared with the general population, HIV-infected populations in particular have a higher smoking prevalence, and have a diet high in saturated fat. Evidence has accumulated that HIV-infected patients in general have a more atherogenic lipid spectrum, putting them at particular high risk for CVD.[11][3] However, the relative contribution of each traditional risk factor for CVD risk within a patient is comparable in HIV-infected and uninfected populations, irrespective of HIV-infection status.[3] As such, although the risk factor prevalence is increased in HIV-infected populations, it likely does not at itself explain the increased risk of CVD in this population, and, therefore, several HIV-related factors need to be taken into consideration. Antiretroviral therapy effects https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 3/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Contemporary ART treatment strategies adhere to a combination of antiretroviral drugs (as such called combined ART (cART)), usually consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a protease inhibitor (PI), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) in combination with an integrase inhibitor. Several reports have indicated an association between ART treatment and CVD. In particular early studies have reported an increased risk for early acute myocardial infarction (AMI) in patients treated with PIs, which was associated with concomitantly raised cholesterol levels, a known side-effect of PI treatment.[3][11] The associated risk was related to the duration of PI exposure. Nonetheless, the increased risk persisted after statistical correction for lipid concentrations, which implicates an independent direct effect of PI treatment on early occurrence of AMI. Importantly, such increased risk has not been as clearly established for all PIs, and conclusive data remains absent for several ART agents from the PI group. Nonetheless, even in the presence of an increased risk for early AMI, the risk-benefit ratio remains positive towards PI use, due to the unequivocal benefits of cART on survival that outweigh the PI-use associated risk for AMI. For the NRTI group of ART, in particular for abacavir and didanosine, such an association between drugs and CVD is less clearly established, as large cohort studies have yielded conflicting results.[3][11] Nonetheless, there seems to be a consistent reporting of increased AMI risk in HIV-positive populations treated with (c)ART. The complex interrelation of HIV-infection, antiretroviral drugs and concomitant co-morbidities in the presence of traditional CVD risk factors makes it difficult to extract the actual origin of an increased risk for AMI. Nevertheless, an association between ART drugs and AMI must be assumed for all subclasses of ART drugs, although PI use is most consistently found a determinant of early AMI risk. HIV-infection related factors Besides the CVD risk conferred by the use of aggressive cART, the HIV-infection itself may add to the accumulated CVD risk in HIV-positive patients. HIV-infection related factors include the persistent inflammatory status and immune dysfunction associated with high viral loads, as well as viral load independent factors. Inflammation In general populations, persistent inflammation is associated with an increased risk for CVD.[29][30] Markers of inflammation are persistently elevated in HIV-positive patients[31], which was shown to be directly associated with (increases in) levels of viral loads.[32][33] Different components of HIV are independently associated with increased markers of endothelial cell activation (sVCAM), systemic inflammation (CCL2, IL-10), and adipose tissue activation (adiponectin), which may actively advance atherosclerosis.[34] Moreover, persistent inflammation in HIV-infected patients is directly associated with mortality in this patient population.[35][36] These findings suggest that inflammation itself may explain (part of) the CVD risk in HIV-positive populations additive to traditional risk factors. Immune dysfunction and immune activation Several studies have indicated that immune dysfunction is associated with CVD risk among HIV-infected patients. CD4+ T-cell counts of <500/IL have been associated with an increase in cardiovascular events, independent of traditional CVD risk factors or ART, carrying an additive risk comparable with that of smoking or sub-optimally treated LDL cholesterol levels.[37] CD4+ T-cell counts of <200/IL were associated with an increased risk of AMI, which was comparable in magnitude to the risk imposed by traditional CVD risk factors.[38] Consistently, episodic CD4+ cell count-guided ART is associated with a substantial increase in risk for AMI compared with continuous ART, indicating an important role of viral load and immune dysfunction for the extent of CVD risk.[39] Moreover, several studies have shown a https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 4/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology decrease in non-AIDS related events following the start of ART, and a notable increase in CVD events in patients with incomplete immune recovery following start of ART.[40][41] In addition, the risk of AMI was recently shown to be significantly increased in patients with a recent episode of immune dysfunction defined as CD4 count <200 or HIV-RNA count of >500 copies.[42] It can therefore be acknowledged that (residual) compromise of immune function is an important determinant of risk for CVD as well. Virologic Suppression and the Risk of CVD The associations discussed in the previous sections may implicate that suppression of HIV replication, and normalization of inflammation and immune function by (c)ART mitigates the associated CVD risk. However, even viral replication suppression with (c)ART does not fully normalize these processes, and even residual levels may result in adverse cardiovascular outcome. Concordantly, it was shown that carotid intima media thickness is increased in all HIV-infected subgroups compared with controls, including HIV-infected patients that maintain an undetectable HIV viral load without the use of (c)ART. [15][43] This finding was independent of prior ART exposure duration, viremia, or advanced immunodeficiency. Moreover, a recent large cohort study of HIV-infected patients compared with age and CVD-risk matched non-infected controls including more than 80.000 subjects indicated that, although mitigated by virologic suppression, the risk for CVD, and AMI in particular, remains present despite virologic suppression.[26] In summary, the available evidence indicates that CVD in HIV-infected population is indeed a complex multi-factorial process, which etiology goes beyond the role of traditional risk factors, and beyond the effects of antiretroviral medication. HIV-infection related factors, as well as persistent inflammation and immune dysfunction most probably constitute important additional factors resulting in premature atherosclerosis and accelerated ageing even when the viral replication is suppressed. Prevention of CVD in HIV-infected patients As a corollary of the aforementioned interplay of CVD risk factors and HIV-infection/ therapy, it may be appreciated that prevention of CVD in HIV-positive patients should be emphasized, especially in the light of the contemporary life expectancy of this patient population. In general, cardiovascular therapy guidelines aimed at prevention of CVD in HIV-patients follow those for the general population, although some HIV-related factors must be taken into consideration.[44] Special emphasis should focus upon the identification and treatment of dyslypidemia, which is frequently present in HIV-infected patients, and which is known to occur in reponse to the start of (c)ART therapy, with a particular association with PIs[45] and first generation NRTIs.[11] Therefore, assessment of lipid status, especially triglycerides, should be performed prior to the start of cART therapy, at 3-6 months after initiation of therapy, and at least yearly in the absence of abnormalities. A special point of care lies within lipid-lowering therapy in concomitance with cART treatment, because of the possibility of interaction between statins and for example PIs and NNRTIs.[11] The primary mode of interaction is seen through the cytochrome P450 (CYP) pathway. PIs mainly inhibit CYP, and could therefore lead to toxicity of statins as these drugs are most frequently metabolized through particular CYP pathways. NNRTIs are associated with CYP induction, leading to impairment of statin efficacy. Statins not or only mildly associated with CYP interactions include rosuvastatine and pravastatin, and may therefore be considered in HIV-infected patients on cART. More novel statins, such as pitavastatin, without CYP interaction have not yet been evaluated in this setting. Ezetemibe, which is not metabolized through the CYP pathway, may be considered in addition to statin therapy or as stand-alone therapy when statin therapy leads to unendured side effects. Nonetheless, statin therapy should be tailored to the specific situation and side effects or inefficacy of agents may necessitate statin or cART agent switch https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 5/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology along the way. Especially when cART leads to a subsequent severe dyslipidemia, switching to another cART combination may be considered.[11] However, no clinical trials have been performed on this subject, and therefore the best approach remains patient-tailored. Moreover, in the light of the complex interplay between all CVD risk factors discussed in the previous paragraphs, it is important to note that the actual role of statin therapy in primary prevention in HIV-infected patients has not been established to date. Nonetheless, the evidence to date indicates a very important role of dyslipidemia in the CVD-risk associated with HIV-infection and therapy, and optimal medical therapy should be pursued. In addition, smoking cessation should be actively pursued in patients with HIV, because of its high prevalence and associated increase in CVD risk in this patient population, as well as the significant benefit of smoking cessation.[46] The recent smoking cessation guidelines consequently indentified the HIV-infected population as and important target population for smoking cessation therapy, both interms of counseling as well as medical therapeutic strategies.[47] In the presence of hypertension, renin angiotensin system blockers are considered first choice owing to their global protective effects on kidney function, glucose metabolism, and the vasculature in general.[11] Antiplatelet regimens have not extensively been investigated in HIV-infected populations and it is therefore currently advocated to adhere to general antiplatelet guidelines. In particular aspirin treatment should be initiated as in the general population in the presence of high CVD risk when contraindications are absent.[48] For more aggressive antiplatelet agents, including clopidogrel, prasugrel and ticagrelor, recent investigations have implicated interactions between cART and these potent platelet inhibitors. Ritonavir, a PI-subclass ART, in particular was found to impair prasugrel activity in in vitro experiments. [49] Furthermore, ticagrelor is metabolized by CYP and is contraindicated in patients on PI therapy, in particular in those patients using ritonavir (both ritonavir and ticagrelor are associated with the CYP 3A4/5 pathway).[50] Although the stent-thrombosis rates in HIV-infected patients after percutaneous coronary intervention and coronary stent implantation have not been found to be substantially higher compared with the general population, it should be borne in mind that evidence on the effectiveness of antiplatelet therapy in terms of platelet activity is very limited, and residual platelet activity levels may well play a role in a particular patient. Clinical presentation and revascularization Clinical presentation of advanced CVD in HIV-infected patients involves an equivalently wide spectrum as in the general non-infected population.[51] Nonetheless, as may be appreciated from the previous sections, clinical presentation is predominated by the occurrence of acute coronary syndrome (ACS).[52] [53] Acute coronary syndrome typically occurs in males, at a relatively young age (<50 years of age), in particular in those patients with a prolonged known HIV-infection (>8 years), who remain on (c)ART. The most frequent presentation occurs with an ST-segment elevation myocardial infarction. Nevertheless, presentation with non-ST-segment elevation myocardial infarction and unstable angina occur frequently as well.[51][53][54][55] Contrariwise, stable CVD is less frequent. The extent of coronary artery disease in general does not differ between HIV-infected and non-infected populations. [53] Clinical outcome after revascularization (predominantly for ACS) is similar for HIV-infected and non- infected populations, regardless of whether revascularization is performed percutaneously or surgically. [56][57] HIV-infected patients, however, do remain at increased risk for recurrent ACS during follow- up[58], which is importantly associated with persistently elevated lipid spectra. https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 6/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Key Points: Patients with human immunodeficiency virus infection are at increased risk for cardiovascular disease compared with the general non-infected population. The increased risk originates from an increased pertinence of traditional risk factors for cardiovascular disease, in combination with the detrimental effects of the HIV-infection itself and the adverse (combined) antiretroviral therapy drug effects. Prevention of cardiovascular disease in HIV-positive patients should in particular focus on prevention of dyslipidemia, and smoking, which are both common in HIV-infected patients, and represent important (modifiable) determinants of the cardiovascular disease risk in these patients. Drug interactions in patients treated with (combined) antiretroviral therapy are frequent, especially between antiretroviral therapy and statins or antiplatelet agents such as prasugrel and ticagrelor, which occurs predominantly through the cytochrome P450 pathway. The increased risk for cardiovascular disease predominantly results in an early occurrence of acute myocardial infarction, for which coronary revascularization is associated with good outcome, although recurrent ischemic events are more common in HIV-infected patients than in the general non-infected population. References 1. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD, and HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006 Sep;43(1):27-34. DOI:10.1097/01.qai.0000233310.90484.16 | 2. van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F, and ATHENA national observational cohort study. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010 Jun 19;24(10):1527-35. DOI:10.1097/QAD.0b013e32833a3946 | 3. Fedele F, Bruno N, and Mancone M. Cardiovascular risk factors and HIV disease. AIDS Rev. 2011 Apr-Jun;13(2):119-29. 4. Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, Gordin FM, Vjecha MJ, Neaton JD, Cooper DA, and INSIGHT ESPRIT & SILCAAT study groups. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS. 2010 Jul 31;24(12):1877- 86. DOI:10.1097/QAD.0b013e32833b1b26 | 5. Mathers CD and Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. DOI:10.1371/journal.pmed.0030442 | 6. Lewden C, May T, Rosenthal E, Burty C, Bonnet F, Costagliola D, Jougla E, Semaille C, Morlat P, Salmon D, Cacoub P, Ch ne G, and ANRS EN19 Mortalit Study Group and Mortavic1. Changes in causes of death among adults infected by HIV between 2000 and 2005: The "Mortalit 2000 and 2005" surveys (ANRS EN19 and Mortavic). J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):590-8. DOI:10.1097/QAI.0b013e31817efb54 | 7. Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010 May 15;50(10):1387-96. DOI:10.1086/652283 | 8. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, Boccara F, Bingham A, Costagliola D, and French Hospital Database on HIV-ANRS CO4. Increased risk of myocardial infarction in HIV- infected patients in France, relative to the general population. AIDS. 2010 May 15;24(8):1228-30. DOI:10.1097/QAD.0b013e328339192f | 9. Triant VA, Lee H, Hadigan C, and Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. DOI:10.1210/jc.2006-2190 | 10. Palella FJ Jr, Baker RK, Buchacz K, Chmiel JS, Tedaldi EM, Novak RM, Durham MD, Brooks JT, and HOPS Investigators. Increased mortality among publicly insured participants in the HIV Outpatient https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 7/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Study despite HAART treatment. AIDS. 2011 Sep 24;25(15):1865-76. DOI:10.1097/QAD.0b013e32834b3537 | 11. Boccara F, Lang S, Meuleman C, Ederhy S, Mary-Krause M, Costagliola D, Capeau J, and Cohen A. HIV and coronary heart disease: time for a better understanding. J Am Coll Cardiol. 2013 Feb 5;61(5):511-23. DOI:10.1016/j.jacc.2012.06.063 | 12. Francisci D, Giannini S, Baldelli F, Leone M, Belfiori B, Guglielmini G, Malincarne L, and Gresele P. HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction. AIDS. 2009 Mar 13;23(5):589-96. DOI:10.1097/QAD.0b013e328325a87c | 13. Solages A, Vita JA, Thornton DJ, Murray J, Heeren T, Craven DE, and Horsburgh CR Jr. Endothelial function in HIV-infected persons. Clin Infect Dis. 2006 May 1;42(9):1325-32. DOI:10.1086/503261 | 14. Grunfeld C, Delaney JA, Wanke C, Currier JS, Scherzer R, Biggs ML, Tien PC, Shlipak MG, Sidney S, Polak JF, O'Leary D, Bacchetti P, and Kronmal RA. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS. 2009 Sep 10;23(14):1841-9. DOI:10.1097/QAD.0b013e32832d3b85 | 15. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, Martin JN, and Deeks SG. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS. 2009 Jun 1;23(9):1059-67. DOI:10.1097/QAD.0b013e32832b514b | 16. Guaraldi G, Stentarelli C, Zona S, Orlando G, Carli F, Ligabue G, Lattanzi A, Zaccherini G, Rossi R, Modena MG, Alexopoulos N, Palella F, and Raggi P. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis. 2010 Jan;208(1):222-7. DOI:10.1016/j.atherosclerosis.2009.06.011 | 17. Lo J, Abbara S, Shturman L, Soni A, Wei J, Rocha-Filho JA, Nasir K, and Grinspoon SK. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS. 2010 Jan 16;24(2):243-53. DOI:10.1097/QAD.0b013e328333ea9e | 18. Sav s M, Ch ne G, Ducimeti re P, Leport C, Le Moal G, Amouyel P, Arveiler D, Ruidavets JB, Reynes J, Bingham A, Raffi F, and French WHO MONICA Project and the APROCO (ANRS EP11) Study Group. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. 2003 Jul 15;37(2):292-8. DOI:10.1086/375844 | 19. Kaplan RC, Kingsley LA, Sharrett AR, Li X, Lazar J, Tien PC, Mack WJ, Cohen MH, Jacobson L, and Gange SJ. Ten-year predicted coronary heart disease risk in HIV-infected men and women. Clin Infect Dis. 2007 Oct 15;45(8):1074-81. DOI:10.1086/521935 | 20. Grinspoon SK. Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. Am J Med. 2005 Apr;118 Suppl 2:23S-28S. DOI:10.1016/j.amjmed.2005.01.047 | 21. Gazzaruso C, Bruno R, Garzaniti A, Giordanetti S, Fratino P, Sacchi P, and Filice G. Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome. J Hypertens. 2003 Jul;21(7):1377-82. DOI:10.1097/01.hjh.0000059071.43904.dc | 22. Baekken M, Os I, Sandvik L, and Oektedalen O. Hypertension in an urban HIV-positive population compared with the general population: influence of combination antiretroviral therapy. J Hypertens. 2008 Nov;26(11):2126-33. DOI:10.1097/HJH.0b013e32830ef5fb | 23. Capeau J. From lipodystrophy and insulin resistance to metabolic syndrome: HIV infection, treatment and aging. Curr Opin HIV AIDS. 2007 Jul;2(4):247-52. DOI:10.1097/COH.0b013e3281e66919 | 24. Dzau V and Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J. 1991 Apr;121(4 Pt 1):1244- 63. DOI:10.1016/0002-8703(91)90694-d | 25. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, and Kannel WB. 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Calmy A, Gayet-Ageron A, Montecucco F, Nguyen A, Mach F, Burger F, Ubolyam S, Carr A, Ruxungtham K, Hirschel B, Ananworanich J, and STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009 May 15;23(8):929-39. DOI:10.1097/qad.0b013e32832995fa | 33. Baker J, Ayenew W, Quick H, Hullsiek KH, Tracy R, Henry K, Duprez D, and Neaton JD. High- density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection. J Infect Dis. 2010 Jan 15;201(2):285-92. DOI:10.1086/649560 | 34. Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genn D, N esch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B, Staccato Study Group, and Swiss HIV Cohort Study. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial. Lancet. 2006 Aug 5;368(9534):459-65. DOI:10.1016/S0140-6736(06)69153-8 | 35. Tien PC, Choi AI, Zolopa AR, Benson C, Tracy R, Scherzer R, Bacchetti P, Shlipak M, and Grunfeld C. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr. 2010 Nov;55(3):316-22. DOI:10.1097/QAI.0b013e3181e66216 | 36. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD, and INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008 Oct 21;5(10):e203. DOI:10.1371/journal.pmed.0050203 | 37. Lichtenstein KA, Armon C, Buchacz K, Chmiel JS, Buckner K, Tedaldi EM, Wood K, Holmberg SD, Brooks JT, and HIV Outpatient Study (HOPS) Investigators. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis. 2010 Aug 15;51(4):435-47. DOI:10.1086/655144 | 38. Triant VA, Regan S, Lee H, Sax PE, Meigs JB, and Grinspoon SK. Association of immunologic and virologic factors with myocardial infarction rates in a US healthcare system. J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):615-9. DOI:10.1097/QAI.0b013e3181f4b752 | 39. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, F tkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 9/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Losso M, Markowitz N, Neuhaus J, Phillips A, and Rappoport C. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006 Nov 30;355(22):2283-96. DOI:10.1056/NEJMoa062360 | 40. Moore RD, Gebo KA, Lucas GM, and Keruly JC. Rate of comorbidities not related to HIV infection or AIDS among HIV-infected patients, by CD4 cell count and HAART use status. Clin Infect Dis. 2008 Oct 15;47(8):1102-4. DOI:10.1086/592115 | 41. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, Girard PM, Grund B, Law M, Losso MH, Palfreeman A, and Wood R. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008 Apr 15;197(8):1133-44. DOI:10.1086/586713 | 42. van Lelyveld SF, Gras L, Kesselring A, Zhang S, De Wolf F, Wensing AM, Hoepelman AI, and ATHENA national observational cohort study. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS. 2012 Feb 20;26(4):465-74. DOI:10.1097/QAD.0b013e32834f32f8 | 43. Kaplan RC, Sinclair E, Landay AL, Lurain N, Sharrett AR, Gange SJ, Xue X, Hunt P, Karim R, Kern DM, Hodis HN, and Deeks SG. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis. 2011 Feb 15;203(4):452-63. DOI:10.1093/infdis/jiq071 | 44. Lundgren JD, Battegay M, Behrens G, De Wit S, Guaraldi G, Katlama C, Martinez E, Nair D, Powderly WG, Reiss P, Sutinen J, Vigano A, and EACS Executive Committee. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med. 2008 Feb;9(2):72-81. DOI:10.1111/j.1468-1293.2007.00534.x | 45. DAD Study Group, Friis-M ller N, Reiss P, Sabin CA, Weber R, Monforte Ad, El-Sadr W, Thi baut R, De Wit S, Kirk O, Fontas E, Law MG, Phillips A, and Lundgren JD. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007 Apr 26;356(17):1723-35. DOI:10.1056/NEJMoa062744 | 46. Petoumenos K, Worm S, Reiss P, de Wit S, d'Arminio Monforte A, Sabin C, Friis-M ller N, Weber R, Mercie P, Pradier C, El-Sadr W, Kirk O, Lundgren J, Law M, and D:A:D Study Group. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(*). HIV Med. 2011 Aug;12(7):412-21. DOI:10.1111/j.1468-1293.2010.00901.x | 47. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 2008 Aug;35(2):158-76. DOI:10.1016/j.amepre.2008.04.009 | 48. Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, and Zidar JP. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012 Aug 14;60(7):645-81. DOI:10.1016/j.jacc.2012.06.004 | 49. Daali Y, Ancrenaz V, Bosilkovska M, Dayer P, and Desmeules J. Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug-drug interaction in HIV patients. Metabolism. 2011 Nov;60(11):1584-9. DOI:10.1016/j.metabol.2011.03.015 | 50. Zhou D, Andersson TB, and Grimm SW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos. 2011 Apr;39(4):703-10. DOI:10.1124/dmd.110.037143 | 51. The Society for Adolescent Medicine, annual meeting. Abstracts and program outline for presentations. March 18-22, 1992, Washington, D.C. J Adolesc Health. 1992 Jan;13(1):1-74. 52. Ambrose JA, Gould RB, Kurian DC, DeVoe MC, Pearlstein NB, Coppola JT, and Siegal FP. Frequency of and outcome of acute coronary syndromes in patients with human immunodeficiency https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 10/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology virus infection. Am J Cardiol. 2003 Aug 1;92(3):301-3. DOI:10.1016/s0002-9149(03)00631-3 | 53. Escaut L, Monsuez JJ, Chironi G, Merad M, Teicher E, Smadja D, Simon A, and Vittecoq D. Coronary artery disease in HIV infected patients. Intensive Care Med. 2003 Jun;29(6):969-973. DOI:10.1007/s00134-003-1740-0 | 54. Varriale P, Saravi G, Hernandez E, and Carbon F. Acute myocardial infarction in patients infected with human immunodeficiency virus. Am Heart J. 2004 Jan;147(1):55-9. DOI:10.1016/j.ahj.2003.07.007 | 55. Matetzky S, Domingo M, Kar S, Noc M, Shah PK, Kaul S, Daar E, and Cercek B. Acute myocardial |
32. Calmy A, Gayet-Ageron A, Montecucco F, Nguyen A, Mach F, Burger F, Ubolyam S, Carr A, Ruxungtham K, Hirschel B, Ananworanich J, and STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009 May 15;23(8):929-39. DOI:10.1097/qad.0b013e32832995fa | 33. Baker J, Ayenew W, Quick H, Hullsiek KH, Tracy R, Henry K, Duprez D, and Neaton JD. High- density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection. J Infect Dis. 2010 Jan 15;201(2):285-92. DOI:10.1086/649560 | 34. Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genn D, N esch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B, Staccato Study Group, and Swiss HIV Cohort Study. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial. Lancet. 2006 Aug 5;368(9534):459-65. DOI:10.1016/S0140-6736(06)69153-8 | 35. Tien PC, Choi AI, Zolopa AR, Benson C, Tracy R, Scherzer R, Bacchetti P, Shlipak M, and Grunfeld C. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr. 2010 Nov;55(3):316-22. DOI:10.1097/QAI.0b013e3181e66216 | 36. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD, and INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008 Oct 21;5(10):e203. DOI:10.1371/journal.pmed.0050203 | 37. Lichtenstein KA, Armon C, Buchacz K, Chmiel JS, Buckner K, Tedaldi EM, Wood K, Holmberg SD, Brooks JT, and HIV Outpatient Study (HOPS) Investigators. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis. 2010 Aug 15;51(4):435-47. DOI:10.1086/655144 | 38. Triant VA, Regan S, Lee H, Sax PE, Meigs JB, and Grinspoon SK. Association of immunologic and virologic factors with myocardial infarction rates in a US healthcare system. J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):615-9. DOI:10.1097/QAI.0b013e3181f4b752 | 39. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, F tkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 9/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology Losso M, Markowitz N, Neuhaus J, Phillips A, and Rappoport C. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006 Nov 30;355(22):2283-96. DOI:10.1056/NEJMoa062360 | 40. Moore RD, Gebo KA, Lucas GM, and Keruly JC. Rate of comorbidities not related to HIV infection or AIDS among HIV-infected patients, by CD4 cell count and HAART use status. Clin Infect Dis. 2008 Oct 15;47(8):1102-4. DOI:10.1086/592115 | 41. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, Girard PM, Grund B, Law M, Losso MH, Palfreeman A, and Wood R. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008 Apr 15;197(8):1133-44. DOI:10.1086/586713 | 42. van Lelyveld SF, Gras L, Kesselring A, Zhang S, De Wolf F, Wensing AM, Hoepelman AI, and ATHENA national observational cohort study. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS. 2012 Feb 20;26(4):465-74. DOI:10.1097/QAD.0b013e32834f32f8 | 43. Kaplan RC, Sinclair E, Landay AL, Lurain N, Sharrett AR, Gange SJ, Xue X, Hunt P, Karim R, Kern DM, Hodis HN, and Deeks SG. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis. 2011 Feb 15;203(4):452-63. DOI:10.1093/infdis/jiq071 | 44. Lundgren JD, Battegay M, Behrens G, De Wit S, Guaraldi G, Katlama C, Martinez E, Nair D, Powderly WG, Reiss P, Sutinen J, Vigano A, and EACS Executive Committee. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med. 2008 Feb;9(2):72-81. DOI:10.1111/j.1468-1293.2007.00534.x | 45. DAD Study Group, Friis-M ller N, Reiss P, Sabin CA, Weber R, Monforte Ad, El-Sadr W, Thi baut R, De Wit S, Kirk O, Fontas E, Law MG, Phillips A, and Lundgren JD. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007 Apr 26;356(17):1723-35. DOI:10.1056/NEJMoa062744 | 46. Petoumenos K, Worm S, Reiss P, de Wit S, d'Arminio Monforte A, Sabin C, Friis-M ller N, Weber R, Mercie P, Pradier C, El-Sadr W, Kirk O, Lundgren J, Law M, and D:A:D Study Group. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(*). HIV Med. 2011 Aug;12(7):412-21. DOI:10.1111/j.1468-1293.2010.00901.x | 47. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 2008 Aug;35(2):158-76. DOI:10.1016/j.amepre.2008.04.009 | 48. Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, and Zidar JP. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012 Aug 14;60(7):645-81. DOI:10.1016/j.jacc.2012.06.004 | 49. Daali Y, Ancrenaz V, Bosilkovska M, Dayer P, and Desmeules J. Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug-drug interaction in HIV patients. Metabolism. 2011 Nov;60(11):1584-9. DOI:10.1016/j.metabol.2011.03.015 | 50. Zhou D, Andersson TB, and Grimm SW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos. 2011 Apr;39(4):703-10. DOI:10.1124/dmd.110.037143 | 51. The Society for Adolescent Medicine, annual meeting. Abstracts and program outline for presentations. March 18-22, 1992, Washington, D.C. J Adolesc Health. 1992 Jan;13(1):1-74. 52. Ambrose JA, Gould RB, Kurian DC, DeVoe MC, Pearlstein NB, Coppola JT, and Siegal FP. Frequency of and outcome of acute coronary syndromes in patients with human immunodeficiency https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 10/11 7/4/23, 12:40 AM HIV and the Heart - Textbook of Cardiology virus infection. Am J Cardiol. 2003 Aug 1;92(3):301-3. DOI:10.1016/s0002-9149(03)00631-3 | 53. Escaut L, Monsuez JJ, Chironi G, Merad M, Teicher E, Smadja D, Simon A, and Vittecoq D. Coronary artery disease in HIV infected patients. Intensive Care Med. 2003 Jun;29(6):969-973. DOI:10.1007/s00134-003-1740-0 | 54. Varriale P, Saravi G, Hernandez E, and Carbon F. Acute myocardial infarction in patients infected with human immunodeficiency virus. Am Heart J. 2004 Jan;147(1):55-9. DOI:10.1016/j.ahj.2003.07.007 | 55. Matetzky S, Domingo M, Kar S, Noc M, Shah PK, Kaul S, Daar E, and Cercek B. Acute myocardial infarction in human immunodeficiency virus-infected patients. Arch Intern Med. 2003 Feb 24;163(4):457-60. DOI:10.1001/archinte.163.4.457 | 56. Boccara F, Teiger E, Cohen A, Ederhy S, Janower S, Odi G, Di Angelantonio E, Barbarini G, and Barbaro G. Percutaneous coronary intervention in HIV infected patients: immediate results and long term prognosis. Heart. 2006 Apr;92(4):543-4. DOI:10.1136/hrt.2005.068445 | 57. Boccara F, Cohen A, Di Angelantonio E, Meuleman C, Ederhy S, Dufaitre G, Odi G, Teiger E, Barbarini G, Barbaro G, and French Italian Study on Coronary Artery Disease in AIDS Patients (FRISCA-2). Coronary artery bypass graft in HIV-infected patients: a multicenter case control study. Curr HIV Res. 2008 Jan;6(1):59-64. DOI:10.2174/157016208783571900 | 58. Boccara F, Mary-Krause M, Teiger E, Lang S, Lim P, Wahbi K, Beygui F, Milleron O, Gabriel Steg P, Funck-Brentano C, Slama M, Girard PM, Costagliola D, Cohen A, and Prognosis of Acute Coronary Syndrome in HIV-infected patients (PACS) Investigators. Acute coronary syndrome in human immunodeficiency virus-infected patients: characteristics and 1 year prognosis. Eur Heart J. 2011 Jan;32(1):41-50. DOI:10.1093/eurheartj/ehq372 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=HIV_and_the_Heart&oldid=2358" This page was last edited on 9 May 2013, at 12:50. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/HIV_and_the_Heart 11/11 |
7/4/23, 12:18 AM ICD indications - Textbook of Cardiology ICD indications An overview of ICD and CRT(D) indications as recommended by the European Society of Cardiology. For all indications patient should be on optimal medical therapy and have a life expectancy of > 1 year. Contents Class I (recommendations) Class IIa (should be considered) Class IIb (may be considered) Class III (not recommended) References Class I (recommendations) Patients with left ventricular dysfunction due to prior myocardial infarction who are at least 40 days post MI with LVEF <30-40%, are NYHA class II or III and are receiving chronic optimal medical therapy and with life expectancy > 1 year. IA[1] LV dysfunction due to prior MI, presenting with hemodynamically unstable sustained VT. IA[1][2] Patients with non-ischemic dilated cardiomyopathy (NI DCM) with LV dysfunction who have sustained VT or VF. IA[1] NI DCM LVEF<30-35%. NYHA II-III. Chronic medical therapy. Life expectancy > 1 year. IB[1] Hypertrophic cardiomyopathy with sustained VT or VF. IB[1] Arrhythmogenic right ventricular cardiomyopathy with documented sustained VT or VF. OMT, LE>1y.IB [1] Sustained VT, hemodynamically unstable VT, VT with syncopy, or VF. LVEF< 40%. IA[1] LQTS with previous cardiac arrest. IA[1] Brugada syndrome with previous cardiac arrest. IC[1] CPVT with previous cardiac arrest. IC[1] An ICD is recommended in a patient with heart failure with a ventricular arrhythmia causing haemodynamic instability. LE>1y. IA [2] CRTD is recommended in patients with sinus rhythm, LBBB, QRS > 130ms, EF<30%, NYHA II. IA [2] [3] CRTD is recommended in patients with sinus rhythm, LBBB, QRS > 120ms, EF<35%, NYHA III-IV. IA [2][3] CRT in patient with an other Class I pacemaker indication who is in NYHA III/IV, LVEF 35%, QRS 120 ms. IB[4] Syncope, documented VT and structural heart disease. IB [4] https://www.textbookofcardiology.org/wiki/ICD_indications 1/4 7/4/23, 12:18 AM ICD indications - Textbook of Cardiology When monomorphic VT is induced at EP study in patients with previous myocardial infarction and syncope. IB [4] Class IIa (should be considered) LV dysfunction due to prior MI, at least 40 days post MI, LVEF < 30-35%, NYHA I, on chronic medical therapy, life expectancy >1y. IIaB[1] Recurrent VT in post MI patient with normal or near normal LVEF on chronic medical therapy, life expectancy > 1y. IIaC[1] In patients with life threatening arrhythmias who are not in the acute phase of myocarditis, on chronic medical therapy, life expectancy >1y. IIaC[1] Unexplained syncope, significant LV dysfunction, non-ischemic DCM. Optimal medical therapy, LE>1y. IIaC[1] Sustained VT with (near) normal LV function and non-ischemic DCM. Optimal medical therapy, LE>1y. IIaC[1] HCM with high risk (>5% in 5y): http://doc2do.com/hcm/webHCM.html [5] Arrhythmogenic right ventricular cardiomyopathy with extensive disease, including those with LV dysfunction 1 or more affected family members with SCD, or undiagnosed syncope when VT or VF has not been excluded as the cause of syncope. OMT, LE>1y.IB [1] CRTD, NYHA III/IV, SR, QRS>120ms. IIaB. [1] LQTS with syncope and / or VT while on beta blockers. [1] Brugada syndrome with spontaneous type I ECG and who have had syncope. [1] Brugada syndrome with documented VT that has not resulted in cardiac arrest. [1] A CRTD should be considered in a patient with non-LBBB, QRS > 150ms, EF<35%, NYHA III-IV . IIaA[2] A CRTD should be considered in a patient with non-LBBB, QRS > 150ms, EF<30%, NYHA II . IIaA[2] [3][3] A CRTD/CRTP may be considered to reduce the risk of HF worsening in a patient with atrial fibrillation who is pacemaker dependant, after AV nodal ablation QRS > 130ms, EF<35%, NYHA III- IV . IIaA[2][3] CRT may be considered to reduce the risk of HF worsening in a patient with atrial fibrillation who requires pacing because of intrinsically slow ventricular rate with QRS > 130ms, EF<35%, NYHA III- IV . IIaC[2][3] In patients with documented VT with inherited cardiomyopathies or channelopathies. IIaB. [4] CRT in patient with an other Class I pacemaker indication who is in NYHA III/IV, LVEF 35%, QRS <120 ms. IIaC[4] Class IIb (may be considered) nonischemic DCM, LVEF < 30-35%, NYHA I. optimal medical therapy, LE>1y. IIbC[1] CRT may be considered to reduce the risk of HF worsening in a patient with atrial fibrillation who requires pacing because of a rate of < 60 bpm in rest and < 90 bpm on exercise with QRS > 120ms, EF<35%, NYHA III-IV . IIbC[2] CRT should be considered in those patient with atrial fibrillation in NYHA functional class II with an EF 35%, irrespective of QRS duration, to reduce the risk of worsening of HF. IIbC[2] https://www.textbookofcardiology.org/wiki/ICD_indications 2/4 7/4/23, 12:18 AM ICD indications - Textbook of Cardiology CRT in patient with an other Class I pacemaker indication who is in NYHA II, LVEF 35%, QRS <120 ms. IIbC[4] Class III (not recommended) ICD implantation is not recommended during the acute phase of myocarditis[1] References 1. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, American College of Cardiology, American Heart Association Task Force, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association, and Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace. 2006 Sep;8(9):746-837. DOI:10.1093/europace/eul108 | 2. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, B hm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, K ber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, R nnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, and ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012 Aug;14(8):803-69. DOI:10.1093/eurjhf/hfs105 | 3. Dickstein K, Vardas PE, Auricchio A, Daubert JC, Linde C, McMurray J, Ponikowski P, Priori SG, Sutton R, van Veldhuisen DJ, and ESC Committee for Practice Guidelines (CPG). 2010 Focused Update of ESC Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J. 2010 Nov;31(21):2677-87. DOI:10.1093/eurheartj/ehq337 | 4. Task Force for the Diagnosis and Management of Syncope, European Society of Cardiology (ESC), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, Deharo JC, Gajek J, Gjesdal K, Krahn A, Massin M, Pepi M, Pezawas T, Ruiz Granell R, Sarasin F, Ungar A, van Dijk JG, Walma EP, and Wieling W. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009 Nov;30(21):2631-71. DOI:10.1093/eurheartj/ehp298 | https://www.textbookofcardiology.org/wiki/ICD_indications 3/4 7/4/23, 12:18 AM ICD indications - Textbook of Cardiology 5. Authors/Task Force members, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, and Watkins H. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014 Oct 14;35(39):2733-79. DOI:10.1093/eurheartj/ehu284 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=ICD_indications&oldid=2548" This page was last edited on 26 May 2015, at 23:02. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/ICD_indications 4/4 |
7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology Infective Endocarditis Author: A. Crystal Contents Introduction Epidemiology Pathogenesis and Causes Diagnosis Definite IE: Possible IE: Rejected IE: Therapy Prophylaxis Complications of Endocarditis Prognosis References Introduction Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non- infective causes of endocarditis occur, this chapter will concentrate on infective causes. Epidemiology The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years[1]. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years[2]. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users[3]. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices[4]. Pathogenesis and Causes https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 1/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology Generally, valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves[5]. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves[6]. endothelial damage to heart While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. Large lesions on non coronary and left coronary cusps normal valves otherwise Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%[7]. S.aureus is a highly virulent organism and may cause significant formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE[8]. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively[6]. valve destruction, abscess Vegetations on tricuspid valve S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%[9]. Viridans group streptococcus often account for 30% of community acquired native valve endocarditis[10]. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high. Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps. Septic emboli to the conjunctiva Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen. https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 2/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users[11]. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%[12]. Diagnosis Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.[13] The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment. Definite IE: Pathologic Criteria: Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis Clinical Criteria 2 major criteria OR 1 major and 3 minor criteria OR 5 minor criteria Possible IE: 1 Major criterion + 1 Minor criterion OR 3 minor criteria Rejected IE: Firm alternate diagnosis explaining evidence of IE OR Resolution of IE syndrome with =<4 days of antibiotics therapy OR No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days OR Does not meet criteria for IE, as above https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 3/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology Major Criteria (microbiology) e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source Typical organisms x 2 blood cultures With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures Persistent bacteremia Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800 Major Criteria (valve) Echocardiogram with evidence of vegetation TTE or TEE New valvular regurgitation Minor Criteria Predisposing cardiac condition or IV drug use >38 degrees celsius or Fever >100.4 fahrenheit) major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions Vascular phenomena Immune phenomena glomerulonephritis, Osler nodes, Roth spots, positive RF Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE The sensitivity of detecting on echocardiogram varies. Transthoracic and echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.[14][15] transesophageal Endocarditis of prosthetic mitral valve PLAX: vegetations on PMVL (http://www. echopedia.org/images/2/24/E00404.swf) Video courtesy: AMC Echolab, AMC, The Netherlands A4CH (http://www.echopedia.org/ima ges/6/6a/E00405.swf) Video courtesy: AMC Echolab, AMC, The Netherlands Endocarditis of the aortic valve PLAX: showing an aortic valve vegetation (http://www.echopedia.org/ima ges/1/10/E00114.swf) Video courtesy: J. Vleugels, AMC, The Netherlands PLAX: aortic valve vegetation (http:// www.echopedia.org/images/5/5b/E0 0117.swf) Video courtesy: J. Vleugels, AMC, The Netherlands Therapy Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 4/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram include negative bacilli. Options for such therapy Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin. When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. As soon as blood cultures become available antibiotics should identified to microorganisms. Roth Spots be adjusted target the In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.[16] The American Heart Association recommendation for specific antimicrobial therapy can be found in their guideline (http://circ.ahajournals.org/content/111/23/3167.full). The European Society of Cardiology guideline for the treatment of Infective endocarditis. (http://eurhea rtj.oxfordjournals.org/content/30/19/2369.long) Prophylaxis According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:[17] Any prosthetic heart valve, or prosthetic material used for valve repair Previous infective endocarditis Congenital heart disease (CHD) Unrepaired cyanotic CHD, including all palliative shunts and conduits Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) Cardiac transplantation recipients who develop cardiac valvulopathy Dental procedures require prophylaxis: Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa Respiratory tract procedures require prophylaxis: https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 5/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.[17] Complications of Endocarditis Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. Heart failure occurs in 26-30% of patients with endocarditis.[18][19] It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%). [12] The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.[20] Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.[21] Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.[22][23] Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.[24] Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.[25] Prognosis Prognosis of IE is largely dependent on the patient s comorbid conditions such as diabetes,[26] hemodialysis, congestive heart failure,[27] complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.[28] Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,[29] while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.[30] References 1. "Infective Endocarditis - N Engl J Med 2013." 12 Sep. 2013 (http://www.nejm.org/doi/full/10.1056/NE JMcp1206782) 2. Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 6/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology 3. Mir JM, del R o A, and Mestres CA. Infective endocarditis in intravenous drug abusers and HIV-1 infected patients. Infect Dis Clin North Am. 2002 Jun;16(2):273-95, vii-viii. DOI:10.1016/s0891- 5520(01)00008-3 | 4. Ipek EG, Guray U, Demirkan B, Guray Y, and Aksu T. Infections of implantable cardiac rhythm devices: predisposing factors and outcome. Acta Cardiol. 2012 Jun;67(3):303-10. DOI:10.2143/AC.67.3.2160719 | 5. Pappelbaum KI, Gorzelanny C, Gr ssle S, Suckau J, Laschke MW, Bischoff M, Bauer C, Schorpp- Kistner M, Weidenmaier C, Schneppenheim R, Obser T, Sinha B, and Schneider SW. Ultralarge von Willebrand factor fibers mediate luminal Staphylococcus aureus adhesion to an intact endothelial cell layer under shear stress. Circulation. 2013 Jul 2;128(1):50-9. DOI:10.1161/CIRCULATIONAHA.113.002008 | 6. Rasmussen RV, H st U, Arpi M, Hassager C, Johansen HK, Korup E, Sch nheyder HC, Berning J, Gill S, Rosenvinge FS, Fowler VG Jr, M ller JE, Skov RL, Larsen CT, Hansen TF, Mard S, Smit J, Andersen PS, and Bruun NE. Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography. Eur J Echocardiogr. 2011 Jun;12(6):414-20. DOI:10.1093/ejechocard/jer023 | 7. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, Doco-Lecompte T, Celard M, Poyart C, Strady C, Chirouze C, Bes M, Cambau E, Iung B, Selton-Suty C, Hoen B, and AEPEI Study Group. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol. 2012 May 29;59(22):1968-76. DOI:10.1016/j.jacc.2012.02.029 | 8. Miro JM, Anguera I, Cabell CH, Chen AY, Stafford JA, Corey GR, Olaison L, Eykyn S, Hoen B, Abrutyn E, Raoult D, Bayer A, Fowler VG Jr, and International Collaboration on Endocarditis Merged Database Study Group. Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. Clin Infect Dis. 2005 Aug 15;41(4):507-14. DOI:10.1086/431979 | 9. Lalani T, Kanafani ZA, Chu VH, Moore L, Corey GR, Pappas P, Woods CW, Cabell CH, Hoen B, Selton-Suty C, Doco-Lecompte T, Chirouze C, Raoult D, Miro JM, Mestres CA, Olaison L, Eykyn S, Abrutyn E, Fowler VG Jr, and International Collaboration on Endocarditis Merged Database Study Group. Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database. Eur J Clin Microbiol Infect Dis. 2006 Jun;25(6):365-8. DOI:10.1007/s10096-006-0141-z | 10. McDonald JR. Acute infective endocarditis. Infect Dis Clin North Am. 2009 Sep;23(3):643-64. DOI:10.1016/j.idc.2009.04.013 | 11. Das M, Badley AD, Cockerill FR, Steckelberg JM, and Wilson WR. Infective endocarditis caused by HACEK microorganisms. Annu Rev Med. 1997;48:25-33. DOI:10.1146/annurev.med.48.1.25 | 12. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, Taubert KA, Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association, and Infectious Diseases Society of America. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005 Jun 14;111(23):e394-434. DOI:10.1161/CIRCULATIONAHA.105.165564 | 13. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, and Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000 Apr;30(4):633-8. DOI:10.1086/313753 | https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 7/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology 14. Evangelista A and Gonzalez-Alujas MT. Echocardiography in infective endocarditis. Heart. 2004 Jun;90(6):614-7. DOI:10.1136/hrt.2003.029868 | 15. M gge A, Daniel WG, Frank G, and Lichtlen PR. Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol. 1989 Sep;14(3):631-8. DOI:10.1016/0735- 1097(89)90104-6 | 16. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, Moreillon P, de Jesus Antunes M, Thilen U, Lekakis J, Lengyel M, M ller L, Naber CK, Nihoyannopoulos P, Moritz A, Zamorano JL, and ESC Committee for Practice Guidelines. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009 Oct;30(19):2369-413. DOI:10.1093/eurheartj/ehp285 | 17. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT, American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, American Heart Association Council on Cardiovascular Disease in the Young, American Heart Association Council on Clinical Cardiology, American Heart Association Council on Cardiovascular Surgery and Anesthesia, and Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007 Oct 9;116(15):1736-54. DOI:10.1161/CIRCULATIONAHA.106.183095 | 18. The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013 (http://www.ncbi.nl m.nih.gov/genome/sts/sts.cgi?uid=85362) 19. Hollanders G, De Scheerder I, De Buyzere M, Ingels G, Bogaert S, and Clement DL. A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features. Acta Cardiol. 1988;43(2):121-32. 20. Kiefer T, Park L, Tribouilloy C, Cortes C, Casillo R, Chu V, Delahaye F, Durante-Mangoni E, Edathodu J, Falces C, Logar M, Mir JM, Naber C, Tripodi MF, Murdoch DR, Moreillon P, Utili R, and Wang A. Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure. JAMA. 2011 Nov 23;306(20):2239-47. DOI:10.1001/jama.2011.1701 | 21. Meine TJ, Nettles RE, Anderson DJ, Cabell CH, Corey GR, Sexton DJ, and Wang A. Cardiac conduction abnormalities in endocarditis defined by the Duke criteria. Am Heart J. 2001 Aug;142(2):280-5. DOI:10.1067/mhj.2001.116964 | 22. Homma S and Grahame-Clarke C. Toward reducing embolic complications from endocarditis. J Am Coll Cardiol. 2003 Sep 3;42(5):781-3. DOI:10.1016/s0735-1097(03)00843-x | 23. Hubert S, Thuny F, Resseguier N, Giorgi R, Tribouilloy C, Le Dolley Y, Casalta JP, Riberi A, Chevalier F, Rusinaru D, Malaquin D, Remadi JP, Ammar AB, Avierinos JF, Collart F, Raoult D, and Habib G. Prediction of symptomatic embolism in infective endocarditis: construction and validation of a risk calculator in a multicenter cohort. J Am Coll Cardiol. 2013 Oct 8;62(15):1384-92. DOI:10.1016/j.jacc.2013.07.029 | 24. Thuny F, Di Salvo G, Belliard O, Avierinos JF, Pergola V, Rosenberg V, Casalta JP, Gouvernet J, Derumeaux G, Iarussi D, Ambrosi P, Calabr R, Riberi A, Collart F, Metras D, Lepidi H, Raoult D, Harle JR, Weiller PJ, Cohen A, and Habib G. Risk of embolism and death in infective endocarditis: https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 8/9 7/4/23, 12:36 AM Infective Endocarditis - Textbook of Cardiology prognostic value of echocardiography: a prospective multicenter study. Circulation. 2005 Jul 5;112(1):69-75. DOI:10.1161/CIRCULATIONAHA.104.493155 | 25. Snygg-Martin U, Gustafsson L, Rosengren L, Alsi A, Ackerholm P, Andersson R, and Olaison L. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis. 2008 Jul 1;47(1):23-30. DOI:10.1086/588663 | 26. Kourany WM, Miro JM, Moreno A, Corey GR, Pappas PA, Abrutyn E, Hoen B, Habib G, Fowler VG Jr, Sexton DJ, Olaison L, Cabell CH, and ICE MD Investigators. Influence of diabetes mellitus on the clinical manifestations and prognosis of infective endocarditis: a report from the International Collaboration on Endocarditis-Merged Database. Scand J Infect Dis. 2006;38(8):613-9. DOI:10.1080/00365540600617017 | 27. Nakagawa T, Wada H, Sakakura K, Yamada Y, Ishida K, Ibe T, Ikeda N, Sugawara Y, Ako J, and Momomura S. Clinical features of infective endocarditis: comparison between the 1990s and 2000s. J Cardiol. 2014 Feb;63(2):145-8. DOI:10.1016/j.jjcc.2013.06.007 | 28. Bikdeli B, Wang Y, Kim N, Desai MM, Quagliarello V, and Krumholz HM. Trends in hospitalization rates and outcomes of endocarditis among Medicare beneficiaries. J Am Coll Cardiol. 2013 Dec 10;62(23):2217-26. DOI:10.1016/j.jacc.2013.07.071 | 29. Wang A, Pappas P, Anstrom KJ, Abrutyn E, Fowler VG Jr, Hoen B, Miro JM, Corey GR, Olaison L, Stafford JA, Mestres CA, Cabell CH, and International Collaboration on Endocarditis Investigators. The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort. Am Heart J. 2005 Nov;150(5):1086-91. DOI:10.1016/j.ahj.2005.01.023 | 30. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG Jr, Corey GR, Chu VH, Fenely M, Pachirat O, Tan RS, Watkin R, Ionac A, Moreno A, Mestres CA, Casab J, Chipigina N, Eisen DP, Spelman D, Delahaye F, Peterson G, Olaison L, Wang A, and International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation. 2010 Mar 2;121(8):1005-13. DOI:10.1161/CIRCULATIONAHA.109.864488 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&oldid=2498" This page was last edited on 8 December 2013, at 20:46. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Infective_Endocarditis 9/9 |
7/4/23, 12:19 AM LQTS - Textbook of Cardiology LQTS Auteur: Louise R.A. Olde Nordkamp Supervisor: Arthur A.M. Wilde The Long QT Syndrome (LQTS) refers to a condition in which there is an abnormally long QT interval on the ECG. This was first recognized by Dr. Jervell and Dr. Lange-Nielsen in 1957. They described 4 children with a long QT interval which was accompanied by hearing deficits, sudden cardiac death and an autosomal recessive inheritance. The LQTS may be divided into two distinct forms: congenital LQTS and acquired LQTS. These forms may however overlap when QT prolongation due to medication occurs in a patient with congenital LQTS. File:De-Formule QTc.png Formula for heart rate corrected QT interval (Bazett s formula) Contents Diagnosis General Physical examination Acquired LQTS Notorious QT prolonging drugs: Concomittant risk factors for medication induced torsade de pointes: Congenital LQTS Clinical diagnosis ECG tests Genetic diagnosis Risk Stratification Treatment "Lifestyle modification": Medication/Other therapies: References Diagnosis General The diagnosis is by measurement of the heart rate corrected QT interval on the ECG, which can be calculated with the QTc calculator. Sometimes the QT interval can be difficult to assess. Read the guidelines for measurement of difficult QT interval. https://www.textbookofcardiology.org/wiki/LQTS 1/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology A QTc of > 500ms in patients with Long QT Syndrome is associated with an increased risk of torsade de pointes and sudden death.[1] In patients suspected of LQTS (e.g. family members of known genotyped LQTS patients) a QTc > 430ms makes it likely that a LQTS gene defect is present. Because the QTc can change with age, it is best to take the ECG with the longest QTc interval (without additional QT-prologing factors) for risk stratification. Physical examination Patients can present with symptoms of arrhythmias: Fast or slow heart beat Weakness, lightheadedness, dizziness, syncope Chest pain Shortness of breath Paleness Sweating Acquired LQTS https://www.textbookofcardiology.org/wiki/LQTS 2/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology Acquired LQTS is most often caused by drugs that prolong the QT interval; combined with risk factors the risk of Torsade de Pointes is likely to increase. Notorious QT prolonging drugs: 1. Amiodarone 2. Chloroquine 3. Chlorpromazine 4. Citalopram 5. Claritromycin 6. Disopyramide 7. Dofetilide 8. Erythromycin 9. Flecainide 10. Halofantrine 11. Haloperidol 12. Quinidine 13. Sotalol Concomittant risk factors for medication induced torsade de pointes: 1. Female sex 2. Hypokalemia 3. Bradycardia 4. Recent conversion of atrial fibrillation, especially if QT prolonging drugs were used (sotalol, amiodarone) 5. Cardiac decompensation 6. Digoxin treatment 7. High or overdosing or rapid infusion of a QT prolonging drug 8. Pre-existing QT prolongation 9. Congenital QT syndrome Congenital LQTS The prevalence of congenital LQTS is about 1:2000-2500. More than 10 different types of congenital LQTS have been described. However, only LQTS 1-3 are relatively common. The three most common forms of LQTS can be recognized by the characteristic clinical features and ECG abnormalities https://www.textbookofcardiology.org/wiki/LQTS 3/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology LQTS type LQTS 1 LQTS 2 LQTS 3 KCNQ1/IKs KCNH2/IKr Gene/current SCN5A/INa B-blokker efficacy ++++ +++ ++ Late onset T wave with normal configuration Early onset broad based T wave ECG Small late T wave Adrenergic triggers, especially nightly noise Arrhythmogenic triggers Exercise, especially swimming Rest Number of mutation carriers with events at age <15 40% 20% 10% Number of mutation carriers with events at age <40 60% 60% 50% Sudden cardiac death incidence Eponyme 0,30% / year 0,60% / year 0,56% / year If condition is homozygous: Jervell and Lange-Nielsen syndrome 1 Eponyme Before the genes involved were known, some syndromes associated with a prolonged QT interval on the ECG had been described earlier: Anton Jervell and Fred Lange-Nielsen from Oslo described in 1957 an congenital syndrome that was associated with QT interval prolongation, deafness and sudden death: the now called Jervell-Lange- Nielsen syndrome. Romano-Ward syndrome is a long QT syndrome with normal auditory function and autosomal dominant inheritance.[2] Andersen-Tawil syndrome was described in 1994 by Tawil et al. and was associated with potassium- sensitive periodic paralysis, ventricular ectopy and dysmorphic features (short stature, low-set ears, hypoplastic mandible, clinodactyly and scoliosis). It later appeared to be associated with a mutation in the KCNJ2 gene (LQTS type 7). Timothy syndrome is a LQTS syndrome (with frequently alternating T-waves) with webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycaemia, cognitive abnormalities and autism. It appeared to be caused by a single mutation in the CACNA1C gene (LQTS type 8). https://www.textbookofcardiology.org/wiki/LQTS 4/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology Findings Points >480 ms 3 460-479 2 ECG QTc: 450-459 (in males) 1 >480 during X-ECG 1 Torsade de pointes 2 T-wave alternans 1 Notched T-wave in 3 leads 1 Low heart rate for age (<2nd percentile for age) 0.5 With stress 2 Syncope: Without stress 1 Congenital deafness 0.5 Clinical history Family members with definite LQTS 1 Family history Unexplained sudden cardiac death before age 30 0.5 Total score 1 Low probability; 1.5-3 Intermediate probability; 3.5 High probability Diagnostic criteria by Schwartz et al. (2011)[3] Clinical diagnosis Diagnosis of LQTS is established by prolongation of the QTc interval in the absence of specific conditions known to lengthen it (for example QT-prolonging drugs) and/or molecular genetic testing of genes associated with LQTS. The prolonged QT interval can cause torsades de pointes, which is usually self-terminating, thus potentially causing a cardiac syncopal event. In LQTS type 1, cardiac symptoms are often precipitated by exercise; especially swimming is notorious for life-threatening cardiac events. In LQTS type 2, arrhythmogenic triggers are adrenergic; especially nightly noise (such as the morning alarm clock or nightly thunderlightening) is known to cause life-threatening cardiac events. On the other hand, in LQTS type 3, QT prolongation and possibly subsequent torsade de pointes is precipitated by bradycardia. ECG tests ECGs can be difficult because there is a considerable overlap between the QT interval of affected and unaffected individuals. https://www.textbookofcardiology.org/wiki/LQTS 5/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology The resting ECG is neither completely sensitive nor specific for the diagnosis of LQTS. The diagnostic criteria for the resting ECG are shown above in the list of diagnostic criteria by Schwartz et al. Besides a prolonged QTc, the T- wave can have different patterns among the different genotypes. Holter recordings appear to be of minimal clinical utility from a diagnostic and prognostic prospective in evaluating LQTS The exercise ECG (X-ECG) commonly shows failure of the QT to shorten normally, thereby prolonging the corrected QT interval, and many individuals develop characteristic T-wave abnormalities. A brisk-standing test ECG, where the QT-interval is measured after abrupt standing with subsequent heart rate acceleration. There appears to be a form of QT-stretching and QT-stunning [4] as demonstrated by Viskin et al. and Adler et al. Epinephrine infusion is a provocative test that might increase the sensitivity of the ECG findings. However, especially the negative predictive value is high. Adenosine infusion is a test provoking transient bradycardia followed by sinus tachycardia and therefore triggers QT changes that can distinguish patients with LQTS from healthy controls[5] Various triggers for cardiac events have been identified among the different genotypes. Genetic diagnosis Today, 14 LQTS genes associated with LQTS have identified. Most commonly, KCNQ1, KCNH2 and SCN5A, which are associated with LQTS type 1, type 2 and type 3 respectively, are found. Other, less frequently involved genes are displayed the table below. been Various triggers for cardiac events have been identified among the different genotypes. There is an important genotype-phenotype relationship on severity of the disease.[3] In genotype phenotype studies in the Rochester LQTS registry it was shown that in both LQTS type 1 and type 2, mutation locations and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder. https://www.textbookofcardiology.org/wiki/LQTS 6/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology LQTS type Gene Protein (Ionchannel) OMIM-link KVLQT1 (IKs) Type 1 KCNQ1 607542 HERG (IKr) Type 2 KCNH2 613688 Sodium channel (INa) Type 3 SCN5A 603830 Ankyrin B (INa, K) Type 4 ANK2 600919 minK (IKs) Type 5 KCNE1 176261 MiRP1 (IKr) Type 6 KCNE2 613693 Kir 2.1 (IK1) Type 7 KCNJ2 170390 Cav1.2 (ICa-L) Type 8 CACNA1C 601005 Type 9 CAV3 Caveolin-3 601253 Sodium channel (INa) Type 10 SCN4B 608256 A-Kinase anchor 9 (IKs) Type 11 AKAP9 604001 Syntrophin (INa) Type 12 SNTA1 601017 Kir3.4 (IK) Type 13 KCNJ5 600734 Type 14 CALM1 Calmodulin 1 114180 Risk Stratification Gene-specific differences of the natural history of LQTS have also been demonstrated and allow genotype-based risk stratification. Indeed, QT interval duration, gender and genotype (including mutation location and degree of ion channel dysfunction) are significantly associated with the outcome, with a QTc interval >500ms, and a LQT2 or LQT3 genotype determining the worst prognosis. Gender differently modulates the outcome according to the underlying genetic defect: the LQT3 males and LQT2 females are the highest risk subgroups. Risk stratification is best done by an expert cardio-genetics cardiologist. Treatment "Lifestyle modification": Probably no competitive sports in all LQTS patients Avoid QT-prolonging drugs in all LQTS patients No swimming or diving in LQT1 patients https://www.textbookofcardiology.org/wiki/LQTS 7/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology Avoid nightly or sudden noise in LQT2 patients (e.g. no alarm clock) Medication/Other therapies: Beta-blockers are the cornerstone of therapy in LQTS. Beta-blockers even reduce the risk of sudden death in patients in whom a genetic defect has been found, but no QT prolon References 1. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, and Cappelletti D. Risk stratification in the long-QT syndrome. N Engl J Med. 2003 May 8;348(19):1866-74. DOI:10.1056/NEJMoa022147 | 2. Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, Alders M, Bikker H, and Christiaans I. Long QT Syndrome. 1993. 3. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, and Bloise R. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001 Jan 2;103(1):89- 95. DOI:10.1161/01.cir.103.1.89 | 4. Adler A, van der Werf C, Postema PG, Rosso R, Bhuiyan ZA, Kalman JM, Vohra JK, Guevara- Valdivia ME, Marquez MF, Halkin A, Benhorin J, Antzelevitch C, Wilde AA, and Viskin S. The phenomenon of "QT stunning": the abnormal QT prolongation provoked by standing persists even as the heart rate returns to normal in patients with long QT syndrome. Heart Rhythm. 2012 Jun;9(6):901-8. DOI:10.1016/j.hrthm.2012.01.026 | 5. Viskin S, Rosso R, Rogowski O, Belhassen B, Levitas A, Wagshal A, Katz A, Fourey D, Zeltser D, Oliva A, Pollevick GD, Antzelevitch C, and Rozovski U. Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome. Eur Heart J. 2006 Feb;27(4):469-75. DOI:10.1093/eurheartj/ehi460 | 6. Shimizu W, Moss AJ, Wilde AA, Towbin JA, Ackerman MJ, January CT, Tester DJ, Zareba W, Robinson JL, Qi M, Vincent GM, Kaufman ES, Hofman N, Noda T, Kamakura S, Miyamoto Y, Shah S, Amin V, Goldenberg I, Andrews ML, and McNitt S. Genotype-phenotype aspects of type 2 long QT syndrome. J Am Coll Cardiol. 2009 Nov 24;54(22):2052-62. DOI:10.1016/j.jacc.2009.08.028 | 7. Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, and McNitt S. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 May 15;115(19):2481-9. DOI:10.1161/CIRCULATIONAHA.106.665406 | 8. Sy RW, van der Werf C, Chattha IS, Chockalingam P, Adler A, Healey JS, Perrin M, Gollob MH, Skanes AC, Yee R, Gula LJ, Leong-Sit P, Viskin S, Klein GJ, Wilde AA, and Krahn AD. Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation. 2011 Nov 15;124(20):2187-94. DOI:10.1161/CIRCULATIONAHA.111.028258 | 9. Schwartz PJ and Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation. 2011 Nov 15;124(20):2181-4. DOI:10.1161/CIRCULATIONAHA.111.062182 | 10. Viskin S, Postema PG, Bhuiyan ZA, Rosso R, Kalman JM, Vohra JK, Guevara-Valdivia ME, Marquez MF, Kogan E, Belhassen B, Glikson M, Strasberg B, Antzelevitch C, and Wilde AA. The response of https://www.textbookofcardiology.org/wiki/LQTS 8/9 7/4/23, 12:19 AM LQTS - Textbook of Cardiology the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol. 2010 May 4;55(18):1955-61. DOI:10.1016/j.jacc.2009.12.015 | 11. Shimizu W, Noda T, Takaki H, Nagaya N, Satomi K, Kurita T, Suyama K, Aihara N, Sunagawa K, Echigo S, Miyamoto Y, Yoshimasa Y, Nakamura K, Ohe T, Towbin JA, Priori SG, and Kamakura S. Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome. Heart Rhythm. 2004 Sep;1(3):276-83. DOI:10.1016/j.hrthm.2004.04.021 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=LQTS&oldid=2283" This page was last edited on 25 March 2013, at 21:14. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/LQTS 9/9 |
7/4/23, 12:37 AM Myocardial and Pericardial Disease - Textbook of Cardiology Myocardial and Pericardial Disease Myocardial Disease Myocardial Disease - Secondary Hypertension or valvular disease Ischemic cardiomyopathy Alcohol Metabolic cardiomyopathy Tako-tsubo cardiomyopathy Peripartum cardiomyopathy Tachycardia-induced cardiomyopathy Myocardial Disease - Primary Hypertrophic cardiomyopathy Dilated cardiomyopathy Cardiomyopathy in muscular dystrophy Restrictive cardiomyopathy Infiltrative cardiomyopathy Storage diseases Arrythmic cardiomyopathy: Arrhythmogenic Right Ventricular Cardiomyopathy Unclassified Cardiomyopathy: Left ventricular non-compaction Pericardial Disease Pericardial Disease - Acute Cardiac Tamponade Acute pericarditis Recurrent pericarditis Pericardial Disease - Chronic Chronic constrictive pericarditis Subacute elastic constriction Effusive-constrictive pericarditis Transient cardiac constriction Pericardial Disease - Specific types Infectious pericarditis Idiopathic/Viral pericarditis Tuberculous pericarditis Purulent pericarditis Post myocardial infarction pericarditis https://www.textbookofcardiology.org/wiki/Myocardial_and_Pericardial_Disease 1/2 7/4/23, 12:37 AM Myocardial and Pericardial Disease - Textbook of Cardiology Neoplastic pericarditis Hypothyroidism Post-pericardiotomy pericarditis Retrieved from "http://www.textbookofcardiology.org/index.php?title=Myocardial_and_Pericardial_Disease&oldid=1597" This page was last edited on 5 December 2012, at 14:35. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Myocardial_and_Pericardial_Disease 2/2 |
7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Myocardial Disease Contents Myocardial Disease - Secondary Hypertension or valvular disease Ischemic cardiomyopathy Alcohol Metabolic cardiomyopathy Tako-tsubo cardiomyopathy Peripartum cardiomyopathy Tachycardia-induced cardiomyopathy Myocardial Disease - Primary Hypertrophic cardiomyopathy Genetics Epidemiology Pathophysiology Diastolic dysfunction Ischemia Arrhythmia Wall thinning and cavity dilation Clinical diagnosis Echocardiography Electrocardiography Medical treatment Invasive treatment of obstructive HCM Dual chamber pacing Prognosis and outcome Dilated cardiomyopathy Genetics Pathophysiology Clinical diagnosis Management of DCM Specific dilated cardiomyopathies Cardiomyopathy in muscular dystrophy Prognosis and outcome Restrictive cardiomyopathy Infiltrative cardiomyopathy Amyloidosis Types of amyloidosis Cardiac amyloidosis https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 1/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Clinical manifestations Clinical diagnosis Physical examination Electrocardiography Echocardiography Management Sarcoidosis Pathophysiology Clinical diagnosis Management Storage diseases Hemochromatosis Diagnostic features Management Fabry disease (angiokeratoma corporis diffusum universale) Gaucher Disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Hypereosinophilic syndrome: L ffler Endocarditis Arrythmic cardiomyopathy: Arrhythmogenic Right Ventricular Cardiomyopathy Diagnosis Treatment Unclassified Cardiomyopathy: Left ventricular non-compaction Clinical Presentation and Diagnosis Treatment and Prognosis Myocardial Disease Overall, myocardial diseases can be subdivided into two types: primary and secondary myocardial diseases. Whereas the primary type most commonly has a genetic cause, secondary myocardial diseases are mostly acquired but may be precipitated by a genetic background. Overall, the dilated type is the most prevalent manifestation of cardiomyopathy, and may be induced by a multitude of precipitating factors, such as chronic ischemia or alcohol abuse. The most common primary myocardial disease is hypertrophic cardiomyopathy, which is associated with a wide variety of genetic abnormalities. In the light of their substantially larger prevalence, we will first describe the secondary myocardial diseases, after which the less frequently occurring primary myocardial diseases will be discussed. Myocardial Disease - Secondary Myocardial disease subsequent to a known origin is termed secondary myocardial disease. Timely correction of the originating disease may result in reversal of the cardiomyopathy. Nine different etiologies can be distinguished: https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 2/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Hypertension Ischaemia Valvular disease Alcohol Metabolic cardiomyopathy Takotsubo cardiomyopathy Peripartum cardiomyopathy Tachycardia Hypertension or valvular disease Inadequately treated hypertension or aortic stenosis results in adaptation of the left ventricle by means of hypertrophy. Although primarily considered an adaptive process to systolic overload, hypertrophy of the left ventricle is associated with ventricular dysfunction, arrhythmias, and sudden cardiac death. The process of hypertrophy involves enlargement and proliferation of myocytes, and interstitial fibrosis characterized by deposition of collagen type I and III. With increasing fibrosis, the compliance of the ventricle decreases resulting in loss of diastolic function before systolic function becomes impaired. Within this process of increasing myocardial mass, the coronary vasculature fails to adapt accordingly. In an attempt to accommodate to the increase in myocardial oxygen demand, coronary autoregulatory vasodilation results in an increase in coronary flow by during resting conditions. This partial exhaustion the coronary vasodilator reserve renders the myocardium at relative high risk for ischemia, and hence, patients may suffer from anginal complaints even in the absence of significant coronary artery disease. In patients with LVH, atrial fibrillation and ventricular arrhythmias, including multifocal ventricular extrasystoles, and short runs of ventricular tachycardia, are frequently found. The combination of myocardial fybrosis, maladaptation of the vasculature causing ischemia, autonomic imbalance and a prolongation of the action potential may serve as arrhythmogenic substrate in patients with LVH, resulting in an increased risk of sudden cardiac death. Adequate antihypertensive treatment can regress left ventricular mass. In patients with aortic stenosis, ultimate treatment is valvular replacement to relief the systolic overload of the ventricle. With regression of the ventricle, improved diastolic, and preserved systolic function result, as well as a relief of vascular maladaptation-induced ischemia; the combination of which results in a decrease in cardiovascular events. Ischemic cardiomyopathy Chronic myocardial ischemia due to diffuse coronary atherosclerosis can cause cardiomyopathy of the dilated type (DCM). This ischemic cardiomyopathy may occur following one or multiple (silent) myocardial infarction(s), but may also occur from chronic (silent) ischemic myocardial damage. As such, it may be a progressive course of ventricular dilatation and ventricular dysfunction, but may also be the first manifestation of ischemic heart disease. The extent of viable, or hibernating, myocardium determines the clinical relevance of revascularization of the ischemic myocardium. In patients with viable myocardial tissue, reperfusion improves symptoms, and supposedly prognosis. Several non-invasive tests may be used for this purpose, such as nuclear techniques, dobutamine echocardiography or contrast-enhanced cardiac MRI. However, the prognosis of https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 3/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology ischemic cardiomyopathy is worse than non-ischemic forms of DCM, mainly due to a high risk of major ventricular arrhythmias. Moreover, subsequent ischemic episodes have a high impact on ventricular function in ischemia-related DCM. As stated previously, revascularization may improve long-term prognosis in patients with objectively viable myocardium. In the absence of viability, routine heart failure therapy is the cornerstone of treatment including beta-blockade and ACE-inhibition (or angiotensine antagonists), and ICD implantation in a selection of patients. Alcohol Long-term alcohol abuse, >80g of alcohol per day (equivalent to 1 liter of wine) for more than 5 years, may lead to a dilated form of cardiomyopathy. Alcohol-induced dilated cardiomyopathy is the leading cause of non-ischemic dilated cardiomyopathy, some claim that it accounts for even up to 50% of cases. Most probably a genetic predisposition for DCM also plays an important role, as excess alcohol consumption itself prevails far more often than alcoholic cardiomyopathy (ACM). Both direct toxic effects of ethanol and its metabolites, as well as frequently occurring concomitant deficiencies of vitamins, minerals or electrolytes may adversely affect myocardial function. Two stages of ACM are recognized when the disease is left untreated. The first stage comprises asymptomatical ventricular dilatation in which diastolic dysfunction may be present, at least partly due to interstitial fibrosis of the myocardium. Fifty percent of asymptomatic patients have echocardiographic signs of LVH with preserved systolic function. The second stage is characterized by impairment of systolic function, and clinically overt heart failure. The prognosis of untreated ACM is comparable to DCM, but is far more favourable in patients that abstain from alcohol use, or dramatically reduce alcohol intake (to less than 60g of ethanol per day). Most of the improvement follows abstinence within 6 months, but ventricular function may improve for up to 2 years. Heart failure therapy may improve ventricular function, but has only been shown to benefit survival in patients that practise abstinence. Metabolic cardiomyopathy The group of metabolic cardiomyopathies comprises a heterogenous group of myocardial disease secondary to a disruption in metabolism. Metabolic cardiomyopathy associated with diabetes mellitus is most common. Independent of its influence on hypertension or coronary artery disease, high levels of plasma glucose are increasingly associated with a direct deteriorative effect on ventricular function. Other examples of metabolic disease able to induce cardiomyopathy are nutritional deficits such as thiamine deficiency, or storage diseases, and mutations in AMP kinase. Tako-tsubo cardiomyopathy The prevalence of tako-tsubo cardiomyopathy is largely unknown, but the syndrome predominantly affects women between 60 and 65 years of age. Patients with Tako-tsubo cardiomyopathy present with electrocardiographic features mimicking an acute coronary syndrome in association with elevated cardiac biomarkers, but in the absence of significant coronary artery disease. The disease has inherited its name from the distinct angiographic feature of apical ballooning, resembling an octopus-pot or "Tako-tsubo". Left ventricular function is typically impaired in the apical and mid ventricular regions, with preserved basal function, although reverse patterns may be seen. High levels of cathecholamines have been suggested to play an important role in the etiology of the syndrome, which can be associated with emotional or physical stress, or in extremes in case of subarachnoidal hemmorhage. This https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 4/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology cathecholamine storm may induce severe peripheral coronary spasm, leading to its clinical presentation. Treatment usually consists of aspirin, ACE-inhibitors or angiotensin receptor antogonists in case of preserved blood pressure, beta-blockers to to reduce heart counteract coronary spasms. LV function may restore rapidly within a few hours or days, even when admission ejection fraction was severely impaired, and clinical outcome is good although the disease may recur in approximately 5% of patients. rate, and nitrates Peripartum cardiomyopathy function Left impairment within 1 month of delivery, or during the first 5 months post partum, in the absence of pre-existing cardiac disease, and in the absence of another recognized cause for the cardiac dysfunction is termed peripartum cardiomyopathy. ventricular systolic Presentation is typically with features of left ventricular failure, although many features from normal changes in pregnancy, due to which mild forms may not even be recognized. An inflammatory component has been suggested, in addition to malnutrition, viral infection, an abnormal immune response, and familial predisposition. Recurrence of the disease in subsequent pregnancies is noted, and makes the previously mentioned etiologies hard to explain. Most probably, peripartum cardiomyopathy results from predisposition to DCM, triggered to uncover by the high cardiovascular burden of the pregnancy. are undistinguishable Tako-tsubo cardiomyopathy Standard heart failure therapy can be instituted in peripartum cardiomyopathy, but the use of ACE- inhibitors and angiotensin receptor antagonists is contraindicated during pregnancy after the first trimester due to their possible adverse effects on the fetus. In extreme cases, the potential risks for the fetus should however be balanced against the critical need for preservation of ventricular function in order to provide both the mother and the fetus the best chance for a favourable clinical outcome. Pregnancy is also associated with a high risk of thrombo-embolism, as it is a hypercoagulable state per definition, which is enhanced by the presence of an impaired ventricular function in case of peripartum cardiomyopathy, and prophylaxis is therefore recommended. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 5/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Despite optimal treatment, LV function may normalize in as less as 50% of patients, and may deteriorate to end-stage heart failure in 15%. Potential recurrence in future pregnancies requires counselling of patients to prevent subsequent episodes of symptomatic heart failure and progression of ventricular dysfunction. Tachycardia-induced cardiomyopathy Persistently high heart rates (above 110 beats per minute), such as in sustained ventricular tachycardia, or associated with atrial fibrillation, results in heart failure when left untreated. Normalization of the heart rate by means of beta-blockade subsequently leads to normalization of ventricular function, and is therefore the cornerstone in treatment of tachycardia-induced cardiomyopathy. Myocardial Disease - Primary Five different groups of primary myocardial disease exist; which are defined as diseases of the myocardium with impaired cardiac function, also referred to as cardiomyopathies. Hypertrophic cardiomyopathy (HCM) Dilated cardiomyopathy (DCM) Restrictive cardiomyopathy (RCM) Arrythmic cardiomyopathy (ACM) Unclassified cardiomyopathy (UCM) Hypertrophic cardiomyopathy The essential characteristics of hypertrophic cardiomyopathy (HCM) are unexplained hypertrophy of the left ventricle in the absence of causal cardiac or systemic disorders. Distinctive features further comprise myocyte disarray, familial occurrence, and an association with sudden cardiac death (SCD). Genetics The identification of the genetic background of HCM resulted in the hypothesis that HCM is a disease of the sarcomere; the contractile unit of the cell. First, mutations were found in the cardiac B-myosin heavy chain gene, while later on other sarcomeric proteins were found to play a role in HCM (Table 1). Table 1. Sarcomeric genes associated with HCM -tropomyosin cardiac troponin T troponin I myosin-binding protein C regulatory myosin light chain essential myosin light chain cardiac actin titin troponin C -myosin heavy chain https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 6/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology It was shown that macroscopic hypertrophy of the myocardium is not essential for neither diagnosis nor prognosis, as mutations for example in troponin T may lead to only minor or no hypertrophy, whereas it is associated with a high incidence of SCD. Nowadays HCM is considered a genetic disorder, inherited mainly autosomal dominant with an incomplete and age-related penetrance. Pathological findings may include myocardial hypertrophy, small-vessel disease and myocyte disarray with or without fibrosis. The prevalence of HCM in the adult population is approximately 1 in 500. But as in only 60% of HCM patients mutations in the abovementioned known sarcomeric genes are present, non-sarcomeric variants of HCM or mutations in regulatory genes, have gained interest. Left ventricular hypertrophy in young children is known most often not to be caused by sarcomeric HCM, but rather by inherited metabolic disorders and syndromes with extracardiac features. These diseases may cause to non-sarcomeric HCM as they include Fabry disease and Danon disease. Recognition and diagnosis of HCM may involve familial counselling, which also helps to find the presence of extracardiac features, and may influence treatment. Epidemiology The prevalence of the HCM phenotype was found to be approximately 0.2%, or 1 in 500, in several epidemiological studies. This frequency is notably higher than its occurrence in daily clinical practice. Hence, a large amount of patients remains undiagnosed, most probably without symptoms of inferences for their prognosis. Pathophysiology Left ventricular outflow tract obstruction (LVOTO) The subdivision of HCM into obstructive and non-obstructive forms is clinically important, and is based on the presence or absence of a LV outflow tract gradient during rest and/or after provocation. The presence of such a gradient typically results in a loud apical systolic ejection murmur. The obstruction leads to an increase in intraventricular pressures, impairing LV function by increasing myocardial wall stress and oxygen demand. The obstruction is located either sub-aortic or mid-cavity, where the sub- aortic location is most common and is caused by systolic anterior motion (SAM) of the mitral valve and mid-systolic contact with the ventricular septum. SAM is thought to be facilitated by either an abnormal valvular apparatus loose enough to allow movement, or a hemodynamic force with an anterior component during systole. A drag-effect probably attributes to SAM, which refers to the force exerted by a fluid in the direction of the flow. Apart from its role in sub-aortic obstruction, SAM also results in concomitant mitral regurgitation. The sub-aortic gradient and associated LV pressure increase are pathophysiologically significant and may worsen outcome. LVOTO is an independent predictor for HCM-related death, progression of the disease in terms of New York Heart Association (NYHA) class III or IV, and death due to heart failure or stroke. A gradient threshold of 30 mmHg is prognostically important, but a further increase is not associated with further increased risk. Chronic outflow tract obstruction results in an increase in LV wall stress, myocardial ischemia and fibrosis, and justifies intervention in severely symptomatic patients when optimal medical management is insufficient. HCM patients can be divided into hemodynamic subgroups based on the representative obstructive gradient: 1. Obstructive - gradient under resting conditions equal to or greater than 30 mm Hg (2.7 m/s by Doppler) 2. Provocable obstructive (latent) - gradient less than 30 mm Hg under resting conditions and equal to or greater than 30 mm Hg with provocation https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 7/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology 3. Nonobstructive - less than 30 mm Hg under both resting and provocated conditions. LV outflow gradients are routinely measured noninvasively with continuous wave Doppler echocardiography. To define provocable gradients, treadmill or bicycle exercise testing is the preferred stress test, given that HCM-related symptoms are typically elicited with exertion. Pharmacological induction of stress by intravenous infusion of dobutamine is considered contra-indicated. Diastolic dysfunction HCM is, in contrast to other cardiomyopathies, characterized by early occurrence of diastolic dysfunction (both active and passive phases), while systolic function is typically preserved, even before signs of hypertrophy. The passive relaxation during filling of the ventricle is hampered by increased chamber stiffness, increasing filling pressures and decreasing myocardial blood flow. Isovolumetric relaxation in early diastole is prolonged in HCM. Diastolic dysfunction may well lie at the basis of heart failure in non- obstructive HCM with preserved systolic function. Ischemia Myocardial hypertrophy disrupts the subtle equilibrium of blood flow throughout the myocardial layers. Patients with HCM show an increase in coronary blood flow velocity compared to healthy individuals reflecting an autoregulatory decrease in microvascular resistance to adapt to an increase in oxygen demand during resting conditions. The coronary reserve is therefore partly exhausted. Apart from the changes in the coronary microcirculation, systolic extravascular compression might play a role. Most importantly, HCM results in a progressive mismatch between muscle tissue and vascular growth, resulting in a high risk of myocardial ischemia especially for the subendocardial layers. The presence of myocardial ischemia is an important determinant of progression of the disease as it promotes scarring and remodelling of the ventricle. Arrhythmia Myocardial fibrosis associated with HCM is an important arrhythmogenic substrate. Functional consequences of HCM may therefore provide a trigger for ventricular arrhythmias, i.e. ischemia and LVOTO, resulting in non-sustained ventricular tachycardia in approximately 20% of patients. Other functional consequences as diastolic dysfunction, mitral regurgitation, as well as LVOTO are associated with atrial fibrillation (AF) which is observed in 20-25% of HCM patients. Wall thinning and cavity dilation https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 8/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Over time, thinning of the hypertrophic LV wall may occur in patients with severe LVH which may account for the lack of marked echocardiographic LVH in the elderly. While mechanisms of LV remodelling in HCM are still to be defined, cavity dilation and hampered systolic function occur in less than 5% of patients. Clinical diagnosis The cornerstone of HCM diagnosis is represented by echocardiography and electrocardiography. In the overall population, the diagnostic criterion of HCM is a maximal wall thickness greater or equal to 15 mm. However, virtually any wall thickness may be associated with the presence of an HCM mutant gene, including wall thickness well within the normal range. Therefore, for both echocardiography and electrocardiography, criteria have been established for the diagnosis of HCM in patients with high risk for HCM. Specificity of these criteria relies significantly on the a-priori chance of HCM, and is therefore only pertinent in first-degree relatives of index cases with confirmed HCM, whom therefore all have a 50% a-priori chance of carrying an HCM mutation. HCM is confirmed in a first-degree relative when either 1 major or 2 minor echocardiographic criteria (Table 2), or 1 minor echocardiographic and 2 minor electrocardiographic criteria (Table 3) are present. Echocardiography Two-dimensional echocardiography is the easiest diagnostic modality for detection of HCM, (Table 2) but cardiac magnetic resonance imaging (CMR) may be used when echocardiography is inconclusive, acoustic windows are insufficient, or when more detailed anatomic information is needed for clinical decision making. Echocardiographic characteristics include thickening of the left ventricular wall without cavity dilatation, and a normal or hyperdynamic left ventricle. Left ventricular outflow tract obstruction is not mandatory for the diagnosis of HCM. Moreover, as mentioned previously, although the diagnosis of HCM is based on a cut-off value for maximal wall thickness of 15 mm in the overall population, multiple HCM-linked mutations are associated with only minor LVH, but represent a high risk of sudden cardiac death. Table 2. Echocardiographic diagnostic criteria for HCM in first-degree relatives of index cases with HCM : Major: LV wall thickness =13 mm in the anterior septum or =15 mm in the posterior septum or free wall Severe SAM (septum leaflet contact) Minor: LV wall thickness of 12mm in the anterior septum or posterior wall or of 14mm in the posterior septum or free wall Moderate SAM (no septum leaflet contact) Redundant mitral valve leaflets Electrocardiography https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 9/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Electrocardiographic signs of HCM are typical as the increase in myocardial tissue increases the size of the QRS complexes. Therefore, a typical ECG characteristic of HCM is that it meets voltage criteria for LVH, and shows changes in repolarization (Table 3). Table 3. Electrocardiographic diagnostic criteria for HCM in first-degree relatives of index cases with HCM : Major: Left ventricular hypertrophy and repolarization changes T-wave inversion in leads I and aVL (=3mm) (with QRS T wave axis difference =30 ), V3 V6 (=3mm) or II and III and aVF (=5mm) Abnormal Q (>40 ms or >25% R wave) in at least two leads from II, III, aVF (in absence of left anterior hemiblock), V1 V4; or I, aVL, V5 V6 Minor: Complete bundle branch block or (minor) interventricular conduction defect (in LV leads) Minor repolarization changes in LV leads Deep S V2 (>25mm) Medical treatment Asymptomatic HCM patients should only receive drugs when symptoms of diastolic dysfunction are present. Verapamil is the treatment of choice, improving diastolic filling and relaxation of the ventricle, decreasing diastolic filling pressures. In symptomatic patients, first line medical treatment consists of a calcium-channel blocker or a betablocker. Verapamil is the first choice, but diltiazem may be used as an alternative. Second, beta- blockers may be used when symptoms prevail, and can be used solitarily or in combination with a calcium-channel blocker. In severely symptomatic patients, diuretics may be used, but with high caution as a small drop in ventricular filling pressure may reduce stroke volume and cardiac output dramatically in HCM patients. A combination can be made with either calcium-channel blockers or beta-blockers. Patients presenting with ventricular tachyarrhythmia or supraventricular atrial fibrillation, amiodarone may be used, and may even improve symptoms and prognosis. Disopyramide has negative inotropic action and results in peripheral vasoconstriction and may improve symptoms when diastolic dysfunction is most prominent (i.e. with preserved ejection fraction). Invasive treatment of obstructive HCM In patients where maximal medical treatment does not control the symptoms, invasive debulking of the myocardial septum may be considered when a marked outflow gradient is present. Treatment options comprise percutaneous alcohol septal ablation, or surgical septal myectomy. Surgical myectomy has shown excellent long-term result, but 15-20% of patients may suffer from ventricular remodelling and dilatation of the left ventricle. Since the introduction of alcohol ablation, surgical myectomy is reserved for patients with HCM with concomitant disease that independently https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 10/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology warrants surgical correction, such as coronary artery bypass grafting of valve repairs, in whom surgical myectomy can be performed as part of the operation. Septal ablation may be considered in patients with outflow tract gradients of more than 30 50 mmHg at rest or 60-100 mmHg after provocation. By injection of 1-3 mL of pure alcohol over 5 minutes into the first or second septal branch, a small myocardial infarction is created. Furthermore, the alcohol induces septal hypokinesis, adding to a reduction of the outflow tract gradient. The gradient may resolve immediately, but this process may take weeks to months. When the outflow tract obstruction persists, patients can be treated a second time. Dual chamber pacing In patients with medically refractory symptoms, whom are suboptimal candidates for invasive treatment, permanent dual chamber pacing may be considered. Pacing may alleviate symptoms by decreasing the outflow tract pressure gradient. However, maintaining a reduction in gradient requires pre-exitation of the right ventricular apex and distal septum, and complete ventricular caption. For optimal results, this should therefore be performed in highly experienced centers only. Prognosis and outcome In general, symptoms of HCM increase with age. Mortality rates have been reported to account between 2 and 3% per year. Most importantly, patients with HCM may be at high risk of sudden cardiac initial death, which may even be presentation, in asymptomatic or mildly symptomatic young patients. HCM is the most common cause of SCD in young people, including athletes. The pathophysiological basis for this predilection is unclarified, and although SCD is most frequent in young people less than 30 to 35 years old, an increased risk for SCD extends thereafter. Although HCM presentation and clinical manifestation is heterogeneous, and it has a clinical markers as shown in Table 4 may identify patients at high risk for SCD. Patients at high risk of SCD are eligible candidates for ICD implantation. its particular in Treatment strategy in HCM relatively low prevalence, https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 11/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 4. Risk factors for SCD Major Cardiac arrest (ventricular fibrillation) Spontaneous sustained ventricular *tachycardia Family history of premature sudden cardiac death Unexplained syncope LV thickness = 30mm Abnormal exercise blood pressure (increase in systolic blood pressure =20 mmHg) Nonsustained ventricular tachycardia (Holter) Minor Atrial fibrillation Myocardial ischemia LV outflow tract obstruction High-risk mutation Intense (competitive) physical exertion Fibrosis on CMR Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by ventricular dilatation (one or both ventricles) and impaired myocardial contractility. The impairment of myocardial function cannot be explained by abnormal loading conditions alone, such as valve disease or systemic hypertension. The prevalence of DCM is approximately 36 per 100 000; in at least 50% of patients with DCM, its cause cannot be determined which is referred to as idiopathic DCM. DCM is a condition of which causes and presentations are highly heterogeneous. The diagnosis of idiopathic DCM should only be made after exclusion of the specific cardiomyopathies with a dilated phenotype. Genetics The genetic background of DCM is not as clear as in HCM. Although previously thought to be sporadic, genetic transmission is now thought to account for 30-40% of cases. Multiple genes have been identified that are linked with the occurrence of DCM. Genetic disease may account in part for the primary forms of DCM, but importantly, genetic predisposure may well lead to DCM in case of exposure to precipitating factors such as (emotional) stress, excessive alcohol use or stress upon the cardiovascular system; secondary DCM. The expression of DCM in the familial form is frequently incomplete, and hence its prevalence is supposedly underestimated to a large extent. Even minor abnormalities may progress into overt DCM, and accurate clinical screening of (asymptomatic) relatives is therefore mandatory for early identification of familial DCM cases. Pathophysiology https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 12/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology In general, a wide variety of factors can induce or contribute to the development of DCM including arterial hypertension, myocarditis, alcohol abuse or tachyarrhythmias. A subsequent increase in wall stress combined with activation of neurohumoral pathways induces complex cellular and molecular maladaptation, and programmed cell death finally leads to a decrease in the number of functioning cardiomyocytes. This process of cardiac remodelling itself results in systolic and/or diastolic dysfunction, leading to increased wall stress, and thereby creating a vicious circle of progressive systolic dysfunction (Figure 1). The failing myocardium has several distinct factors promoting apoptosis of cardiomyocytes in vitro; cathecholamines, wall stress, angiotensin II, nitric oxide and inflammatory cytokines. Hence, medical management of DCM aims at antagonizing these pathways, reducing stress signalling in, and remodelling of the failing heart. Clinical diagnosis The most common initial manifestation of DCM is heart failure, in which clinical symptoms do not differ from heart failure of other causes. An important feature of is a gallop the physical examination rhythm of S3 and S4. S3 and S4 may fuse in tachycardic patients with new onset of heart failure. Special attention should focus upon excluding valvular heart disease as a cause, and excluding right- sided involvement. Figure 1. Process of cardiac remodelling Diagnostic testing in DCM focuses on identification of reversible causes, which focuses on the history (alcohol use) but also includes plasma biomarker evaluation, non-invasive imaging, electrocardiography, and exercise testing. Echocardiography is an important diagnostic modality in DCM, as it can be used to assess both the size and shape of the LV, but also to determine LV function by assessing the LV ejection fraction (LVEF). Furthermore, valvular heart disease or pericardial abnormalities can be excluded. CMR evaluation may contribute to identification of specific cardiomyopathic conditions, especially when acoustic windows are suboptimal. The cardiac response to exertion is an established risk factor in DCM patients, which may be evaluated by cardiopulmonary exercise testing. Dilatation of the ventricular cavity results in myocyte stretch. In response, B-type natriuretic peptide is released, which is a well-known neurohormone that can be used to evaluate progression of DCM and to guide medical treatment. High plasma concentrations (twice the ULN) are strongly associated with increased long-term mortality. Electrocardiography does not provide an accurate diagnostic mean in DCM, but can identify several characteristics associated with unfavourable prognosis, or identify factors contributing to DCM, and therefore is an important modality in the evaluation of DCM patients. Sinus tachycardia is frequently present, and non-specific ST-segment or T-wave changes as well as changes in P-wave morphology may well be present. AF is an important feature associated with high mortality; its control may contribute to improve cardiac performance. Furthermore, the presence of AF may indicate tachycardia-induced DCM. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 13/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology 24-hour Holter monitoring can reveal decreased heart rate variability or complex ventricular arrhythmias which are associated with a high risk for mortality. Finally, prolonged QTc intervals are associated with high mortality. Management of DCM Management of symptoms and progression of DCM accord to those described in the management of heart failure. Hence, also in DCM, diuretics and neurohumoral antagonists provide the basis for management of symptoms, and preventive ICD or pacemaker implantation is indicated in selected patients. Most importantly, surgical or percutaneous correction of underlying conditions facilitating progression of DCM, such as coronary artery disease, valvular heart disease or congenital abnormalities is warranted. Specific dilated cardiomyopathies It is important to note that there are several causes of secondary DCM. A foursome of these is of utmost importance to recognize early on, as accurate diagnosis influences the patients treatment strategy and chance for complete recovery. Tako-tsubo Is described under Secondary Myocardial Disease Peripartum cardiomyopathy Is described under Secondary Myocardial Disease Tachycardia-induced cardiomyopathy Is described under Secondary Myocardial Disease Alcoholic cardiomyopathy Is described under Secondary Myocardial Disease Cardiomyopathy in muscular dystrophy Defined as primary disorders of skeletal and/or cardiac muscles of genetic etiology, muscular dystrophies were primarily described based upon the distribution and extent of skeletal muscle involvement. The involvement of the heart was commonly attributed to processes extrinsic to the heart, resulting in restrictive lung disease, subsequent pulmonary hypertension, and secondary myocardial dysfunction. Intrinsic dysfunction is increasingly recognized as an important etiology for myocardial function impairment in the presence of muscular dystrophy. Typical forms of dystrophy are based on deficiency of dystrophin, of which mutations have been described in X-linked DCM. Furthermore, histological changes were found in the myocardium similar to those in skeletal muscles, which suggest a common etiology, and moreover cardiac manifestations may be present even in the absence of myopathic symptoms. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 14/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Treatment of cardiac dysfunction is treated according to the nature of cardiac involvement. Conduction disorders may present which require pacing, and standard heart failure therapy may be instituted in case of ventricular dilatation and functional impairment. Ventricular tachyarrhythmias may be found in particular in myotonic dystrophia, and require the implantation of an internal cardiac defibrillator to prevent its associated sudden cardiac death. Prognosis and outcome DCM has a highly variable clinical course. Approximately half of DCM patients respond well to routine heart failure medication, and a minority of patients even shows an improving clinical course. Conversely, a subgroup can be identified with a highly unfavourable clinical course, not responsive to heart failure medication and rapidly progressing to inotropy- or LVAD-dependency. Overall, 5-year survival rates approximate 30%. Restrictive cardiomyopathy Restrictive cardiomyopathy is characterized by an increase in ventricular wall stiffness, impairing its diastolic function. Systolic function is usually preserved in early stages of the disease, but may deteriorate with progression of the disease. RCM is less frequent in the developed world than the previously described HCM and DCM, but is an important cause of death in Africa, India, South and Central America, and Asia due to the high endemic incidence of endomyocardial fibrosis. The spectrum of restrictive cardiomyopathies can be classified as shown in Table 5, according to its cause. The most important specific causes of RCM will be discussed in detail below. An important differentiation is that between RCM and constrictive pericarditis. Constrictive pericarditis is similarly characterized by impaired ventricular filling with preserved systolic function, but may be adequately treated by pericardiectomy, which makes this distinction of major clinical importance. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 15/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 5 - Classification of Restrictive Cardiomyopathy Myocardial Noninfiltrative Idiopathic cardiomyopathy Familial cardiomyopathy Hypertrophic cardiomyopathy Scleroderma Pseudoxanthoma elasticum Diabetic cardiomyopathy Infiltrative Amyloidosis Sarcoidosis Hurler disease Fatty infiltration Storage Disease Hemochromatosis Fabry disease Gaucher disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Hypereosinophilic syndrome Carcinoid heart disease Metastatic cancers Radiation Toxic effects of anthracycline Drugs causing fibrous endocarditis(serotonin, methysergide, ergotamine, mercurial agents, busulfan) Adapted from Kushwaha S, Fallon JT, Fuster V: Restrictive cardiomyopathy. N Engl J Med 336:267, 1997. Copyright 1997, Massachusetts Medical Society. Infiltrative cardiomyopathy Amyloidosis |
Clinical diagnosis The most common initial manifestation of DCM is heart failure, in which clinical symptoms do not differ from heart failure of other causes. An important feature of is a gallop the physical examination rhythm of S3 and S4. S3 and S4 may fuse in tachycardic patients with new onset of heart failure. Special attention should focus upon excluding valvular heart disease as a cause, and excluding right- sided involvement. Figure 1. Process of cardiac remodelling Diagnostic testing in DCM focuses on identification of reversible causes, which focuses on the history (alcohol use) but also includes plasma biomarker evaluation, non-invasive imaging, electrocardiography, and exercise testing. Echocardiography is an important diagnostic modality in DCM, as it can be used to assess both the size and shape of the LV, but also to determine LV function by assessing the LV ejection fraction (LVEF). Furthermore, valvular heart disease or pericardial abnormalities can be excluded. CMR evaluation may contribute to identification of specific cardiomyopathic conditions, especially when acoustic windows are suboptimal. The cardiac response to exertion is an established risk factor in DCM patients, which may be evaluated by cardiopulmonary exercise testing. Dilatation of the ventricular cavity results in myocyte stretch. In response, B-type natriuretic peptide is released, which is a well-known neurohormone that can be used to evaluate progression of DCM and to guide medical treatment. High plasma concentrations (twice the ULN) are strongly associated with increased long-term mortality. Electrocardiography does not provide an accurate diagnostic mean in DCM, but can identify several characteristics associated with unfavourable prognosis, or identify factors contributing to DCM, and therefore is an important modality in the evaluation of DCM patients. Sinus tachycardia is frequently present, and non-specific ST-segment or T-wave changes as well as changes in P-wave morphology may well be present. AF is an important feature associated with high mortality; its control may contribute to improve cardiac performance. Furthermore, the presence of AF may indicate tachycardia-induced DCM. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 13/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology 24-hour Holter monitoring can reveal decreased heart rate variability or complex ventricular arrhythmias which are associated with a high risk for mortality. Finally, prolonged QTc intervals are associated with high mortality. Management of DCM Management of symptoms and progression of DCM accord to those described in the management of heart failure. Hence, also in DCM, diuretics and neurohumoral antagonists provide the basis for management of symptoms, and preventive ICD or pacemaker implantation is indicated in selected patients. Most importantly, surgical or percutaneous correction of underlying conditions facilitating progression of DCM, such as coronary artery disease, valvular heart disease or congenital abnormalities is warranted. Specific dilated cardiomyopathies It is important to note that there are several causes of secondary DCM. A foursome of these is of utmost importance to recognize early on, as accurate diagnosis influences the patients treatment strategy and chance for complete recovery. Tako-tsubo Is described under Secondary Myocardial Disease Peripartum cardiomyopathy Is described under Secondary Myocardial Disease Tachycardia-induced cardiomyopathy Is described under Secondary Myocardial Disease Alcoholic cardiomyopathy Is described under Secondary Myocardial Disease Cardiomyopathy in muscular dystrophy Defined as primary disorders of skeletal and/or cardiac muscles of genetic etiology, muscular dystrophies were primarily described based upon the distribution and extent of skeletal muscle involvement. The involvement of the heart was commonly attributed to processes extrinsic to the heart, resulting in restrictive lung disease, subsequent pulmonary hypertension, and secondary myocardial dysfunction. Intrinsic dysfunction is increasingly recognized as an important etiology for myocardial function impairment in the presence of muscular dystrophy. Typical forms of dystrophy are based on deficiency of dystrophin, of which mutations have been described in X-linked DCM. Furthermore, histological changes were found in the myocardium similar to those in skeletal muscles, which suggest a common etiology, and moreover cardiac manifestations may be present even in the absence of myopathic symptoms. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 14/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Treatment of cardiac dysfunction is treated according to the nature of cardiac involvement. Conduction disorders may present which require pacing, and standard heart failure therapy may be instituted in case of ventricular dilatation and functional impairment. Ventricular tachyarrhythmias may be found in particular in myotonic dystrophia, and require the implantation of an internal cardiac defibrillator to prevent its associated sudden cardiac death. Prognosis and outcome DCM has a highly variable clinical course. Approximately half of DCM patients respond well to routine heart failure medication, and a minority of patients even shows an improving clinical course. Conversely, a subgroup can be identified with a highly unfavourable clinical course, not responsive to heart failure medication and rapidly progressing to inotropy- or LVAD-dependency. Overall, 5-year survival rates approximate 30%. Restrictive cardiomyopathy Restrictive cardiomyopathy is characterized by an increase in ventricular wall stiffness, impairing its diastolic function. Systolic function is usually preserved in early stages of the disease, but may deteriorate with progression of the disease. RCM is less frequent in the developed world than the previously described HCM and DCM, but is an important cause of death in Africa, India, South and Central America, and Asia due to the high endemic incidence of endomyocardial fibrosis. The spectrum of restrictive cardiomyopathies can be classified as shown in Table 5, according to its cause. The most important specific causes of RCM will be discussed in detail below. An important differentiation is that between RCM and constrictive pericarditis. Constrictive pericarditis is similarly characterized by impaired ventricular filling with preserved systolic function, but may be adequately treated by pericardiectomy, which makes this distinction of major clinical importance. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 15/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 5 - Classification of Restrictive Cardiomyopathy Myocardial Noninfiltrative Idiopathic cardiomyopathy Familial cardiomyopathy Hypertrophic cardiomyopathy Scleroderma Pseudoxanthoma elasticum Diabetic cardiomyopathy Infiltrative Amyloidosis Sarcoidosis Hurler disease Fatty infiltration Storage Disease Hemochromatosis Fabry disease Gaucher disease Glycogen storage disease Endomyocardial Endomyocardial fibrosis Hypereosinophilic syndrome Carcinoid heart disease Metastatic cancers Radiation Toxic effects of anthracycline Drugs causing fibrous endocarditis(serotonin, methysergide, ergotamine, mercurial agents, busulfan) Adapted from Kushwaha S, Fallon JT, Fuster V: Restrictive cardiomyopathy. N Engl J Med 336:267, 1997. Copyright 1997, Massachusetts Medical Society. Infiltrative cardiomyopathy Amyloidosis Amyloidosis is a disease that results from tissue deposition of fibrils that have a distinct secondary structure of a beta-pleated sheet configuration, leading to characteristic histological changes. Amyloid depositions can occur in almost any organ, but usually remains clinically undetected unless extensive depositions are present. Types of amyloidosis https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 16/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology The most frequent types of amyloidosis are the AL (primary) and AA (secondary) types. AL amyloidosis is a plasma cell dyscrasia, which can occur solitarily or in association with multiple myeloma. AA amyloidosis can be considered a complication of chronic inflammatory disease states such as rheumatoid arthritis, in which the depositions consist of fragments of serum amyloid A, which is an acute phase reactant. Hereditary amyloidosis has been increasingly recognized in the last decade, and results from mutations in the gene for thransthyretin. Some mutations are clinically limited to the myocardium. Its incidence increases with increasing age, with a predilection for men, but its prognosis is better than that of the AL type. Senile systemic amyloidosis results from deposition of normal wild-type transthyretin. This form of amyloidosis is clinically predominated by an infiltrative cardiomyopathy, but progression is slow and prognosis is better than of other acquired forms. Cardiac amyloidosis Cardiac amyloidosis is a progressive infiltrative cardiomyopathy. The primary form carries the highest cardiac involvement of approximately one third to half of patients, where deposits may be present even in the absence of clinical symptoms. Secondary amyloidosis is less frequently accompanied by cardiac infiltration, approximately 5% of cases, and is less likely associated with ventricular dysfunction due to a smaller size and more favourable location of the depositions. Familial amyloidosis is associated with clinical signs of cardiac involvement in a quarter of patients, typically presenting after the age of 35 with a distinct involvement of the cardiac conduction system. In senile amyloidosis, the extent of deposits may vary widely from solitarily atrial involvement up to extensive ventricular infiltration. Clinical manifestations Apart from the occurrence of cardiac disease in the presence of known AL amyloidosis or connective tissue disease or other chronic inflammatory disorders, cardiac amyloidosis should be considered in case of: Restrictive cardiomyopathy of unknown origin Left ventricular hypertrophy with a converse low-voltage ECG Congestive heart failure of unknown origin, not responding to contemporary medical management. Clinical diagnosis Diagnostic testing should include a 12-lead ECG, possibly with Holter monitoring, and routine echocardiography. Specific characteristics are a low-voltage 12-lead ECG with increase septal and posterior wall ventricular thickness. Physical examination https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 17/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology A physical examination may reveal an elevated jugular venous pressure, and signs of systemic edema. Auscultation frequently reveals an apical murmur due to mitral regurgitation, and a third heart sound, but the presence of a fourth heart sound may exclude amyloidosis, as atrial infiltration causes impaired atrial contraction. Electrocardiography Routine 12-lead ECG shows low voltage in the limb leads, and a pseudoinfarct pattern in approximately 50% of patients. Furthermore, conduction abnormalities occur frequently, as does atrial fibrillation. Echocardiography Thickening of the left ventricular wall with diastolic dysfunction are early echocardiografic features of the disease. In advancing disease, wall thickening increases, resulting in a restrictive cardiomyopathy. Sparkling myocardium is a distinct characteristic of cardiac amyloidosis, referring to an increased echogenicity of the myocardium. However, only a minority of patients has this pattern. Doppler evaluation shows a restrictive pattern with E dominance and a short deceleration time. Furthermore, intracardiac thrombus is common, which is associated with atrial fibrillation and left ventricular diastolic dysfunction. The thickening of the ventricular wall caused by amyloidosis may be misinterpreted as hypertrophy on echocardiography. An important distinctive characteristic of amyloidosis is the voltage-to-mass ratio. Unlike normal hypertrophic myocardium, the increased ventricular mass in amyloidosis is associated with a decrease in electrocardiographic voltage. Management Few treatments for cardiac amyloidosis exist, and those available are dependent on the type of amyloidosis present. Hence, typing of the disease is pertinent. AL amyloidosis may be treated with chemotherapy using alkylating agents alone or in combination with bone marrow transplantation. Heart transplantation in combination with bone marrow transplantation after high-dose chemotherapy was shown to be result in approximately a third of treated patients surviving over 5 years, but as the great majority of patients with AL amyloidosis has severe non-cardiac amyloidosis, most patients are not suitable transplant candidates. Patients with other types of amyloidosis frequently have less affected hearts, and progression of the disease is slow. AA amyloidosis may respond to anti-inflammatory and immunosupressive drugs that reduce production of the acute-phase reactant protein. If heart failure is present, it is usually more prone to routine medical treatment to reduce symptoms. If needed, heart transplantation can be performed successfully. In patients where transthyretine is the amyloidogenic protein, liver transplantation may be curative as tranthyretine is produced in the liver, but the cardiac disease may progress regardless in some patients. Overall, caution should be taken in prescribing digitalis, nifedipine, verapamil and ACE-inhibitors to cardiac amyloidosis patients. There is a high susceptibility to digitalis intoxication, nifedipine-induced hemodynamic deterioration, verapamil-induced left ventricular dysfunction, and ACE-inhibitor induced profound hypotension. If atrial fibrillation is present, or systolic ventricular function is severely impaired https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 18/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology anticoagulation is indicated to prevent intracardiac thrombi. In selected patients with conduction disorders, pacemaker implantation may be considered. If ventricular function is severely impaired, ICD implantation may be considered. Nonetheless, prognosis of especially AL amyloidosis is poor. Sarcoidosis Sarcoidosis is a multisystem inflammatory condition characterized by the formation of non-caseating granulomas, most frequently affecting the lungs and lymphatic system. Myocardial involvement is seen in one quarter of cases only. Genetic factors are suggested as there was found to be an aggregation of cases within families. Pathophysiology Non-caseating granulomas may infiltrate the myocardium, leading to fibrotic scarring of the myocardium. Involvement of the myocardium is usually patchy, resulting in a relatively high likelihood of false-negative results from biopsy. Cardiac sarcoidosis must be differentiated from chronic active myocarditis and giant cell myocarditis. Clinical diagnosis Patients may present with syncope, heart block or congestive heart failure. Sudden cardiac death may well be the initial manifestation of the disease due to malignant ventricular arrhythmias, but both atrial and ventricular arrhythmia is common at initial presentation. Symptoms of heart failure may result from direct myocardial involvement, but can also be due to extensive pulmonary fibrosis; cor pulmonale. Physical examination may include signs of extracardiac sarcoidosis, a right sided third heart sound, and both S3 and S4, as well as murmurs of tricuspid regurgitation or mitral regurgitation. Initial consideration of the diagnosis is often based on chest radiographs showing bilateral hilar lymfadenopathy. CMR is emerging as a highly sensitive and specific test for sarcoidosis, and nuclear imaging techniques may show regional perfusion defect due to the granulomatous inflammation on SPECT, or focal uptake on PET CT. electrocardiography is useful to assess the extent of conduction system involvement. Echocardiography shows left ventricular dilatation with hypokinesis, right ventricular enlargement and hypertrophy and possibly left ventricular aneurysm formation. Minimal evaluation of a patient suspected of cardiac sarcoidosis consists of a 12-lead ECG, Holter monitoring and echocardiography. Management Early detection of the disease is critical for its clinical course. Immunosuppression using corticosteroids to halt the progression of inflammation is the treatment of choice in sarcoidosis, to which myocardial dysfunction, conduction disturbances, and arrhythmias may all respond. Most important is the differentiation of sarcoidosis from giant cell myocarditis, which is a more aggressive disorder requiring https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 19/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology intensive medical and mechanical support and frequently necessitating heart transplantation. Pacemaker or ICD implantation is indicated in patients with conduction disorders or malignant arrhythmias, as medical treatment is usually ineffective in these cases. Storage diseases Hemochromatosis Hemochromatosis is defined as a disorder of the iron metabolism, resulting in accumulation of iron in parenchymal tissues. In particular cardiac, liver, gonadal and pancreatic involvements are typical for hemochromatosis, in which the toxicity of redox-active iron results in organ dysfunction. Typically, hemochromatosis leads to a combination of heart failure, cirrhosis, impotence, diabetes and arthritis. Although several organ systems are usually involved, cardiac complications predominate the initial presentation, which are dependent on the site and amount of cardiac depositions. DCM is the typical phenotype of cardiac involvement, but a restrictive pattern may be present. The most frequent, adult-onset, form of hemochromatosis was found arise from mutations in the HFE- gene, coding for a transmembrane protein involved in iron uptake in the liver and the intestine. Less frequently, mutations in the transferrine 2-encoding gene may result in hemochromatosis. The juvenile form of hemochromatosis results from mutations in the genes encoding hepcidin and hemojuvelin. The disease may also be acquired and result from ineffective erythropoiesis secondary to a defect in haemoglobin synthesis, chronic liver disease, chronic excessive oral or parenteral intake of iron, or from multiple blood transfusions. Three stages of the natural history of adult-onset hemochromatosis can be differentiated. The first stage, the biochemical stage, is characterized by an iron overload which remains confined to the plasma compartment. Transferrin saturation is increased. The second phase, the deposition phase, is characterized by iron accumulation in parenchymal tissues, accommodated by an increase in serum ferritine levels. The third and final stage is that of organ dysfunction. Juvenile hemochromatosis is a more rapidly progressing disease, which leads to early organ dysfunction, around the age of 30, and is frequently characterized by premature death due to severe cardiac complications. The invariably present symptoms of heart failure may frequently be accompanied by arrhythmias, especially ventricular extrasystoles, supraventricular tachycardia, and atrial fibrillation or flutter; either due to atrial iron depositions, or ventricular dysfunction resulting in increased ventricular pressure. Furthermore, conduction system involvement may lead to AV block or sick sinus syndrome. Diagnostic features Symptoms at initial presentation may vary. Echocardiography may show increased left ventricular wall thickness, ventricular dilatation, and ventricular dysfunction. CMR imaging represents a sensitive mean and may aid in early detection of the disease. Electrocardiographic characteristics include ST-segment https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 20/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology and T-wave abnormalities as well as supraventricular arrhythmias, but occur as the disease advances. Biochemical testing reveals increased elevated transferrine saturation, increase plasma iron levels with low or normal iron binding capacity. Management Repeated phlebotomy is the cornerstone of hemochromatosis treatment, although chelating agents such as deferoxamine may be considered. Early detection of the disease is critical, as depletion of iron overload may result in complete reversal of symptoms at this stage. Evidence was found that a threshold exists beyond which iron depletion does not result in recovery of function. At end-stage disease, heart transplantation is a viable option with good survival rates. Importantly, screening of first degree relatives is important to ensure early detection of hereditary forms of hemochromatosis. Fabry disease (angiokeratoma corporis diffusum universale) Fabry disease is an X-linked inheritable deficiency of the lysosomal alpha-galactosidase A, resulting in an accumulation of glycosphingolipids in the lysosomes. There is a wide variety of know mutations, which all result in a different level of alpha-galactosidase inactivity, and hence, clinical manifestation may range from isolated myocardial disease to systemic involvement. Patients may suffer from angina pectoris and myocardial infarction due to the accumulation of the aforementioned lipids in the endothelium of the coronary arteries, but the epicardial vessels show no abnormalities on angiography. Ventricular function is hampered due to thickening of the ventricular walls, which results in impaired diastolic compliance with a preserved systolic function, and may even precede myocardial hypertrophy. Other common features of the disorder include systemic hypertension, congestive heart failure, and mitral valve prolapse. The surface electrocardiogram may reveal a short P-R interval, atrioventricular block, and ST-segment and T wave abnormalities. Echocardiography may be inconclusive, but CMR imaging may differentiate Fabry disease from other infiltrative processes. Definite diagnosis is made on endomyocardial biopsy. Treatment of Fabry is safe and effective, and consists of enzyme-replacement therapy. Gaucher Disease Gaucher disease is an inheritable deficiency of beta-glucosidase, resulting in accumulation of cerebrosides. Cardiac involvement results in impaired cardiac function due to reduced ventricular compliance. Treatment of Gaucher disease consists of enzyme replacement therapy, or liver transplantation as a last resort. Response to treatment with respect to recovery of symptoms is heterogeneous. Glycogen storage disease https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 21/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Glycogen storage disease may result in cardiac involvement in case of type II, III, IV and V, but survival until adulthood is rare except for type III disease. Cardiac involvement is characterized by left ventricular hypertrophy, electrographically and echocardiographically, but cardiac symptoms are frequently absent. Endomyocardial Endomyocardial fibrosis Endomyocardial fibrosis is an important cause of congestive heart failure in equatorial Africa. Prevalence up to 20% has been reported, mostly familial in children or young adults, although symptoms occurred only in a minority of detected cases. The disease predominantly occurs in black individuals, but may rarely present in white subjects. The fibrous lesions hamper cardiac function by impairing the inflow of the ventricles, affecting the left or both ventricles most commonly. Solitaire right-sided involvement is less frequent, occurring in approximately 10% of cases. Symptoms are concordant with the ventricles involved, an atrial fibrillation and ascites are known factors associated with a poor prognosis. Clinical diagnosis is based upon clinical presentation, lab testing, and angiography. Left-sided myocardial biopsy is relatively contraindicated, as it may result in systemic emboli. Endomyocardial fibrosis is a relentless disease, half of patients not making it beyond 2 years after detection, depending on the extent of symptoms at presentation. Medical management is only effective in the early stages of the disease, and is aimed at relief of symptoms. Surgical correction of the clinical consequences of the disease, i.e. valve replacement, improves hemodynamic characteristics, but mortality is high, and fibrosis may reoccur. Hypereosinophilic syndrome: L ffler Endocarditis The hypereosinophilic syndrome is a systemic disease, involving several organ systems. Cardiac involvement, L ffler endocarditis, is usually present when eosinophil counts are high for a longer period of time. The eosinophilia itself may occur from several different causes. Histopathology shows eosinophilic myocarditis extending into the subendocardium, endocardial thickening, and inflammation of the small intramural coronary vessels. Clinical features of the disease are weight loss, cough, fever, and a rash. Cardiac involvement may not induce clinical symptoms in the early stages of the disease, but as the disease progresses as much as 50% of patients develop cardiomegaly or congestive heart failure. Cardiomegaly may be suspected on chest radiography, and the electrocardiogram shows non-specific abnormalities of the ST-segment and T-waves. Conduction defects may also occur. Echocardiography often shows a normal systolic function, and may show apical obliteration by thrombus. Obliteration of the apex with a preserved systolic function is a key characteristic of the disease on angiography. Endomyocardial biopsy can provide the diagnosis, but may be false-negative. Routine care applies to these patients. Diuretics and neurohumoral blockade are appropriate, as is anticoagulation. Corticosteroids and cytotoxic drugs increase survival in patients with L ffler endocarditis, and interferon may be used as a last option in refractory patients. Surgical therapy may be https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 22/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology considered as palliative treatment in the fibrotic fase of the disease. Arrythmic cardiomyopathy: Arrhythmogenic Right Ventricular Cardiomyopathy Arrhythmogenic Right Ventricular Cardiomyopathy, (ARVC, or ARVD: Arrhythmogenic Right Ventricular Disease, also AC Arrhythmogenic Cardiomyopathy) is characterized by fatty replacement and fibrosis of the heart. Most commonly, the right ventricle apex and outflow tract are involved. However, the left ventricle can be affected too. As a result of the fatty replacement and fibrosis, ventricular arrhythmias are common in this disease and can lead to palpitations, syncope and sudden death. At more advanced ages, right ventricular failure can occur. ARVC is a progressive disease, and its incidence is estimated to be 1:3.000-1:10.000. The disease usually manifests at adolescence. Although the diagnosis is more often confirmed in athletes, physical activity is not thought to have a causal relationship with the disease. ARVC can occur in families; more than 9 different chromosomal defects have been described, most often with autosomal dominant inheritance. One unique form of ARVC, called Naxos disease (after the Greek island where it was first diagnosed), has an autosomal recessive pattern of inheritance. A section throughout the heart of an ARVC patient. (A) Transmural fatty replacement of the right ventricular free wall. (B) Myocardial atrophy is confined to the right ventricle and substantially spares the interventricular septum as well as the left ventricular free wall. [1] Reproduced with permission from BMJ Publishing Group Ltd. Diagnosis ARVC is a difficult diagnosis to make. Therefore, the European Society of Cardiology has created a list of diagnostic criteria for the diagnosis of ARVC, which were updated in 2009 (Table 6). An online calculator (http:// www.arvc.ca/pdg/public.php?rep=arvc_cri) can help in assessing the risk in an individual patient. ECG with an epsilon wave in V1 https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 23/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Table 6. The Revised Task Force Criteria for ARVD / ARVC Revised Task Force Criteria I. Global or regional dysfunction and structural alterations Major By 2D echo: Regional RV akinesia, dyskinesia, or aneurysm and 1 of the following (end diastole): PLAX RVOT =32 mm (corrected for body size [PLAX/BSA] =19 mm/m2) PSAX RVOT =36 mm (corrected for body **[PSAX/BSA] =21 mm/m2) or fractional area change =33% By MRI: Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and 1 of the following: Ratio of RV end-diastolic volume to BSA =110 mL/m2 (male) or =100 mL/m2 (female) or RV ejection fraction =40% By RV angiography: Regional RV akinesia, dyskinesia, or aneurysm Minor By 2D echo: Regional RV akinesia or dyskinesia and 1 of the following (end diastole): PLAX RVOT =29 to <32 mm (corrected for body size [PLAX/BSA] =16 to <19 mm/m2) PSAX RVOT =32 to <36 mm (corrected for body size [PSAX/BSA] =18 to <21 mm/m2) or fractional area change >33% to =40% By MRI: Regional RV akinesia or dyskinesia or dyssynchronous RV contraction and 1 of the following: Ratio of RV end-diastolic volume to BSA =100 to <110 mL/m2 (male) or =90 to <100 mL/m2 (female) or RV ejection fraction >40% to =45% II. Tissue characterization of wall Major Residual myocytes <60% by morphometric analysis (or <50% if estimated), with fibrous replacement of the RV free wall myocardium in =1 sample, with or without fatty replacement of tissue on endomyocardial biopsy Minor Residual myocytes 60% to 75% by morphometric analysis (or 50% to 65% if estimated), with fibrous replacement of the RV free wall myocardium in =1 sample, with or without fatty replacement of tissue on endomyocardial biopsy III. Repolarization abnormalities Major https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 24/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology Inverted T waves in right precordial leads (V1, V2, and V3) or beyond in individuals >14 years of age (in the absence of complete right bundle-branch block QRS =120 ms) Minor Inverted T waves in leads V1 and V2 in individuals >14 years of age (in the absence of complete right bundle-branch block) or in V4, V5, or V6 Inverted T waves in leads V1, V2, V3, and V4 in individuals >14 years of age in the presence of complete right bundle-branch block IV. Depolarization/conduction abnormalities Major Epsilon wave (reproducible low-amplitude signals between end of QRS complex to onset of the T wave) in the right precordial leads (V1 to V3) Minor Late potentials by SAECG in =1 of 3 parameters in the absence of a QRS duration of =110 ms on the standard ECG Filtered QRS duration (fQRS) =114 ms Duration of terminal QRS <40 V (low-amplitude signal duration) =38 ms Root-mean-square voltage of terminal 40 ms =20 V Terminal activation duration of QRS =55 ms measured from the nadir of the S wave to the end of the QRS, including R , in V1, V2, or V3, in the absence of complete right bundle-branch block V. Arrhythmias Major Nonsustained or sustained ventricular tachycardia of left bundle-branch morphology with superior axis (negative or indeterminate QRS in leads II, III, and aVF and positive in lead aVL) Minor Nonsustained or sustained ventricular tachycardia of RV outflow configuration, left bundle- branch block morphology with inferior axis (positive QRS in leads II, III, and aVF and negative in lead aVL) or of unknown axis >500 ventricular extrasystoles per 24 hours (Holter) VI. Family history Major ARVC/D confirmed in a first-degree relative who meets current Task Force criteria ARVC/D confirmed pathologically at autopsy or surgery in a first-degree relative Identification of a pathogenic mutation categorized as associated or probably associated with ARVC/D in the patient under evaluation Minor History of ARVC/D in a first-degree relative in whom it is not possible or practical to determine whether the family member meets current Task Force criteria Premature sudden death (<35 years of age) due to suspected ARVC/D in a first-degree relative ARVC/D confirmed pathologically or by current Task Force Criteria in second-degree relative https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 25/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology PLAX indicates parasternal long-axis view; RVOT, RV outflow tract; BSA, body surface area; PSAX, parasternal short-axis view; aVF, augmented voltage unipolar left foot lead; and aVL, augmented voltage unipolar left arm lead. Diagnostic terminology for original criteria: This diagnosis is fulfilled by the presence of 2 major, or 1 major plus 2 minor criteria or 4 minor criteria from different groups. Diagnostic terminology for revised criteria: definite diagnosis: 2 major or 1 major and 2 minor criteria or 4 minor from different categories; borderline: 1 major and 1 minor or 3 minor criteria from different categories; possible: 1 major or 2 minor criteria from different categories. Hypokinesis is not included in this or subsequent definitions of RV regional wall motion abnormalities for the proposed modified criteria. A pathogenic mutation is a DNA alteration associated with ARVC/D that alters or is expected to alter the encoded protein, is unobserved or rare in a large non ARVC/D control population, and either alters or is predicted to alter the structure or function of the protein or has demonstrated linkage to the disease phenotype in a conclusive pedigree. E.g.: in TMEM43, DSP, PKP2, DSG2, DSC2, JUP. Arvd ecg1.png Arvd ecg2.png Arvd ecg3.png An ECG of a patient with ARVD Onset of a VT from right inferior the ventricle, typical for ARVD Sustained VT with LBBB pattern and superior in ARVD axis Treatment Treatment focuses on avoiding complications. Medication: Anti-arrhythmics: Sotalol better than Amiodarone. ACE-inhibitors to prevent cardiac remodelling ICD implantation is recommended for the prevention of sudden cardiac death in patients with ARVC with documented sustained VT or VF who are receiving chronic optimal medical therapy. ICD implantation can be considered for the prevention of sudden cardiac death in patients with ARVC with extensive disease, including those with left ventricular involvement, 1 or more affected family member with SCD, or undiagnosed syncope when ventricular tachycardia or ventricular Fibrillation has not been excluded as the cause of syncope, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. Radiofrequency ablation can be useful as adjunctive therapy in management of patients with ARVC https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 26/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology with recurrent ventricular tachycardia, despite optimal anti-arrhythmic drug therapy. Unclassified Cardiomyopathy: Left ventricular non-compaction Left ventricular non-compaction (LVNC) is characterized by distinct structural abnormalities: A two-layered structure of the myocardium, with a thin compacted epicardial band and a thick non- compacted endomyocardial part, overall resulting in a thickened myocardium. LVNC is diagnosed by the ratio between the maximal non-compacted and compacted myocardial layer thickness measured during end-systole. In adults, a non-compacted/compacted thickness ratio of =2 confirms the diagnosis, whereas a ratio of =1.4 is considered diagnostic in children. The non-compacted layer is further characterized by prominent trabeculations, with intertrabecular spaces in direct connection with the left ventricular cavity. The non-compacted regions are predominantly found in the lateral, apical or inferior wall of the left ventricle. Where normal myocardium, originally consisting of a sponge-like structure of myocardial fibres, shows a pattern of basal to apical, and epicardial to endocardial compaction of the myocardial fibres during the 5th to 8th week of embryonal development, non-compaction supposedly originates from halting of this process due to a genetic defect. Clinical Presentation and Diagnosis Age of onset may be highly variable, with cyanosis, failure to thrive or dysmorphic features described in the neonatal period, to adult patients presenting with LV failure or ventricular arrhythmia. Possibly, sudden cardiac death entails one of the manifestations of LVNC, although evidence is only limited at this moment. Owing to technical advances in the field of echocardiography, predominantly an increase in image resolution, LVNC has only recently been recognized as an independent entity in the spectrum of cardiomyopathies, which supposedly has frequently been misdiagnosed as HCM in the past. Two-dimensional echocardiography entails the cornerstone of LVNC diagnostics, enhanced by intravenous contrast agents if necessary. Magnetic resonance imaging may pose an option in case acoustic windows are insufficient. ECG abnormalities in patients with LVNC are mostly non-specific. Considering the genetic background of LVNC, inheriting most commonly autosomal dominant, echocardiographic evaluation of family members of LVNC patients is pertinent. Treatment and Prognosis Treatment strategies are mainly extrapolated from other cardiomyopathies: standard heart failure therapy in case of LV dysfunction, beta-blockade and/or amiodarone in non-sustained VT in the absence of LV dysfunction, and ICD placement indicated in patients with LVEF <35%, sustained VT or recurrent unexplained syncope. Routine anticoagulation in not indicated, but anticoagulation may be instituted in case of ventricular dilatation or systolic LV function impairment. The prognosis of LVNC has currently not yet been defined. One small report indicates a high mortality risk, owing to a high prevalence of sudden death, but community-based populations may well show a different prognosis as many patients with LVNC are non-symptomatic at the initial diagnosis. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Myocardial_Disease&oldid=2363" https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 27/28 7/4/23, 12:37 AM Myocardial Disease - Textbook of Cardiology This page was last edited on 9 May 2013, at 12:59. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Myocardial_Disease#Myocardial_Disease_-_Secondary 28/28 |
7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology Myocardial Infarction An acute coronary syndrome (ACS) is most commonly caused by rupture or erosion of with an superimposed thrombus formation. The underlying process is atherosclerosis, a in which artery walls chronic disease thicken by deposition of fatty materials such as cholesterol and inflammatory cells. The accumulation of this material results in the formation of an atherosclerotic plaque, encapsulated by connective tissue, which can narrow the lumen of the arteries significantly and progressively causing symptoms as angina pectoris or lead to an the presence of ACS. Depending on myocardial damage and typical ECG characteristics, ACS can be divided into ST-segment myocardial elevation infarction (STEMI), and non-ST-segment ACS including non-ST-segment elevation MI (NSTEMI) and unstable angina. In the case of STEMI and NSTEMI, there is biochemical of myocardial evidence damage (infarction). [1] atherosclerotic plaque Myocardial Infarction Contents History Physical Examination Electrocardiogram (ECG) Cardiac Markers Treatment ST-segment elevation Myocardial Infarction Non-ST-segment elevation Acute Coronary Syndrome Selective invasive ( or conservative ) management Routine invasive management Cardiac rehabilitation A myocardial infarction results from a coronary occlusion (1) with necrosis of myocardial tissue (2) distal to the occlusion References History https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 1/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology The most typical characteristic of an ACS is acute prolonged chest pain. [2] The pain does not decrease at rest and is only temporarily relieved with nitroglycerin. Frequent accompanying symptoms include a radiating pain to shoulder, arm, back and/or jaw. [3] Shortness of breath can occur, as well as sweating, fainting, nausea and vegetative so symptoms. Some patients including elderly and diabetics may present with aspecific symptoms. [4], [5] vomiting, called It is important to complete the medical history (prior history of ischemic events or vascular for cardiovascular disease (a.o. diabetes mellitus, current smoking, hypertension, hyperlipidemia) and family history (first degree relatives with myocardial infarction before the age 55 of (males) or 65 (females) and/or sudden cardiac death). [6] disease), risk factors Different terminology is used during different phases of the chest pain workup. The ECG classifies into ST elevtion or not. Troponine definitely classifies into myocardial infarction (damage) or not. Symptoms of heart orthopnea (dyspnoea when progressive dyspnoea and peripheral oedema are indicative of the extent of the problem. [7] failure such as lying flat), Physical Examination The focus of the physical examination should be to recognize signs of systemic hypoperfusion such as hypotension, tachycardia, impaired cognition, pale and ashen skin. [7] Furthermore, signs of heart failure are important, such as pulmonary crackles during auscultation and pitting oedema of the ankles. In more stable ACS patients, history and physical examination are helpful to exclude other causes of chest pain, such as aortic valve stenosis, aorta dissection, arrhythmias, pulmonary embolism, pneumonia, heartburn, hyperventilation or musculoskeletal problems. [7] Electrocardiogram (ECG) An electrocardiogram (ECG) should be made on arrival in every patient with suspected ACS. [7] The ECG is an important and easy modality which can assist in the diagnosis and prognostication of ACS. However, a single ECG may not reflect the dynamic pathophysiology of the ACS. Therefore it is important to make serial ECGs, certainly if a patient has ongoing symptoms. [7] Furthermore, the ECG is also helpful in localising the ischemia: Anterior wall ischemia - One or more of leads V2-V5 https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 2/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology Anteroseptal ischemia - Leads V1 to V3 Apical or lateral ischemia - Leads aVL and I, and leads V4 to V6 Inferior wall ischemia - Leads II, III, and aVF Posterior wall Leads V7-V9 Right ventricle Leads V3R, V4R, V1 Left main coronary artery ischemia Lead aVR More information abou the ECG during myocardial infarction (http://en.ecgpedia.org/wiki/Myocardial _Infarction) can be found on ECGpedia. Cardiac Markers Cardiac markers are essential in order to confirm the diagnosis of MI, indicated by elevated Creatine Kinase isoenzyme MB (high-sensitive) (CK MB) and/or troponins. Troponins are more specific and sensitive than CK MB. The cardiac troponin concentration begins to rise around 4 hours after the onset of myocardial cell damage.[8] With high-sensitive troponins, myocardial cell damage can be detected even earlier. It can take 4-6 hours before the CK MB elevated. Serial measurements are useful in order to estimate infarct size and increase the sensitivity of the (older) assays. [9] concentration is Rise and fall of several cardiac markers based on whether the myocardium was reperfused or not A pitfall concerning mildly elevated cardiac markers can be patients with renal failure or pulmonary embolism. [10] Treatment As the formation of an intracoronary thrombus is a central mechanism in ACS and (recurrent) subsequent outcomes, the cornerstone in the treatment of ACS is antithrombotic treatment. All patients diagnosed with ACS should start with aspirin and a P2Y12 receptor blocker (clopidogrel, prasugrel or ticagrelor). [11] Aspirin and the P2Y12 receptor blocker are both platelet aggregation inhibitors. The treatment of ACS also focuses on medication to reduce the workload of the heart. blockers lower heart rate and blood pressure, to decrease the oxygen demand of the heart. [12] Nitrates dilatate the coronary arteries. [13] Depending on the (working) diagnosis STEMI or NSTE-ACS, the revascularisation strategy varies. ST-segment elevation Myocardial Infarction Initial treatment of STEMI is relief of ischemic pain, stabilisation of hemodynamic status and restoration of coronary flow and myocardial tissue perfusion. Reperfusion therapy should be initiated as quickly as possible by preferably primary percutaneous coronary intervention (PCI) or fibrinolysis. Reperfusion is https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 3/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology beneficial up to 12 hours after the onset of symptoms. In severe hemodynamic compromise, reperfusion therapy may be attempted up to 24 hours onset. symptom after Meanwhile other measures as ECG continuous monitoring, oxygen supply and intravenous access are indicated. [7] case of Primary PCI is the preferred revascularisation method for patients with STEMI. It is an effective method of securing and maintaining coronary the patency and avoids higher risk associated with fibrinolysis. If a patient is referred to a non-PCI-capable hospital, and transfer to a PCI-capable hospital in order to perform PCI within 2 hours after the onset of symptoms is not possible, fibrinolytic therapy is recommended. Reperfusion strategies. The thick arrow indicates the preferred strategy. bleeding There are circumstances in which transfer to a PCI qualified hospital is recommended: Patients with contraindications for fibrinolysis, such as: active bleedings, recent surgery, past history of intracranial bleeding. [14] Patients with cardiogenic shock, severe heart failure and/or pulmonary oedema complicating the myocardial infarction. [15], [16] Available data support the pre-hospital initiation of fibrinolytics if this reperfusion strategy is indicated. Fibrinolytics like streptokinase and rtPA stimulate the conversion of plasminogen to plasmin. Plasmin degrades fibrin which is an important constituent of the thrombus. Fibrinolytics are most effective the first hours after the onset of symptoms, and a benefit is observed in terms of reducing mortality within the first twelve hours. [17] The hazards of thrombolysis are increased bleeding risk, including hemorrhagic strokes. Because re occlusion after fibrinolysis is possible patients should be transferred if possible to a PCI qualified hospital once fibrinolysis is done. [18] In rare cases, CABG is indicated, such as failed fibrinolysis with coronary anatomy unsuited for PCI and/or failed PCI, when the patient develops cardiogenic shock, life threatening ventricular arrhythmias, has three vessel disease, or mechanical complications of the MI. [19] Non-ST-segment elevation Acute Coronary Syndrome Comparable to STEMI, revascularization in NSTE-ACS relieves symptoms, shortens hospital stay, and improves prognosis. However, NSTE-ACS patients represent a heterogenous population, and indication and timing of revascularization depend on many factors, including the baseline risk of the patient. https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 4/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology According to current guidelines, depending on early risk stratification a choice has to be made between a routine invasive or a conservative selective strategy ) [20] invasive (or Early risk stratification to identify patients at high risk who might benefit the most from a more aggressive therapeutic approach in order to prevent further ischemic events. [21] is helpful https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 5/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology The GRACE risk score model (http://www.outcomes-umassmed.or g/grace/acs_risk/acs_risk_content.html) GRACE risk score Risk Category low Intermediate High NSTEMI Probability of Death In-hospital (%) <1 1-3 >3 NSTEMI 6 Month Post-discharge Mortality <3 3-8 >8 STEMI In-hospital Mortality (%) <2 2-5 >5 STEMI 6 Month Post-discharge Mortality <4.4 4.5-11 >11 Early risk stratification can be performed using one of the validated risk scores, such as the GRACE risk score. GRACE calculates the probability of death while in hospital. The following characteristics are taken into account: Age Heart rate and systolic BP Creatinine Killip class Cardiac arrest at admission Elevated cardiac markers ST segment deviation Regarding treatment strategies in NSTE-ACS, many randomized controlled trials (RCTs) and meta- analyses have assessed the effects of a routine invasive vs. conservative or selective invasive approach in the short and long term. Recent meta-analyse suggest a benefit of the routine invasive management that is mainly visible in intermediate- to high-risk patients. (referentie) Selective invasive ( or conservative ) management https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 6/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology Patients undergoing a selective invasive ( or conservative ) management are initially stabilized by medication only, including aspirin and clopidogrel orally and nitro-glycerin, heparin and a beta blocker intravenously. If the patients is unstable or has refractory angina, he/she is referred for coronary angiography. Patients stabilized on medical therapy should undergo a stress test before discharge. Potential advantages of this treatment strategy are a reduction of the number of catherization procedures. A potential disadvantage is a prolonged stay in the hospital. Although meta-analyses suggest the superiority of a routine invasive management, trials in which the selective invasive strategy was characterized by high rates of revascularization show equivalence of the two strategies. Routine invasive management The routine invasive strategy consists of routine, early coronary angiography within 24 hours after admission and subsequent revascularization if appropriate by PCI or CABG based on the angiographic findings. The optimal timing of coronary angiography with an intended routine invasive management is debated. In patients with high risk features, including hypotension, ventricular arrhythmias or a large myocardial area at risk, should undergo urgent angiography (<2 hours). Cardiac rehabilitation Cardiac rehabilitation reduces mortality, helps the patient to regain confidence and to resocialise, and helps to reduce risk factors for atherosclerosis. Post-ACS patient should be referred for cardiac rehabilitation. References 1. Davies MJ. Pathophysiology of acute coronary syndromes. Indian Heart J. 2000 Jul-Aug;52(4):473- 9. 2. Swap CJ and Nagurney JT. Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes. JAMA. 2005 Nov 23;294(20):2623-9. DOI:10.1001/jama.294.20.2623 | 3. Foreman RD. Mechanisms of cardiac pain. Annu Rev Physiol. 1999;61:143-67. DOI:10.1146/annurev.physiol.61.1.143 | 4. Canto JG, Shlipak MG, Rogers WJ, Malmgren JA, Frederick PD, Lambrew CT, Ornato JP, Barron HV, and Kiefe CI. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA. 2000 Jun 28;283(24):3223-9. DOI:10.1001/jama.283.24.3223 | 5. Pope JH, Ruthazer R, Beshansky JR, Griffith JL, and Selker HP. Clinical Features of Emergency Department Patients Presenting with Symptoms Suggestive of Acute Cardiac Ischemia: A Multicenter Study. J Thromb Thrombolysis. 1998 Jul;6(1):63-74. DOI:10.1023/A:1008876322599 | 6. Lloyd-Jones DM, Nam BH, D'Agostino RB Sr, Levy D, Murabito JM, Wang TJ, Wilson PW, and O'Donnell CJ. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle- aged adults: a prospective study of parents and offspring. JAMA. 2004 May 12;291(18):2204-11. DOI:10.1001/jama.291.18.2204 | 7. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, and American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). ACC/AHA guidelines for the management of patients with ST-elevation https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 7/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology myocardial infarction executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004 Aug 3;110(5):588-636. DOI:10.1161/01.CIR.0000134791.68010.FA | 8. Macrae AR, Kavsak PA, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, Yerna MJ, and Jaffe AS. Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem. 2006 May;52(5):812-8. DOI:10.1373/clinchem.2005.059550 | 9. Puleo PR, Meyer D, Wathen C, Tawa CB, Wheeler S, Hamburg RJ, Ali N, Obermueller SD, Triana JF, and Zimmerman JL. Use of a rapid assay of subforms of creatine kinase MB to diagnose or rule out acute myocardial infarction. N Engl J Med. 1994 Sep 1;331(9):561-6. DOI:10.1056/NEJM199409013310901 | 10. Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez- Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fern ndez-Avil s F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, and Al-Attar N. Universal definition of myocardial infarction. Circulation. 2007 Nov 27;116(22):2634-53. DOI:10.1161/CIRCULATIONAHA.107.187397 | 11. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D, and ESC Committee for Practice Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011 Dec;32(23):2999-3054. DOI:10.1093/eurheartj/ehr236 | 12. Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, De Backer G, Hjemdahl P, Lopez-Sendon J, Marco J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology, and ESC Committee for Practice Guidelines (CPG). Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006 Jun;27(11):1341-81. DOI:10.1093/eurheartj/ehl001 | 13. Abrams J. Hemodynamic effects of nitroglycerin and long-acting nitrates. Am Heart J. 1985 Jul;110(1 Pt 2):216-24. 14. Grzybowski M, Clements EA, Parsons L, Welch R, Tintinalli AT, Ross MA, and Zalenski RJ. Mortality benefit of immediate revascularization of acute ST-segment elevation myocardial infarction in patients with contraindications to thrombolytic therapy: a propensity analysis. JAMA. 2003 Oct 8;290(14):1891-8. DOI:10.1001/jama.290.14.1891 | 15. Thune JJ, Hoefsten DE, Lindholm MG, Mortensen LS, Andersen HR, Nielsen TT, Kober L, Kelbaek H, and Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI)-2 Investigators. Simple risk stratification at admission to identify patients with reduced mortality from primary angioplasty. Circulation. 2005 Sep 27;112(13):2017-21. DOI:10.1161/CIRCULATIONAHA.105.558676 | 16. Kent DM, Schmid CH, Lau J, and Selker HP. Is primary angioplasty for some as good as primary angioplasty for all?. J Gen Intern Med. 2002 Dec;17(12):887-94. DOI:10.1046/j.1525- https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 8/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology 1497.2002.11232.x | 17. Bassand JP, Danchin N, Filippatos G, Gitt A, Hamm C, Silber S, Tubaro M, and Weidinger F. Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology. Eur Heart J. 2005 Dec;26(24):2733-41. DOI:10.1093/eurheartj/ehi673 | 18. Silber S, Albertsson P, Avil s FF, Camici PG, Colombo A, Hamm C, J rgensen E, Marco J, Nordrehaug JE, Ruzyllo W, Urban P, Stone GW, Wijns W, and Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J. 2005 Apr;26(8):804-47. DOI:10.1093/eurheartj/ehi138 | 19. Canadian Cardiovascular Society, American Academy of Family Physicians, American College of Cardiology, American Heart Association, Antman EM, Hand M, Armstrong PW, Bates ER, Green LA, Halasyamani LK, Hochman JS, Krumholz HM, Lamas GA, Mullany CJ, Pearle DL, Sloan MA, Smith SC Jr, Anbe DT, Kushner FG, Ornato JP, Pearle DL, Sloan MA, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, and Yancy CW. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008 Jan 15;51(2):210-47. DOI:10.1016/j.jacc.2007.10.001 | 20. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, and American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004 Aug 3;110(5):588-636. DOI:10.1161/01.CIR.0000134791.68010.FA | 21. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, and Braunwald E. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000 Aug 16;284(7):835-42. DOI:10.1001/jama.284.7.835 | 22. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, and American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004 Aug 3;110(5):588-636. DOI:10.1161/01.CIR.0000134791.68010.FA | 23. Anderson JL, Karagounis LA, and Califf RM. Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction. Am J Cardiol. 1996 Jul 1;78(1):1-8. DOI:10.1016/s0002-9149(96)00217-2 | 24. Bassand JP, Danchin N, Filippatos G, Gitt A, Hamm C, Silber S, Tubaro M, and Weidinger F. Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology. Eur Heart J. 2005 Dec;26(24):2733-41. DOI:10.1093/eurheartj/ehi673 | https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 9/10 7/4/23, 12:20 AM Myocardial Infarction - Textbook of Cardiology Retrieved from "http://www.textbookofcardiology.org/index.php?title=Myocardial_Infarction&oldid=2608" This page was last edited on 2 March 2021, at 07:53. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Myocardial_Infarction 10/10 |
7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Pericardial Disease Contents Pericardial Disease - Acute Cardiac Tamponade Acute pericarditis Recurrent pericarditis Pericardial effusion Chronic pericardial effusion Pericardial Disease - Chronic Chronic constrictive pericarditis Subacute elastic constriction Effusive-constrictive pericarditis Transient cardiac constriction Pericardial Disease - Specific types Infectious pericarditis Idiopathic/Viral pericarditis Tuberculous pericarditis Purulent pericarditis Post myocardial infarction pericarditis Neoplastic pericarditis Hypothyroidism Post-pericardiotomy pericarditis Pericardial Disease The pericardium comprises two layers; the visceral layer that adheres to epicardial surface of the heart, and the parietal layer that surrounds most of the heart. Pericardial disease is common, and diagnosis is usually straightforward as the pericardium reacts to disruption by a wide variety of agents and processes in a relatively uniform manner. Typical presentation is with chest pain and fever, production of pericardial fluid with possible cardiac tamponade, or a constrictive pattern by thickening, retraction and calcification. Pericardial Disease - Acute Cardiac Tamponade https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 1/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology An increase in intrapericardial pressure, resulting in compression of the heart, and thereby a resitriction of cardiac inflow, is termed cardiac tamponade. Tamponade may result from pericardial effusion of any cause. The intrapericardial pressure importantly determines to what extent cardiac inflow is decreased, but two factors need to be taken into consideration. First, intrapericardial pressure is determined not only on the amount of fluid that accumulates, but also on the rate with which this accumulation proceeds, and the available distensibility of the pericardium. Chronic effusions may therefore lead to small increases in intrapericardial pressures in the presence of large fluid accumulations, and small accumulations may directly lead to severe cardiac tamponade for example after free wall rupture. Second, the intravascular volume and intra-atrial, and -ventricular pressures determine at what pressure inflow becomes impaired. When intrapericardial pressure exceeds right atrial pressure (approximately 8 mmHg), tamponade typically follows. However, in patients in whom intra-atrial pressure is decreased, for example due to volume depletion, tamponade may already occur at lower intrapericardial pressures; low-pressure cardiac tamponade. With increasing intrapericardial pressure, clinical features increase with severe hemodynamic compromise as its end stage. First, small changes in intrapericardial pressure induce subtle changes in arterial pressure, cardiac output, and variations in arterial pressure with inspiration (pulsus paradoxus). When intrapericardial pressure reaches levels similar to right atrial and diastolic right ventricular pressure echocardiographic evidence of tamponade may be found in diastolic collapsing of the right atrium, and increased variations of blood flow velocity over the cardiac valves with respiration. Fulminant clinical tamponade presents with symptoms that depend on its etiology. Acute cardiac tamponade based upon aortic or free wall rupture presents with syncope and sudden collapse, whereas tamponade in the setting of an acute inflammatory pericardits may present with pericardial chest pain, and dyspnoea. Therefore, in patients presenting with chest discomfort, dyspnoea, tachycardia or tachypnoea, cardiac tamponade should be suspected when jugular distension, hypotension or pulsus paradoxus is present. Auscultation may reveal pericardial friction rub, and heart sounds may be faint. Echocardiography shows pericardial effusion, the previously mentioned diastolic collapsing of the cardiac cavities, increased flow velocity over tricuspid and pulmonary valves, and decreased flow velocity over the aortic and mitral valves. When secondary to inflammatory pericarditis, tamponade up to moderate severity may be treated by anti-inflammatory drugs. In severe tamponade, pericardiocentesis should be performed to immediately alleviate intrapericardial pressure. Surgical drainage should be considered when pericardiocentesis is unsuccessful, or when tamponade recurs. Acute pericarditis Acute inflammation of the pericardium may result from a wide variety of etiologies (Table 1), and typically presents with chest pain, a pericardial friction rub on auscultation, and repolarization changes on the electrocardiogram. https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 2/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Table 1. Causes of acute pericarditis Acute idiopathic pericarditis Infectious pericarditis: Viral Tuberculosis Bacterial Others Postpericardiotomy syndrome Postmyocardial infarction pericarditis Renal insufficiency Neoplastic disease Chest trauma Irradiation Collagen diseases Patients present with a rapid-onset chest pain syndrome located precordial and retrosternal, and radiating to the subclavian region, the back and the trapezoid region. Chest pain is of moderate severity, lasting for several days, and increases with inspiration or chest movement. Patients typically alleviate the pain by sitting and leaning forward. A pericardial friction rub is pathognomonic of pericarditis, and ECG changes are frequently present, which comprise diffuse concave ST-segment elevation, with positive T-waves in several leads. Atrial injury is accompanied by PR-segment depression. After several hours to a few days, ST-segments return iso-electric, and negative T-waves may occur subsequently, which may persist for several weeks although they frequently normalize within days. Pericardial effusion may be present, and can be diagnosed by chest X-ray when fluid accumulation exceeds 250mL, or by echocardiography. Although initial presentation may mimic ST-segment elevation myocardial infarction (STEMI). Onset of chest pain is less abrupt in acute pericarditis, and varies with respiration. Furthermore, diffuse ST- segment changes are present in pericarditis, whereas STEMI presents with ST-segment elevation, and reciprocal depression, in leads corresponding to the ischemic myocardium. Biomarkers can be positive in both syndromes. Treatment consists of aspirin while pain and fever are present, which usually adequately alleviates symptoms. Another option is NSAIDs, which are recommended when aspirin in insufficient or contraindicated. Corticosteroids should, however, be avoided as they are associated with relapsing pericarditis. Hospital admission may be necessary in patients with high fever, large effusions or cardiac tamponade. Recurrent pericarditis In 8 to 80% of patients, pericarditis recurs after a first episode of acute pericarditis. A continuous type, in which symptoms recur shortly after cessation of anti-inflammatory therapy, and an intermittent type, in which symptom-free periods of more than 6 weeks separate recurrences, can be distinguished. Frequently resulting from inadequate therapy or corticosteroid-use during the initial episode, subsequent recurrences are usually less severe. A recurrence should be treated according to the same https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 3/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology procedures as for the first event. Pericardiectomy may be considered the last resort in severely refractory recurrent pericarditis, but its results are unpredictable. Prognosis of the disease is excellent, as severe complications are rare. Pericardial effusion Fluid accumulation in the pericardium, pericardial effusion, is a common finding on routine echocardiography, and is asymptomatic in the absence of inflammation or cardiac tamponade. It may result from any disease of the pericardium, or be iatrogenic. Most frequently it results from idiopathic pericarditis, malignancy, or iatrogenic defects (Table 2). Table 2. Causes of pericardial effusion Any type of acute pericarditis Cardiac surgery Acute myocardial infarction Heart failure Chronic renal failure Iatrogenic Metabolic diseases Autoimmune diseases Trauma Chylopericardium Pregnancy Idiopathic Where the use of electrocardiography and chest radiography is limited in pericardial effusion, echocardiography may reveal an echo-free space in the anterior or posterior sacs, present throughout the cardiac cycle. The absence of cavity collaps indicates the absence of tamponade. Treatment of pericardial effusion depends on the extent of symptoms, and the etiology underlying the effusion. Asymptomatic mild pericardial effusion (<10mm sum of echo-free spaces in anterior and posterior sacs) may be left untreated. Control echocardiography is indicated at 3-6 months. In moderate (10-20mm sum of echo-free space) to large effusions, a complete history, routine physical examination, ECG, chest radiography and routine blood analysis is indicated. Treatment is then based upon its expected etiology, standard treatment with aspirin or NSAIDs to relief pain, with invasive procedures indicated in case of tamponade with hemodynamic compromise or recurrent pericarditis as discussed previously. Specific etiologies of pericardial effusion must be managed accordingly. Chronic pericardial effusion https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 4/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Pericardial effusion is considered chronic when moderate to large effusions persist for at least 3 months. Resulting most frequently from idiopathic cause, intrapericardial pressure is frequently elevated in these patients, which may lead to unexpected tamponade in up to 30% of patients. Hence, pericardiocentesis is indicated to alleviate the fluid accumulation, and pericardiectomy should be considered when large effusions recur. Long term outcome is excellent with this approach. Pericardial Disease - Chronic The pericardial layers may become rigid, thickened, and may fuse, resulting in restriction of cardiac filling; constrictive pericarditis. In contrast to cardiac tamponade, where cardiac is hampered throughout diastole, cardiac filling is prohibited in the last two-thirds of diastole in constrictive pericarditis, with preserved abrupt filling in early diastole. Chronic constrictive pericarditis Any form of pericarditis may end in constrictive pericarditis, presenting with chronic fatigue, dyspnoea, jugular distension, proto-diastolic pericardial knock, hepatomegaly, ascites, peripheral oedema, and pleural effusion. Atrial fibrillation is a common finding, and diffuse flattened or negative T-waves are usually present. These suggestive clinical findings, in addition to a physiology of restriction or constriction on echocardiography, and the presence of a thickened pericardium provide the diagnosis. However, a thickened pericardium may be absent, which does not rule out constrictive pericarditis. Pericardiectomy is the only effective treatment, which should be instituted shortly after diagnosis, as surgical mortality increases with increasing age and functional impairment. https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 5/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Table 3. Differential diagnosis between chronic constrictive pericarditis and restrictive cardiomyopathy Constrictive pericarditis Restrictive cardiomyopathy Physical examination Early diastolic precordial impulse Apical impulse may be prominent Pericardial knock Third sound may be present No murmur Regurgitant murmur common Electrocardiography Low voltage Low voltage in amiloidosis Frequent atrial fibrillation Frequent atrial fibrillation Normal QRS complex Bundle branch block Chest radiogram Pericardial calcification possible Non-specific cardiomegaly Echocardiography Normal wall thickness Pericardial thickening https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 6/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Diastolic notch of interventricular septum Increased wall thickness (amyloidosis) Enlarged left and right atria Doppler studies e' septal =8 cm/sec and normal S' mitral annular velocity Mitral inflow velocity without respiratory variation Mitral inflow increase during expiration Mitral colour =45cm/s flow propagation velocity M-mode Mitral flow propagation velocity M-mode colour <45cm/s Increased diastolic flow reversal in the hepatic vein with expiration e' septal <8cm/s and decreased mitral annular velocity Increased diastolic flow reversal in vein with inspiration the hepatic Cardiac catheterization RVEDP >one-third of RV systolic pressure RVEDP and LVEDP usually equal LVEDP often >5mm greater than RVEDP RV systolic pressure <50mmHg Endomyocardial biopsy Normal or non-specific changes May reveal specific causes CT/MR imaging Pericardium thickened or calcified Normal pericardium CT, computer tomography; e', e wave velocity by tissue velocity imaging; RV, right ventricular; LVEDP, left ventricular end-diastolic pressure; RVEDP, right ventricular end- diastolic pressure. MR, magnetic resonance; Subacute elastic constriction Elastic cardiac constriction, in contrast to the rigid chronic constriction, results from an elastic thickened pericardium, which still allows distension during the respiratory cycle. It may be seen in the first period after acute inflammatory or infectious pericarditis, and may progress to chronic pericardial constriction, or prove to be a transient process. Effusive-constrictive pericarditis https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 7/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology Presenting with cardiac tamponade on admission, effusive-constrictive pericarditis is characterized by a persistent increase in right atrial and end-diastolic ventricular pressures after intrapericardial pressure has been alleviated by pericardiocentesis. Apart from idiopathic cases, it may accompany chest radiation, cardiac surgery, neoplasia, and tuberculosis. Most frequently, the disease will progress to persistent constriction for which epicardiectomy is indicated, but it may rarely be a transient phenomenon. Transient cardiac constriction Clinical and hemodynamic features of constrictive pericarditis may dissipate spontaneously, which is seen commonly (20%) in idiopathic acute pericarditis with effusion, but may also be seen in tuberculous and purulent pericarditis. Hence, a primarily conservative approach may alleviate the need for epicardiectomy. Pericardial Disease - Specific types Infectious pericarditis Idiopathic/Viral pericarditis This is the most frequent form of pericarditis, accounting for more than 80% of cases, of which most probably are of viral etiology, but virus identification is cumbersome and no treatment consequences exist. The disease is frequently accompanied by pericardial effusion, cardiac tamponade, and left pleural effusion, but prognosis is notably good. Tuberculous pericarditis Predominantly found in developing countries, and in patients with human immunodeficiency virus (HIV) infection, tuberculous pericarditis is rare in the Western world and presents typically with symptoms of acute pericarditis. Identification of Mycobacterium tuberculosis yields the diagnosis, which may be found in pericardial or other bodily fluids, or may be assumed when caseating granulomas are found. Routine tuberculosis treatment, comprising three antituberculous agents, yields a good prognosis although a subacute constrictive pericarditis is common, requiring pericardiectomy but with excellent outcome. Purulent pericarditis Purulent pericarditis has a high mortality, owing to the intangible diagnosis and the related severity of the underlying disease. Cardiac tamponade is frequent, and acute constrictive pericarditis may occur. The disease should be considered in all patients presenting with high fever, dyspnoea, and tachycardia with intrathoracic or subphrenic infections, or sepsis with symptoms that suggest pericardial https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 8/9 7/4/23, 12:38 AM Pericardial Disease - Textbook of Cardiology involvement. Pericardiocentesis is indicated even in the absence of tamponade when the disease is confirmed, and appropriate antibiotic treatment should be instituted. Long-term prognosis is however excellent in patients that survive until discharge. Post myocardial infarction pericarditis Pericardial effusion frequently occurs in the early stage after myocardial infarction, which remains asymptomatic and can be left untreated. Within the first week after myocardial infarction, acute pericarditis may occur, which is related to the extent of the infarction. The presence of a pericardial rub may distinguish chest pain and ECG changes resulting from acute pericarditis from recurrent ischemia. Weeks to months after myocardial infarction, pleuropericarditis of autoimmune nature may prevail, termed Dressler s syndrome. However, this syndrome is rare, and treatment with corticosteroids yields a good prognosis. Neoplastic pericarditis Lung cancer is the most frequent cause of neoplastic pericarditis. Cardiac tamponade in patients with a history of malignancy, in the absence of inflammatory signs indicates a possible malignant etiology, as is lack of response to NSAIDs in this patient group. When the effusion is indeed of malignant origin (approximately 40% of cases), treatment aims at alleviation of symptoms and the prevention of recurrences. A balance should be sought between pericardiocentisis in which recurrence is frequent, and pericardiectomy, which may be overly aggressive in this critically ill subset of patients. Hypothyroidism With increasing severity of primary hypothyroidism, the prevalence of pericardial effusion increases. Thyroid hormone replacement therapy results in remission of the effusion. Post-pericardiotomy pericarditis Pericarditis is common after cardiac surgery (18%), of which the etiology is unclear although an autoimmune origin has been proposed. In contrast to other forms of pericarditis, post-pericardiotomy pericarditis may be effectively treated with corticosteroids and NSAIDs. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Pericardial_Disease&oldid=2369" This page was last edited on 9 May 2013, at 13:05. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Pericardial_Disease#Acute_pericarditis 9/9 |
7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Physical Examination The examination of the patient s history is a critical in the evaluation of (suspected) heart disease. It includes information about the present complaints, development of symptoms over time, medical history and the patient's family. By combining this information, a chronology should be constructed in order to get a profound insight of the patient s disease process. Determining what information is pivotal requires a detailed knowledge of the pathophysiology of cardiac disease. The time invested in carefully examining the patients history is well invested because this information is often very valuable in the diagnostic process. Contents History The Present Illness Antecedent Conditions Atherosclerotic Risk Factors Family History Common Symptoms Chest Pain Dyspnoea Syncope and Pre-syncope Transient Central Nervous System Deficits Fluid Retention Palpitation Cough Physical Findings Physical Examination - General inspection General appearance in severe disease Body position Consciousness Nutrient status Body composition Vital signs Height and weight Blood Pressure Pulse Jugular Venous Pulse Lungs Assessment of the praecordium Inspection Palpitation Presence of the apex beat https://www.textbookofcardiology.org/wiki/Physical_Examination 1/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Location of the apex beat Abnormal types (Size, amplitude, duration) of apex beat: Cardiac Auscultation S1 S2 Extra heart sounds S3 S4 Murmurs Murmurs categorized by time in cardiac cycle History The Present Illness The history taking starts with a careful exploration of the patient s symptoms currently and in the past. The exploration will consist of a thorough questioning of the frequency, intensity, severity, and duration of all patient reported symptoms. Also aggravating and relieving causes should be asked for. In addition to the patient reported symptoms, a strategic questioning of suspected symptoms can be added. Furthermore, current medications, including dosages, the frequency and administration, should be listed. Antecedent Conditions There are several systemic disease which may have cardiac involvement. Disease related to cardiac disease include, but are not limited to, are diabetes mellitus, cancer, thyroid disorders, inflammatory disease, and rheumatic fever. Prior treatments should be asked for because they could reveal the nature of the current problems and/or pre-existing disease. Atherosclerotic Risk Factors Atherosclerotic cardiovascular disease is the most prevalent type of heart disease in industrialized nations. The most important risk factors for atherosclerotic cardiovascular disease should be asked for are: family history of atherosclerotic disease (including age); diabetes mellitus; lipid disorders; hypertension; and smoking history. Family History A family history could provide important information not only in atherosclerotic cardiovascular disease but also for many other cardiac diseases. For example, congenital heart diseases are more common in the offspring of parents, family members or siblings. Genetic diseases, such as neuromuscular disorders, https://www.textbookofcardiology.org/wiki/Physical_Examination 2/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology connective tissue disorders (eg, Marfan syndrome), lipid metabolism disorders can affect the cardiovascular system as well [1] (https://www.textbookofcardiology.org/wiki/Chronic_Coronary_Disea se). Common Symptoms Chest Pain Chest pain has a broad range of causes ranging from non-serious to serious to life threatening (Table 1). Chest pain is one of the important symptoms of ischemic heart disease. Furthermore, it is also associated with several other forms of heart disease. The most commonly used classification of stable angina is the CSS score (Table 2), and the Braunwald classification of unstable angina (Table 3) https://www.textbookofcardiology.org/wiki/Physical_Examination 3/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Table 1. Cause of Chest Pain Cardiovascular Acute coronary syndrome Stable angina pectoris Aortic dissection (Acute) Pericarditis Cardiac tamponade Arrhythmia Pulmonary Pulmonary embolism Pneumonia (Spontaneous) pneumothorax and tension pneumothorax Tuberculosis Pleurisy Gastrointestinal Disorders of the esophagus (Acid reflu disease, esophagitis, esophageal spasm) Hiatus hernia Achalasia, nutcracker esophagus and other neuromuscular disorders of the esophagus Functional dyspepsia Musculoskeletal Costochondritis Radiculopathy Bornholm disease Psychological Panic attack Anxiety Clinical depression Somatization disorder Hypochondria Others Hyperventilation syndrome Carbon monoxide poisoning Sarcoidosis Lead poisoning Precordial catch syndrome High abdominal pain Breast conditions Herpes zoster commonly known as shingles https://www.textbookofcardiology.org/wiki/Physical_Examination 4/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Table 2. Canadian Cardiovascular Society Functional Classification of Angina Pectoris Class Definition Specific Activity Scale Ability to ski, play basketball, jog at 5 mph, or shovel snow without angina. Ordinary physical activity (e.g., walking and climbing stairs) does not cause angina; angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. I Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, in cold, in wind, or under emotional stress, or only during the few hours after awakening, when walking more than two blocks on level ground, or when climbing more than one flight of stairs at a normal pace and in normal conditions. Ability to garden, rake, roller skate, walk at 4 mph on level ground, have sexual intercourse without stopping. II Marked limitation of ordinary physical activity. Angina occurs on walking one to two blocks on level ground or climbing one flight of stairs at a normal pace in normal conditions. Ability to shower or dress without stopping, walk 2.5 mph, bowl, make a bed, play golf. III Inability to perform any physical activity without discomfort. Anginal symptoms may be present at rest. Inability to perform activities requiring 2 or fewer metabolic equivalents without angina. IV Table 3. Braunwald Classification of Unstable Angina (UA) Clinical Circumstances A B C Develops in presence of extracardiac condition that intensifies myocardial ischemia (secondary UA) Develops within 2 weeks after acute myocardial infarction (postinfarction UA) Severity Develops in the absence of extracardiac condition (primary UA) New onset of severe angina or accelerated angina; no rest pain I IA IB IC Angina at rest within past month but not within preceding 48 hr (angina at rest, subacute) II IIA IIB IIC IIIB Troponin negative Angina at rest within 48 hr (angina at rest, acute) III IIIA IIIC IIIB Troponin positive hr, hours; IAM, myocardial infarction; UA, unstable angina. The five most common characteristics of ischemic chest pain are: https://www.textbookofcardiology.org/wiki/Physical_Examination 5/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology The pain is classically deep, visceral, and intense. Patient often describe this pain as pressing , tearing , constricting , burning . Another common presentation is described as chest heaviness such as a band across the chest , or weight in the centre of the chest . The anginal pain is usually substernal located, but may extend to the left or right chest. Furthermore radiation of the pain is common, typically to the left shoulder and arm. Other locations are possible such as the neck, jaw, epigastrium, and, occasionally, the upper back. The duration of the pain is minutes, not seconds. The pain tends to be precipitated by exercise. The pain can also be provoked by heavy meals or emotional stress. The pain ablates promptly by resting (within minutes) or taking sublingual nitroglycerin. Table 4. Typical feature in various types of chest pain Response to food/fluid Referred pain Response to posture/movement Response to nitroglycerin Cause of pain Type of pain Tenderness Cardiovascular Ischemic cardiac pain Visceral Yes No No No Yes Aortic dissection Visceral Yes No No No No Pericarditis Visceral Yes Yes No No No Arrhythmia Visceral No No No No No Pulmonary disease Visceral/cutaneous Usually no No No No No Pneumothorax Visceral/cutaneous No Yes No Usually no No Musculoskeletal Cutaneous No Yes No Yes No Gastrointestinal Visceral Sometimes No Yes No Sometimes Psychiatric Visceral/cutaneous No No No No No Dyspnoea Dyspnoea is a frequent complaint of patients with a variety of cardiac diseases. Generally four types of dyspnoea can be distinguished: Exertional dyspnoea. Dyspnoea provoked by exercise, usually caused by a mild underlying condition because an increased demand of exertion is needed to precipitate symptoms. Dyspnoea at rest. Dyspnoea is suggestive for severe cardiac disease. Paroxysmal nocturnal dyspnoea. Dyspnoea characterized by the patient awakening after being asleep or recumbent for an hour or more. This type of dyspnoea is commonly caused by the redistribution of body fluids from the lower extremities into the vascular space and back to the heart, resulting in volume overload. Because of this pathophysiological background it suggests a more severe condition. Orthopnoea. Dyspnoea that occurs immediately on assuming the recumbent position. The mild increase in venous return (caused by lying down), before any fluid is mobilized from interstitial spaces in the lower extremities, is responsible for the symptom. https://www.textbookofcardiology.org/wiki/Physical_Examination 6/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology The cause of dyspnoea is certainly not limited to cardiac disease. Exertional dyspnoea, for example, can be due to pulmonary disease or anaemia. Orthopnoea is also a frequent complaint in patients with chronic obstructive pulmonary disease and postnasal drip. Resting dyspnoea is also a common sign of pulmonary disease such as pneumonia or bronchial infection. However, paroxysmal nocturnal dyspnoea is the most specific symptom for an underlying cardiac cause because alternative diagnoses are limited. Syncope and Pre-syncope Light-headedness, dizziness, pre-syncope, and syncope are important symptoms, often caused by a reduction in cerebral blood flow. The mentioned symptoms are nonspecific and can be due to a broad caused by a broad range of underlying pathophysiology such as metabolic conditions, dehydration, primary central nervous system disease, or inner-ear problems. Because bradyarrhythmias and tachyarrhythmias are important cardiac causes of these symptoms, they are of importance in the cardiovascular examination. A careful history taking, including preceding symptoms such as palpitations or chest pain, are of great importance. Further information on this topic can be found in [2] (https://ww w.textbookofcardiology.org/wiki/Syncope). Transient Central Nervous System Deficits Transient central nerves system deficits such as transient ischemic attacks (TIAs) suggest the existence of (micro) emboli originating form greater vessels, the carotid arteries or the heart. Rarely a TIA can also be caused by emboli from the venous circulation through an intracardiac shunt. As a result, a TIA should prompt the search for underlying cardiovascular disease. Any sudden loss of blood flow to (parts of) the limbs are also suggestive for an underlying cardioembolic event. Fluid Retention Fluid retention is not a very specific symptom for heart disease but may be caused due to reduced cardiac function. Symptoms associated with fluid retention are peripheral oedema, weight gain, bloating, and/or abdominal pain from an enlarged liver or spleen. Decreased appetite, jaundice, nausea and vomiting can also occur from gut and hepatic dysfunction due to a build up of fluids. Palpitation Cardiac activity usually cannot be experienced by individuals in normal resting condition. If a patient is aware of its heart activity it is usually referred to as palpitation. Among cultures and patients there is no standard definition for the type of sensation represented by palpitation. It is often very illustrative to ask the patients to tap with their hand the perceived heartbeat. Most commonly palpitations are caused by an unusually forceful heart beat at a normal rate (60 100 bpm). When a patient senses more forceful contractions as usual without a significant increased heart rate, the palpitations are most commonly the result of endogenous catecholamine excretion. A customary cause of this phenomenon is anxiety. Another common experienced feeling is that of the heart stopping transiently and/or the occurrence of isolated forceful beats. The nature of this sensation is usually premature ventricular contractions. The rapid regular or irregular heart rates most linked to the term palpitations are the least common https://www.textbookofcardiology.org/wiki/Physical_Examination 7/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology sensation reported by individual patients and is usually supraventricular of origin. More information on palpitations caused by arrhythmias can be found in the subsequent chapter [3] (https://www.textbookof cardiology.org/wiki/Cardiac_Arrhythmias). Cough Although cough is usually associated with disease of pulmonary origin, there are also several cardiac conditions that lead to pulmonary abnormalities which causes subsequent pulmonary disease and subsequent cough. A cough from cardiac origin is usually dry and non-productive. Pleural fluid retention from conditions such as heart failure or pulmonary hypertension from any cause may present as cough. Finally, it should be mentioned that angiotensin-converting enzyme inhibitors, which are frequently used in cardiac conditions, can cause a typical dry cough. Physical Findings Physical Examination - General inspection The inspection of the patient is an observational task starting from the first contact all the way during the examination. All signs have to be carefully noticed because they can be of importance in the further diagnostic process. General appearance in severe disease Signs of acute life threatening disease which need acute intervention to avert death. First important symptom is the colour of the face and skin which could be pallor or cyanotic as a sign of diminished circulation and/or respiration. Furthermore, the respiratory pattern and rate should be assessed for severe signs such as slow and irregular pattern, an audible rasp breathing with foam around the mouth, or in some cases a very fast and superficial breathing pattern. Additionally, the absence or a very weak pulsation could also be a sign of an acute life threatening disease. (For more detailed assessment of the pulse please notice the paragraph on this topic [4] (https://www.textbookofcardiolo gy.org/wiki/Physical_Examination#Pulse)) Be aware that these symptoms can be apparent, but there absence does not rule out an acute life threatening disease. Signs of severe diseases which are life threatening demands a similar approach with special attention to face colour, respiration and pulse. The face colour can be pallor, cyanotic or red. Respiration can be fast and superficial, often a sign of severe disease. The pulse is also important in case of severe disease, for more information see [5] (https://www.textbookofcardiology.org/wiki/Physi cal_Examination#Pulse). Furthermore it is important to assess signs of lowered degree of consciousness, emaciation, high body temperature and agitation. Body position https://www.textbookofcardiology.org/wiki/Physical_Examination 8/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Observe the patients position and if there is any preferred position in order to reduce or eliminate pain. For example, the pain of acute pericarditis is often minimized by sitting up, leaning forward, and breathing shallowly. When patients need to sit up right because of increasing dyspnoea when declining, so called orthopnoea, could be a sign of sever heart failure. Consciousness The consciousness state of the patient needs to be assessed to be assured of adequate brain functions or any disturbance. Subtle changes in consciousness are not easy to recognize and need special attention. Orientation in time, place and person need to be questioned. Gradual changes in consciousness can be very subtle, such changing conditions due to a delirium, or more apparent, such as somnolence or coma due to severe disease. In respect to heart disease we should be aware of these signs because they can relate to metabolic disease, such as hypoglycaemia in diabetes, and intoxication by medication or carbon monoxide. Nutrient status A lowered nutrient status can be a sign of several diseases. Generally there can be less intake, due to starvation, a lack of uptake, due to bowel disease, or a high combustion, due to chronic disease in for example metabolic disease or malign tumor growth. Emaciation, (extreme) low body weight, could be a sign of chronic heart failure or another systemic disorder (e.g., malignancy, infection). Body composition The body composition is a combination of skeletal build and soft tissue such as muscles and fat tissue. An abnormal body composition could be one of the signs of syndromes or non-cardiovascular conditions associated with cardiovascular abnormalities, such as for example Marfan syndrome, Down syndrome, Turner syndrome and ankylosing spondylitis [link congenital heart disease]. Vital signs The vital signs, including height, weight, temperature, heart rate, blood pressure, respiratory pattern and rate, and peripheral oxygen saturation, can guide diagnosis and management in heart disease. Height and weight The height and weight permit the calculation of body mass index (BMI) and body surface area (BSA). Regular weight assessment is an important tool in the follow up of heart failure patients with significant fluid retention. Additionally, weight can be used for the adjustment of medication levels. Central obesity, as assed by the waist circumference (measured at the iliac crest) and waist-to-hip ratio (using the widest circumference around the buttocks), is a important determinant in the metabolic syndrome and one of the predictors of long-term cardiovascular risk. Blood Pressure https://www.textbookofcardiology.org/wiki/Physical_Examination 9/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology One of the keystones of the cardiovascular physical examination is the proper measurement of the systemic arterial pressure by cuff sphygmomanometry at both arms. Blood pressure in the arterial system varies during the cardiac cycle, with a peak in the systole and the lowest level in diastole. The difference between the systolic and diastolic pressure is known as the pulse pressure. The arterial pressure is influenced by four important factors: Stroke volume of the left ventricle Compliance of the aorta and large arteries Resistance of the peripheral vasculature, particularly at the arteriolar level Blood volume and viscosity in the arterial system A change in one or more of these factors alters systolic and/or diastolic pressure. The blood pressure fluctuates constantly and is influenced by a variety of factors such as pain, emotional state, physical activity, tobacco, coffee, drug use and consciousness. In order to measure a reproducible blood pressure several aspects have to been taken into account, most important summarized in Table 5. Table 5. Important aspects of blood pressure measurements Patient seated comfortably, back supported, bared upper arm, legs uncrossed Arm should be at heart level Cuff length/width should be 80%/40% of arm circumference Cuff should be deflated at <3 mm Hg/sec Column or dial should be read to nearest 2 mm Hg First audible Korotkoff sound is systolic pressure; last sound, diastolic pressure No talking between subject and observer The best way to measure the blood pressure starts with the palpation of the brachial artery, over which the diaphragm of the stethoscope has to be placed over it in the antecubital fossa. The onset and disappearance of the Korotkoff sounds define the systolic and diastolic pressures, respectively. There are some exceptions where the described assessment of the Korotkoff sounds is obsolete. For example, if the diastolic pressure drops near to zero, the point of muffling of the sounds is usually wrongly recorded as the diastolic pressure. The definition of hypertension dictates repeated measures under the same conditions, therefore the operator should record the arm (left/right) and the body position (lying/suspine/upright) of the patient to allow reproducible measurements to be made on serial visits. Normal and abnormal blood pressure levels in adult are represented in table 6. Please note that the normal levels in children are lower. The risk of cardiovascular disease increases progressively above 115/75 mmHg. Regarding hypotension, in daily practice blood pressure is considered too low only if noticeable symptoms are present. Clinical trials have demonstrated that humans who maintain arterial pressures at the low end of these pressure ranges have much better long term cardiovascular health. Elevations in all age categories, although more commonly seen in elderly, are generally associated with increased morbidity and mortality. https://www.textbookofcardiology.org/wiki/Physical_Examination 10/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Table 6. Classification of blood pressure for adults Category systolic, mmHg diastolic, mmHg Hypotension <90 <60 Desirable 90 120 60 79 Prehypertension 121 139 or 80 89 Stage 1 Hypertension 140 159 or 90 99 Stage 2 Hypertension 160 179 or 100 119 Hypertensive Crisis 180 or 120 Measuring the blood pressure in a different position can be of clinical importance, for example to determine any orthostatic changes in blood pressure. In order to measure orthostatic hypotension the patient has to move from a supine to a standing position with a significant blood pressure drop within 3 minutes. Orthostatic hypotension is defined as a fall in blood pressure of more than 20 mm Hg systolic and/or more than 10 mm Hg diastolic. Orthostatic changes are of special interest in patients complaining of transient central nervous system symptoms, weakness, or unstable gait. Especially elderly have an increased tendency toward orthostatic hypotension due to a decreased compliance of the arteries and/or a decreased compensation mechanism increasing the stroke volume, resulting in a sudden drop of blood pressure which can cause dizziness or syncope. A difference in pressure between the right and left arm of 10 mmHg or more suggests an arterial obstruction in the arterial system of the arm were the lowest pressure is measured. Causes of significant differences between the blood pressure at the right an left arm are subclavian artery disease, aortic coarctation, supravalvular aortic stenosis or dissection. Additionally, in future assessment of the blood pressure the arm with the highest pressure should be measured. Furthermore, note that the pulse pressure is a crude measure of left ventricular stroke volume. A widened pulse pressure suggests that the stroke volume is large; a narrowed pressure, that the stroke volume is small. A widened pulse pressure also can be an indication of atherosclerotic disease, characterised by lengthened, more tortuous, and harder and less resistant arteries. Pulse The peripheral pulsations should be assed by both palpitation of the pulse and auscultation for bruits. Pulse abnormalities and bruits increase the likelihood of peripheral arterial disease. Pulsations should be assessed and documented in several arteries in the body in order to get an idea of the state of peripheral vasculature. Easily and fast palpable pulses in healthy individuals include the brachial, radial, and ulnar arteries of the upper extremities and the femoral, popliteal, dorsalis pedis, and posterior tibial arteries of the lower extremities. Minor or absent pulsations suggest a severe stenotic lesion proximal of the palpation site. To asses the cardiac (dys)function through the pulse generally an artery close to the heart should be selected, such as the carotid. Bounding high-amplitude carotid pulses suggest an increase in stroke volume and should be accompanied by a wide pulse pressure on the blood pressure measurement. A weak carotid pulse suggests a reduced stroke volume. [Figure 1] When examining the peripheral arterial pulsations by palpitation three important aspects should be noticed: The amplitude of the pulse, which correlates with the pulse pressure The contour of the pulse wave, depicted by the speed of up- and downstroke and the duration of its summit. In a physiological situation the upstroke is rapid, smooth and almost directly after the first https://www.textbookofcardiology.org/wiki/Physical_Examination 11/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology heart sound. The summit is roughly midsystolic and has a smooth and rounded nature. The downstroke is generally less abrupt than the upstroke in a normal situation. Variations in the amplitude, either with respiration or from beat to beat. The contour of the pulses depends on the stroke volume, ejection velocity, vascular capacity and compliance, and systemic resistance. The palpable pulsations reflect both the antegrade pulsatile flow of blood and reflection of the propagated pulse the peripheral artery returning system. The arterial pulse upstroke increases with distance from the heart. In a physiological state, the percussion wave begins with systolic ejection (just after the is the mainly first heart sound) and the monophasic pulse appreciated at (an notch bedside. exaggerated, diastolic wave) demonstrates the aortic valve closure. A bounding pulse may occur in hyperkinetic states such as fever, anaemia, and thyrotoxicosis, or in pathologic states such as severe bradycardia, aortic regurgitation, fistula. Two distinct or arteriovenous pressure peaks in systole relate to a bifid pulse. This phenomenon is consistent with increased vascular compliance and may occur with fever or after exercise in a normal individual. With chronic severe aortic regurgitation, a large stroke volume ejected rapidly into a noncompliant arterial tree produces a reflected wave of sufficient amplitude to be palpated during systole. Hypertrophic obstructive cardiomyopathy can rarely produce a bifid systolic pulse with percussion and tidal (or reflected) waves. Usually the strength of the pulse is graded on a scale of 1 to 4, where 2 is a normal pulse amplitude, 3 or 4 is a hyperdynamic pulse, and 1 is a weak pulse. A low- amplitude, slow-rising pulse, which may be associated with a palpable vibration (thrill), suggests aortic stenosis. In patients over 70 years of age it is particularly important to palpate the abdominal aorta because abdominal aortic aneurysms are more prevalent. from The dicrotic early, Figure 1. Body locations for examining the pulse. A more than 10 mm Hg fall in systolic pressure with inspiration (pulsus paradoxus) is considered pathologic and a sign of pericardial or pulmonary disease, and can also occur in obesity and pregnancy without clinical disease. Pulsus paradoxus is measured by noting the difference between the systolic pressure at which the Korotkoff sounds are first heard (during expiration) and the systolic pressure at which the Korotkoff sounds are heard with each beat, independent of respiratory phase. Between these two pressures, the sounds are heard only intermittently (during expiration). In order to appreciate this subtle finding, the cuff pressure must be decreased slowly. Tachycardia, AF, and tachypnea make its https://www.textbookofcardiology.org/wiki/Physical_Examination 12/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology assessment difficult. Pulsus paradoxus may also be palpable when the pressure difference exceeds 15 to 20 mm Hg. Pulsus paradoxus is not specific for pericardial tamponade and can also accompany massive pulmonary embolus, hemorrhagic shock, severe obstructive lung disease, or tension pneumothorax. Pulsus alternans is defined by a beat-to-beat variability of the pulse amplitude. When only every other phase 1 Korotkoff sound is audible as the cuff pressure is slowly lowered, in a patient with a regular heart rhythm, independent of the respiratory cycle. Pulsus alternans is generally seen in severe heart failure. Important provoking factors of this phenomenon are severe aortic regurgitation, hypertension, and hypovolemic states. This phenomenon is attributed to cyclic changes in intracellular calcium levels and action potential duration. If it is the pulsus alternans is associated with electrocardiographic T wave the combination appears to increase arrhythmic risk. Bruits often indicate accelerated blood flow velocity and/or flow disturbance at sites of arterial stenosis. By auscultation the supraclavicular and infraclavicular fossae should be assessed for evidence of subclavian artery stenosis. Additionally, the abdomen, flank, and pelvis should be examined with a stethoscope for evidence of stenosis in the aorta and its branch vessels; and each groin for evidence of femoral artery stenosis. When patients suffer from aortoiliac disease, muscle atrophy in the legs may be seen. Other signs of chronic low-grade ischemia include thickened and brittle toenails, smooth and shiny skin, and subcutaneous fat atrophy of the digital pads. Patients with limb ischemia with dysfunction of the small arteries have a prolonged capillary refill of 3 seconds or more. Jugular Venous Pulse Assessment of the jugular venous pulse (JVP) is a method to assess central venous pressure and right atrium pressure. The examination can provide information about the patient s volume status and cardiac function. Note that the JVP is not useful to asses in children younger than 12 years, because it is hard to asses in this age group. Ideally the patient is positioned into the semi-upright posture, with an elevation of the head of the bed to 30 , that permits visualization of the top of the right internal jugular venous blood column. A venous arch may be used to measure the JVP more accurately. The JVP is the elevation at which the highest oscillation point of the jugular venous pulsations is usually seen in euvolemic patients. The height of the column of blood seen in the internal jugular vein, vertically from the sternal angle, is added to 5 cm of blood (the presumed distance to the centre of the right atrium from the sternal angle) to obtain an estimate of central venous pressure in centimetres of blood. In patients who are hypovolemic, you may anticipate that the jugular venous pressure will be low. Likewise, in hypervolemic patients, you may anticipate that the JVP will be high. As a result, in hypovolemic patients the head should be in a lowered position (up to 0 ), while in a hypervolemic state the head should be subsequently raised of the bed. Additionally, the characteristics of the right internal jugular pulse should be assessed, because they can be reveal clinical signs of right-heart function and rhythm disturbances. The distinctive waves of the jugular vein are summarized in Table 7 and visualized in Figure 2. https://www.textbookofcardiology.org/wiki/Physical_Examination 13/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Figure 2. Jugular venous pulse waveform. Table 7. The jugular venous pulsation has a biphasic waveform. The a wave corresponds to right Atrial contraction and ends synchronously with the carotid artery pulse. The peak of the 'a' wave demarcates the end of atrial systole. The c wave corresponds to right ventricular Contraction causing the triCuspid valve to bulge towards the right atrium. The x descent follows the 'a' wave and corresponds to atrial relaXation and rapid atrial filling due to low pressure. The x'(x prime) descent follows the 'c' wave and occurs as a result of the right ventricle pulling the tricuspid valve downward during ventricular systole. The x' (x prime) descent can be used as a measure of right ventricle contractility. The v wave corresponds to Venous filling when the tricuspid valve is closed and venous pressure increases from venous return - this occurs during and following the carotid pulse. The " y " descent corresponds to the rapid emptYing of the atrium into the ventricle following the opening of the tricuspid valve. An elevated JVP is the classic sign of venous hypertension, typically in right sided heart failure. JVP elevation can be visualized as jugular venous distension, whereby the JVP is visualized at a level of the neck that is higher than normal. The paradoxical increase of the JVP with inspiration (instead of the expected decrease) is referred to as the Kussmaul sign, and indicates impaired filling of the right ventricle. The differential diagnosis of Kussmaul's sign includes constrictive pericarditis, restrictive cardiomyopathy, pericardial effusion, and severe right-sided heart failure. https://www.textbookofcardiology.org/wiki/Physical_Examination 14/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology There are many JVP abnormalities which can be appreciated after careful assessment. These abnormalities can be linked a broad spectrum of disease as highlighted below: Raised JVP, normal waveform Bradycardia Fluid overload Heart Failure Raised JVP, absent pulsation Superior vena cava syndrome Large a wave (increased atrial contraction pressure) Tricuspid stenosis Right heart failure Pulmonary hypertension Cannon 'a' wave (atria contracting against closed tricuspid valve) Atrial flutter Premature atrial rhythm (or tachycardia) Third degree heart block Ventricular ectopics Ventricular tachycardia Absent a wave (no univocal atrial depolarisation) Atrial fibrillation Large v wave (c-v wave) Tricuspid regurgitation Slow y descent Tricuspid stenosis Parodoxical JVP (Kussmaul's sign: JVP rises with inspiration, drops with expiration) Pericardial effusion Constrictive pericarditis Pericardial tamponade Lungs Evaluation of the lungs and respiration is an important part of the physical examination: Both diseases of the lung can affect the heart, as well as diseases of the heart can affect the lungs. Auscultation and percussion is also a very important feature of the clinical examination of the lungs and respiratory system. The borders of the lung should be assessed by percussion. Furthermore percussion can reveal dullness, associated with for example abnormal pleural effusion. Several areas of the lungs should examined by auscultation in an upright position, if possible, both at the back and front of the patients, both base and apical fields covering all lung lobes. https://www.textbookofcardiology.org/wiki/Physical_Examination 15/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology During auscultation the patient s respiratory pattern and rate should be assed. Tachypnoea is defined as increased breaths 20 or more breaths per minute. Physiological causes of tachypnoea are, for example, heightened oxygen demand due to exercise or labour during pregnancy. Amongst pathophysiological causes, tachypnoea can be a symptom of carbon monoxide poisoning, haemothorax or pneumothorax. Furthermore, pursing of the lips, a breathy quality to the voice, and an increased anteroposterior chest diameter would favour a pulmonary rather than cardiovascular cause of dyspnoea. Special attention is needed in case of so called Cheyne-Stokes respiration or Kussmaul breathing. Cheyne-Stokes is an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing called an apnoea. These phenomena can occur during wakefulness or during sleep, where they are called the Central sleep apnoea syndrome. It may be caused by physiological abnormalities in chronic heart failure or damage to respiratory centres. Kussmaul breathing is defined as abnormally slow deep respiration characteristic of air hunger. This typical breathing pattern is caused by respiratory compensation for a metabolic acidosis, most commonly occurring in diabetics in diabetic ketoacidosis. The observation of respiration during sleep may reveal signs of disordered breathing associated with cardiovascular disease (e.g. obstructive sleep apnoea). A clinical significant finding in the cardiovascular examination is rales at the pulmonary bases, indicating alveolar fluid collection. This fluid collection can be an important sign of heart failure in patients, however it is not always possible to distinguish rales caused by heart failure from those caused by pulmonary disease. Also the presence of pleural fluid, although useful in the diagnosis of heart failure, can be due to other causes. An additional combination of symptoms, dullness at the left base combined with bronchial breath sounds suggests an increase in heart size from pericardial effusion (Ewart sign) or cardiac enlargement due to another cause. Pathophysiological it is thought to be due to compression by the heart of a left lower lobe bronchus. If severe right-heart failure develops or when venous return is restricted from entering the heart, venous pressure will increase in the abdomen, leading to hepatosplenomegaly and eventually ascites. These physical findings are not specific for heart disease, nonetheless they do help establish the diagnosis. Heart failure also leads to generalized fluid retention, usually manifested as lower extremity oedema. Oedema in de lower extremities is a sign of fluid retention, the skin can be compressed and will stay in this shape for a limited time. Oedema in lower extremities can also be caused by decreased venous return due to thrombosis or dysfunction of the venous system. Assessment of the praecordium Inspection The praecordium is the front of the chest overlying the heart. First a global inspection should include the assessment shape and symmetry of the chest. A barrel chest could be a sign of chronic breathing problems. Also abnormalities of the shape of spine such as a kyphosis or scoliosis should be noticed, not only because of pathophysiological implications, but also demanding special care with regarding cardiac auscultation. Scars could be found at different locations as signs of prior thoracic surgery. Most common locations include: Midline sternal scar: prior major thoracic surgery such as coronary artery bypass grafting and/or valve replacement Left sided thoracic scar (diagonal from under left breast to left axilla): Mitral valve surgery. https://www.textbookofcardiology.org/wiki/Physical_Examination 16/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Inferior of clavicula (left and/or right sided): Pacemaker / internal cardiac defibrillator implantation. Above all, focus should be on visible cardiac pulsations, mostly in the apex region of the heart. In lean people the apex beat may be visible. A visible apex beat could also be a sign of abnormal conditions such as left ventricular aneurysm. Palpitation |
https://www.textbookofcardiology.org/wiki/Physical_Examination 13/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Figure 2. Jugular venous pulse waveform. Table 7. The jugular venous pulsation has a biphasic waveform. The a wave corresponds to right Atrial contraction and ends synchronously with the carotid artery pulse. The peak of the 'a' wave demarcates the end of atrial systole. The c wave corresponds to right ventricular Contraction causing the triCuspid valve to bulge towards the right atrium. The x descent follows the 'a' wave and corresponds to atrial relaXation and rapid atrial filling due to low pressure. The x'(x prime) descent follows the 'c' wave and occurs as a result of the right ventricle pulling the tricuspid valve downward during ventricular systole. The x' (x prime) descent can be used as a measure of right ventricle contractility. The v wave corresponds to Venous filling when the tricuspid valve is closed and venous pressure increases from venous return - this occurs during and following the carotid pulse. The " y " descent corresponds to the rapid emptYing of the atrium into the ventricle following the opening of the tricuspid valve. An elevated JVP is the classic sign of venous hypertension, typically in right sided heart failure. JVP elevation can be visualized as jugular venous distension, whereby the JVP is visualized at a level of the neck that is higher than normal. The paradoxical increase of the JVP with inspiration (instead of the expected decrease) is referred to as the Kussmaul sign, and indicates impaired filling of the right ventricle. The differential diagnosis of Kussmaul's sign includes constrictive pericarditis, restrictive cardiomyopathy, pericardial effusion, and severe right-sided heart failure. https://www.textbookofcardiology.org/wiki/Physical_Examination 14/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology There are many JVP abnormalities which can be appreciated after careful assessment. These abnormalities can be linked a broad spectrum of disease as highlighted below: Raised JVP, normal waveform Bradycardia Fluid overload Heart Failure Raised JVP, absent pulsation Superior vena cava syndrome Large a wave (increased atrial contraction pressure) Tricuspid stenosis Right heart failure Pulmonary hypertension Cannon 'a' wave (atria contracting against closed tricuspid valve) Atrial flutter Premature atrial rhythm (or tachycardia) Third degree heart block Ventricular ectopics Ventricular tachycardia Absent a wave (no univocal atrial depolarisation) Atrial fibrillation Large v wave (c-v wave) Tricuspid regurgitation Slow y descent Tricuspid stenosis Parodoxical JVP (Kussmaul's sign: JVP rises with inspiration, drops with expiration) Pericardial effusion Constrictive pericarditis Pericardial tamponade Lungs Evaluation of the lungs and respiration is an important part of the physical examination: Both diseases of the lung can affect the heart, as well as diseases of the heart can affect the lungs. Auscultation and percussion is also a very important feature of the clinical examination of the lungs and respiratory system. The borders of the lung should be assessed by percussion. Furthermore percussion can reveal dullness, associated with for example abnormal pleural effusion. Several areas of the lungs should examined by auscultation in an upright position, if possible, both at the back and front of the patients, both base and apical fields covering all lung lobes. https://www.textbookofcardiology.org/wiki/Physical_Examination 15/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology During auscultation the patient s respiratory pattern and rate should be assed. Tachypnoea is defined as increased breaths 20 or more breaths per minute. Physiological causes of tachypnoea are, for example, heightened oxygen demand due to exercise or labour during pregnancy. Amongst pathophysiological causes, tachypnoea can be a symptom of carbon monoxide poisoning, haemothorax or pneumothorax. Furthermore, pursing of the lips, a breathy quality to the voice, and an increased anteroposterior chest diameter would favour a pulmonary rather than cardiovascular cause of dyspnoea. Special attention is needed in case of so called Cheyne-Stokes respiration or Kussmaul breathing. Cheyne-Stokes is an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing called an apnoea. These phenomena can occur during wakefulness or during sleep, where they are called the Central sleep apnoea syndrome. It may be caused by physiological abnormalities in chronic heart failure or damage to respiratory centres. Kussmaul breathing is defined as abnormally slow deep respiration characteristic of air hunger. This typical breathing pattern is caused by respiratory compensation for a metabolic acidosis, most commonly occurring in diabetics in diabetic ketoacidosis. The observation of respiration during sleep may reveal signs of disordered breathing associated with cardiovascular disease (e.g. obstructive sleep apnoea). A clinical significant finding in the cardiovascular examination is rales at the pulmonary bases, indicating alveolar fluid collection. This fluid collection can be an important sign of heart failure in patients, however it is not always possible to distinguish rales caused by heart failure from those caused by pulmonary disease. Also the presence of pleural fluid, although useful in the diagnosis of heart failure, can be due to other causes. An additional combination of symptoms, dullness at the left base combined with bronchial breath sounds suggests an increase in heart size from pericardial effusion (Ewart sign) or cardiac enlargement due to another cause. Pathophysiological it is thought to be due to compression by the heart of a left lower lobe bronchus. If severe right-heart failure develops or when venous return is restricted from entering the heart, venous pressure will increase in the abdomen, leading to hepatosplenomegaly and eventually ascites. These physical findings are not specific for heart disease, nonetheless they do help establish the diagnosis. Heart failure also leads to generalized fluid retention, usually manifested as lower extremity oedema. Oedema in de lower extremities is a sign of fluid retention, the skin can be compressed and will stay in this shape for a limited time. Oedema in lower extremities can also be caused by decreased venous return due to thrombosis or dysfunction of the venous system. Assessment of the praecordium Inspection The praecordium is the front of the chest overlying the heart. First a global inspection should include the assessment shape and symmetry of the chest. A barrel chest could be a sign of chronic breathing problems. Also abnormalities of the shape of spine such as a kyphosis or scoliosis should be noticed, not only because of pathophysiological implications, but also demanding special care with regarding cardiac auscultation. Scars could be found at different locations as signs of prior thoracic surgery. Most common locations include: Midline sternal scar: prior major thoracic surgery such as coronary artery bypass grafting and/or valve replacement Left sided thoracic scar (diagonal from under left breast to left axilla): Mitral valve surgery. https://www.textbookofcardiology.org/wiki/Physical_Examination 16/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Inferior of clavicula (left and/or right sided): Pacemaker / internal cardiac defibrillator implantation. Above all, focus should be on visible cardiac pulsations, mostly in the apex region of the heart. In lean people the apex beat may be visible. A visible apex beat could also be a sign of abnormal conditions such as left ventricular aneurysm. Palpitation Palpitation of the praecordium should focus on the apex beat (defined as the most inferior point where the cardiac impulse is still palpable). The flat of your hand should be positioned so that the middle finger lies on the left 5th intercostal space of the patient, covering the anterolateral ribcage. The other fingers are positioned on the spaces above and below of the point of maximum pulsation. If no pulsation is felt, move the hand in all directions, feeling for a pulsation. Asking the patient to lean forward may help locate the apex beat if it is hard to palpate. Several aspects of the apex beat should be noticed: Presence: In normal conditions the apex beat is palpable in the majority of patients. Location: The normal apex beat should be in the 5th intercostal space in the mid clavicular line. Size: The normal size of the apex beat has a diameter of about 3-4 cm in adults. Amplitude: The normal character of apex is a short pulsating beat. Duration: The duration of a normal apex beat is short during systole Thrills: A thrill is a palpable vibration caused by turbulent blood flow and is always pathological. Feel for a thrill (rather like a cat purring) at the apex, the upper part of the praecordium and in the sternal notch. The commonest cause of a thrill is aortic stenosis. Presence of the apex beat Several causes, both physiological and pathological, can be found for the absence of the apex beat. A mnemonic to remember these causes is DR POPE: Physiological causes: Dextrocardia; the apex will be absent at the on the left side, but it will be present on the right side. Rib; if the apex beat is behind a rib it can not be found in an intercostal space. Turning the patient to the left lateral position will reveal the apex beat, confirming this cause. Pathological causes: Pericardial effusion Obesity and thick chest wall Pleural effusion (left sided) Emphysema Location of the apex beat https://www.textbookofcardiology.org/wiki/Physical_Examination 17/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology The location of the apex beat has to be assessed with respect to the tracheal position. If trachea is also shifted along with the displacement of apex beat, then it is due to mediastinal shift as a result of conditions such as lung fibrosis, collapse or pneumothorax. If the trachea is central but the apex is displaced, the causes may be: Left ventricular enlargement - the apex will be displaced downwards and laterally. Right ventricular enlargement - the apex will displaced laterally. Cardiomegaly due to significant enlargement of other chambers can also cause displacement Pectus excavatum resulting in a different location due to congenital thoracic deformity Abnormal types (Size, amplitude, duration) of apex beat: Tapping Apex - This is a close to normal apex beat regarding to size, duration and amplitude with a palpable first heart sound. The palpable first heart sound is mostly caused by mitral stenosis. Hyperdynamic Apex The amplitude and duration of the apex beat is forceful but ill-sustained and is palpable over a larger area size than normal (diffuse). A hyperdynamic apex beat is classically seen in ventricular dilatation due to volume overload conditions (aortic regurgitation, hyperdynamic circulation etc). Heaving Apex The amplitude of this apex beat is a forceful, the duration sustained and dislocated. Classically seen in ventricular hypertrophy due to pressure overload conditions (aortic stenosis, systemic hypertension etc). Double Impulse Apex - Two impulses felt during systole rather than the normal single upstroke. This apex beat characteristic can be observed in hypertrophic cardiomyopathy Dyskinetic Apex - An uncoordinated apex beat can be seen due to dyskinetic movements in the infarcted myocardium. Left parasternal impulse or heave An apex beat felt at the left side of the sternum due to right ventricular enlargement Cardiac Auscultation The acceleration and deceleration of blood and the subsequent vibration of the cardiac structures during the phases of the cardiac cycle are causing heart sounds. In healthy adults, there are two normal heart sounds often described as a lub and a dub (or dup), that occur in sequence with each heart beat. These are the first heart sound (S1) and second heart sound (S2), produced by the closing of the atroventricular valves and semilunar valves respectively. In addition to these normal sounds, a variety of other sounds may be present including heart murmurs, adventitious sounds, and gallop rhythms S3 and S4.To hear cardiac sounds, use a stethoscope with a bell and a tight diaphragm. The bell is best used to hear low- frequency sounds which are associated with ventricular filling. The diaphragm is best used to appreciate the medium-frequency sounds that are associated with valve opening and closing. Cardiac murmurs are caused due to turbulent blood flow and are usually high-to-medium frequency. In most cases the diaphragm is best used to hear cardiac murmurs. An important exception to this is the low-frequency atrioventricular valve inflow murmurs, such as that produced by mitral stenosis, which are best heard with the bell. Murmurs may be physiological or pathological. Abnormal murmurs can be caused by stenosis restricting the opening of a heart valve, resulting in turbulence as blood flows through it. Abnormal murmurs may also occur with valvular insufficiency (or regurgitation), which allows backflow of blood when the incompetent valve closes with only partial effectiveness. https://www.textbookofcardiology.org/wiki/Physical_Examination 18/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Auscultation should take place in areas that correspond to the location of the heart and great vessels. Such placement will, of course, need to be modified for patients with unusual body habitus or an unusual cardiac position. When no cardiac sounds can be heard over the precordium, they can often be heard in either the subxiphoid area or the right supraclavicular area. The body positions for the placement of the stethoscope are shown in Figure 3. Auscultation is recommended to appreciate sounds and murmurs at maximally. For the first examination the patient should be in a suspine position. Furthermore, the patient should be asked to roll partly onto the left side into the left lateral decubitus position. This position brings the left ventricle close this position to accentuates or brings out a left-side S3 and S4 an mitral murmurs. The other important position is sitting and forward leaning. The patient should be asked to completely exhale and stop breathing in expiration. The stethoscope diaphragm should be pressed along the left sternal border and at the apex. This position accentuates or brings out aortic murmurs maximally. in various positions the chest wall. In Figure 3. Locations for cardiac auscultation S1 The first heart tone, or S1, is composed of components mitral (M1) and tricuspid valve closure (T1). Normally the sound of mitral valve closure precedes valve closure slightly. The first heart tone is caused by the sudden block of reverse blood flow due to closure of the atrioventricular valves, i.e. tricuspid and mitral (bicuspid), at the beginning of ventricular contraction, or systole. The papillary muscles in each ventricle start with contraction parallel to the ventricles. The papillary muscles are attached to the tricuspid and mitral valves via chordae tendineae, which hold the cusps or leaflets of the valve to a closed position. During systole the chordae tendineae prevent the valves from blowing into the atria. The closing of the inlet valves prevents regurgitation of blood from the ventricles back into the atria. The S1 sound results from reverberation within the blood associated with the sudden block of flow reversal by the valves. If T1 occurs slightly after M1, then the patient likely has a dysfunction of conduction of the right side of the heart such as a right bundle branch block. S2 The second heart tone, or S2, is composed of components the closure of the aortic (A2) an pulmonary valve (P2). Normally A2 precedes P2 especially during inspiration when a split of S2 can be heard in normal conditions. It is caused by the sudden block of reversing blood flow due to closure of the aortic and pulmonary valve at the end of ventricular systole, i.e. beginning of ventricular diastole. As the left ventricle empties, its pressure falls below the pressure in the aorta. Aortic blood flow quickly reverses back toward the left ventricle, catching the pocket-like cusps of the aortic valve, and is stopped by aortic https://www.textbookofcardiology.org/wiki/Physical_Examination 19/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology (outlet) valve closure. Similarly, as the pressure in the right ventricle falls below the pressure in the pulmonary artery, the pulmonary (outlet) valve closes. The S2 sound results from reverberation within the blood associated with the sudden block of flow reversal. Splitting of S2, also known as physiological split, normally occurs during inspiration because the decrease in intrathoracic pressure increases the time needed for pulmonary pressure to exceed that of the right ventricular pressure. A widely split S2 can be associated with several different cardiovascular conditions, including right bundle branch block and pulmonary stenosis. Extra heart sounds The rarer extra heart sounds are heard in both normal and abnormal situations. The presence of a extra heart sound is also referred to as a gallop rhythm, because together with the normal heart tones the additional heart sounds resemble this typical sound. S3 The third heart sound also called a protodiastolic gallop or ventricular gallop. The third heart sound occurs at the beginning of diastole after S2 and is lower in pitch than S1 or S2 as it is not of valvular origin. S3 is thought to be caused by the oscillation of blood back and forth between the walls of the ventricles initiated by inrushing blood from the atria. The reason the third heart sound does not occur until the middle third of diastole is probably that during the early part of diastole, the ventricles are not filled sufficiently to create enough tension for reverberation. The third heart sound is best heard with the bell-side of the stethoscope (used for lower frequency sounds). A left-sided S3 is best heard in the left lateral decubitus position and at the apex of the heart, which is normally located in the 5th left intercostal space at the midclavicular line. A right-sided S3 is best heard at the lower-left sternal border. The way to distinguish between a left and right-sided S3 is to observe whether it increases in intensity with inspiration or expiration. A right-sided S3 will increase on inspiration whereas a left-sided S3 will increase on expiration. The third heart sound is benign in youth, some trained athletes, and sometimes in pregnancy. If the sound re-emerges later in life it may be caused by pathological diseases conditions such as a failing left ventricle as in dilated congestive heart failure. The third heart sound may also be a result of tensing of the chordae tendineae during rapid filling and expansion of the ventricle due to volume overload. S4 The fourth heart sound when audible in an adult is called a pre-systolic gallop or atrial gallop. This gallop is produced by the sound of blood being forced into a stiff and/or hypertrophic ventricle. The sound occurs just after atrial contraction at the end of diastole and immediately before S1. It is best heard at the cardiac apex with the patient in the left lateral decubitus position and holding his breath. The pathological fourth heart sound is a sing of a failing left ventricle or other pathological conditions such as restrictive cardiomyopathy. https://www.textbookofcardiology.org/wiki/Physical_Examination 20/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology The combined presence of S3 and S4 is a quadruple gallop. At rapid heart rates, S3 and S4 may merge to produce a summation gallop. Murmurs Heart murmurs are produced as a result of turbulent flow of blood. They are usually heard as a whooshing sound. The term murmur only refers to a sound believed to originate within blood flow through or near the heart associated structures. In order to produce an audible noise rapid blood velocity is necessary. It is important to keep in mind that most heart problems do not produce any murmur and most valve problems also do not produce an audible murmur. Traditionally, the origin of heart murmurs can be based on six important factors: Location The hearth sounds can be typically best heard in the following areas: Aortic in the parasternal second right intercostal space Pulmonic in the parasternal second left intercostal space Tricuspid area in the parasternal fourth left intercostal space The mitral area in the midclavicular fifth left intercostal space. Keep in mind that due to many diseases the position of the heart can be altered. Intensity The intensity of murmurs has a wide range. In general the lower intensity is associated with more benign conditions, while higher intensities are associated with pathological conditions. However, keep in mind that a lot of diseases do not produce any heart murmur and valvular diseases do not always produce audible murmurs. The intensity of the murmur can be classified according to Table 8. Table 8. Graduation of Murmurs Grade Description Very faint, heard only after listener has "tuned in"; may not be heard in all positions. Only heard if the patient "bears down" or performs the Valsalva manoeuvre. Grade 1 Grade 2 Quiet, but heard immediately after placing the stethoscope on the chest. Grade 3 Moderately loud. Grade 4 Loud, with palpable thrill (i.e., a tremor or vibration felt on palpation) Grade 5 Very loud, with thrill. May be heard when stethoscope is partly off the chest. Grade 6 Very loud, with thrill. May be heard with stethoscope entirely off the chest. Timing in the cardiac cycle Murmurs could be heard early, mid or late in systole, throughout systole (holosystolic), early, mid or late in diastole or continuous. See below for more detail. Shape Several shapes can be distinguished as shown in Figure 4. Radiation Some of the underlying pathologic disease cause murmurs to radiate. The distinctive pattern follows the blood flow from the point of maximal intensity: Aortic regurgitation From the aortic valve area into the apex Aortic stenosis From the aortic valve area into the carotid arteries Hypertrophic cardiomyopathy From the tricuspid area into to the aortic area https://www.textbookofcardiology.org/wiki/Physical_Examination 21/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Mitral regurgitation From the mitral area into the left axilla. Response to manoeuvres: Normal respiration The patient should be in a suspine position and breathing normally. In general right- sided cardiac murmurs should increase in intensity with normal inspiration. The increasing intensity during inspiration is caused due to the reductions in intrathoracic pressure that increase venous return from the abdomen and the head, leading to an increased flow through the right heart chambers. The consequent increase in pressure increases the intensity of right-sided murmurs. Sitting and leaning forward - Changes in position are an important part of normal auscultation and can also be of great value in determining the origin of cardiac murmurs. Murmurs dependent on venous return, such as innocent flow murmurs, are softer or absent in upright positions. Murmurs associated with hypertrophic obstructive cardiomyopathy, are accentuated by reduced left ventricular volume associated with the upright position. Rapid squat from the standing position The rapid change of body position increases venous return and left ventricular volume and therefore accentuates flow murmurs but diminishes the murmur of hypertrophic obstructive cardiomyopathie. The stand-squat manoeuvre is also useful for altering the timing of the midsystolic click caused by mitral valve prolapse during systole. When the ventricle is small during standing, the prolapse occurs earlier in systole, moving the midsystolic click to early systole. During squatting, the ventricle dilates and the prolapse is delayed in systole, resulting in a late midsystolic click. Lateral decubitis In this manoeuvre the patient rolls partly onto the left side and the apex should be auscultated. By bringing the left ventricle closer tot the chest, left-sided murmurs an generally louder. Vasalva manoeuvre During this manoeuvre the patient bears down and expires against a closed glottis (hold the breathe and strain hard for 10 seconds). A increasing intrathoracic pressure and markedly reducing venous return to the heart will be caused by this manoeuvre. Almost all cardiac murmurs decrease in intensity, however during strain the murmur of hypertrophic obstructive cardiomyopathy may become louder because and the murmur associated with mitral regurgitation from mitral valve prolapse may become longer and louder because of the earlier occurrence of prolapse during systole. After release of the strain the murmur will decrease and most other murmurs will increase in intensity. Isometric hand grip The patient has to relax his body while squeezing both fists. The manoeuvre increases arterial and left ventricular pressure, thus increasing afterload and flow gradient for mitral regurgitation, ventricular septal defect, and aortic regurgitation; the murmurs should then increase in intensity. The manoeuvre is in particular useful in distinguishing the increasing murmur of mitral regurgitation from a similar or lowering pitch aortic stenosis. Figure 4. Murmur sound shapes. https://www.textbookofcardiology.org/wiki/Physical_Examination 22/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology Murmurs categorized by time in cardiac cycle A schematic scheme of the sounds and heart heart murmurs are in Figure 5. shown are Systolic murmurs very common and do not always cardiac imply disease. Most murmurs fall in the 1 3 audible intensity range, however murmurs in the 4 6 range are almost always due to pathologic conditions. Again, severe disease can exist with grades 1 3 or no cardiac murmurs. Distinguishing benign from pathologic flow murmurs is one of the major clinical challenges cardiology. Benign flow murmurs are heard in 80% of children with a declining increasing incidence with age. physical Other conditions known for benign heart systolic murmurs are pregnancy or thin adults or athletic adults. The murmur is usually benign in a patient with a soft flow murmur that diminishes in intensity in sitting position and the neither of cardiovascular disease nor other cardiac findings. The physiological flow murmurs are usually heard in grades 1 2 and occur very early in systole. These murmurs have a vibratory quality and are usually less apparent when the patient is in the sitting position (when venous return is less). If an ejection sound is heard, there is usually some abnormality of the aortic or pulmonary valve. The most common systolic murmur is the becoming stronger and fading (crescendo/decrescendo) murmur. This murmur increases in intensity as blood flows early in systole and diminishes in intensity through the second half of systole. This murmur can be caused by a strong flow in a normal heart or to obstructions of flow, as occurs with a stenotic semilunar valve, or hypertrophic cardiomyopathy. systolic of a history Figure 5. Representation of the sound waves of murmurs associated with heart disease. https://www.textbookofcardiology.org/wiki/Physical_Examination 23/24 7/3/23, 11:57 PM Physical Examination - Textbook of Cardiology The holosystolic, or pansystolic, murmur is almost always associated with cardiac pathology. The most common cause of this murmur is atrioventricular valve regurgitation. A holosystolic murmur can also be heard in conditions such as ventricular septal defect, in which an abnormal communication exists between two chambers of markedly different systolic pressures. Although it is relatively easy to determine that these murmurs represent an abnormality, it is more of a challenge to determine their origins. Conditions such as mitral regurgitation, which usually produce holosystolic murmurs, may produce crescendo/decrescendo murmurs, adding to the difficulty in differentiating benign from pathologic systolic flow murmurs. Diastolic murmurs are always abnormal. The most frequently heard diastolic murmur is the high- frequency decrescendo early diastolic murmur of aortic regurgitation. This murmur however needs careful listening because it can be hard to hear due to its high frequency. This murmur is usually heard best at the upper left sternal border or in the aortic area (upper right sternal border) and may radiate to the lower left sternal border and the apex. Although the murmur of pulmonic regurgitation may sound like that of aortic regurgitation when pulmonary artery pressures are high, it is usually best heard in the in a different location. The pulmonic area in the left second intercostal space parasternally is usually the best place to appreciate the murmur. If structural disease of the valve is present with normal pulmonary pressures, the murmur usually has a midrange frequency and begins with a slight delay after the pulmonic second heart sound. Mitral stenosis produces a low-frequency rumbling diastolic murmur that is decrescendo in early diastole, but may become crescendo up to the first heart sound with moderately severe mitral stenosis and sinus rhythm. The murmur is best heard at the apex in the left lateral decubitus position with the bell of the stethoscope. Similar findings are heard in tricuspid stenosis, but the murmur is loudest at a different location, the lower left sternal border. A continuous murmur implies a connection between a high- and a low-pressure chamber throughout the cardiac cycle, such as occurs with a fistula between the aorta and the pulmonary artery. If the connection is a congenital patent ductus arteriosus, the murmur is heard best under the left clavicle; it has a machine-like quality. The most challenging is to distinguish the continuous murmurs from the combination of systolic and diastolic murmurs in patients with combined valve disease (eg, aortic stenosis and regurgitation). Retrieved from "http://www.textbookofcardiology.org/index.php?title=Physical_Examination&oldid=1676" This page was last edited on 19 December 2012, at 20:04. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Physical_Examination 24/24 |
7/4/23, 12:18 AM Primary Arrhythmias - Textbook of Cardiology Primary Arrhythmias Auteur: Louise R.A. Olde Nordkamp Supervisor: Arthur A.M. Wilde Primary cardiac arrhythmias are inherited cardiac syndromes associated with sudden cardiac death in patients with structurally normal hearts. They are caused by mutations in genes primarily encoding ion channels Key features The genetic basis for most arrhythmia syndromes is heterogeneous, which means that a given disorder may be caused by mutations in different genes. Mutations in cardiac ion channels lead to abnormal ionic current characteristics via mechanisms such as defective channel gating or reduction in sarcolemmal channel expression. This leads to the ECG features and/or arrhythmias in the inherited arrhythmia syndromes. It is becoming increasingly clear that treatment should take the type of gene affected into consideration (gene specific therapy). The identification of a proband with a primary cardiac arrhythmia should trigger screening of family members to identify all affected relatives (presymptomatically). However, considerable heterogeneity may exist in disease manifestation (both in severity as well as differences in disease features) among family members carrying the same mutation. In this respect, a genetic test is vital in uncovering all carriers of the genetic defect within a family. Ion channels involved in primary arrhythmia syndromes[1] https://www.textbookofcardiology.org/wiki/Primary_Arrhythmias 1/2 7/4/23, 12:18 AM Primary Arrhythmias - Textbook of Cardiology References <biblio> 1. Wilde pmid=16162633 </bibliio> Retrieved from "http://www.textbookofcardiology.org/index.php?title=Primary_Arrhythmias&oldid=2239" This page was last edited on 22 March 2013, at 09:32. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Primary_Arrhythmias 2/2 |
7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology Pulmonary Embolism James Heilman, MD, CCFP-EM. This text is currently a copy of the Pulmonary Embolism entry on Wikipedia Pulmonary embolism (PE) is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream (embolism). Usually this is due to embolism of a thrombus (blood clot) from the |deep veins in the legs, a process termed venous thromboembolism. A small proportion is due to the embolization of air, fat, talc in drugs of intravenous drug abusers or amniotic fluid. The obstruction of the blood flow through the lungs and the resultant pressure on the right ventricle of the heart leads to the symptoms and signs of PE. The risk of PE is increased in various situations, such as cancer or prolonged bed rest.[1] Symptoms of pulmonary embolism include difficulty breathing, chest pain on inspiration, and palpitations. Clinical signs include low blood oxygen saturation and cyanosis, rapid breathing, and a rapid heart rate. Severe cases of PE can lead to collapse, abnormally low blood pressure, and sudden death.[1] https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 1/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology Diagnosis is based on these clinical findings in combination with laboratory tests (such as the D-dimer test) and imaging studies, usually CT pulmonary angiography. Treatment is typically with anticoagulant medication, including heparin and warfarin. Severe cases may require thrombolysis with drugs such as tissue plasminogen activator (tPA) or may require surgical intervention via pulmonary thrombectomy.[1] Contents Signs and symptoms Risk factors Diagnosis Blood tests Imaging Electrocardiogram Echocardiography Algorithms Treatment Anticoagulation Thrombolysis Surgery Inferior vena cava filter Prognosis Predicting mortality Underlying causes References Signs and symptoms Symptoms of PE are sudden-onset dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of a "pleuritic" nature (worsened by breathing), cough and hemoptysis (coughing up blood). More severe cases can include signs such as cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability due to decreased blood flow through the lungs and into the left side of the heart. About 15% of all cases of sudden death are attributable to PE.[1] On physical examination, the lungs are usually normal. Occasionally, a pleural friction rub may be audible over the affected area of the lung (mostly in PE with infarct) . A pleural effusion is sometimes present that is transudative, detectable by decreased percussion note, audible breath sounds and vocal resonance. Strain on the right ventricle may be detected as a left parasternal heave, a loud pulmonary component of the second heart sound, and raised jugular venous pressure.[1] A low-grade fever may be present, particularly if there is associated pulmonary hemorrhage or infarction.[2] https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 2/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology More rarely, inability of the right ventricle to remove fluid from the tissues leads to fluid accumulation in the legs (peripheral edema), congestion of the liver with mild jaundice and tenderness, and ascites (fluid in the abdominal cavity). Risk factors The most common sources of embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation, which happens in up to 15% of all DVTs. The conditions are generally regarded as a continuum termed venous thromboembolism (VTE). The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present. Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) Factors in the vessel wall: of limited direct relevance in VTE Factors affecting the properties of the blood (procoagulant state): Estrogen-containing hormonal contraception Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders) Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria) Cancer]] (due to secretion of pro-coagulants) Diagnosis The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation (shortness of breath, chest pain) cannot be definitively differentiated from other causes of chest pain and shortness of breath. The decision to do medical imaging is usually based on clinical grounds, i.e. the medical history, symptoms and findings on physical examination, followed by an assessment of clinical probability.[1] The most commonly used method to predict clinical probability, the Wells score, is a clinical prediction rule, whose use is complicated by multiple versions being available. In 1995, Wells et al. initially developed a prediction rule (based on a literature search) to predict the likelihood of PE, based on clinical criteria.[3] The prediction rule was revised in 1998 [4] This prediction rule was further revised when simplified during a validation by Wells et al. in 2000. [5] In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule. [5] In 2001, Wells published results using the more conservative cutoff of 2 to create three categories.[6] An additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from Wells's initial studies[7] [8] were proposed. [9] Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points [5] to create only two categories. [10] There are additional prediction rules for PE, such as the Geneva rule. More importantly, the use of any rule is associated with reduction in recurrent thromboembolism. [11] https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 3/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology The Wells score: [12] clinically suspected DVT - 3.0 points alternative diagnosis is less likely than PE - 3.0 points tachycardia - 1.5 points immobilization/surgery in previous four weeks - 1.5 points history of DVT or PE - 1.5 points hemoptysis - 1.0 points malignancy (treatment for within 6 months, palliative) - 1.0 points Traditional interpretation [5][6] [13] Score >6.0 - High (probability 59% based on pooled data [14]) Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data [14]) Score <2.0 - Low (probability 15% based on pooled data [14]) Alternative interpretation [5][10] Score > 4 - PE likely. Consider diagnostic imaging. Score 4 or less - PE unlikely. Consider D-dimer to rule out PE. Blood tests Early primary research has shown that in low/moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of thrombotic PE. [15] This has been corroborated by a recent systematic review of studies of patients with low pre-test probability (PTP) of PE and negative D-dimer results that found the three month risk of thromboembolic events in patients excluded in this manner was 0.14%, with 95% confidence intervals from 0.05 to 0.41%, though this review was limited by its use of only one randomized-controlled clinical trial, the remainder of studies being prospective cohorts. [16] D-dimer is highly sensitive but not very specific (specificity around 50%). In other words, a positive D-dimer is not synonymous with PE, but a negative D-dimer is, with a good degree of certainty, an indication of absence of a PE. [17] When a PE is being suspected, a number of blood tests are done, in order to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, aPTT, TT), and some screening tests (erythrocyte sedimentation rate, renal function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted. Imaging The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography. Pulmonary angiography is used less often due to wider acceptance of CT scans, which are non-invasive. CT pulmonary angiography is the recommended first line diagnostic imaging test in most people. Non-invasive imaging CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of identifying other lung https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 4/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology disorders from the differential diagnosis in case there is no pulmonary embolism. Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in in the number of rows of detectors available multidetector CT (MDCT) machines. [18] According to a cohort study, single-slice spiral CT may help diagnose detection among patients with suspected pulmonary embolism. [19] In this study, the sensitivity was 69% and specificity was 84%. In this study which had a prevalence of detection was 32%, the positive predictive value of 67.0% and negative predictive value of 85.2% (click here (http://medinformatics.uthscsa.edu/calculator/calc.sht ml?calc_dx_SnSp.shtml?prevalence=32&sensitivity=69 &specificity=84) to adjust these results for patients at higher or lower risk of detection). However, this study's results may be biased due to possible incorporation bias, since the CT scan was the final diagnostic tool in patients with pulmonary embolism. The authors noted that a negative single slice CT scan is insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of 4 slice and 16 slice scanners reported a sensitivity of 83% and a specificity of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results. [20] CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily improving the outcome) compared to VQ scanning. [21] Selective pulmonary angiogram revealing significant thrombus (labelled A) causing a central obstruction in the left main pulmonary artery. ECG tracing shown at bottom. Ventilation/perfusion scan (or V/Q scan or lung scintigraphy), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast or in pregnancy due to lower radiation exposure than CT. [22] Low probability diagnostic tests/non-diagnostic tests Tests that are frequently done that are not sensitive for PE, but can be diagnostic. Chest X-rays are often done on patients with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal, [23] but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign, Hampton's hump). Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism. Electrocardiogram https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 5/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology An electrocardiogram (ECG) is routinely done on patients with chest pain to quickly diagnose myocardial infarctions (heart attacks). An ECG may show signs of right heart strain or acute cor pulmonale in cases of large PEs - the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III ("S1Q3T3"). [24] This is occasionally (up to 20%) present, but may also occur lung conditions and has therefore limited diagnostic value. The most commonly seen signs in the ECG is sinus tachycardia, right axis deviation and right bundle branch block. [25] Sinus tachycardia was however still only found in 8 - 69% of people with PE. [26] in other acute Echocardiography In massive and submassive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication is severely obstructed and the heart is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every patient with a (suspected) an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and warrant an echocardiogram. [27] that the pulmonary artery CT pulmonary angiography (CTPA) showing a saddle embolus and substantial thrombus burden in the lobar branches of both main pulmonary arteries. pulmonary embolism requires The specific appearance of the right ventricle on echocardiography is referred to as the McConnell's sign. This is the finding of akinesia of the mid-free wall but normal motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism in the setting of right ventricular dysfunction. [28] Ventilation-perfusion scintigraphy in a woman taking hormonal contraceptives and valdecoxib. (A) After inhalation of 20.1 mCi of Xenon-133 gas, scintigraphic images were obtained in the posterior projection, showing uniform ventilation to lungs. (B) After intravenous injection of 4.1 mCi of Technetium-99m-labeled macroaggregated albumin, scintigraphic images were obtained, shown here in the posterior projection. This and other views showed decreased activity in multiple regions. Algorithms Recent recommendations for a diagnostic algorithm have been published by the PIOPED investigators; however, these recommendations do not reflect research using 64 slice MDCT. [29] These investigators recommended: Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results. Moderate clinical probability. If negative D-dimer, PE is excluded. However, the authors were not concerned that a negative MDCT with negative D- dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 6/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology slice MDCT is more commonly used. If positive D- dimer, obtain MDCT and based treatment on results. High clinical probability. Proceed to MDCT. If positive, treat, if negative, additional tests are needed to exclude PE. Pulmonary Embolism Rule-out Criteria The Pulmonary Embolism Rule-out Criteria, or PERC rule, helps assess people in whom pulmonary embolism is suspected, but unlikely. Unlike the Wells Score and Geneva score, which are clinical prediction rules intended to risk stratify patients with suspected PE, the PERC rule is designed to rule out risk of PE in patients when the physician has already stratified them into a low-risk category. Electrocardiogram of a patient with pulmonary embolism showing sinus tachycardia of approximately 150 beats per minute and right bundle branch block. Patients in this low risk category without any of these criteria may undergo no further diagnostic testing for PE: Hypoxia - Sa02 <95%, unilateral leg swelling, hemoptysis, prior DVT or PE, recent surgery or trauma, age >50, hormone use, tachycardia. The rationale behind this decision is that further testing (specifically CT angiogram of the chest) may cause more harm (from radiation exposure and contrast dye) than the risk of PE. [30] The PERC rule has a sensitivity of 97.4% and specificity of 21.9% with a false negative rate of 1.0% (16/1666). [31] Treatment In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, are often required. Anticoagulation In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins (such as enoxaparin and dalteparin), or fondaparinux is administered initially, while warfarin, acenocoumarol, or phenprocoumon therapy is commenced (this may take several days, usually while the patient is in the hospital). Low molecular weight heparin may reduce bleeding among patients with pulmonary embolism as compared to heparin according to a systematic review of randomized controlled trials by the Cochrane Collaboration. [32] The relative risk reduction was 40.0%. For patients at similar risk to those in this study (2.0% had bleeding when not treated with low molecular weight heparin), this leads to an absolute risk reduction of 0.8%. 125.0 patients must be treated for one to benefit. It is possible to treat low risk patients (risk class I or class II) as outpatients. [33] A randomised trial of 344 patients (171 outpatients and 168 inpatients) found that outcomes were equivalent whether patients were treated in hospital or at home (there was one death at 90 days in each group). [33] [34] This confirms the findings of an earlier systematic review of observational studies. [35] Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 7/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin. In patients with an underlying malignancy, therapy with a course of low molecular weight heparin may be favored over warfarin based on the results of the CLOT trial. [36] Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known teratogenic effects of warfarin, especially in the early stages of pregnancy. People are usually admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until INR has reached therapeutic levels. Increasingly, low-risk cases are managed on an outpatient basis in a fashion already common in the treatment of DVT. [37] Warfarin therapy is usually continued for 3 6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. An abnormal D-dimer level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus. [38] Thrombolysis Massive PE causing hemodynamic instability (shock and/or hypotension, defined as a systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for>15 min if not caused by new-onset arrhythmia, hypovolemia or sepsis) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. It is the best available medical treatment in this situation and is supported by clinical guidelines. [39] [40] [41] The use of thrombolysis in non-massive PEs is still debated. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke. [42] The main indication for thrombolysis is in submassive PE where right ventricular dysfunction can be demonstrated on echocardiography, and the presence of visible thrombus in the atrium. [43] Surgery Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit selected patients. [44] Chronic pulmonary embolism leading to pulmonary hypertension thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy. (known as chronic Used inferior vena cava filter. Inferior vena cava filter https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 8/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology If anticoagulant therapy is contraindicated and/or ineffective, or to prevent new emboli from entering the pulmonary artery and combining with an existing blockage, an inferior vena cava filter may be implanted. [45] Prognosis Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan [46], which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs. Large saddle embolus seen at PA. Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension. After a massive PE, the embolus must be resolved somehow if the patient is to survive. In thrombotic PE, the blood clot may be broken down by fibrinolysis, or it may be organized and recanalized so that a new channel forms through the clot. Blood flow is restored most rapidly in the first day or two after a PE. [47] Improvement slows thereafter and some deficits may be permanent. There is controversy over whether or not small subsegmental PEs need to be treated at all [48] and some evidence exists that patients with subsegmental PEs may do well without treatment. [49] [50] Once anticoagulation is stopped, the risk of a fatal pulmonary embolism is 0.5% per year. [51] Predicting mortality The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy. [52] Underlying causes After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities. References 1. Kasper, Dennis L., Braunwald, Eugene, Hauser, Stephen, Longo, Dan, Jameson, J. Larry, Fauci, Anthony S. Harrison's Principles of Internal Medicine 16e (Two-Volume Set). McGraw-Hill https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 9/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology Professional. (https://isbndb.com/book/9780071391405) ISBN:0071391401 2. Stein PD, Sostman HD, Hull RD, Goodman LR, Leeper KV Jr, Gottschalk A, Tapson VF, and Woodard PK. Diagnosis of pulmonary embolism in the coronary care unit. Am J Cardiol. 2009 Mar 15;103(6):881-6. DOI:10.1016/j.amjcard.2008.11.040 | 3. Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, and Prandoni P. Accuracy of clinical assessment of deep-vein thrombosis. Lancet. 1995 May 27;345(8961):1326-30. DOI:10.1016/s0140-6736(95)92535-x | 4. Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, and Hirsh J. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med. 1998 Dec 15;129(12):997-1005. DOI:10.7326/0003-4819-129-12-199812150-00002 | 5. Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, and Hirsh J. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000 Mar;83(3):416-20. 6. Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, and Kovacs MJ. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001 Jul 17;135(2):98-107. DOI:10.7326/0003- 4819-135-2-200107170-00010 | 7. Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, and Prandoni P. Accuracy of clinical assessment of deep-vein thrombosis. Lancet. 1995 May 27;345(8961):1326-30. DOI:10.1016/s0140-6736(95)92535-x | 8. Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, and Hirsh J. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med. 1998 Dec 15;129(12):997-1005. DOI:10.7326/0003-4819-129-12-199812150-00002 | 9. Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, and B ller HR. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group. Thromb Haemost. 2000 Feb;83(2):199-203. 10. van Belle A, B ller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, Kramer MH, Kruip MJ, Kwakkel-van Erp JM, Leebeek FW, Nijkeuter M, Prins MH, Sohne M, Tick LW, and Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-9. DOI:10.1001/jama.295.2.172 | 11. Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A, and EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006 Feb 7;144(3):157-64. DOI:10.7326/0003-4819-144-3- 200602070-00003 | 12. Neff MJ and ACEP. ACEP releases clinical policy on evaluation and management of pulmonary embolism. Am Fam Physician. 2003 Aug 15;68(4):759-60. 13. Yap KS, Kalff V, Turlakow A, and Kelly MJ. A prospective reassessment of the utility of the Wells score in identifying pulmonary embolism. Med J Aust. 2007 Sep 17;187(6):333-6. DOI:10.5694/j.1326-5377.2007.tb01274.x | 14. Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV Jr, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD, and PIOPED II Investigators. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators. Radiology. 2007 Jan;242(1):15-21. DOI:10.1148/radiol.2421060971 | 15. Bounameaux H, de Moerloose P, Perrier A, and Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost. 1994 Jan;71(1):1-6. https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 10/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology 16. Carrier M, Righini M, Djurabi RK, Huisman MV, Perrier A, Wells PS, Rodger M, Wuillemin WA, and Le Gal G. VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies. Thromb Haemost. 2009 May;101(5):886-92. 17. Schrecengost JE, LeGallo RD, Boyd JC, Moons KG, Gonias SL, Rose CE Jr, and Bruns DE. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem. 2003 Sep;49(9):1483-90. DOI:10.1373/49.9.1483 | 18. Schaefer-Prokop C and Prokop M. MDCT for the diagnosis of acute pulmonary embolism. Eur Radiol. 2005 Nov;15 Suppl 4:D37-41. DOI:10.1007/s10406-005-0144-3 | 19. Van Strijen MJ, De Monye W, Kieft GJ, Pattynama PM, Prins MH, and Huisman MV. Accuracy of single-detector spiral CT in the diagnosis of pulmonary embolism: a prospective multicenter cohort study of consecutive patients with abnormal perfusion scintigraphy. J Thromb Haemost. 2005 Jan;3(1):17-25. DOI:10.1111/j.1538-7836.2004.01064.x | 20. Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, Leeper KV Jr, Popovich J Jr, Quinn DA, Sos TA, Sostman HD, Tapson VF, Wakefield TW, Weg JG, Woodard PK, and PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-27. DOI:10.1056/NEJMoa052367 | 21. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, Lang E, Stiell I, Kovacs G, Dreyer J, Dennie C, Cartier Y, Barnes D, Burton E, Pleasance S, Skedgel C, O'Rouke K, and Wells PS. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007 Dec 19;298(23):2743-53. DOI:10.1001/jama.298.23.2743 | 22. Scarsbrook AF and Gleeson FV. Investigating suspected pulmonary embolism in pregnancy. BMJ. 2007 Feb 24;334(7590):418-9. DOI:10.1136/bmj.39071.617257.80 | 23. Worsley DF, Alavi A, Aronchick JM, Chen JT, Greenspan RH, and Ravin CE. Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study. Radiology. 1993 Oct;189(1):133-6. DOI:10.1148/radiology.189.1.8372182 | 24. McGinn S., White PD. Acute cor pulmonale resulting from pulmonary embolism. JAMA 1935:104:1473-80 25. Rodger M, Makropoulos D, Turek M, Quevillon J, Raymond F, Rasuli P, and Wells PS. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol. 2000 Oct 1;86(7):807-9, A10. DOI:10.1016/s0002-9149(00)01090-0 | 26. Emergency Medicine: Avoiding the Pitfalls and Improving the Outcomes. BMJ Books. (https://isbndb. com/book/9781405141666) ISBN:1-4051-4166-2 27. Kucher N and Goldhaber SZ. Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation. 2003 Nov 4;108(18):2191-4. DOI:10.1161/01.CIR.0000100687.99687.CE | 28. McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, and Lee RT. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol. 1996 Aug 15;78(4):469-73. DOI:10.1016/s0002-9149(96)00339-6 | 29. Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV Jr, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD, and PIOPED II Investigators. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators. Radiology. 2007 Jan;242(1):15-21. DOI:10.1148/radiol.2421060971 | 30. Kline JA, Mitchell AM, Kabrhel C, Richman PB, and Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004 Aug;2(8):1247-55. DOI:10.1111/j.1538-7836.2004.00790.x | https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 11/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology 31. Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC, Richman PB, O'Neil BJ, and Nordenholz K. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008 May;6(5):772-80. DOI:10.1111/j.1538-7836.2008.02944.x | 32. van Dongen CJ, van den Belt AG, Prins MH, and Lensing AW. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. 2004 Oct 18(4):CD001100. DOI:10.1002/14651858.CD001100.pub2 | 33. Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M, Renaud B, Verhamme P, Stone RA, Legall C, Sanchez O, Pugh NA, N'gako A, Cornuz J, Hugli O, Beer HJ, Perrier A, Fine MJ, and Yealy DM. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011 Jul 2;378(9785):41-8. DOI:10.1016/S0140-6736(11)60824-6 | 34. Drahomir Aujesky, MD. Safety Study of Outpatient Treatment for Pulmonary Embolism (OTPE). NCT00425542 35. Squizzato A, Galli M, Dentali F, and Ageno W. Outpatient treatment and early discharge of symptomatic pulmonary embolism: a systematic review. Eur Respir J. 2009 May;33(5):1148-55. DOI:10.1183/09031936.00133608 | 36. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M, and Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146- 53. DOI:10.1056/NEJMoa025313 | 37. Davies CW, Wimperis J, Green ES, Pendry K, Killen J, Mehdi I, Tiplady C, Kesteven P, Rose P, and Oldfield W. Early discharge of patients with pulmonary embolism: a two-phase observational study. Eur Respir J. 2007 Oct;30(4):708-14. DOI:10.1183/09031936.00140506 | 38. Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A, Pengo V, Ghirarduzzi A, Pattacini C, Testa S, Lensing AW, Tripodi A, and PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med. 2006 Oct 26;355(17):1780-9. DOI:10.1056/NEJMoa054444 | 39. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003 Jun;58(6):470-83. DOI:10.1136/thorax.58.6.470 | 40. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Gali N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP, and ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. DOI:10.1093/eurheartj/ehn310 | 41. Hirsh J, Guyatt G, Albers GW, Harrington R, and Sch nemann HJ. Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):71S-109S. DOI:10.1378/chest.08-0693 | 42. Dong B, Jirong Y, Liu G, Wang Q, and Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2006 Apr 19(2):CD004437. DOI:10.1002/14651858.CD004437.pub2 | 43. Goldhaber SZ. Pulmonary embolism. Lancet. 2004 Apr 17;363(9417):1295-305. DOI:10.1016/S0140-6736(04)16004-2 | 44. Augustinos P and Ouriel K. Invasive approaches to treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I27-34. DOI:10.1161/01.CIR.0000140900.64198.f4 | https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 12/13 7/4/23, 12:40 AM Pulmonary Embolism - Textbook of Cardiology 45. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, and Simonneau G. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Pr vention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998 Feb 12;338(7):409- 15. DOI:10.1056/NEJM199802123380701 | 46. BARRITT DW and JORDAN SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960 Jun 18;1(7138):1309-12. DOI:10.1016/s0140-6736(60)92299-6 | 47. Walker RH, Goodwin J, and Jackson JA. Resolution of pulmonary embolism. Br Med J. 1970 Oct 17;4(5728):135-9. DOI:10.1136/bmj.4.5728.135 | 48. Le Gal G, Righini M, Parent F, van Strijen M, and Couturaud F. Diagnosis and management of subsegmental pulmonary embolism. J Thromb Haemost. 2006 Apr;4(4):724-31. DOI:10.1111/j.1538- 7836.2006.01819.x | 49. Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, Leeper KV Jr, Popovich J Jr, Quinn DA, Sos TA, Sostman HD, Tapson VF, Wakefield TW, Weg JG, Woodard PK, and PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-27. DOI:10.1056/NEJMoa052367 | 50. Perrier A and Bounameaux H. Accuracy or outcome in suspected pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2383-5. DOI:10.1056/NEJMe068076 | 51. White RH. Risk of fatal pulmonary embolism was 0.49 per 100 person-years after discontinuing anticoagulant therapy for venous thromboembolism. Evid Based Med. 2008 Oct;13(5):154. DOI:10.1136/ebm.13.5.154 | 52. Jim nez D, Yusen RD, Otero R, Uresandi F, Nauffal D, Laserna E, Conget F, Oribe M, Cabezudo MA, and D az G. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Chest. 2007 Jul;132(1):24-30. DOI:10.1378/chest.06-2921 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Pulmonary_Embolism&oldid=1599" This page was last edited on 5 December 2012, at 14:36. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Pulmonary_Embolism 13/13 |
7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Rheumatic Heart Disease This website is currently being developed and in a testing phase. Content is incomplete and may be incorrect. This text is largely based on the Wikipedia lemma for rheumatic fever Rheumatic Fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as streptococcal pharyngitis or scarlet fever. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain,[1] the illness typically develops two to three weeks after a streptococcal infection. Acute rheumatic fever commonly appears in children between the ages of 6 and 15, with only 20% of first-time attacks occurring in adults.[1] The in illness presentation to rheumatism.[2] is so named because of its similarity Streptococcus pyogenes bacteria, Pappenheim's stain. Contents Diagnosis Major criteria Minor criteria Other signs and symptoms Pathophysiology Rheumatic heart disease Prevention Treatment Vaccine Infection Inflammation Heart failure Epidemiology References Diagnosis https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 1/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Modified first published in 1944 by T. Duckett Jones, MD.[3] They have been periodically revised by the American Heart Association in collaboration with other groups.[4] According to revised Jones criteria, the diagnosis of rheumatic fever can be made when two of the major criteria, or one major criterion plus two minor criteria, are present of streptococcal infection: elevated or rising antistreptolysin O titre or DNAase.[1] indolent Exceptions are chorea and itself can carditis, each of which by indicate rheumatic fever.[5][6][7] Jones criteria were along with evidence Rheumatic heart disease at autopsy with characteristic findings (thickened mitral valve, thickened chordae tendineae, hypertrophied left ventricular myocardium). Major criteria Polyarthritis: A temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards. Carditis: Inflammation of the heart muscle (myocarditis) which can manifest as congestive heart failure with shortness of breath, pericarditis with a rub, or a new heart murmur. Subcutaneous nodules: Painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees. Erythema marginatum: A long-lasting reddish rash that begins on the trunk or arms as macules, which spread outward and clear in the middle to form rings, which continue to spread and coalesce with other rings, ultimately taking on a snake-like appearance. This rash typically spares the face and is made worse with heat. Sydenham's chorea (St. Vitus' dance): A characteristic series of rapid movements without purpose of the face and arms. This can occur very late in the disease for at least three months from onset of infection. Minor criteria Fever of 38.2 38.9 C (101 102 F) Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is present as a major symptom) Raised erythrocyte sedimentation rate or C reactive protein Leukocytosis ECG showing features of heart block, such as a prolonged PR interval[8] [9] (Cannot be included if carditis is present as a major symptom) Previous episode of rheumatic fever or inactive heart disease Other signs and symptoms Abdominal pain https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 2/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Nose bleeds Preceding streptococcal infection: recent scarlet fever, raised antistreptolysin O or other streptococcal antibody titre, or positive throat culture.[9] Pathophysiology Rheumatic fever is a systemic disease affecting the peri-arteriolar connective tissue and can occur after an untreated Group A Beta hemolytic streptococcal pharyngeal infection. It is believed to be caused by antibody cross-reactivity. This II is cross-reactivity hypersensitivity reaction and is termed molecular mimicry. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a Streptococcus infection, mature antigen presenting cells such as B cells present the bacterial antigen to CD4-T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints,[10] producing the symptoms of rheumatic fever. a Type Pathophysiology of rheumatic heart disease Group A streptococcus pyogenes has a cell wall composed of branched polymers which sometimes contain M protein that are highly antigenic. The antibodies which the immune system generates against the M protein may cross react with cardiac myofiber protein myosin,[11] heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross reaction is with perivascular connective tissue.[citation needed] This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Acute rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.[12] Micrograph showing an Aschoff body (right of image), as seen in rheumatic heart disease. H&E stain. In acute rheumatic fever, these lesions can be found in any layer of the heart and is hence called pancarditis. The inflammation may cause a serofibrinous pericardial exudate described as "bread-and- butter" pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 3/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology results in fibrinoid necrosis and verrucae formation along the lines of closure of the left-sided heart valves. Warty projections arise from the deposition, while subendocardial lesions may induce irregular thickenings called MacCallum plaques. Rheumatic heart disease Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous resolution. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords.[12] It is caused by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular damage.[13] Fibrosis and scarring of valve leaflets, commissures and cusps leads to abnormalities that can result in valve stenosis or regurgitation.[14] The inflammation caused by rheumatic fever, usually during childhood, is referred to as rheumatic valvulitis. About half of patients with acute rheumatic fever develop inflammation involving valvular endothelium.[15] The majority of morbidity and mortality associated with rheumatic fever is caused by its destructive effects on cardiac valve tissue.[14] The pathogenesis of RHD is complex and not fully understood, but it is known to involve molecular mimicry and genetic predisposition that lead to autoimmune reactions. Molecular mimicry occurs when epitopes are shared between host antigens and GAS antigens.[16] This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as "foreign" due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD.[17] Normally, T cell activation is triggered by the presentation of GAS antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes.[18] Self-antigen-specific antibodies generated via molecular mimicry between human proteins and GAS antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration.[18] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6.[19] Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions.[19] The mechanism by which MHC class II molecules increase a host's susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response. Also found on human chromosome 6 is the cytokine TNF- which is also associated with RHD.[19] High expression levels of TNF- may exacerbate valvular tissue inflammation, contributing to RHD pathogenesis. Mannose- binding lectin (MBL) is an inflammatory protein involved in pathogen recognition. Different variants of MBL2 gene regions are associated in RHD. RHD-induced mitral valve stenosis has been associated with https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 4/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology MBL2 alleles encoding for high production of MBL.[20] Aortic valve regurgitation in RHD patients has been associated with different MBL2 alleles that encode for low production of MBL.[21] Other genes are also being investigated to better understand the complexity of autoimmune reactions that occur in RHD. Prevention Prevention of recurrence is achieved by eradicating the acute infection and prophylaxis with antibiotics. The American Heart Association recommends that daily or monthly prophylaxis continue long-term, perhaps for life.[22] Treatment This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2012) The management of acute rheumatic fever is geared toward the reduction of inflammation with anti- inflammatory medications such as aspirin or corticosteroids. Individuals with positive cultures for strep throat should also be treated with antibiotics. Aspirin is the drug of choice and should be given at high doses of 100 mg/kg/day. One should watch for side effects like gastritis and salicylate poisoning. In children and teenagers, the use of aspirin and aspirin-containing products can be associated with Reye's syndrome, a serious and potentially deadly condition. The risks, benefits and alternative treatments must always be considered when administering aspirin and aspirin-containing products in children and teenagers. Ibuprofen for pain and discomfort and corticosteroids for moderate to severe inflammatory reactions manifested by rheumatic fever should be considered in children and teenagers. Steroids are reserved for cases where there is evidence of involvement of heart. The use of steroids may prevent further scarring of tissue and may prevent development of sequelae such as mitral stenosis. Monthly injections of longacting penicillin must be given for a period of five years in patients having one attack of rheumatic fever. If there is evidence of carditis, the length of therapy may be up to 40 years. Another important cornerstone in treating rheumatic fever includes the continual use of low-dose antibiotics (such as penicillin, sulfadiazine, or erythromycin) to prevent recurrence. Vaccine No vaccines are currently available to protect against S. pyogenes infection, although there has been research into the development of one. Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and people that will be needed for appropriate trials for safety and efficacy of the vaccine.[23] Infection Patients with positive cultures for Streptococcus pyogenes should be treated with penicillin as long as allergy is not present. This treatment will not alter the course of the acute disease. The most appropriate treatment stated in the Oxford Handbook of Clinical Medicine for rheumatic fever is benzathine benzylpenicillin. Inflammation https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 5/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Patients with significant symptoms may require corticosteroids. Salicylates are useful for pain. Heart failure Some patients develop significant carditis which manifests as congestive heart failure. This requires the usual treatment for heart failure: ACE Inhibitors, diuretics, beta blockers, and digoxin. Unlike normal heart failure, rheumatic heart failure responds well to corticosteroids. Epidemiology no data less than 20 20 40 40 60 60 80 80 100 100 120 Disability-adjusted life year for rheumatic heart disease per 100,000 inhabitants in 2004.[24] 120 140 140 160 160 180 180 200 200 330 more than 330 Rheumatic fever is common worldwide and responsible for many cases of damaged heart valves. In Western countries, it became fairly rare since the 1960s, probably due to widespread use of antibiotics to treat streptococcus infections. While it has been far less common in the United States since the beginning of the 20th century, there have been a few outbreaks since the 1980s. Although the disease seldom occurs, it is serious and has a case-fatality rate of 2 5%.[25] Rheumatic fever primarily affects children between ages 5 and 17 years and occurs approximately 20 days after strep throat. In up to a third of cases, the underlying strep infection may not have caused any symptoms. The rate of development of rheumatic fever in individuals with untreated strep infection is estimated to be 3%. The incidence of recurrence with a subsequent untreated infection is substantially greater (about 50%).[26] The rate of development is far lower in individuals who have received antibiotic treatment. Persons who have suffered a case of rheumatic fever have a tendency to develop flare-ups with repeated strep infections. The recurrence of rheumatic fever is relatively common in the absence of maintenance of low dose antibiotics, especially during the first three to five years after the first episode. Heart complications may be long-term and severe, particularly if valves are involved. https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 6/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Survivors of rheumatic fever often have to take penicillin to prevent streptococcal infection which could possibly lead to another case of rheumatic fever that could prove fatal. References 1. Kumar, Vinay; Abbas, Abul K; Fausto, Nelson; Mitchell, Richard N (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 403 6. ISBN 978-1-4160-2973-1. 2. "Rheumatic Fever" at Dorland's Medical Dictionary 3. Jones, T Duckett (1944). "The diagnosis of rheumatic fever". JAMA 126 (8): 481 4. doi:10.1001/jama.1944.02850430015005. 4. Ferrieri, P; Jones Criteria Working, Group (2002). "Proceedings of the Jones Criteria workshop". 2521 3. Working Circulation doi:10.1161/01.CIR.0000037745.65929.FA. PMID 12417554. (Jones Criteria Group) 106 (19): 5. Parrillo, Steven J. "Rheumatic Fever". eMedicine. DO, FACOEP, FACEP. Retrieved 2007-07-14. 6. "Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update". JAMA (Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association) 268 (15): 2069 73. 1992. doi:10.1001/jama.268.15.2069. PMID 1404745. 7. Saxena, Anita (2000). "Diagnosis of rheumatic fever: Current status of Jones criteria and role of echocardiography". Indian Journal of Pediatrics 67 (4): 283 6. doi:10.1007/BF02758174. PMID 11129913. 8. Aly, Ashraf (2008). "Rheumatic Fever". Core Concepts of Pediatrics. University of Texas. Retrieved 2011-08-06. 9. Ed Boon, Davidson's General Practice of Medicine, 20th edition. P. 617. 10. Abbas, Abul K.; Lichtman, Andrew H.; Baker, David L.; et al (2004). Basic immunology: functions and disorders of the immune system (2 ed.). Philadelphia, Pennsylvania: Elsevier Saunders. ISBN 978-1- 4160-2403-3. 11. Fa KC, da Silva DD, Oshiro SE, et al. (May 2006). "Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease". J. Immunol. 176 (9): 5662 70. PMID 16622036. https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 7/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology 12. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. ISBN 0- 7216-0187-1. 13. Kaplan, MH; Bolande, R; Rakita, L; Blair, J (1964). "Presence of Bound Immunoglobulins and Complement in the Myocardium in Acute Rheumatic Fever. Association with Cardiac Failure". The New England journal of medicine 271 (13): 637 45. doi:10.1056/NEJM196409242711301. PMID 14170842. 14. Brice, Edmund A. W; Commerford, Patrick J. (2005). "Rheumatic Fever and Valvular Heart Disease". In Rosendorff, Clive. Essential Cardiology: Principles and Practice. Totowa, New Jersey: Humana Press. pp. 545 563. doi:10.1007/978-1-59259-918-9_30. ISBN 978-1-59259-918-9. 15. Caldas, AM; Terreri, MT; Moises, VA; Silva, CM; Len, CA; Carvalho, AC; Hil rio, MO (2008). "What is the true frequency of carditis in acute rheumatic fever? A prospective clinical and Doppler blind study of 56 children with up to 60 months of follow-up evaluation". Pediatric cardiology 29 (6): 1048 53. doi:10.1007/s00246-008-9242-z. PMID 18825449. 16. Guilherme, L; Kalil, J; Cunningham, M (2006). "Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease". Autoimmunity 39 (1): 31 9. doi:10.1080/08916930500484674. PMID 16455580. 17. Kemeny, E; Grieve, T; Marcus, R; Sareli, P; Zabriskie, JB (1989). "Identification of mononuclear cells and T cell subsets in rheumatic valvulitis". Clinical immunology and immunopathology 52 (2): 225 37. PMID 2786783. 18. Roberts, S; Kosanke, S; Terrence Dunn, S; Jankelow, D; Duran, CM; Cunningham, MW (2001). "Pathogenic mechanisms in rheumatic carditis: Focus on valvular endothelium". The Journal of infectious diseases 183 (3): 507 11. doi:10.1086/318076. PMID 11133385. 19. Stanevicha, V; Eglite, J; Sochnevs, A; Gardovska, D; Zavadska, D; Shantere, R (2003). "HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia". Arthritis Research & Therapy 5 (6): R340 R346. doi:10.1186/ar1000. PMC 333411. 20. Schafranski, MD; Pereira Ferrari, L; Scherner, D; Torres, R; Jensenius, JC; De Messias-Reason, IJ (2008). "High-producing MBL2 genotypes increase the risk of acute and chronic carditis in patients with 3827 31. doi:10.1016/j.molimm.2008.05.013. PMID 18602696. history of rheumatic fever". Molecular immunology 45 (14): 21. Ramasawmy, R; Spina, GS; Fae, KC; Pereira, AC; Nisihara, R; Messias Reason, IJ; Grinberg, M; Tarasoutchi, F et al. (2008). "Association of Mannose-Binding Lectin Gene Polymorphism but Not of Mannose-Binding Serine Protease 2 with Chronic Severe Aortic Regurgitation of Rheumatic https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 8/9 7/4/23, 12:36 AM Rheumatic Heart Disease - Textbook of Cardiology Etiology". Clinical and Vaccine Immunology : CVI 15 (6): 932 936. doi:10.1128/CVI.00324-07. PMC 2446618. 22. "Rheumatic Heart Disease/Rheumatic Fever". American Heart Association. Retrieved 2008-02-17. 23. "Initiative for Vaccine Research (IVR) - Group A Streptococcus". World Health Organization. Retrieved 15 June 2012. 24. "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov. 11, 2009. 25. "Rheumatic fever". Medline Plus Medical Encyclopedia. NLM/NIH. 26. Porth, Carol (2007). Essentials of pathophysiology: concepts of altered health states. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7087-4. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Rheumatic_Heart_Disease&oldid=2397" This page was last edited on 22 May 2013, at 20:19. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Rheumatic_Heart_Disease 9/9 |
7/4/23, 12:19 AM SQTS - Textbook of Cardiology SQTS Auteur: Louise R.A. Olde Nordkamp Supervisor: Arthur A.M. Wilde The short QT syndrome is a very rare syndrome characterized by an abnormally short QT interval and increased risk of ventricular fibrillation and cardiac death. Contents Clinical diagnosis Physical examination ECG tests Genetic diagnosis Risk Stratification Treatment References Clinical diagnosis The diagnosis is based on the presence a short QT interval, in which the upper limit is mostly set on 330 ms. Males are more often affected than women. A history of cardiac arrest is present in one-third. for both atrial Patients are at risk ventricular (AF) arrhythmias arrhythmias (VT/VF). and Physical examination Patients can present with symptoms of arrhythmias: Out-of-hospital-cardiac-arrest Syncope, pre-syncope (weakness, lightheadedness, dizziness) ECG tests https://www.textbookofcardiology.org/wiki/SQTS 1/3 7/4/23, 12:19 AM SQTS - Textbook of Cardiology The ECG demonstrates a corrected QT interval significantly below the limit of normal (<330 ms). Additionally, notable ECG findings are the presence of a sharp T-wave beginning at the end of the QRS complex, preceded by a brief or absent ST-segment. Exercise electrocardiographic studies in SQTS patients also characteristically reveal a non-physiologic lack of QT shortening at increased heart rates. Genetic diagnosis In a quarter of the patients a mutation is found, predominantly in the KCNH2 gene (SQTS1). This gain- of-function mutation causes an increase in the potassium efflux and, subsequently, to a decrease of the myocyte refractory period. Mutations in the KCNQ1, KCNJ2 and possibly CACNxxx genes are also associated with the SQTS. Risk Stratification Risk stratification in SQTS is still ill-defined and should be done by a specialized cardio-genetic cardiologist. Treatment Hydroquinidine is suggested for normalization of the QT interval in patients with a KCNH2 mutation. ICD therapy is advised in SQTS patients for secondary prevention of sudden cardiac death and could be considered References 1. Giustetto C, Di Monte F, Wolpert C, Borggrefe M, Schimpf R, Sbragia P, Leone G, Maury P, Anttonen O, Haissaguerre M, and Gaita F. Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J. 2006 Oct;27(20):2440-7. DOI:10.1093/eurheartj/ehl185 | 2. Giustetto C, Schimpf R, Mazzanti A, Scrocco C, Maury P, Anttonen O, Probst V, Blanc JJ, Sbragia P, Dalmasso P, Borggrefe M, and Gaita F. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol. 2011 Aug 2;58(6):587-95. DOI:10.1016/j.jacc.2011.03.038 | 3. Patel C, Yan GX, and Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol. 2010 Aug;3(4):401-8. DOI:10.1161/CIRCEP.109.921056 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=SQTS&oldid=2298" This page was last edited on 26 March 2013, at 07:34. https://www.textbookofcardiology.org/wiki/SQTS 2/3 7/4/23, 12:19 AM SQTS - Textbook of Cardiology Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/SQTS 3/3 |
7/4/23, 12:18 AM Syncope - Textbook of Cardiology Syncope Auteur: Louise R.A. Olde Nordkamp Supervisor: Wouter Wieling Contents Definition Classification Of Syncope Pathophysiology Epidemiology Clinical features Reflex syncope Diagnostic evaluation Treatment Orthostatic hypotension Diagnostic evaluation Treatment Cardiac syncope Diagnostic evaluation Treatment References Definition Syncope is a transient loss of consciousness (TLOC) due to global cerebral hypoperfusion characterized by rapid onset, short duration and spontaneous complete recovery. This excludes other causes of TLOC such as neurological, psychological and metabolic causes. https://www.textbookofcardiology.org/wiki/Syncope 1/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology Causes of (non-traumantic) transient loss of consciousness: 1. Syncope a. Reflex syncope b. Orthostatic hypotension c. Cardiac syncope 2. Neurological disorders 3. Psychiatrical disorders 4. Metabolic disorders Classification Of Syncope Syncope can be classified into: https://www.textbookofcardiology.org/wiki/Syncope 2/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology Pathophysiology The mean arterial blood pressure is determined by the cardiac output (CO), systemic vascular resistance (SVR) and central venous pressure. Syncope can be caused by a low peripheral resistance (vasodepressor type), a low cardiac output (cardioinhibitory type) or a combination of both. A low peripheral resistance can be caused by an inappropriate reflex, or autonomic failure. A low cardiac output can be caused by reflex bradycardia, arrhythmias, or structural cardiac diseases or inadequate venous return. Mean arterial blood pressure = Cardiac output * Total peripheral resistance https://www.textbookofcardiology.org/wiki/Syncope 3/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology Epidemiology Syncope is common in the general population. The life-time cumulative incidence of 1 syncopal episodes in teenagers in the general population is high, with about 40 % by the age of 21 years. Reflex syncope is by far (>95%) the most common cause. The majority have experienced reflex-mediated syncope episodes as teenagers and adolescents. The frequency of orthostatic hypotension and cardiac syncope increases with age. Approximately 10-30% of the syncope episodes in patients above 60 years visiting a hospital for their syncope episodes are of cardiac origin. Pataphysiological basis of the classification. ANF = autonomic nervous failure; ANS = autonomic nervous system; BP = blood pressure; low periph. resist. = low peripheral resistance; OH = orthostatic hypotension Clinical features History taking is the most important feature in syncope evaluation. Adequate history taking reveals the clinical features associated with a syncopal event that are important to differentiate the different causes of syncope. These clinical features are suggestive for a specific cause of syncope: Reflex (neurally mediated) syncope Absence of cardiac disease Long history of syncope After sudden, unexpected, unpleasant sight, sound, smell, or pain Prolonged standing or crowded, hot places Nausea, vomiting associated with syncope During or in the absorptive state after a meal With head rotation, pressure on carotid sinus (as in tumous, shaving, tight collars) After exertion Syncope due to orthostatic hypotension After standing up Temporal relationship with start of medication leading to hypotension or changes of dosage Prolonged standing especially in crowded, hot places Presence of autonomic neuropathy or Parkinsonism After exertion Cardiac syncope Presence of severe structural heart disease During exertion, or supine Preceded by palpitation or accompanied by chest pain Family history of sudden death In all patients presenting to a physician with syncope in the hospital an ECG is recommended to screen for a cardiac cause of syncope. Holter monitoring is indicated only in patients who have very frequent syncopes or https://www.textbookofcardiology.org/wiki/Syncope 4/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology presyncope. In-hospital monitoring (in bed or telemetric) is warranted only when the patient has important structural heart disease and is at high risk of life-threatening arrhythmias. In >60% a certain or highly likely diagnosis is made after initial evaluation (history taking, physical examination and ECG). When the mechanism of syncope remains unclear after full evaluation, including a head-up tilt test and carotis sinus massage, an implantable loop recorder is indicated in patients who have clinical or ECG features suggesting arrhythmic syncope. Reflex syncope Diagnostic evaluation Reflex syncope refers to a heterogeneous group of conditions in which there is a relatively sudden change in autonomic nervous system activity (decreased sympathic tonus causing less vasoconstriction and increased parasympathic (vagal) tonus causing bradycardia), triggered by a central (e.g. emotions, pain, blood phobia) or peripheral (e.g. prolonged orthostasis or increased carotid sinus afferent activity). It leads to a fall in blood pressure and cerebral perfusion. The range of bradycardia varies widely in reflex syncope, from a small reduction in peak heart rate to several seconds of asystole. As reflex syncope requires a reversal of the normal autonomic outflow, it only occurs in people with a functional autonomic nervous system and should therefore be distinguished from syncope due to neurogenic orthostatic hypotension in patients with chronic autonomic failure. Vasovagal syncope, a specific form of reflex syncope, is diagnosed if syncope is precipitated by emotional distress or orthostatic stress and is associated with typical prodromes (such as nausea, warmth, pallor, light- headedness, and/or diaphoresis). Head-up-tilt testing is used to examine the susceptibility to reflex syncope in patients who present with syncope of unknown cause. During head-up-tilt-testing a patient is passively changed from supine to upright position using a tilt-table. Treatment The prognosis of reflex syncope is excellent. However, syncope episodes can have a considerable impact on quality of life, because of its unexpected nature and fear for recurrences. Initial treatment of reflex syncope consists of non-pharmacological treatment measures, including reassurance regarding the benign nature of the condition, increasing the dietary salt and fluid intake, moderate exercise training, and physical counterpressure maneuvres (muscle tensing). Orthostatic hypotension Diagnostic evaluation Orthostatic hypotension can be divided into 3 variants depending on the time interval between rising from supine position to complaints of light-headedness and/or fainting. 1. Initial orthostatic hypotension is defined as a transient blood pressure decrease (>40 mmHg systolic blood pressure (BP) and/or >20 mmHg diastolic BP) within 15 seconds of standing. It can only be present during active standing, because the initial drop in BP is not seen during head-up-tilt test in which both BP and heart rate (HR) gradually increases https://www.textbookofcardiology.org/wiki/Syncope 5/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology until stabilization is reached. Because of the rapid initial changes, it can only be detected by continuous beat-to-beat BP measuring of finger arterial. 2. Classical orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg within 3 min of standing or head-up tilt to at least 60 degree on a tilt table. Because the fall of BP is dependent on the baseline BP, a reduction in systolic BP of 30 mmHg may be a more appropriate criterion for OH in patients with supine hypertension. Orthostatic hypotension is a clinical sign and may be symptomatic or asymptomatic and can be a result of primary or secondary autonomic failure. Classical orthostatic hypotension can be detected during bedside evaluation with an active lying-to-standing test using the manual cuff. 3. Delayed orthostatic hypotension is a sustained reduction of systolic BP beyond 3 minutes of standing. These delayed falls in BP may be a mild or early form of sympathetic adrenergic failure. It can be detected with an extended lying-to-standing test or during head-up-tilt test. Treatment Initial treatment is educating regarding awareness and possible avoidance of triggers (e.g. hot crowded environments, volume depletion), early recognition of premonitory symptoms and performing manoeuvres to abort the episode (e.g. supine posture, muscle tensing). Drug-induced autonomic failure is probably the most frequent cause of orthostatic hypotension; in these cases elimination of the offending agents, mainly diuretics and vasodilators, is the main strategy. Alcohol is also commonly associated with orthostatic intolerance. Additionally, in some patients expanding intravascular volume by encouraging a higher than normal salt- and fluid intake can be helpful. Cardiac syncope Diagnostic evaluation Cardiac arrhythmias, both brady- and tachyarrhythmias can cause syncope, due to a decrease in cardiac output. Additional factors which determine the susceptibility to syncope due to arrhythmias are the type of arrhythmia (atrial or ventricular), the status of left ventricular function, posture and the adequacy of vascular compensation are important. Structural heart disease can cause syncope when circulatory demands outweigh the impaired ability of the heart rate to increase its output. Higher age, an abnormal ECG (rhythm abnormalities, conduction disorders, hypertrophy, old myocardial infarction, possible acute ischaemia, and AV block), a history of cardiovascular disease, especially ventricular arrhythmia, heart failure, syncope occurring without prodrome or during effort or supine, were found to be predictors of arrhythmia and/or mortality within 1 year. https://www.textbookofcardiology.org/wiki/Syncope 6/7 7/4/23, 12:18 AM Syncope - Textbook of Cardiology If cardiac syncope is suspected cardiac evaluation (echocardiography, stress testing, electrophysiological study, and prolonged ECG monitoring including loop recorder) is recommended. Treatment Syncope due to documented cardiac arrhythmias must receive treatment appropriate to the cause in all patients. Cardiac pacing, ICDs, and catheter ablation are the usual treatments of syncope due to cardiac arrhythmias, depending on the mechanism of syncope. For structural heart diseases treatment is best directed at amelioration of the specific structural lesion or its consequences. References 1. The ESC Textbook of Cardiovascular Medicine. Second edition. Editors: Camm AJ, Luscher TF, Serruys PW. 2009. Oxford university press. 2. Task Force for the Diagnosis and Management of Syncope, European Society of Cardiology (ESC), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, Deharo JC, Gajek J, Gjesdal K, Krahn A, Massin M, Pepi M, Pezawas T, Ruiz Granell R, Sarasin F, Ungar A, van Dijk JG, Walma EP, and Wieling W. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009 Nov;30(21):2631-71. DOI:10.1093/eurheartj/ehp298 | 3. R. Pathophysiology of syncope. Clin Auton Res 2004; 14: Suppl 1:18-24 4. Wieling W, Thijs RD, van Dijk N, Wilde AA, Benditt DG, and van Dijk JG. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain. 2009 Oct;132(Pt 10):2630-42. DOI:10.1093/brain/awp179 | 5. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, and van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. DOI:10.1007/s10286-011-0119-5 | 6. Colman N, Nahm K, van Dijk JG, Reitsma JB, Wieling W, and Kaufmann H. Diagnostic value of history taking in reflex syncope. Clin Auton Res. 2004 Oct;14 Suppl 1:37-44. DOI:10.1007/s10286-004-1006-0 | Retrieved from "http://www.textbookofcardiology.org/index.php?title=Syncope&oldid=2272" This page was last edited on 25 March 2013, at 03:38. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Syncope 7/7 |
7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Tachycardia S bastien Krul, MD, Louise Olde Nordkamp, MD, Jonas de Jong, MD Contents Introduction Supra-ventricular tachycardia Atrial arrhythmias Sinus Tachycardia Pathophysiology: Clinical diagnosis: Management: Atrial Tachycardia (AT) Pathophysiology: Clinical diagnosis: Management: Atrial Flutter (AFL) Pathophysiology: Clinical diagnosis: Management: Atrial Fibrillation (AF) Pathophysiology: Clinical diagnosis: Management: AV-nodal arrhythmias AV junctional tachycardia Atrioventricular Nodal Reciprocating Tachycardia (AVNRT) Pathophysiology: Clinical diagnosis: Management: AV Re-entry Tachycardia (AVRT) Pathophysiology: Clinical diagnosis: Management: Ventricular tachycardia History Physical Examination Diagnostic Evaluation Overview of ventricular tachycardias Ventricular tachycardia Definitions Localisation of the origin of a ventricular tachycardia Differential diagnosis Treatment Ventricular flutter Treatment Ventricular fibrillation Treatment Accelerated idio-ventricular rhythm Treatment Torsades de Pointes Causes of Torsade de Pointes Concomittant risk factors for medication induced torsade de pointes: Notorious QT prolonging drugs: Treatment Differentiation between SVT and VT Definitions https://www.textbookofcardiology.org/wiki/Tachycardia 1/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Differentiation Treatment References Introduction Differentiation between supraventricular tachycardias (SVT) and ventricular tachycardias (VT) can be challenging, especially in acute emergency settings. SVT's are arrhythmias in the atria or AV-node or arrhythmias in which these structures are involved. Supraventricular arrhythmias are relatively common and rarely life-threatening. VT's are rhythm disorders that origin from the ventricles. VTs can both take place in the myocardial tissue and the conduction system tissue (Figure 1). Supra-ventricular tachycardia Atrial arrhythmias The following arrhythmias arise in the atrium. Dependent on the refractory period of the AV-node the ventricles follow the atrial activation at the same rate at higher atrial rates the AV-node starts to block conduction from atrium to ventricle.[2][3] Figure 1. Classification of tachyarrhythmias.[1] Sinus Tachycardia Pathophysiology: When the sinus node fires with a frequency rate between 100-180bpm, the term sinustachycardia is used. The maximum heart rate a person can achieve during exercise can be calculatedbe estimated by subtracting the age in years from 210, although it is not uncommon for sinus rates to peak above 200/min during vigorous exercise. Usually it is a physiological reaction to stress (exercise, inflammation, stress). External factors can increase the heart rate like coffee and alcohol or drugs.[4] The term inappropriate sinus tachycardia is a persistent increase in resting heart rate or sinus rate unrelated to or an exaggerated response to stress in a person without structural heart disease.[5] Clinical diagnosis: A sinus tachycardia usually has a gradual start and ending. Diagnosis on the ECG can be made by the morphology of the P-wave. The P-wave has the same morphology during sinus tachycardia as during normal sinus rhythm (Figure 2).[6][7] An inappropriate sinus tachycardia is diagnosed by when the sinus tachycardia is persistent (therefore non-paroxysmal) and no trigger can be identified. Management: No treatment is indicated; usually the sinustachycardia will pass when the external trigger is removed. If patients have persistent complaints, the trigger cannot be removed or in case of an inappropriate sinus tachycardia a beta-blocker can be administered. Patients with a contra-indication for beta-blockers can use nondihydropyridine calcium-channel blockers. Atrial Tachycardia (AT) Pathophysiology: Atrial tachycardia (AT) is a tachycardia resulting from fast firing in an ectopic focus or micro re-entry circuit in the atria.[8] It has a rate of 100bpm. In some patients the tachycardia has multiple foci (multifocal atrial tachycardia). This results in different P-wave morphologies on the ECG during the arrhythmia. Atrial tachycardia can be caused by all the mechanisms of arrhythmia formation. Patients after earlier surgery or catheter ablation usually present with macro re-entry AT located around functional or anatomical sides of block. Atrial flutter is a distinct type of AT, but due to its unique mechanism it is discussed separately. Clinical diagnosis: ATs have a wide range clinical presentation. They can occur in paroxysms or can be the permanent underlying rhythm. Complaints of palpitation and a fast regular heart rate are common and as a result of the tachycardia complaints of dizziness, dyspnoea and syncope can be experienced. Focal AT that with a progressive increase at onset and decrease before termination are likely based on abnormal automaticity. Digoxine intoxication is a common cause for ATs. On the ECG an atrial tachycardia can be detected through the P-wave morphology. The P-wave has a different morphology depending on the foci of the atrial tachycardia (Figure 2). An ECG in resting condition of sinus rhythm can help distinguish different morphologies and help in localization of the source of the atrial tachycardia. Vagal manoeuvres or administration of adenosine can block the AV-conduction and https://www.textbookofcardiology.org/wiki/Tachycardia 2/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology reveal firing from the atrium, thereby clearly identifying the atrial source of the tachycardia. Some ATs are sensitive to adenosine and will terminate after administration of adenosine. However sometimes only an electrophysiological study can differentiate between the different SVT and localize the precise location or circuit of the AT.[6][7][9] Management: Vagal manoeuvres or adenosine can be effective in terminating focal AT.[10] If AT persist and is drug-resistant DC cardioversion can be indicated. Recurrent episodes of AT can be prevented with anti-arrhythmic medication, for instance with beta-blockers or calcium antagonists. However not all AT are sensitive to medication and success rate of medication is usually low. If these drugs are unsuccessful Class IC in combination with AV-nodal- blocking agents or Class III drugs can be tried.[11] The treatment of choice for symptomatic AT is catheter ablation. In an experienced centre up to 90% of the ATs can be ablated, recurrence rate is relatively high often due to a new focus of AT. Treatment of multifocal atrial tachyardia is difficult and therapy is usually directed at the management of underlying disease.[12][13] Atrial Flutter (AFL) Pathophysiology: Atrial flutter (AFL) is the most common type of atrial tachycardia. The typical AFL is dependent of the cavotricuspid isthmus.[8] The isthmus between the caval vein and tricuspid is an area of slow conduction. Due to this slow conduction counter clockwise re-entry around the tricuspid annulus can exist. This re-entry produces a typical arrhythmia with activates the atria at a rate between 250-350 beats per minute. If the re- entry circuit moves counter clockwise a typical AFL is produced. If the re-entry circuit moves clockwise, a atypical AFL is seen.[14] The causes and risk are comparable with atrial fibrillation. Clinical diagnosis: An AFL is usually paroxysmal, with a sudden onset, and is diagnosed on the ECG by it typical saw tooth pattern. Patients experience complaints of palpitations, dyspnoea, fatigue or chest pain. An AFL typically has an atrial rate of 280-320 bpm, which conducts to the ventricles in 2:1, 3:1 or 4:1 manner. The P-wave morphology has a saw tooth like appearance and in a typical AFL has a negative vector in the inferior leads. The upstroke or down stroke of the first part of the P-wave is fast, the second path slow (Figure 2). In an atypical AFL the inferior leads have a positive vector. Atrial fibrillation is a common finding in patients with an AFL (up to 35%).[6][7][9][15] Management: Figure 2. The different atrial arrhythmias. Note the differences in P wave morphology or absence of P-waves in case of atrial fibrillation.[1] A patient with an acute episode of AFL requires cardioversion. This can be achieved with anti-arrhythmic drugs or electrical cardioversion. Vagal manoeuvres increase the AV-block on the ECG and demonstrate the AFL more clearly. Anti-arrhythmic drugs are modestly effective in the acute setting (ibutilide or dofetilide) and, but have the risk of pro-arrhythmic effects.[16][17][18] DC cardioversion is an effective methods to cardiovert AFL, especially in patients with heart failure or hemodynamic instability. AFL is amendable to catheter ablation and this is the treatment of choice in AFL. Targeted ablation of the area between the inferior vena cava and the tricuspid annulus can block the re-entry circuit. This is a very successful procedure, with few complications in the hands of an experienced electrophysiologist.[19][20][21] If patients are not eligible for ablation, anti-arrhythmic drugs class IC or III can be started. However they are of limited efficacy and class IC drugs not be administered without AV-nodal slowing agent because of atrial slowing can result in 1:1 AV conduction. Patients with AFL require anti-coagulation as in atrial fibrillation according to the CHADSVASc score.[22][23] Atrial Fibrillation (AF) Pathophysiology: The pathophysiology of AF is complex and incompletely understood.[24] In most patients the trigger of AF results from extra beats in from the pulmonary veins.[25] This is due to myocardial sleeves growing into the pulmonary veins, which are triggered to fire extra beats due a variety of modulators (i.e. the autonomic nerve system).[26] These triggers can trigger the atria into forming multiple self-perpetuating re-entry circuits. These multiple wavelets, are self-perpetuating circuits than constantly change and move through the atria. The ability of the atria to sustain AF is dependable on atrial structural changes (fibrosis/inflammation). AF induces electromechanical changes in the atrium. These changes make it easier for AF to perpetuate; AF begets AF.[27] Due to the fast and rapid activation of the atria, there is no functional mechanical activity left. This results in the most feared complication of AF, namely forming of blood clots (with for instance stroke as a result). During atrial standstill the atria does not effectively pump blood to the ventricle, and blood can coagulate the left atrium or left atrial appendage.[28] The strokes resulting from AF are often more severe than other causes of stroke. Another complication of AF is a tachycardiomyopathy. Due to the constant chaotic activity in the atria, the AV-node can conduct these signals at high rate. The result is an irregular fast ventricular activation. These fast activation of the ventricle can lead to a (reversible) dilated cardiomyopathy.[29] https://www.textbookofcardiology.org/wiki/Tachycardia 3/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Classification of Atrial Fibrillation (AF) related symptoms based on the European Heart Rhythm Association (EHRA) score are: [30] EHRA I No symptoms EHRA II Mild symptoms; normal daily activity not affected EHRA III Severe symptoms; normal daily activity affected EHRA IV Disabling symptom; normal daily activity discontinued Clinical diagnosis: AF is the most common supraventricular arrhythmia in Western society. Patients can experience complaints from palpitations, dyspnoea and dizziness. Prevalence increases with age and reaches 7-10% in 80 year olds. It is characterized by the absence of clear P-waves on the surface ECG and an irregular ventricular rate (Figure 2). On physical examination an irregular pulse can be felt, however this is not diagnostic of AF as other causes can cause an irregular pulse (mainly atrial or ventricular extra systoles). The cardiac output is 10% reduced due to lack of atrial kick. Furthermore due to the higher ventricular rate the heart has not enough time to completely fill with blood thereby reducing stroke volume. The development of AF is associated with different diseases, e.g. hypertension, mitral valve disease, thyroid disease and diabetes.[31] AF usually starts with short single isolated episodes of AF which are self terminating. Progressively over time these episodes are of longer duration and occur more frequently. These episodes progress to persistent AF, which is defined as AF lasting longer than 7 days or which can only be terminated by cardioversion. In the end AF is permanent and cardioversion is not possible or duration of sinus rhythm is short.[32] Episodes of AF can be symptomatic, but patients can experience no symptoms during AF. However it is important to note that the risks of complications of AF are unrelated to the duration of the episodes.[33] AF is classified according to the clinical presentation of AF:[34] Paroxysmal atrial fibrillation: Episodes AF lasting shorter than 7 days and terminating spontaneously usually within 48 hours. Persistent atrial fibrillation: Episodes of AF not terminating spontaneously or lasting longer than 7 days or requires cardioversion Long standing persistent atrial fibrillation: Persistent AF for more than one year. Permanent atrial fibrillation: Accepted AF, no strategies of rhythm control are pursued. Management: Acute Management: The acute management of AF depends on the presentation of the patient. In stable patients with little complaints, rate control can be initiated with beta-blockers, non-dihydropyridine Ca-antagonists and digoxine. If the patient has recent onset of AF, is highly symptomatic or hemodynamicly compromised, cardioversion is indicated. Cardioversion can be performed medically or with electricity. The most effective drug for chemical cardioversion is flecainide, although this drug is contra-indicated in patients with structural heart disease or ischemia.[35] Another option is ibutilide, but this is mostly used and more effective to terminate AFL, and has a small risk of ventricular arrhythmias.[18] In patients with severe structural heart disease amiodarone can be given.[36] Electrical cardioversion can achieved by a DC shock after sedation of the patient. If the AF persist for longer than >48 hours or the start of the episode is not clear, anti-coagulation should be initiated before (medical or electrical) cardioversion. Three weeks of adequate anti-coagulation is advised before cardioversion and it should be continued after cardioversion for 4 weeks to minimize thromboembolic risk. Long-Term Management: The management of AF consists of several key targets. Firstly, any underlying potential reversible cause of AF should be treated. Secondly, care should be taken to prevent the complications of AF. This means that adequate oral-anticoagulation should be initiated and rate control should be started to reduce heart rate. Thirdly, symptoms should be treated with medical or invasive therapy. There are two strategies to reduce symptoms of AF. Rate control is a strategy where a reduction of ventricular heart rate is the main goal. In rhythm control the aim is to maintain sinus rhythm and prevent recurrences of AF.[34] [37] Rate control: In AF the ventricle can have a fast irregular rate that can lead to complaints of palpitations and a tachycardiomyopathy. One of the strategies in managing AF is to control ventricular rate <110bpm.[38][39] In patients with persistent complaints or with heart failure a resting heart rate of <80 is advised. In this strategy no attempt is made to achieve sinus rhythm. This is the only treatment option in patients with permanent AF. Due to the fast irregular ventricular rate a dilated tachycardiomyopathy can develop and proper rate control can revert these ventricular changes. Rate control can be achieved with beta-blockers or non-dihydropyridine Ca-antagonists. Digoxine can be added to rate control, however a recent study showed an increase in mortality in patients using digoxine.[40] If rate control cannot be achieved with drugs, His ablation after pacemaker implant is indicated. His-Ablation with pacemaker implantation: Patients with accepted AF and complaints of a high irregular ventricular rate who do not tolerate medication can be helped with a targeted His bundle ablation with catheter ablation to induce complete AV-block. Before His ablation a pacemaker should be implanted to assure an adequate ventricular rate and response to exercise. Rhythm control: In rhythm control all efforts are made to achieve and maintain sinus rhythm. This can be done with anti-arrhythmic drugs. Most effective are the Class IC and III anti-arrhythmic drugs.[41] Overall rhythm control is difficult and anti-arrhythmic drugs might have (pro-arrhythmic) side effects, if patients have contra-indications.[42][43] Therefore prescription of these drugs should occur with caution. If patients experience serious side effects https://www.textbookofcardiology.org/wiki/Tachycardia 4/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology of anti-arrhythmic drugs or have a low frequency of AF episodes a one month treatment with anti-arrhythmic drugs (especially flecainide combined with beta blocker or non-dihydropiridine calcium antagonist) after cardioversion can prevent the majority of recurrences.[44] Amiodarone is unsuitable for short-term treatment due to its pharmacological properties.[45] Invasive treatment:[46] Catheter ablation: Medical therapy is not always sufficient to maintain sinus rhythm. In the last decade of 20th century it was discovered that AF is triggered from the pulmonary veins and that selective ablation of these trigger sites can reduce AF recurrence.[47] As this technique evolved it is now common to ablate an area around the pulmonary veins to isolate them from the atrial tissue. The left atrium is approached through the inter-atrial septum and with the use of imaging and electrocardiographic signals a 3D map is made to navigate the atria. The pulmonary vein isolation can be performed with multiple energy sources (cryo-cooling, radiofrequent energy). This is a complex procedure that depending on the technique used has a minor chance of (severe) complications (1-5%), primarily caused by damage of the surrounding structures. The one year success rate of the procedure varies on the experience of the operator and is a freedom of AF in 57-71% of the patients after one or more procedures.[48][49] Catheter ablation is suitable for patients with a with drug-refratory rhythm control strategy.[50] Certain selected patients with heart failure might benefit from catheter ablation, although success is lower.[51][52] Surgical treatment: Surgery is a more invasive, but effective modality to treat AF. The classical cut and sew Maze procedure is an open chest procedure that requires extra-corporeal circulation. In this procedure the atrium is cut and sewn again to compartmentalize the atrium en therefore prevent the atrium maintaining AF.[53][54] In recent years a less invasive procedure has developed to treat AF. This minimal invasive surgery is performed through thoracotomy or thoracoscopy and is performed on a beating heart.[55] A pulmonary vein isolation is performed with a clamp and if patients have persistent AF additional left atrial lesions are made on the atrium to compartmentalize the atrium. Finally the left atrial appendage is removed to reduce the occurrence of stroke. This procedure has a success rate of 68% after one year.[56][57][58] Recently hybrid surgical procedures have been described that combine the minimal invasive thoracoscopic surgery with (epicardial or endocardial) elektrophysiological measurement. Patients with a large left atrium (diameter>45mm) or a failed catheter ablation are eligible for AF surgery.[59][60] Studies have shown no benefit of rhythm control over rate control, thus the selection of strategy is mainly dependent of patient and AF characteristics.[38][61][62][63][64][65][66] Patients with AF and heart failure have limited medical options of rate control, as most anti-arrhythmic drugs are contra-indicated, and no benefit of rate vs. rhythm control was detected in studies.[67][68] This means that, since rate control is easier to achieve, rate control should be the initial strategy in all patients, especially in old patients and patients with no or few symptoms of AF. The target heart rate to achieve in rest is <110 beats per minute.[69] In patients with persistent complaints of AF rhythm control can be initiated on top of rate control. Young patients with paroxysmal AF and no underlying heart disease might benefit from early (invasive) rhythm control to halt progression of the disease.[70] However, independent of the treatment strategy, proper anti-coagulation is important and necessary in patients with risk factors. [34][37] CHA2DS2VASc score to estimate stroke risk Risk Factor Points C: Congestive heart failure 1 point H: Hypertension 1 point A: Age>75years 2 point D: Diabetes 1 point S: Stroke/Embolism 2 points V: Vascular Disease 1 point A: Age>65years 1 point Sc: Female Sex 1 point Anticoagluation treatment: Proper anti-coagulation is important in patients with AF to reduce the occurrence of stroke.[28] In patients with AF the indication of anti- coagulation is based on certain patient-related risk-factors. A score is created to facilitate the clinical decision making. The CHADS2VASc2 score incorporates these risk factors. A patient has no indication for anti-coagulation if there is a low-risk of thromboembolic complications.[71][72] These patients are defined as males or females <65 years old with no other risk factors. This translates ins a CHADSVASc score of 0, or a CHADSVASc score of 1, where 1 point is based on the female sex. In all other cases anti-coagulation with coumarins or other new anticoagulation drugs (dabigatran, rivaroxiban, apixaban)[73][74][75] is indicated if no strong bleeding-risk exist. It is important to note that anti-coagulation is independent of the underlying rhythm. AV-nodal arrhythmias This section covers the arrhythmias in which the AV-node is critical in maintaining the arrhythmia. Most of these arrhythmias share the common characteristic that AV-node blocking or delaying manoeuvres or medication (adenosine) can terminate the arrhythmia.[2][3] AV junctional tachycardia https://www.textbookofcardiology.org/wiki/Tachycardia 5/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology An AV junctional tachycardia is a tachycardia resulting from regular frequent firing (110-250 bpm) of the AV-node. It has the characteristics of a small QRS with a retrograde or no P-wave. The P-wave is not always visible because it can be hidden in the QRS complex. If it is visible it is negative in the inferior leads and narrow, suggesting an AV-nodal origin. The small QRS is not preceded by a p-wave as atrium and ventricle are both activated from the AV-node. For management of this arrhythmia variable success is achieved with anti-arrhythmic drugs. Atrioventricular Nodal Reciprocating Tachycardia (AVNRT) Pathophysiology: AVNRT is a regular arrhythmia relying on the dual AV-physiology for its maintenance. The AV-node usually has two pathways in these patients; a fast pathway with fast conduction times and a slow pathway, which conducts slowly. The fast pathway has a longer refractory period than the slow pathway. Due to these characteristics re-entry formation is possible. Normally the impulse from the atria is conducted through the fast pathway to the ventricle. The impulse also travels through the slow pathway, but reaches tissue still in the refractory period at the end of the AV-node (as the fast pathway has already conducted the impulse and activated this part of the AV-node). When an extra premature atrial contraction occurs it encounters a refractory fast- pathway (which has a longer refractory period). It enters the slow pathway and when it reaches the end of this pathway it can conduct to the (now restored) end of the AV- node to the ventricles and back up into the fast pathway. The result is a ventricular activation with a retrograde P-wave. If the slow pathway is restored when the impulse reaches the beginning (atrial side) of the fast pathway, the impulse can re-enter the slow-pathway and a re-entry mechanism is established. This is the mechanism of a typical AVNRT, which is found in 90% of the patient with an AVNRT (Figure 3). Two other forms of AVNRT exist that take a different route through the AV-node. Firstly there is an atypical AVNRT in which the impulse travels through the fast pathway and returns through the slow pathway. The result of this AVNRT is a retrograde P-wave which appears far from the QRS complex. Finally there is a rare AVNRT which in patients with two slow pathways. The impulse enters en re-enters through a slow pathway.[6][76][77] Figure 3. The mechanism of AV-nodal re-entry.[1] Clinical diagnosis: It is a fast regular small complex tachycardia with a rate of 180-250 bpm. It is more common in women than in men (3:1) and has a sudden onset. Palpitations are experienced due to the fast regular heartbeat. The Frog sign can be observed; neck vein pulsations which occur due to simultaneous contraction of the atria and ventricles. The atria cannot empty into the ventricles and therefore expulse their contents into the venous circulation. A typical AVNRT can be diagnosed on the ECG by a RP distance of 100ms, resulting in a P wave hidden in the QRS complex or appearing directly after the QRS complex. An atypical AVNRT has a retrograde P appearing far away from the QRS, as it has to travel through the slow pathway. A registration of the onset can often be quite helpful in establishing the diagnosis AVNRT.[6][9] Management: Termination of acute episodes is possible by vagal manoeuvres (blowing on the wrist, carotid sinus massage) or medication (adenosine, verapamil, diltiazem).[78] If vagal manoeuvres or medication fail ECV can be performed. Catheter ablation can be the treatment of first choice in AVNRT. Electrophysiological studies can demonstrate dual AV-node physiology and evoke the arrhythmia in these patients. Selective ablation of the slow pathway has a high success rate (up to 98%) and the risk of inducing AV-block is low (<0,5%).[79] Long term medical therapy can be initiated in patients not suitable for catheter ablation, or who do not desire a catheter ablation. Calcium channel blocker, beta-blockers and digoxin are used as first option or in a pill in the pocket approach.[80] Other options are class IC or class III anti-arrhythmic drugs. AV Re-entry Tachycardia (AVRT) Pathophysiology: AVRT are tachycardias with a re-entry circuit comprising the entire heart. The atria, AV-node, ventricles and an extra bundle (accessory pathway, AP) are essential parts of this circuit. The pre-requisite for an AVRT is the existence of an AP between the atrium and the ventricle. This bundle can bypass the AV-node and connect directly to the His bundle, ventricular myocardium or one of the fascicles. Bundles have variety of anatomical locations and can run epicardially.[81][82] The conduction direction of these bundles can be anterograde (atrium-ventricle), retrograde (ventricle-atrium) or bidirectional. Some of the bundles exhibit AV-nodal conduction properties, these are also known as Mahaeim fibres. If a bundle can conduct anterograde at a high rate (a refractory period of <260ms), then a risk of VF exists if the patients develops AF due to fast conduction of fibrillatory activity. Depending on the conduction characteristics of the bundle and the direction of conduction two different AVRT circuits can manifest (Figure 4): Figure 4. An example of orthodrome AVRT and antidrome AVRT. Note the differences in the direction of the arrhythmia.[1] Orthodrome AV re-entry tachycardia: https://www.textbookofcardiology.org/wiki/Tachycardia 6/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology The impulse travels through the normal conduction system in the standard direction and returns to the atria via the accessory bundle. Antidrome AV re-entry tachycardia: The impulse travels antrograde through the accessory bundle and activates the ventricles. The impulse returns through the normal conduction system to the atria. Clinical diagnosis: If an accessory bundle excites the ventricle earlier than normal AV-conduction, thus has antegrade conduction properties, and can activate the ventricles, pre-excitation is visible on the ECG. Pre-excitation can be visible on the ECG by a shortened PQ interval and a widened QRS complex due to slurring of the initial part of the QRS complex (delta wave). This is also called the Wolf-Parkinson-White symptom and can occur intermittently. If a patient has pre-excitation and complaints of arrhythmia caused by an AVRT the combination of these two is called the Wolf-Parkinson-White syndrome.[83] Some patient have an AVRT, but no traces of pre-excitation. The bundle is then called a concealed bundle, which only conduct in one direction: from ventricles to atria. Patients can be asymptomatic if they only have pre-excitation and this ECG pattern is commonly an incidental finding.[6][9] When an arrhythmia develops using the AP, both types of AVRT can develop depending on the conduction characteristics of the bundle: Orthodrome AV re-entry tachycardia: There is a P-wave (other morphology than sinus rhythm) followed by a narrow QRS-complex Antidrome AV re-entry tachycardia: This is a wide-complex tachycardia, where the wide QRS complex is followed by a retrograde P-wave originating from the AV-node. Management: The circuit of the arrhythmia uses the AV-node; therefore vagal maneuvers are able to terminate the AVRT. However adenosine should be used with care, as it may induce AF and cause 1:1 conduction.[84] Anti-arrhythmic drugs (Class IC, II, III, IV) can be useful to prevent paroxysms of arrhythmia, and a pill-in-the-pocket approach can be used for patients with infrequent episodes.[80] Catheter ablation can target the accessory pathway and destroy the bundle. The success of the procedure is dependent on the location of the bundle as not all anatomical positions can be easily targeted with ablation.[85][86] It is controversial if patients with an asymptomatic WPW ECG pattern and no co-morbidities should have an ablation. To determine the risk of 1:1 conduction, an exercise test can be performed to determine the response of the accessory bundle to an increased atria rate. If the pre-excitation persists an electrophysiological procedure can be performed to assess the conduction properties of the accessory bundle. While the characteristics of the bundle predict the risk for an event, the life-style and\or profession of the patient can influence the decision for ablation.[87][88][89] Ventricular tachycardia Auteur: Louise R.A. Olde Nordkamp Supervisor: Jonas S.S.G. de Jong Ventricular tachycardias (VT's) are rhythm disturbances that arise in the ventricles. History Symptoms can arise in every ventricular tachycardia, depending on the heart rate, the presence of underlying heart disease and the degree of systolic and diastolic heart failure. Various symptoms are: Palpitations Abnormal chest sensation Dyspnea Angina Presyncope (lightheadedness, weakness, diaphoresis) Syncope Cardiogenic shock Additional information about drug use is mandatory. Toxic levels of digoxin and cocain can lead to VT's. Anti-arrhythmics such as amiodarone can influence VT rate. Also additional information about family history of sudden cardiac death is helpfull, as it is a strong predictor of susceptibility to ventricular arrhythmias and sudden cardiac death. Physical Examination Although the diagnosis of VT is generally made by a 12 lead ECG, the following physical symptoms may be present: https://www.textbookofcardiology.org/wiki/Tachycardia 7/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Decreased or variable amplitude of the carotid or peripheral pulses. This is related to the intermittent periods of atrial and ventricular synchronization, which transiently augment cardiac output. Cannon "A" waves on the jugular venous pulse in the neck. These represent intermittent retrograde propulsion of blood into the jugular veins during right atrial contraction against a closed AV valve. This is evidence of AV dissociation. Variable intensity of the first heart sound (although this is difficult with a rapid heart rate). Variable splitting of the first and second heart sounds, and intermittent presence of a third and/or fourth heart sound. Diagnostic Evaluation Exercise testing: Exercise testing is recommended in adult patients with ventricular tachycardias who have an intermediate or greater probability of having coronary heart disease by age, gender and symptoms. It is meant to provoke ischemic changes or ventricular arrhythmias. Ambulatory (Holter) ECG: An ambulatory ECG can be necessary if the diagnosis needs to be clarified, by detecting arrhythmias, QT-interval changes, T-wave alternans (TWA) or ST-segment changes. Echocardiography, Cardiac CT, MRI: Echocardiography is recommended in patients with ventricular tachycardias who are suspected of having a structural heart disease. If echocardiography does not provide accurate assessment of the left and right ventricular function and/or structural changes, cardiac CT or MRI can be done. Exercise testing with an image modality (echocardiography or nuclear perfusion): Some patients with ventricular arrhythmias have an intermediate probability of coronary heart disease, but their ECG is less reliable (because of digoxin use, LVH, greater than 1mm ST-segment depression at rest, WPW syndrome or LBBB). For detecting silent ischemia in these patients exercise testing with an image modality can be done. If patients are unable to perform exercise, a pharmacological stress test with an imaging modality can be done. Coronary angiography: Coronary angiography can diagnose or exclude the presence of significant obstructive coronary heart disease in patients with ventricular arrhythmias who have an intermediate or greater probability of having coronary heart disease. Electrophysiological testing: Electrophysiological testing can be performed to guide and assess the efficacy of VT ablation in patients with ventricular arrhythmias. It can also be done to clarify the mechanism of broad complex tachycardias in patients with coronary heart disease. Overview of ventricular tachycardias An overview of ventricular tachycardias, follow the Approach to the Wide Complex Tachycardia atrial frequency ventricular frequency origin (SVT/VT) example regularity p-wave effect of adenosine Wide complex (QRS>0.12) regular (mostly) ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) Ventricular Tachycardia 200px 60-100 bpm 110-250 bpm ventricle (VT) AV- dissociation Ventricular Fibrillation 200px irregular 60-100 bpm 400-600 bpm none ventricle (VT) AV- dissociation Ventricular Flutter 200px regular 60-100 bpm 150-300 bpm none Accelerated Idioventricular Rhythm regular (mostly) ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) 200px 60-100 bpm 50-110 bpm ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) Torsade de Pointes 200px regular 150-300 bpm Bundle-branch re- entrant tachycardia* ventricles (VT) AV- dissociation regular 60-100 bpm 150-300 bpm no rate reduction Bundle-branch re-entrant tachycardia is extremely rare Ventricular tachycardia Ventricular tachycardia (VT) is defined as a sequence of three or more ventricular beats. The rate is between 110-250 bpm. Ventricular tachycardias often origin around old scar tissue in the heart, e.g. after myocardial infarction. Also electrolyte disturbances and ischemia can cause ventricular tachycardias. The cardiac output is often strongly reduced during VT resulting in hypotension and loss of consciousness. VT is a medical emergency as it can deteriorate into ventricular fibrillation and thus mechanical cardiac arrest. Definitions Non-sustained VT: three or more ventricular beats with a maximal duration of 30 seconds. Sustained VT: a VT of more than 30 seconds duration (or less if treated by electrocardioversion within 30 seconds). Monomorphic VT: all ventricular beats have the same configuration. Polymorphic VT: the ventricular beats have a changing configuration. The heart rate is 100-333 bpm. Biphasic VT: a ventricular tachycardia with a QRS complex that alternates from beat to beat. Associated with digoxin intoxication and long QT syndrome. Localisation of the origin of a ventricular tachycardia https://www.textbookofcardiology.org/wiki/Tachycardia 8/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Determination of the location (or exit site) where a ventricular tachycardia originated can be helpful in understanding the cause of the VT and is very helpful when planning an ablation procedure to treat a ventricular tachycardia. The location can be determined with the QRS morphology: RBBB/LBBB morphology: RBBB: origin in the left ventricle LBBB: origin in the right ventricle Inferior/superior axis (lead II, III and aVF): Inferior axis (positive in lead II, III and aVF): origin superior wall Superior axis (negative in lead II, III and aVF): origin inferior wall Basal/apical (lead V5-V6): Positive concordance in V5-6: basal origin Negative concordance in V5-6: apical origin Differential diagnosis (Non)sustained VT may be idiopathic, but occurs most frequently in patients with underlying structural heart disease of various types including: Coronary heart disease (CHD) with prior myocardial infarction. This is the most frequent cause in developed countries Hypertrophic cardiomyopathy Dilated cardiomyopathy Mitral valve prolapse Aortic stenosis Complex congenital heart disease Cardiac sarcoidosis Arrhythmogenic RV cardiomyopathy/dysplasia If no structural heart disease is present the differential diagnosis includes: Electrolyte disorders, especially hyper- / hypokalemia\ Drugs: e.g. digoxin Channelopathies (e.g. long QT syndrome, Brugada syndrome, CPVT) Idiopathic ventricular tachycardia (e.g. RVOT tachycardia, idiopathic left ventricular tachycardia) Purkinje VT s (e.g. Belhassen) Treatment Hemodynamical instability: Electrocardioversion Haemodynamical stability in a regular monomorphic broadcomplex tachycardia (systolic blood pressure >100 mmHg): Pharmacological treatment can be considered with Proca namide or Amiodaron Ventricular flutter Ventricular flutter is a ventricular tachycardia that occurs at a very rapid rate (often around 300 bpm), mostly caused by re-entry. The QRS complexes are regular and usually monomorphic and show a typical sinusoidal pattern. During ventricular flutter the ventricles depolarize in a circular pattern, which prevents good function. Most often this results in a minimal cardiac output and subsequent ischemia. Often deteriorates into ventricular fibrillation. Treatment Treatment Electrocardioversion is the only treatment for ventricular flutter. Ventricular fibrillation https://www.textbookofcardiology.org/wiki/Tachycardia 9/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology |
Additional information about drug use is mandatory. Toxic levels of digoxin and cocain can lead to VT's. Anti-arrhythmics such as amiodarone can influence VT rate. Also additional information about family history of sudden cardiac death is helpfull, as it is a strong predictor of susceptibility to ventricular arrhythmias and sudden cardiac death. Physical Examination Although the diagnosis of VT is generally made by a 12 lead ECG, the following physical symptoms may be present: https://www.textbookofcardiology.org/wiki/Tachycardia 7/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Decreased or variable amplitude of the carotid or peripheral pulses. This is related to the intermittent periods of atrial and ventricular synchronization, which transiently augment cardiac output. Cannon "A" waves on the jugular venous pulse in the neck. These represent intermittent retrograde propulsion of blood into the jugular veins during right atrial contraction against a closed AV valve. This is evidence of AV dissociation. Variable intensity of the first heart sound (although this is difficult with a rapid heart rate). Variable splitting of the first and second heart sounds, and intermittent presence of a third and/or fourth heart sound. Diagnostic Evaluation Exercise testing: Exercise testing is recommended in adult patients with ventricular tachycardias who have an intermediate or greater probability of having coronary heart disease by age, gender and symptoms. It is meant to provoke ischemic changes or ventricular arrhythmias. Ambulatory (Holter) ECG: An ambulatory ECG can be necessary if the diagnosis needs to be clarified, by detecting arrhythmias, QT-interval changes, T-wave alternans (TWA) or ST-segment changes. Echocardiography, Cardiac CT, MRI: Echocardiography is recommended in patients with ventricular tachycardias who are suspected of having a structural heart disease. If echocardiography does not provide accurate assessment of the left and right ventricular function and/or structural changes, cardiac CT or MRI can be done. Exercise testing with an image modality (echocardiography or nuclear perfusion): Some patients with ventricular arrhythmias have an intermediate probability of coronary heart disease, but their ECG is less reliable (because of digoxin use, LVH, greater than 1mm ST-segment depression at rest, WPW syndrome or LBBB). For detecting silent ischemia in these patients exercise testing with an image modality can be done. If patients are unable to perform exercise, a pharmacological stress test with an imaging modality can be done. Coronary angiography: Coronary angiography can diagnose or exclude the presence of significant obstructive coronary heart disease in patients with ventricular arrhythmias who have an intermediate or greater probability of having coronary heart disease. Electrophysiological testing: Electrophysiological testing can be performed to guide and assess the efficacy of VT ablation in patients with ventricular arrhythmias. It can also be done to clarify the mechanism of broad complex tachycardias in patients with coronary heart disease. Overview of ventricular tachycardias An overview of ventricular tachycardias, follow the Approach to the Wide Complex Tachycardia atrial frequency ventricular frequency origin (SVT/VT) example regularity p-wave effect of adenosine Wide complex (QRS>0.12) regular (mostly) ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) Ventricular Tachycardia 200px 60-100 bpm 110-250 bpm ventricle (VT) AV- dissociation Ventricular Fibrillation 200px irregular 60-100 bpm 400-600 bpm none ventricle (VT) AV- dissociation Ventricular Flutter 200px regular 60-100 bpm 150-300 bpm none Accelerated Idioventricular Rhythm regular (mostly) ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) 200px 60-100 bpm 50-110 bpm ventricle (VT) AV- dissociation no rate reduction (sometimes accelerates) Torsade de Pointes 200px regular 150-300 bpm Bundle-branch re- entrant tachycardia* ventricles (VT) AV- dissociation regular 60-100 bpm 150-300 bpm no rate reduction Bundle-branch re-entrant tachycardia is extremely rare Ventricular tachycardia Ventricular tachycardia (VT) is defined as a sequence of three or more ventricular beats. The rate is between 110-250 bpm. Ventricular tachycardias often origin around old scar tissue in the heart, e.g. after myocardial infarction. Also electrolyte disturbances and ischemia can cause ventricular tachycardias. The cardiac output is often strongly reduced during VT resulting in hypotension and loss of consciousness. VT is a medical emergency as it can deteriorate into ventricular fibrillation and thus mechanical cardiac arrest. Definitions Non-sustained VT: three or more ventricular beats with a maximal duration of 30 seconds. Sustained VT: a VT of more than 30 seconds duration (or less if treated by electrocardioversion within 30 seconds). Monomorphic VT: all ventricular beats have the same configuration. Polymorphic VT: the ventricular beats have a changing configuration. The heart rate is 100-333 bpm. Biphasic VT: a ventricular tachycardia with a QRS complex that alternates from beat to beat. Associated with digoxin intoxication and long QT syndrome. Localisation of the origin of a ventricular tachycardia https://www.textbookofcardiology.org/wiki/Tachycardia 8/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Determination of the location (or exit site) where a ventricular tachycardia originated can be helpful in understanding the cause of the VT and is very helpful when planning an ablation procedure to treat a ventricular tachycardia. The location can be determined with the QRS morphology: RBBB/LBBB morphology: RBBB: origin in the left ventricle LBBB: origin in the right ventricle Inferior/superior axis (lead II, III and aVF): Inferior axis (positive in lead II, III and aVF): origin superior wall Superior axis (negative in lead II, III and aVF): origin inferior wall Basal/apical (lead V5-V6): Positive concordance in V5-6: basal origin Negative concordance in V5-6: apical origin Differential diagnosis (Non)sustained VT may be idiopathic, but occurs most frequently in patients with underlying structural heart disease of various types including: Coronary heart disease (CHD) with prior myocardial infarction. This is the most frequent cause in developed countries Hypertrophic cardiomyopathy Dilated cardiomyopathy Mitral valve prolapse Aortic stenosis Complex congenital heart disease Cardiac sarcoidosis Arrhythmogenic RV cardiomyopathy/dysplasia If no structural heart disease is present the differential diagnosis includes: Electrolyte disorders, especially hyper- / hypokalemia\ Drugs: e.g. digoxin Channelopathies (e.g. long QT syndrome, Brugada syndrome, CPVT) Idiopathic ventricular tachycardia (e.g. RVOT tachycardia, idiopathic left ventricular tachycardia) Purkinje VT s (e.g. Belhassen) Treatment Hemodynamical instability: Electrocardioversion Haemodynamical stability in a regular monomorphic broadcomplex tachycardia (systolic blood pressure >100 mmHg): Pharmacological treatment can be considered with Proca namide or Amiodaron Ventricular flutter Ventricular flutter is a ventricular tachycardia that occurs at a very rapid rate (often around 300 bpm), mostly caused by re-entry. The QRS complexes are regular and usually monomorphic and show a typical sinusoidal pattern. During ventricular flutter the ventricles depolarize in a circular pattern, which prevents good function. Most often this results in a minimal cardiac output and subsequent ischemia. Often deteriorates into ventricular fibrillation. Treatment Treatment Electrocardioversion is the only treatment for ventricular flutter. Ventricular fibrillation https://www.textbookofcardiology.org/wiki/Tachycardia 9/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Ventricular fibrillation (VF) is identified by the complete absence of properly formed QRS complexes and no obvious P waves. Instead of uniform activation of the ventricular myocardium, there are unco rdinated series of very rapid, ineffective contractions of the ventricle caused by many chaotic electrical impulses. In recent onset VF the QRS complexes are of high amplitude at rates greater than 320 bpm, which manifest random changes in morphology, width and height. It appears as a completely chaotic rhythm. If VF continues, the fibrillatory waves become fine and can resemble asystole in these cases. Treatment VF is lethal if the patient is not treated immediately. It gives rise to a mechanical standstill of the heart, because the heart is not able to pump normally anymore. Electrocardioversion is the only treatment for ventricular fibrillation. Accelerated idio-ventricular rhythm Accelerated idioventricular rhythm (AIVR) is a relatively benign form of ventricular tachycardia. It is (mostly) a regular repetitive ventricular rhythm with a rate around 60-120 bpm, but mostly 80-100. It is the result of an enhanced ectopic ventricular rhythm, which is faster than normal intrinsic ventricular escape rhythm (<40 bpm), but slower than ventricular tachycardia (over 100-120 bpm). It often occurs during reperfusion after a myocardial infarction. AIVR is not predictive marker for early VF; however, recent debate has started whether among patients with successfull coronary intervention, AIVR is a sign of ventricular dysfunction and therefore a slightly worse prognosis. AIVR can also occur in infants. By this definition, this is a ventricular rhythm of no more than 20% faster than the sinus rate and occuring in the absence of other heart disease. This arrhythmia typically resolves spontaneously during the first months of life (in contrast to an infant with incessant VT which can be due to discrete myocardial tumors or congenital cardiomyopathy). Treatment AIVR is generally a transient, self-limiting rhythm and resolves as sinus rate surpasses the rate of AIVR. It rarely causes hemodynamic instability and rarely requires treatment. Torsades de Pointes Torsade de pointes (TdP) is a ventricular tachycardia associated with a prolonged QTc interval on the resting ECG. The ECG is characterized by twisting of the peaks of the QRS complexes around the isoelectric baseline during the arrhythmia (changing axis). Torsade de pointes is initiated by a short-long-short interval. A ventricle extrasystole (first beat: short) is followed by a compensatory pause. The following beat (second beat: long) has a longer QT interval. If the next beat follows shortly thereafter, there is a good chance that this third beat falls within the QT interval, resulting in the R on T phenomenon and subsequent Torsades de pointes. Causes of Torsade de Pointes Torsade de Pointes, preceded by bigemini. Aquired long QT syndrome (complete list of drugs causing long QT syndrome: http://www.torsades.org http://www.torsades.org]) https://www.textbookofcardiology.org/wiki/Tachycardia 10/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Congenital long QT syndrome Concomittant risk factors for medication induced torsade de pointes: 1. Female sex 2. Hypokalemia 3. Bradycardia 4. Recent conversion of atrial fibrillation, especially if QT prolonging drugs were used (sotalol, amiodarone) 5. Cardiac decompensation 6. Digoxin treatment 7. High or overdosing or rapid infusion of a QT prolonging drug 8. Pre-existing QT prolongation 9. Congenital QT syndrome Notorious QT prolonging drugs: 1. Amiodarone 2. Chloroquine 3. Chlorpromazine 4. Citalopram 5. Claritromycin 6. Disopyramide 7. Dofetilide 8. Erythromycin 9. Flecainide 10. Halofantrine 11. Haloperidol 12. Quinidine 13. Sotalol Treatment Electrocardioversion is the first treatment for TdP. Additional treatments are: Withdrawal of any offending drugs and correction of electrolyte abnormalities (potassium repletion up to 4.5 to 5 mmol/liter). Acute and long-term cardiac pacing in patients with TdP presenting with heart block, symptomatic bradycardia or recurrent pause-dependent TdP Intravenous magnesium sulfate for patients with QT prolongation and few episodes of TdP. Beta blockers combined with cardiac pacing as acute therapy for patients with TdP and sinus bradycardia. Isoproterenol as temporary treatment in patients with recurrent pause-dependent TdP who do not have congenital long QT syndrome. Differentiation between SVT and VT To differentiate between supraventricular tachycardias and ventricular tachycardias a 12 lead ECG is the cornerstone of the diagnostic process. At first, the physician has to make a differentiation between a narrow or wide complex tachycardia. Definitions Narrow complex tachycardia: QRS duration < 120 ms. A narrow complex tachycardia is most likely to be a SVT. However, also a septal VT or His-tachycardia can appear as a narrow complex tachycardia. Wide complex tachycardia: QRS duration > 120 ms. A wide complex tachycardia can be due to a SVT with aberration, pre-exited tachycardia (eg antidrome re-entry tachycardia) or VT. 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Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS). Heart Rhythm. 2012 Jun;9(6):1006-24. DOI:10.1016/j.hrthm.2012.03.050 | 72. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004 Mar 4;350(10):1013-22. DOI:10.1056/NEJMra032426 | 73. Cox JL, Schuessler RB, D'Agostino HJ Jr, Stone CM, Chang BC, Cain ME, Corr PB, and Boineau JP. The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg. 1991 Apr;101(4):569-83. 74. Cox JL. The surgical treatment of atrial fibrillation. IV. Surgical technique. J Thorac Cardiovasc Surg. 1991 Apr;101(4):584-92. 75. Wolf RK, Schneeberger EW, Osterday R, Miller D, Merrill W, Flege JB Jr, and Gillinov AM. Video-assisted bilateral pulmonary vein isolation and left atrial appendage exclusion for atrial fibrillation. J Thorac Cardiovasc Surg. 2005 Sep;130(3):797-802. DOI:10.1016/j.jtcvs.2005.03.041 | 76. Boersma LV, Castella M, van Boven W, Berruezo A, Yilmaz A, Nadal M, Sandoval E, Calvo N, Brugada J, Kelder J, Wijffels M, and Mont L. Atrial fibrillation catheter ablation versus surgical ablation treatment (FAST): a 2-center randomized clinical trial. Circulation. 2012 Jan 3;125(1):23-30. DOI:10.1161/CIRCULATIONAHA.111.074047 | 77. de Groot JR, Driessen AH, Van Boven WJ, Krul SP, Linnenbank AC, Jackman WM, and De Bakker JM. Epicardial confirmation of conduction block during thoracoscopic surgery for atrial fibrillation a hybrid surgical-electrophysiological approach. Minim Invasive Ther Allied Technol. 2012 Jul;21(4):293-301. DOI:10.3109/13645706.2011.615329 | 78. La Meir M, Gelsomino S, Luc F, Pison L, Colella A, Lorusso R, Crudeli E, Gensini GF, Crijns HG, and Maessen J. Minimal invasive surgery for atrial fibrillation: an updated review. Europace. 2013 Feb;15(2):170-82. DOI:10.1093/europace/eus216 | 79. Lip GY, Frison L, Halperin JL, and Lane DA. Identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary |
57. Ogawa S, Yamashita T, Yamazaki T, Aizawa Y, Atarashi H, Inoue H, Ohe T, Ohtsu H, Okumura K, Katoh T, Kamakura S, Kumagai K, Kurachi Y, Kodama I, Koretsune Y, Saikawa T, Sakurai M, Sugi K, Tabuchi T, Nakaya H, Nakayama T, Hirai M, Fukatani M, Mitamura H, and J-RHYTHM Investigators. Optimal treatment strategy for patients with paroxysmal atrial fibrillation: J-RHYTHM Study. Circ J. 2009 Feb;73(2):242-8. DOI:10.1253/circj.cj-08-0608 | 58. Ionescu-Ittu R, Abrahamowicz M, Jackevicius CA, Essebag V, Eisenberg MJ, Wynant W, Richard H, and Pilote L. Comparative effectiveness of rhythm control vs rate control drug treatment effect on mortality in patients with atrial fibrillation. Arch Intern Med. 2012 Jul 9;172(13):997-1004. DOI:10.1001/archinternmed.2012.2266 | 59. Camm AJ, Breithardt G, Crijns H, Dorian P, Kowey P, Le Heuzey JY, Merioua I, Pedrazzini L, Prystowsky EN, Schwartz PJ, Torp-Pedersen C, and Weintraub W. 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10;373(9658):155-66. DOI:10.1016/S0140-6736(09)60040-4 | 40. Friberg L, Hammar N, and Rosenqvist M. Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation. Eur Heart J. 2010 Apr;31(8):967-75. DOI:10.1093/eurheartj/ehn599 | 41. Jahangir A, Lee V, Friedman PA, Trusty JM, Hodge DO, Kopecky SL, Packer DL, Hammill SC, Shen WK, and Gersh BJ. Long-term progression and outcomes with aging in patients with lone atrial fibrillation: a 30-year follow-up study. Circulation. 2007 Jun 19;115(24):3050-6. DOI:10.1161/CIRCULATIONAHA.106.644484 | 42. Mart nez-Marcos FJ, Garc a-Garmendia JL, Ortega-Carpio A, Fern ndez-G mez JM, Santos JM, and Camacho C. Comparison of intravenous flecainide, propafenone, and amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol. 2000 Nov 1;86(9):950-3. DOI:10.1016/s0002-9149(00)01128-0 | 43. Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, and Touboul P. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2003 Jan 15;41(2):255-62. DOI:10.1016/s0735-1097(02)02705-5 | 44. Stambler BS, Wood MA, and Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy. Circulation. 1997 Dec 16;96(12):4298-306. DOI:10.1161/01.cir.96.12.4298 | 45. Kirchhof P, Andresen D, Bosch R, Borggrefe M, Meinertz T, Parade U, Ravens U, Samol A, Steinbeck G, Treszl A, Wegscheider K, and Breithardt G. Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial. Lancet. 2012 Jul 21;380(9838):238-46. DOI:10.1016/S0140-6736(12)60570-4 | 46. Ahmed S, Rienstra M, Crijns HJ, Links TP, Wiesfeld AC, Hillege HL, Bosker HA, Lok DJ, Van Veldhuisen DJ, Van Gelder IC, and CONVERT Investigators. Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial. JAMA. 2008 Oct 15;300(15):1784-92. DOI:10.1001/jama.300.15.1784 | 47. Ghuran A, van Der Wieken LR, and Nolan J. Cardiovascular complications of recreational drugs. BMJ. 2001 Sep 1;323(7311):464-6. DOI:10.1136/bmj.323.7311.464 | 48. van Hemel, N. M. Klinische elektrocardiografie: Een handleiding voor zelfstandige beoordeling van het ECG (Dutch Edition). Bohn Stafleu van Loghum. (https://isbndb.com/book/9789031313983) ISBN:9789031313983 49. Coss SF and Steinberg JS. Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics. Prog Cardiovasc Dis. 1998 Jul-Aug;41(1):51-63. DOI:10.1016/s0033-0620(98)80022-4 | 50. Alboni P, Tomasi C, Menozzi C, Bottoni N, Paparella N, Fuc G, Brignole M, and Cappato R. Efficacy and safety of out-of-hospital self- administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. J Am Coll Cardiol. 2001 Feb;37(2):548-53. DOI:10.1016/s0735-1097(00)01128-1 | 51. Clague JR, Dagres N, Kottkamp H, Breithardt G, and Borggrefe M. Targeting the slow pathway for atrioventricular nodal reentrant tachycardia: initial results and long-term follow-up in 379 consecutive patients. Eur Heart J. 2001 Jan;22(1):82-8. DOI:10.1053/euhj.2000.2124 | 52. Akhtar M, Jazayeri MR, Sra J, Blanck Z, Deshpande S, and Dhala A. Atrioventricular nodal reentry. Clinical, electrophysiological, and therapeutic considerations. Circulation. 1993 Jul;88(1):282-95. DOI:10.1161/01.cir.88.1.282 | 53. Wellens MD PhD, Hein J. J., Conover RN BSN, Mary Boudreau. The ECG in Emergency Decision Making. Saunders. (https://isbndb.com/book/ 9781416002598) ISBN:9781416002598 54. Pappone C, Santinelli V, Rosanio S, Vicedomini G, Nardi S, Pappone A, Tortoriello V, Manguso F, Mazzone P, Gulletta S, Oreto G, and Alfieri O. Usefulness of invasive electrophysiologic testing to stratify the risk of arrhythmic events in asymptomatic patients with Wolff-Parkinson-White https://www.textbookofcardiology.org/wiki/Tachycardia 18/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology pattern: results from a large prospective long-term follow-up study. J Am Coll Cardiol. 2003 Jan 15;41(2):239-44. DOI:10.1016/s0735- 1097(02)02706-7 | 55. Priori SG, Aliot E, Blomstrom-Lundqvist C, Bossaert L, Breithardt G, Brugada P, Camm AJ, Cappato R, Cobbe SM, Di Mario C, Maron BJ, McKenna WJ, Pedersen AK, Ravens U, Schwartz PJ, Trusz-Gluza M, Vardas P, Wellens HJ, and Zipes DP. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J. 2001 Aug;22(16):1374-450. DOI:10.1053/euhj.2001.2824 | 56. Jackman WM, Wang XZ, Friday KJ, Roman CA, Moulton KP, Beckman KJ, McClelland JH, Twidale N, Hazlitt HA, and Prior MI. Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med. 1991 Jun 6;324(23):1605- 11. DOI:10.1056/NEJM199106063242301 | 57. Mazgalev TN, Ho SY, and Anderson RH. Anatomic-electrophysiological correlations concerning the pathways for atrioventricular conduction. Circulation. 2001 Jun 5;103(22):2660-7. DOI:10.1161/01.cir.103.22.2660 | 58. Wolff L, Parkinson J, and White PD. Bundle-branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia. 1930. Ann Noninvasive Electrocardiol. 2006 Oct;11(4):340-53. DOI:10.1111/j.1542-474X.2006.00127.x | 59. Cos o FG, Anderson RH, Kuck KH, Becker A, Borggrefe M, Campbell RW, Gaita F, Guiraudon GM, Ha ssaguerre M, Rufilanchas JJ, Thiene G, Wellens HJ, Langberg J, Benditt DG, Bharati S, Klein G, Marchlinski F, and Saksena S. Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. A Consensus Statement from the Cardiac Nomenclature Study Group, Working Group of Arrhythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE. Circulation. 1999 Aug 3;100(5):e31-7. DOI:10.1161/01.cir.100.5.e31 | 60. Wu J and Zipes DP. Mechanisms underlying atrioventricular nodal conduction and the reentrant circuit of atrioventricular nodal reentrant tachycardia using optical mapping. J Cardiovasc Electrophysiol. 2002 Aug;13(8):831-4. DOI:10.1046/j.1540-8167.2002.00831.x | 61. Becker AE, Anderson RH, Durrer D, and Wellens HJ. The anatomical substrates of wolff-parkinson-white syndrome. A clinicopathologic correlation in seven patients. Circulation. 1978 May;57(5):870-9. DOI:10.1161/01.cir.57.5.870 | 62. Tebbenjohanns J, Pfeiffer D, Schumacher B, Jung W, Manz M, and L deritz B. Intravenous adenosine during atrioventricular reentrant tachycardia: induction of atrial fibrillation with rapid conduction over an accessory pathway. Pacing Clin Electrophysiol. 1995 Apr;18(4 Pt 1):743- 6. DOI:10.1111/j.1540-8159.1995.tb04673.x | 63. Saoudi N, Cos o F, Waldo A, Chen SA, Iesaka Y, Lesh M, Saksena S, Salerno J, Schoels W, and Working Group of Arrhythmias of the European of Cardiology and the North American Society of Pacing and Electrophysiology. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 2001 Jul;22(14):1162-82. DOI:10.1053/euhj.2001.2658 | 64. Markowitz SM, Stein KM, Mittal S, Slotwiner DJ, and Lerman BB. Differential effects of adenosine on focal and macroreentrant atrial tachycardia. J Cardiovasc Electrophysiol. 1999 Apr;10(4):489-502. DOI:10.1111/j.1540-8167.1999.tb00705.x | 65. Anguera I, Brugada J, Roba M, Mont L, Aguinaga L, Geelen P, and Brugada P. Outcomes after radiofrequency catheter ablation of atrial tachycardia. Am J Cardiol. 2001 Apr 1;87(7):886-90. DOI:10.1016/s0002-9149(00)01531-9 | 66. Chen SA, Tai CT, Chiang CE, Ding YA, and Chang MS. Focal atrial tachycardia: reanalysis of the clinical and electrophysiologic characteristics and prediction of successful radiofrequency ablation. J Cardiovasc Electrophysiol. 1998 Apr;9(4):355-65. DOI:10.1111/j.1540- 8167.1998.tb00924.x | 67. Chen SA, Chiang CE, Yang CJ, Cheng CC, Wu TJ, Wang SP, Chiang BN, and Chang MS. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation. 1994 Sep;90(3):1262-78. DOI:10.1161/01.cir.90.3.1262 | 68. Volgman AS, Carberry PA, Stambler B, Lewis WR, Dunn GH, Perry KT, Vanderlugt JT, and Kowey PR. Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation. J Am Coll Cardiol. 1998 May;31(6):1414- 9. DOI:10.1016/s0735-1097(98)00078-3 | 69. Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, and Billing CB Jr. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation. 2000 Nov 7;102(19):2385-90. DOI:10.1161/01.cir.102.19.2385 | 70. Dunn MI. Thrombolism with atrial flutter. Am J Cardiol. 1998 Sep 1;82(5):638. DOI:10.1016/s0002-9149(98)00420-2 | 71. Lip GY and Kamath S. Thromboprophylaxis for atrial flutter. Eur Heart J. 2001 Jun;22(12):984-7. DOI:10.1053/euhj.2000.2490 | 72. Kottkamp H, H gl B, Krauss B, Wetzel U, Fleck A, Schuler G, and Hindricks G. Electromagnetic versus fluoroscopic mapping of the inferior isthmus for ablation of typical atrial flutter: A prospective randomized study. Circulation. 2000 Oct 24;102(17):2082-6. DOI:10.1161/01.cir.102.17.2082 | 73. Natale A, Newby KH, Pisan E, Leonelli F, Fanelli R, Potenza D, Beheiry S, and Tomassoni G. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol. 2000 Jun;35(7):1898-904. DOI:10.1016/s0735-1097(00)00635-5 | 74. Chen SA, Chiang CE, Wu TJ, Tai CT, Lee SH, Cheng CC, Chiou CW, Ueng KC, Wen ZC, and Chang MS. Radiofrequency catheter ablation of common atrial flutter: comparison of electrophysiologically guided focal ablation technique and linear ablation technique. J Am Coll Cardiol. 1996 Mar 15;27(4):860-8. DOI:10.1016/0735-1097(95)00565-x | 75. Yang Y, Cheng J, Bochoeyer A, Hamdan MH, Kowal RC, Page R, Lee RJ, Steiner PR, Saxon LA, Lesh MD, Modin GW, and Scheinman MM. Atypical right atrial flutter patterns. Circulation. 2001 Jun 26;103(25):3092-8. DOI:10.1161/01.cir.103.25.3092 | 76. Bochoeyer A, Yang Y, Cheng J, Lee RJ, Keung EC, Marrouche NF, Natale A, and Scheinman MM. Surface electrocardiographic characteristics of right and left atrial flutter. Circulation. 2003 Jul 8;108(1):60-6. DOI:10.1161/01.CIR.0000079140.35025.1E | 77. Heemstra HE, Nieuwlaat R, Meijboom M, and Crijns HJ. The burden of atrial fibrillation in the Netherlands. Neth Heart J. 2011 Sep;19(9):373-8. DOI:10.1007/s12471-011-0175-4 | 78. ESC Textbook of Cardiovascular Medicine: Hardback with Online Access, isbn=9780199566990 79. elektrocardiografie: Een handleiding voor zelfstandige beoordeling van het ECG (Dutch Edition), isbn=9789031313983 80. Wellens, Hein J. J. Wellens. Ecg in Emergency Decision Making. W.B. Saunders Company. isbn=9781416002598 https://www.textbookofcardiology.org/wiki/Tachycardia 19/20 7/4/23, 12:17 AM Tachycardia - Textbook of Cardiology Retrieved from "http://www.textbookofcardiology.org/index.php?title=Tachycardia&oldid=2597" This page was last edited on 3 February 2021, at 17:14. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Tachycardia 20/20 |
7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Valvular Heart Disease The four cardiac valves consist of either cusps or leaflets that close to prevent the blood from flowing backwards. When pressure behind the valve builds up, the valve opens, after blood has passed through, the pressure is reduced and the valve closes, actively or passively. Contents Epidemiology Pathophysiology Normal valves Aortic valve Mitral Valve Pulmonary Valve Tricuspid valve Rheumatic valve disease Aortic valve Stenosis Clinical Presentation Diagnostic options Chest Radiography Electrocardiography Echocardiography Computed tomography Cardiac Magnetic Resonance Imaging Cardiac Catheterization Exercise Testing Treatment Medical treatment Surgery Transcatheter intervention Prognosis Bicuspid Aortic valve Clinical Presentation Diagnostic options Echocardiography Cardiac Magnetic Resonance Imaging and Computed Tomography Treatment Medical treatment Surgery Prognosis Aortic Regurgitation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 1/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Pathophysiology Acute aortic regurgitation Chronic Aortic regurgitation Clinical presentation Diagnostics Chest Radiography Electrocardiography Echocardiography Treatment Medical treatment Surgical treatment Mitral Stenosis Etiology and pathology Clinical presentation Diagnostics Chest Radiography Electrocardiography Echocardiography Cardiac Catheterization Prognosis Treatment Medical treatment Percutaneous mitral commissurotomy Surgical intervention Mitral regurgitation Etiology Chronic mitral valve regurgitation Clinical Presentation Acute mitral regurgitation Diagnostic Options Chest Radiography Electrocardiography Echocardiography Cardiac Catheterization Treatment Surgical Tricuspid stenosis Clinical presentation Diagnostic Options Chest radiography Electrocardiography Echocardiography Treatment https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 2/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Tricuspid regurgitation Clinical presentation Diagnostic options Chest Radiography Echocardiography Cardiac catheterization Treatment Medical Surgical Pulmonary valve stenosis Etiology and pathology Clinical presentation Diagnostic options Chest Radiography Electrocardiography Echocardiography Cardiac catheterization Treatment Medical Surgical Pulmonary valve regurgitation Etiology and pathology Clinical presentation Diagnostic options Chest Radiography Electrocardiography Echocardiography Treatment References Epidemiology Valvular heart diseases are a major burden to society and it is expected that the prevalence will increase. Rheumatic valve disease used to be the most prevalent etiology of valvular cardiac diseases worldwide. Still, in developing countries, rheumatic heart disease remains the most common cause of valvular heart disease. Over the past 60 years, the etiology of most valvular heart diseases in industrialized countries shifted towards degenerative etiologies, mainly because of a decrease in acute rheumatic fever. However cardiac valve diseases remain common in industrialized countries, mainly because the decrease in rheumatic valve disease is compensated by an increase in degenerative valve disease, with an important contributing fact being the aging population of industrialized countries. The shift in pathologic etiology accounts for differences in patient characteristics and distribution of type of valvular lesions. [1] https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 3/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology In the US population, the national prevalence of moderate and severe valve disease determined by echocardiography was estimated at 2,5%. In another cohort, prevalence based on clinical signs and symptoms, confirmed by echocardiographic imaging, the estimated prevalence of at least moderate valvular diseas was estimated at 1,8%. This difference indicates the under diagnosing of valvular heart disease, and illustrates the fact that diagnosis on the basis of clinical information alone is not reliable.[2] Prevalence did not change according to gender, but increased substantially with advancing age, with 13,2 % after the age of 75 years, versus <2% prior to 65 years old. The predominance of degenerative etiologies accounts for the higher prevalence in the elderly. The prevalence of degenerative valve disease is expected to rise with the aging population of Western countries. Mitral regurgitation was found to be the most frequent valvular disease, with a prevalence of 1,7 %, followed by aortic regurgitation (0,5%), aortic stenosis (0,4%) and mitral stenosis (0,1%) Mean age of patients presenting to the hospital in the Euro heart survey was 65 years.[3] In this survey, 63% of all cases of native valve disease were of degenerative aetiology. Aortic stenosis was found to be the most frequent valvular disease of patients referred for treatment. In 22% of all patients aetiology was rheumatic heart disease. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 4/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology In developing countries, approximately 30 milion cases of rheumatic fever occur annually, in general before the age of 20.[4] Approximately 60% of patients will develop rheumatic heart disease, which becomes clinically evident 1 to 3 decades later.[5] Rheumatic heart disease remains the most common cause of valvular heart disease in third world countries. In western countries, rheumatic heart disease is the second most common cause of valvular heart disease Pathophysiology 'Diagram of the human heart) Normal valves All cardiac valves have similar well defined interstitial cell layers, covered by endothelium. The three cell layers have specific features, and are named fibrose, spongiosa, and the ventricularis. During the cardiac cycle, the spongiosa rich in glycosaminoglycans, the relative rearrangements of collagenous and elastic layers. Valvular interstitial cells (VIC) are abundant in all layers of the cardiac valves and comprise a diverse, dynamic population of resident cells. Regulation of collagen and other matrix is ensured by enzymes, components facilitates https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 5/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology synthesized by VICs. Integrity of valvular tissue is maintained by interaction of valvular endothelial cells (VECs) with remodeling of VICs. Changes and valvular interstitial and endothelium cell leads to changes in properties of the valve and potentially also valve function. Aortic valve This video shows a normal aortic valve on the left and mitral valve on the right. Video from the Visible Human Heart (http://www.vhlab.umn.e du/) This animation shows the aortic valve of a pig's heart. The tricuspid aortic valve separates the left ventricle outflow tract from the aorta. Behind the three semilunar shaped cusps of the aortic valve are dilated pockets of the aortic root, called sinuses of Valsalva. The right coronary sinus gives rise to the right coronary artery, the left coronary sinus gives rise to the left coronary artery. The commissures are the areas where attachments of two adjacent cusps to the aorta meet. The commissure between the left en non coronary leaflets is positioned along the area of mitro-aortic continuity. The three cusps ascend towards the commissures and descend to the basal attachment with the aorta. Opening and closure of the aortic valve is a passive, pressure driven mechanism in contrast to the mitral valve. Tissue of the aortic cusps is stretched via backpressure in diastolic phase with elongation and stretching of elastin. In the systolic phase, recoil of elastin ensures relaxation and shortening of the cuspal tissue.[6] Optimal functioning of the valve requires perfect alignment of the three cusps. Mitral Valve The mitral valve was named after a Mitre, by Andreas Vesalius (De Humani Corporis Fabrica, 1543).[7] This active valve is located at the junction of the left atrium and left ventricle. The mitral valve apparatus contains five functional components; leaflets, annulus, chordae tendineae, papillary muscles and subajacent myocardium. The annulus is a junctional zone of discontinuous fibrous and muscular tissue that joins the left atrium and ventricle. The anterior leaflet spans about one third of the primary fibrous, anterior part of the annulus. Part of the mitral valve anterior leaflet is in direct fibrous continuity with the aortic valve annulus, the mitro-aortic continuity. The posterior, ventricular leaflet is attached to the posterior predominantly muscular half to two third of the annulus. Due to the asymmetric leaflets, the mitral valve orifice has a funnel shape. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 6/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Chordae tendinae from both the anterior and posterior papillary muscles are attached to each leaflet. The papillary muscles contract and pull the chordae tendinae during systole, which closes the two mitral valve leaflets. The mitral valvular complex comprises the mitral valve apparatus and left atrial en ventricular myocardium, endocardium and the mitro-aortic continuity. It contributes to the formation of the left ventricular outflow tract. The timed passage of blood through the valve as well as the tight closure during systole is facilitated by combined actions of the mitral valvular complex.[8] Pulmonary Valve The structure of the pulmonary valve is analogous to the aortic valve structure. The leaflets are semilunar shaped, with semilunar attachments. The pulmonary valve has no traditional annulus. Anatomically, three rings can be distinguished, superior at the sinotubular junction, at the musculoarterial junction and a third ring at the base of the sinuses.[9] Tricuspid valve The tricuspid valve is located at the junction between the right atrium and right ventricle. The tricuspid valve apparatus consists of 3 leaflets, chordae tendinae, an anterior, posterior and often a third papillary muscle. The peripheral ends of the septal, anterosuperior and inferior or mural leaflets are referred to as commissures. The tricuspid valve has no well defined collagenous annulus. The three leaflets are attached to a fibrous elliptic shaped annulus. The direct attachment of the septal leaflet is a distinctive feature of the tricuspid valve. The prominent papillary muscles support the leaflets at the commissures. The anterior papillary muscle provides chords to the anterior and mural leaflets, the posterior papillary muscle provides chords to the mural and septal leaflets. Normal valve function requires structural integrity and coordinated interactions among multiple anatomic components.[10] A variety of pathophysiologic mechanisms can cause cardiac valve disease. Valvular stenosis, defined as inhibition of forward flow secondary to obstruction caused by failure of a valve to open completely, is almost always caused by a primary cuspal abnormality and a chronic disease process. Valvular insufficiency, defined as reverse flow caused by failure of a valve to close completely, may result from either intrinsic disease of the valve cusps or from damage to or distortion of supporting structures without primary cuspal pathology Rheumatic valve disease Chronic rheumatic valve disease is characterized by chronic, progressive deforming valvular disease. Anatomic lesions combine to varying degrees fibrous, or fibrocalcific distortion of leaflets or cusps, valve commissures and chordae tendineae, with or without annular or papillary muscle deformities. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 7/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Stenosis results from fibrous leaflet and chordal thickening and commissural and chordal fusion with or without secondary calcification. Fusion of a commisure in an open position can cause regurgitation, as well as scarring induced retraction of chordae and leaflets. Aortic valve Stenosis Obstruction of the left ventricle outflow can occur at (eg level hypertrophic cardiomyopathy), supravalvular level or valvular level. Aortic valve stenosis is left ventricle outflow obstruction at valvular level. subvalvular In industrialized countries, aortic stenosis is the most common lesion among patients referred for treatment of valvular disease. [11] Age-related degenerative calcified aortic stenosis is the most common cause of aortic stenosis in North America and Western Europe. The second most common cause is calcification of a congenitally bicuspid aortic valve. Other rare causes of calcified aortic stenosis lupus include erythematosus, and Paget ochronosis with alkaptonuria. The most common etiology of aortic stenosis worldwide remains rheumatic heart disease. in adults Gross pathology of rheumatic heart disease: aortic stenosis. Aorta has been removed to show thickened, fused aortic valve leaflets and opened coronary arteries from above. Autopsy, CDC/Dr. Edwin P. Ewing, Jr. Fabry disease, disease, Prevalence of aortic valve abnormalities increases due to age-related pathology in the ageing population. The first detectable macroscopic modifications of the calcification process is named aortic valve sclerosis. [6] Aortic sclerosis, seen as calcification or focal leaflet thickening with normal valve function, was detected in 25% of people at 65 years of age, this increases to 48% in people aged >75% in a population-based echocardiographic study.[12] [13] The prevalence of calcified aortic stenosis is estimated at 2 % of people 65 years of age, increasing to 3- 9% after the age of 80 years.[2][13] Calcified degenerative aortic valve stenosis was previously considered to be the result of a passive degenerative process due to longterm mechanical stress in combination with calcium accumulation. Recently this concept is revised. Calcified degenerative aortic stenosis is considered an active pathobiological process, including proliferative and inflammatory changes, lipid accumulation, renin- angiotensin system activation, valular interstitial cell transformation, ultimately resulting in calcification of the aortic valve.[14][15] [16] [17] Risk factors for development of calcific aortic stenosis are similar to those for vascular atherosclerosis such as diabetes, hypertension, and cholesterol levels.[18] [19] Progressive calcification leads to immobilization of the cusps causing stenosis. Severity of outflow obstruction gradually increases in aortic valve stenosis. Left ventricular output is maintained by adaptation of the increasingly hypertrophic left ventricle. This compensational mechanism serves to normalize the left ventricle wall stress. Left ventricular hypertrophy in combination https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 8/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology with the prolonged systolic phase of the cardiac cycle results in increased myocardial oxygen demand. The mismatch between oxygen demand and supply is the main mechanism for angina in aortic stenosis. As the stenosis progresses, the left ventricle becomes less compliant with subsequent limited preload reserve. Eventually, the left ventricle will decompensate with a decline in cardiac output and rise in pulmonary artery pressure. Aortic stenosis is assessed by estimating the mean systolic pressure gradient and aortic valve area (AVA). The normal aortic valve area is 3-4 cm2. Mild aortic stenosis is defined as an aortic valve area 1.5 cm2, mean gradient less than 25 mm Hg, or jet velocity less than 3.0 m per second, moderate aortic stenosis as an area of 1.0 to 1.5 cm2, mean gradient 25 to 40 mmHg, or jet velocity 3.0 to 4.0 m per second. A valve area of <1 cm2, a mean gradient greater than 40 mm Hg, or jet velocity greater than 4.0 m per second implies severe aortic stenosis The valve area may decrease by as much as 0.12 0.19cm2 per year.[20] In late stages of severe aortic stenosis, cardiac output declines due to systolic dysfunction of the left ventricle, with a decline in the transvalvular gradient. Aortic stenosis severity Mean pressure gradient Valve area Jet velocity less than 3.0 m per second Mild area 1.5 cm2 less than 25 mm Hg area 1.0 to 1.5 cm2 Moderate 25 to 40 mmHg 3.0 to 4.0 m per second area less than 1.0 cm2 greater than 40 mm Hg greater than 4.0 m per second Severe Clinical Presentation Symptoms of degenerative aortic stenosis manifest with progression of the disease. The first symptoms usually commence in the seventh or eight decade. Symptoms are typically noted on exertion. Dyspnoea on exertion is the most common encountered first symptom. Other symptoms are angina, precipitated by exertion and relieved by rest, syncope and heart failure. The findings on physical examination vary with the severity of the disease. On auscultation, a systolic ejection crescendo-decrescendo murmur, radiating to the neck is audible, often accompanied by a thrill. An elevated left ventricular pressure in patients with aortic stenosis, in conjunction with mitral annulus calcifications predisposes to rupture of mitral chordae tendineae, which may produce a regurgitant systolic murmur.[21] [22] The first heart sound is usually normal or soft in patients with aortic stenosis. The second heart sound may be delayed due to prolongation of systolic ejection time. The S2 also may be single because of superimposed aortic and pulmonic valve components, or the aortic valve component is absent or soft because the aortic valve is too calcified and has become immobile. If the aortic component is audible, this may give rise to a paradoxical splitting of S2. A pronounced atrial contraction can give rise to a palpable and audible S4. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 9/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology When stroke volume and systolic pulse pressures fall in severe aortic stenosis, a pulsus parvus (small pulse) may be present. A wide pulse pressure is also characteristic of aortic stenosis. A pulsus parvus et tardus (the arterial pulse is slow to increase and has a reduced peak) can be appreciated by palpating the carotid pulse of patients with severe aortic stenosis. The stenotic valve decreases the amplitude and delays the timing of the carotid upstroke. Rigidity of the vasculature may hamper this sign in the elderly. Diagnostic options Chest Radiography In aortic stenosis, cardiac silhouette and pulmonary vascular distribution are normal unless cardiac decompensation is present. Post-stenotic dilatation of the ascending aorta is frequent. Calcification of the valve is found in almost all adults with severe aortic stenosis; however, fluoroscopy may be necessary to detect it. A late feature in patients with aortic valve stenosis is cardiomegaly. In patients with heart failure, the heart is enlarged, with congestion of pulmonary vasculature. Electrocardiography In approximately 85% of patients with aortic stenosis, left ventricle hypertrophy, with or without repolarization abnormalities is seen on electrocardiography (ECG). Left atrial enlargement, left axis deviation and conduction disorders are also common. Atrial fibrillation can be seen at late state and in older patients or those with hypertension. Echocardiography The best non-invasive diagnostic tool to confirm the diagnosis of aortic stenosis, assess the number of cusps and the annular size, is ultrasonic examination of the heart. Quantification of valvular calcification is possible. In 1998, the American college of cardiology/American Heart Association (ACC/AHA) task force [23] recommended the diagnostic use of echocardiography. Echocardiographic imaging evaluates the severity and etiology of the primary valvular lesion, secondary lesions, and coexisting abnormalities. The size and function of the atria and ventricles can be evaluated as well as hemodynamic characteristics. Echocardiography is also performed for postprocedural evaluation of patients. Transthoracic echocardiography is recommended for re-evaluation of asymptomatic patients: every year for severe AS; every 1 to 2 years for moderate AS; and every 3 to 5 years for mild AS.[24] To assess the severity of aortic stenosis, transvalvular gradients and maximum jet velocity is measured using Doppler echocardiography, and aortic valve area is calculated. The systolic gradient across the stenotic aortic valve depends on stroke volume, systolic ejection period, and systolic pressure in the ascending aorta. The stenotic valve area is inversely related to the square root of the mean systolic gradient. Due to their flow-dependency these measurements are most valuable in normotensive patients. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 10/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Valve thickening and calcification, as well as reduced leaflet motion can also be assessed using Doppler. Computed tomography Although the role of computed tomography (CT) in clinical management is currently not well defined, this imaging modality could improve assessment of the ascending aorta. CT has an established role in evaluating the presence and severity of aortic root and ascending aortic dilatation in patients with associated aortic aneurysms. The high sensitivity and specificity of CT in detecting high-grade coronary artery stenosis could be useful to preoperatively rule out coronary artery disease. Both electron beam and multislice cardiac CT can be useful in quantifying valve calcification, which have been shown to correlate with echocardiographic assessment and clinical outcome. Prior to transcatheter aortic valve implantations, CT provides information concerning the aortic valve area, annulus size, and the distance between the aortic cusps and the coronary ostia. Cardiac Magnetic Resonance Imaging Cardiac MRI (CMR) has an established role in evaluating aortic root and ascending aorta anatomy. It can be used to measure the aortic valve area, but the role of CMR in the management of aortic stenosis is currently not well defined. Cardiac Catheterization Cardiac catheterization remains the gold standard to detect coronary artery disease. Currently, in patients with aortic stenosis, cardiac catheterization is most often performed to identify the presence of concomitant coronary artery disease (CAD). In patients with inconclusive noninvasive tests, hemodynamic abnormalities can be assessed by cardiac catheterization. Coronary angiography is recommended prior to aortic valve replacement. Exercise Testing Since aortic stenosis is a progressive disease, most common in the elderly population, many patients with aortic stenosis do not recognize gradually developing symptoms and cannot differentiate fatigue and dyspnea from aging and physical deconditioning. Lifestyle modification may mask symptoms. Although contraindicated in patients with severe aortic stenosis, Exercise testing is useful for risk stratification and eliciting symptoms. Under supervision, it is reasonable to propose exercise testing in patients >70 years who are still highly active. Treatment Medical treatment https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 11/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology For many years the standard of care for patients with significant aortic valve stenosis has been to provide antibiotic prophylaxis against infective endocarditis. However, current AHA guidelines for prevention of infective endocarditis no longer recommend antibiotic prophylaxis for this group of patients. Exceptions are patients with a prior episode of endocarditis, patients with prosthetic valves or with additional complex cardiac lesions with a high risk for the development of endocarditis. Patients who have had rheumatic fever should still receive antibiotic prophylaxis against recurrences of rheumatic fever No medical treatment has proven to delay the progression of aortic stenosis. Surgery is inevitable for symptomatic patients. Patients at prohibitive risk for intervention may benefit from medical treatment including digitalis, diuretics, ACE inhibitors, or angiotensin receptor blockers, if experiencing heart failure. Beta-blockers should be avoided in these circumstances. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 12/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Current Guidelines Indications for aortic valve replacement: Class I 1. AVR is indicated for symptomatic patients with severe AS. (Level of Evidence: B) 2. AVR is indicated for patients with severe AS undergoing coronary artery bypass graft surgery (CABG). (Level of Evidence: C) 3. AVR is indicated for patients with severe AS undergoing surgery on the aorta or other heart valves. (Level of Evidence: C) 4. AVR is recommended for patients with severe AS and LV systolic dysfunction (ejection fraction less than 0.50). (Level of Evidence: C) Class IIa AVR is reasonable for patients with moderate AS undergoing CABG or surgery on the aorta or other heart valves (Level of Evidence: B) Class IIb 1. AVR may be considered for asymptomatic patients with severe AS and abnormal response to exercise (e.g., development of symptoms or asymptomatic hypotension). (Level of Evidence: C) 2. AVR may be considered for adults with severe asymptomatic AS if there is a high likelihood of rapid progression (age, calcification, and CAD) or if surgery might be delayed at the time of symptom onset. (Level of Evidence: C) 3. AVR may be considered in patients undergoing CABG who have mild AS when there is evidence, such as moderate to severe valve calcification, that progression may be rapid. (Level of Evidence: C) 4. AVR may be considered for asymptomatic patients with extremely severe AS (aortic valve area less than 0.6 cm2, mean gradient greater than 60mmHg, and jet velocity greater than 5.0 m per second) when the patient s expected operative mortality is 1.0% or less. (Level of Evidence: C) Class III AVR is not useful for the prevention of sudden death in asymptomatic patients with AS who have none of IIa/IIb recommendations. (Level of Evidence: B) the findings listed under the Class Surgery The infinitive treatment for aortic valve stenosis is aortic valve replacement. The first cardiac valve surgery under direct vision was an aortic valve replacement, performed in 1960 by dr. Dwight Harken.[25] The aortic valve was replaced by a caged ball valve, which became the standard for aortic valve replacement.[26] [27] A total of more than 70 different mechanical aortic valve models have been introduced in aortic valve replacement and implanted in humans in the past 5 decades. The mechanical prostheses can be divided into 3 large groups: the first generation of ball valves, second generation of tilting-disc valves, and the last generation of bileaflet valves.[28] Mechanical prosthesis are extremely durable but require continuous use of anticoagulants. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 13/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Biological valves include homografts and autografts, as well as stented bioprostheses. Stented bioprostheses are constructed of porcine valves or bovine pericardium sewn onto an artificial stent. All heterograft valvs are preserved with glutaraldehyde, to reduce the antigenicity of the tissue and prevent calcification. The fixation process can be performed at various pressures. Higher fixation pressures may lead to earlier calcification. First-generation bioprostheses were porcine valves, preserved with high- pressure fixation (60 to 80 mmHg) and placed in the annular position Second-generation prostheses are of porcine or pericardial origin, and are treated with low- pressure (0.1 to 2 mmHg)or zero-pressure fixation. Several second-generation bioprostheses may be placed in the supra-annular position, which allows implantation of a slightly larger prosthesis. Third-generation prostheses are treated with zero- or low-pressure fixation and additional processes to reduce calcification. In 1962 Donald Ross implanted the first aortic valve allograft. In 1967 he replaced a patient s malfunctioning aortic valve with the patients own pulmonary valve. An aortic or pulmonary valve homograft was then used to replace the patient s pulmonary valve. This procedure is known as the Ross Procedure. Currently, the Ross procedure may be considered for bicuspid aortic valve stenosis, in particular for young women of reproductive age. Transcatheter intervention In 2002, the first transcatheter aortic valve implantation was performed by Dr. Alain Cribier [29]. A transcatheter aortic valve implantation is a less invasive treatment option for patients at prohibitive risk for conventional aortic valve replacement. In this technique, the native valve is not excised. After balloon valvuloplasty, the prosthetic valve is implanted in the aortic position, with the frame of the prosthesis covering the native valve. The bioprosthesis can be implanted retrograde or antegrade. Currently 4 different approaches may be used in this technique. (table ). Transcatheter aortic valve implantation is assessed in randomized clinical trials and registries. The current 4 different approaches are: Transfemoral, retrograde Transapical, antegrade Transaortic, retrograde Transsubclavian, retrograde Prognosis Aortic valve stenosis has a severe prognosis when any symptoms are present, with survival rates of only 15 50% at 5 years. Strongest predictors of poor outcome in the elderly population are high New York Heart Association (NYHA) class (III/IV), associated mitral regurgitation and left ventricular dysfunction. Survival is only 30% at 3 years with the combination of these three factors. Bicuspid Aortic valve https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 14/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Bicuspid Aortic valve disease affects as many as 1-2% of the population, and is the most frequent congenital cardiovascular malformation in humans.[30] A bicuspid aortic valve may be part of a phenotypic continuum of congenital aortic valve disorders, associated with unicuspid valves, bicuspid valves, the normal tricuspid valves and the rare quadricuspid forms. Understanding of the pathogenesis of aortic valve malformation remains incomplete. Bicuspid aortic valves are three to four times more common in men than in women. Bicuspid aortic valve disease results from abnormal cusp formation during valvulogenesis, but coexisting genetic abnormalities of the aorta and proximal coronary vasculature are often present. Moreover, nonvalvular findings occur in up to 50% of patients with bicuspid aortic valves. Associated findings are aortic dilation, aneurysms and dissection. Heart bicuspid aortic valve anatomy by Patrick J. Lynch, medical illustrator, 2006 During valvulogenesis, adjacent cusps of the bicuspid valve fuse to form a single aberrant cusp. This fusion results in large leaflet, yet smaller than 2 normal cusps, with most often a central raphe or ridge. Fusion of the right coronary and noncoronary cusps is associated with cuspal pathology. Fusion of the right and left coronary cusps is associated with coarctation of the aorta. Although endocarditis can be a devastating complication of bicuspid aortic valve disease, straightforward bicuspid aortic valve disease is no longer an indication for bacterial endocarditis prophylaxis according to the ACC/AHA practice guidelines. The risk of endocarditis is felt to be low in patients with straightforward bicuspid aortic valve disease. An exception to this recommendation is a patient with a prior history of endocarditis.[31] Clinical Presentation In infancy, bicuspid aortic valve disease is often asymptomatic. By adolescence an estimate 1 of 50 children born with these abnormalities will have clinically significant obstruction or regurgitation.[24] Complications of bicuspid aortic valve disease are common in adulthood.[32] The abnormal shear stress leads to valve calcification and further aortic root dilation has been reported. [33] The most common complication is aortic stenosis, caused by premature fibrosis, stiffening, and calcium deposition. The majority of patients under 65 years of age with significant aortic valve stenosis have bicuspid aortic valve disease. A more rare complication of bicuspid aortic valve disease is aortic regurgitation. 15% of all cases https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 15/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology of aortic regurgitation in the Euro Heart survey had bicuspid aortic valve disease. On auscultation, an ejection sound can be audible, best heard at the apex. There may be associated murmurs of aortic stenosis, incompetence, or coarctation of the aorta when these lesions are present. Diagnostic options Echocardiography Echocardiography is used to confirm the diagnosis of bicuspid aortic valve disease. Reported sensitivities and specificities of echocardiography for detecting BAV anatomy are 92% and 96% respectively. To establish the diagnosis, visualization of the aortic valve in systole in the short-axis view is essential. During diastole, the raphe can make the valve appear trileaflet. In the long-axis view, the valve often has an eccentric closure line and there is doming of the leaflets. Transesophageal echocardiography may improve visualization of the leaflets in case of inconclusive transthoracic echocardiography. In all patients, serial transthoracic echocardiography should be performed to evaluate the valve and disease progression. Annual cardiac imaging is recommended for patients with significant valve lesions or with aortic root diameters >40 mm. Complete imaging of the thoracic aorta should be performed periodically for surveillance.[34] Cardiac Magnetic Resonance Imaging and Computed Tomography The thoracic aorta is visualized by alternative imaging modalities such as cardiac magnetic resonance imaging (MRI) or computer tomography (CT). Both cardiac MRI and CT images can help to confirm the bicuspid anatomy of the aortic valve. Treatment Medical treatment In patients with bicuspid aortic valve disease, high blood pressure should be treated aggressively. The ACC/AHA guidelines for the management of adult congenital heart disease and guidelines for the management of patients with valvular heart disease suggest that it is reasonable to use beta-blockers in this population (Class IIa recommendation).[35] This is in accordance with the standard of care at many centers to slow the progression in Marfan-associated aortopathy. Surgery Indications for surgery are similar to indications for patients with degenerative aortic valve disease ; intervention is indicated for severe valvular dysfunction, symptomatic patients, and patients with evidence of abnormal left ventricular dimensions and function. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 16/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology In children and young adults, the bicuspid valve is not calcified and balloon valvuloplasty is recommended. A prosthetic valve implantation would be suboptimal due to the continuing growth of the child. Indications for valvuloplasty in children include peak-to peak gradients >50 mm Hg with ST- or T-wave changes at rest or with exercise. Valvuloplasty is also indicated for symptomatic children with peak-to- peak gradients >60 mm Hg. [35] Surgical options for adult bicuspic aortic valve disease include valve replacement (bioprosthetic or mechanical valves), Ross procedure or valve repair (for those with aortic incompetence) Surgical aortic valve replacement is the most common procedure in adults with bicuspid aortic valve disease, for either aortic valve stenosis or regurgitation. Indications of interventions are similar to those described for tricuspid aortic valve disease in the ACC/AHA guidelines for the management of patients with valvular heart disease.[33] Approximately 30% of adults with bicuspid aortic valve disease undergoing aortic valve replacement will need aortic root surgery. Surgical attention for dimensions of the aortic root is essential because of the risk for further root dilation. The ascending aorta in patients with bicuspid aortic valve disease increases 0.2 to 1.2 mm/year.[36] Guidelines suggest that changes in root size more than 0.5 cm/year are an indication for root replacement. Aortic root dimensions of 5.0 cm require intervention and aortic root dimensions of 4.5 cm require intervention if surgery is performed for valvular indications according to current guidelines. Prognosis Life expectancy in adult patients with bicuspid aortic valve disease is not shortened when compared to the general population. 10-year survival in asymptomatic adults with bicuspid aortic valve disease with a spectrum of valve function, was 96%.[32] In asymptomatic adults with bicuspid aortic valve disease without significant valve dysfunction the 20-year survival was 90%.[37] Aortic Regurgitation A variety of aetiologies can cause aortic regurgitation by preventing proper coaptation of the aortic valve leaflets with a subsequent diastolic reflux of blood from the aorta into the left ventricle. Etiology of aortic regurgitation can be primary valvular, or it can be primarily caused by aortic root or disease. The origin of primary valve disease may be calcific aortic disease, idiopathic degenerative disease, endocarditis, rheumatic disease, a biscuspid aortic valve, or myxomatous proliferation of valvular tissue. In the majority of patients the disease is caused by rheumatic disease. However, in Western countries the disease is most often of degenerative origin. In the Euro Heart Survey degenerative aortic regurgitation accounted for approximately half of the cases of aortic regurgitation, 15% of cases had a bicuspid aortic valve.[11] Accelerated degeneration of valve leaflets, resulting in regurgitation similar carcinoid syndrome related regurgitation, can be caused by certain anorectic medications, such as fenfluramine and phentermine.[22] Aortic annulus dilation, without primary involvement of the leaflets may result in aortic regurgitation due to leaflet separation. Aortic regurgitation of primary aortic root or annulus aetiology includes idiopathic aortic root dilatation, aortic dissection, trauma, and chronic severe systemic hypertension. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 17/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Aortitis represents less than 5% of the aetiologies of aortic regurgitation and may be due to inflammatory disease, such as giant cell, Takayasu and Behcet syndrome. Syphilis and ankylosing spondylitis may affect the aortic valve, but may also be associated with aortic dilatation. Other systemic arteritides and connective tissue disorders such as Marfan syndrome, Reiter disease, Ehlers-Danlos syndrome, osteogenesis imperfecta, and rheumatoid arthritis can lead to annular dilatation and valvular insufficiency. In patients without generalized tissue disease the same pattern of ascending aortic enlargement is known as annuloaortic ectasia. Chronic aortic regurgitation itself may lead to progressive aortic root dilatation. |
Clinical Presentation In infancy, bicuspid aortic valve disease is often asymptomatic. By adolescence an estimate 1 of 50 children born with these abnormalities will have clinically significant obstruction or regurgitation.[24] Complications of bicuspid aortic valve disease are common in adulthood.[32] The abnormal shear stress leads to valve calcification and further aortic root dilation has been reported. [33] The most common complication is aortic stenosis, caused by premature fibrosis, stiffening, and calcium deposition. The majority of patients under 65 years of age with significant aortic valve stenosis have bicuspid aortic valve disease. A more rare complication of bicuspid aortic valve disease is aortic regurgitation. 15% of all cases https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 15/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology of aortic regurgitation in the Euro Heart survey had bicuspid aortic valve disease. On auscultation, an ejection sound can be audible, best heard at the apex. There may be associated murmurs of aortic stenosis, incompetence, or coarctation of the aorta when these lesions are present. Diagnostic options Echocardiography Echocardiography is used to confirm the diagnosis of bicuspid aortic valve disease. Reported sensitivities and specificities of echocardiography for detecting BAV anatomy are 92% and 96% respectively. To establish the diagnosis, visualization of the aortic valve in systole in the short-axis view is essential. During diastole, the raphe can make the valve appear trileaflet. In the long-axis view, the valve often has an eccentric closure line and there is doming of the leaflets. Transesophageal echocardiography may improve visualization of the leaflets in case of inconclusive transthoracic echocardiography. In all patients, serial transthoracic echocardiography should be performed to evaluate the valve and disease progression. Annual cardiac imaging is recommended for patients with significant valve lesions or with aortic root diameters >40 mm. Complete imaging of the thoracic aorta should be performed periodically for surveillance.[34] Cardiac Magnetic Resonance Imaging and Computed Tomography The thoracic aorta is visualized by alternative imaging modalities such as cardiac magnetic resonance imaging (MRI) or computer tomography (CT). Both cardiac MRI and CT images can help to confirm the bicuspid anatomy of the aortic valve. Treatment Medical treatment In patients with bicuspid aortic valve disease, high blood pressure should be treated aggressively. The ACC/AHA guidelines for the management of adult congenital heart disease and guidelines for the management of patients with valvular heart disease suggest that it is reasonable to use beta-blockers in this population (Class IIa recommendation).[35] This is in accordance with the standard of care at many centers to slow the progression in Marfan-associated aortopathy. Surgery Indications for surgery are similar to indications for patients with degenerative aortic valve disease ; intervention is indicated for severe valvular dysfunction, symptomatic patients, and patients with evidence of abnormal left ventricular dimensions and function. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 16/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology In children and young adults, the bicuspid valve is not calcified and balloon valvuloplasty is recommended. A prosthetic valve implantation would be suboptimal due to the continuing growth of the child. Indications for valvuloplasty in children include peak-to peak gradients >50 mm Hg with ST- or T-wave changes at rest or with exercise. Valvuloplasty is also indicated for symptomatic children with peak-to- peak gradients >60 mm Hg. [35] Surgical options for adult bicuspic aortic valve disease include valve replacement (bioprosthetic or mechanical valves), Ross procedure or valve repair (for those with aortic incompetence) Surgical aortic valve replacement is the most common procedure in adults with bicuspid aortic valve disease, for either aortic valve stenosis or regurgitation. Indications of interventions are similar to those described for tricuspid aortic valve disease in the ACC/AHA guidelines for the management of patients with valvular heart disease.[33] Approximately 30% of adults with bicuspid aortic valve disease undergoing aortic valve replacement will need aortic root surgery. Surgical attention for dimensions of the aortic root is essential because of the risk for further root dilation. The ascending aorta in patients with bicuspid aortic valve disease increases 0.2 to 1.2 mm/year.[36] Guidelines suggest that changes in root size more than 0.5 cm/year are an indication for root replacement. Aortic root dimensions of 5.0 cm require intervention and aortic root dimensions of 4.5 cm require intervention if surgery is performed for valvular indications according to current guidelines. Prognosis Life expectancy in adult patients with bicuspid aortic valve disease is not shortened when compared to the general population. 10-year survival in asymptomatic adults with bicuspid aortic valve disease with a spectrum of valve function, was 96%.[32] In asymptomatic adults with bicuspid aortic valve disease without significant valve dysfunction the 20-year survival was 90%.[37] Aortic Regurgitation A variety of aetiologies can cause aortic regurgitation by preventing proper coaptation of the aortic valve leaflets with a subsequent diastolic reflux of blood from the aorta into the left ventricle. Etiology of aortic regurgitation can be primary valvular, or it can be primarily caused by aortic root or disease. The origin of primary valve disease may be calcific aortic disease, idiopathic degenerative disease, endocarditis, rheumatic disease, a biscuspid aortic valve, or myxomatous proliferation of valvular tissue. In the majority of patients the disease is caused by rheumatic disease. However, in Western countries the disease is most often of degenerative origin. In the Euro Heart Survey degenerative aortic regurgitation accounted for approximately half of the cases of aortic regurgitation, 15% of cases had a bicuspid aortic valve.[11] Accelerated degeneration of valve leaflets, resulting in regurgitation similar carcinoid syndrome related regurgitation, can be caused by certain anorectic medications, such as fenfluramine and phentermine.[22] Aortic annulus dilation, without primary involvement of the leaflets may result in aortic regurgitation due to leaflet separation. Aortic regurgitation of primary aortic root or annulus aetiology includes idiopathic aortic root dilatation, aortic dissection, trauma, and chronic severe systemic hypertension. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 17/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Aortitis represents less than 5% of the aetiologies of aortic regurgitation and may be due to inflammatory disease, such as giant cell, Takayasu and Behcet syndrome. Syphilis and ankylosing spondylitis may affect the aortic valve, but may also be associated with aortic dilatation. Other systemic arteritides and connective tissue disorders such as Marfan syndrome, Reiter disease, Ehlers-Danlos syndrome, osteogenesis imperfecta, and rheumatoid arthritis can lead to annular dilatation and valvular insufficiency. In patients without generalized tissue disease the same pattern of ascending aortic enlargement is known as annuloaortic ectasia. Chronic aortic regurgitation itself may lead to progressive aortic root dilatation. Aortic valve regurgitation is often accompanied by other valvular abnormalities. Aortic valvular insufficiency is most commonly seen in combination with aortic stenosis. Aortic insufficiency due to rheumatic aetiology is often associated with mitral valve disease. The valve leaflets are retracted by fused commissures and by fibrotic scarring of the leaflets itself. Aortic cusp prolapse can be isolated, or due to myxomatous degeneration, sometimes with associated mitral or tricuspid valve involvement. In 15% of patients with ventricular septum defect, prolapse of an aortic cusp leads to aortic insufficiency. Isolated aortic regurgitation is often caused by a primary aortic annular etiology. Rheumatic origin is much less common in patients with pure aortic regurgitation. In approximately 10% of cases, aortic regurgitation results from infective endocarditis, with perforation or erosion of leaflets. It is of considerable clinical importance to distinguish between acute aortic regurgitation and chronic regurgitation since acute aortic regurgitation can be life-threatening if not treated immediately, in contrast to chronic regurgitation which can be tolerated for years. Pathophysiology In patients with aortic insufficiency the regurgitating volume increases the total stroke volume. This volume might equal the effective forward stroke volume in patients with severe aortic regurgitation. In chronic aortic regurgitation, several compensatory mechanisms ensure cardiac output. Acute aortic regurgitation Acute aortic regurgitation is a sudden hemodynamically significant aortic incompetence, which can often be catastrophic. An increase in left ventricular end diastolic volume with absence of ventricular remodelling may lead to elevated left atrial and pulmonary artery wedge pressure and decreased effective cardiac output, with compensatory tachycardia to maintain sufficient output. Acute severe aortic regurgitation typically occurs with infective endocarditis, trauma, and aortic dissection. The left ventricle cannot dilate sufficiently. The patient may present with chest pain due to increased myocardical oxygen consumption combined with decreased coronary bloodflow from changes in diastolic perfusion. Coronary bloodflow in acute aortic insufficiency occurs during stystolic cardiac phase. Other symptoms of acute aortic regurgitation are tachypnea, tachycardia and rapidly progressive pulmonary edema and/or cardiogenic shock. Chronic Aortic regurgitation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 18/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Aortic root dilatation, annular dilation and congenital bicuspid valve are, in developed countries, the most common causes of severe chronic aortic valve regurgitation. The slow process of chronic aortic regurgitation allows adaptation of the ventricle to the increased preload and afterload. The left ventricular compensates to the regurgitant flow, the increased volume and pressure by enlargement. The left ventricle end diastolic pressure remains relatively low and does not approach the aortic diastolic pressure. The additional stroke volume is responsible for increased systolic pressure and eventually the wide pulse pressure. The systolic hypertension further increases left ventricle afterload. In contrast to the compensatory mechanism in mitral valve regurgitation, a modest concentric left ventricular hypertrophy accompanies the eccentric hypertrophy, with a normal mass-to-volume ratio. [38] In a chronic state, progressive left ventricle dilatation leads to pre- and afterload mismatch. With gradually decompensation and deterioration of systolic function, the ventricle is not able to sustain perfusion. Causes of chronic aortic regurgitation Aortic root/annular dilation Congenital bicuspid valve Previous infective endocarditis Rheumatic In association with other diseases Clinical presentation Patients with aortic regurgitation typically present with symptoms of left sided heart failure including dyspnea on exertion, orthopnea, fatigue, and occasionally paroxysmal nocturnal dyspnea. Angina is less common in patients with aortic regurgitation compared to aortic stenosis. The reduced aortic diastolic blood pressure reduces the coronary blood flow, resulting in angina. The same mechanism is presumed to cause syncope. Diagnostics Chest Radiography Chest Radiography in acute aortic regurgitation reveals minimal cardiac enlargement, with normal aortic root and arch. In acute aortic regurgitation, signs of left heart failure are frequent. Cardiomegaly with left ventricular enlargement is the main feature on chest radiography in chronic aorta regurgitation. The ascending aorta may be enlarged in case of an aortic aneurysm or aortic dissection but Chest X-ray is not a sensitive examination to detect ascending aortic aneurysm. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 19/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Pulmonary congestion is noted at advanced stages of chronic AR, when heart failure has developed. Electrocardiography Electrocardiography in patients with aortic regurgitation may be normal early in the disease. Left ventricular hypertrophy is the main feature of aortic regurgitation, with or without associated repolarization abnormalities. Left axis deviation may be present. Echocardiography Echocardiography is used to evaluate the anatomy of the aortic valve and other valves, as well as aortic leaflets and the aortic root. The regurgitation mechanism and aetiology can be assessed. Three types of mechanisms can be identified; enlargement of aortic root with normal cusps, cusp prolapse or fenestration and poor cusp tissue quality or quantity. Doppler is used for quantifying the aortic regurgitation by the width of regurgitant jet and its extension into the LV, the rate of decline of aortic regurgitant flow and diastolic flow reversal in the descending aorta. Severe aortic regurgitation is defined as effective regurgitant orifice (ERO) area of >0.30cm2, regurgitant volume >60mL, or a regurgitant fraction of >50% Preoperatively transoesophageal echocardiography is performed to more accurately evaluate the anatomy and mechanism of the aortic valve regurgitation Treatment The only direct method to reduce aortic regurgitation is surgical treatment. However, some patients may benefit from medical treatment. Medical treatment The relative reduction of myocardial blood supply due to increased demand and/or associated obstructive coronary artery disease may cause angina. Angina may be treated by reducing aortic regurgitation, reduction of myocardial demand of revascularization of the myocardium. Clinical heart failure is treated with traditional therapy, including digitalis, diuretics, and ACEI. In severe heart failure, parenteral inotropic and vasodilator therapy may be needed. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 20/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Current Guidelines: Medical treatment of Aortic Regurgitation Class I Vasodilator therapy is indicated for chronic therapy in patients with severe AR who have symptoms or LV dysfunction when surgery is not recommended because of additional cardiac or noncardiac factors. (Level of Evidence: B) Class IIa the Vasodilator hemodynamic profile of patients with severe heart failure symptoms and severe LV dysfunction before proceeding with AVR. (Level of Evidence: C) therapy is reasonable for short-term therapy to improve Class IIb Vasodilator therapy may be considered for long-term therapy in asymptomatic patients with severe AR who have LV dilatation but normal systolic function. (Level of Evidence: B) Class III 1. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with mild to moderate AR and normal LV systolic function. (Level of Evidence: B) 2. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with LV systolic dysfunction who are otherwise candidates for AVR. (Level of Evidence: C) 3. Vasodilator therapy is not indicated for long-term therapy in symptomatic patients with either normal LV function or mild to moderate LV systolic dysfunction who are otherwise candidates for AVR. (Level of Evidence: C) Surgical treatment Surgical treatment in case of isolated Aortic valve regurgitation is aortic valve replacement. Aortic valve replacement is indicated in all symptomatic patients with severe Aortic regurgitation and in all asymptomatic patients with severe Aortic regurgitation with left ventricular ejection fraction (LVEF) <50% or left ventricular dilatation (end-diastolic diameter >75 mm or end-systolic diameter >55 mm). When an aneurysm of the aortic root is associated with severe aortic regurgitation a Bentall procedure can be indicated. The ascending aorta is replacement by a composite graft comprising an aortic prosthesis, with re-implantation of the coronary arteries. When aortic enlargement is localized in the supra-coronary part of ascending aorta, replacing the supra-coronary section of the ascending aorta may be sufficient which is considered technically easier. Although the prosthetic valve replacement remains the standard for aortic valve regurgitation, aortic valve repair procedures are performed with a combination of different surgical techniques. The quality of the cusps is essential for repair. The annulus and sinotubular junction can be surgically readapted to the cusps, eliminating the regurgitation. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 21/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Current Guidelines Class I 1. An adolescent or young adult with chronic severe AR* with onset of symptoms of angina, syncope, or dyspnea on exertion should receive aortic valve repair or replacement. (Level of Evidence: C) 2. Asymptomatic adolescent or young adult patients with chronic severe AR* with LV systolic dysfunction (ejection fraction less than 0.50) on serial studies 1 to 3 months apart should receive aortic valve repair or replacement. (Level of Evidence: C) 3. Asymptomatic adolescent or young adult patients with chronic severe AR* with progressive LV enlargement (end-diastolic dimension greater than 4 standard deviations above normal) should receive aortic valve repair or replacement. (Level of Evidence: C) 4. Coronary angiography is recommended before AVR in adolescent or young adult patients with AR in whom a pulmonary autograft (Ross operation) is contemplated when the origin of the coronary arteries has not been identified by noninvasive techniques. (Level of Evidence: C) Class IIb 1. An asymptomatic adolescent with chronic severe AR* with moderate AS (peak LV to peak aortic gradient greater than 40 mm Hg at cardiac catheterization) may be considered for aortic valve repair or replacement. (Level of Evidence: C) 2. An asymptomatic adolescent with chronic severe AR* with onset of ST depression or T-wave inversion over the left precordium on ECG at rest may be considered for aortic valve repair or replacement. (Level of Evidence: C) Mitral Stenosis Etiology and pathology The leading cause of mitral stenosis is rheumatic fever, causing postrheumatic deformities. Other rare aetiologies of left atrial outflow obstruction include congenital and degenerative mitral valve stenosis, severe mitral annular and/or leaflet calcification carcinoid disease, neoplasm, left atrial thrombus, infective endocarditis with large vegetations, certain inherited metabolic disorders such as Fabry s disease, mucopolysaccharidosis, Whipple s disease, gout, rheumatic arthritis, lupus erythematosus, methysergide therapy, and cases related to previous implanted prosthesis or commisurotomy. Rheumatic valvular disease causes diffuse thickening of the valve leaflets by fibrous, or fibrocalcific distortion, with fusion of one or more commisures valve commisures, and fusion and shortening of the subvalvular apparatus. This combined with increasingly rigid cusps results in narrowing of the valve. The area of the normal mitral valve orifice is 4-6 cm2. In patients with mitral stenosis, when the valve area approaches 2 cm2 or less, an early, mid and late diastolic transvalvular gradient is present between the left atrium and ventricle. With progressive mitral stenosis, transvalvular pressure gradient increases. Mitral transvalvular flow depends on cardiac output and heart rate. Shortening of diastolic phase in increased heart rate causes symptoms by reducing forward cardiac output. Mitral stenosis develops gradually, and may be asymptomatic for years. Clinical presentation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 22/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Patients with mitral stenosis may be asymptomatic for years. Mean age of presentation of symptoms is fifty to sixty years old. The presenting symptom in patients with mild mitral stenosis is typically dyspnea precipitated by stress or atrial fibrillation. Progression of disease with increasing left atrial and pulmonary venous pressures will cause progressive dyspnea. At advanced stage, patients are often thin and frail and complain of weakness and fatigue due to low cardiac output. When pulmonary hypertension and right ventricular failure develop, signs of tricuspid regurgitation, abdominal discomfort due to hepatomegaly and ascites can be present. On physical examination, heart size is usually normal. An apical diastolic thrill can be palpated. A holodiastolic murmur can be auscultated at the apex with a presystolic accentuation in sinus rhythm. The intensity of this murmur is determined by the transmitral gradient. In patients with severe stenosis, calcified leaflets, or low cardiac output no diastolic murmur may be audible. An opining snap may be present due to sudden tensing of the pliable leaflets during opening. S1 may be loud when the mitral leaflets are pliable. Thickening and calcification will diminish S1 in more advanced stages. With pulmonary hypertension, S2 becomes prominent and a murmur of tricuspid regurgitation located at the xyphoid can be present. In severe mitral valve stenosis with pulmonary hypertension, pulmonary rales are audible. Intermittent malar flushes, jugular distension, and peripheral cyanosis may be present Diagnostics Chest Radiography Signs of left atrial enlargement are often the earliest changes on chest radiography. Straightening of the left heart border by prominent pulmonary arteries coupled with left atrial enlargement can be observed as well as a double contour of the left atrium and elevation of the left main stem bronchus. Distension of the pulmonary arteries and veins in the upper lung fields and pleural effusions indicate elevated pulmonary pressures. Kerley B lines may be observed in severe mitral stenosis. Electrocardiography Electrocardiography is in many cases normal and cannot asses the severity of mitral stenosis accurately. Atrial arrhythmias are more common in patients with advanced mitral stenosis. In sinus rythm signs of left atrial enlargement may be present with a prolonged P wave and a negative deflection in lead V1 and left axial deviation of P wave. Signs of right ventricular hypertrophy with right-axis deviation, a tall R wave in V1, and secondary ST-T-wave changes may be present in cases of severe pulmonary hypertension Echocardiography The primary diagnostic method for assessing mitral valve pathology and pathophysiology is echocardiography. The severity and consequences of the mitral stenosis can be evaluated. The valvular anatomy and morphology including valve thickening, mobility, calcification, subvalvular deformity and anatomic lesions can be assessed Rheumatic mitral stenosis can cause reduced diastolic excursion of the leaflets and thickening or calcification of the valvular and subvalvular apparatus. Doppler is used to determine the peak and mean transvalvular pressure gradients. The valve area can be measured accurately by three-dimensional https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 23/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology echocardiogram. Transesophageal echocardiography is able to provide more detailed information of the mitral valvular pathology than transthoracic echocardiography. Cardiac Catheterization Cardiac catheterization can provide information regarding coronary artery status. This diagnostic tool is not necessary to establish the diagnosis of mitral stenosis. Prognosis The progression of mitral stenosis ranges from 0.1 0.3cm2/year.[39] Survival rates of 80% at 10 years have been reported with asymptomatic mitral valve stenosis. Once symptoms develop related to pulmonary hypertension 10-year survival is 0 15%. Progressive heart failure is the most common cause death in the untreated patients with mitral stenosis. Treatment Medical treatment No medical treatments will relief mitral stenosis. Dyspnea may be transiently relieved by diuretics or long acting nitrates. In order to slow the heart rate, Beta-blockers or calcium-channel blockers can be prescribed. Patients with atrial fibrillation should be on anticoagulants with a target INR of 2-3. In patients with severe mitral stenosis, cardioversion should not be performed prior to intervention since it does not durably restore sinus rhythm. After successful intervention cardioversion is indicated if atrial fibrillation is of recent onset and the left atrium only moderately enlarged. Percutaneous mitral commissurotomy Mitral stenosis can be relieved by percutaneous mitral commisurotomy. This procedure was introduced in 1980 and used worldwide ever since [40][41]. The results of balloon valvotomy are comparable to open commissurotomy.[42] The commissural splitting of percutaneous mitral commissurotomy substantially increases the valvular area. Pulmonary pressures decrease immediately. Procedural mortality has been reported 0 3%. In 2- 10% leaflet tearing results in severe mitral regurgitation. Preprocedural condition of the patients and the experience of the operator and operating team are of major influence on the complication rate of percutaneous mitral commissurotomy. Longterm results of a successful procedure have been reported with event-free survival ranges from 35 70% after 10 15 years. Surgical intervention Open commissurotomy or valve replacement is indicated if balloon valvotomy is unfeasible. The concept of surgical repair of the mitral valve was first introduced in 1902 by Sir Thomas Lauder Brunton, a Scottish physician.( Brunton L, Edin MD: Preliminary note on the possibility of treating mitral stenosis by surgical methods. Lancet 1902; 1:352[43]). The first successful mitral valve operation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 24/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology was a transventricular commissurotomy by Elliot Cutler in 1923. The following transventricular valvultomies performed with the cardiovalvulotome resulted in regurgitation and Cutler abandoned the procedure. In 1948, Dwight Harken reported his series of patients with mitral stenosis successfully treated with a valvuloplasty procedure.[44] After development of cardiopulmonary bypass, the closed commissurotomy has been replaced by an open mitral commissurotomy. This allows not only correction of commissural fusion, but also chordal and papillary fusion. Surgical intervention can improve the functional capacity and long-term survival of patients with mitral stenosis substantially. Survival rates of 96% and freedom from valve-related complications of 92% at 15 years have been reported.[45] Surgery should be performed before New York Heart Association (NYHA) class III symptoms are present. Mitral regurgitation Mitral valve regurgitation results from inadequate mitral leaflet coaptation during systole. This allows the systolic regurgitation of blood from the high-pressure LV to the normally low-pressure LA. The regurgitating volume depends on both the size of the regurgitant orifice and the pressure gradient between the left ventricle and the left atrium. In primary mitral regurgitation, inadequate mitral leaflet coaptation results from an abnormality in any of the functional components of the mitral apparatus. Secondary or functional mitral regurgitation results from left ventricle disease and remodeling. During systole, combined papillary muscle contraction and contraction of the dynamic annulus promote leaflet coaptation. Calcification of the annulus may hinder the sphincter-like contraction of the annulus allowing regurgitation. Secondary mitral regurgitation due to annulus dilation may be caused by ischemic or dilated cardiomyopathy. The regurgitant volume causes left ventricular enlargement and contractile dysfunction. Left ventricle dilation may cause enlargement of the mitral annulus and the regurgitant orifice, increasing the mitral regurgitation. Positive inotropes, diuretics and vasodilators reduce the size of the left ventricle and the regurgitant orifice, and decrease the regurgitant flow. Etiology Three different types of primary mitral regurgitation can be defined; leaflet retraction from fibrosis and calcification, annular dilatation and chordal abnormalities (including rupture, elongation, or shortening). Functional mitral regurgitation results from LV dysfunction with or without annular dilation. Mitral regurgitation was classified by Carpentier into three types based on leaflet and chordal motion: normal leaflet motion (type I), leaflet prolapse or excessive motion (type II), and restricted leaflet motion (type III).[46] Chronic mitral valve regurgitation Degenerative mitral valve disease is the most common cause of mitral regurgitation in Europe. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 25/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Myxomatous mitral valve degeneration is also known as floppy mitral valve or mitral valve prolapse. Prolapse is defined as excursion of one or both leaflets above the plane of the annulus during systole.[47] Prolapse of the middle portion of the posterior leaflet is the most common finding in degenerative MR. [48] Mitral regurgitation in Barlow syndrome or parachute mitral valve is due to annular dilatation and extensive hooding of leaflets with large amounts of excessive leaflet tissue. In mitral regurgitation, the mass-to-volume ratio of the enlarged, thin walled left ventricle is less than one.[38] Clinical Presentation Patients with mild to moderate compensated chronic mitral regurgitation may remain asymptomatic for many years. The adapted left ventricle maintains normal forward cardiac output. The left ventricle ejection fraction in chronic mitral regurgitation may be greater than normal due to the compensatory cardiac adaptations. Progression of severity depends on etiology of regurgitation; in patients with connective tissue disease regurgitation tends to progress more rapidly than patients with mitral valve prolapse or rheumatic mitral regurgitation. Progression in acute rheumatic fever is often rapid. Acute progression may by caused by endocarditis or chordae rupture. Gradual progression and eventually decompensation results in decreased cardiac output with physical activity and pulmonary congestion. Patients present with weakness, fatigue, palpitations, dyspnea on exertion. Hepatomegaly, peripheral edema and ascites due to right sided heart failure can be associated with rapid clinical deterioration. Acute mitral regurgitation is associated with sudden pulmonary congestion and edema. On physical examination the apical impulse is displaced laterally, indicating left ventricular enlargement. S1 is normal or diminished. S2 may be single, closely split, normally split, or even widely split as a consequence of the reduced resistance to LV ejection. A widely split S2 is often audible, due to shortening of LV systole and early closure of the aortic valve. The P2 component of the second heart sound may be increased if pulmonary hypertension has developed. The apical systolic murmur is typically holosystolic and radiates to the axilla, depending on the direction of the regurgitant jet. It can be blowing, moderately harsh, or even soft. An S3 gallop often is present, reflecting the transmitral diastolic flow during the rapid filling phase. Early in the disease process of patients with Barlow syndrome, a characteristic midsystolic click can be appreciated, followed by a late systolic murmur; with disease progression the murmur becomes holosystolic, and the midsystolic click may become inaudible.[46] Acute mitral regurgitation Immediate intervention is often necessary in acute mitral regurgitation. Etiology can be organic or functional. Organic causes include rupture of a major chorda tendinea (in myxomatous mitral valve disease) or papillary muscle (due to myocardial infarction), leaflet perforation (of endocarditic origin), and dysfunction of a prosthetic valve due to endocarditis or paravalvular regurgitation. Regurgitation of functional etiology results from left ventricular abnormalities such as dyskinetic wall due to ischemia or dilated ventricle due to cardiomyopathy. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 26/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Acute mitral regurgitation is associated with dyspnea and orthopnea, caused by sudden pulmonary congestion and edema. Acute papillary muscle rupture may mimic the presentation of a patient with a postinfarction ventricular septal defect.[49] On physical examination no signs of cardiac compensatory mechanisms are present. The increase in left atrial pressure diminishes the pressure gradient between the left ventricle and left atrium by midsystole. The murmur of mitral regurgitation is shortened and of decreased intensity, it may be soft, short of even inaudible. An S3 gallop usually is present. The volume overload is increasing the severity of MR over time, and leads to a greater percentage of the LV stroke volume being ejected in a retrograde fashion. Diagnostic Options Chest Radiography In chronic mitral regurgitation chest radiography demonstrates enlargement of the left ventricle and atrium. The mitral annulus may be calcified. In acute mitral regurgitation, no adaptive left atrium or ventricle enlargement has developed. Signs of interstitial or alveolar pulmonary edema may be present. Electrocardiography Signs of left ventricular hypertrophy and left atrial enlargement due to chronic volume overload may be seen on the electrocardiogram. Atrial fibrillation is a common finding late in the natural history of the disease. Q-waves may be seen in ischemic mitral regurgitation. In patients with acute mitral regurgitation, left atrial and ventricular enlargement may not be evident and the electrocardiogram may be normal or show only nonspecific findings. The resting electrocardiogram of patients with asymptomatic mitral valve prolaps is normal. A variety of ST-T-wave changes, including T-wave inversion and sometimes ST-segment depression, particularly in the inferior leads, can be found in patients with symptomatic mitral valve prolapse. Echocardiography Mitral valve pathology and pathophysiology is primary assessed by echocardiography. Left atrial and ventricular dimensions can be quantified. The etiology and mechanism of mitral regurgitation can be identified by echocardiography. Leaflet abnormalities and chordal morphology and function is assessed by echocardiography. Fused subvalvular apparatus due to rheumatic valvulitis and leaflet destruction due to endocarditis can be visualized by echocardiography. Myxoid degeneration of the mitral valve is characterized by an excess of tissue and by leaflets of more than 5mm thickness. Annular dilatation is characterized by a ratio of >1.3 anterior posterior diameter of the annulus to the length of the anterior leaflet in diastole. The regurgitation caused by annular dilatation and incomplete leaflet coaptation is directed straight back into the left atrium. In ischaemic MR, the apical displacement of the leaflets can be quantified by measuring the tenting area and the leaflet opening angles. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 27/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Color doppler analysis can be used to grade the severity of the regurgitation and permits visualization of the origin, extent, direction, duration, and velocity of disturbed backward flow of the regurgitant leak or leaks into the left atrium.[46] MR is considered severe when the jet area is >10cm2 or >40% of the left atrial area. Cardiac Catheterization Coronary ischemic causes of mitral regurgitation can be identified by cardiac catheterization. Treatment Surgical The hemodynamic overload on the heart caused by mitral regurgitation can ultimately only be corrected by surgically restoring valve competence. For all valve surgery timing of surgery is essential. Irreversible left ventricular dysfunction will result in suboptimal results indelayed surgery. Due to the operative risk and risk of valve prosthesis surgery should however be delayed as long as possible Mitral valve regurgitation is surgically corrected by mitral valve replacement or repair. Mitral valve repair is generally found to be superior to replacement, with preservation of left ventricular function and part of the mitral valve apparatus [50] [51] [52] [53] and without the use of a prosthesis. In mitral valve regurgitation indication for valve surgery is influenced by symptomatic status, ventricular functional status, and the procedure to be performed. Repair might be considered in asymptomatic patients with normal left ventricular function or patients with severe impairment of left ventricular function who might not be candidates for mitral valve replacement. For most patients, mitral valve surgery is performed for the relief of symptoms or to prevent worsening of asymptomatic left ventricular dysfunction. Tricuspid stenosis Tricuspid stenosis (TS) is most commonly of rheumatic origin and combined with tricuspid regurgitation. The anatomical characteristics are similar to those of mitral stenosis, including fibrous leaflet thickening and fusion and shortening of the subvalvular apparatus. The preponderance of cases is in young women. Other aetiologies of right atrial obstruction are rare and include congenital tricuspid atresia, right atrial tumors and carcinoid syndrome The normal valve area of the tricuspid valve is 7 8cm2. Reduction of valve area to <2 cm2 causes a pressure gradient. A small diastolic pressure gradient (<5 mmHg), gradient between the right atrium and ventricle can be present due to tricuspid stenosis. The gradient is increasing on inspiration. A mean pressure gradient >5mmHg is considered indicative of significant TS and is usually associated with symptoms Clinical presentation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 28/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology A tricuspid opening snap and a characteristic mid-diastolic murmur may be audible along the left sternoid border on auscultation. Carvallo s sign, an increase of murmur intensity on inspiration, may be present. Distention of jugular veins, ascites, pleural effusion and peripheral edema may be present due to increased right atrial pressures. Reduced cardiac output causes symptoms of fatigue and malaise. The pulmonary congestion of mitral stenosis may be masked in severe tricuspid stenosis. Diagnostic Options Chest radiography Cardiomegaly with an increase in right atria and pulmonary artery size is demonstrated on chest radiography. Electrocardiography An increased P-wave amplitude is seen on the electrocardiogram if the patient is in normal sinus rhythm. Echocardiography |
Early in the disease process of patients with Barlow syndrome, a characteristic midsystolic click can be appreciated, followed by a late systolic murmur; with disease progression the murmur becomes holosystolic, and the midsystolic click may become inaudible.[46] Acute mitral regurgitation Immediate intervention is often necessary in acute mitral regurgitation. Etiology can be organic or functional. Organic causes include rupture of a major chorda tendinea (in myxomatous mitral valve disease) or papillary muscle (due to myocardial infarction), leaflet perforation (of endocarditic origin), and dysfunction of a prosthetic valve due to endocarditis or paravalvular regurgitation. Regurgitation of functional etiology results from left ventricular abnormalities such as dyskinetic wall due to ischemia or dilated ventricle due to cardiomyopathy. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 26/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Acute mitral regurgitation is associated with dyspnea and orthopnea, caused by sudden pulmonary congestion and edema. Acute papillary muscle rupture may mimic the presentation of a patient with a postinfarction ventricular septal defect.[49] On physical examination no signs of cardiac compensatory mechanisms are present. The increase in left atrial pressure diminishes the pressure gradient between the left ventricle and left atrium by midsystole. The murmur of mitral regurgitation is shortened and of decreased intensity, it may be soft, short of even inaudible. An S3 gallop usually is present. The volume overload is increasing the severity of MR over time, and leads to a greater percentage of the LV stroke volume being ejected in a retrograde fashion. Diagnostic Options Chest Radiography In chronic mitral regurgitation chest radiography demonstrates enlargement of the left ventricle and atrium. The mitral annulus may be calcified. In acute mitral regurgitation, no adaptive left atrium or ventricle enlargement has developed. Signs of interstitial or alveolar pulmonary edema may be present. Electrocardiography Signs of left ventricular hypertrophy and left atrial enlargement due to chronic volume overload may be seen on the electrocardiogram. Atrial fibrillation is a common finding late in the natural history of the disease. Q-waves may be seen in ischemic mitral regurgitation. In patients with acute mitral regurgitation, left atrial and ventricular enlargement may not be evident and the electrocardiogram may be normal or show only nonspecific findings. The resting electrocardiogram of patients with asymptomatic mitral valve prolaps is normal. A variety of ST-T-wave changes, including T-wave inversion and sometimes ST-segment depression, particularly in the inferior leads, can be found in patients with symptomatic mitral valve prolapse. Echocardiography Mitral valve pathology and pathophysiology is primary assessed by echocardiography. Left atrial and ventricular dimensions can be quantified. The etiology and mechanism of mitral regurgitation can be identified by echocardiography. Leaflet abnormalities and chordal morphology and function is assessed by echocardiography. Fused subvalvular apparatus due to rheumatic valvulitis and leaflet destruction due to endocarditis can be visualized by echocardiography. Myxoid degeneration of the mitral valve is characterized by an excess of tissue and by leaflets of more than 5mm thickness. Annular dilatation is characterized by a ratio of >1.3 anterior posterior diameter of the annulus to the length of the anterior leaflet in diastole. The regurgitation caused by annular dilatation and incomplete leaflet coaptation is directed straight back into the left atrium. In ischaemic MR, the apical displacement of the leaflets can be quantified by measuring the tenting area and the leaflet opening angles. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 27/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Color doppler analysis can be used to grade the severity of the regurgitation and permits visualization of the origin, extent, direction, duration, and velocity of disturbed backward flow of the regurgitant leak or leaks into the left atrium.[46] MR is considered severe when the jet area is >10cm2 or >40% of the left atrial area. Cardiac Catheterization Coronary ischemic causes of mitral regurgitation can be identified by cardiac catheterization. Treatment Surgical The hemodynamic overload on the heart caused by mitral regurgitation can ultimately only be corrected by surgically restoring valve competence. For all valve surgery timing of surgery is essential. Irreversible left ventricular dysfunction will result in suboptimal results indelayed surgery. Due to the operative risk and risk of valve prosthesis surgery should however be delayed as long as possible Mitral valve regurgitation is surgically corrected by mitral valve replacement or repair. Mitral valve repair is generally found to be superior to replacement, with preservation of left ventricular function and part of the mitral valve apparatus [50] [51] [52] [53] and without the use of a prosthesis. In mitral valve regurgitation indication for valve surgery is influenced by symptomatic status, ventricular functional status, and the procedure to be performed. Repair might be considered in asymptomatic patients with normal left ventricular function or patients with severe impairment of left ventricular function who might not be candidates for mitral valve replacement. For most patients, mitral valve surgery is performed for the relief of symptoms or to prevent worsening of asymptomatic left ventricular dysfunction. Tricuspid stenosis Tricuspid stenosis (TS) is most commonly of rheumatic origin and combined with tricuspid regurgitation. The anatomical characteristics are similar to those of mitral stenosis, including fibrous leaflet thickening and fusion and shortening of the subvalvular apparatus. The preponderance of cases is in young women. Other aetiologies of right atrial obstruction are rare and include congenital tricuspid atresia, right atrial tumors and carcinoid syndrome The normal valve area of the tricuspid valve is 7 8cm2. Reduction of valve area to <2 cm2 causes a pressure gradient. A small diastolic pressure gradient (<5 mmHg), gradient between the right atrium and ventricle can be present due to tricuspid stenosis. The gradient is increasing on inspiration. A mean pressure gradient >5mmHg is considered indicative of significant TS and is usually associated with symptoms Clinical presentation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 28/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology A tricuspid opening snap and a characteristic mid-diastolic murmur may be audible along the left sternoid border on auscultation. Carvallo s sign, an increase of murmur intensity on inspiration, may be present. Distention of jugular veins, ascites, pleural effusion and peripheral edema may be present due to increased right atrial pressures. Reduced cardiac output causes symptoms of fatigue and malaise. The pulmonary congestion of mitral stenosis may be masked in severe tricuspid stenosis. Diagnostic Options Chest radiography Cardiomegaly with an increase in right atria and pulmonary artery size is demonstrated on chest radiography. Electrocardiography An increased P-wave amplitude is seen on the electrocardiogram if the patient is in normal sinus rhythm. Echocardiography The tricuspid valve structure and function is commonly assessed by echocardiography. The annular size can be measured and the right pressures can be evaluated. Tricuspid stenosis due to rheumatic disease is characterized by leaflet thickening with reduced motion and frequent commissural fusion. The chordae are shortened and thickened, and diastolic doming is present. Carcinoid syndrome is characterized by retraction of leaflets towards the apex during systole. A prolonged slope of antegrade flow across the tricuspid valve can be seen on Doppler. Tricuspid stenosis is considered severe when the mean transvalvular gradient is >5 mmHg. Treatment The therapeutic approach for tricuspid regurgitation is dictated by the aetiology of the regurgitation and overall condition of the patient. In a limited number of patients percutaneous balloon tricuspid dilatation has been performed. This is a treatment option in cases of isolated and pure tricuspid stenosis, but it frequently induces regurgitation.[54] Tricuspid balloon valvotomy, combining commissurotomy leaflet augmentation and annuloplasty, can be used to treat tricuspid stenosis; however, with this treatment the potential for inducing severe tricuspid regurgitation still exists. A biological prosthesis is preferred in case of tricuspid valve replacement,since it heas satisfactory long-term durability and mechanical prosthesis caries a higher risk of thrombosis. Tricuspid regurgitation https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 29/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Functional tricuspid regurgitation results from distortion of the architecture and coordinated actions of the tricuspid leaflets, annulus, chords, papillary muscles, and right ventricular (RV) wall. This distortion is most commonly caused by right ventricular dilation and dysfunction from left sided heart disease with pressure/volume overload conditions. Pressure volume overload conditions cause enlargement of the tricuspid annulus and the shaddle shape becomes more circular. The normal annular excursion can be reduced by 50% in severe tricuspid regurgitation.[55] Functional tricuspid regurgitation is a marker of poor prognosis in patients with left ventricular cardiomyopathy. Pure tricuspid regurgitation may result from rheumatic fever, infective endocarditis, carcinoid causes, rheumatoid arthritis, radiation therapy, anorectic drugs, trauma, Marfan s syndrome, tricuspid valve prolapse, papillary muscle dysfunction, or congenital disorders. Right ventricular infarction with severe regional wall motion abnormality or disruption of the papillary muscle may cause regurgitation. Right ventricular dilatation with annular enlargement and valvular incompetence can be seen in Eisenmenger syndrome and pulmonary hypertension. Clinical presentation A reduction in cardiac output related to tricuspid regurgitation, may cause symptoms of fatigue and weakness. Right-sided heart failure may cause ascites, congestive hepatosplenomegaly, pulsatile liver, pleural effusions, and peripheral edema. With progression of the disease, patients become cachexic, cyanotic and jaundice may be present. A parasternal pansytolic murmur increasing on inspiration may be appreciated on auscultation(Carvallo s sign). An S3, increasing with inspiration and decreasing with a Valsalva maneuve may be audible, as well as an increased P2 if pulmonary hypertension has developed. Diagnostic options Chest Radiography Cardiomegaly, increased right atrial and ventricular size and a prominent azygous vein can be demonstrated on chest x-ray. Chest Radiography may reveal pleural effusion, and ascites by upward diaphragmatic displacement. Echocardiography The tricuspid valve structure and function can be assessed echocardiographically and specific abnormalities can be identified. Distinction between primary and functional forms of tricuspid regurgitation can be made with echocardiography. The annular size can be measured. This imaging https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 30/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology modality is used to evaluate the degree of regurgitation, pressures and ventricular function. Severe regurgitation is characterized by systolic flow reversal in the hepatic veins and a vena contracta diameter of more than 7 mm. Cardiac catheterization Cardiac catheterization is not necessary to diagnose tricuspid regurgitation. Increased right atrial and right ventricular end-diastolic pressures and the degree of pulmonary artery hypertension can be evaluated by catheterization. Pulmonary artery pressures of over 60 mmHg are usually due to left-sided lesions leading to secondary tricuspid regurgitation. Treatment Treatment strategy for tricuspid regurgitation is dictated by the aetiology and the underlying cause of the disease and the overall condition of the patient. Primary tricuspid regurgitation has a poor prognosis without treatment. Functional tricuspid regurgitation may improve following treatment of its cause. Correction of concomitant mitral regurgitation may worsen tricuspid regurgitation. Risk factors for persistence or worsening of tricuspid regurgitation are reduced right ventricular function and the diameter of tricuspid annulus. Medical When pulmonary hypertension is the underlying cause of tricuspid annular dilation, medical management alone may minimize the need for surgical intervention Surgical Surgical treatment can be recommended for primary tricuspid regurgitation, when there is pulmonary hypertension, important dilatation of the annulus (diameter >40mm or >21mm/m2). Surgical options for tricuspid regurgitation include annuloplasty or valve replacement with a mechanical valve or bioprosthesis. Functional tricuspid regurgitation may be repaired by suture annuloplasty (De Vega procedure) or by ring annuloplasty. Longterm outcomes of ring annuloplasty are superior to those of suture annuloplasty. Annuloplasty can be optimized by the use of intraoperative transesophageal echocardiography. Bioprostheses are generally preferred above mechanical prostheses for the tricuspid position, as mentioned in the section about tricuspid stenosis. Pulmonary valve stenosis Etiology and pathology Pulmonary valve stenosis can be caused congenital, carcinoid and rheumatic disorders or extrinsic compression. The typical domeshaped pulmonary valve stenosis is the most common form of right ventricular outflow tract obstruction. Stenosis is caused by fusion of the pulmonary valve lea ets and a https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 31/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology narrowed central ori ce. The valve is usually mobile and associated with medial abnormalities the valve pulmonary stenosis may be associated with Noonan, Williams, Alagille, Keutel or rubella syndromes.[56] and dilation of trunk. Pulmonary The diagram shows a healthy heart and one suffering from Pulmonary valve stenosis Clinical presentation Most patients with mild to moderate pulmonary valve stenosis are asymptomatic. Severe pulmonary valve stenosis may cause exertional dyspnea and fatigue, chest pain, palpitations and syncope. On physical examination, thrill along the left sternal edge, and a long systolic ejection murmur with late peak may be appreciated. S2 may be widely split with reduced or absent P2. Diagnostic options Chest Radiography Chest radiography may show dilated pulmonary arteries, occasionally with calcification of the pulmonic valve. In case of severe pulmonary valve stenoisis, oligemic lung fields can be seen. Electrocardiography Right ventricular hypertrophy can be seen on electrocardiography as an axis deviation to the right. Right bundle branch block may also be present. Patients with Noonan syndrome invariably have a left bundle branch block. Echocardiography https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 32/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology Transthoracic echocardiography confirms the diagnosis. The level of obstruction, valvular, supravalvular or right ventricular outflow tract, can be identified. Valvular stenosis is characterized by mildly thickened leaflets with restricted systolic excursion. The pressure gradient can be measured. Associated cardiac conditions can be demonstrated with echocardiography. Cardiac catheterization Cardiac catheterization is not necessary to diagnose pulmonic valve stenosis. Hemodynamic consequences and severity of pulmonary valve stenosis can be assessed with cardiac catheterization. Treatment Invasive intervention is recommended in case of symptomatic disease, or when the gradient across the valve is >40 mmHg. Medical Supportive and symptomatic treatment of right ventricular failure is recommended. Surgical The treatment of choice for stenosis at the valvular level is balloon valvuloplasty. Long-term results are satisfactory and the procedure relatively safe. Surgical valvotomy is very effective with minimal recurrence, however significant pulmonary regurgitation may occur. Pulmonary valve replacement is indicated if the patient is not suitable for balloon valvuloplasty or surgical valvotomy. Pulmonary valve regurgitation Etiology and pathology Physiologic pulmonic regurgitation, qualified as trace to mild, is present in nearly all individuals. Pulmonary valve regurgitation can be caused by valvular disease such as infective endocarditis (rarely involves pulmonic valve) or connective tissue disease, carcinoid, congenital heart disease, or it can be secondary to pulmonary hypertension, which causes dilation of the valve ring. Pulmonic regurgitation can result in impairment of right ventricular function and eventual clinical manifestations of right-sided volume overload and heart failure. Clinical presentation Patients are often asymptomatic. Symptoms of right-sided heart failure develop when the severity and duration of the regurgitation results in right ventricular enlargement and decompensation. Symptoms include dyspnea on exertion, light-headedness, lethargy, peripheral edema, chest pain, palpitations, and abdominal pain. Often these symptoms are accepted by the patient and attributed to poor physical https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 33/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology fitness, causing a delay in presentation. The jugular venous pressure is usually increased in pulmonary valve regurgitation. A palpable impulse may be present at the left lower sternal border due to right ventricular enlargement. On auscultation P2 may be delayed due to increased right ventricular end- diastolic volume and increased ejection time with large stroke volume. P2 can be accentuated in case of pulmonary hypertension, The murmur of pulmonary regurgitation is heard best at the third to fourth intercostal space along the left sternal border and increases with inspiration. Diagnostic options Chest Radiography Chest radiography of patients with pulmonic regurgitation with tricuspid regurgitation may demonstrate cardiomegaly and enlargement of the right-sided heart contour. Pure pulmonic regurgitation may to have specific signs on chest radiography. Prominent central pulmonary arteries with enlarged hilar vessels and loss of vascularity in the peripheral lung fields suggest severe pulmonary hypertension. Electrocardiography Signs of right ventricular hypertrophy can be seen on the Electrocardiogram if pulmonary hypertension is present including a tall R wave in V1 or qR in V1, R wave greater than S wave in V1, R wave progression reversal in the precordial leads and Right axis deviation. A right bundle branch block can be present. Echocardiography Echodoppler is the main diagnostic tool for recognizing pulmonic regurgitation. Regurgitant jet and velocity is visualized by Doppler. The width of the regurgitating jet can be used to quantify the severity. Diastolic regurgitation as well as early peak flow velocity in systole suggests the presence of pulmonary hypertension. Echocardiography can reveal right ventricular hypertrophy and dilatation. Right ventricular volume overload is characterized by abnormal septal wall motion. Structural abnormalities of the pulmonic valve or congenital absence of the valve can be demonstrated by echocardiography. Treatment The right ventricle normally adapts to low-pressure volume, high-pressure volume overload in contrast, ultimately leads to heart failure. Determining the underlying cause of pulmonic regurgitation and possible coexisting pulmonary hypertension is essential for appropriate therapy. Treating the cause of pulmonary hypertension can relieve symptoms and decrease the severity of PR If medical management is insufficient, surgical treatment options should be evaluated. The presence of severe right heart failure due to pulmonic regurgitation surgical pulmonic valve reconstruction or replacement can be considered. References 1. Soler-Soler J and Galve E. Worldwide perspective of valve disease. Heart. 2000 Jun;83(6):721-5. DOI:10.1136/heart.83.6.721 | https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 34/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology 2. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, and Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006 Sep 16;368(9540):1005-11. DOI:10.1016/S0140-6736(06)69208-8 | 3. Iung B, Baron G, Tornos P, Gohlke-B rwolf C, Butchart EG, and Vahanian A. Valvular heart disease in the community: a European experience. Curr Probl Cardiol. 2007 Nov;32(11):609-61. DOI:10.1016/j.cpcardiol.2007.07.002 | 4. Burge DJ and DeHoratius RJ. Acute rheumatic fever. Cardiovasc Clin. 1993;23:3-23. 5. Carapetis JR, Currie BJ, and Mathews JD. Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?. Epidemiol Infect. 2000 Apr;124(2):239-44. DOI:10.1017/s0950268800003514 | 6. Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL, Heistad DD, Simmons CA, Masters KS, Mathieu P, O'Brien KD, Schoen FJ, Towler DA, Yoganathan AP, and Otto CM. Calcific aortic valve disease: not simply a degenerative process: A review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: Calcific aortic valve disease-2011 update. Circulation. 2011 Oct 18;124(16):1783-91. DOI:10.1161/CIRCULATIONAHA.110.006767 | 7. Di Mauro M, Gallina S, D'Amico MA, Izzicupo P, Lanuti P, Bascelli A, Di Fonso A, Bartoloni G, Calafiore AM, Di Baldassarre A, and Italian Group of Study for Heart Valve Disease (Italian Society of Cardiology). Functional mitral regurgitation: from normal to pathological anatomy of mitral valve. Int J Cardiol. 2013 Mar 10;163(3):242-248. DOI:10.1016/j.ijcard.2011.11.023 | 8. Muresian H. The clinical anatomy of the mitral valve. Clin Anat. 2009 Jan;22(1):85-98. DOI:10.1002/ca.20692 | 9. Mill M.R., Wilcox B.R., and Anderson R.H. "Surgical Anatomy of the Heart." Cardiac Surgery in the Adult. Ed. Cohn LH. New York: McGraw-Hill, 2012. 29-50. 10. Padera R Fi J r and Schoen F Ji. "Pathology of Cardiac Surgery." Cardiac Surgery in the Adult. Ed. Cohn L.H. New York: McGraw-Hill, 2012. 111-78. 11. Iung B, Baron G, Tornos P, Gohlke-Barwolf C, Butchart EG, Vahanian A. Valvular heart disease in the community: a European experience. Curr Probl Cardiol 2007 November;32(11):609-61. 12. Otto CM, Lind BK, Kitzman DW, Gersh BJ, and Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999 Jul 15;341(3):142-7. DOI:10.1056/NEJM199907153410302 | 13. Otto CM. Calcific aortic stenosis time to look more closely at the valve. N Engl J Med. 2008 Sep 25;359(13):1395-8. DOI:10.1056/NEJMe0807001 | 14. Rajamannan NM, Gersh B, and Bonow RO. Calcific aortic stenosis: from bench to the bedside emerging clinical and cellular concepts. Heart. 2003 Jul;89(7):801-5. DOI:10.1136/heart.89.7.801 | 15. Rajamannan NM. Low-density lipoprotein and aortic stenosis. Heart. 2008 Sep;94(9):1111-2. DOI:10.1136/hrt.2007.130971 | 16. O'Brien KD, Shavelle DM, Caulfield MT, McDonald TO, Olin-Lewis K, Otto CM, and Probstfield JL. Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation. 2002 Oct 22;106(17):2224-30. DOI:10.1161/01.cir.0000035655.45453.d2 | 17. Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, and Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001 Mar 20;103(11):1522-8. DOI:10.1161/01.cir.103.11.1522 | https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 35/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology 18. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, and Otto CM. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997 Mar 1;29(3):630-4. DOI:10.1016/s0735-1097(96)00563-3 | 19. Stritzke J, Linsel-Nitschke P, Markus MR, Mayer B, Lieb W, Luchner A, D ring A, Koenig W, Keil U, Hense HW, Schunkert H, and MONICA/KORA Investigators. Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey. Eur Heart J. 2009 Aug;30(16):2044-53. DOI:10.1093/eurheartj/ehp287 | 20. Otto CM, Burwash IG, Legget ME et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997 May 6;95(9):2262- 70. 21. Brener SJ, Duffy CI, Thomas JD, and Stewart WJ. Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction. J Am Coll Cardiol. 1995 Feb;25(2):305-10. DOI:10.1016/0735-1097(94)00406-g | 22. Mihaljevic T. et al. "Pathophysiology of Aortic Valve Disease." Cardiac Surgery in the Adult. Ed. Cohn L.H. Third Edition ed. McGraw-Hill Education, 2012. 825-40. 23. Bonow RO, Carabello B, de Leon AC, Edmunds LH Jr, Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O'Gara PT, O'Rourke RA, Rahimtoola SH, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Gibbons RJ, Russell RO, Ryan TJ, and Smith SC Jr. ACC/AHA Guidelines for the Management of Patients With Valvular Heart Disease. Executive Summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Valvular Heart Disease). J Heart Valve Dis. 1998 Nov;7(6):672-707. 24. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, 2006 Writing Committee Members, and American College of Cardiology/American Heart Association Task Force. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008 Oct 7;118(15):e523-661. DOI:10.1161/CIRCULATIONAHA.108.190748 | 25. Stephenson L Wi. "History of Cardiac Surgery." Cardiac Surgery in the Adult. Ed. Cohn L.H. Third Edition ed. New York: McGraw-Hill, 2012. 3-28. 26. Emery R Wi et al. "Aortic Valve Replacement With a Mechanical Cardiac Valve Prosthesis." Cardiac Surgery in the Adult. Ed. Cohn L.H. Third ed. New York: McGraw-Hill, 2012. 841-56. 27. Chaikof EL. The development of prosthetic heart valves lessons in form and function. N Engl J Med. 2007 Oct 4;357(14):1368-71. DOI:10.1056/NEJMp078175 | 28. Vitale N, De Feo M, De Siena P, Cappabianca G, Onorati F, Gregorio R, Branzoli S, de Luca L, Schinosa T, Vigan M, Scardone M, and Cotrufo M. Tilting-disc versus bileaflet mechanical prostheses in the aortic position: a multicenter evaluation. J Heart Valve Dis. 2004 May;13 Suppl 1:S27-34. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 36/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology 29. Cribier A, Eltchaninoff H, Bash A et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation 2002 December 10;106(24):3006-8. 30. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, and Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation. 2002 Aug 20;106(8):900-4. DOI:10.1161/01.cir.0000027905.26586.e8 | 31. Nishimura RA, Carabello BA, Faxon DP, Freed MD, Lytle BW, O'Gara PT, O'Rourke RA, and Shah PM. ACC/AHA 2008 Guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Aug 19;52(8):676-85. DOI:10.1016/j.jacc.2008.05.008 | 32. Tzemos N, Therrien J, Yip J, Thanassoulis G, Tremblay S, Jamorski MT, Webb GD, and Siu SC. Outcomes in adults with bicuspid aortic valves. JAMA. 2008 Sep 17;300(11):1317-25. DOI:10.1001/jama.300.11.1317 | 33. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS, and American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. DOI:10.1016/j.jacc.2008.05.007 | 34. Siu SC and Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010 Jun 22;55(25):2789-800. DOI:10.1016/j.jacc.2009.12.068 | 35. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, Del Nido P, Fasules JW, Graham TP Jr, Hijazi ZM, Hunt SA, King ME, Landzberg MJ, Miner PD, Radford MJ, Walsh EP, and Webb GD. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Dec 2;52(23):e143-e263. DOI:10.1016/j.jacc.2008.10.001 | 36. Thanassoulis G, Yip JW, Filion K, Jamorski M, Webb G, Siu SC, and Therrien J. Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves. Nat Clin Pract Cardiovasc Med. 2008 Dec;5(12):821-8. DOI:10.1038/ncpcardio1369 | 37. Michelena HI, Desjardins VA, Avierinos JF, Russo A, Nkomo VT, Sundt TM, Pellikka PA, Tajik AJ, and Enriquez-Sarano M. Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community. Circulation. 2008 May 27;117(21):2776-84. DOI:10.1161/CIRCULATIONAHA.107.740878 | 38. Feiring AJ and Rumberger JA. Ultrafast computed tomography analysis of regional radius-to-wall thickness ratios in normal and volume-overloaded human left ventricle. Circulation. 1992 Apr;85(4):1423-32. DOI:10.1161/01.cir.85.4.1423 | 39. Alec Vahanian, Bernard Iung, Luc Pi rard, Robert Dion, John Pepper. Valvular Heart Disease . In: A.JOHN CAMM, THOMAS F.LUSCHER, PATRICK W.SERRUYS, editors. The ESC Textbook of Cardiovascular Medicine. third ed. Oxford University Press; 2012. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 37/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology 40. Vahanian A, Cormier B, Iung B. Mitral valvuloplasty. In: Topol, editor. Textbook of Interventional Cardiology. 5th ed. Philadelphia: Saunders Elsevier; 2012. p. 879-93. 41. Chen CR, Cheng TO. Percutaneous balloon mitral valvuloplasty by the Inoue technique: a multicenter study of 4832 patients in China. Am Heart J 1995 June;129(6):1197-203. 42. Reyes VP, Raju BS, Wynne J et al. Percutaneous balloon valvuloplasty compared with open surgical commissurotomy for mitral stenosis. N Engl J Med 1994 October 13;331(15):961-7. 43. Chen F Y, Cohn LH. Mitral Valve Repair. In: Cohn LH, editor. Cardiac surgery in the adult. Third ed. New York: McGraw-Hill; 2012. p. 1013-30. 44. HARKEN DE, ELLIS LB, . The surgical treatment of mitral stenosis; valvuloplasty. 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Zalaquett R, Scheu M, Campl C, Mor n S, Irarr zaval MJ, Becker P, Arretz C, C rdova S, Braun S, Chamorro G, and Godoy I. [Long-term results of repair versus replacement for degenerative mitral https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 38/39 7/4/23, 12:36 AM Valvular Heart Disease - Textbook of Cardiology valve regurgitation]. Rev Med Chil. 2005 Oct;133(10):1139-46. DOI:10.4067/s0034- 98872005001000002 | 54. Vahanian A, Palacios IF. Percutaneous approaches to valvular disease. Circulation 2004 April 6;109(13):1572-9. 55. Fukuda S, Saracino G, Matsumura Y, Daimon M, Tran H, Greenberg NL, Hozumi T, Yoshikawa J, Thomas JD, and Shiota T. Three-dimensional geometry of the tricuspid annulus in healthy subjects and in patients with functional tricuspid regurgitation: a real-time, 3-dimensional echocardiographic study. Circulation. 2006 Jul 4;114(1 Suppl):I492-8. DOI:10.1161/CIRCULATIONAHA.105.000257 | 56. Elisabeth B dard, Michael A Gatzoulis. Adult congenital heart disease. In: S.Yusuf JACAJCELFaBJG, editor. evidence based cardiology. third ed. 2012. 57. Retrieved from "http://www.textbookofcardiology.org/index.php?title=Valvular_Heart_Disease&oldid=2566" This page was last edited on 11 January 2021, at 20:05. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Valvular_Heart_Disease 39/39 |
7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Women's Heart Health https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 1/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Dr. Janneke Wittekoek - Version 1 Contents Facts & Figures Epidemiology Gender Differences in the Pathofysiology of Atherosclerosis Atheroma burden and vascular function Microvascular angina pectoris Syndrome X Risk Factors Smoking Hypertension Dyslipidemia Obesity Diabetes Women specific risk factors Novel risk factors Depression & Acute stress Risk Factor Assessment Which risk factors should be assessed? Other important information to establish: Additional parameters to consider are: Which patients can be managed for global cardiovascular risk by a menopause physician? Clinical Presentation Treatment Smoking: TARGET: permanently stop smoking all forms of tobacco Diet: TARGET: Adopt healthy diet Physical Fitness: TARGET: Undertake regular physical exercise Obesity: TARGET: Body Mass Index < 25 kg.m2 or waist circumference < 88 Lipids (table 3) Bloodpressure (table 4) Post-menopausal hormone therapy Conclusions Case 1: Case 2: References Facts & Figures Epidemiology https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 2/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Cardiovascular disease (CVD) is the leading cause of death in women worldwide. According to the Global Burden of disease CVD caused almost 32% of deaths in women worldwide vs. 27% in men.[1] In Europe 54% of all female deaths are from CVD vs. 43% men.[2] After at least two decades of growing awareness regarding sex differences in coronary artery disease, the evolving knowledge of the clinical consequences is emerging. Although recent reports document decreases in CHD mortality for women, reductions lag behind those realized for men.[3] Another worrying fact is that we see a mortality increase among younger women.[4] In general cardiovascular events among women appear approximately 7-10 years later in women than in men. The lower incidence of CVD in premenopausal women compared with men of similar age and the menopause associated increase in CVD have long suggested that estrogens underlie a protective effect on the cardiovascular system for women. It is known that estrogens improve the arterial wall response to injury and inhibit the development of atherosclerosis by promoting re-endotheliazation, inhibiting smooth muscle cell proliferation, and matrix deposition following vascular injury.[5] Estrogens also decrease systemic vascular resistance, improve coronary and peripheral endothelial function and prevent coronary artery spasm in women with and without atherosclerosis. Pre- menopausal women with hormonal imbalances and estrogen deficiencies have a higher risk of developing premature atherosclerosis.[6] Gender Differences in the Pathofysiology of Atherosclerosis Atheroma burden and vascular function There is emerging evidence that there are gender- differences in the atherosclerotic process and the mechanisms underlying ischemic heart disease. Recent data support a sex-specific role for microvascular dysfunction in ischemic heart diseases. Most important findings are listed below: 1. Women have more symptoms and physical limitations but less obstructive coronary artery disease then men along the entire spectrum of acute coronary syndromes. 2. The syndrome of chest pain without obstructive coronary artery disease is distinctly more common in women than in men. 3. In women chest pain symptoms and disability do not correlate with severity of coronary stenoses. 4. Young and middle-aged females show higher rates of adverse outcomes after acute MI than men of similar age, despite less severe coronary narrowing, smaller infarcts, and more preserved systolic function. Given the lower burden of obstructive coronary artery disease (CAD) and preserved systolic function in women, which contrasts with greater rates of myocardial ischemia and near-term mortality compared with men, we propose the term ischemic heart disease as more appropriate specific to women rather than CAD or coronary heart disease (CHD). Microvascular angina pectoris This paradoxical difference, where women have lower rates of anatomical CAD but more symptoms, ischemia, and adverse outcomes, appears linked to abnormal coronary reactivity that includes microvascular dysfunction. Symptoms as the result of microvascular dysfunction should be called https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 3/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology microvascular angina. Abnormal coronary reactivity is often the result of diffuse (microvascular) atherosclerosis which is often seen in women, in contrast to the obstructive atherosclerosis which is more common in men (figure 2). the plaque Studies have shown morphology changes after menopause. At younger age (<65 yrs) women with an acute myocardial infarction have more often plaques erosions then the classical pattern of plaque rupture and thrombus formation as seen in men. These erosive plaques can cause distal embolization with micro-emboli, endothelial leading dysfunction of the microvascular beds with angina-like chest pain. This diffuse pattern of atherosclerosis often in atypical chest pain. that to translates When obstructive coronary artery is absent these women do not receive the proper preventive the medication atherosclerosis in the microvasculature progresses, leading to ischemia an possibly fatal arrhythmia s. After menopause it is known that the microvascular atherosclerosis can progress towards more pronounced atherosclerosis with eventually obstructive plaque formation. as It is this combination of non-obstructive cardiovascular disease with loss of endothelial function in the epicardial and microvascular beds which can lead to chest pain which is not well understood. For women with evidence of ischemia but no obstructive CAD, anti-anginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life; however, trials evaluating impact on adverse outcomes are needed. Women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies. Continued research is indicated to devise therapeutic regimens to improve symptom burden and reduce risk in women with ischemic heart disease. Syndrome X Cardiac syndrome X (CSX; differentiated from the metabolic syndrome X) is currently defined by typical, angina like chest pain without flow-limiting stenoses on coronary angiography and exclusion of non-cardiac chest pain. Microvascular angina is more prevalent in women then in men. There is a whole range of factors that contribute to the dysfunction of the microvascular beds: 1. Distal embolization of erosive plaques 2. Chronic inflammation 3. Spasm which is often a result of disfunctional smooth muscle cells https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 4/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology 4. Smoking, hypertension and dyslipidemia can result in endothelial dysfunction Risk Factors Risk estimates associated with traditional cardiovascular risk factors are overall similar in women and men across various regions of the World. However, the increased risk associated with hypertension and diabetes and the protective effect of exercise and alcohol appear to be larger in women than in men.[7] It is also important to make a difference between pre and post menopausal status. Table 1 gives an overview of the global cardiovascular risk factors in women Smoking Smoking is the single most important preventable cause of IHD in women. It is a relatively large risk factor for myocardial infarction in women under the age of 55 when compared to men. Smoking enhances the inflammatory process, activates the coagulation system en promotes LDL oxidation. Smoking leads to down-regulation of the estrogen receptor in the endothelial wall leading to endothelial dysfunction and atherosclerosis. The combination of smoking and the use of oral contraceptives has a synergistic effect by inducing endothelial dysfunction and activation of the coagulation system. After cessation the risk declines rapidly. Hypertension Hypertension is a highly prevalent risk factor that becomes more common in women then in men and is particularly prevalent among black women.[7] After menopause the renine activity in plasma increases which leads to sodium retention. By the age of 60 almost 50% of all women have clinically manifest hypertension, defined as a systolic blood pressure > 140 mmHg and a diastolic blood pressure of 90 mmHg.[6] Hypertension in women compared to men more often leads to CVA, left ventricular hypertrophy en diastolic dysfunction. The structural changes of the myocardium can become clinical manifest by dyspnea, supraventricular tachycardia such as atrial fibrillation, angina due to endothelial dysfunction. Slightly elevated blood pressure leads in women more then in men to endothelial dysfunction.[6] Hypertension is 2 to 3 times more common in women taking oral contraceptives, especially among obese and older women. Blood pressure lowering strategies have demonstrated to reduce the risk of ischemic heart disease and stroke Dyslipidemia In women there is a stronger fluctuation of lipid levels throughout life. Due to hormonal changes total and LDL cholesterol levels increase with an average of 10-14% after menopause.[6] Low HDL and high triglycerides seems to be more important risk factors in women than in men. Data from the Nurses Health Study shows that HDL was the lipid parameter that best discriminated the risk of ischemic heart disease.[7] Hypertriglyceridemia is associated with a 37% increase in CVD risk in women compared to 14% in men.[7] The dynamic changes of the lipidprofiles due to age and menopausal status play an important role in the prevention of cardiovascular disease in women. Obesity https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 5/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Obesity is an important risk factor for diabetes, hypertension and cardiovascular disease. There is a gradient of coronary risk with increasing overweight, with the heaviest category of women having a four- fold increased risk for CVD compared with lean women. Around menopause there is a shift from gynoid fat distribution to android. This central obesity in women leads more than in men to the metabolic syndrome, with an increased relative risk of insulin resistance, dyslipidemia and hypertension. Diabetes Diabetes is associated with a higher risk for ischemic heart disease in women than in men (RR2.0). This is partly due to a higher rate of coexisting risk factors in women with diabetes compared to men. Another important factor is that diabetes is more difficult to treat since less women reach treatment goals when compared to men. In women diabetes is an independent risk factor for developing heart failure. Diabetes during pregnancy has a 7-12 fold risk for developing diabetes later in life. Women specific risk factors Estrogens improve the arterial wall response to injury and inhibit the development of atherosclerosis by promoting re-endotheliazation, inhibiting smooth muscle cell proliferation and matrix deposition following vascular injury. They also have a vasodilative effect. Premenopausal women with hormonal dysfunction and estrogen deficiency have a higher risk for developing premature atherosclerosis.[6] The polycystic ovarian syndrome, a condition also known as PCOS have a high risk for developing the metabolic syndrome and type 2 diabetes and are therefore an at risk population. Also women with premature ovarian failure (menopause before the age of 40) have a higher risk for developing CVD. Novel risk factors In an effort to make a more accurate estimation of cardiovascular risk, more than 100 new risk markers have been proposed. There is however a slight resistance to use these markers since the lack of evidence that they really make risk estimation more accurate. A recent summary of systematic reviews conducted for the United States Preventive Services Task force has reviewed the evidence of 9 novel risk factors (Table 1). Of the risk markers evaluated C-reactive protein was the best candidate for screening, however, evidence is still lacking to recommend routine use. The Reynolds Risk score, which is a risk score specifically designed for women, incorporated CRP which reclassified 15 % of the intermediate risk women to high risk. Depression & Acute stress Data from the INTERHEART study shows, that particular in women the combined exposure psychological risk factors such as depression, chronic emotional distress and acute stress such as major live events, are significantly associated with acute myocardial infarction (OR 2.6 in men and 3.5 in women). A stress-induced condition known as Takotsubo cardiomyopathy is almost exclusively seen among women. Due to severe emotional stress these women present with symptoms mimicking acute https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 6/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology myocardial infarction. Also the ECG and echocardiogram show all the signs of infarction. However the CAG is often signs of coronary normal with no obstruction. The severe left impaired ventricular function usually normalizes completely after a couple of months. Risk Factor Assessment Which risk factors should be assessed? Global cardiovascular risk should be assessed in ALL women in menopause consulting the physician. Many women appear healthy with no symptoms of CVD nevertheless, they are potentially at increased risk The assessed following risk factors should be Age Blood pressure Total plasma cholesterol Cigarette smoking Takotsubo cardiomyopathy Other important information to establish: Personal and family history of cardiovascular disease Gynecological and obstetric history, including age at menopause Body weight Waist circumference Diet Alcohol consumption Physical fitness Fasting plasma low density (LDL) cholesterol Additional parameters to consider are: Fasting plasma glucose 75-g oral glucose tolerance test (advisable in high risk patients or in those with abnormal fasting plasma glucose Fasting plasma high-density lipoprotein (HDL) cholesterol https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 7/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Fasting plasma triglycerides Which patients can be managed for global cardiovascular risk by a menopause physician? A woman with a high-risk profile or overt cardiovascular disease requires intensive management including drug therapy Collaboration with a cardiovascular specialist is essential if global cardiovascular risk is high, or if cardiovascular disease is present. Clinical Presentation The cardiac complaints differ between men and women. Female patients as well as their treating physicians often do not recognize or interpret their complaints as heart problems. Women present less typical as what we are used when men present with heart problems. Typical symptoms, as we have learned from our male patients, such as heavy pressure on the chest which radiates to the left arm or the jaws are often absent in women. Women more often present with complaints such as tightness , out of breath en tiredness . When women get older (>60 yrs) and the risk of obstructive coronary artery disease rises, the clinical presentation becomes more typical (substernal pain, with radiation to jaw and/or left arm). clinical presentation of As a result women are often not recognized and do not receive the proper preventive medication. This could in part explain the higher mortality of cardiovascular diseases in women. Women who are diagnosed with non cardiac chest pain have twofold increased risk to develop a coronary event in the next 5-7 years and have a four times higher risk for re-hospitalization. This implicates that diagnostic testing is limited and that women should be more aggressively treated for their risk factors. Chest pain syndromes are more common in women then in men and are less related to the presence of atherosclerosis in the epicardial coronary arteries.[8] There are no gender-specific criteria for the interpretation of ECG s. Non specific ECG changes at rest, a lower exercise capacity and a smaller vessel size contribute to the lower sensitivity and specificity of non- invasive testing in women. At younger ages, endogenous estrogen level scan induce ECG changes mimicking ischemia. https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 8/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Chest pain complaints in women should always be related to their risk factor profile. It should also be noted that in women, very often chest pain is related to not well regulated hypertension. Blood pressure changes increase vascular wall pressure of the coronary arteries which translates in chest discomfort often at rest. In addition hypertension more often leads to diastolic dysfunction in women en hypertrophy which can result in chest pain. A small dose of nitrates can be effective. Treatment Symptom management in patients with non-obstructive cardiovascular disease is a challenge. Important to differentiate between vasospastic forms and complaints related to endothelial dysfunction. Table 2 gives an overview of current treatment options. Lifestyle behaviors can prevent and reduce the risk of getting heart disease and should therefore be primary focus in the GP-practice. Strategies adapt health lifestyle changes are listed below Adapted from Assessment and Management of cardiovascular risk in women ESC/ESH/2007):[9] Smoking: TARGET: permanently stop smoking all forms of tobacco Explain detrimental effects Assess the degree of addiction and readiness to cease smoking Gain commitment Establish a smoking cessation strategy (nicotine replacement, counseling and/or pharmacological intervention Arrange a schedule of follow up visits to monitor progression. Diet: TARGET: Adopt healthy diet Explain importance of a varied diet and the need to adjust energy intake to achieve and maintain ideal body weight. Encourage the consumption of: Fruits and vegetables (the five-a-day guideline) Whole grain cereal and bread Low-fat dairy products Fish, especially those rich in omega-3 Lean meat Total fat intake should be no more than 30% of energy intake, with saturated fats comprising in one third of total fat intake. Total cholesterol intake < 300mg/day Help to identify Foods that are high in saturated fats and cholesterol in order to reduce or remove them. Suggest replacement of saturated fats with complex carbohydrates, monounsaturated and polyunsaturated fats from vegetables and fish. https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 9/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Stress the importance of avoiding Foods containing high levels of salt. Reduce overall intake of salts. Physical Fitness: TARGET: Undertake regular physical exercise Explain health benefits of increased physical activity (regain and maintain energy levels, improvement of lipid levels, managing bodyweight, relieving stress) Encourage to increase physical activity by climbing stairs, walking or cycling The standard for physical activity is > 30 minutes of moving activity for 7 days per week A health women should exercise at 60-75% of the average maximum heart rate Obesity: TARGET: Body Mass Index < 25 kg.m2 or waist circumference < 88 Explain that by consuming 500-1000 calories/day less than required to maintain the current weight, she can lose about 500 grams/week and ultimately achieve weight loss of 5-15% Stress that regular exercise assists in weight loss Give diet advice (as described earlier) Lipids (table 3) Elevated lipid levels are a significant cardiovascular risk factor. Due to hormonal changes in menopause, total and LD cholesterol levels rise by approximately 10-14%. A low HDL cholesterol as well as high triglycerides is a stronger risk factor for CVD then in men. HDL and triglycerides play an important role in the metabolic syndrome. Women in menopause have an increased risk of developing the metabolic syndrome. This is partly due to the changes in body weight and the distribution of fat tissue since there is a shift from gynoid tot android fat distribution. HDL is hardly influenced by menopause. The dynamic changes in lipid profiles remain an important point in the prevention of cardiovascular disease in women. Bloodpressure (table 4) In women, after the age of 55 the systolic blood pressure rises. After menopause plasmarenine levels increase and there is an increase in the sensitivity for salt. By the age of 60 more then half of all women have clinically manifest hypertension (defined as a blood pressure > 140/90 mmHg). In women hypertension is more often associated with CVA, left ventricular hypertrophy and diastolic dysfunction. These structural changes can give an array of complaints such as dyspnea, palpitations and chest pain. Post-menopausal hormone therapy The initation or continuation of hormone replacement therapy should be decided according to the individual patient. Given the many potentially beneficial effects of estrogens on cardiovascular physiology, much expectation was placed on hormone therapy for CVD prevention. However several studies did not support beneficial effects of hormone therapy and in the WHI study (women's health initiative) the study was terminated due to a small increase in CVD. In a woman < 60 years, who recently menopaused with menopausal symptoms and without CVD, the initiation of replacement therapy does https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 10/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology not cause early harm. If a woman is at increased risk, HRT therapy is safe to use in the younger women with indications. It should be notes however, that HRT should not be initiated solely for the prevention of cardiovascular disease and should not be regarded as a substitute for antihypertensive treatment. Conclusions Cardiovascular disease in women is the number 1 cause of death in the Western World. Cardiovascular risk increases after menopause, regardless of the age it occurs. Women share similar cardiovascular risk factors however there are important sex differences in the prevalence of coronary atherosclerosis and coronary vascular physiology. There are gender differences in the regulation of vasomotor function of microvessels. Women more often have chest pain by less obstructive coronary artery disease. In women with persistent chest pain with the absence of obstructive coronary artery disease treatment of symptoms en risk factors is essential. The GP or menopause physician plays an important role in the identification of global cardiovascular risk factors (e.g. hypertension, dyslipidemia, diabetes) Cardiovascular specialists and menopause physicians must work as a team to assess global risk for the individual woman. Atherosclerosis is the underlying cause of cardiovascular disease. Prevention and reduction of cardiovascular disease as early as possible must be a priority Case 1: Case 1: 60- year old woman with risk factor (mis)management Patient presented at the emergency room with atypical complaints. She was nauseaus had a burning sensation in the chest. She had consulted her GP several times with atypical chest pain. No further action was taken then. History: Several weeks of extreme tiredness, burning chest pains, not related to exercise. Her father had his First heart attack at age 50. She had hypertension during both pregnancies. Menopausa She menopaused at age 46 with a lot of menopausal complaints such as flushes. She had a smoking history of 10 years. Risk factors: Physical examination: BMI=26, blood pressure: 180/100 mmHg, pulse: 80 r.a., normal heart sounds, grade II/VI systolic murmur. 7 mmol/L, Total cholesterol: 7,1 mmol/L, LDL-cholesterol: 4,5 mmol/L, HDL cholesterol: 0,9 mmol/L, Triglycerides: 2,5 mmol/L. Lab: glucose: ECG showed T-wave inversion in the precordial leads. Cardiac enzymes were positive. Cardiac catheterization showed an 80% stenosis of the left main coronary artery. The echocardiogram show wall segment disorders of the anterior wall and a grad II mitral valve insufficiency. Additional Cardiac Investigation: She received PTCA of the left main en her lipid profile and blood pressure was treated. She recovered and is doing well. Follow-up: Atypical presentation of acute coronary syndrome In women cardiac complaints are often atypical She was not categorized as a high risk patient Risk factors should always be optimized, Learning points: https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 11/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology Case 2: Case 2: 52-year old woman with microvascular disease Patient is referred for a second opinion to the cardiologist with complaints of tiredness and chest pain. She was evaluated 3 months earlier with chest pain. Cardiovascualr analysis then showed no cardiac pathology. Patient, who runs every week 10 kilometers, complains that she noticed shortness of breath and tiredness during her weekly run which she describes as abnormal. During running she has no chest pain. She does however experience chest pain, which she describes as heavy" feeling on the chest, when there is an abrupt change of temperature. Also slight radiation to the left arm. History: Menopausal, positive family history, smoking history (she quit 15 years ago), obstetric history normal, Alcohol consumption: 2U/day Risk factors: Physical examination: BMI=26, blood pressure: 145/90 mmHg, pulse: 70 r.a., normal heart sounds, no murmurs. 5 mmol/L, Total cholesterol: 6,9 mmol/L, LDL-cholesterol: 3,5 mmol/L, HDL cholesterol: 1,3 mmol/L, Triglycerides: 4,5 mmol/L. Lab: glucose: ECG and exercise stress test were completely normal. Vascular scanning of the carotis arteries showed moderatie plaqueformation in de the carotid bulb. No chest pain during exercise. Myocardial perfusion scan showed ischemia in the inferior segments of the heart. Cardiac catheterization: vessel wall irregularities in all coronary arteries, no significant obstructions. Additional Cardiac Investigation: Blood pressure and lipidprofiles was optimized with ACE inhibition and a statine. She was advised to lose weight and drink less alcohol with regard to her elevated triglycerides. She received a low dose b-blocker and was without complaints within 3 months. Follow-up: Complaints without obstructive heart disease Risk factors should always be optimized, blood pressure in lipidprofile was inadequate Limitation of diagnostic tests. Learning points: References 1. WRITING GROUP MEMBERS, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J, and American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics 2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):e46-e215. DOI:10.1161/CIRCULATIONAHA.109.192667 | 2. Steven Allender, Peter Scarborough, Viv Peto and Mike Rayner. European cardiovascular disease statistics 2008. British Heart Foundation Health Promotion Research Group. (http://www.bhf.org.uk/p ublications/view-publication.aspx?ps=1001443) 3. Heron M, Hoyert DL, Murphy SL, Xu J, Kochanek KD, and Tejada-Vera B. Deaths: final data for 2006. Natl Vital Stat Rep. 2009 Apr 17;57(14):1-134. 4. Ford ES and Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007 Nov https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 12/13 7/4/23, 12:40 AM Women's Heart Health - Textbook of Cardiology 27;50(22):2128-32. DOI:10.1016/j.jacc.2007.05.056 | 5. Vaccarino V. Ischemic heart disease in women: many questions, few facts. Circ Cardiovasc Qual Outcomes. 2010 Mar;3(2):111-5. DOI:10.1161/CIRCOUTCOMES.109.925313 | 6. Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, Hodgson TK, Matthews KA, Pepine CJ, Reis SE, Reichek N, Rogers WJ, Pohost GM, Kelsey SF, Sopko G, and WISE Study Group. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003 Feb 5;41(3):413-9. DOI:10.1016/s0735-1097(02)02763-8 | 7. Vaccarino V, Badimon L, Corti R, de Wit C, Dorobantu M, Hall A, Koller A, Marzilli M, Pries A, Bugiardini R, and Working Group on Coronary Pathophysiology and Microcirculation. Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European Society of Cardiology. Cardiovasc Res. 2011 Apr 1;90(1):9-17. DOI:10.1093/cvr/cvq394 | 8. Mandelzweig L, Battler A, Boyko V, Bueno H, Danchin N, Filippatos G, Gitt A, Hasdai D, Hasin Y, Marrugat J, Van de Werf F, Wallentin L, Behar S, and Euro Heart Survey Investigators. The second Euro Heart Survey on acute coronary syndromes: Characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004. Eur Heart J. 2006 Oct;27(19):2285-93. DOI:10.1093/eurheartj/ehl196 | 9. Assessment and Management of cardiovascular risk in women ESC/ESH/2007 Retrieved from "http://www.textbookofcardiology.org/index.php?title=Women%27s_Heart_Health&oldid=1454" This page was last edited on 25 October 2012, at 18:50. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/Women%27s_Heart_Health 13/13 |
7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology World Burden of Cardiovascular Diasease: Data from the https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 1/6 7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology WHO World Data Table 1 2 3 4 5 6 7 8 Rheumatic heart disease Policies and legislation Smoking prevalence Heart disease Stroke Diabetes Research Percentage of smokers aged 18 years and above 2003 or latest available data Population Disability Mortality Disability Mortality Legal status of smoking in government buildings 2004 or latest available data Percentage of people aged 20 years and above with diabetes 200 Country Country Number of publications on cardiovascular disease 1991 2001 Number of deaths 2002 DALYS lost per 1000 population 2003 or latest available data DALYS lost per 1000 population 2003 or latest available data Number of deaths 2002 Number of deaths 2002 Millions 2002 men women Afghanistan 22,930 36 33,157 13 11,532 1,938 4.7% unknown Afghanistan not regulated Albania 3,141 13 3,989 13 4,169 42 46.2% 22.8% 4.5% Albania Algeria 31,266 7 14,948 8 16,223 756 40.2% 11.5% 2.6% 1 unknown Algeria Andorra 69 3 67 3 52 3 49.6% 35.9% 8.8% banned Andorra not regulated Angola 13,184 13 7,130 15 7,640 615 0.9% Angola Antigua and Barbuda Antigua and Barbud 73 6 52 13 92 0 7.3% unknown not regulated Argentina 37,981 6 34,292 6 22,668 234 32.00% 18.90% 6.10% 110 Argentina not regulated Armenia 3,072 20 8,515 10 4,212 151 67.40% 4.10% 4.70% 1 Armenia Australia 19,544 5 25,474 3 11,730 243 30.70% 23.10% 6.80% 710 restricted Australia Austria 8,111 6 15,418 4 7,559 185 37.40% 26.30% 3.80% 320 restricted Austria Azerbaijan 8,297 28 22,302 9 6,540 184 32.00% 1.70% 6.80% 1 banned Azerbaijan Bahamas 310 5 154 6 155 1 0.00% 16.00% 6.20% unknown Bahamas Bahrain 709 8 283 3 84 6 29.50% 0.00% 9.10% 4 unknown Bahrain Bangladesh 143,809 18 130,006 9 64,515 10,253 63.00% 34.50% 4.60% 3 restricted Bangladesh Barbados 269 6 286 7 270 2 19.80% 3.00% 5.80% 1 banned Barbados Belarus 9,940 28 59,719 14 22,892 550 63.60% 22.00% 9.90% 3 restricted Belarus Belgium 10,296 5 14,985 4 9,234 68 33.20% 22.90% 4.00% 345 restricted Belgium Belize 251 8 153 7 111 1 4.20% restricted Belize Benin 6,558 10 3,017 12 3,279 236 0.00% 5.40% 3.30% 1 unknown Benin Bhutan 2,190 20 2,672 10 1,370 195 3.50% unknown Bhutan Bolivia 8,645 6 3,948 7 3,138 70 36.70% 19.20% 4.90% restricted Bolivia Bosnia and Herzegovina Bosnia and Herzegovina 4,126 10 5,590 13 6,508 21 54.60% 31.50% 3.80% banned Botswana 1,770 8 697 8 670 15 3.60% restricted Botswana Brazil 176,257 9 139,601 11 129,172 3,055 29.40% 18.40% 4.30% 307 banned Brazil Brunei Darussalam Brunei Darussalam 350 5 92 6 90 7 9.40% banned Bulgaria 7,965 14 26,243 13 20,882 232 47.30% 28.20% 7.70% 18 banned Bulgaria not regulated Burkina Faso 12,624 11 5,877 13 6,604 466 25.60% 13.20% 2.70% 2 Burkina Faso not regulated Burundi 6,602 10 3,084 12 3,492 82 1.00% Burundi Cambodia 13,810 13 7,635 11 5,963 614 0.00% 6.50% 1.90% restricted Cambodia Cameroon 15,729 10 9,443 12 10,198 621 20.70% 2.40% 1.00% 4 restricted Cameroon Canada 31,271 5 43,246 3 15,621 422 30.00% 26.60% 8.80% 1,237 restricted Canada Cape Verde 454 6 202 9 266 4 3.40% restricted Cape Verde https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 2/6 7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology Central African Rep. not regulated Central African Rep. 3,819 10 2,513 12 2,727 51 1.00% not regulated Chad 8,348 10 4,385 12 4,747 300 19.70% 3.10% 2.80% Chad Chile 15,613 4 9,075 5 8,142 315 44.10% 36.60% 5.20% 53 restricted Chile China 1,294,867 4 702,925 12 1,652,885 97,245 58.90% 3.60% 2.40% 472 restricted China Colombia 43,526 8 31,289 6 17,745 380 3.60% 11 unknown Colombia Comoros 747 8 282 10 310 23 30.50% 18.40% 1.40% unknown Comoros Congo 3,633 9 1,577 10 1,718 39 20.80% 3.90% 1.10% 2 restricted Congo Congo, Dem. Rep. Congo, Dem. Rep. 51,201 11 24,217 13 26,439 1,930 1.40% unknown not regulated Cook Islands 18 10 11 12 11 0 6.30% Cook Islands Costa Rica 4,094 6 2,937 3 1,194 45 24.30% 10.00% 3.30% 2 restricted Costa Rica C te d Ivoire 16,365 11 9,257 12 9,530 233 21.00% 4.00% 3.60% restricted C te d Ivoire Croatia 4,439 10 11,653 11 8,653 152 41.40% 27.40% 4.40% 41 banned Croatia Cuba 11,271 8 16,275 5 7,684 196 48.80% 28.50% 6.00% 15 restricted Cuba Cyprus 796 7 1,358 3 795 1 9.20% restricted Cyprus Czech Republic Czech Republic 10,246 11 25,899 7 15,663 286 42.60% 26.20% 4.30% 78 banned Denmark 5,351 5 10,013 4 4,871 17 40.30% 36.90% 3.80% 308 restricted Denmark Djibouti 693 21 727 7 248 27 2.50% unknown Djibouti Dominica 78 3 30 4 30 0 6.20% unknown Dominica Dominican Republic Dominican Republic 8,616 11 7,271 9 4,833 54 22.10% 16.20% 5.20% restricted Ecuador 12,810 5 5,826 5 4,374 117 31.90% 7.40% 4.80% 3 banned Ecuador Egypt 70,507 21 103,829 8 35,054 3,398 47.90% 1.80% 7.20% 20 restricted Egypt El Salvador 6,415 10 5,328 4 1,684 39 3.00% unknown El Salvador Equatorial Guinea Equatorial Guinea 481 11 313 12 333 18 3.80% unknown not regulated Eritrea 3,991 9 1,326 10 1,474 42 2.80% 4 Eritrea Estonia 1,338 16 6,235 9 2,964 65 57.10% 28.80% 4.40% 7 banned Estonia not regulated Ethiopia 68,961 10 32,477 11 35,329 2,482 9.70% 0.80% 2.80% 4 Ethiopia not regulated Fiji 831 18 783 17 685 21 47.30% 14.00% 8.30% 1 Fiji Finland 5,197 7 12,488 4 4,875 77 31.60% 22.30% 3.90% 331 banned Finland France 59,850 3 46,132 3 37,750 1,136 42.60% 33.90% 3.90% 1,407 restricted France not regulated Gabon 1,306 11 1,001 11 951 57 1.20% Gabon Gambia 1,388 10 789 11 837 48 43.40% 6.20% 3.30% 4 restricted Gambia not regulated Georgia 5,177 23 26,035 17 15,680 59 61.40% 6.30% 5.30% 159 Georgia Germany 82,414 6 172,717 4 79,326 2,241 39.00% 30.90% 4.10% 2,276 restricted Germany Ghana 20,471 9 10,471 11 11,337 705 14.20% 1.90% 3.30% 1 restricted Ghana Greece 10,970 7 16,825 6 22,694 10 53.50% 33.60% 10.30% 245 restricted Greece Grenada 80 9 85 13 91 1 7.30% unknown Grenada Guatemala 12,036 4 2,796 4 2,232 14 24.50% 3.70% 2.70% restricted Guatemala Guinea 8,359 11 4,137 12 4,415 289 0.90% 3 banned Guinea Guinea- Bissau not regulated Guinea- Bissau 1,449 11 783 13 844 52 3.10% Guyana 764 12 791 18 880 8 4.20% unknown Guyana Haiti 8,218 5 2,469 16 6,764 62 25.20% 5.40% 4.10% unknown Haiti Honduras 6,781 10 4,544 8 2,786 79 2.70% unknown Honduras Hungary 9,923 13 29,502 8 17,148 354 47.20% 27.70% 4.40% 103 banned Hungary Iceland 287 5 416 3 189 3 26.50% 27.10% 3.20% 9 banned Iceland India 1,049,549 20 1,531,534 10 771,067 103,913 34.60% 3.40% 5.50% 294 banned India Indonesia 217,131 14 220,372 8 123,684 11,660 59.80% 5.30% 6.70% 4 restricted Indonesia https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 3/6 7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology Iran, Isl. Rep. 68,070 17 81,983 8 31,768 1,138 33.40% 3.50% 6.00% banned Iran, Isl. Rep. Iraq 24,510 19 22,036 8 8,291 695 6.10% 1 unknown Iraq Ireland 3,911 8 6,527 4 2,650 51 33.80% 26.50% 3.20% 142 restricted Ireland Israel 6,304 4 5,705 3 2,233 170 35.80% 19.70% 6.70% 634 banned Israel Italy 57,482 4 92,928 4 69,075 1,790 37.90% 29.70% 9.20% 1,976 banned Italy not regulated Jamaica 2,627 5 1,877 11 3,559 59 56.10% 21.20% 5.40% 23 Jamaica Japan 127,478 3 90,196 5 134,952 2,585 52.50% 12.40% 6.70% 3,769 restricted Japan Jordan 5,329 13 3,788 6 1,428 127 66.80% 5.30% 8.10% 6 banned Jordan Kazakhstan 15,469 28 51,948 17 26,874 919 57.50% 6.40% 4.40% 3 restricted Kazakhstan not regulated Kenya 31,540 9 13,661 10 14,843 360 66.30% 27.30% 1.40% Kenya not regulated Kiribati 87 1 7 18 81 0 8.60% Kiribati Korea, Dem. People s Rep. of Korea, Dem. People s Rep. of 22,541 13 26,953 8 14,337 1,317 2.50% unknown Korea, Republic of Korea, Republic of 47,430 3 15,811 9 46,151 202 69.50% 5.10% 5.60% 19 restricted Kuwait 2,443 10 940 3 213 7 35.70% 2.70% 9.80% 17 restricted Kuwait not regulated Kyrgyzstan 5,067 22 10,850 22 8,366 351 64.10% 41.40% 3.60% Kyrgyzstan Lao People s Dem. Rep. Lao People s Dem. Rep. 5,529 19 5,539 12 3,620 484 68.90% 16.10% 1.80% restricted Latvia 2,329 17 9,928 12 7,278 109 64.50% 29.20% 4.50% 1 restricted Latvia Lebanon 3,596 17 5,471 7 2,072 119 60.70% 46.90% 7.00% 65 restricted Lebanon Lesotho 1,800 9 1,200 11 1,299 24 3.10% unknown Lesotho Liberia 3,239 12 1,442 14 1,559 130 3.10% unknown Liberia Libyan Arab Jamahiriya Libyan Arab Jamahiriya 5,445 15 5,309 6 1,762 130 3.10% banned Lithuania 3,465 16 14,662 7 5,089 186 46.40% 15.90% 4.20% 5 restricted Lithuania Luxembourg 447 4 455 5 390 0 41.40% 30.20% 3.60% 3 restricted Luxembourg Macedonia, Former Yugos. Rep. of Macedonia, Former Yugos. Rep. of 2,046 9 2,544 13 3,772 41 3.80% 5 banned not regulated Madagascar 16,916 10 8,327 11 9,020 609 1.40% 2 Madagascar not regulated Malawi 11,871 10 6,773 11 7,249 106 31.00% 7.40% 1.10% 1 Malawi Malaysia 23,965 8 13,445 7 10,169 464 52.40% 3.00% 7.60% 16 banned Malaysia Maldives 309 17 282 10 152 16 5.00% banned Maldives Mali 12,623 11 5,406 13 5,946 478 26.90% 4.70% 2.90% restricted Mali not regulated Malta 393 9 865 4 338 6 13.90% 5 Malta Marshall Islands Marshall Islands 52 20 57 20 54 2 8.60% 9 banned not regulated Mauritania 2,807 11 1,640 13 1,756 111 25.00% 4.30% 2.80% Mauritania Mauritius 1,210 18 2,034 11 1,235 5 54.70% 3.10% 14.60% 2 restricted Mauritius Mexico 101,965 6 51,454 4 26,478 1,093 36.50% 14.30% 3.90% 201 restricted Mexico Micronesia, Federated States of Micronesia, Federated States of not regulated 108 12 64 14 69 2 8.60% Moldova, Republic of Moldova, Republic of 4,270 23 18,559 15 7,848 264 5.90% restricted Monaco 34 3 27 3 22 1 8.80% 7 unknown Monaco Mongolia 2,559 8 1,153 25 2,515 145 46.20% 7.30% 2.50% 1 restricted Mongolia Morocco 30,072 14 29,934 5 10,607 808 32.60% 0.60% 2.60% 7 restricted Morocco Mozambique 18,537 8 7,969 10 8,896 246 1.60% 1 unknown Mozambique Myanmar 48,852 17 58,478 11 33,406 3,746 55.50% 12.20% 2.00% unknown Myanmar https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 4/6 7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology not regulated Namibia 1,961 8 996 10 1,108 25 33.80% 16.10% 3.10% Namibia Nauru 13 22 17 10 7 0 56.80% 64.70% 27.80% banned Nauru Nepal 24,609 18 23,314 10 11,961 1,648 61.50% 34.60% 3.90% 3 banned Nepal Netherlands 16,067 5 19,045 4 12,459 16 38.30% 32.80% 3.50% 917 restricted Netherlands New Zealand 3,846 7 6,141 4 2,699 139 28.10% 28.70% 6.70% 131 restricted New Zealand Nicaragua 5,335 8 2,680 7 1,768 70 2.90% restricted Nicaragua Niger 11,544 11 4,423 13 4,831 439 2.50% unknown Niger Nigeria 120,911 11 64,778 12 69,932 4,795 16.30% 3.60% 3.40% 18 banned Nigeria Niue 2 10 1 12 1 0 36.80% 14.00% 6.30% restricted Niue Norway 4,514 5 8,886 3 4,817 103 40.30% 39.00% 3.90% 185 restricted Norway Oman 2,768 17 1,765 4 375 12 23.60% 2.90% 9.90% 19 unknown Oman Pakistan 149,911 18 154,338 9 78,512 11,604 30.30% 3.80% 7.70% 12 banned Pakistan Palau 20 14 17 14 16 0 50.90% 22.60% 8.60% banned Palau Panama 3,064 5 1,628 5 1,489 30 35.10% 17.70% 3.50% 1 unknown Panama Papua New Guinea Papua New Guinea 5,586 18 3,994 10 1,960 351 48.90% 0.00% 6.50% 3 banned Paraguay 5,740 7 2,606 10 2,881 36 45.80% 15.60% 3.70% 1 restricted Paraguay Peru 26,767 4 10,615 4 8,084 157 5.20% 3 restricted Peru Philippines 78,580 10 45,378 7 24,368 2,812 59.60% 13.80% 7.10% 2 restricted Philippines Poland 38,622 10 77,151 7 43,032 1,277 51.50% 27.90% 4.10% 187 banned Poland Portugal 10,049 5 10,927 9 20,069 189 44.20% 19.70% 8.60% 51 restricted Portugal Qatar 601 9 238 4 75 4 10.10% 7 unknown Qatar Romania 22,387 13 60,718 13 52,272 566 33.30% 10.80% 6.60% 16 unknown Romania Russian Federation Russian Federation 144,082 27 674,881 19 517,424 8,126 58.10% 15.80% 4.20% 13 banned not regulated Rwanda 8,272 10 3,493 12 3,811 101 0.90% Rwanda Saint Kitts and Nevis Saint Kitts and Nevis 42 10 46 19 84 0 7.30% unknown Saint Lucia 148 6 71 11 120 4 34.60% 5.00% 6.20% restricted Saint Lucia Saint Vincent and Grenadines Saint Vincent and Grenadines 119 9 103 10 88 2 34.60% 5.60% 7.30% unknown Samoa 176 14 117 14 128 3 67.40% 28.80% 6.10% banned Samoa San Marino 27 5 40 3 26 1 9.20% unknown San Marino Sao Tome and Principe not regulated Sao Tome and Principe 157 7 81 10 107 2 0.90% Saudi Arabia 23,520 17 16,438 4 3,818 126 29.10% 1.20% 9.30% 51 banned Saudi Arabia not regulated Senegal 9,855 10 3,838 12 4,154 355 21.20% 1.50% 3.40% 3 Senegal Serbia & Montenegro not regulated Serbia & Montenegro 10,535 12 23,610 12 21,756 238 55.50% 51.80% 4.20% 21 Seychelles 80 7 54 2 15 1 32.50% 15.00% 14.60% unknown Seychelles Sierra Leone 4,764 13 2,813 15 3,035 216 3.30% unknown Sierra Leone Singapore 4,183 7 3,946 3 1,716 39 23.70% 3.20% 11.40% 76 restricted Singapore Slovakia 5,398 12 14,609 5 4,445 131 42.30% 28.00% 3.90% 25 banned Slovakia Slovenia 1,986 6 2,803 6 2,003 87 32.70% 20.80% 4.30% 34 restricted Slovenia Solomon Islands Solomon Islands 463 12 213 13 220 6 6.40% restricted Somalia 9,480 19 6,818 13 4,426 333 2.70% unknown Somalia South Africa 44,759 9 27,013 11 30,306 792 43.40% 13.90% 3.40% 77 restricted South Africa Spain 40,977 4 45,018 3 34,880 1,738 43.90% 31.20% 8.70% 689 restricted Spain Sri Lanka 18,910 8 16,297 7 13,348 175 38.70% 3.10% 5.40% 6 banned Sri Lanka Sudan 32,878 15 28,458 10 16,532 800 27.70% 2.70% 2.90% restricted Sudan not regulated Suriname 432 13 397 12 362 4 3.80% Suriname not regulated Swaziland 1,069 8 529 8 499 13 19.60% 4.90% 2.90% Swaziland https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 5/6 7/4/23, 12:41 AM World Burden of Cardiovascular Diasease: Data from the WHO - Textbook of Cardiology Sweden 8,867 5 20,122 3 9,984 143 21.30% 24.90% 4.30% 654 banned Sweden Switzerland 7,171 4 10,746 2 4,508 112 37.60% 28.30% 3.90% 440 restricted Switzerland Syrian Arab Republic Syrian Arab Republic 17,381 13 11,168 11 7,675 1,715 44.00% 16.70% 8.20% banned not regulated Tajikistan 6,195 23 11,447 7 3,048 419 3.10% Tajikistan Tanzania, United Republic of Tanzania, United Republic of not regulated 36,276 10 14,720 12 16,115 439 48.90% 7.20% 1.30% Thailand 62,193 6 28,425 5 24,810 456 32.20% 2.70% 3.80% 59 restricted Thailand Timor-Leste 739 18 635 10 315 49 unknown Timor-Leste not regulated Togo 4,801 10 2,474 12 2,675 175 3.10% 2 Togo Tonga 103 10 70 12 79 2 62.10% 14.20% 6.30% banned Tonga Trinidad and Tobago not regulated Trinidad and Tobago 1,298 15 2,156 10 1,253 23 7.30% 5 Tunisia 9,728 15 12,956 6 4,798 298 52.90% 2.50% 2.90% 8 restricted Tunisia Turkey 70,318 16 102,552 13 62,782 1,584 51.10% 18.50% 7.30% 578 banned Turkey Turkmenistan 4,794 34 11,671 7 2,182 221 3.20% banned Turkmenistan Tuvalu 10 18 11 20 11 0 6.30% banned Tuvalu Uganda 25,004 10 10,163 11 11,043 288 33.40% 7.10% 1.10% 2 restricted Uganda Ukraine 48,902 28 335,610 13 126,117 3,085 55.50% 14.70% 4.40% 19 restricted Ukraine United Arab Emirates United Arab Emirates 2,937 17 2,235 4 363 16 27.60% 4.00% 20.50% 8 restricted United Kingdom not regulated United Kingdom 59,068 7 120,530 4 59,322 1,712 34.60% 34.40% 3.90% 2,667 United States of America United States of America 291,038 8 514,450 4 163,768 3,479 27.80% 22.30% 8.80% 12,502 restricted Uruguay 3,391 6 3,980 7 3,773 32 39.40% 30.80% 6.80% 2 restricted Uruguay not regulated Uzbekistan 25,705 24 55,693 12 23,436 1,558 28.70% 1.40% 3.20% 1 Uzbekistan Vanuatu 207 13 120 13 122 3 47.90% 4.80% 6.90% restricted Vanuatu Venezuela 25,226 10 17,967 5 8,720 208 51.90% 20.50% 4.30% unknown Venezuela Viet Nam 80,278 10 66,179 8 58,308 4,210 53.20% 3.00% 1.80% banned Viet Nam Yemen 19,315 22 16,217 9 6,464 743 60.00% 29.00% 4.40% unknown Yemen Zambia 10,698 8 4,153 9 4,604 135 21.40% 8.80% 1.60% restricted Zambia Zimbabwe 12,835 8 5,752 10 6,264 158 32.20% 4.60% 2.00% 2 unknown Zimbabwe [1] (http://www.who.int/cardiovascular_diseases/en/cvd_atlas_29_world_data_table.pdf) Retrieved from "http://www.textbookofcardiology.org/index.php?title=World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO&oldid=349" This page was last edited on 13 December 2011, at 00:26. Content is available under Attribution-NonCommercial-ShareAlike 3.0 Unported unless otherwise noted. https://www.textbookofcardiology.org/wiki/World_Burden_of_Cardiovascular_Diasease:_Data_from_the_WHO 6/6 |
7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Carotid endarterectomy : Jeffrey Jim, MD, MPHS, FACS : John F Eidt, MD, Joseph L Mills, Sr, MD, Scott E Kasner, MD : Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Nov 14, 2022. INTRODUCTION Treatment aimed at carotid atherosclerotic lesions may be beneficial for symptomatic or asymptomatic patients. This topic will review the preoperative evaluation and surgical technique of carotid endarterectomy (CEA). The indications for carotid revascularization and perioperative stroke risk assessment for patients with carotid atherosclerosis are discussed elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease".) Carotid artery stenting is also discussed separately. (See "Overview of carotid artery stenting".) CAROTID ATHEROSCLEROTIC DISEASE The effectiveness of CEA in the management of selected patients with symptomatic or asymptomatic carotid atherosclerotic disease has been established by large randomized clinical trials. The specific indications for CEA are discussed in detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid endarterectomy' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CEA'.) Special considerations Bilateral carotid stenoses Some patients have varying degrees of bilateral carotid disease. No randomized clinical trials have evaluated the effectiveness of bilateral CEA for such patients. https://www.uptodate.com/contents/carotid-endarterectomy/print 1/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate However, bilateral carotid occlusive disease appears to increase the risk for complications during and after unilateral CEA (whichever of the two carotids is treated first) [1-5]. In a follow-up analysis of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the risk of stroke was significantly increased for a severely stenosed ipsilateral carotid artery associated with an occluded contralateral carotid artery [4]. In spite of higher perioperative morbidity in the presence of an occluded contralateral artery, the longer-term outlook for patients who had endarterectomy performed for a recently symptomatic, severely stenosed ipsilateral carotid artery was better compared with medically treated patients. The impact of bilateral disease appears to be greater for CEA compared with carotid stenting. In a systematic review and meta- analysis, patients with contralateral carotid occlusion had a significantly higher rate of cerebral events and death for CEA compared with carotid artery stenting [5] The impact of severe contralateral carotid artery stenosis or occlusion on the benefit and risk of unilateral CEA in patients with symptomatic and asymptomatic disease is discussed in more detail separately. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Factors influencing benefit and risk'.) A combined approach (ie, bilateral repair during a single operation) is generally contraindicated due to the risks associated with respiratory compromise secondary to neck hematomas or recurrent laryngeal nerve injury, frequent difficulty with blood pressure control after manipulation of the carotid sinus, and concerns about cerebral hyperperfusion syndrome and the unknown effect of bilateral cerebral ischemia (although temporary). (See 'Perioperative morbidity and mortality' below.) When the extent of contralateral carotid disease is sufficiently severe to warrant bilateral CEA, most surgeons use a staged approach. When one side is symptomatic and the other asymptomatic, the symptomatic lesion is generally addressed first and the asymptomatic side addressed once the patient has recovered from the first CEA. If both sides are asymptomatic and of similar severity, the lesion supplying the dominant hemisphere is addressed first. When one lesion is significantly worse than the other and both are asymptomatic, the lesion of greater severity is addressed first and the second later as a staged procedure. Vocal cord paralysis following the first procedure should be excluded by otolaryngologic examination prior to performing the second procedure. (See 'Otolaryngologic examination' below.) Tandem proximal lesions Patients with internal carotid artery or carotid bifurcation disease can present with multilevel atherosclerotic disease involving the innominate artery or proximal https://www.uptodate.com/contents/carotid-endarterectomy/print 2/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate common carotid artery. Clinicians often prefer to combine treatment of these tandem lesions at the time of CEA. However, combined procedures are associated with a higher periprocedural risk compared with CEA alone. In an analysis of 404 patients undergoing CEA combined with proximal endovascular interventions compared with 66,115 patients undergoing CEA alone, patients undergoing a combined procedure had higher rates of perioperative stroke (3 versus 1.4 percent) and higher 30-day stroke and death rates (3.5 versus 1.8 percent). The increased risk was seen only in symptomatic patients; outcomes were similar for patients who were asymptomatic. These data suggest the need for caution when considering a combined approach [6]. In a systematic review, the pooled technical success rate for treating tandem lesions was high (99.8 percent), and pooled morbidity and mortality were as follows: death (1.5 percent), stroke (2.6 percent), combined stroke/death (3.3 percent), and myocardial infarction (3.2 percent) [7]. This study provided some insight on the optimal sequence for a combined procedure. For those in whom CEA was performed first, the risk of perioperative stroke was higher compared with those in whom the proximal intervention was performed first (5.7 versus 0 percent), suggesting that proximal stenting should be done prior to CEA. Distal lesions The data evaluating concomitant CEA with distal endovascular intervention are limited. The use of the term "distal intervention" can refer to treatment of a truly distinct lesion (eg, distal internal carotid artery) away from the carotid bifurcation. However, these combined procedures can also refer to the use of endovascular techniques to salvage complications caused by CEA (such as dissection or inadequate distal endpoint). In an analysis of 327 patients undergoing CEA combined with a distal endovascular intervention compared with 105,192 isolated CEA cases, patients undergoing a combined procedure had higher rates of perioperative stroke and mortality for both asymptomatic and symptomatic patients. However, this study was limited in determining if the distal intervention was planned preoperatively or performed as a salvage maneuver during CEA [6,8]. Carotid endarterectomy prior to other procedures Carotid intervention prior to other high-risk surgical procedures in patients with carotid artery stenosis is rarely needed, and a decision to proceed should be individualized depending upon the clinician's best estimate of the risk of perioperative stroke. Coronary artery bypass surgery Neurologic complications are second only to heart failure as a cause of morbidity and mortality following cardiac surgery. New stroke or transient ischemic attack occurs in approximately 3 percent of patients following coronary artery bypass grafting. As a result, CEA is often considered in conjunction with coronary artery bypass grafting in patients with significant carotid stenosis. However, there have been no trials examining the use of CEA in patients having coronary artery bypass grafting. https://www.uptodate.com/contents/carotid-endarterectomy/print 3/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate The indications for, timing of, and method of carotid revascularization in conjunction with coronary artery bypass grafting is discussed in detail elsewhere. (See "Coronary artery bypass grafting in patients with cerebrovascular disease", section on 'Prophylactic carotid intervention'.) General surgery The incidence of stroke appears to be lower following general (nonvascular) surgical procedures than following cardiac surgery, with a reported incidence in patients undergoing general anesthesia of less than 0.5 percent [9-11]. The risk may be slightly higher (1 percent) in asymptomatic patients with a carotid bruit who undergo general surgery [12]. There have been no randomized trials examining CEA in patients with carotid stenosis prior to general surgery. A retrospective review suggests that CEA is probably not warranted in most patients with asymptomatic carotid disease to lower their risk of perioperative stroke as a complication of their anticipated general surgical procedure [13]. This study was a chart review of 284 patients who had undergone nonvascular surgery requiring general anesthesia and had preoperative carotid ultrasound. While a previous history of stroke or transient ischemic attack, a carotid bruit, or both were present in 250 patients, all were considered to have asymptomatic carotid stenosis [14]. Ten of 284 patients (3.5 percent) had perioperative ischemic strokes within 30 days of the index procedure, and 8 of 224 (3.6 percent) with >50 percent carotid stenosis had an ipsilateral perioperative stroke (bilateral lesions were present in three patients). While this stroke risk exceeds that of the general population and of patients with carotid bruits, the increased risk appears to be insufficient to mandate CEA for asymptomatic carotid stenosis in the general surgical population. Major peripheral vascular procedures Although there are no trials of CEA prior to abdominal aortic aneurysm repair or other major peripheral vascular procedures, many vascular surgeons support performing CEA in those patients with appropriate indications for CEA, in anticipation of a major vascular procedure that may involve significant hemodynamic fluctuations. Endarterectomy in patients with intracranial aneurysm Ipsilateral intracranial aneurysms that are distal to a cervical internal carotid artery stenosis may be susceptible to sudden hemodynamic changes associated with CEA leading to aneurysm rupture [15]. On the other hand, surgical clipping of an aneurysm distal to a severe internal carotid stenosis may increase the risk of ischemic stroke. Unfortunately, data are too sparse to allow firm conclusions as to which problem should be treated first. However, caution is advised if CEA is performed in this setting, especially if the https://www.uptodate.com/contents/carotid-endarterectomy/print 4/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate ipsilateral aneurysm is 7 mm in diameter or if there is a history of subarachnoid hemorrhage from another aneurysm. (See "Unruptured intracranial aneurysms".) CONTRAINDICATIONS The only absolute contraindication to CEA is asymptomatic complete carotid occlusion. When an internal carotid occlusion occurs, thrombus propagates distally and intracranially to at least the first branch of the internal carotid artery, which is the ophthalmic artery. This precludes achieving an endpoint for a CEA performed at the carotid bifurcation in the neck. Whether it is appropriate to perform carotid revascularization for acute symptomatic carotid occlusion is discussed elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Occlusion' and "Management of symptomatic carotid atherosclerotic disease".) Relative contraindications The following conditions may increase the risk of local or systemic complications and may support the use of alternative treatments such as medical management and/or carotid angioplasty and stenting [16]: History of prior neck irradiation resulting in "woody fibrosis" of the skin and subcutaneous tissues Presence of tracheostomy Prior radical neck dissection with or without radiation Contralateral vocal cord paralysis from prior endarterectomy Atypical lesion location, either high or low, that is surgically inaccessible Severe recurrent carotid stenosis Unacceptably high medical risk (eg, unstable cardiac status) (see 'Risk factors for poor outcome' below) Patients with these conditions may be candidates for carotid artery stenting. (See "Overview of carotid artery stenting".) PREOPERATIVE EVALUATION https://www.uptodate.com/contents/carotid-endarterectomy/print 5/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate A thorough vascular history and physical examination are essential components of the evaluation of a patient being considered for CEA. A search can be made for evidence of atherosclerotic disease elsewhere, including abdominal aortic aneurysm and peripheral artery disease. The cost effectiveness and medical benefit of screening under such circumstances is unknown. (See "Screening for abdominal aortic aneurysm" and "Noninvasive diagnosis of upper and lower extremity arterial disease" and "Atrial fibrillation in patients undergoing noncardiac surgery".) Risk factors for poor outcome Identification of risk factors for morbidity and mortality associated with CEA is important to avoid surgery in patients who may face an unacceptably high risk for endarterectomy. Advances in perioperative management have led at least some surgeons to conclude that among patients with appropriate indications for CEA, the proportion of patients with an unacceptable surgical risk is extremely small and continues to shrink. Modifications in surgical practice, refinement of anesthetic techniques and alternatives, the use of vasoactive medications in the perioperative period, and the declining use of routine preoperative contrast angiography (risk for acute kidney injury) may be responsible for the observed reduction in perioperative complication rates [17]. For patients at high risk for general anesthesia, regional anesthesia is an alternative that has equally good perioperative outcomes [18]. (See 'Anesthesia' below.) The following characteristics have each been associated with an increased risk of poor outcome (eg, stroke, myocardial infarction, death) at 30 days after CEA in some, but not all, studies [16,19- 37]. Later database reviews support the listed risk factors [29,30]. Older age (>70 years in one and 80 years in other studies) Severe heart disease Severe pulmonary dysfunction Renal insufficiency or failure Stroke as the indication for endarterectomy Anatomic issues, including limited surgical access, prior cervical irradiation, prior ipsilateral CEA, and contralateral carotid occlusion (see 'Relative contraindications' above) Among patients already selected to undergo CEA, there is no convincing evidence that female sex is a significant risk factor for adverse outcomes [38-43]. However, in a large database review from the American College of Surgeons National Surgical Quality Improvement Program of over 100,000 patients who underwent carotid intervention (104,412 CEA, 2156 carotid artery stenting) https://www.uptodate.com/contents/carotid-endarterectomy/print 6/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate between 2005 to 2017, the rate of postoperative neurologic complications was higher for females compared with males in both the asymptomatic and symptomatic cohorts. Although the specific patient factors that increase perioperative risk following CEA are debated, patients deemed to be at high risk have worse long-term outcomes following CEA [16,25,44]. In a retrospective review that compared 323 patients at high risk (anatomic or pathophysiologic) with 453 patients at normal risk, differences in perioperative outcomes were not significant [16]. However, two-year survival was worse in high-risk patients. Medical risk assessment Cardiac evaluation should be considered selectively since patients undergoing CEA are most likely to have morbidity related to coronary heart disease. This evaluation may be performed with exercise stress testing, dobutamine echocardiography, dipyridamole imaging, or, when warranted, coronary catheterization [45,46]. However, there is no evidence that immediate cardiac intervention alone reduces perioperative procedural risk of stroke or death for CEA. (See "Evaluation of cardiac risk prior to noncardiac surgery".) Preoperative chest radiography is generally not warranted for most patients undergoing elective surgery. However, a chest radiograph for most patients prior to CEA may be justified due to the association of carotid atherosclerosis with smoking and coronary heart disease [47]. (See "Preoperative medical evaluation of the healthy adult patient", section on 'Chest radiographs' and "Overview of established risk factors for cardiovascular disease".) Preoperative imaging Patients suspected of having carotid atherosclerosis are typically evaluated with carotid duplex ultrasound as the initial test to assess the severity and extent of carotid stenosis. Other useful noninvasive methods to assess the degree of stenosis of the internal carotid artery include computed tomography angiography, magnetic resonance angiography, and contrast-enhanced magnetic resonance angiography. The utility of these noninvasive methods and cerebral angiography in the initial evaluation of carotid stenosis is discussed in detail separately. (See "Evaluation of carotid artery stenosis".) In patients with a hemodynamically significant atherosclerotic lesion identified on duplex ultrasound, it remains controversial if further imaging is needed prior to endarterectomy in asymptomatic patients to verify the degree of stenosis or further evaluate arterial anatomy. Carotid duplex Prior to performing CEA in asymptomatic patients, we obtain a duplex ultrasound within one to two weeks of elective CEA to be certain that the carotid artery has not occluded, which contraindicates CEA. Some surgeons may feel the sensitivity of carotid duplex at their institution is not sufficient to reliably determine the degree of internal carotid artery stenosis or to rule out occlusion [48,49]. https://www.uptodate.com/contents/carotid-endarterectomy/print 7/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate In support of this point of view is a lack of uniformly applied, prospectively validated criteria in some settings for quantifying the degree of internal carotid artery stenosis with duplex ultrasound. However, there are disadvantages, risks, and costs associated with other imaging modalities including catheter-based angiography; magnetic resonance angiography, which tends to overestimate the degree of stenosis; and computed tomographic angiography, which may underestimate the degree of stenosis [50-52]. (See "Evaluation of carotid artery stenosis".) Experts in carotid ultrasound developed consensus-based recommendations for using duplex- derived velocity and imaging parameters to quantify internal carotid artery stenosis with duplex ultrasound [53]. These state that the utility of the recommendations should be verified in individual vascular laboratories, and the suggested parameters should not replace duplex parameters that are locally documented to provide accurate assessment of carotid stenosis. As such, it may be reasonable for the surgeon who has access to a certified vascular laboratory with ongoing quality assurance programs and staffed by registered vascular technologists to use duplex ultrasound as a sole imaging modality of the cervical internal carotid artery prior to performing CEA. Brain imaging In the symptomatic patient, the preoperative evaluation should also include computed tomography or magnetic resonance imaging of the brain to assess the degree of cerebral infarction, if any, and to exclude other disorders that might be responsible for symptoms (eg, subdural hematoma, tumor). The added risk and costs of catheter-based arteriography probably outweigh the benefit of obtaining more anatomic detail. The incidence of stroke associated with routine arteriography was 1.6 percent in the Asymptomatic Carotid Atherosclerosis Study (ACAS) , although this risk was lower than in other reports [54]. However, arteriography is the gold standard for evaluating intracranial atherosclerotic disease, which is present to some degree in many patients with stenosis of the extracranial internal carotid artery [55-57]. In an analysis of a subset of patients from North American Symptomatic Carotid Endarterectomy Trial (NASCET), the relative risk of stroke associated with intracranial atherosclerotic disease in medically treated patients was 1.3 for extracranial stenosis <50 percent and 1.8 for extracranial stenosis 85 to 99 percent [57]. CEA reduced this risk, suggesting that detection of intracranial atherosclerotic disease, particularly in those with moderate extracranial carotid stenosis, may help stratify patients into a group that is more likely to benefit from CEA. Of the available noninvasive tests (ie, transcranial Doppler, computed tomographic angiography, magnetic resonance angiography), CTA may be more accurate for identifying intracranial large artery stenosis. (See "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation' and "Evaluation of carotid artery stenosis".) https://www.uptodate.com/contents/carotid-endarterectomy/print 8/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Otolaryngologic examination Otolaryngologic examination, which may include laryngoscopy, should be performed in patients who have a residual vocal disturbance (tone change, hoarseness) after a prior neck surgery (eg, CEA, thyroid surgery). (See "Hoarseness in adults", section on 'Neurologic dysfunction' and "Complications of carotid endarterectomy", section on 'Nerve injury'.) PREOPERATIVE PREPARATION Medication management Antiplatelet therapy Aspirin Antiplatelet therapy with aspirin reduces the risk of stroke of any cause in patients undergoing CEA [58,59]. In addition, lower-dose aspirin (81 to 325 mg daily) is more effective than higher-dose aspirin (650 to 1300 mg daily). In a randomized trial involving 232 patients, aspirin (75 mg daily) or placebo treatment was started preoperatively and continued for six months [60]. Patients assigned to aspirin had significantly fewer strokes at one month and six months compared with those assigned to placebo. However, this study was likely underpowered [61]. The ASA and Carotid Endarterectomy (ACE) trial randomly assigned 2849 patients scheduled for endarterectomy to aspirin at doses of 81, 325, 650, or 1300 mg daily [62]. Aspirin was started before surgery and continued for three months. At three-month follow- up, the primary endpoint (stroke, myocardial infarction, vascular death) was significantly reduced in the lower-dose (81 or 325 mg daily) aspirin group compared with the higher- dose group (6.2 versus 8.4 percent). Consensus guidelines from the American Academy of Neurology and the American College of Chest Physicians recommend aspirin for symptomatic and asymptomatic patients undergoing CEA [61,63]. We recommend starting aspirin (81 to 325 mg daily) prior to CEA and continuing indefinitely in the absence of contraindications. Although other agents are available, aspirin is the best studied antiplatelet agent following CEA, and aspirin alone is generally deemed adequate for postoperative management given that the carotid plaque has been removed. However, for patients who are allergic or sensitive to aspirin, clopidogrel can be used as an alternative agent. For those patients with atherosclerotic plaque elsewhere (eg, lower extremity), other agents or combinations may be favored for long-term secondary prevention of cardiovascular events. https://www.uptodate.com/contents/carotid-endarterectomy/print 9/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Dual antiplatelet therapy or other regimens Without clear high-level data, any decision to use an agent other than aspirin or to proceed with dual antiplatelet therapy (DAPT) or triple antithrombotic therapy after CEA should be individualized and depends on the indications for antiplatelet therapy, clinical status, as well as operative findings [64-66]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk" and "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke" and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".) It may be reasonable to allow patients with chronically administered DAPT for other indications to continue these throughout the perioperative period. Most studies report an increased risk for bleeding with DAPT, but other outcomes are variable. In one trial of 102 patients undergoing CEA, rates of perioperative bleeding were similar for patients taking dipyridamole/aspirin (n = 39), dipyridamole/aspirin plus dextran (n = 30), or dipyridamole/aspirin plus clopidogrel (n = 33) [66]. In a database review from the Vascular Quality Initiative, 25 percent of patients (7059 of 28,683) undergoing CEA were on aspirin plus clopidogrel [67]. While DAPT significantly increased the risk of bleeding and reoperation after CEA, the risk for perioperative neurologic events was significantly reduced. In a later meta-analysis, operating times were shorter, and the incidence of neck hematoma, major bleeding, myocardial infarction, and perioperative (30 day) mortality was reduced for single antiplatelet therapy (125,850 patients) compared with DAPT (14,280 patients) [68]. In systematic review that included 11 studies involving 47,411 patients, 30 percent received DAPT and the remainder received aspirin only [69]. The rates of perioperative stroke were similar, but the risk of neck hematoma and reoperation for bleeding were increased. Long-term anticoagulation A decision to stop versus bridge long-term oral anticoagulation prior to CEA is individualized and made together with the patient's cardiologist or medical physician [70]. (See "Perioperative management of patients receiving anticoagulants" and "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy".) Regardless of whether oral anticoagulation is continued or temporarily discontinued (with or without bridging anticoagulation), antiplatelet therapy (ie, aspirin or clopidogrel) is initiated prior to CEA in the manner discussed above. (See 'Antiplatelet therapy' above.) https://www.uptodate.com/contents/carotid-endarterectomy/print 10/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Following CEA, if oral anticoagulation was temporarily discontinued, it is resumed and aspirin or clopidogrel initiated preoperatively is continued. Any new ischemic or bleeding episodes (or change in bleeding risk) should lead to a reevaluation of antithrombotic therapy. Statins The use of statins in symptomatic patients undergoing CEA may be associated with improved outcomes. In a retrospective observational study of 3360 CEAs, statin use was associated with reduced in-hospital mortality and combined in-hospital ischemic stroke or death (adjusted odds ratio 0.25, 95% CI 0.07-0.90 and 0.55, 95% CI 0.32-0.95, respectively), but in- hospital cardiac outcomes were not significantly improved [71]. A later, large database study reported similar results [72]. In contrast, statin use by patients with asymptomatic carotid stenosis was not associated with significantly different outcomes. Similar results were reported in another retrospective study involving 1566 patients with symptomatic and asymptomatic disease who received statins for at least one week before CEA [73]. These findings require confirmation in randomized clinical trials. Evidence is also emerging that statins may be of benefit in the perioperative period, and that this benefit might be lost if statins are discontinued. This issue is discussed elsewhere. (See "Perioperative medication management", section on 'Non-statin hypolipidemic agents'.) Sedative-analgesic medications Certain sedative-analgesic medications may be warranted to relieve preoperative anxiety. When an anxiolytic is chosen, a short-acting agent should be used, and it should be administered only after the patient's neurologic examination has been documented. (See "Anesthesia for carotid endarterectomy and carotid stenting".) Prophylactic antibiotics We recommend administration of antibiotics prior to CEA to control surgical site infection due to the frequent use of prosthetic material ( table 1) [74]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Vascular surgery'.) SURGICAL ANATOMY AND PHYSIOLOGY Carotid artery The left common carotid artery originates from the aortic arch, whereas the right common carotid artery originates from the innominate artery ( figure 1). The common carotid artery divides into the internal carotid artery and external carotid artery typically at the level of the superior border of the thyroid cartilage corresponding to the C3/C4 disc space. The vagus nerve is posterior to the common carotid artery in most individuals, although it may be located anteriorly in 5 to 10 percent of cases. Cranial nerve or other nerve injuries can occur https://www.uptodate.com/contents/carotid-endarterectomy/print 11/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate during dissection, retraction, or clamp placement ( figure 2). (See "Complications of carotid endarterectomy", section on 'Nerve injury'.) External carotid artery The external carotid artery has multiple branches that supply the face and scalp and provide collateral circulation to the brain ( figure 3). These branches include (caudal to cranial) the superior thyroid, lingual, facial, ascending pharyngeal, occipital, posterior auricular, maxillary, and superficial temporal arteries. The ascending pharyngeal artery arises very near the bifurcation of the carotid artery. In one anatomic study, the ascending pharyngeal artery originated from the external carotid artery in 80 percent of specimens (56 percent medially, 44 percent posteriorly) [75]. In the other 20 percent, the ascending pharyngeal artery originated from the internal carotid artery (5 percent), carotid bifurcation (5 percent), occipital artery (5 percent), and a trunk common to the lingual and facial arteries (5 percent). Internal carotid artery The internal carotid artery normally has no branches in the neck ( figure 4). The cervical segment of the internal carotid extends from the carotid bifurcation until it enters the carotid canal anterior to the jugular foramen. The internal carotid artery runs cranially within the carotid sheath and lies posterior and lateral to the external carotid artery beneath the medial border of the sternocleidomastoid muscle. In its distal (cranial) course, it passes beneath the hypoglossal nerve, the digastric muscle, the stylohyoid muscle, the occipital artery, and the posterior auricular artery. More cranially, the styloglossus and stylopharyngeus muscles, the tip of the styloid process and the stylohyoid ligament, the glossopharyngeal nerve, and the pharyngeal branch of the vagus nerve separate the internal from the external carotid artery. Location and influence of the carotid baroreceptor Baroreceptors are stretch-sensitive mechanoreceptors that respond to alterations in blood pressure. The carotid sinus baroreceptors are located within the adventitia of the origin of the internal carotid artery and are innervated by the sinus nerve of Hering, which is a branch of glossopharyngeal nerve. In response to low blood pressure, the nerve fibers decrease their firing rates, stimulating the sympathetic nervous system and inhibiting the parasympathetic nervous system via a centrally acting mechanism. Carotid sinus reactivity may be altered in patients with carotid atherosclerosis. Patients display varying degrees of heart rate or blood pressure alterations during manipulation of the carotid bifurcation, carotid clamping, or postoperatively following CEA [76]. Endarterectomy, removal of atheromatous debris, and reconstruction of the carotid artery may increase tension on the carotid sinus baroreceptor, increasing its activity [77]. The opposite is also possible if damage to the carotid sinus or sinus nerve occurs. As an example, eversion endarterectomy requires division of the carotid artery, and as a result, the longitudinal fibers of https://www.uptodate.com/contents/carotid-endarterectomy/print 12/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate the carotid sinus nerve are transected. A study that measured baroreceptor sensitivity following CEA found increased sensitivity with conventional CEA and decreased sensitivity with an eversion technique [78]. Correspondingly, postoperative blood pressures were significantly increased for eversion compared with conventional CEA (systolic: 127, diastolic: 64, mean: 86; versus systolic: 111, diastolic: 55, mean: 75). Compensation over time occurs due to intact baroreceptor mechanisms from the contralateral side and aortic arch. (See 'Conventional versus eversion endarterectomy' below.) ANESTHESIA Carotid endarterectomy can be performed using local/regional anesthesia or general anesthesia. Ideally, surgical and anesthetic teams should be competent in both techniques because a patient might prefer, or there might be a medical reason to choose, one anesthetic technique rather than another [79]. In an analysis of 26,070 cases in the American College of Surgeons National Surgical Quality Improvement Program database, general anesthesia was used in 84.6 percent and regional anesthesia was used in 15.4 percent of cases [80]. In another study looking at over 75,000 cases, 8.9 percent were performed under local/regional anesthesia. CEA performed under general anesthesia was associated with twice the odds of in-hospital myocardial infarctions, four times the odds of acute congestive heart failure, 1.5 times the odds of hemodynamic instability, and 1.8 times the odds of staying in the hospital for >1 day. However, the authors noted that the overall risk of adverse cardiac events after CEA was overall low, which made the differences clinically irrelevant [81]. Local/regional anesthesia may be more beneficial for some patients but can be uncomfortable for the patient and may necessitate urgent conversion to general anesthesia or urgent shunt placement. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Selection of the anesthetic technique'.) Anesthetic choice The use of general anesthesia for CEA or performing awake carotid surgery with local anesthesia (with or without cervical block) is generally determined by surgeon preference and patient characteristics and preference. The available evidence suggests that the choice of anesthetic technique has no significant impact on clinically important outcomes after CEA. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Selection of the anesthetic technique'.) Assessing brain perfusion Although 80 to 85 percent of patients tolerate clamping of the carotid artery without consequence, the collateral circulation via the circle of Willis should be https://www.uptodate.com/contents/carotid-endarterectomy/print 13/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate assessed in all patients who do not undergo mandatory shunting. (See 'Preoperative imaging' above and 'Carotid shunting' below.) During local/regional anesthesia in cooperative patients, clinical assessments are made during the procedure by monitoring mental status, speech, and extremity function. Agitation, slurred speech, disorientation, and extremity weakness are indications for shunt placement. During general anesthesia, assessment of cerebral perfusion to determine which patients should receive a shunt can be accomplished with a variety of methods (eg, measurement of carotid stump pressure, transcranial Doppler, somatosensory evoked potentials, jugular venous oxygen saturation). The most commonly used methods are discussed in detail elsewhere. (See 'Carotid shunting' below and "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Neuromonitoring modalities'.) SURGICAL TECHNIQUE Endarterectomy procedure General conduct of operation CEA is performed through a neck incision, either a longitudinal one along the anterior border of the sternocleidomastoid muscle or with a transverse incision in a skin crease at the level of carotid bulb. For the latter incision, preoperative imaging with ultrasound will guide the surgeon to the optimal placement of the incision. No significant differences between these approaches have been identified in terms of stroke, wound complications, or nerve complications [82]. The underlying platysma muscle and subcutaneous tissues are divided, the carotid sheath exposed, and the internal carotid artery is carefully identified and dissected. The extent of exposure of the artery is dependent upon the distribution of disease determined by intraoperative findings. Typically, dissection is needed from the common carotid artery to a point distal to the bifurcation of the internal carotid artery and external carotid artery that is beyond palpable internal carotid artery plaque to allow for clamping of normal soft artery. Following carotid dissection, the patient is systemically anticoagulated (heparin given as bolus, or using an alternative agent, as indicated). Monitoring the activated clotting time is not usually needed, owing to the short duration of carotid clamping, which is typically less than an hour. Carotid stump pressures can be obtained to help guide the need for shunt placement. The internal, common, and external arteries are clamped sequentially; the internal carotid artery is always clamped first to prevent embolization. A needle attached to a transducer is introduced into the common carotid artery. The clamp on the internal carotid artery is released and a https://www.uptodate.com/contents/carotid-endarterectomy/print 14/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate waveform is obtained. Mean pressures greater than 30 to 50 mmHg imply adequate collateralization via the circle of Willis down the ipsilateral carotid artery. Lower stump pressures are an indication for shunt placement, and higher pressures are associated with stroke rates <0.5 percent [83]. Critics of this technique caution that pressures are only obtained after initial clamping and, therefore, represent a "snapshot" in time. In addition, the criteria above should be used with caution in patients who have suffered prior ipsilateral strokes (potential vulnerable penumbra surrounding the prior infarct) since there is a poor correlation between adequate perfusion pressures and outcomes in this setting. The accuracy of the pressure in the face of a preocclusive (string) lesion may also be questionable. (See 'Assessing brain perfusion' above.) |
and the pharyngeal branch of the vagus nerve separate the internal from the external carotid artery. Location and influence of the carotid baroreceptor Baroreceptors are stretch-sensitive mechanoreceptors that respond to alterations in blood pressure. The carotid sinus baroreceptors are located within the adventitia of the origin of the internal carotid artery and are innervated by the sinus nerve of Hering, which is a branch of glossopharyngeal nerve. In response to low blood pressure, the nerve fibers decrease their firing rates, stimulating the sympathetic nervous system and inhibiting the parasympathetic nervous system via a centrally acting mechanism. Carotid sinus reactivity may be altered in patients with carotid atherosclerosis. Patients display varying degrees of heart rate or blood pressure alterations during manipulation of the carotid bifurcation, carotid clamping, or postoperatively following CEA [76]. Endarterectomy, removal of atheromatous debris, and reconstruction of the carotid artery may increase tension on the carotid sinus baroreceptor, increasing its activity [77]. The opposite is also possible if damage to the carotid sinus or sinus nerve occurs. As an example, eversion endarterectomy requires division of the carotid artery, and as a result, the longitudinal fibers of https://www.uptodate.com/contents/carotid-endarterectomy/print 12/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate the carotid sinus nerve are transected. A study that measured baroreceptor sensitivity following CEA found increased sensitivity with conventional CEA and decreased sensitivity with an eversion technique [78]. Correspondingly, postoperative blood pressures were significantly increased for eversion compared with conventional CEA (systolic: 127, diastolic: 64, mean: 86; versus systolic: 111, diastolic: 55, mean: 75). Compensation over time occurs due to intact baroreceptor mechanisms from the contralateral side and aortic arch. (See 'Conventional versus eversion endarterectomy' below.) ANESTHESIA Carotid endarterectomy can be performed using local/regional anesthesia or general anesthesia. Ideally, surgical and anesthetic teams should be competent in both techniques because a patient might prefer, or there might be a medical reason to choose, one anesthetic technique rather than another [79]. In an analysis of 26,070 cases in the American College of Surgeons National Surgical Quality Improvement Program database, general anesthesia was used in 84.6 percent and regional anesthesia was used in 15.4 percent of cases [80]. In another study looking at over 75,000 cases, 8.9 percent were performed under local/regional anesthesia. CEA performed under general anesthesia was associated with twice the odds of in-hospital myocardial infarctions, four times the odds of acute congestive heart failure, 1.5 times the odds of hemodynamic instability, and 1.8 times the odds of staying in the hospital for >1 day. However, the authors noted that the overall risk of adverse cardiac events after CEA was overall low, which made the differences clinically irrelevant [81]. Local/regional anesthesia may be more beneficial for some patients but can be uncomfortable for the patient and may necessitate urgent conversion to general anesthesia or urgent shunt placement. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Selection of the anesthetic technique'.) Anesthetic choice The use of general anesthesia for CEA or performing awake carotid surgery with local anesthesia (with or without cervical block) is generally determined by surgeon preference and patient characteristics and preference. The available evidence suggests that the choice of anesthetic technique has no significant impact on clinically important outcomes after CEA. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Selection of the anesthetic technique'.) Assessing brain perfusion Although 80 to 85 percent of patients tolerate clamping of the carotid artery without consequence, the collateral circulation via the circle of Willis should be https://www.uptodate.com/contents/carotid-endarterectomy/print 13/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate assessed in all patients who do not undergo mandatory shunting. (See 'Preoperative imaging' above and 'Carotid shunting' below.) During local/regional anesthesia in cooperative patients, clinical assessments are made during the procedure by monitoring mental status, speech, and extremity function. Agitation, slurred speech, disorientation, and extremity weakness are indications for shunt placement. During general anesthesia, assessment of cerebral perfusion to determine which patients should receive a shunt can be accomplished with a variety of methods (eg, measurement of carotid stump pressure, transcranial Doppler, somatosensory evoked potentials, jugular venous oxygen saturation). The most commonly used methods are discussed in detail elsewhere. (See 'Carotid shunting' below and "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Neuromonitoring modalities'.) SURGICAL TECHNIQUE Endarterectomy procedure General conduct of operation CEA is performed through a neck incision, either a longitudinal one along the anterior border of the sternocleidomastoid muscle or with a transverse incision in a skin crease at the level of carotid bulb. For the latter incision, preoperative imaging with ultrasound will guide the surgeon to the optimal placement of the incision. No significant differences between these approaches have been identified in terms of stroke, wound complications, or nerve complications [82]. The underlying platysma muscle and subcutaneous tissues are divided, the carotid sheath exposed, and the internal carotid artery is carefully identified and dissected. The extent of exposure of the artery is dependent upon the distribution of disease determined by intraoperative findings. Typically, dissection is needed from the common carotid artery to a point distal to the bifurcation of the internal carotid artery and external carotid artery that is beyond palpable internal carotid artery plaque to allow for clamping of normal soft artery. Following carotid dissection, the patient is systemically anticoagulated (heparin given as bolus, or using an alternative agent, as indicated). Monitoring the activated clotting time is not usually needed, owing to the short duration of carotid clamping, which is typically less than an hour. Carotid stump pressures can be obtained to help guide the need for shunt placement. The internal, common, and external arteries are clamped sequentially; the internal carotid artery is always clamped first to prevent embolization. A needle attached to a transducer is introduced into the common carotid artery. The clamp on the internal carotid artery is released and a https://www.uptodate.com/contents/carotid-endarterectomy/print 14/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate waveform is obtained. Mean pressures greater than 30 to 50 mmHg imply adequate collateralization via the circle of Willis down the ipsilateral carotid artery. Lower stump pressures are an indication for shunt placement, and higher pressures are associated with stroke rates <0.5 percent [83]. Critics of this technique caution that pressures are only obtained after initial clamping and, therefore, represent a "snapshot" in time. In addition, the criteria above should be used with caution in patients who have suffered prior ipsilateral strokes (potential vulnerable penumbra surrounding the prior infarct) since there is a poor correlation between adequate perfusion pressures and outcomes in this setting. The accuracy of the pressure in the face of a preocclusive (string) lesion may also be questionable. (See 'Assessing brain perfusion' above.) After measurement of the stump pressure, the clamp is placed back on the distal internal carotid artery, and the transducer needle is removed. Manipulation of the carotid bulb during CEA not infrequently results in hemodynamic instability intraoperatively and in the early postoperative period [84]. Adequate cerebral perfusion pressure (ie, systolic blood pressure) should be maintained during periods of hemodynamic instability to avoid low cerebral blood flow and cerebral ischemia. A longitudinal arteriotomy is performed below the level of the bifurcation and extended proximally and distally. If shunting is required, the shunt is placed after the vessel is opened and prior to the endarterectomy. For patients who are undergoing general anesthesia, some surgeons routinely place a carotid shunt while others use cerebral perfusion monitoring to guide the need for selective shunt placement. For these patients and those undergoing awake CEA using local anesthesia (with or without cervical block), the endarterectomy is often completed prior to the need to place a shunt, as indicated by brain monitoring. (See 'Carotid shunting' below and 'Assessing brain perfusion' above.) The carotid plaque, which is consistently found at the carotid bifurcation and the origin of the internal carotid artery, is then freed and removed through a dissection plane developed in the layers of the deep media. Great care is taken to create a smoothly tapered transition between the endarterectomized portion of the artery and its normal distal extent. This maneuver avoids intimal flaps that might lead to arterial dissection after flow is reestablished. Some surgeons will place "tacking sutures" at the distal end of the endarterectomy to further guard against possible dissection of the distal internal carotid artery following restoration of blood flow. A variation of the procedure removes the plaque after transecting the internal carotid near its origin. (See 'Conventional versus eversion endarterectomy' below.) After meticulous inspection of the endarterectomized surface to remove any residual plaque or debris, attention is directed at repair. Some surgeons choose to repair primarily, while others patch the artery with saphenous vein or prosthetic material such as polyester (eg, Dacron), https://www.uptodate.com/contents/carotid-endarterectomy/print 15/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate polytetrafluoroethylene (eg, Gore-Tex), or bovine pericardium. There is evidence that routine patch use lowers the risk of perioperative carotid thrombosis, stroke, and late restenosis of the endarterectomy site. (See 'Patch angioplasty versus primary closure' below.) Just prior to completion of the arterial closure, the carotid clamps are sequentially briefly released and re-clamped to back bleed (external carotid artery, internal carotid artery) and forward flush (common carotid artery) the vessel, which is then irrigated (eg, heparinized saline) and suctioned of any residual debris. After the suture line is completed, flow is restored first to the external carotid artery, then to the internal carotid artery to avoid any distal embolization to the cerebral hemisphere. A topical hemostatic agent may be used over the suture line to slow any oozing of blood. At the completion of the procedure, we suggest reversal of heparin with protamine. The only randomized trial comparing protamine with no protamine reported significantly lower rates of wound drainage but cautioned that protamine might increase the risk for thrombotic complications [85]. In a retrospective analysis of 4587 patients in a regional registry, reversal of heparin with protamine was associated with a lower incidence of serious bleeding requiring reoperation (0.64 versus 1.7 percent) compared with no reversal, without increasing the risk of myocardial infarction, stroke, or death [86]. A later systematic review that included the randomized trial, the registry study, and 10 other observational studies similarly found no significant differences for stroke (nine studies), myocardial infarction (three studies), or mortality (seven studies) for those who received protamine compared with those who did not; however, protamine use significantly decreased the risk of major bleeding complications requiring reoperation (relative risk [RR] 0.57; 95% CI 0.39-0.84; 10 studies) [87]. Dosing of heparin (fixed dosing, per body weight), dosing of protamine, and use of monitoring via activated clotting time varied across the studies and could not be adequately evaluated. A subgroup analysis suggested that stroke risk may be higher for primary carotid closure compared with patch closure when using protamine, but the overall number of events was small, limiting the ability to draw a firm conclusion. Although a small Jackson-Pratt drain can be placed, drains are generally not required and have not been shown to definitively reduce the rates of significant postoperative incisional hematomas. The platysma and skin are closed and the wound dressed. A completion study to assess the integrity of the repair can be performed intraoperatively using Doppler evaluation, duplex ultrasound, or contrast arteriogram, depending upon resources and operator preference [88-100]. A retrospective review that categorized surgeons as rarely, selectively, or routinely using completion imaging found no significant differences in perioperative stroke or death after adjustment for patient characteristics [92]. A small but https://www.uptodate.com/contents/carotid-endarterectomy/print 16/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate significant reduction in restenosis (>70 percent) was found for surgeons who performed completion imaging. High access More distal (cranial) access may be needed. As the internal carotid artery is dissected, the hypoglossal nerve will be seen to cross anteriorly. The nerve is isolated and gently retracted. The ansa hypoglossus (ansa cervicalis) nerve, which innervates the strap muscles of the neck, is typically seen coursing along the carotid sheath. The ansa can be divided without clinically significant consequence when dissection needs to be carried more cranially. The posterior belly of the digastric muscle can also be divided. Subluxation of the jaw facilitated by nasotracheal intubation, or mandibular osteotomies, while frequently discussed, are rarely warranted. Conventional versus eversion endarterectomy Eversion endarterectomy is a variant of CEA. The internal carotid artery is transected horizontally at its origin at the carotid bulb and then the artery is everted, or turned inside out, which creates an exposure not seen with vertical arteriotomy. A modification of the technique that uses a linear incision over the common carotid artery and proximal internal carotid artery has been described [101]. Eversion endarterectomy is particularly appealing in small arteries and in patients with significant carotid redundancy as a means to eliminate carotid kinks and coils. However, in our opinion, the bulk of the evidence does not favor one technique over the other. The largest and best designed trial comparing eversion endarterectomy with conventional endarterectomy (EVEREST trial) was a multicenter trial that included 1342 patients [102]. No significant differences were found for the primary endpoints (perioperative stroke and death, carotid occlusion) or secondary endpoints (any stroke, ipsilateral stroke, transient ischemic attack, cranial nerve injury, neck hematoma, myocardial infarction). For eversion CEA compared with conventional CEA, the odds ratio for a combined endpoint of perioperative major stroke or death was 1.0 (95% CI 0.4-2.9), and for any perioperative stroke, 1.2 (95% CI 0.5-2.7). Compared with CEA performed without a patch, eversion CEA and conventional patched CEA each had a lower risk of carotid restenosis (hazard ratio [HR] 0.3, 95% CI 0.2-0.6, and HR 0.2, 95% CI 0.07-0.6, respectively). A meta-analysis that included the EVEREST trial and five other smaller trials [102- 108] identified a trend toward a reduced risk of perioperative (30 day) stroke for eversion CEA compared with conventional CEA (odds ratio [OR] 0.56, 95% CI 0.33-0.96) [109]. Randomized trials and other observational studies that have evaluated conventional versus eversion CEA have included patients with asymptomatic and symptomatic disease [102-110]. A post hoc analysis of data from the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial found no overall difference between the techniques; https://www.uptodate.com/contents/carotid-endarterectomy/print 17/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate however, perioperative outcomes were better for conventional CEA, while later outcomes favored eversion CEA [111]. Ipsilateral stroke or death 30 days was significantly reduced for conventional versus eversion CEA (9 versus 3 percent), but the risk of ipsilateral stroke >30 days was significantly lower for eversion compared with conventional CEA (3 versus 0 percent). Interestingly, eversion CEA was not found to have a significantly lower incidence of restenosis in contrast to other studies [109,112]. Proponents of eversion CEA feel that once the technique has been mastered, it may be easier to perform than conventional CEA. Although this may be so, advocates of conventional CEA point out that shunt insertion during eversion CEA can be more difficult since the plaque must be completely removed before the shunt can be inserted. In addition, eversion CEA is less commonly introduced during vascular surgery training, and, for those who adopt it later, the technique may be associated with a learning curve. A retrospective review at an academic medical center compared the outcomes of the first 100 patients on whom they performed eversion endarterectomy with 100 patients who underwent conventional endarterectomy [113]. The rate of perioperative neurologic deficits and deaths were not significantly different. One case of amaurosis occurred after eversion CEA, and one case each of transient cerebral ischemia and retinal infarction after conventional CEA; one cardiac death occurred with each. No significant differences were seen in the rate of critical (>80 percent) residual or recurrent stenosis, late stroke, or late carotid occlusion at 36 months follow-up. However, eversion endarterectomy had a higher rate of >50 percent recurrent stenosis (38 versus 6 percent) compared with conventional CEA in spite of similar residual stenosis rates. The significance of this late mild-to-moderate stenosis is unknown. A systematic review comparing techniques found a higher risk of early postoperative hypertension for eversion endarterectomy; conventional techniques were more often associated with hypotension [114]. Patch angioplasty versus primary closure As noted above, some surgeons choose to repair to the carotid artery primarily, while others patch the artery with saphenous vein or synthetic material (eg, polytetrafluoroethylene, Dacron, bovine pericardium) [115-121]. We recommend patch closure for all patients undergoing CEA (noneversion technique). In a review of 118,711 patients undergoing CEA from the Vascular Quality Initiative, 6,668 (5.6 percent) patients had primary repair [122]. Among these patients, the rate of neurologic events was higher compared with those who underwent patch closure. Trials performed in patients undergoing CEA suggest two benefits from use of a patch: a marked reduction in the frequency of 50 percent restenosis and a lower rate of ipsilateral stroke [123,124]. A systematic review of patch angioplasty versus primary closure during CEA identified 10 trials involving 1967 patients undergoing 2157 operations [124]. Many of the trials were https://www.uptodate.com/contents/carotid-endarterectomy/print 18/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate limited by significant methodological flaws; most were small, and none could be analyzed on a true intention-to-treat basis because of losses to follow-up. The use of a patch is associated with: Reduction in the risk of ipsilateral stroke in the perioperative period (OR 0.31, 95% CI 0.1- 0.63 and long-term OR 0.32, 95% CI 0.16-0.63). A reduced risk of perioperative arterial occlusion (OR 0.18, 95% CI 0.08-0.41). Decreased restenosis during long-term follow-up in eight trials (OR 0.24, 95% CI 0.17-0.34). These results are more certain than those of the previous review since the number of operations and events have increased. However, the sample sizes are still relatively small, data were not available from all trials, and there was significant loss to follow-up. No significant correlation was found between use of patch angioplasty and the risk of either perioperative or long-term all-cause death rates. A separate systematic review identified 14 trials comparing various types of patches: seven compared vein patch closure with polytetrafluoroethylene patch closure; five compared Dacron patches with other synthetic materials; and two compared bovine pericardium with other synthetic materials [116]. No significant differences were found comparing synthetic patches versus vein patches for stroke, death, arterial occlusion, arterial rupture, nerve palsy, wound infection, or recurrent arterial stenosis during perioperative at one-year follow-up. The review identified one high-quality trial comparing Dacron with polytetrafluoroethylene patches, reporting that Dacron patches were associated with an increased risk for perioperative stroke and an increased risk for both perioperative and late recurrent carotid stenosis [119,120]. Using a synthetic patch decreased the risk of pseudoaneurysm relative to using a vein patch (OR 0.09, 95% CI 0.02-0.49). However, the studies that examined pseudoaneurysm outcomes were older [125-127], using saphenous vein, jugular vein, or other vein sites; the technical aspects of vein handling were not included. In one of these studies, the incidence of pseudoaneurysm was 17 percent using jugular vein, 9 percent using saphenous vein or polytetrafluoroethylene, and 5 percent with primary closure [125]. The use of vein during initial CEA has declined, but when vein is needed (eg, graft infection, redo carotid surgery), we prefer to use proximal saphenous vein harvested from the groin rather than more distal vein, which is associated with rupture. A later trial comparing polytetrafluoroethylene (eg, Acuseal) with bovine pericardium also found no significant differences between these materials for ipsilateral stroke, recurrent carotid stenosis, or other perioperative complications (eg, neck hematoma); mean hemostasis time was slightly lower for the polytetrafluoroethylene patch. https://www.uptodate.com/contents/carotid-endarterectomy/print 19/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Very few studies have evaluated arterial complications, such as hemorrhage, infection, cranial nerve injury, or pseudoaneurysm formation for patch repair compared with primary closure, but the available data suggest no significant differences [128]. Carotid shunting If the patient demonstrates evidence of cerebral ischemia by any neuromonitoring technique, carotid shunting should be performed expeditiously if one is not already in place. For surgeons using "selective shunting," shunt placement is indicated for: Awake patients who develop agitation, slurred speech, disorientation, or extremity weakness, or the presence of theta and delta waves or disorganized rhythms on electroencephalography monitoring [129]. For patients undergoing general anesthesia, electroencephalography (raw or processed) is commonly used to monitor brain perfusion. A neuromonitoring team assesses the electroencephalography tracings for cerebral ischemia indicating the need for shunting (eg, presence of theta and delta waves or disorganized rhythms). Another method is to measure carotid stump pressures. (See 'Assessing brain perfusion' above.) In an updated Cochrane meta-analysis of three trials [130-132], compared with no shunting, the risk of perioperative stroke was lower for routine shunting (OR 0.15, 95% CI 0.03-0.78), as was the risk of ipsilateral stroke within 30 days of surgery (OR 0.41, 95% CI 0.18-0.97) and stroke- related death within 30 days of surgery (OR 0.13, 95% CI 0.02-0.96) [133]. The authors noted though that the analysis was inadequately powered to reliably detect these effects. Routine versus selective shunting Studies targeted at defining the best approach to shunting have been equivocal with respect to demonstrating any difference in important clinical outcomes when comparing routine versus selective shunting. Given that there is no consensus, the approach to shunting remains largely a matter of surgeon preference [133-135]. In an analysis of 13,469 CEAs performed for symptomatic carotid stenosis in the Vascular Quality Initiative database between 2010 to 2019, 3186 (24 percent) were performed by surgeons considered routine shunters (ie, utilization in >95 percent of cases). The overall in-hospital stroke and death rates were similar between routine shunters and selective shunters [136]. In a trial that randomly assigned 200 patients undergoing CEA to general anesthesia with routine shunting (98 patients) or selective shunting based on stump pressure, the difference in the combined outcome of perioperative transient ischemic attack or stroke rates was not statistically significant (routine shunting: 2 percent; selective shunting: 2.9 percent) as was the https://www.uptodate.com/contents/carotid-endarterectomy/print 20/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate difference in perioperative complication rates (routine shunting: 8.3 percent; selective shunting: 7.8 percent) [137]. Proponents of selective carotid shunting argue that shunting exposes patients to risks that may include the following: Formation of an intimal flap during shunt insertion, resulting in arterial dissection Dislodgement of plaque emboli during vessel manipulation Air embolism due to bubbles in the shunt Several studies have identified factors that may increase the need for a shunt, including older age, female sex, hypertension, contralateral carotid artery occlusion, and history of contralateral carotid artery surgery [138]. Surgeons who routinely shunt feel that shunt complications are less likely to occur if shunting is routinely practiced. The advantages of routine shunting may include: Familiarity of the surgeon and surgical team with the technique. Among patients with contralateral carotid occlusion undergoing CEA, data from the Vascular Study Group of New England database reported that surgeons who routinely shunted had lower stroke rates compared with those who selectively shunted [139]. The higher rate of stroke amongst practitioners who selectively shunted may be attributable to a lack of familiarity with the procedure. Other groups have also reported a higher rate of shunting in patients with contralateral carotid occlusion [140,141]. Cerebral flow is assured with a properly placed shunt without need for neurological monitoring (electroencephalography, stump pressure, awake neurologic examination). However, it should be recognized that although routine shunting may avoid the need for intraoperative neuromonitoring, approximately 90 percent of patients would not require a shunt based on the results of neuromonitoring. In a meta-analysis that included eight studies, fewer arteries were shunted when local anesthesia was used compared with general anesthesia (15 versus 42 percent); however, the rate of stroke or death was similar [142]. Shunt type and placement There are insufficient data to support one type of carotid shunt over another. Many shunts are available for use (Argyle, Pruitt-Inahara, Brenner, Burbank, Sundt), and each has its advantages and disadvantages. The features (stiff versus flexible, inline Doppler, balloons https://www.uptodate.com/contents/carotid-endarterectomy/print 21/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate for occlusion) and use of these shunts can be found on proprietary websites. The selection of a particular shunt is based largely on surgeon experience. Most surgeons become comfortable using one particular shunt. When a shunt is used, it is placed beyond the proximal and distal extent of the arteriotomy from the common to the internal carotid artery. Blood flows through the shunt, providing continuous cerebral perfusion during the procedure. The distal end is placed first into the internal carotid artery and the shunt back is bled to wash out any debris or air bubbles within the shunt prior to placing it into the common carotid artery and restoring antegrade cerebral perfusion. To minimize trapping debris within the shunt, it is mandatory to place the shunt in relatively disease-free segments of the internal and common carotid arteries. After shunt placement, neurologic reassessment is performed again. POSTOPERATIVE CARE Upon recovery from anesthesia, a neurologic assessment is performed and repeated every hour during recovery. Because blood pressure lability is common in the first 12 to 24 hours postoperatively, it is standard care for CEA patients to be placed in a monitored setting with an arterial line in place. Systolic blood pressure should be maintained between 100 to 150 mmHg in the postoperative period to prevent complications related to hypertension (eg, neck hematoma) or hypotension (eg, cerebral ischemia). (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Blood pressure control'.) Minor headache is common following CEA, but increasing or severe headache in the postoperative period may be an indicator of cerebral hyperperfusion syndrome or intracranial hemorrhage and should be evaluated with a computed tomographic scan. (See "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome'.) PERIOPERATIVE MORBIDITY AND MORTALITY While a number of controlled trials have highlighted the patient population most likely to benefit from CEA, this operation is not without risk [143]. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CEA'.) Perioperative mortality associated with CEA ranges from <0.5 to 4.3 percent and may be higher when this procedure is performed at nontertiary care centers [1,144-146]. Surgeons are encouraged to keep accurate records of their individual stroke rates to ensure that standards are upheld. Low patient volume (<3 CEAs performed every two years) and a greater number of https://www.uptodate.com/contents/carotid-endarterectomy/print 22/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate years since licensure of the surgeon are associated with worse outcomes following CEA [147,148]. In experienced hands, the risk of stroke associated with CEA is generally 2 percent or less. However, certain anatomic and physiologic high-risk criteria are associated with worse clinical outcomes for CEA. In a review of 6370 patients undergoing CEA in the Society for Vascular Surgery Vascular Registry, high-risk patients had a higher rate of composite death, stroke, and myocardial infarction compared with normal anatomic or physiologic risk patients (symptomatic: 7.3 versus 4.6 percent; asymptomatic: 5 versus 2.2 percent) [149]. In another review of 25,788 patients undergoing CEA in the American College of Surgeons National Surgical Quality Improvement Program, 30-day stroke/death rates were significantly higher in physiologic high-risk (4.6 percent) and anatomic high-risk (3.6 percent) patients compared with normal-risk patients (2.3 percent) [150]. In a review of the Vascular Quality Initiative that included all who underwent from 2013 to 2016, patients were stratified as being normal or high risk for undergoing CEA based on criteria set forth by the US Centers for Medicare and Medicaid Services [151]. Among over 44,000 patients who underwent CEA, perioperative stroke occurred in 1.0 percent in normal-risk and 1.4 percent in high-risk patients. At two years, stroke occurred in 1.9 percent in normal-risk and 2.4 percent in high-risk patients. A retrospective review of the United States Medicare database evaluated outcomes of 454,717 CEA and 27,943 carotid artery stenting patients before and after the 2005 National Coverage Determination to reimburse carotid artery stenting for Medicare beneficiaries [148]. CEA rates declined from 18.1 to 12.7 per 10,000 beneficiaries between 2002 and 2008 (overall rates also declined). Even though patients undergoing CEA in later years were older and had more comorbidities compared with earlier years, perioperative (30 day) mortality declined from 1.4 to 1.17 percent. In a later systematic review of only large (>1000 participants each) observational cohort studies, the composite risk of procedural stroke/death among over 130,000 patients undergoing CEA decreased from before 2005 compared with from 2005 onward for symptomatic patients and asymptomatic patients (5.1 versus 2.7 percent and 3.2 versus 1.5 percent, respectively) [152]. By comparison, procedural stroke/death rates for carotid artery stenting did not change significantly over time (symptomatic: 4.8 percent; asymptomatic: 2.6 percent). For studies that reported stroke alone or death alone, no differences were seen from before 2005 compared with from 2005 onward for either procedure. The authors speculated that a trend toward https://www.uptodate.com/contents/carotid-endarterectomy/print 23/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate centralization of CEA in high-volume centers, and specialist support, may have contributed to the decrease in CEA procedural risks. Complications associated with CEA include perioperative events such as myocardial infarction; stroke; hyperperfusion syndrome; nerve injury; parotitis and bleeding, which can lead to neck hematoma requiring reoperation; and late carotid restenosis. These complications are discussed in detail elsewhere. (See "Complications of carotid endarterectomy".) FOLLOW-UP CARE Following CEA, patients are typically discharged within one to three days. The most common cause of delay in discharge is difficulty controlling blood pressure. Control of blood pressure prior to performing CEA cannot be overemphasized. We follow up with the patient at one month postoperatively, at which time we also obtain a carotid duplex study. If there are any wound- related issues or other problems, arrangements should be made to see the patient sooner. Readmission following CEA is relatively high. In a review that included 235,247 patients undergoing carotid intervention, 8.8 percent of the patients undergoing CEA required readmission, which was lower compared with carotid artery stenting [153]. Significant factors that increased the likelihood of readmission included age >80 years (odds ratio [OR] 1.25, 95% CI 1.20-1.30), renal failure (OR 1.6, 95% CI 1.56-1.73), heart failure (OR 1.6, 95% CI 1.57-1.73), and diabetes (OR 1.4, 95% CI 1.27-1.52). A separate review of data from 2005 to 2010 from the National Surgical Quality Improvement Program found that 33 percent of strokes, 53 percent of deaths, and 32 percent of cardiac events occurred after hospital discharge [154]. Care of the incision The postoperative dressing is removed on the first postoperative day. If a drain has been placed, it should be removed as soon as possible in the postoperative period (day 1 or 2) to decrease the potential for wound infection provided there is no significant drainage. Antibiotics are limited to perioperative prophylaxis. (See 'Prophylactic antibiotics' above.) Duplex surveillance Repeat duplex ultrasonography should be obtained three to six weeks following CEA to establish a new baseline for future comparison. Duplex surveillance is performed at six months and annually. More frequent intervals may be warranted if a contralateral stenosis is being observed. (See "Complications of carotid endarterectomy", section on 'Carotid restenosis'.) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/carotid-endarterectomy/print 24/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Carotid artery disease (The Basics)") SUMMARY AND RECOMMENDATIONS Carotid endarterectomy The effectiveness of carotid endarterectomy (CEA) for moderate-to-severe asymptomatic or symptomatic carotid artery stenosis has been established in large, randomized trials. CEA in patients with asymptomatic carotid stenosis prior to cardiac or general surgery has no demonstrated benefit. For patients with indications for bilateral CEA, a staged rather than combined procedure is performed. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic extracranial carotid atherosclerotic disease" and 'Introduction' above and 'Carotid atherosclerotic disease' above.) Preoperative imaging Prior to CEA for asymptomatic carotid stenosis, duplex ultrasound may be sufficient to reliably determine the degree of internal carotid artery stenosis and assess local anatomy when performed in a certified vascular laboratory using validated criteria. If these standards cannot be met, additional vascular imaging to verify the degree of stenosis should be performed. (See 'Carotid duplex' above.) https://www.uptodate.com/contents/carotid-endarterectomy/print 25/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Antiplatelet therapy Prior to CEA, we recommend starting aspirin (81 to 325 mg daily) and continuing treatment indefinitely (Grade 1B). For patients who are sensitive to aspirin, clopidogrel is an alternative agent. (See 'Antiplatelet therapy' above.) Statin therapy For patients with symptomatic carotid stenosis, we suggest initiation of statin therapy prior to CEA (or maintenance in patients already being treated) (Grade 2B). The use of statins in symptomatic patients is associated with reduced morbidity and mortality following CEA. For patients with asymptomatic carotid stenosis undergoing CEA, statin therapy has not shown the same benefit but may be indicated for other medical reasons. (See 'Statins' above.) |
percent) patients compared with normal-risk patients (2.3 percent) [150]. In a review of the Vascular Quality Initiative that included all who underwent from 2013 to 2016, patients were stratified as being normal or high risk for undergoing CEA based on criteria set forth by the US Centers for Medicare and Medicaid Services [151]. Among over 44,000 patients who underwent CEA, perioperative stroke occurred in 1.0 percent in normal-risk and 1.4 percent in high-risk patients. At two years, stroke occurred in 1.9 percent in normal-risk and 2.4 percent in high-risk patients. A retrospective review of the United States Medicare database evaluated outcomes of 454,717 CEA and 27,943 carotid artery stenting patients before and after the 2005 National Coverage Determination to reimburse carotid artery stenting for Medicare beneficiaries [148]. CEA rates declined from 18.1 to 12.7 per 10,000 beneficiaries between 2002 and 2008 (overall rates also declined). Even though patients undergoing CEA in later years were older and had more comorbidities compared with earlier years, perioperative (30 day) mortality declined from 1.4 to 1.17 percent. In a later systematic review of only large (>1000 participants each) observational cohort studies, the composite risk of procedural stroke/death among over 130,000 patients undergoing CEA decreased from before 2005 compared with from 2005 onward for symptomatic patients and asymptomatic patients (5.1 versus 2.7 percent and 3.2 versus 1.5 percent, respectively) [152]. By comparison, procedural stroke/death rates for carotid artery stenting did not change significantly over time (symptomatic: 4.8 percent; asymptomatic: 2.6 percent). For studies that reported stroke alone or death alone, no differences were seen from before 2005 compared with from 2005 onward for either procedure. The authors speculated that a trend toward https://www.uptodate.com/contents/carotid-endarterectomy/print 23/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate centralization of CEA in high-volume centers, and specialist support, may have contributed to the decrease in CEA procedural risks. Complications associated with CEA include perioperative events such as myocardial infarction; stroke; hyperperfusion syndrome; nerve injury; parotitis and bleeding, which can lead to neck hematoma requiring reoperation; and late carotid restenosis. These complications are discussed in detail elsewhere. (See "Complications of carotid endarterectomy".) FOLLOW-UP CARE Following CEA, patients are typically discharged within one to three days. The most common cause of delay in discharge is difficulty controlling blood pressure. Control of blood pressure prior to performing CEA cannot be overemphasized. We follow up with the patient at one month postoperatively, at which time we also obtain a carotid duplex study. If there are any wound- related issues or other problems, arrangements should be made to see the patient sooner. Readmission following CEA is relatively high. In a review that included 235,247 patients undergoing carotid intervention, 8.8 percent of the patients undergoing CEA required readmission, which was lower compared with carotid artery stenting [153]. Significant factors that increased the likelihood of readmission included age >80 years (odds ratio [OR] 1.25, 95% CI 1.20-1.30), renal failure (OR 1.6, 95% CI 1.56-1.73), heart failure (OR 1.6, 95% CI 1.57-1.73), and diabetes (OR 1.4, 95% CI 1.27-1.52). A separate review of data from 2005 to 2010 from the National Surgical Quality Improvement Program found that 33 percent of strokes, 53 percent of deaths, and 32 percent of cardiac events occurred after hospital discharge [154]. Care of the incision The postoperative dressing is removed on the first postoperative day. If a drain has been placed, it should be removed as soon as possible in the postoperative period (day 1 or 2) to decrease the potential for wound infection provided there is no significant drainage. Antibiotics are limited to perioperative prophylaxis. (See 'Prophylactic antibiotics' above.) Duplex surveillance Repeat duplex ultrasonography should be obtained three to six weeks following CEA to establish a new baseline for future comparison. Duplex surveillance is performed at six months and annually. More frequent intervals may be warranted if a contralateral stenosis is being observed. (See "Complications of carotid endarterectomy", section on 'Carotid restenosis'.) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/carotid-endarterectomy/print 24/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Carotid artery disease (The Basics)") SUMMARY AND RECOMMENDATIONS Carotid endarterectomy The effectiveness of carotid endarterectomy (CEA) for moderate-to-severe asymptomatic or symptomatic carotid artery stenosis has been established in large, randomized trials. CEA in patients with asymptomatic carotid stenosis prior to cardiac or general surgery has no demonstrated benefit. For patients with indications for bilateral CEA, a staged rather than combined procedure is performed. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic extracranial carotid atherosclerotic disease" and 'Introduction' above and 'Carotid atherosclerotic disease' above.) Preoperative imaging Prior to CEA for asymptomatic carotid stenosis, duplex ultrasound may be sufficient to reliably determine the degree of internal carotid artery stenosis and assess local anatomy when performed in a certified vascular laboratory using validated criteria. If these standards cannot be met, additional vascular imaging to verify the degree of stenosis should be performed. (See 'Carotid duplex' above.) https://www.uptodate.com/contents/carotid-endarterectomy/print 25/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Antiplatelet therapy Prior to CEA, we recommend starting aspirin (81 to 325 mg daily) and continuing treatment indefinitely (Grade 1B). For patients who are sensitive to aspirin, clopidogrel is an alternative agent. (See 'Antiplatelet therapy' above.) Statin therapy For patients with symptomatic carotid stenosis, we suggest initiation of statin therapy prior to CEA (or maintenance in patients already being treated) (Grade 2B). The use of statins in symptomatic patients is associated with reduced morbidity and mortality following CEA. For patients with asymptomatic carotid stenosis undergoing CEA, statin therapy has not shown the same benefit but may be indicated for other medical reasons. (See 'Statins' above.) Antibiotic prophylaxis We recommend antibiotic prophylaxis prior to CEA to reduce the risk of surgical site infection due to the frequent use of prosthetic material (Grade 1B). Antibiotics should be discontinued within 24 hours. (See 'Prophylactic antibiotics' above.) Anesthesia CEA can be performed using general anesthesia or local anesthesia (with or without cervical block). Statistically significant differences for major endpoints (perioperative stroke, myocardial infarction, and death) have not been consistently shown for differing anesthetic approaches. The choice of anesthetic technique is largely dependent on the preferences of the patient, the anesthesiologist, and the surgeon. (See 'Anesthesia' above.) Carotid endarterectomy technique No one technique for plaque removal has been found to be superior over another with respect to the incidence of stroke, death, or other morbidity. As with many surgical techniques, one technique may be preferable to another for specific circumstances, and the choice of technique is largely dependent on the preferences and experience of the surgeon. (See 'Endarterectomy procedure' above and 'Conventional versus eversion endarterectomy' above.) Prior to carotid artery clamping, the patient is systemically anticoagulated, typically using heparin. At the completion of the procedure, we suggest reversal of heparin with protamine over no reversal (Grade 2B). (See 'General conduct of operation' above.) Following carotid plaque removal, we recommend patch closure of the carotid artery over no patch (noneversion technique) (Grade 1B). With conventional CEA, carotid patch techniques are associated with decreased rates of stroke and carotid restenosis. No one patch material (synthetic, vein, bovine pericardium) has been shown to be superior over another. (See 'Patch angioplasty versus primary closure' above.) https://www.uptodate.com/contents/carotid-endarterectomy/print 26/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Postoperative care After the completion of the procedure, the patient's neurologic status and blood pressure are carefully monitored. We keep the systolic blood pressure between 100 and 150 mmHg. Hypotension and hypertension are both associated with adverse outcomes. (See 'Postoperative care' above.) Perioperative morbidity and mortality The perioperative mortality associated with CEA ranges from <0.5 to 3 percent. Complications associated with CEA include perioperative complications such as myocardial infarction; stroke; hyperperfusion syndrome; nerve injury; parotitis and bleeding, which can lead to neck hematoma requiring reoperation; and late carotid restenosis. (See 'Perioperative morbidity and mortality' above and "Complications of carotid endarterectomy".) ACKNOWLEDGMENTS The editorial staff at UpToDate acknowledges Ronald M Fairman, MD, who contributed to an earlier version of this topic review. The editorial staff also acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic. UpToDate also wishes to acknowledge Dr. Mohler's work as our Section Editor for Vascular Medicine. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Knappich C, Kuehnl A, Haller B, et al. 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105. Ballotta E, Da Giau G, Saladini M, et al. Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study. Surgery 1999; 125:271. 106. Balzer, K. Eversion versus conventional endarterectomy. In: Perioperative monitoring in car otid surgery, Horsch, S, Ktenidis, K (Eds), Steinkopff Spinger, Darmstadt 1998. p.159-165. 107. Cao P, Giordano G, De Rango P, et al. Eversion versus conventional carotid endarterectomy: late results of a prospective multicenter randomized trial. J Vasc Surg 2000; 31:19. 108. Vanmaele RG, Van Schil PE, DeMaeseneer MG, et al. Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study. Cardiovasc Surg 1994; 2:573. 109. Antonopoulos CN, Kakisis JD, Sergentanis TN, Liapis CD. Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies. Eur J Vasc Endovasc Surg 2011; 42:751. 110. Ballotta E, Toniato A, Da Giau G, et al. Durability of eversion carotid endarterectomy. J Vasc Surg 2014; 59:1274. https://www.uptodate.com/contents/carotid-endarterectomy/print 35/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate 111. Demirel S, Attigah N, Bruijnen H, et al. Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial. Stroke 2012; 43:1865. 112. Cao PG, de Rango P, Zannetti S, et al. Eversion versus conventional carotid endarterectomy for preventing stroke. Cochrane Database Syst Rev 2001; :CD001921. 113. Brothers TE. Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients. J Vasc Surg 2005; 42:429. 114. Demirel S, Goossen K, Bruijnen H, et al. Systematic review and meta-analysis of postcarotid endarterectomy hypertension after eversion versus conventional carotid endarterectomy. J Vasc Surg 2017; 65:868. 115. Lazarides MK, Christaina E, Argyriou C, et al. Editor's Choice - Network Meta-Analysis of Carotid Endarterectomy Closure Techniques. Eur J Vasc Endovasc Surg 2021; 61:181. 116. Orrapin S, Benyakorn T, Howard DP, et al. Patches of different types for carotid patch angioplasty. Cochrane Database Syst Rev 2021; 2:CD000071. 117. Huizing E, Vos CG, van den Akker PJ, et al. A systematic review of patch angioplasty versus primary closure for carotid endarterectomy. J Vasc Surg 2019; 69:1962. 118. Stone PA, AbuRahma AF, Mousa AY, et al. Prospective randomized trial of ACUSEAL versus Vascu-Guard patching in carotid endarterectomy. Ann Vasc Surg 2014; 28:1530. 119. AbuRahma AF, Hannay RS, Khan JH, et al. Prospective randomized study of carotid endarterectomy with polytetrafluoroethylene versus collagen-impregnated Dacron (Hemashield) patching: perioperative (30-day) results. J Vasc Surg 2002; 35:125. 120. AbuRahma AF, Hopkins ES, Robinson PA, et al. Prospective randomized trial of carotid endarterectomy with polytetrafluoroethylene versus collagen-impregnated dacron (Hemashield) patching: late follow-up. Ann Surg 2003; 237:885. 121. Kim JH, Cho YP, Kwon TW, et al. Ten-year comparative analysis of bovine pericardium and autogenous vein for patch angioplasty in patients undergoing carotid endarterectomy. Ann Vasc Surg 2012; 26:353. 122. Zaza SI, Bennett KM. The role of patch closure in current-day carotid endarterectomy. J Vasc Surg 2023; 77:170. 123. AbuRahma AF, Robinson PA, Saiedy S, et al. Prospective randomized trial of carotid endarterectomy with primary closure and patch angioplasty with saphenous vein, jugular vein, and polytetrafluoroethylene: long-term follow-up. J Vasc Surg 1998; 27:222. https://www.uptodate.com/contents/carotid-endarterectomy/print 36/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate 124. Rerkasem K, Rothwell PM. Patch angioplasty versus primary closure for carotid endarterectomy. Cochrane Database Syst Rev 2009; :CD000160. 125. AbuRahma AF, Khan JH, Robinson PA, et al. Prospective randomized trial of carotid endarterectomy with primary closure and patch angioplasty with saphenous vein, jugular vein, and polytetrafluoroethylene: perioperative (30-day) results. J Vasc Surg 1996; 24:998. 126. Gonz lez-Fajardo JA, P rez JL, Mateo AM. Saphenous vein patch versus polytetrafluoroethylene patch after carotid endarterectomy. J Cardiovasc Surg (Torino) 1994; 35:523. 127. Hayes PD, Allroggen H, Steel S, et al. Randomized trial of vein versus Dacron patching during carotid endarterectomy: influence of patch type on postoperative embolization. J Vasc Surg 2001; 33:994. 128. Ho KJ, Nguyen LL, Menard MT. Intermediate-term outcome of carotid endarterectomy with bovine pericardial patch closure compared with Dacron patch and primary closure. J Vasc Surg 2012; 55:708. 129. Blume WT, Ferguson GG, McNeill DK. Significance of EEG changes at carotid endarterectomy. Stroke 1986; 17:891. 130. Palombo D, Lucertini G, Mambrini S, Zettin M. Subtle cerebral damage after shunting vs non shunting during carotid endarterectomy. Eur J Vasc Endovasc Surg 2007; 34:546. 131. Gumerlock MK, Neuwelt EA. Carotid endarterectomy: to shunt or not to shunt. Stroke 1988; 19:1485. 132. Sandmann W, Kolvenbach R, Willeke F. Risks and benefits of shunting in carotid endarterectomy. Stroke 1993; 24:1098. 133. Chuatrakoon B, Nantakool S, Rerkasem A, et al. Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting). Cochrane Database Syst Rev 2022; 6:CD000190. 134. Halsey JH Jr. Risks and benefits of shunting in carotid endarterectomy. The International Transcranial Doppler Collaborators. Stroke 1992; 23:1583. 135. Whitney DG, Kahn EM, Estes JW, Jones CE. Carotid artery surgery without a temporary indwelling shunt. 1,917 consecutive procedures. Arch Surg 1980; 115:1393. 136. Squizzato F, Siracuse JJ, Shuja F, et al. Impact of Shunting Practice Patterns During Carotid Endarterectomy for Symptomatic Carotid Stenosis. Stroke 2022; 53:2230. 137. Aburahma AF, Stone PA, Hass SM, et al. Prospective randomized trial of routine versus selective shunting in carotid endarterectomy based on stump pressure. J Vasc Surg 2010; 51:1133. https://www.uptodate.com/contents/carotid-endarterectomy/print 37/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate 138. Aburahma AF, Mousa AY, Stone PA. Shunting during carotid endarterectomy. J Vasc Surg 2011; 54:1502. 139. Goodney PP, Wallaert JB, Scali ST, et al. Impact of practice patterns in shunt use during carotid endarterectomy with contralateral carotid occlusion. J Vasc Surg 2012; 55:61. 140. Kretz B, Abello N, Astruc K, et al. Influence of the contralateral carotid artery on carotid surgery outcome. Ann Vasc Surg 2012; 26:766. 141. Tan TW, Garcia-Toca M, Marcaccio EJ Jr, et al. Predictors of shunt during carotid endarterectomy with routine electroencephalography monitoring. J Vasc Surg 2009; 49:1374. 142. Rerkasem A, Orrapin S, Howard DP, et al. Local versus general anaesthesia for carotid endarterectomy. Cochrane Database Syst Rev 2021; 10:CD000126. 143. Matsumoto GH, Cossman D, Callow AD. Hazards and safeguards during carotid endarterectomy. Technical considerations. Am J Surg 1977; 133:458. 144. Wennberg DE, Lucas FL, Birkmeyer JD, et al. Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics. JAMA 1998; 279:1278. 145. Brott T, Thalinger K. The practice of carotid endarterectomy in a large metropolitan area. Stroke 1984; 15:950. 146. Barnett HJ, Plum F, Walton JN. Carotid endarterectomy an expression of concern. Stroke 1984; 15:941. 147. O'Neill L, Lanska DJ, Hartz A. Surgeon characteristics associated with mortality and morbidity following carotid endarterectomy. Neurology 2000; 55:773. 148. Kumamaru H, Jalbert JJ, Nguyen LL, et al. Surgeon case volume and 30-day mortality after carotid endarterectomy among contemporary medicare beneficiaries: before and after national coverage determination for carotid artery stenting. Stroke 2015; 46:1288. 149. Schermerhorn ML, Fokkema M, Goodney P, et al. The impact of Centers for Medicare and Medicaid Services high-risk criteria on outcome after carotid endarterectomy and carotid artery stenting in the SVS Vascular Registry. J Vasc Surg 2013; 57:1318. 150. Rao V, Liang P, Swerdlow N, et al. Contemporary outcomes after carotid endarterectomy in high-risk anatomic and physiologic patients. J Vasc Surg 2020; 71:104. 151. Hicks CW, Nejim B, Locham S, et al. Association between Medicare high-risk criteria and outcomes after carotid revascularization procedures. J Vasc Surg 2018; 67:1752. 152. Lokuge K, de Waard DD, Halliday A, et al. Meta-analysis of the procedural risks of carotid endarterectomy and carotid artery stenting over time. Br J Surg 2018; 105:26. https://www.uptodate.com/contents/carotid-endarterectomy/print 38/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate 153. Gali anes EL, Dombroviskiy VY, Hupp CS, et al. Evaluation of readmission rates for carotid endarterectomy versus carotid artery stenting in the US Medicare population. Vasc Endovascular Surg 2014; 48:217. 154. Fokkema M, Bensley RP, Lo RC, et al. In-hospital versus postdischarge adverse events following carotid endarterectomy. J Vasc Surg 2013; 57:1568. Topic 8193 Version 46.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 39/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate GRAPHICS Antimicrobial prophylaxis for vascular surgery in adults Nature of Common Recommended Usual adult Redose operation pathogens antimicrobials dose* interval Arterial surgery Staphylococcus Cefazolin <120 kg: 2 g IV 4 hours involving a prosthesis, the aureus, S. epidermidis, 120 kg: 3 g IV OR vancomycin 15 mg/kg IV (max N/A abdominal aorta, enteric gram- 2 g) or a groin incision negative bacilli OR clindamycin 900 mg IV 6 hours Lower extremity amputation for S. aureus, S. epidermidis, Cefazolin <120 kg: 2 g IV 4 hours 120 kg: 3 g IV ischemia enteric gram- OR vancomycin 15 mg/kg IV (max 2 g) N/A negative bacilli, clostridia OR clindamycin 900 mg IV 6 hours IV: intravenous. Parenteral prophylactic antimicrobials can be given as a single IV dose begun within 60 minutes before the procedure. If vancomycin is used, the infusion should be started within 60 to 120 minutes before the initial incision to have adequate tissue levels at the time of incision and to minimize the possibility of an infusion reaction close to the time of induction of anesthesia. For prolonged procedures (>3 hours) or those with major blood loss, or in patients with extensive burns, additional intraoperative doses should be given at intervals one to two times the half-life of the drug for the duration of the procedure in patients with normal renal function. Use of vancomycin is appropriate in hospitals in which methicillin-resistant S. aureus (MRSA) and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with methicillin-resistant S. aureus, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with diphenhydramine and further slowing of the infusion rate may be helpful. For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside (such as gentamicin 5 mg/kg IV), aztreonam (2 g), or a fluoroquinolone (such as ciprofloxacin 400 mg IV or levofloxacin 500 mg IV). Adapted from: 1. Antimicrobial prophylaxis for surgery. Med Lett Drugs Ther 2016; 58:63. 2. Bratzler DW, et al. Clinical guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt) 2013; 14:73. Graphic 87206 Version 11.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 40/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Anatomy of the cerebral arterial circulation Frontal view of the carotid arteries, vertebral arteries, and intracranial vessels and their communication with each other via the circle of Willis. Reproduced with permission from: U acker R. Atlas Of Vascular Anatomy: An Angiographic Approach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2006. Copyright 2006 Lippincott Williams & Wilkins. Graphic 51410 Version 6.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 41/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Hypoglossal nerve Graphic 86991 Version 1.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 42/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate External carotid artery anatomy External carotid artery and its branches in the lateral view. Reproduced with permission from: U acker R. Atlas Of Vascular Anatomy: An Angiographic Approach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2007. Copyright 2007 Lippincott Williams & Wilkins. Graphic 50495 Version 1.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 43/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Lateral view of the internal carotid artery Lateral view of a schematic drawing of the carotid arteries, vertebral arteries, and intracranial vessels and their relationships in the neck and brain. Reproduced with permission from: U acker R. Atlas Of Vascular Anatomy: An Angiographic Approach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2007. Copyright 2007 Lippincott Williams & Wilkins. Graphic 63286 Version 1.0 https://www.uptodate.com/contents/carotid-endarterectomy/print 44/45 7/5/23, 11:36 AM Carotid endarterectomy - UpToDate Contributor Disclosures Jeffrey Jim, MD, MPHS, FACS Consultant/Advisory Boards: Endospan [Aortic interventions]; Medtronic [Aortic interventions]; Silk Road Medical [Carotid stent]. All of the relevant financial relationships listed have been mitigated. John F Eidt, MD Grant/Research/Clinical Trial Support: Syntactx [Clinical events, data/safety monitoring for medical device trials]. All of the relevant financial relationships listed have been mitigated. Joseph L Mills, Sr, MD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Kathryn A Collins, MD, PhD, FACS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/carotid-endarterectomy/print 45/45 |
7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Complications of carotid endarterectomy : Jeffrey Jim, MD, MPHS, FACS : John F Eidt, MD, Joseph L Mills, Sr, MD, Scott E Kasner, MD : Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 27, 2022. INTRODUCTION The accepted indications for carotid endarterectomy (CEA) balance the long-term benefit of stroke reduction with the risk of perioperative complications, requiring overall morbidity and mortality rates associated with CEA to be low; otherwise, the intervention cannot be justified. Complications following CEA can be related to underlying cardiovascular disease or other comorbid conditions, or to the technique of performing carotid endarterectomy. Postoperative complications of CEA, including myocardial infarction; perioperative stroke; postoperative bleeding; and the potential consequences of cervical hematoma, nerve injury, infection, and carotid restenosis, which may require repeat carotid intervention, are reviewed here. The indications for carotid intervention are reviewed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease" and "Carotid endarterectomy".) GENERAL CONSIDERATIONS The accepted indications for carotid endarterectomy (CEA) balance the long-term benefit of stroke reduction with the risk of perioperative complications, requiring that overall morbidity and mortality rates associated with CEA should be low (<6 percent in symptomatic patients, <3 percent in asymptomatic patients) to justify the intervention [1,2]. The morbidity and mortality rates used by the American Heart Association (AHA) to formulate recommendations for CEA are https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 1/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate more than 10 years old and based upon data that are even older. Two large trials likely more accurately reflect the contemporary risk of stroke or death following CEA: The European trial (International Carotid Stenting Study [ICSS]) randomly assigned patients to receive carotid endarterectomy or carotid stenting for treatment of symptomatic carotid stenosis [3]. The 120-day all-cause mortality for the 857 symptomatic patients in the endarterectomy group was 0.8 percent. The 120 day combined any stroke or procedural death rate was 4.2 percent. In North America, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) reported combined results for symptomatic and asymptomatic patients [4]. In 1240 patients assigned to endarterectomy (47.3 percent asymptomatic), the 30 day death rate was 0.3 percent, and the rate of any periprocedural (30 day) stroke or death or postprocedural ipsilateral stroke was 2.3 percent (with a rate of 1.4 percent for the 587 asymptomatic patients and 3.2 percent for the 653 symptomatic patients) [5]. Appropriate perioperative medication management is important to reduce the risk of cardiovascular and procedure-specific complications. (See "Carotid endarterectomy", section on 'Preoperative preparation' and "Overview of carotid artery stenting", section on 'Medication management'.) PERIOPERATIVE STROKE Stroke is the second most common cause of death following carotid endarterectomy (CEA). Stroke rates associated with CEA in large trials are generally <3 percent for asymptomatic patients and <5 percent for symptomatic patients. Rates range from less than 0.25 percent to more than 3 percent depending upon the indication for CEA and other factors, including the experience of the surgeon [6-13]. Multiple factors can contribute to postoperative stroke in patients who have undergone CEA. These include: Plaque emboli Platelet aggregates Improper flushing Poor cerebral protection Relative hypotension https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 2/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate However, early postoperative neurologic changes in the patient after CEA must be considered related to problems at the endarterectomy site (eg, thrombosis, intimal flap) until proven otherwise. Technical errors must be ruled out. The optimal time to heparinize the postoperative patient with new neurologic symptoms is also controversial [14]. Some surgeons heparinize immediately upon suspicion of the diagnosis, while others first obtain a head CT to rule out hemorrhagic stroke. Head CT performed immediately after an embolic event is frequently normal; follow-up CT in a few days may reveal injury. Evaluation and treatment Evaluation and treatment of new neurologic deficits that occur immediately following CEA varies. It is important to assess the operative site for technical defects, rule out intracranial hemorrhage, and identify other treatable causes of acute cerebral ischemia (eg, middle cerebral artery embolus). How these are accomplished depends largely upon on the availability of resources, surgeon experience, and preferences. Surgeons with access to high-quality duplex ultrasound may prefer to obtain a study in the recovery room or in the operating room, while others immediately return the patient to the operating room to explore the wound and directly inspect the endarterectomy site. If ultrasound shows good flow throughout the carotid artery with no thrombosis or intimal flaps, a head computed tomography (CT) scan should be obtained to rule out intracranial bleeding. A CT angiogram of the head and neck can also be obtained to identify for any treatable vascular lesion (eg, distal large vessel embolus). For surgeons who have access to a hybrid operating room, another approach may be to obtain head CT first and, if no bleeding is identified, proceed with intraoperative arteriography to identify any correctable lesions. Any technical issues found at the endarterectomy site should be corrected with preferably open surgical technique. Carotid artery stenting may also be effective for managing perioperative stroke after CEA, particularly if the cause is a flow-limiting dissection. As an example, one study evaluated 13 patients with major or minor neurologic complications after CEA who underwent emergency carotid arteriography and stent placement [15]. The angiographic success was 100 percent, and 11 patients had complete resolution of neurologic symptoms. In contrast, only one of five patients undergoing surgical re-exploration had neurologic recovery. Stenting, however, is not considered standard for treatment of acute complications of carotid endarterectomy. (See "Overview of carotid artery stenting".) If distal emboli are identified during the evaluation of a perioperative stroke, then considerations should be made to pursue further treatment. Due to the recent operation, systemic intravenous thrombolytic therapy is contraindicated. However, mechanical thrombectomy or intra-arterial thrombolytic therapy may be considered. At this time, there are https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 3/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate no controlled trials evaluating the outcomes of these interventions in post-procedure stroke. As such, the consideration of these treatment options should depend on specific patient factors and circumstances and the decision to proceed made in conjunction with a neurologist and neurointerventionalist on a case-by-case basis. (see "Approach to reperfusion therapy for acute ischemic stroke") Intra-arterial thrombolytic therapy, in highly selected cases, may be another treatment option for patients with a postoperative stroke proven by arteriography to be embolic, presumably occurring during the CEA. The rationale for the administration of tissue-type plasminogen activator (alteplase) in this setting is based upon trials in acute stroke for which a benefit has been demonstrated if therapy is initiated within 4.5 hours in highly selected patients. However, the incidence of intracranial hemorrhage in patients treated with thrombolytic therapy for acute stroke is approximately 6 percent [16]. Furthermore, it is not known if the results obtained from the intravenous systemic administration of alteplase can be extrapolated to localized intra- arterial therapy. Intra-arterial thrombolysis for patients with postoperative stroke has only been described in case reports and retrospective studies and is currently experimental. There are, as yet, no controlled trials, and its use is therefore not justified. Nevertheless, some neurologists advocate searching for distal thrombosis via arteriogram and, if found, proceeding with intra- arterial thrombolytic therapy. MYOCARDIAL INFARCTION In randomized trials, myocardial infarction has occurred at a slightly higher rate for carotid endarterectomy compared with carotid artery stenting, with a reported incidence between 0 and 2 percent [3,4,17-19]. In one systematic review that collected data on over 60,000 patients who underwent CEA, the pooled absolute risk of perioperative (30 day) myocardial infarction was 0.87 percent [20]. Risk factors for myocardial infarction included older age, coronary heart disease, peripheral artery disease, and carotid restenosis. In the CREST trial, a periprocedural myocardial infarction was associated with an increased risk of death at 10-year follow-up [21]. (See "Evaluation of cardiac risk prior to noncardiac surgery" and "Perioperative myocardial infarction or injury after noncardiac surgery".) HYPERPERFUSION SYNDROME Cerebral hyperperfusion syndrome is an uncommon sequela of carotid endarterectomy (CEA) occurring in only a small percentage of patients after carotid revascularization (from less than 1 https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 4/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate to as high as 3 percent in various reports) [22-25]. It is probably the cause of most postoperative intracerebral hemorrhages and seizures in the first two weeks after CEA. The mechanism of hyperperfusion is related to changes that occur in the ischemic or low-flow carotid vascular bed. To maintain sufficient cerebral blood flow, small vessels compensate with chronic maximal dilatation. After surgical correction of the carotid stenosis, blood flow is restored to a normal or elevated perfusion pressure within the previously hypoperfused hemisphere. The dilated vessels are thought to be unable to vasoconstrict sufficiently to protect the capillary bed because of a loss of cerebral blood flow autoregulation. Breakthrough perfusion pressure then causes edema and hemorrhage, which in turn results in the clinical manifestations. Hypertension is a frequent predecessor of the syndrome, underscoring the importance of good perioperative blood pressure control. Hyperperfusion syndrome appears to be more likely with revascularization of a high-grade (80 percent or greater stenosis) carotid lesion, and it may be more likely when CEA is performed after recent cerebral infarction [26-29]. Reduced cerebral blood flow or cerebral vasoreactivity prior to CEA may also be a risk factor for postoperative hyperperfusion [30]. (See "Carotid endarterectomy", section on 'Risk factors for poor outcome'.) Transcranial Doppler techniques have been used to monitor flow velocities of the middle cerebral artery in order to predict the occurrence of hyperperfusion syndrome [26,31-33], but the utility of these methods for this indication is not clearly established. Hyperperfusion syndrome is characterized by the following clinical features: Headache ipsilateral to the revascularized internal carotid, typically improved in upright posture, may herald the syndrome in the first week after endarterectomy. Focal motor seizures are common, sometimes with postictal Todd's paralysis mimicking post-endarterectomy stroke from carotid thrombosis. Intracerebral hemorrhage is the most feared complication, occurring in approximately 0.6 percent of patients after CEA, usually within two weeks of surgery [34]. Neuroimaging studies, including head computed tomography (CT) and magnetic resonance (MR) imaging with T2 or fluid-attenuated inversion recovery (FLAIR) sequences, typically show cerebral edema, petechial hemorrhages, or frank intracerebral hemorrhage. Postrevascularization ipsilateral cerebral blood flow (CBF) is markedly increased compared with preprocedure flow [35]. Ipsilateral CBF after revascularization may be two to three times that of homologous regions in the contralateral hemisphere [36]. However, hyperperfusion syndrome may develop in the presence of only moderate (20 to 44 percent) increases in ipsilateral cerebral https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 5/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate blood flow, as measured by perfusion magnetic resonance imaging, and in the absence of increases in middle cerebral artery flow velocity, as measured by transcranial Doppler (TCD) [37]. Treatment The best management is prevention. Strict control of postoperative hypertension is important. Systolic blood pressure should be maintained at or below 150 mmHg. Aggressive measures (eg, intravenous beta blockers, nitroglycerin) may be necessary to achieve this goal. Treatment should begin at the time of restoration of internal carotid flow and be maintained during the hospital stay and for the first weeks postprocedure. Fortunately, most postoperative blood pressure lability resolves in the first 24 hours. Any patient who complains of severe headache following CEA should be evaluated with head CT and potentially admitted for observation and blood pressure control. Seizures related to hyperperfusion are usually successfully treated with standard antiepileptic drugs such as phenytoin [38]. In addition to control of blood pressure, antithrombotic therapies should be discontinued. For patients on aspirin, platelet transfusions may be useful to reverse the antiplatelet effect. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Platelet function disorders'.) CERVICAL HEMATOMA A postoperative neck hematoma can be catastrophic and result in abrupt loss of the airway. In the International Carotid Stenting trial, the overall incidence of severe hematoma following carotid endarterectomy was 3.4 percent. Hematoma was associated with cranial nerve palsy in 28 of 45 patients [39]. When a significant neck hematoma develops in the postoperative period, immediate return to the operating room and re-exploration of the neck wound is necessary and can be lifesaving. The incidence of cervical hematoma following carotid endarterectomy (CEA) is higher for patients receiving antiplatelet therapy preoperatively or remaining on anticoagulant therapy postoperatively [39-43]. Reversal of intraoperative anticoagulation with protamine has reduced the incidence of serious bleeding that would require reoperation without a significant increase in other complications (eg, stroke, coronary events) [44]. Uncontrolled hypertension while awakening from anesthesia or in the postoperative period can also lead to hematoma formation. (See "Anesthesia for carotid endarterectomy and carotid https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 6/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate stenting", section on 'Hematoma' and "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Hemodynamic monitoring'.) Significant bleeding is also more likely in patients who have undergone a combined CEA and coronary artery bypass graft (CABG), generally because of a coagulopathy. When these procedures are combined, the CEA is performed first, and the neck is packed and left open; CABG is then performed and, when completed, the neck wound is closed. In this way, the likelihood of achieving adequate hemostasis is maximized in these coagulopathic patients. NERVE INJURY Frequency and distribution Cranial nerve or other nerve injuries occur in approximately 5 percent of patients following carotid endarterectomy (CEA) [45-49]. The majority of cranial nerve injuries (CNIs) resolve after surgery, and the risk of permanent CNI is low at <1 percent [48,49]. Among the 1739 patients who underwent CEA in the European Carotid Surgery Trial (ECST), the rate of motor CNIs in the immediate postoperative period was 5.1 percent, but by hospital discharge, the CNI rate declined to 3.7 percent [49]. In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), CNI was identified in 4.6 percent (53 of 1151) of patients. CNIs occurred in 5 percent of patients receiving general anesthesia and 0.9 percent of patients operated on under local anesthesia. The deficit resolved in 18 (34 percent) at one month and in 42 of 52 (81 percent) by one year. The group with CNIs had a negative effect in eating/swallowing parameters within the first month, but this resolved at one year [50]. In a review of 6878 patients from the Vascular Study Group of New England (VSGNE) database, the overall rate of nerve injury at discharge was 5.6 percent; 0.7 percent of patients had more than one nerve affected [48]. In the VSGNE study discussed above, the hypoglossal nerve was most frequently involved, occurring in 2.7 percent, followed the facial nerve at 1.9 percent, and the vagus nerve and glossopharyngeal nerve each at 0.7 percent [48]. This cited distribution of injuries was similar in the ECST, with injuries involving the hypoglossal nerve (27/1739), marginal mandibular nerve (a branch of the facial nerve; 17/1739), recurrent laryngeal nerve (a branch of the vagus nerve; 17/1739), accessory nerve (1/1739), and sympathetic chain injury leading to Horner syndrome (3/1739). Duration of surgery longer than two hours was the only independent risk factor for CNI. In the vascular registry study, patients who suffered a perioperative stroke had a significantly increased risk of CNI. Other factors that significantly increased the risk of CNI included urgent procedures (odds ratio [OR] 1.6, 95% CI 1.2-2.1), immediate re-exploration after closure under the same anesthetic (OR 2.0, 95% CI 1.3-3.0), and return to the operating room for https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 7/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate a neurologic event or bleeding (OR 2.3, 95% CI 1.4-3.8). Redo CEA or prior cervical radiation were not associated with an increased risk. In a meta-analysis combining 26 published studies between 1970 and 2015, CNI most frequently involved the vagus nerve (pooled incidence 3.99 percent) followed by the hypoglossal nerve (pooled incidence 3.79 percent). Fewer than 1 in 7 of the injuries were permanent [45]. The authors noted that the rates of cranial nerve injuries have significantly decreased over the 35- year study period. Furthermore, urgent procedures as well as return to the operating room were associated with an increased risk of nerve injury. Specific nerves The most commonly encountered nerves during CEA including the following: Hypoglossal nerve The hypoglossal nerve supplies motor function to the tongue. It is routinely identified during CEA with exposure of the distal internal carotid artery. Injury to this nerve is one of the more frequent cranial nerve injuries associated with CEA and can result from inadvertent retraction or, rarely, transection. On physical examination, hypoglossal nerve injury is manifested as tongue deviation toward the side of injury (ie, ipsilateral to the CEA). Facial nerve/mandibular nerve The facial nerve exits the stylomastoid foramen and courses along the inferior portion of the ear. The most common branch affected during CEA is the marginal mandibular branch, which may be damaged during improper or prolonged retraction. The resulting paresis of the lateral aspect of the orbicularis oris muscle ipsilateral to the CEA may be identified during bedside examination as an asymmetric smile with a drooped lip. Vagus/laryngeal nerves The vagus nerve, which usually lies posterolaterally in the carotid sheath, may be injured during dissection of the carotid from the internal jugular vein. The vagus nerve may be stretched, inadvertently clamped, or cut at this level, leading to hoarseness. The laryngeal nerves are branches of the vagus nerve ( figure 1A-B). ( figure 2) The recurrent laryngeal nerve is generally distal to the area of carotid artery dissection; however, a nonrecurrent right laryngeal nerve can occur (<1 percent; left side even rarer) crossing transversely from the vagus nerve and behind the common carotid artery, increasing its risk for injury during CEA. Injury to the recurrent laryngeal nerve results in unilateral vocal cord paralysis. The superior laryngeal nerve is rarely injured during CEA; the internal branch supplies sensation to the larynx, while the external branch innervates the cricothyroid muscle. Changes in voice quality may result from superior laryngeal nerve injury. Glossopharyngeal nerve The glossopharyngeal nerve is more cephalad than the extent of the typical neck dissection during CEA. A branch of this nerve, the nerve of Hering, is clinically important since it innervates the carotid sinus and is responsible for the bradycardic and https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 8/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate hypotensive responses that can be seen with manipulation of baroreceptors at this structure. Excessive dissection in the carotid bifurcation can injure this nerve branch. Sympathetic nerves Injury to the sympathetic nerves can result in Horner s syndrome or, rarely, an entity called "first bite syndrome." Horner syndrome can be complete (miosis, ptosis, anhydrosis) or partial (no anhydrosis). (See "Horner syndrome".) First bite syndrome is characterized by unilateral pain in the parotid region after the first bite of each meal felt to be due to sympathetic denervation of the parotid gland [51]. Local botulinum toxin injection is a potential treatment option. Only a handful of cases have been reported following CEA. INFECTION Surgical site/patch infection Wound infections rarely occur following carotid endarterectomy (CEA), and, when they occur, most are superficial and self-limiting with antibiotic treatment. Although some proponents of primary repair cite reports of an increased incidence of infection when a prosthetic patch has been used, there are no definitive data to support this conclusion. Nevertheless, all patients undergoing CEA should receive antibiotic prophylaxis to prevent surgical site infection. (See "Carotid endarterectomy", section on 'Patch angioplasty versus primary closure' and "Carotid endarterectomy", section on 'Prophylactic antibiotics'.) Most of the information regarding deep wound infections involving a carotid patch, which are rare, comes from small case series [52-62]. There are insufficient data to determine whether a specific type of nonautogenous carotid patch material is more prone to infection. Deep wound infection following CEA can present early or in a delayed fashion (85 months in one series) [52]. When these present early in the postoperative course, the patient typically has neck swelling and drainage from the neck incision, while those occurring later may present with a draining sinus tract or pulsatile neck mass indicative of a carotid pseudoaneurysm. Initial management includes wound drainage and antibiotic therapy, which is initially empiric and directed at the most common organisms, Staphylococcus and Streptococcus, until definitive culture and sensitivity results are available. In one case series, 13 of 25 patients were successfully managed in a conservative manner [52]. However, if infection persists, patch excision is indicated with either carotid artery ligation, reconstruction with autogenous vein, or bypass [63]. Parotitis Parotitis is an unusual complication after CEA that results from manipulation of the parotid gland during the procedure. For this reason, most surgeons use this landmark as the https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 9/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate cephalad extent of their dissection. The evaluation and management of parotitis is discussed elsewhere. (See "Suppurative parotitis in adults".) CAROTID RESTENOSIS Restenosis of the carotid artery after carotid endarterectomy (CEA) was reported in up to 20 percent of patients in early studies [64], although lower values (2.6 to 10 percent at five years) have been reported in later studies [53,65-80]. The pathology of the restenotic lesion is related to the time of presentation after initial surgery [81,82]. Most patients with restenosis are asymptomatic and are identified with routine follow-up carotid imaging. "Early" restenosis is that which occurs within two to three years after CEA. Patients with early restenosis frequently have highly cellular and minimally ulcerated intimal hyperplasia, similar to that which occurs after angioplasty or with stent placement. As a result, there is a low likelihood of symptomatic embolization. "Late" restenosis occurs more than two to three years after CEA and generally results from progression of atherosclerotic disease. It is frequently associated with irregular plaques that may serve as an embolic source. Risk factors Patients at increased risk for restenosis include those below age 65, smokers, and females (probably due to the smaller size of their carotid arteries) [76,81,83]. Elevated creatinine has been associated with the development of early restenosis and elevated serum cholesterol with late restenosis [84]. Lipid-lowering drugs may be protective for both early and late restenosis [84], although this finding requires confirmation. The cellular features of the atheroma at the time of CEA may predict the occurrence of restenosis. In a prospective study of 500 patients that examined target lesion atherosclerotic plaque composition from specimens obtained at carotid endarterectomy, both low macrophage infiltration and a small or absent lipid core were associated with an increased risk of restenosis at one year [85]. In another study of 150 patients, an abundance of smooth muscle cells and a scarcity of macrophages were seen in the primary lesion of those who had neointima development six months after surgery, whereas the lesions were rich in lymphocytes and macrophages in those who did not develop neointima [86]. Patch angioplasty appears to be associated with a decreased risk of long-term recurrent stenosis compared with primary closure [87]. (See "Carotid endarterectomy", section on 'Patch angioplasty versus primary closure'.) https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 10/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Indications for reintervention Once the diagnosis of restenosis has been established, a decision for or against reintervention needs to be made. There is variability in practice regarding who should be intervened upon for recurrent stenosis following carotid endarterectomy. For patients who have neurologic symptoms referable to the carotid with >50 percent stenosis and those with asymptomatic carotid restenosis >80 percent, we consider intervention. As with the primary intervention, reintervention should address management of ongoing risk factors (hypertension, hyperglycemia, smoking, hyperlipidemia). (See "Carotid endarterectomy", section on 'Medical risk assessment'.) A systematic review identified 50 studies reporting on the indications for carotid intervention in patients with recurrent stenosis after CEA or carotid artery stenting (CAS). The majority (3478/3525) underwent CEA as the initial intervention [88]. Patients were generally treated when the degree of recurrent stenosis exceeded 80 percent. Just over one half (55 percent) of the patients were treated for any symptoms, but only 23 percent (444/1926) of symptomatic patients had documented ipsilateral symptoms. None of the studies reported whether the patients were evaluated for other sources of emboli. The remaining 45.3 percent of patients had asymptomatic restenosis. Reintervention was by redo CEA in 68 percent of patients and by CAS in 32 percent. The time to repeat intervention was significantly longer in patients with recurrent atherosclerosis, in asymptomatic patients, and in patients undergoing CEA. Approach to reintervention The best approach to intervention for restenosis when it is indicated has not been definitively established. As with selecting the best approach for index carotid intervention, each approach, carotid endarterectomy (CEA), transfemoral carotid artery stenting (TF-CAS), and transcarotid artery revascularization (TCAR) has its advantages and disadvantages. Reoperative CEA may be associated with a significant incidence of complications, although much of the evidence is retrospective and conflicting, with some authors reporting good outcomes for redo surgery [89]. The following studies illustrate the range of findings reported for redo CEA: An early series described 69 patients (48 percent men, 66 percent symptomatic) who had 82 reoperative CEA procedures [90]. Nine patients had two reoperative CEAs and two patients had three reoperative CEAs for either bilateral recurrence or a second recurrence on the same side. The average time to presentation with recurrent carotid stenosis was 6.5 years. The incidence of postoperative stroke (4.8 percent), transient ischemic attack (7.3 percent), and hematomas (7.3 percent) were nearly twice as high as reported for a first CEA [90]. https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 11/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate A later series described 145 patients (56 percent men, 36 percent symptomatic) who had 153 reoperative CEA procedures [91]. The incidence of perioperative stroke (1.9 percent) and death (0) was very low. While the average time from primary to reoperative CEA was 6.1 years in this series, 41 percent of the cohort were patients with early (<2 years) restenosis. There are concerns that there are no controlled studies of redo carotid intervention in patients with restenosis. The presumed benefits of intervention in this group of patients are an extrapolation of the results of trials performed on patients at initial presentation, which generally have favored CEA. CAS is evolving to be the treatment of choice when intervention is deemed appropriate because recurrent lesions are typically smooth intimal hyperplasia amenable to percutaneous intervention, which also avoids complications related to repeat neck dissection. For relatively young patients, redo CEA may also appropriate. Prior to the introduction of TCAR, one systematic review identified 59 studies involving 4399 patients who underwent redo carotid intervention for restenosis following CEA [92]. There were no significant differences in the perioperative (30 day) rates for mortality, stroke, or transient ischemic attack (TIA) when comparing redo CEA with TF-CAS performed for restenosis. Patients undergoing redo CEA had significantly increased incidence of cranial nerve injury compared with those undergoing CAS, but most patients recovered within three months. However, the risk of stenosis after intervention for restenosis was greater in TF-CAS patients compared with redo CEA patients. In a later review of patients who underwent intervention for restenosis (479 CEA, 653 transfemoral CAS), the primary endpoint of stroke and death for TF-CAS was also similar (2.7 and 2.3 percent) [93]. In reviews of the Vascular Quality Initiative (VQI) since the introduction of TCAR, TCAR for restenosis following CEA is associated with decreased risk of perioperative ischemic events compared with TF-CAS or redo CEA [65,94]. The later of these reviews identified 4425 patients operated on between September 2016 and April 2020 and who underwent redo CEA (21.8 percent), TF-CAS (40.4 percent), or TCAR (37.9 percent) after ipsilateral CEA [65]. Compared with redo CEA, TCAR was associated with lower risk of stroke/TIA (1.31 versus 3.53 percent) and stroke (1.02 versus 2.49 percent), which remained significant after adjustment for other risk factors. Mortality was not significantly different between the groups (0.54 percent and 0.42 percent, respectively). TCAR was also associated with lower risk of stroke/TIA compared with TF- CAS (1.3 versus 3.1 percent). Other differences between TCAR and TF-CAS were not significant after adjustment. Data regarding the risk for restenosis after TCAR either performed as the index operation or for restenosis following CEA are not available. However, although the technique for placement of the stent differs for TCAR compared with TF-CAS, once the stent is in place, any long-term problems seen with TF-CAS may also occur with TCAR. https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 12/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) SUMMARY AND RECOMMENDATIONS The accepted indications for carotid endarterectomy (CEA) balance the long-term benefit of stroke reduction with the risk of perioperative complications, which can be related to the technique of performing carotid endarterectomy or to underlying cardiovascular disease and other comorbid conditions. Postoperative complications diminish the overall long-term benefit of performing the procedure. (See 'Introduction' above and 'General considerations' above.) Myocardial infarction occurs at a low rate (0 to 2 percent) following CEA. Stroke rates range from less than 0.25 to more than 3 percent depending upon the indication for CEA (asymptomatic, symptomatic) and other factors, including the experience of the surgeon. Although neurologic changes following CEA can be related to physiologic changes, or intracerebral etiologies, technical problems related to the carotid surgery must be identified and corrected. (See 'Myocardial infarction' above and 'Perioperative stroke' above.) Cerebral hyperperfusion syndrome is an uncommon sequela of CEA. Risk factors include perioperative hypertension, high-grade carotid stenosis, and possibly recent cerebral infarction. The mechanism of hyperperfusion is related to loss of autoregulation that impairs the ability of the brain to accommodate to restored blood flow. Clinical manifestations may include headache, seizures, and stroke. The best management is prevention with strict control of postoperative hypertension through the first weeks postprocedure. (See 'Hyperperfusion syndrome' above.) Cervical hematoma can become life-threatening due to airway compromise. The main risk factor for cervical hematoma is perioperative antithrombotic therapy. When a significant neck hematoma develops in the postoperative period, immediate return to the operating room and re-exploration of the neck wound is mandatory. (See 'Cervical hematoma' above.) Nerve injuries can occur following CEA. The majority of cranial nerve injuries resolve after surgery, and the risk of permanent cranial nerve deficit is low. The most common nerves https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 13/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate injured include the hypoglossal nerve, recurrent laryngeal (vagus nerve), and marginal mandibular branch of facial nerve. Risk factors for nerve injury include prolonged procedure duration, urgent procedure, the need for re-exploration (immediate or delayed), and perioperative stroke. (See 'Nerve injury' above.) Wound infection rarely occurs following CEA, and when it occurs, most are superficial and self-limited, resolving with antibiotic therapy. Deep wound infections involving a carotid patch can present early or in a delayed fashion months after the procedure. Initial management includes wound drainage and empiric antibiotic therapy until definitive culture and sensitivity results are available. (See 'Infection' above.) Carotid restenosis after CEA occurs in 2 to 10 percent of patients at five years. Early restenosis CEA is frequently a highly cellular intimal hyperplasia and minimally ulcerated with a low likelihood of symptomatic embolization, whereas late restenosis occurring more than two to three years after CEA is due to progression of atherosclerotic disease. Risk factors for restenosis include age <65, smoking, female sex, and possibly primary closure of the carotid artery at the time of CEA. Lipid-lowering drugs may be protective for both early and late restenosis. Treatment options for significant restenosis include repeat CEA, transfemoral carotid artery stenting, or transcarotid artery stenting. (See 'Carotid restenosis' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review. The editorial staff at UpToDate also acknowledges Ronald M Fairman, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Moore WS, Barnett HJ, Beebe HG, et al. Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the Ad Hoc Committee, American Heart Association. Circulation 1995; 91:566. 2. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 14/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Heart Association. Circulation 1998; 97:501. 3. International Carotid Stenting Study investigators, Ederle J, Dobson J, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010; 375:985. 4. Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11. 5. Silver FL, Mackey A, Clark WM, et al. Safety of stenting and endarterectomy by symptomatic status in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). Stroke 2011; 42:675. 6. Wu TY, Anderson NE, Barber PA. Neurological complications of carotid revascularisation. J Neurol Neurosurg Psychiatry 2012; 83:543. |
no significant differences in the perioperative (30 day) rates for mortality, stroke, or transient ischemic attack (TIA) when comparing redo CEA with TF-CAS performed for restenosis. Patients undergoing redo CEA had significantly increased incidence of cranial nerve injury compared with those undergoing CAS, but most patients recovered within three months. However, the risk of stenosis after intervention for restenosis was greater in TF-CAS patients compared with redo CEA patients. In a later review of patients who underwent intervention for restenosis (479 CEA, 653 transfemoral CAS), the primary endpoint of stroke and death for TF-CAS was also similar (2.7 and 2.3 percent) [93]. In reviews of the Vascular Quality Initiative (VQI) since the introduction of TCAR, TCAR for restenosis following CEA is associated with decreased risk of perioperative ischemic events compared with TF-CAS or redo CEA [65,94]. The later of these reviews identified 4425 patients operated on between September 2016 and April 2020 and who underwent redo CEA (21.8 percent), TF-CAS (40.4 percent), or TCAR (37.9 percent) after ipsilateral CEA [65]. Compared with redo CEA, TCAR was associated with lower risk of stroke/TIA (1.31 versus 3.53 percent) and stroke (1.02 versus 2.49 percent), which remained significant after adjustment for other risk factors. Mortality was not significantly different between the groups (0.54 percent and 0.42 percent, respectively). TCAR was also associated with lower risk of stroke/TIA compared with TF- CAS (1.3 versus 3.1 percent). Other differences between TCAR and TF-CAS were not significant after adjustment. Data regarding the risk for restenosis after TCAR either performed as the index operation or for restenosis following CEA are not available. However, although the technique for placement of the stent differs for TCAR compared with TF-CAS, once the stent is in place, any long-term problems seen with TF-CAS may also occur with TCAR. https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 12/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) SUMMARY AND RECOMMENDATIONS The accepted indications for carotid endarterectomy (CEA) balance the long-term benefit of stroke reduction with the risk of perioperative complications, which can be related to the technique of performing carotid endarterectomy or to underlying cardiovascular disease and other comorbid conditions. Postoperative complications diminish the overall long-term benefit of performing the procedure. (See 'Introduction' above and 'General considerations' above.) Myocardial infarction occurs at a low rate (0 to 2 percent) following CEA. Stroke rates range from less than 0.25 to more than 3 percent depending upon the indication for CEA (asymptomatic, symptomatic) and other factors, including the experience of the surgeon. Although neurologic changes following CEA can be related to physiologic changes, or intracerebral etiologies, technical problems related to the carotid surgery must be identified and corrected. (See 'Myocardial infarction' above and 'Perioperative stroke' above.) Cerebral hyperperfusion syndrome is an uncommon sequela of CEA. Risk factors include perioperative hypertension, high-grade carotid stenosis, and possibly recent cerebral infarction. The mechanism of hyperperfusion is related to loss of autoregulation that impairs the ability of the brain to accommodate to restored blood flow. Clinical manifestations may include headache, seizures, and stroke. The best management is prevention with strict control of postoperative hypertension through the first weeks postprocedure. (See 'Hyperperfusion syndrome' above.) Cervical hematoma can become life-threatening due to airway compromise. The main risk factor for cervical hematoma is perioperative antithrombotic therapy. When a significant neck hematoma develops in the postoperative period, immediate return to the operating room and re-exploration of the neck wound is mandatory. (See 'Cervical hematoma' above.) Nerve injuries can occur following CEA. The majority of cranial nerve injuries resolve after surgery, and the risk of permanent cranial nerve deficit is low. The most common nerves https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 13/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate injured include the hypoglossal nerve, recurrent laryngeal (vagus nerve), and marginal mandibular branch of facial nerve. Risk factors for nerve injury include prolonged procedure duration, urgent procedure, the need for re-exploration (immediate or delayed), and perioperative stroke. (See 'Nerve injury' above.) Wound infection rarely occurs following CEA, and when it occurs, most are superficial and self-limited, resolving with antibiotic therapy. Deep wound infections involving a carotid patch can present early or in a delayed fashion months after the procedure. Initial management includes wound drainage and empiric antibiotic therapy until definitive culture and sensitivity results are available. (See 'Infection' above.) Carotid restenosis after CEA occurs in 2 to 10 percent of patients at five years. Early restenosis CEA is frequently a highly cellular intimal hyperplasia and minimally ulcerated with a low likelihood of symptomatic embolization, whereas late restenosis occurring more than two to three years after CEA is due to progression of atherosclerotic disease. Risk factors for restenosis include age <65, smoking, female sex, and possibly primary closure of the carotid artery at the time of CEA. Lipid-lowering drugs may be protective for both early and late restenosis. Treatment options for significant restenosis include repeat CEA, transfemoral carotid artery stenting, or transcarotid artery stenting. (See 'Carotid restenosis' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review. The editorial staff at UpToDate also acknowledges Ronald M Fairman, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Moore WS, Barnett HJ, Beebe HG, et al. Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the Ad Hoc Committee, American Heart Association. Circulation 1995; 91:566. 2. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 14/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Heart Association. Circulation 1998; 97:501. 3. International Carotid Stenting Study investigators, Ederle J, Dobson J, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010; 375:985. 4. Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11. 5. Silver FL, Mackey A, Clark WM, et al. Safety of stenting and endarterectomy by symptomatic status in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). Stroke 2011; 42:675. 6. Wu TY, Anderson NE, Barber PA. Neurological complications of carotid revascularisation. J Neurol Neurosurg Psychiatry 2012; 83:543. 7. Hill MD, Brooks W, Mackey A, et al. Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Circulation 2012; 126:3054. 8. Saedon M, Singer DR, Pang R, et al. Registry report on kinetics of rescue antiplatelet treatment to abolish cerebral microemboli after carotid endarterectomy. Stroke 2013; 44:230. 9. Heyer EJ, Mergeche JL, Bruce SS, et al. Statins reduce neurologic injury in asymptomatic carotid endarterectomy patients. Stroke 2013; 44:1150. 10. Faggioli G, Pini R, Mauro R, et al. Perioperative outcome of carotid endarterectomy according to type and timing of neurologic symptoms and computed tomography findings. Ann Vasc Surg 2013; 27:874. 11. Sfyroeras GS, Bessias N, Moulakakis KG, et al. New cerebral ischemic lesions after carotid endarterectomy. Ann Vasc Surg 2013; 27:883. 12. Barbetta I, Carmo M, Mercandalli G, et al. Outcomes of urgent carotid endarterectomy for stable and unstable acute neurologic deficits. J Vasc Surg 2014; 59:440. 13. Goldberg JB, Goodney PP, Kumbhani SR, et al. Brain injury after carotid revascularization: outcomes, mechanisms, and opportunities for improvement. Ann Vasc Surg 2011; 25:270. 14. Chamorro A, Vila N, Saiz A, et al. Early anticoagulation after large cerebral embolic infarction: a safety study. Neurology 1995; 45:861. 15. Anzuini A, Briguori C, Roubin GS, et al. Emergency stenting to treat neurological complications occurring after carotid endarterectomy. 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Boulanger M, Cameli re L, Felgueiras R, et al. Periprocedural Myocardial Infarction After Carotid Endarterectomy and Stenting: Systematic Review and Meta-Analysis. Stroke 2015; 46:2843. 21. Jones MR, Howard G, Roubin GS, et al. Periprocedural Stroke and Myocardial Infarction as Risks for Long-Term Mortality in CREST. Circ Cardiovasc Qual Outcomes 2018; 11:e004663. 22. Youkey JR, Clagett GP, Jaffin JH, et al. Focal motor seizures complicating carotid endarterectomy. Arch Surg 1984; 119:1080. 23. Reigel MM, Hollier LH, Sundt TM Jr, et al. Cerebral hyperperfusion syndrome: a cause of neurologic dysfunction after carotid endarterectomy. J Vasc Surg 1987; 5:628. 24. Naylor AR, Ruckley CV. The post-carotid endarterectomy hyperperfusion syndrome. Eur J Vasc Endovasc Surg 1995; 9:365. 25. Coutts SB, Hill MD, Hu WY. Hyperperfusion syndrome: toward a stricter definition. Neurosurgery 2003; 53:1053. 26. Kablak-Ziembicka A, Przewlocki T, Pieniazek P, et al. Predictors of cerebral reperfusion injury after carotid stenting: the role of transcranial color-coded Doppler ultrasonography. J Endovasc Ther 2010; 17:556. 27. Bouri S, Thapar A, Shalhoub J, et al. Hypertension and the post-carotid endarterectomy cerebral hyperperfusion syndrome. Eur J Vasc Endovasc Surg 2011; 41:229. 28. Pennekamp CW, Tromp SC, Ackerstaff RG, et al. Prediction of cerebral hyperperfusion after carotid endarterectomy with transcranial Doppler. Eur J Vasc Endovasc Surg 2012; 43:371. 29. Clagett, GP, Robertson, JT. Surgical considerations in symptomatic disease. In: Stroke: Patho physiology, diagnosis and management, Barnett, HJM, Mohr, JP, Stein, BM, Yatsu, FM (Eds), C hurchill Livingstone, New York 1998. p.1209. https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 16/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate 30. Hosoda K, Kawaguchi T, Ishii K, et al. 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Cranial Nerve Injury After Carotid Endarterectomy: Incidence, Risk Factors, and Time Trends. Eur J Vasc Endovasc Surg 2017; 53:320. 46. Tamaki T, Node Y, Saitoum N, et al. Vernet's syndrome after carotid endarterectomy. Perspect Vasc Surg Endovasc Ther 2013; 25:65. 47. Grieff AN, Dombrovskiy V, Beckerman W, et al. Anesthesia Type is Associated with Decreased Cranial Nerve Injury in Carotid Endarterectomy. Ann Vasc Surg 2021; 70:318. 48. Fokkema M, de Borst GJ, Nolan BW, et al. Clinical relevance of cranial nerve injury following carotid endarterectomy. Eur J Vasc Endovasc Surg 2014; 47:2. 49. Cunningham EJ, Bond R, Mayberg MR, et al. Risk of persistent cranial nerve injury after carotid endarterectomy. J Neurosurg 2004; 101:445. 50. Hye RJ, Mackey A, Hill MD, et al. Incidence, outcomes, and effect on quality of life of cranial nerve injury in the Carotid Revascularization Endarterectomy versus Stenting Trial. J Vasc Surg 2015; 61:1208. 51. Wang TK, Bhamidipaty V, MacCormick M. First bite syndrome following ipsilateral carotid endarterectomy. Vasc Endovascular Surg 2013; 47:148. 52. Stone PA, Srivastava M, Campbell JE, et al. A 10-year experience of infection following carotid endarterectomy with patch angioplasty. J Vasc Surg 2011; 53:1473. 53. L onore FT, Elsa F, David PC, et al. Short- and Long-Term Outcomes Following Biological Pericardium Patches Versus Prosthetic Patches for Carotid Endarterectomy: A Retrospective Bicentric Study. Ann Vasc Surg 2021; 72:66. 54. Haddad F, Wehbe MR, Hmedeh C, et al. Bilateral Carotid Patch Infection Occurring 12 years Following Endarterectomy. Ann Vasc Surg 2020; 65:285.e11. 55. Azouz V, Fahmy JN, Kornbau C, Petrinec D. Recurrent pseudoaneurysm after carotid endarterectomy. J Vasc Surg Cases Innov Tech 2019; 5:128. 56. Fatima J, Federico VP, Scali ST, et al. Management of patch infections after carotid endarterectomy and utility of femoral vein interposition bypass graft. J Vasc Surg 2019; 69:1815. 57. Hillman Terzian WT, Schadt S, Sheth SU. Right carotid-cutaneous fistula and right carotid pseudoaneurysm formation secondary to a chronically infected polyethylene terephthalate patch. Int J Crit Illn Inj Sci 2018; 8:48. https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 18/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate 58. Varetto G, Trevisan A, Barile G, et al. Carotid Pseudoaneurysm After Eversion Endarterectomy: A Case Report and Review of the Literature. Vasc Endovascular Surg 2018; 52:309. 59. Xu JH, Altaf N, Tosenovsky P, Mwipatayi BP. Management challenges of late presentation Dacron patch infection after carotid endarterectomy. BMJ Case Rep 2017; 2017. 60. Naylor R. Management of prosthetic patch infection after CEA. J Cardiovasc Surg (Torino) 2016; 57:137. 61. Menna D, Ruggiero M, Speziale F. Infected pseudoaneurysm after carotid endarterectomy: mismatch between clinical presentation and origin. Ann Vasc Surg 2014; 28:740.e17. 62. Le L, Charlton-Ouw K, Safi HJ, Azizzadeh A. Late expulsion of a Dacron patch after carotid endarterectomy. J Vasc Surg 2012; 56:1721. 63. Mann CD, McCarthy M, Nasim A, et al. Management and outcome of prosthetic patch infection after carotid endarterectomy: a single-centre series and systematic review of the literature. Eur J Vasc Endovasc Surg 2012; 44:20. 64. Zierler RE, Bandyk DF, Thiele BL, Strandness DE Jr. Carotid artery stenosis following endarterectomy. Arch Surg 1982; 117:1408. 65. Elsayed N, Ramakrishnan G, Naazie I, et al. Outcomes of Carotid Revascularization in the Treatment of Restenosis After Prior Carotid Endarterectomy. Stroke 2021; 52:3199. 66. Goodney PP, Nolan BW, Eldrup-Jorgensen J, et al. Restenosis after carotid endarterectomy in a multicenter regional registry. J Vasc Surg 2010; 52:897. 67. Lal BK, Beach KW, Roubin GS, et al. Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial. Lancet Neurol 2012; 11:755. 68. Hertzer NR, Bena JF. Patching plus extended exposure and tacking of the common carotid cuff may reduce the late incidence of recurrent stenosis after carotid endarterectomy. J Vasc Surg 2013; 58:926. 69. Pavela J, Ahanchi S, Steerman SN, et al. Grayscale median analysis of primary stenosis and restenosis after carotid endarterectomy. J Vasc Surg 2014; 59:978. 70. Chan RC, Chan YC, Cheung GC, Cheng SW. Predictors of restenosis after carotid endarterectomy: 17-year experience in a tertiary referral vascular center. Vasc Endovascular Surg 2014; 48:201. 71. Li Q, Liu B, Zhao Y, et al. Echolucent carotid plaque is associated with restenosis after carotid endarterectomy. 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Topic 15843 Version 20.0 https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 21/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate GRAPHICS Nerve supply of the thyroid gland It is critical that the superior and recurrent laryngeal nerves be routinely identified and protected in thyroid surgery to reduce the risk of injury. Graphic 82397 Version 4.0 https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 22/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Variations in nerve supply of the thyroid gland (A) The external branch of the superior laryngeal nerve innervates the inferior constrictor and cricothyroid muscles. The external branch travels with the superior thyroid artery until approximately 1 cm before the artery enters the superior thyroid pole and then divides into branches that enter the lateral inferior pharyngeal constrictor muscle and the cricothyroid muscle. A few smaller branches may be seen entering the superior thyroid. (B) The RLN is associated with the inferior thyroid artery at approximately the junction of the lower and middle thirds of the thyroid gland. On the left, the RLN ascends in the tracheoesophageal groove and crosses deep to the inferior thyroid artery; on the right, the RLN crosses more obliquely and is oriented more laterally than caudally. While the nerve most often crosses deep to the inferior thyroid artery, documented variations include passing anterior to the artery as well as passing between branches of the inferior thyroid artery. Another variation of the nerve is the nonrecurrent laryngeal nerve, in which the https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 23/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate laryngeal nerve branches directly from the vagus nerve. This variation occurs more commonly on the right side. STA: superior thyroid artery; IPC: inferior pharyngeal constrictor muscle; CT: cricothyroid muscle. (A) Adapted from: Morton RP, Whit eld Al-Ali S. Anatomical and surgical considerations of the external branch of the superior laryngeal nerve: a systematic review. Clin Otolaryngol 2006; 31:368-374. (B) Adapted from: Makay O, Icoz G, Yilmaz M, Akyildiz M, Yetkin E. The recurrent laryngeal nerve and the inferior thyroid artery-anatomical variations during surgery. Langenbecks Arch Surg 2008; 393:681. Graphic 61802 Version 9.0 https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 24/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Proximity of thyroid nerves to vascular structure in the neck n: nerve; a: artery; R: right; L: left. Graphic 139715 Version 1.0 https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 25/26 7/5/23, 11:38 AM Complications of carotid endarterectomy - UpToDate Contributor Disclosures Jeffrey Jim, MD, MPHS, FACS Consultant/Advisory Boards: Endospan [Aortic interventions]; Medtronic [Aortic interventions]; Silk Road Medical [Carotid stent]. All of the relevant financial relationships listed have been mitigated. John F Eidt, MD Grant/Research/Clinical Trial Support: Syntactx [Clinical events, data/safety monitoring for medical device trials]. All of the relevant financial relationships listed have been mitigated. Joseph L Mills, Sr, MD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Kathryn A Collins, MD, PhD, FACS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/complications-of-carotid-endarterectomy/print 26/26 |
7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Coronary artery bypass grafting in patients with cerebrovascular disease : Harold L Lazar, MD, Christina A Wilson, MD, PhD, Steven R Mess , MD : Scott E Kasner, MD : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jan 05, 2023. INTRODUCTION Cerebrovascular complications are among the most feared consequences after coronary artery bypass graft surgery (CABG). Patients with concomitant cerebrovascular and coronary heart disease represent a subset with advanced atherosclerosis in whom other areas of the arterial system are also involved. In addition to a higher risk of perioperative stroke (see 'Risk factors' below), these patients also have a higher incidence of left main coronary disease and a reduced left ventricular ejection fraction compared with patients who have isolated coronary heart disease [1,2]. This topic will focus mainly on coexistent coronary and extracranial carotid atherosclerosis. Issues that will be discussed include the management of the patient with an asymptomatic carotid stenosis undergoing CABG, the role of combined or staged CABG and carotid revascularization in these patients, and which strategies will result in the lowest operative morbidity and mortality. The indications for CABG are discussed elsewhere. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention" and "Coronary artery bypass graft surgery in patients with acute ST-elevation myocardial infarction", section on 'Indications'.) STROKE ASSOCIATED WITH CABG https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 1/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Neurologic complications are among the most feared complications of coronary artery bypass graft surgery (CABG). Information from large databases published before 2002 suggested that a new clinical stroke or transient ischemic attack (TIA) occurred in approximately 3 percent of patients [3,4]. While data from large retrospective reports published in 2008 and 2011 suggested that the overall incidence of perioperative stroke had declined to 1.6 percent [5,6], a 2014 prospective study found a clinically apparent perioperative stroke rate of 3.1 percent [7]. Radiographically evident but clinically silent strokes occur much more frequently [7-9]. Approximately 40 percent of strokes occur intraoperatively and most of the remaining strokes occur during the first 48 hours postoperatively [6]. Perioperative strokes have significant impact on length of hospital stay and mortality outcome, with 10-fold higher hospital mortality rates in patients who suffered a perioperative stroke [5,6]. Other well-recognized neurologic complications of CABG include delirium, seizures, and neurocognitive dysfunction. (See "Neurologic complications of cardiac surgery", section on 'Encephalopathy'.) Etiology The mechanisms of stroke in patients undergoing CABG are discussed in detail separately. (See "Neurologic complications of cardiac surgery".) Summarized briefly, the most common mechanism is embolism, as changes in hemodynamics and aortic manipulation such as cross-clamping, cannulation, and/or proximal graft anastomosis can cause embolization of thrombotic or atheromatous debris from complex plaques in the ascending aorta [5,10,11]. (See "Thromboembolism from aortic plaque", section on 'Cardiovascular procedures' and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".) Atrial fibrillation is a common arrhythmia following CABG, occurring in 25 to 30 percent of patients, and is a frequent cause of postoperative embolic stroke as well. Other causes of perioperative stroke include large and small vessel occlusive disease and hypoperfusion. As an example, a stenotic large artery can lead to focal cerebral hypoperfusion, resulting in a watershed or borderzone infarct between two cerebrovascular territories. Perioperative myocardial infarction (MI) and arterial dissection are also potential mechanisms of ischemic stroke. The development of postsurgical systemic inflammatory response and the withholding of antithrombotic therapy in the perioperative period may also contribute to perioperative stroke risk. In one series of 76 patients with stroke post-CABG, 75 percent were attributed to a cardioembolic source (aortic arch atherosclerosis or atrial fibrillation), 13 percent to small-vessel disease, and 5 to percent large artery stenosis, including carotid artery disease [12]. https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 2/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Risk factors There are multiple risk factors for perioperative stroke with CABG. The following have been described as independent risk factors in the literature [3,5,13-17]: Patient characteristics: Moderate to severe atherosclerosis of ascending aorta Atrial fibrillation Prior stroke or TIA Subcortical small vessel disease Moderate to severe carotid stenosis Peripheral vascular disease Diabetes Hypertension Pulmonary disease Heart failure Unstable angina Recent myocardial infarction Moderate to severe left ventricular dysfunction Prior cardiac surgery Older age Female sex Elevated pulse pressure Tobacco use Chronic kidney disease Intraoperative features: Severe hypotension Manipulation of atherosclerotic aorta Prolonged cardiopulmonary bypass time Use of intra-aortic balloon pump Air emboli during cardiopulmonary bypass Iatrogenic ascending aortic dissection Postoperative features: Atrial fibrillation Low cardiac output syndrome https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 3/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate The stroke risk associated with aortic atherosclerosis and carotid stenosis is elaborated in the sections that follow. Aortic atherosclerosis Atherosclerosis of the ascending aorta may be a more important cause of perioperative stroke than carotid artery stenosis [18]. In a study of over 900 patients undergoing cardiac surgery, the risk of perioperative stroke among patients with and without significant atherosclerosis of the ascending aorta was 9 versus 2 percent, respectively [19]. However, aortic stenosis may be a marker for high atherosclerotic burden and stroke risk and not a direct perioperative stroke mechanism in most patients. Predictors of aortic atherosclerosis are similar to predictors of generalized atherosclerosis and include older age, hypertension, hyperlipidemia, smoking, kidney disease, peripheral artery disease, and/or cerebrovascular disease. Aortic atheromas that are large ( 5 mm thick) or mobile carry a higher risk of stroke [20]. Carotid stenosis The rate of stroke is elevated in patients with carotid stenosis who have CABG. However, similar to the presence of significant aortic atherosclerosis, carotid stenosis likely is a marker for high atherosclerotic burden and not often a direct perioperative stroke mechanism. The available data, summarized below, suggest that unilateral asymptomatic carotid stenosis of 50 to 99 percent is not an independent risk factor for ipsilateral ischemic stroke with CABG. By contrast, certain groups of patients with carotid artery disease appear to have an increased risk of stroke with CABG, including the following: Symptomatic carotid stenosis of 50 to 99 percent in men and 70 to 99 percent in women Bilateral asymptomatic stenosis of 80 to 99 percent Unilateral asymptomatic stenosis of 70 to 99 percent and contralateral carotid occlusion However, the quality of the data is generally poor, since most studies are single-center, nonrandomized, and retrospective: A 2011 meta-analysis demonstrated that the risk of perioperative stroke after cardiac surgery was approximately 7 percent in those with 50 percent carotid stenosis and 9 percent in those with 80 percent stenosis, higher than the reported rate of 1.6 to 3 percent in the general population undergoing surgery [21]. The main stroke predictors were symptomatic carotid stenosis and bilateral carotid stenosis/occlusion. Exclusion of patients with prior stroke/TIA or those with complete occlusion of the carotid decreased the stroke risk to approximately 4 percent in the setting of 50 to 99 percent stenosis and 3 percent with 70 to 99 percent stenosis. https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 4/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate The presence of a recently symptomatic carotid artery stenosis probably increases the risk of a postoperative stroke in patients undergoing CABG, but there are few data directly addressing this question. In one study, 28 patients with prior symptomatic unilateral carotid disease did not undergo prophylactic carotid endarterectomy, and ischemic stroke occurred in 4 (14 percent) [13]. However, only one of the four strokes was attributed to ipsilateral carotid stenosis and was therefore potentially preventable by prophylactic carotid revascularization. Asymptomatic carotid stenosis is not a proven independent risk factor for ipsilateral carotid territory ischemic stroke in patients having CABG [12,21]. The following represents a summary of the range of findings that have been noted in individual reports: One retrospective study of patients with preoperative carotid duplex ultrasound having CABG compared 117 patients who had severe asymptomatic carotid stenosis ( 75 percent) with 761 patients who did not have severe carotid stenosis [22]. Both groups had similar rates of in-hospital stroke (3.4 versus 3.6) and mortality (3.4 versus 4.2 percent). In another retrospective report, there were 18 patients with 50 percent carotid stenosis who had a perioperative ischemic stroke, but only 4 occurred in the territory of the stenotic or occluded carotid artery, and in 3 of these, the carotid was totally occluded on preoperative evaluation and not amenable to treatment [12]. Thus, only 1 of the 18 carotid territory strokes was potentially preventable by carotid intervention. Since 2005, four studies have reported patients with asymptomatic carotid stenosis of 70 to 99 percent (n = 156) or 50 to 99 percent (n = 42) who did not have prophylactic carotid revascularization; the rate of perioperative stroke with CABG in these patients was 0 percent [12,23-26]. While not high-quality data, these studies suggest that patients with asymptomatic unilateral carotid artery stenoses are at little or no increased risk of perioperative stroke during CABG. As such, while it remains unresolved whether patients with asymptomatic internal carotid artery stenosis would benefit from revascularization, it appears more likely that carotid stenosis is merely a surrogate stroke risk marker associated with multiple other potential stroke risk factors and mechanisms, in which case carotid revascularization would be expected to have little or no benefit. Although there is little direct evidence, it is plausible that characteristics of the carotid lesion, such as plaque morphology and the presence of downstream microemboli on transcranial https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 5/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Doppler, may impact the risk of perioperative stroke with CABG and therefore inform the need for revascularization [27]. Prevalence and predictors of carotid stenosis The reported prevalence of carotid artery disease in patients undergoing CABG has varied from 2 to 22 percent, with an average of approximately 8 percent [1,16,28-33]. This wide variation in the reported incidence of carotid artery disease is related to the populations studied, the methods used for screening of carotid disease, how frequently screening was performed, and the definition of a significant carotid stenosis. The prevalence of carotid artery disease in patients having CABG increases with age. One series found that the prevalence of high-grade ( 75 percent) carotid artery stenosis was three times higher in patients 60 years of age or older compared with younger patients (11.3 versus 3.8 percent) [34]. Clinical predictors other than age for significant carotid artery stenosis in patients considered for CABG include the following [13,30]: Diabetes Peripheral vascular disease Left main coronary artery stenosis 60 percent Carotid bruit Prior stroke or TIA Prior vascular operation Smoking Female sex PREVENTION OF PERIOPERATIVE STROKE Strategies for prevention of stroke with coronary artery bypass graft surgery (CABG) include: Preoperative evaluation for identification and potential treatment of pre-existing stroke risk factors, including aortic atherosclerosis and carotid stenosis potentially associated with increased surgical risk (ie, symptomatic 50 to 99 percent stenosis, or bilateral asymptomatic stenosis of 80 to 99 percent, or unilateral asymptomatic stenosis of 70 to 99 percent and contralateral carotid occlusion) (see "Neurologic complications of cardiac surgery") Medical therapy, including the use of aspirin, antiarrhythmic drugs, and statins (see "Coronary artery bypass surgery: Perioperative medical management") https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 6/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Identification of aortic atherosclerosis is recommended to reduce the risk of perioperative stroke. Current guidelines endorse evaluation of the aorta by routine intraoperative epiaortic ultrasound to determine the severity of ascending aortic plaque in an effort to reduce perioperative emboli [35-37]. Although there have been no randomized controlled trials, lower perioperative stroke rates (0 to 1.4 percent) were reported when epiaortic ultrasound was utilized to guide surgical decisions, such as determination of sites for aortic cross-clamping and cannula placement [38,39]. Surgical methods that reduce aortic manipulation may decrease the incidence of cerebral embolization with CABG. When performing on-pump CABG surgery, performing the distal and proximal anastomoses under one crossclamp period may decrease the incidence of perioperative strokes. (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Clinical use" and "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Improvements in surgical technique'.) The evaluation for carotid disease and carotid revascularization is discussed below. (See 'Screening for carotid disease' below and 'Prophylactic carotid intervention' below.) A separate issue is that intracranial atherosclerosis leading to stenosis of the distal intracranial internal carotid artery (ICA) or proximal large vessels of the circle of Willis is a common cause of stroke, particularly in people of Asian and African-American descent (see "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Racial and ethnic differences'). In patients with a recent ischemic stroke or transient ischemic attack, aggressive medical management has been shown to be superior to endovascular stenting in patients with symptomatic intracranial 70 to 99 percent stenosis, due to the early risk of stroke following the procedure. (See "Intracranial large artery atherosclerosis: Treatment and prognosis", section on 'Secondary prevention'.) For long-term stroke risk reduction, all patients with significant cerebrovascular and cardiac disease, regardless of surgical intervention, warrant aggressive medical management for control of vascular risk factors, including use of a statin (with a goal LDL <70 mg/dL) and assiduous blood pressure control. (See "Overview of secondary prevention of ischemic stroke".) Screening for carotid disease We agree with current guidelines from the American College of Cardiology Foundation and American Heart Association, which recommend selective pre- CABG screening for carotid artery disease by carotid duplex ultrasound in patients who are 65 years old, have left main coronary disease, peripheral vascular disease, history of tobacco use, history of prior stroke/transient ischemic attack (TIA), or a carotid bruit [35-37,40]. The data supporting this recommendation is summarized above. (See 'Prevalence and predictors of carotid stenosis' above.) https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 7/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate One analysis of 1138 patients concluded that screening patients with age 65 years, a carotid bruit, or a history of stroke or TIA would reduce the screening burden by 40 percent compared with unselected screening of all patients and would miss only 2 percent of all candidates with a carotid stenosis of 70 percent [30]. There are a number of noninvasive methods for establishing the presence and significance of a carotid artery stenosis, including carotid duplex ultrasound scanning (CDUS), magnetic resonance angiography, and computed tomographic angiography. A detailed discussion of these methods is found separately. (See "Evaluation of carotid artery stenosis".) Prophylactic carotid intervention In approximate agreement with major guidelines [35,40,41], we suggest carotid revascularization for patients needing CABG who have one of the following conditions (see 'Carotid stenosis' above): A recently symptomatic carotid stenosis (50 to 99 percent stenosis in men or 70 to 99 percent stenosis in women) Bilateral asymptomatic 80 to 99 percent carotid stenoses A unilateral asymptomatic stenosis of 70 to 99 percent and contralateral carotid occlusion We suggest not performing prophylactic carotid revascularization for patients with isolated unilateral asymptomatic 50 to 99 percent carotid artery stenosis. However, there are few randomized controlled trials addressing the effectiveness of prophylactic carotid revascularization in patients scheduled for CABG, and despite a large volume of retrospective data, there is no clear consensus on the optimal strategy [23,42,43]. The major considerations include the following issues: Patients with asymptomatic unilateral carotid artery stenoses, who account for the majority of patients with carotid disease undergoing cardiac surgery, appear to be at little or no increase in risk of perioperative stroke during CABG (see 'Carotid stenosis' above). Thus, any potential benefit of carotid intervention is likely to be offset by the procedural risks [21,43-45]. A systematic review suggested that at least one-half of perioperative strokes are not preventable by carotid intervention, as 50 percent of patients with stroke did not have significant carotid stenosis, and 60 percent of strokes identified radiographically or by autopsy could not be attributed to carotid disease [46]. A controlled trial randomly assigned 129 patients with asymptomatic high-grade internal carotid artery stenosis who required CABG surgery to synchronous (ie, combined) carotid endarterectomy (CEA) plus CABG or to CABG alone [44]. The study was stopped early due to slow recruitment and withdrawal of funding. At 30 days, the rate of any stroke or death was higher for the group assigned to combined CEA plus CABG group compared with the group assigned to CABG https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 8/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate alone (18.5 versus 9.7 percent, 95% CI -3.2 to 20.8 percent) but the difference was not statistically significant. This difference persisted throughout follow-up, with a nonsignificant higher rate of stroke or death at five years for the CEA plus CABG group (40.6 versus 35.0 percent) [45]. All patients were examined by a neurologist, which may explain in part the relatively high overall event rates compared with historical data. Although not definitive, these results suggest that combined CEA plus CABG is not beneficial and may be harmful for patients with asymptomatic carotid stenosis. As noted above, the benefit of carotid revascularization with CEA or carotid stenting in patients requiring CABG has not been systematically addressed. In the general population (ie, patients who do not require concomitant cardiac surgery), large randomized clinical trials have demonstrated the benefit of CEA for patients who have asymptomatic carotid stenosis of 60 to 99 percent, provided that their perioperative risk is less than 3 percent and their life expectancy is at least five years. Similarly, major clinical trials have established clear benefit of CEA compared with medical treatment for patients who have symptomatic carotid disease, provided that their perioperative risk is less than 6 percent. (See "Management of asymptomatic extracranial carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease".) One major caveat regarding these data is that optimal medical management of stroke risk factors has evolved since the major trials of CEA were conducted (generally the late 1980s through early 2000s), particularly with regard to use of statin therapy for management of hypercholesterolemia, more aggressive lipid and blood pressure goals, and the availability of newer antiplatelet agents. In reports published since the mid-2000s, rates of stroke in patients with significant carotid stenosis who are managed on medical therapy have declined when compared with those who were enrolled in the earlier surgical trials. Accumulating data suggest that aggressive medical therapy alone may be appropriate treatment for patients with asymptomatic carotid disease (see "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Intensive medical therapy and follow-up' and "Management of symptomatic carotid atherosclerotic disease", section on 'Intensive medical management'). Moreover, the trials that established the benefit of CEA excluded patients who had a recent (within six months) history of myocardial infarction or unstable angina. As a result, the applicability of these data to patients undergoing CABG is uncertain. Ongoing randomized trials comparing contemporary revascularization techniques with advanced medical therapy may better inform these issues. Existing data are conflicting with regard to the benefit of carotid revascularization in patients with a severe (ie, 80 to 99 percent) carotid stenosis who also require cardiac https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 9/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate surgery: In a nonrandomized study of patients with 80 to 99 percent carotid stenosis, there were no neurologic events in 53 patients undergoing CEA and CABG, compared with the development of a permanent neurologic defect in 3 of 15 patients undergoing CABG alone [47]. The results were similar in a second nonrandomized study of patients with prior stroke or TIA and 80 to 99 percent carotid stenosis; there were no carotid territory strokes among 114 who underwent staged or combined CEA and CABG, compared with carotid strokes in 4 of 12 patients who had CABG without prophylactic CEA [48]. By contrast, several subsequent studies published since 2005 have reported no perioperative strokes with CABG among a total of over 200 patients with asymptomatic carotid stenosis of 50 to 99 percent who did not have prophylactic carotid revascularization [12,23-26]. (See 'Carotid stenosis' above.) CAROTID TREATMENT OPTIONS Options for patients requiring both carotid and cardiac revascularization include the following treatment decisions: Choice of carotid revascularization (ie, carotid endarterectomy [CEA] versus carotid artery stenting [CAS]) Timing of revascularization (ie, combined carotid revascularization and coronary artery bypass graft surgery [CABG], staged carotid revascularization followed by CABG, or staged CABG prior to carotid revascularization) These choices are inextricably linked for CAS because the use of dual antiplatelet therapy beginning at the time of stenting and lasting for weeks or months thereafter generally precludes concomitant cardiac surgery, as discussed in the sections that follow. Highly selected patients undergoing CABG may be candidates for carotid revascularization (see 'Prophylactic carotid intervention' above). Given the available data, summarized in the sections that follow, and our clinical experience, we suggest staged carotid revascularization with CEA or CAS prior to CABG in patients with chronic stable angina in the absence of a recent myocardial infarction, severe left main coronary artery disease, or diffuse coronary heart disease without satisfactory collaterals. We suggest a combined procedure of CEA plus CABG for patients with severe left main coronary heart disease, diffuse coronary heart disease without satisfactory https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 10/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate collaterals, or unstable angina. However, the optimal approach to carotid revascularization will be established only by future prospective randomized controlled trials. Regardless of the choice and timing of revascularization, all patients with concomitant cardiac and carotid atherosclerosis should be treated with aggressive medical management unless contraindicated, including long-term antiplatelet treatment, statin therapy, aggressive blood pressure control, and tobacco cessation. (See "Overview of secondary prevention of ischemic stroke".) Method of carotid revascularization Accumulating evidence suggests that CEA and CAS provide similar long-term outcomes for patients with asymptomatic and symptomatic carotid occlusive disease, although the periprocedural risk of stroke and death may be higher with CAS, while the periprocedural risk of myocardial infarction may be higher with CEA. However, these data come from trials that excluded patients requiring cardiac revascularization. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid stenting' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CAS'.) An important concern in patients also slated to undergo coronary revascularization is that a dual antiplatelet regimen (aspirin plus clopidogrel) is typically recommended for one to three months following stenting to prevent stent thrombosis. As a result, the strategy of CAS immediately prior to CABG is not recommended, since the incidence of perioperative bleeding would be significantly increased. This risk is illustrated by results from the nonrandomized SHARP study of 101 patients who had same-day CAS and CABG [49]. All patients received aspirin beginning at least three days before carotid stenting, and clopidogrel was started within 6 to 10 hours after the end of CABG. At 30 days, major bleeding occurred in four patients (4 percent), a rate we consider four times higher than acceptable or expected for CABG. Furthermore, this major bleeding risk could exceed the risk of stroke and thus outweigh any potential benefit from the carotid procedure. Thus, patients who need immediate CABG and who require a carotid intervention should have an open CEA rather than a stenting procedure. For patients with significant coronary heart disease, CAS can be considered only if the CABG is not urgent. Such patients could receive a carotid stent with dual antiplatelet therapy for a circumscribed amount of time, followed by CABG surgery. A systematic review published in 2009 identified 11 studies with 760 patients who had staged CAS followed by CABG, which was done at different time intervals in individual studies, ranging from immediately after stenting to a mean of 70 days after stenting [50]. Eighty-seven percent of https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 11/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate the patients had asymptomatic carotid stenosis; all of the studies were retrospective and most were single-center. Combined event rates, from CAS to 30 days after CABG, were as follows: Ipsilateral stroke, 3.3 percent Any stroke, 4.2 percent Myocardial infarction, 1.8 percent Death, 5.5 percent Death and any stroke, 9.1 percent The investigators concluded that these event rates for CAS followed by CABG [50] were similar to those reported for patients who had staged CEA and CABG [51]. Timing of revascularization Operating on the carotid lesion first might increase the risk of myocardial infarction, while operating on the coronary lesion first might increase the risk of perioperative stroke [52]. Furthermore, an additional episode of anesthesia might increase the risk of either of the staged procedures. Advocates of the combined procedure believe that there is more efficient use of the operating room facility and surgical personnel, resulting in shorter hospitalization and lower medical cost compared with staged procedures [53]. One concern with combined CEA and CABG is that the operative morbidity and mortality may be higher than for each procedure alone [54-56]. However, one of the problems in comparing observational series of patients who have carotid artery revascularization and CABG is selection bias; as an example, patients undergoing a combined procedure may have more high-risk features or differ in other important ways from patients who have staged procedures. Comparative studies The available evidence regarding the optimal strategy is conflicting, and there are few randomized trials comparing these strategies (ie, combined carotid revascularization and CABG, staged carotid revascularization followed by CABG, or staged CABG prior to carotid revascularization) with each other or with CABG alone. A systematic review published in 2005 by the American Academy of Neurology (AAN) identified studies with 50 patients that evaluated CEA before or simultaneous with CABG [57]. All were retrospective and observational in nature. Nine studies evaluated combined CEA and CABG and included a total of 1923 patients who had combinations of stable and unstable coronary heart disease as well as symptomatic and asymptomatic carotid disease, typically marked by a >70 percent carotid stenosis or by the presence of an ulcerated plaque. Overall average perioperative complication rates were stroke in 3 percent (range 0 to 9 percent), https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 12/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate myocardial infarction in 2.2 percent (range 0 to 6 percent), and death in 4.7 percent (range 2.6 to 8.9 percent). Five- to six-year survival among 492 subjects in the three studies that reported long-term survival was 73 to 91 percent. One study evaluated CEA before CABG and included 297 patients with stable coronary heart disease. The perioperative complication rates were stroke in 1.9 percent, myocardial infarction in 4.7 percent, and death in 1.6 percent. Based on these retrospective data, the AAN concluded that perioperative complication rates were probably similar with combined CEA and CABG compared with CEA before CABG. A 2013 single-center retrospective analysis evaluated the outcome of 350 patients with severe coronary and carotid stenosis who underwent combined CEA and cardiac surgery (n=195), staged CEA followed by cardiac surgery (n=45), or staged CAS followed by cardiac surgery (n=110) [58]. Most of the cardiac procedures (92 percent) involved CABG, either alone or combined with other cardiac interventions such as valve surgery. Carotid disease was asymptomatic in 81 percent; there was a contralateral carotid stenosis (80 to 99 percent) in 9 percent, and a contralateral carotid occlusion in 13 percent. The following outcomes were reported: There was a significantly lower risk of interstage myocardial infarction (MI) for the staged CAS/cardiac surgery group compared with the staged CEA/cardiac surgery group (3 versus 11 percent), although the rates were similar for stroke (1 versus 2 percent) and death (5 versus 7 percent). For the composite endpoint of death, MI, and stroke, the staged CAS/cardiac surgery group and the combined CEA/cardiac surgery group had lower rates compared with the staged CEA/cardiac surgery group at 30 days after cardiac surgery (10 versus 10 versus 31 percent, respectively) and at one year (16 versus 17 versus 40 percent, respectively). These results were driven largely by the higher interstage (ie, precardiac surgery) MI event rate for the staged CEA/cardiac surgery group. During the period beyond one year after cardiac surgery, the staged CAS/cardiac surgery group had a lower composite event rate compared with the combined CEA/cardiac surgery group and staged CEA/cardiac surgery group (12 versus 39 versus 27 percent, respectively). These data suggest that staged CAS followed by CABG is the optimal strategy for patients with high-grade carotid stenosis who do not require urgent coronary revascularization, https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 13/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate while combined CEA and cardiac surgery is optimal for those who do require urgent coronary intervention. One of the relative strengths of this study is that patients in the staged CAS/cardiac surgery group were evaluated by a neurologist before and after CAS, suggesting that the stroke event rate for this group is reliable; by contrast, patients in the CEA groups were examined by a neurologist on an as-needed basis, as is true of nearly all such studies. However, limitations to this study, particularly the lack of randomization and retrospective methodology, precluded definitive conclusions. Surgical techniques of combined CEA and CABG Once the decision has been made to perform a combined CEA and CABG procedure, does it make a difference whether the CEA is done before or during cardiopulmonary bypass? As noted previously (see 'Comparative studies' above), retrospective data suggest that perioperative complication rates are probably similar with combined CEA and CABG compared with CEA before CABG. In addition, performing CEA during cardiopulmonary bypass does not appear to increase the incidence of bleeding or prolong hospital stay [59-61]. Our preference is to perform the CEA before cardiopulmonary bypass. After general anesthesia is induced and the patient is prepared for operation and draped, the CEA team proceeds to expose the carotid artery. Simultaneously, the cardiac team is harvesting the saphenous vein or the radial artery, if such grafts are necessary. The CEA is performed using systemic heparinization and a shunt. Once the CEA is completed, the heparin is not reversed, and the neck wound is packed but not closed. The chest is opened, the internal mammary artery is harvested, and the patient is placed on cardiopulmonary bypass, and the revascularization is completed. After the heparin is reversed, the neck excision is carefully checked for bleeding and the wound is closed. TIMING OF CABG AFTER STROKE Patients with a prior history of stroke or transient ischemic attack (TIA) have an increased risk of perioperative stroke with coronary artery bypass graft surgery (CABG) (see 'Risk factors' above), which may be as high as 8.5 percent [46]. The optimal timing of CABG surgery following a stroke has not been systematically addressed and depends upon multiple factors, including how recently the stroke occurred, the size of the stroke, the risk of stroke recurrence (which is in turn dependent on the stroke mechanism), and the urgency of cardiac intervention. A study of 14,030 patients undergoing surgical aortic valve replacement in Denmark, including 616 with prior stroke, reported a high risk of adverse events if the surgery was performed early after stroke, but the risk declined over time and stabilized after three months [62]. Unless urgent cardiac revascularization is necessary, surgery should be delayed pending a thorough work-up for the https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 14/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate stroke mechanism, including evaluation for large artery stenosis and any cardioembolic source, to clarify the risk of subsequent stroke and ensure appropriate stroke prevention therapies. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack".) Optimal timing of cardiac surgery should also include a sufficient delay to allow for poststroke recovery of autoregulatory capabilities of the cerebral vasculature prior to exposure to periprocedural hypotension, and for sufficient remodeling of the damaged parenchyma to decrease the risk of hemorrhagic transformation of the infarct. Deferral of cardiac surgery for several weeks is suggested, although patients with large strokes (ie, those with damage involving the majority of a vascular territory or a sizeable portion of multiple territories) would likely benefit from additional delay. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) SUMMARY AND RECOMMENDATIONS The main mechanisms of ischemic stroke associated with coronary artery bypass graft surgery (CABG) are atheroembolization, particularly from the aortic arch, and cerebral hypoperfusion, which is less common. (See 'Stroke associated with CABG' above.) Atherosclerosis of the ascending aorta may be a more important cause of perioperative stroke than carotid artery stenosis. (See 'Risk factors' above and 'Aortic atherosclerosis' above.) The presence of a symptomatic carotid artery stenosis probably increases the risk of a |
carotid stenosis or by the presence of an ulcerated plaque. Overall average perioperative complication rates were stroke in 3 percent (range 0 to 9 percent), https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 12/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate myocardial infarction in 2.2 percent (range 0 to 6 percent), and death in 4.7 percent (range 2.6 to 8.9 percent). Five- to six-year survival among 492 subjects in the three studies that reported long-term survival was 73 to 91 percent. One study evaluated CEA before CABG and included 297 patients with stable coronary heart disease. The perioperative complication rates were stroke in 1.9 percent, myocardial infarction in 4.7 percent, and death in 1.6 percent. Based on these retrospective data, the AAN concluded that perioperative complication rates were probably similar with combined CEA and CABG compared with CEA before CABG. A 2013 single-center retrospective analysis evaluated the outcome of 350 patients with severe coronary and carotid stenosis who underwent combined CEA and cardiac surgery (n=195), staged CEA followed by cardiac surgery (n=45), or staged CAS followed by cardiac surgery (n=110) [58]. Most of the cardiac procedures (92 percent) involved CABG, either alone or combined with other cardiac interventions such as valve surgery. Carotid disease was asymptomatic in 81 percent; there was a contralateral carotid stenosis (80 to 99 percent) in 9 percent, and a contralateral carotid occlusion in 13 percent. The following outcomes were reported: There was a significantly lower risk of interstage myocardial infarction (MI) for the staged CAS/cardiac surgery group compared with the staged CEA/cardiac surgery group (3 versus 11 percent), although the rates were similar for stroke (1 versus 2 percent) and death (5 versus 7 percent). For the composite endpoint of death, MI, and stroke, the staged CAS/cardiac surgery group and the combined CEA/cardiac surgery group had lower rates compared with the staged CEA/cardiac surgery group at 30 days after cardiac surgery (10 versus 10 versus 31 percent, respectively) and at one year (16 versus 17 versus 40 percent, respectively). These results were driven largely by the higher interstage (ie, precardiac surgery) MI event rate for the staged CEA/cardiac surgery group. During the period beyond one year after cardiac surgery, the staged CAS/cardiac surgery group had a lower composite event rate compared with the combined CEA/cardiac surgery group and staged CEA/cardiac surgery group (12 versus 39 versus 27 percent, respectively). These data suggest that staged CAS followed by CABG is the optimal strategy for patients with high-grade carotid stenosis who do not require urgent coronary revascularization, https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 13/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate while combined CEA and cardiac surgery is optimal for those who do require urgent coronary intervention. One of the relative strengths of this study is that patients in the staged CAS/cardiac surgery group were evaluated by a neurologist before and after CAS, suggesting that the stroke event rate for this group is reliable; by contrast, patients in the CEA groups were examined by a neurologist on an as-needed basis, as is true of nearly all such studies. However, limitations to this study, particularly the lack of randomization and retrospective methodology, precluded definitive conclusions. Surgical techniques of combined CEA and CABG Once the decision has been made to perform a combined CEA and CABG procedure, does it make a difference whether the CEA is done before or during cardiopulmonary bypass? As noted previously (see 'Comparative studies' above), retrospective data suggest that perioperative complication rates are probably similar with combined CEA and CABG compared with CEA before CABG. In addition, performing CEA during cardiopulmonary bypass does not appear to increase the incidence of bleeding or prolong hospital stay [59-61]. Our preference is to perform the CEA before cardiopulmonary bypass. After general anesthesia is induced and the patient is prepared for operation and draped, the CEA team proceeds to expose the carotid artery. Simultaneously, the cardiac team is harvesting the saphenous vein or the radial artery, if such grafts are necessary. The CEA is performed using systemic heparinization and a shunt. Once the CEA is completed, the heparin is not reversed, and the neck wound is packed but not closed. The chest is opened, the internal mammary artery is harvested, and the patient is placed on cardiopulmonary bypass, and the revascularization is completed. After the heparin is reversed, the neck excision is carefully checked for bleeding and the wound is closed. TIMING OF CABG AFTER STROKE Patients with a prior history of stroke or transient ischemic attack (TIA) have an increased risk of perioperative stroke with coronary artery bypass graft surgery (CABG) (see 'Risk factors' above), which may be as high as 8.5 percent [46]. The optimal timing of CABG surgery following a stroke has not been systematically addressed and depends upon multiple factors, including how recently the stroke occurred, the size of the stroke, the risk of stroke recurrence (which is in turn dependent on the stroke mechanism), and the urgency of cardiac intervention. A study of 14,030 patients undergoing surgical aortic valve replacement in Denmark, including 616 with prior stroke, reported a high risk of adverse events if the surgery was performed early after stroke, but the risk declined over time and stabilized after three months [62]. Unless urgent cardiac revascularization is necessary, surgery should be delayed pending a thorough work-up for the https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 14/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate stroke mechanism, including evaluation for large artery stenosis and any cardioembolic source, to clarify the risk of subsequent stroke and ensure appropriate stroke prevention therapies. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack".) Optimal timing of cardiac surgery should also include a sufficient delay to allow for poststroke recovery of autoregulatory capabilities of the cerebral vasculature prior to exposure to periprocedural hypotension, and for sufficient remodeling of the damaged parenchyma to decrease the risk of hemorrhagic transformation of the infarct. Deferral of cardiac surgery for several weeks is suggested, although patients with large strokes (ie, those with damage involving the majority of a vascular territory or a sizeable portion of multiple territories) would likely benefit from additional delay. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) SUMMARY AND RECOMMENDATIONS The main mechanisms of ischemic stroke associated with coronary artery bypass graft surgery (CABG) are atheroembolization, particularly from the aortic arch, and cerebral hypoperfusion, which is less common. (See 'Stroke associated with CABG' above.) Atherosclerosis of the ascending aorta may be a more important cause of perioperative stroke than carotid artery stenosis. (See 'Risk factors' above and 'Aortic atherosclerosis' above.) The presence of a symptomatic carotid artery stenosis probably increases the risk of a perioperative stroke in patients undergoing CABG. In addition, the presence of bilateral 50 to 99 percent carotid stenoses or total carotid occlusion on one side combined with a 50 to 99 percent carotid stenosis on the other side may be associated with an increased stroke risk. However, patients with an asymptomatic unilateral carotid artery stenosis are likely to have little or no increased risk of carotid-related perioperative stroke during CABG and, therefore, we do not recommend carotid intervention in this population prior to CABG. (See 'Carotid stenosis' above.) https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 15/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Strategies for prevention of stroke with CABG include (see 'Prevention of perioperative stroke' above): Preoperative evaluation for identification and potential treatment of preexisting stroke risk factors, including aortic atherosclerosis and carotid stenosis Medical therapy, including the use of aspirin, antiarrhythmic drugs, and statins, and antihypertensive therapy For patients undergoing CABG who have carotid stenosis, we suggest carotid revascularization rather than no carotid intervention for the following subgroups only (Grade 2C) (see 'Prophylactic carotid intervention' above): A recently symptomatic carotid stenosis (50 to 99 percent stenosis in men or 70 to 99 percent stenosis in women) Bilateral asymptomatic 80 to 99 percent carotid stenoses A unilateral asymptomatic stenosis of 70 to 99 percent combined with a contralateral total (100 percent) carotid occlusion For patients undergoing CABG who have an isolated unilateral asymptomatic 50 to 99 percent carotid artery stenosis, we suggest not performing prophylactic carotid revascularization (Grade 2C). (See 'Prophylactic carotid intervention' above.) For patients undergoing CABG who are selected for carotid revascularization, we suggest a combined procedure with carotid endarterectomy (CEA) plus CABG, rather than a staged procedure, for those who have severe left main coronary artery disease, diffuse coronary heart disease without satisfactory collaterals, or unstable angina (Grade 2C). We suggest a staged carotid revascularization with CEA or carotid artery stenting (CAS) before CABG, rather than a combined procedure, for patients with chronic stable angina in the absence of a recent myocardial infarction (Grade 2C). (See 'Carotid treatment options' above.) For patients undergoing CABG who require carotid revascularization, we recommend not performing CAS immediately prior to CABG (Grade 1C). We make this recommendation because dual antiplatelet therapy is required following stenting, a factor that likely increases the perioperative risk of bleeding with the CABG procedure. However, CAS is an alternative to CEA if the CABG is not urgent. Such patients could receive a carotid stent with antiplatelet therapy for several weeks, followed by CABG surgery. (See 'Method of carotid revascularization' above.) https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 16/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate Timing of cardiac surgery after a stroke should include sufficient delay to allow identification of the cause of stroke, restoration of cerebral autoregulatory mechanisms, and remodeling of the parenchymal damage to minimize the risk of hemorrhagic transformation. Unless emergent cardiac surgery is warranted, we suggest a delay of at least a month and preferably up to three months, particularly for strokes involving larger territories. (See 'Timing of CABG after stroke' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. 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Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting: A Randomized Clinical Trial. Stroke 2017; 48:2769. 45. Knipp SC, Holst T, Bilbilis K, et al. Five-Year Results of Coronary Artery Bypass Grafting With or Without Carotid Endarterectomy in Patients With Asymptomatic Carotid Artery Stenosis: CABACS RCT. Stroke 2022; 53:3270. 46. Naylor AR, Mehta Z, Rothwell PM, Bell PR. Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature. Eur J Vasc Endovasc Surg 2002; 23:283. https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 20/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate 47. Hines GL, Scott WC, Schubach SL, et al. Prophylactic carotid endarterectomy in patients with high-grade carotid stenosis undergoing coronary bypass: does it decrease the incidence of perioperative stroke? Ann Vasc Surg 1998; 12:23. 48. Gott JP, Thourani VH, Wright CE, et al. Risk neutralization in cardiac operations: detection and treatment of associated carotid disease. Ann Thorac Surg 1999; 68:850. 49. Versaci F, Reimers B, Del Giudice C, et al. Simultaneous hybrid revascularization by carotid stenting and coronary artery bypass grafting: the SHARP study. JACC Cardiovasc Interv 2009; 2:393. 50. Naylor AR, Mehta Z, Rothwell PM. A systematic review and meta-analysis of 30-day outcomes following staged carotid artery stenting and coronary bypass. Eur J Vasc Endovasc Surg 2009; 37:379. 51. Naylor R, Cuffe RL, Rothwell PM, et al. A systematic review of outcome following synchronous carotid endarterectomy and coronary artery bypass: influence of surgical and patient variables. Eur J Vasc Endovasc Surg 2003; 26:230. 52. Moore WS, Barnett HJ, Beebe HG, et al. Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc Committee, American Heart Association. Stroke 1995; 26:188. 53. Daily PO, Freeman RK, Dembitsky WP, et al. Cost reduction by combined carotid endarterectomy and coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996; 111:1185. 54. Hertzer NR, Loop FD, Taylor PC, Beven EG. Combined myocardial revascularization and carotid endarterectomy. Operative and late results in 331 patients. J Thorac Cardiovasc Surg 1983; 85:577. 55. Rizzo RJ, Whittemore AD, Couper GS, et al. Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath. Ann Thorac Surg 1992; 54:1099. 56. Dubinsky RM, Lai SM. Mortality from combined carotid endarterectomy and coronary artery bypass surgery in the US. Neurology 2007; 68:195. 57. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005; 65:794. 58. Shishehbor MH, Venkatachalam S, Sun Z, et al. A direct comparison of early and late outcomes with three approaches to carotid revascularization and open heart surgery. J Am Coll Cardiol 2013; 62:1948. https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 21/22 7/5/23, 11:39 AM Coronary artery bypass grafting in patients with cerebrovascular disease - UpToDate 59. Minami K, Sagoo KS, Breymann T, et al. Operative strategy in combined coronary and carotid artery disease. J Thorac Cardiovasc Surg 1988; 95:303. 60. Matar AF. Concomitant coronary and cerebral revascularization under cardiopulmonary bypass. Ann Thorac Surg 1986; 41:431. 61. Kouchoukos NT, Daily BB, Wareing TH, Murphy SF. Hypothermic circulatory arrest for cerebral protection during combined carotid and cardiac surgery in patients with bilateral carotid artery disease. Ann Surg 1994; 219:699. 62. Andreasen C, J rgensen ME, Gislason GH, et al. Association of Timing of Aortic Valve Replacement Surgery After Stroke With Risk of Recurrent Stroke and Mortality. JAMA Cardiol 2018; 3:506. Topic 1097 Version 25.0 Contributor Disclosures Harold L Lazar, MD No relevant financial relationship(s) with ineligible companies to disclose. Christina A Wilson, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Steven R Mess , MD Equity Ownership/Stock Options: Neuralert Technologies [Stroke monitoring]. Grant/Research/Clinical Trial Support: Biogen [Hemispheric ischemic stroke]; Mallinkrodt, Inc [Nitric oxide and cerebral perfusion]; Novartis [Intracerebral hemorrhage]; WL Gore & Associates [PFO closure for secondary stroke prevention, neurologic outcomes from proximal aortic repair]. Consultant/Advisory Boards: Boston Scientific [steering committee for PROTECTED-TAVR trial of embolic protection during TAVR]; EmStop [embolic protection during TAVR]; WL Gore [DSMB for post marketing study of PFO closure for secondary stroke prevention]. Other Financial Interest: Novo Nordisk [ONWARDS trial event adjudication committee]; Terumo [Patient selection committee, Relay Branch trial]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/coronary-artery-bypass-grafting-in-patients-with-cerebrovascular-disease/print 22/22 |
7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Evaluation of carotid artery stenosis : Brett L Cucchiara, MD : Scott E Kasner, MD, John F Eidt, MD, Joseph L Mills, Sr, MD : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 01, 2023. INTRODUCTION Four diagnostic modalities are used to directly image the internal carotid artery: Carotid duplex ultrasound (CDUS) Magnetic resonance angiography (MRA) Computed tomography angiography (CTA) Catheter cerebral angiography (often called conventional angiography or digital subtraction angiography) This topic will review the clinical use of these different techniques and their unique advantages and disadvantages. In addition, we will review the different methods of measuring the degree of carotid stenosis used with angiography. Other aspects of carotid disease are discussed separately. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic extracranial carotid atherosclerotic disease".) GOALS OF IMAGING The main goal of carotid artery imaging is to assess for vascular abnormalities that may contribute to stroke, of which the most common is atherosclerotic disease. Determining the degree of atherosclerotic stenosis (or whether complete occlusion is present) has critical management implications. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 1/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Measurement of stenosis The benefit of carotid revascularization with endarterectomy or stenting is dependent on the severity of the stenosis. The methods of evaluating the degree of carotid stenosis vary in technique and accuracy. If the results of clinical trials are to be generalized, there is a need for uniformity in measurement [1]. Stenosis determination by angiography The two major randomized clinical trials evaluating the utility of endarterectomy in symptomatic patients (NASCET and ECST) used different methods to measure carotid stenosis ( figure 1), though both relied on catheter angiography [2]. An additional method, the common carotid (CC) method, has also been used: NASCET The North American Symptomatic Carotid Endarterectomy Trial (NASCET) method measures the residual lumen diameter at the most stenotic portion of the vessel and compares this with the lumen diameter in the normal internal carotid artery distal to the stenosis [3]. ECST The European Carotid Surgery Trial (ECST) method measures the lumen diameter at the most stenotic portion of the vessel and compares this with the estimated probable original diameter at the site of maximum stenosis [4]. CC The common carotid (CC) method measures the residual lumen diameter at the most stenotic portion of the vessel and compares this with the lumen diameter in the proximal common carotid artery [2,5]. The maximum degree of stenosis is generally in the carotid bulb, which is a wider portion of the artery than the distal segment. As a result, the same degree of stenosis is quantified as a higher percentage stenosis when measured by the ECST or CC methods than when measured by the NASCET method. The ECST methodology also requires an assumption of the true lumen, which increases the risk of interobserver variability ( figure 1). Despite these differences, the results of all three methods have a nearly linear relationship to each other and provide data of similar prognostic value [2]. Equivalent measurements for the three methods have been determined [2,6]: A 50 percent stenosis with the NASCET method is comparable to a 65 percent stenosis for both the ECST and CC methods. A 70 percent stenosis with the NASCET method is comparable to an 82 percent stenosis for both the ECST and CC methods. Given its better interrater reliability, the NASCET method has been most widely adopted over time [7]. All three methods (NASCET, ECST, and CC) were originally devised for use with https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 2/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate catheter angiography, though these methods can also be used with magnetic resonance and computed tomography angiography. Stenosis determination by carotid duplex ultrasound (CDUS) In contrast to the angiographic measurements described above, CDUS generally estimates the degree of stenosis based on elevations in blood flow velocity observed in the target vessel as opposed to anatomic measurements of luminal narrowing. Velocity criteria correlating with specific degrees of angiographically-confirmed stenosis (usually using the NASCET method) have been established; these are typically categorical as opposed to linear (ie, <50 percent stenosis, 50 to 69 percent stenosis, >70 percent stenosis). Diagnosis of complete occlusion No surgical treatment has been proven to be of benefit for preventing a subsequent stroke in patients with complete carotid artery occlusion. Additionally, revascularization in these patients is often technically not feasible. Thus, it is important to adequately distinguish between completely occluded vessels and those with some remaining flow, since the latter group may benefit from carotid revascularization. Identifying other arteriopathies Carotid imaging can also provide crucial information about the presence and characteristics of other arteriopathies that are potential risk factors and mechanisms of ischemic symptoms. These include the following: Dissection (see "Cerebral and cervical artery dissection: Clinical features and diagnosis", section on 'Evaluation and diagnosis') Fibromuscular dysplasia (see "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Fibromuscular dysplasia') Carotid web (see "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Carotid web') Carotid aneurysm (see "Extracranial carotid artery aneurysm") Evaluating carotid plaque characteristics Determination of carotid plaque characteristics (eg, ulceration, plaque area, intraplaque hemorrhage, plaque echogenicity) may be useful to identify patients with asymptomatic carotid occlusive disease who are at higher risk of stroke and therefore likely to benefit from carotid revascularization. This is discussed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid plaque morphology'.) CHOICE OF IMAGING TEST https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 3/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Patients with carotid stenosis are generally identified using one or more of the noninvasive tests, which have largely replaced catheter angiography in the presurgical evaluation of carotid stenosis: Carotid duplex ultrasound (CDUS) Computed tomography angiography (CTA) Time-of-flight magnetic resonance angiography (TOF MRA) Contrast-enhanced magnetic resonance angiography (CEMRA) Catheter cerebral angiography has been considered the gold standard for the evaluation of internal carotid artery stenosis [8]. However, catheter angiography is invasive, time-consuming, resource-intensive, and associated with a small but real risk of procedural stroke and other vascular complications. Selection of initial test The choice among the noninvasive carotid artery imaging methods depends mainly upon the clinical indications for imaging, the availability and expertise at individual centers, and the initial patient presentation [9]. Our approach to patients with suspected carotid stenosis depends on whether the patient is symptomatic or asymptomatic. Symptomatic For patients with stroke or transient ischemic attack (TIA) potentially due to carotid stenosis, we generally perform CTA or MRA of the head and neck initially. This expedites imaging of both the extracranial and intracranial circulation and allows for identification of unusual vascular abnormalities implicated as stroke mechanisms, such as carotid webs or dissections, in addition to more typical atherosclerotic stenosis. However, other experts prefer CDUS as the initial imaging test, followed most often by CTA if carotid revascularization is being considered. In patients presenting with acute stroke or TIA, immediate CTA is often performed in the emergency department to risk-stratify and rapidly guide acute treatment. In patients with stroke or suspected TIA undergoing brain magnetic resonance imaging (MRI) who have not already had CTA, combining brain MRI with MRA of the head and neck can be an efficient diagnostic strategy. In patients with stroke or TIA in whom an obvious stroke mechanism is apparent (eg, atrial fibrillation) and for whom thrombolysis or thrombectomy is not a consideration, CDUS alone may be the efficient strategy. Asymptomatic For asymptomatic patients (eg, when a carotid bruit is heard), we generally use CDUS as our initial imaging modality. CDUS is an accurate and cost-effective imaging test. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 4/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Confirmation of stenosis Less than 50 percent stenosis CDUS, CTA, or MRA demonstrating less than 50 percent carotid stenosis generally rules out significant atherosclerotic stenosis that would require revascularization, and no further testing is typically needed. Important exceptions to this include carotid stenosis that is unusually distal and beyond the field of insonation for CDUS as well as short-segment stenosis in regions of heavily calcified plaque on CTA in which adequate assessment of the residual lumen may be difficult. Severe calcification may also hamper duplex imaging. Symptomatic 50 to 99 percent stenosis When >50 percent stenosis is identified on any of the above noninvasive tests, confirmation with an alternative modality is generally advisable, as two separate noninvasive diagnostic modalities concordant for high-grade stenosis increase accuracy. For instance, the combination of carotid duplex and MRA is highly specific (range 80 to 90 percent) for high-grade carotid stenosis when concordant [10-13], is cost effective [14,15], and results in an overall error rate (approximately 3 to 6 percent) that is comparable to the interobserver reliability when two radiologists are presented with the same catheter angiogram revealing carotid artery disease [16]. Similar findings are likely with combined CDUS and CTA, though this has been less extensively studied. When these tests are concordant, we proceed to revascularization if appropriate. If discordant results are found, we then consider either catheter angiography or alternate angiographic imaging different than the initial modality (ie, CTA if MRA was done initially, and vice versa) depending on image quality and the suspected reasons for the discordant results. However, other experts disagree about the need for additional imaging, and carotid revascularization is performed in some centers using CDUS as the sole preoperative imaging modality for the cervical carotid artery in some patients [17,18]. If CDUS is to be used as the single modality for identifying patients for carotid revascularization, evidence of extremely elevated velocity parameters or transcranial Doppler results indicating collateral patterns corresponding to hemodynamically significant proximal carotid stenosis (reversal of ophthalmic artery or ipsilateral anterior cerebral artery flow) increase the reliability for identification of high-grade stenosis. Asymptomatic 50 to 99 percent stenosis If a >50 percent carotid stenosis is identified on the initial study, typically CDUS, the next steps depend upon whether carotid https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 5/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate revascularization is being considered. (See "Management of asymptomatic extracranial carotid atherosclerotic disease".) If carotid revascularization will not be pursued (based on assessment of relative risks and benefits in the individual patient), patients with asymptomatic carotid stenosis can be followed with noninvasive vascular imaging of the carotid artery, typically CDUS, particularly if they may be candidates for revascularization in the setting of stenosis progression. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Imaging surveillance'.) If carotid revascularization is being considered, we generally proceed to CTA or MRA, with a similar approach to concordant and discordant results as for symptomatic patients. The role of carotid revascularization for patients with asymptomatic carotid stenosis is reviewed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Role of carotid revascularization'.) Importantly, all patients with carotid stenosis should receive intensive medical therapy including antiplatelet and statin therapy and other measures to address risk factors for atherosclerosis. Specific recommendations are discussed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Intensive medical therapy and follow-up' and "Overview of primary prevention of cardiovascular disease".) Occlusion Both CDUS and MRA are quite accurate at discriminating between occlusion and severe stenosis. One systematic review pooled data across multiple studies and used digital subtraction angiography (DSA) as the gold standard; for determination of complete carotid occlusion, the sensitivity and specificity with CDUS was 96 and 100 percent, respectively, and with MRA was 98 and 100 percent [19]. Some authors have suggested that, as with high-grade stenosis, concordant results from the combination of MRA and CDUS should be considered diagnostic of occlusion, while discordant results should prompt additional imaging modalities such as DSA [20]. Despite a widespread perception that CTA is highly accurate for discrimination between occlusion and severe stenosis, data supporting this are limited and confounded by technical changes in CTA over time and variable timing schemes for image acquisition. Early reports suggested CTA was 97 to 100 percent sensitive and 99 to 100 percent specific for detection of carotid occlusion [21,22], but the increasing speed of image acquisition with multidetector computed tomography (CT) scans has led to recognition of the phenomenon of carotid "pseudo-occlusion," whereby image acquisition occurs with insufficient time for the contrast bolus to fully opacify the affected vessel, creating the https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 6/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate erroneous appearance of complete occlusion [23]. This problem can be avoided with multiphase CTA, but this is not widely used. In the author s practice, carotid occlusion identified by CTA prompts further study with CDUS to confirm the occlusion if the patient would be a candidate for carotid revascularization and if atherosclerotic stenosis at the bifurcation is suspected to be the source of the occlusion. When carotid occlusion is identified by CEMRA or CDUS, additional testing is generally not performed. COMPUTED TOMOGRAPHY ANGIOGRAPHY Computed tomography angiography (CTA) provides an anatomic depiction of the carotid artery lumen and allows imaging of adjacent soft tissue and bony structures ( image 1A-B). Three- dimensional reconstruction allows relatively accurate measurements of residual lumen diameter. Advantages CTA may be particularly useful when carotid duplex ultrasound is not reliable (eg, in cases with severe kinking, short neck, or high bifurcation) or when an overall view of the vascular field is required [24]. Additionally, CTA can be obtained extremely rapidly (typically <1 minute from contrast bolus injection to completion of image acquisition with modern multidetector CT), an important advantage in patients who are uncooperative or claustrophobic. Disadvantages CTA requires a contrast bolus comparable to that administered during a catheter angiogram. As a result, impaired renal function may raise concern for contrast nephropathy, particularly in patients with diabetes, congestive heart failure, or pre-existing kidney disease. (See "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management".) In addition, radiation exposure is a potential risk, particularly in young patients or those undergoing multiple repeated studies. (See "Radiation-related risks of imaging".) Accuracy A meta-analysis published in 2006 concluded that CTA compared with catheter cerebral angiography for the diagnosis of 70 to 99 percent carotid stenosis had a sensitivity of 0.77 (95% CI 0.68-0.84) and a specificity of 0.95 (95% CI 0.91-0.97) [25]. An earlier systematic review and meta-analysis that compared CTA with arteriography or digital subtraction angiography concluded that CTA is an accurate method for detection of severe carotid artery disease, particularly for detection of carotid occlusion, where CTA had a sensitivity and specificity of 97 and 99 percent, respectively [22]. The accuracy of CTA may be limited when severe calcifications are present. Evolving technologies, such as dual energy CT angiography, may improve accuracy in these situations https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 7/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate [26]. MAGNETIC RESONANCE ANGIOGRAPHY Magnetic resonance angiography (MRA) generates a reproducible three-dimensional image of the carotid bifurcation with good sensitivity for detecting high-grade carotid stenosis ( image 2). Techniques The techniques most often employed for evaluating the extracranial carotid arteries utilize either two- or three-dimensional time-of-flight (TOF) MRA or gadolinium- enhanced MRA (also known as contrast-enhanced MRA or CEMRA). (See "Principles of magnetic resonance imaging".) CEMRA offers several advantages over traditional TOF techniques. The use of a paramagnetic agent acting as a vascular contrast allows for higher-quality images that are less prone to artifacts. CEMRA is superior to TOF MRA at identifying plaque ulceration [27]. Advantages Compared with carotid duplex ultrasound (CDUS), MRA is less operator- dependent and produces an image of the artery throughout its entire cervical course. Disadvantages MRA is more expensive and time-consuming than CDUS and is less readily available. Furthermore, MRA may be difficult to adequately perform if the patient is critically ill, unable to lie supine, or has claustrophobia, a pacemaker, or ferromagnetic implants [28]. In different series, up to 17 percent of MRA studies are incomplete because the patient could not tolerate the study or could not lie still enough to produce an image of adequate quality for interpretation [29]. Accuracy Both TOF MRA and CEMRA are accurate for the identification of high-grade carotid artery stenosis and occlusion, but they appear to be less accurate for detecting moderate stenosis [30]. In a 2008 meta-analysis that compared MRA with catheter angiography, the sensitivities of either MRA technique for the identification of carotid artery occlusion or severe stenosis were similar and ranged from 91 to 99 percent, while specificities ranged from 88 to 99 percent. In earlier studies, MRA was found to generally overestimate the degree and length of stenosis [28,31]. However, a later study of three-dimensional TOF MRA found that it did not overestimate the degree of stenosis when corresponding MRA and digital subtraction angiography (DSA) projections were compared [32]. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 8/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate CAROTID DUPLEX ULTRASOUND Techniques CDUS Carotid duplex ultrasound (CDUS) uses B-mode (grayscale) ultrasound imaging and Doppler ultrasound to detect focal increases in blood flow velocity indicative of high-grade carotid stenosis [28,33,34]. The peak systolic velocity is the most frequently used measurement to gauge the severity of the stenosis ( image 1A-B), but the end-diastolic velocity, spectral configuration, and the carotid ratio (the peak internal carotid artery velocity to common carotid artery velocity ratio) provide important additional information [35,36]. Consensus criteria on velocity measurements correlating with varying categories of stenosis have been published ( table 1) and are widely used [17,37]. Note that while these categorical criteria were developed to optimize accuracy in clinical practice, the specificity of an elevated velocity for severe carotid stenosis rises steadily with increasing absolute peak systolic velocities. Color Doppler flow imaging may simplify test performance by allowing the technician to more easily identify the lesion, but it has not been shown to improve accuracy [33,34,38,39]. The role of CDUS in the evaluation of carotid plaque morphology is reviewed elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid plaque morphology'.) Contrast-enhanced ultrasound Contrast-enhanced ultrasound is performed after intravenous injection of a microbubble contrast agent. This technique may be useful for evaluating carotid plaque neovascularization, a possible marker of plaque instability [40- 42]. In addition, contrast-enhanced ultrasound may help distinguish complete carotid occlusion from near occlusion and improve lumen visualization in carotid arteries that are technically challenging to study by conventional CDUS. 3D ultrasound Three-dimensional ultrasound improves visualization of vascular anatomy [43]. Advantages compared with B-mode ultrasound include the potential for quantitative monitoring of plaque volume changes in all three directions (circumferentially as well as length and thickness) rather than one or two directions [44]. This in turn could allow measurement of plaque volume change, which may be a more sensitive marker of plaque https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 9/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate progression than measurements of plaque area, intima-media thickness, and carotid stenosis. Disadvantages of three-dimensional ultrasound include a tendency for underestimation of vessel stenosis and difficulty imaging areas of calcification [45]. It is also not widely available or utilized in routine clinical care. Advantages CDUS is a noninvasive, safe, and inexpensive technique for evaluation of the carotid arteries. It is generally associated with greater patient comfort than other modalities as it does not require placement of an intravenous line for contrast injection, nor are there issues of claustrophobia as sometimes seen with magnetic resonance angiography (MRA). Using published consensus velocity criteria, diagnosis of carotid stenosis and stratification into relevant categories of degree of stenosis can be performed with high sensitivity and specificity [37]. CDUS is easily repeated to monitor for change in stenosis over time, which may be useful in certain scenarios. Disadvantages The absence of flow in the internal carotid artery may be due to occlusion, but hairline residual lumens can be missed on CDUS (as with other imaging modalities) [46]. In addition, several studies have found that CDUS tends to overestimate the degree of stenosis [10,47]. CDUS is less precise in determining stenoses of <50 percent compared with stenoses of higher degrees [28,33]. However, this rarely impacts its clinical utility as intervention is not indicated for any condition associated with internal carotid artery stenosis at the bifurcation of <50 percent. CDUS may also be less accurate in determining stenoses in the range of 50 to 69 percent compared with 70 percent stenosis [47]. However, this, too, rarely impacts its clinical utility because most patients with asymptomatic carotid stenosis who are considered for endarterectomy have 70 percent stenosis. In addition, while patients with relevant symptoms and 50 to 69 percent stenosis may be appropriate for carotid intervention, most patients with symptomatic internal carotid artery stenosis have 70 percent stenosis. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid endarterectomy' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients likely to benefit' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CEA'.) CDUS imaging may be limited by features such as calcific carotid lesions, tortuous or kinked carotid arteries, and patient body habitus. Furthermore, CDUS must be interpreted carefully in patients with contralateral carotid occlusion to avoid overestimation of an ipsilateral carotid stenosis, since the peak systolic velocity may be increased in the presence of a contralateral https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 10/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate internal carotid occlusion [48]. In this scenario, the peak internal carotid to the ipsilateral common carotid artery velocity ratio will usually accurately reflect the degree of stenosis. An additional limitation of CDUS is that only a portion of the cervical internal carotid artery extending just past the carotid bifurcation can be evaluated. Fortunately, the vast majority of atherosclerotic stenoses occur within this region. However, other carotid pathologies, such as carotid dissection, often occur in the more distal portion of the cervical carotid artery and thus will not be accurately identified by CDUS [49]. When suspected, angiographic imaging with computed tomography angiography (CTA), MRA, or catheter angiography should be used instead. Transcranial Doppler may also provide additional information about intracranial vessels that may inform the assessment of carotid disease. (See 'Transcranial Doppler' below.) Accuracy A 2022 Cochrane systematic review concluded that CDUS compared with digital subtraction angiography (DSA) for the diagnosis of 50 to 99 percent carotid stenosis had a sensitivity of 0.97 (95% CI 0.95-0.98) and specificity of 0.70 (95% CI 0.67-0.73) [50]. For the 70 to 99 percent stenosis range, sensitivity was 0.85 (95% CI 0.77-0.91) and specificity 0.98 (95% CI 0.74-0.90). For complete carotid occlusion, sensitivity was 0.91 (95% CI 0.81-0.97) and specificity was 0.95 (95% CI 0.76-0.99). As noted above, studies clearly demonstrate that increasing absolute peak systolic velocities are associated with increasing specificity for high-grade stenosis. For example, while both a peak systolic velocity of 240 and a peak systolic velocity of 500 would meet criteria for >70 percent stenosis, the latter has greater specificity than the former. The accuracy of CDUS relies heavily upon the experience and expertise of the ultrasonographer [34,51]. Measurement threshold properties may vary widely between laboratories, and the magnitude of the variation is clinically important [52,53]. There may be substantial variability in interpretation even when the same scanner and same criteria for carotid stenosis are used [51,54]. Although important, it may be difficult for the clinician to know the accuracy of the local ultrasound laboratory. Accreditation for vascular testing by the multidisciplinary Intersocietal Accreditation Commission (IAC) assures that the ultrasound data meet certain criteria, including correlation against the gold standard of catheter angiography. TRANSCRANIAL DOPPLER As an adjunct to carotid duplex ultrasound (CDUS), transcranial Doppler (TCD) examines the major intracerebral arteries through the orbit, temporal windows, and at the base of the brain. TCD is often used in conjunction with CDUS to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis, and it can be used to improve the accuracy of CDUS in identifying surgical carotid disease [55]. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 11/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate TCD can evaluate the intracranial hemodynamic consequences of high-grade carotid lesions, such as the development of collateral flow patterns in the circle of Willis, reversal of flow in the ophthalmic and anterior cerebral arteries, absence of ophthalmic or carotid siphon flow, and reduced MCA flow velocity and pulsatility [56,57]. An assessment of TCD by the American Academy of Neurology (AAN) concluded that TCD is possibly useful for the evaluation of severe extracranial ICA stenosis or occlusion [58]. The AAN report noted that the clinical utility of TCD to detect impaired cerebral hemodynamics distal to high-grade extracranial ICA stenosis or occlusion and assist with stroke risk assessment requires evaluation and confirmation in randomized clinical trials. TCD can also be used for detection of middle cerebral artery microemboli that arise from the carotid artery. These are visualized as high intensity transient signals within the Doppler spectrum and have a characteristic audible "chirp" sound. TCD monitoring for microembolic signals is a powerful tool for risk-stratifying patients with asymptomatic carotid stenosis. This issue is discussed in more detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Asymptomatic embolism'.) CATHETER CEREBRAL ANGIOGRAPHY Catheter angiography is considered the gold standard for imaging the carotid arteries. However, most patients with suspected carotid stenosis are evaluated using one or more of the noninvasive tests (ultrasound, magnetic resonance angiography, or computed tomography angiography) in lieu of catheter angiography. (See 'Choice of imaging test' above.) Technique The development of intra-arterial digital subtraction angiography (DSA) reduces the dose of contrast, uses smaller catheters, and shortens the length of the procedure. Although there is lower spatial resolution, DSA has largely replaced conventional catheter angiography [59]. The introduction of a radial as opposed to femoral artery approach for DSA has improved patient comfort with the procedure and is likely associated with a reduced risk of local vascular complications [60]. The quality of catheter angiogram images depends upon selective catheterization of the carotid artery with at least two unimpeded views (typically an anteroposterior and lateral view, often with additional oblique views) to identify the projection with the most severe degree of stenosis; this method is consistent with how stenosis was determined in the ECST and NASCET trials. (See 'Measurement of stenosis' above.) https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 12/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Aortic arch injections alone are inadequate; suboptimal studies can lead to misinterpretations as an irregular stenosis can be either underestimated or overestimated in a single projection. Advantages Cerebral angiography permits an evaluation of the entire carotid artery system, providing information about tandem atherosclerotic disease, plaque morphology/ulceration, and collateral circulation that may affect management [61]. The presence of irregular or ulcerated plaque identified on catheter angiography is associated with a greater risk of recurrent stroke and greater benefit from carotid endarterectomy [62]. Disadvantages The disadvantages of catheter angiography include its invasive nature, high cost, and risk of morbidity and mortality. In a 1990 review of prospective studies using cerebral angiography, the risk of all neurologic complications was approximately 4 percent and the risk of serious neurologic complications or death was approximately 1 percent (range 0 to 6 percent) [59]. In a 2003 single-center prospective study of 986 patients undergoing angiography for diagnosis of carotid stenosis or ischemic stroke, an overall neurologic complication rate of 1.7 percent was reported, with a 0.6 percent rate of neurologic complications resulting in permanent sequelae [63]. The risk of morbidity is increased with cerebrovascular symptoms, advanced age, diabetes, hypertension, elevated serum creatinine, and peripheral vascular disease. The size of the catheter, amount of contrast, and procedure duration also affect the likelihood of complications [63,64]. One study found that embolic events following angiography occur more frequently than the apparent neurologic complication rate [65]; the clinical significance of this finding is unclear. Although often considered the "gold standard" of carotid neurovascular imaging methods, conventional DSA has the disadvantage of a limited number of projections, typically two or three, depicting the carotid artery and bifurcation. This limitation could lead to an underestimation of the degree of carotid stenosis in arteries that have asymmetrical rather than concentric stenotic lumens [66,67]. Rotational angiography provides 16 to 32 projections and is far less subject to this problem, but it is less often used in practice. Accuracy As already noted, catheter cerebral angiography has been considered the gold standard for the evaluation of internal carotid artery stenosis [8]. Noninvasive imaging versus catheter angiography In a 2006 meta-analysis of 41 studies and 2541 patients that assessed the accuracy of noninvasive imaging compared with catheter angiography, CDUS, magnetic resonance angiography (MRA), contrast-enhanced MRA (CEMRA), and CTA, all had high sensitivities and specificities for diagnosing 70 to 99 percent internal carotid artery stenosis in patients with ipsilateral carotid territory ischemic symptoms [25]. The https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 13/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate accuracy of the noninvasive tests for 50 to 69 percent carotid stenosis appeared to be substantially reduced compared with 70 to 99 percent stenosis. However, data were limited. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Carotid artery disease (The Basics)" and "Patient education: Stroke (The Basics)" and "Patient education: Duplex ultrasound (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Goals The main goal of carotid artery imaging is determining the presence and degree of atherosclerotic stenosis or complete occlusion. In addition, carotid imaging can identify other arteriopathies (eg, dissection) and evaluate carotid plaque characteristics. (See 'Goals of imaging' above.) https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 14/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Stenosis measurement The main methods of carotid stenosis measurement are the NASCET, ECST, and common carotid (CC) methods. The NASCET method is the most widely adopted. The NASCET and ECST methods were used in two major randomized clinical trials evaluating the utility of endarterectomy in symptomatic patients ( figure 1). The results of all three methods have a nearly linear relationship to each other and provide data of similar prognostic value. (See 'Measurement of stenosis' above.) Choice of imaging test Most patients are evaluated for carotid disease using one of the noninvasive tests (carotid duplex ultrasound [CDUS], time-of-flight magnetic resonance angiography [TOF MRA], contrast-enhanced MRA [CEMRA], or computed tomography angiography [CTA]). These noninvasive imaging modalities all have high sensitivities and specificities for diagnosing 70 to 99 percent internal carotid artery stenosis in patients with ipsilateral carotid territory ischemic symptoms. The accuracy of the noninvasive tests for 50 to 69 percent carotid stenosis is reduced compared with 79 to 99 percent stenosis. (See 'Choice of imaging test' above.) Symptomatic patients For patients with stroke or transient ischemic attack (TIA) potentially due to carotid stenosis, we generally perform CTA or MRA of the head and neck initially. If >50 percent carotid stenosis is identified, we then perform confirmatory CDUS. If discordant results are found, we then consider alternate angiographic imaging different than the initial modality (ie, CTA if MRA was done initially, and vice versa). (See 'Selection of initial test' above and 'Confirmation of stenosis' above.) The management of symptomatic carotid stenosis is reviewed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) Asymptomatic patients For patients who have suspected asymptomatic carotid disease, we generally use CDUS as our initial imaging modality. If >50 percent stenosis is identified and carotid revascularization will not be pursued (eg, based on assessment of relative risks and benefits in the individual patient), patients with asymptomatic carotid stenosis can be followed with noninvasive vascular imaging of the carotid artery, typically with CDUS, particularly if they may be candidates for revascularization in the setting of stenosis progression. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Imaging surveillance'.) |
12/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Aortic arch injections alone are inadequate; suboptimal studies can lead to misinterpretations as an irregular stenosis can be either underestimated or overestimated in a single projection. Advantages Cerebral angiography permits an evaluation of the entire carotid artery system, providing information about tandem atherosclerotic disease, plaque morphology/ulceration, and collateral circulation that may affect management [61]. The presence of irregular or ulcerated plaque identified on catheter angiography is associated with a greater risk of recurrent stroke and greater benefit from carotid endarterectomy [62]. Disadvantages The disadvantages of catheter angiography include its invasive nature, high cost, and risk of morbidity and mortality. In a 1990 review of prospective studies using cerebral angiography, the risk of all neurologic complications was approximately 4 percent and the risk of serious neurologic complications or death was approximately 1 percent (range 0 to 6 percent) [59]. In a 2003 single-center prospective study of 986 patients undergoing angiography for diagnosis of carotid stenosis or ischemic stroke, an overall neurologic complication rate of 1.7 percent was reported, with a 0.6 percent rate of neurologic complications resulting in permanent sequelae [63]. The risk of morbidity is increased with cerebrovascular symptoms, advanced age, diabetes, hypertension, elevated serum creatinine, and peripheral vascular disease. The size of the catheter, amount of contrast, and procedure duration also affect the likelihood of complications [63,64]. One study found that embolic events following angiography occur more frequently than the apparent neurologic complication rate [65]; the clinical significance of this finding is unclear. Although often considered the "gold standard" of carotid neurovascular imaging methods, conventional DSA has the disadvantage of a limited number of projections, typically two or three, depicting the carotid artery and bifurcation. This limitation could lead to an underestimation of the degree of carotid stenosis in arteries that have asymmetrical rather than concentric stenotic lumens [66,67]. Rotational angiography provides 16 to 32 projections and is far less subject to this problem, but it is less often used in practice. Accuracy As already noted, catheter cerebral angiography has been considered the gold standard for the evaluation of internal carotid artery stenosis [8]. Noninvasive imaging versus catheter angiography In a 2006 meta-analysis of 41 studies and 2541 patients that assessed the accuracy of noninvasive imaging compared with catheter angiography, CDUS, magnetic resonance angiography (MRA), contrast-enhanced MRA (CEMRA), and CTA, all had high sensitivities and specificities for diagnosing 70 to 99 percent internal carotid artery stenosis in patients with ipsilateral carotid territory ischemic symptoms [25]. The https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 13/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate accuracy of the noninvasive tests for 50 to 69 percent carotid stenosis appeared to be substantially reduced compared with 70 to 99 percent stenosis. However, data were limited. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Carotid artery disease (The Basics)" and "Patient education: Stroke (The Basics)" and "Patient education: Duplex ultrasound (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Goals The main goal of carotid artery imaging is determining the presence and degree of atherosclerotic stenosis or complete occlusion. In addition, carotid imaging can identify other arteriopathies (eg, dissection) and evaluate carotid plaque characteristics. (See 'Goals of imaging' above.) https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 14/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Stenosis measurement The main methods of carotid stenosis measurement are the NASCET, ECST, and common carotid (CC) methods. The NASCET method is the most widely adopted. The NASCET and ECST methods were used in two major randomized clinical trials evaluating the utility of endarterectomy in symptomatic patients ( figure 1). The results of all three methods have a nearly linear relationship to each other and provide data of similar prognostic value. (See 'Measurement of stenosis' above.) Choice of imaging test Most patients are evaluated for carotid disease using one of the noninvasive tests (carotid duplex ultrasound [CDUS], time-of-flight magnetic resonance angiography [TOF MRA], contrast-enhanced MRA [CEMRA], or computed tomography angiography [CTA]). These noninvasive imaging modalities all have high sensitivities and specificities for diagnosing 70 to 99 percent internal carotid artery stenosis in patients with ipsilateral carotid territory ischemic symptoms. The accuracy of the noninvasive tests for 50 to 69 percent carotid stenosis is reduced compared with 79 to 99 percent stenosis. (See 'Choice of imaging test' above.) Symptomatic patients For patients with stroke or transient ischemic attack (TIA) potentially due to carotid stenosis, we generally perform CTA or MRA of the head and neck initially. If >50 percent carotid stenosis is identified, we then perform confirmatory CDUS. If discordant results are found, we then consider alternate angiographic imaging different than the initial modality (ie, CTA if MRA was done initially, and vice versa). (See 'Selection of initial test' above and 'Confirmation of stenosis' above.) The management of symptomatic carotid stenosis is reviewed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) Asymptomatic patients For patients who have suspected asymptomatic carotid disease, we generally use CDUS as our initial imaging modality. If >50 percent stenosis is identified and carotid revascularization will not be pursued (eg, based on assessment of relative risks and benefits in the individual patient), patients with asymptomatic carotid stenosis can be followed with noninvasive vascular imaging of the carotid artery, typically with CDUS, particularly if they may be candidates for revascularization in the setting of stenosis progression. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Imaging surveillance'.) If >50 percent stenosis is identified and if carotid revascularization is being considered, we then proceed to CTA or MRA with a similar approach to concordant and discordant https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 15/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate results as described above. (See 'Selection of initial test' above and 'Confirmation of stenosis' above.) Importantly, all patients with carotid stenosis should receive intensive medical therapy including antiplatelet and statin therapy and other measures to address risk factors for atherosclerosis. Specific recommendations are discussed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Intensive medical therapy and follow-up' and "Overview of primary prevention of cardiovascular disease".) The role of carotid revascularization for patients with asymptomatic carotid stenosis is also reviewed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Role of carotid revascularization'.) CTA CTA provides an anatomic depiction of the carotid artery lumen and allows imaging of adjacent soft tissue and bony structures. Three-dimensional reconstruction allows accurate measurements of residual lumen diameter and degree of stenosis. (See 'Computed tomography angiography' above.) MRA The MRA techniques most often employed for evaluating the extracranial carotid arteries utilize either two- or three-dimensional TOF MRA or gadolinium-enhanced MRA (contrast-enhanced MRA [CEMRA]). MRA produces a reproducible three-dimensional image of the carotid bifurcation with good sensitivity for detecting high-grade carotid stenosis ( image 2). Both TOF MRA and CEMRA are accurate for the identification of high-grade carotid artery stenosis and occlusion. (See 'Magnetic resonance angiography' above.) Ultrasound CDUS uses B-mode ultrasound imaging and Doppler ultrasound to detect focal increases in blood flow velocity indicative of high-grade carotid stenosis ( image 1A). It is noninvasive, safe, and inexpensive, with good sensitivity and specificity for detecting high-grade carotid stenosis. (See 'Carotid duplex ultrasound' above.) TCD Transcranial Doppler (TCD) examines the major intracerebral arteries through the orbit and at the base of the brain. TCD is often used in conjunction with CDUS to evaluate the hemodynamic significance of internal carotid artery stenosis. TCD monitoring for microembolic signals is a powerful tool for risk-stratifying patients with asymptomatic carotid stenosis. (See 'Transcranial Doppler' above.) Catheter angiography Cerebral catheter angiography remains the gold standard for imaging the carotid arteries. However, catheter angiography is invasive, time-consuming, resource-intensive, and associated with a small but real risk of procedural stroke and other https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 16/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate vascular complications. Given this and the high sensitivity/specificity of noninvasive approaches, catheter angiography is used infrequently. (See 'Catheter cerebral angiography' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Janet Wilterdink, MD, J Philip Kistler, MD, and Karen L Furie, MD, MPH, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Toole JF, Castaldo JE. Accurate measurement of carotid stenosis. Chaos in methodology. J Neuroimaging 1994; 4:222. 2. Rothwell PM, Gibson RJ, Slattery J, et al. Equivalence of measurements of carotid stenosis. A comparison of three methods on 1001 angiograms. European Carotid Surgery Trialists' Collaborative Group. Stroke 1994; 25:2435. 3. North American Symptomatic Carotid Endarterectomy Trial. Methods, patient characteristics, and progress. Stroke 1991; 22:711. 4. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991; 337:1235. 5. Wardlaw JM, Lewis SC, Humphrey P, et al. How does the degree of carotid stenosis affect the accuracy and interobserver variability of magnetic resonance angiography? J Neurol Neurosurg Psychiatry 2001; 71:155. 6. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003; 361:107. 7. Del Brutto VJ, Gornik HL, Rundek T. Why are we still debating criteria for carotid artery stenosis? Ann Transl Med 2020; 8:1270. 8. Rothwell PM. 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Dual Energy Computed Tomography of Internal Carotid Artery: A Modified Dual-Energy Algorithm for Calcified Plaque Removal, Compared With Digital Subtraction Angiography. Front Neurol 2020; 11:621202. 27. Etesami M, Hoi Y, Steinman DA, et al. Comparison of carotid plaque ulcer detection using contrast-enhanced and time-of-flight MRA techniques. AJNR Am J Neuroradiol 2013; 34:177. 28. Tsuruda JS, Saloner D, Anderson C. Noninvasive evaluation of cerebral ischemia. Trends for the 1990s. Circulation 1991; 83:I176. 29. Sitzer M, F rst G, Fischer H, et al. Between-method correlation in quantifying internal carotid stenosis. Stroke 1993; 24:1513. 30. Debrey SM, Yu H, Lynch JK, et al. Diagnostic accuracy of magnetic resonance angiography for internal carotid artery disease: a systematic review and meta-analysis. Stroke 2008; 39:2237. 31. Bowen BC, Quencer RM, Margosian P, Pattany PM. MR angiography of occlusive disease of the arteries in the head and neck: current concepts. 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Timing of spontaneous recanalization and risk of hemorrhagic transformation in acute cardioembolic stroke. Stroke 2001; 32:1079. 58. Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004; 62:1468. 59. Hankey GJ, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke 1990; 21:209. 60. Stone JG, Zussman BM, Tonetti DA, et al. Transradial versus transfemoral approaches for diagnostic cerebral angiography: a prospective, single-center, non-inferiority comparative effectiveness study. J Neurointerv Surg 2020; 12:993. 61. Wolpert SM, Caplan LR. Current role of cerebral angiography in the diagnosis of cerebrovascular diseases. AJR Am J Roentgenol 1992; 159:191. 62. Rothwell PM, Mehta Z, Howard SC, et al. Treating individuals 3: from subgroups to individuals: general principles and the example of carotid endarterectomy. Lancet 2005; 365:256. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 21/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate 63. Willinsky RA, Taylor SM, TerBrugge K, et al. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Radiology 2003; 227:522. 64. Edwards JH, Kricheff II, Riles T, Imparato A. Angiographically undetected ulceration of the carotid bifurcation as a cause of embolic stroke. Radiology 1979; 132:369. 65. Bendszus M, Koltzenburg M, Burger R, et al. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet 1999; 354:1594. 66. Bosanac Z, Miller RJ, Jain M. Rotational digital subtraction carotid angiography: technique and comparison with static digital subtraction angiography. Clin Radiol 1998; 53:682. 67. Elgersma OE, Buijs PC, W st AF, et al. Maximum internal carotid arterial stenosis: assessment with rotational angiography versus conventional intraarterial digital subtraction angiography. Radiology 1999; 213:777. Topic 1118 Version 24.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 22/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate GRAPHICS Methods of measuring carotid stenosis in NASCET and ECST Modi ed from Donnan, GA, Davis, SM, Chambers, BR, Gates, PC, Lancet 1998; 351:1372. NASCET: North American Symptomatic Carotid Endarterectomy Trial; ECST: European Carotid Surgery Trial; CC: Common Carotid Method. Graphic 58353 Version 2.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 23/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Carotid artery stenosis assessed by duplex ultrasonography Carotid duplex ultrasound demonstrating high-grade left carotid stenosis. Note the elevated peak systolic and end diastolic velocities (upper right) as well as large echolucent plaque visible in the bulb (arrow). Courtesy of Brett L Cucchiara, MD. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 24/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Graphic 69525 Version 7.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 25/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate CTA left carotid stenosis Corresponding CTA from the same patient demonstrating a long- segment focal high-grade stenosis in the left internal carotid artery just past the bifurcation (arrow). CTA: computed tomography angiography. Courtesy of Brett L Cucchiara, MD. https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 26/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Graphic 140388 Version 1.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 27/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Carotid artery stenosis assessed by magnetic resonance angiography A magnetic resonance angiogram (MRA) shows marked narrowing and stenosis at the origin of the right internal carotid artery (arrow). Courtesy of Jonathan Kruskal, MD. Graphic 79993 Version 4.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 28/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Consensus panel grayscale and Doppler US criteria for diagnosis of ICA stenosis Primary parameters Additional parameters Degree of stenosis (%) ICA PSV Plaque ICA/CCA PSV ICA EDV (cm/sec) estimate (%)* ratio (cm/sec) Normal <125 None <2.0 <40 <50 <125 <50 <2.0 <40 50 50 to 69 125 to 230 2.0 to 4.0 40 to 100 70 but less than near occlusion 50 >230 <4.0 >100 Near occlusion High, low, or Visible Variable Variable undetectable Total occlusion Undetectable Visible, no Not applicable Not applicable detectable lumen US: ultrasound; ICA: internal carotid artery; PSV: peak systolic velocity; CCA: common carotid artery; EDV: end diastolic velocity. Plaque estimate (diameter reduction) with grayscale and color Doppler US. Reproduced with permission from: Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis: Grayscale and Doppler ultrasound diagnosis Society of Radiologists in Ultrasound Consensus Conference. Ultrasound Q 2003; 19(4):190-8. Copyright 2003 Wolters Kluwer Health, Inc. https://journals.lww.com/ultrasound-quarterly/pages/default.aspx. Graphic 140389 Version 1.0 https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 29/30 7/5/23, 11:40 AM Evaluation of carotid artery stenosis - UpToDate Contributor Disclosures Brett L Cucchiara, MD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Eidt, MD Grant/Research/Clinical Trial Support: Syntactx [Clinical events, data/safety monitoring for medical device trials]. All of the relevant financial relationships listed have been mitigated. Joseph L Mills, Sr, MD No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/evaluation-of-carotid-artery-stenosis/print 30/30 |
7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Management of asymptomatic extracranial carotid atherosclerotic disease : Michael T Mullen, MD, Jeffrey Jim, MD, MPHS, FACS : Scott E Kasner, MD, John F Eidt, MD, Joseph L Mills, Sr, MD : John F Dashe, MD, PhD, Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 02, 2023. INTRODUCTION This topic will review the treatment of asymptomatic extracranial carotid atherosclerotic disease. The management of symptomatic extracranial carotid disease is discussed separately. (See "Management of symptomatic carotid atherosclerotic disease".) Other aspects of carotid atherosclerotic disease, including technical aspects of carotid revascularization, are reviewed elsewhere: (See "Evaluation of carotid artery stenosis".) (See "Percutaneous carotid artery stenting" and "Carotid endarterectomy".) (See "Overview of carotid artery stenting".) (See "Percutaneous carotid artery stenting" and "Carotid endarterectomy".) (See "Transcarotid artery revascularization".) EXTRACRANIAL CAROTID ATHEROSCLEROSIS Extracranial carotid atherosclerosis most frequently involves the origin of the internal carotid artery and the common carotid artery bifurcation (ie, carotid bulb). This is distinguished from intracranial carotid atherosclerosis. (See "Intracranial large artery atherosclerosis: Epidemiology, https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 1/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate clinical manifestations, and diagnosis" and "Intracranial large artery atherosclerosis: Treatment and prognosis".) Asymptomatic disease Asymptomatic carotid atherosclerotic disease, as discussed in this topic, refers to the presence of atherosclerosis in individuals with no history of ipsilateral carotid territory ischemic stroke or transient ischemic attack (TIA) within the preceding six months. Symptoms associated with carotid atherosclerotic disease are discussed separately. (See "Definition, etiology, and clinical manifestations of transient ischemic attack" and "Clinical diagnosis of stroke subtypes", section on 'Brain ischemia'.) Note that isolated unilateral carotid stenosis does not cause vertigo, diplopia, lightheadedness, or syncope. Therefore, in patients with these symptoms, but no other focal neurologic symptoms, the carotid lesion should be considered asymptomatic. Prevalence The prevalence of asymptomatic carotid atherosclerotic disease varies by population studied and demographics, with age and sex as the most important factors. The prevalence is low in the general population. In a meta-analysis of four population-based studies with individual data from over 23,000 participants, the prevalence estimates of asymptomatic carotid stenosis ( 50 percent of the lumen diameter) for males and females aged <50 years were 0.2 and 0 percent, respectively [1]. The prevalence estimates for males and females aged 80 years were 7.5 and 5 percent, respectively. (See "Screening for asymptomatic carotid artery stenosis", section on 'Prevalence'.) Detection General population screening for carotid stenosis in asymptomatic individuals is not warranted, as reviewed elsewhere. (See "Screening for asymptomatic carotid artery stenosis".) However, asymptomatic carotid stenosis due to atherosclerosis may be identified incidentally when a carotid bruit is detected on physical examination or when patients undergo carotid imaging during evaluation of atherosclerotic disease, or for the evaluation of an unrelated condition, including a stroke or TIA involving an unrelated vascular territory. Some patients will come to attention following private health screening studies. Counseling Once extracranial carotid atherosclerosis has been identified, patients should be screened for signs or symptoms of prior stroke or TIA to ensure that they are asymptomatic. They should also be counseled on the symptoms and signs of stroke and instructed to seek emergency care if a stroke is suspected (eg, by calling 911 in the United States or other phone number appropriate to their location). In addition, patients should be screened for treatable cardiovascular risk factors [2,3]. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 2/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Degree of stenosis and clinical significance Once asymptomatic carotid stenosis is identified, it is important to determine the severity of carotid stenosis both to identify individuals who may be candidates for revascularization and, if revascularization is not performed, to monitor for disease progression over time. The severity of carotid stenosis can be determined by a variety of imaging modalities (ultrasound, computed tomographic angiography, magnetic resonance angiography, and catheter-based angiography). In addition, interpretation of ultrasound-derived physiological parameters (eg, velocity and turbulence) and plaque may be used to further characterize carotid stenosis. For angiographic imaging studies, the severity of stenosis is recorded as the percent diameter reduction by comparing the residual lumen at the site of stenosis with the diameter of the normal distal internal carotid artery. Stenosis greater than 50 percent is generally regarded as potentially significant, though lesser degrees of stenosis may serve as embolic sources. (See "Evaluation of carotid artery stenosis".) RISK OF STROKE AND CARDIOVASCULAR EVENTS Progression of atherosclerotic plaque at the carotid bifurcation results in luminal narrowing, often accompanied by plaque ulceration. This process can lead to ischemic stroke or transient ischemic attack from embolization, thrombosis, or reduced brain perfusion (more likely in the setting of bilateral disease). Asymptomatic carotid atherosclerosis also serves as a marker of increased risk for myocardial infarction and vascular death [4-6]. Thus, asymptomatic carotid atherosclerosis is considered a risk equivalent for cardiovascular disease. (See "Overview of established risk factors for cardiovascular disease", section on 'Noncoronary atherosclerotic disease'.) Ipsilateral stroke risk Ischemic stroke is the most feared outcome of carotid atherosclerosis, although the risk is low in asymptomatic patients. The annual risk of ipsilateral stroke in patients with asymptomatic extracranial carotid atherosclerosis with stenosis 50 percent is estimated to be 0.5 to 1.0 percent annually [4,7,8]. In a retrospective cohort study of over 3700 participants diagnosed between 2008 and 2012 with severe (70 to 99 percent) asymptomatic carotid stenosis who did not undergo carotid revascularization, the estimated annual rate of ipsilateral ischemic stroke was 0.9 percent (95% CI 0.7-1.2 percent) [9]. This finding is consistent with other studies suggesting that the risk of ipsilateral stroke in patients with medically treated asymptomatic carotid stenosis is lower than the risk in surgically treated patients who participated in the landmark endarterectomy trials from the late 1980s through the early 2000s. (See 'Is revascularization beneficial?' below.) https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 3/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Factors potentially associated with stroke risk Potential factors that might identify patients with asymptomatic extracranial carotid disease who have a high risk of ischemic stroke include the following [10-12]: Initial degree of carotid stenosis (see 'Initial degree of carotid stenosis' below) Progression in the severity of asymptomatic carotid stenosis (see 'Progressive stenosis despite optimal medical therapy' below) Asymptomatic embolism detected on transcranial Doppler ultrasound (see 'Asymptomatic embolism' below) Ipsilateral silent embolic infarcts on neuroimaging (see 'Silent embolic infarcts' below) High-risk morphologic features of the carotid plaque (see 'Carotid plaque morphology' below) Reduced cerebral blood flow reserve (see 'Reduced cerebrovascular reserve' below) The utility of using these factors to select patients with asymptomatic extracranial carotid stenosis for revascularization remains to be proven; treatment of those who exhibit one or more of these features should be individualized [10]. Initial degree of carotid stenosis The relationship between the degree of asymptomatic extracranial carotid stenosis at baseline and the risk of stroke is uncertain, as the data are inconsistent. Randomized controlled trials comparing carotid endarterectomy (CEA) with medical therapy in patients with 60 to 99 percent carotid stenosis (the Asymptomatic Carotid Atherosclerosis Study [ACAS] and the Asymptomatic Carotid Surgery Trial [ACST]) found that stroke rates for patients assigned to medical therapy were not clearly related to the severity of carotid stenosis, and that the benefit of carotid revascularization was not increased with more severe degrees of stenosis (see 'Endarterectomy trials' below). This is in contrast to symptomatic carotid stenosis, in which CEA trials have consistently found an increased risk of stroke and a greater benefit with revascularization with higher degrees of stenosis. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CEA'.) By contrast, observational data suggest that ipsilateral stroke risk increases with the degree of asymptomatic carotid stenosis, as shown in a population-based cohort study of 207 patients with asymptomatic 50 to 99 percent carotid stenosis [13]. The five-year ipsilateral stroke risk was greater among 53 patients with 70 to 99 percent carotid stenosis (14.6 percent, 95% CI 3.5-25.7) compared with 154 patients with 50 to 69 percent stenosis, none of whom had a stroke. Similarly, the five-year ipsilateral stroke risk was greater https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 4/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate among 34 patients with 80 to 99 percent stenosis (18.3 percent, 95% CI 7.7-29.9) compared with 173 patients with 50 to 79 percent stenosis (1 percent, 95% CI 0.0-2.9). The investigators also performed a systematic review and meta-analysis of studies done from 1980 to 2020 and identified 23 studies with data for ipsilateral stroke risk among 8419 medically treated patients with asymptomatic carotid stenosis [13]. Stroke risk during follow-up (generally three to five years) increased linearly with the degree of ipsilateral stenosis, being greater for 70 to 99 percent stenosis compared with 50 to 69 percent stenosis (10.2 versus 4.8 percent, odds ratio [OR] 2.1, 95% CI 1.7-2.5), and greater for 80 to 99 percent stenosis compared with 50 to 79 percent stenosis (10.6 percent versus 5.1 percent, OR 2.5, 95% CI 1.8-3.5). Progressive stenosis despite optimal medical therapy Natural history studies of asymptomatic extracranial carotid stenosis found that progression of stenosis over time was associated with an increased stroke risk [14-22]. As an example, one study analyzed the natural history of asymptomatic carotid disease in 714 patients who had serial carotid ultrasound examinations biannually for a mean follow- up of 3.2 years [14]. Progression to carotid stenosis of 80 percent was associated with a higher risk for cerebrovascular events and death. In the prospective ACSRS cohort study of 1121 patients with asymptomatic carotid stenosis of 50 to 99 percent who were followed by serial duplex ultrasonography biannually for a mean follow-up of four years, there was regression of carotid stenosis in 4 percent, no change in 76 percent, and progression of stenosis in 20 percent of patients [17]. The corresponding eight-year cumulative ipsilateral stroke rate was 0 percent in the subgroup with regression, 9 percent in the subgroup with no change, and 16 percent in the subgroup with progression of stenosis. In a retrospective analysis of data from the ACST trial, the annual incidence of progression of carotid luminal narrowing was 5 percent [23]. A high rate of progression over one year was significantly associated with ipsilateral neurologic events, though only a small number of patients had such progression. These data have been used to support the use of CEA for patients with progression of asymptomatic carotid disease, particularly as the degree of carotid stenosis approaches 70 to 80 percent [18,21,24-26]. However, this approach has not been confirmed by randomized controlled trials. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 5/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Asymptomatic embolism Evidence from observational studies suggests that asymptomatic cerebral embolism, detected by transcranial Doppler (TCD) ultrasound, is associated with an increased risk of ischemic stroke in patients with asymptomatic extracranial carotid atherosclerosis [27-30]. Some experts advocate using TCD emboli detection to identify patients with asymptomatic carotid stenosis who are at high and low risk of stroke and thus to help select those most likely to benefit from carotid revascularization [27,31]. However, the utility of this approach has not been tested in a randomized trial, and TCD is not widely available. Silent embolic infarcts The presence of silent embolic infarcts ipsilateral to asymptomatic carotid stenosis on neuroimaging may predict the risk of ipsilateral stroke [11]. In the prospective ACSRS study, 462 patients with asymptomatic 60 to 99 percent carotid artery stenosis by duplex ultrasound had a baseline head computed tomography (CT) scan and were monitored every six months for up to eight years [32]. At a mean follow-up of 3.7 years, the rate of ipsilateral stroke was significantly higher for patients with silent embolic infarcts on baseline CT (n = 86) compared with patients without embolic infarcts (annual event rate 3.6 versus 1.0 percent, hazard ratio [HR] 3.0, 95% CI 1.46-6.29). Previous studies have found that the presence of silent brain infarcts on CT or magnetic resonance imaging (MRI) scans were associated with an increased risk of ischemic stroke in the general population (see "Clinical diagnosis of stroke subtypes", section on 'Silent brain infarcts'), but these studies did not consider the status of the carotid arteries [32]. Carotid plaque morphology Limited data suggest that ultrasound or MRI determination of carotid plaque morphology (eg, ulceration, plaque area, intraplaque hemorrhage, plaque echogenicity) may be useful to identify patients with asymptomatic carotid occlusive disease who are at higher risk of stroke and therefore likely to benefit from carotid revascularization. However, this approach requires additional study. In patients with asymptomatic carotid stenosis, several imaging features on ultrasonography or MRI have been associated with elevated stroke risk [11,31,33]: Carotid ulceration In a report of 253 patients with asymptomatic carotid stenosis, the carotid arteries were scanned with three-dimensional (3D) ultrasound, and the risk of stroke or death at three years was significantly higher for patients with three or more carotid plaque ulcers (the sum of both carotid arteries) compared with those who had less than three ulcers (18 versus 2 percent) [29]. Large plaque area In the ACSRS study, increased plaque area was independently associated with an increased risk of ipsilateral cerebrovascular or retinal ischemic events https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 6/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate [34]. Plaque echolucency on ultrasonography Echogenicity refers to the appearance of plaque based on whether ultrasound waves pass through or are reflected, ranging from purely hypoechoic (ie, echolucent; no echoes, black) to hyperechoic (white). A standardized method for evaluating plaque echogenicity has been described [35]. Several studies have reported an increased stroke risk for purely echolucent plaques [30,36,37]. In a report of 435 patients with asymptomatic carotid stenosis, echolucent plaques were independently associated with an increased risk of ipsilateral stroke even after controlling for the presence of embolic signals at baseline [30]. Increased size of juxtaluminal black (ie, hypoechoic) area on ultrasonography The size of the plaque core (hypoechoic; juxtaluminal black area [JBA]) and position relative to the carotid lumen may predict stroke risk [38-40]. In the ACSRS study, the JBA on ultrasound images of asymptomatic carotid plaque demonstrated a linear relationship with 2 stroke risk [39]. With a JBA <4 mm , the mean annual stroke rate was <1 percent; with a JBA 2 2 4 to 8 mm , the rate was 1.4 percent; with a JBA 8 to 10 mm , the rate was 3.2 percent; and 2 with JBA >10 mm , the stroke rate was 5 percent. Intraplaque hemorrhage on MRI In a meta-analysis of individual patient data from seven cohort studies, intraplaque hemorrhage detected by MRI was present in 40 of 136 patients (29 percent) with 50 percent asymptomatic carotid stenosis and was associated with an increased annualized rate of ipsilateral stroke compared with no intraplaque hemorrhage (5.4 percent versus 0.8 percent, unadjusted hazard ratio [HR] 7.9, 95% CI 1.3- 47.6) [41]. A 2023 systematic review and meta-analysis evaluating imaging characteristics of carotid atherosclerosis found that all plaque features studied (eg, size, calcification, intraplaque hemorrhage, ulceration) were either larger or more severe in males compared with females [42]. Reduced cerebrovascular reserve Several reports have found that a reduction in cerebrovascular reserve (CVR), also called cerebral blood flow reserve, is associated with increased risk of ischemic stroke in patients with asymptomatic carotid stenosis [11]. However, the utility of using this measure to select patients for carotid revascularization is unproven. In most studies, CVR is estimated using transcranial Doppler measurements of middle cerebral artery blood flow velocity change in response to a vasodilatory stimulus with acetazolamide, inhaled carbon dioxide, or breath holding [11,43,44]. A normal CVR reflects an increase in middle cerebral artery blood flow of 15 to 40 percent, while the CVR is considered impaired if blood flow increases by <10 percent. Other methods involve direct cerebral blood flow measurement with https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 7/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate imaging modalities such as positron emission tomography, CT perfusion, MR perfusion, or nuclear medicine techniques. A meta-analysis of four studies evaluating patients with asymptomatic carotid stenosis reported that impaired CVR increased the risk of ischemic stroke or TIA (OR 4.07, 95% CI 2.00-11.07) [43]. The clinical availability of all these methods of measuring CVR is generally limited. INTENSIVE MEDICAL THERAPY AND FOLLOW-UP Asymptomatic carotid atherosclerosis is a risk equivalent for cardiovascular disease, and patients are at increased risk for future cerebrovascular (eg, transient ischemic attack [TIA], stroke) and cardiovascular (eg, myocardial infarction, limb ischemia) events. All patients with carotid stenosis should undergo intensive medical therapy, which includes several strategies to reduce their cardiovascular risk. Periodic clinical follow-up to evaluate compliance with medical therapies and to evaluate for symptoms and signs of TIA or stroke is also important. Risk reduction strategies Importantly, intensive medical therapy lowers the risk of stroke in patients with asymptomatic carotid stenosis. With intensive medical therapy, the risk of stroke is low enough that the benefit of carotid revascularization for asymptomatic disease is disputed by some experts [7,8,28,45-49]. However, since this level of intensive medical therapy was not available during the trials of revascularization for asymptomatic carotid disease, we await further trials that aim to reassess the relative benefits and risks of carotid endarterectomy and carotid artery stenting compared with intensive medical therapy. (See 'Role of carotid revascularization' below.) Intensive medical therapy includes rigorous and compliant use of the following risk reduction strategies; each is discussed in detail separately: Statin treatment (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Statins and other lipid-lowering agents') Antithrombotic therapy, generally using aspirin monotherapy unless there is an indication for anticoagulation (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Adjunctive therapies') https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 8/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Treatment of hypertension (see "Overview of hypertension in adults", section on 'Treatment') Glycemic control in patients with diabetes (see "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Macrovascular disease') Smoking cessation (see "Cardiovascular risk of smoking and benefits of smoking cessation") Healthy diet (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Diet') Regular physical activity and exercise (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Physical activity') Weight reduction in patients with obesity (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Weight reduction') Imaging surveillance Patients with asymptomatic carotid stenosis can be followed with noninvasive vascular imaging of the carotid artery, particularly if they may be candidates for revascularization in the setting of stenosis progression. This is most easily accomplished using duplex ultrasonography performed annually by a qualified technologist in an accredited vascular laboratory with the goal of assessing the progression or regression of disease [50]. Magnetic resonance angiography and computed tomographic angiography are alternatives if duplex ultrasonography cannot be done, but they are more burdensome and expensive. (See "Evaluation of carotid artery stenosis", section on 'Carotid duplex ultrasound'.) ROLE OF CAROTID REVASCULARIZATION Is revascularization beneficial? As already noted, intensive medical management is indicated for all patients with asymptomatic carotid atherosclerosis. (See 'Intensive medical therapy and follow-up' above.) Optimal patient selection for carotid revascularization is controversial given the periprocedural risk relative to the low absolute risk reduction associated with revascularization. Three large randomized trials have compared carotid endarterectomy (CEA) with medical therapy in asymptomatic carotid stenosis (50 to 99 percent stenosis in the VA trial and 60 to 99 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 9/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate percent in the Asymptomatic Carotid Atherosclerosis Study [ACAS] and the Asymptomatic Carotid Surgery Trial [ACST]) [51-53]. In these studies, CEA was associated with a 2.9 percent risk of perioperative stroke or death. CEA reduced the risk of subsequent stroke, but the benefit was small with an absolute risk reduction of approximately 1 percent per year [54]; the corresponding number needed to treat (NNT) to prevent one stroke at three years was approximately 33. (See 'Endarterectomy trials' below.) On the basis of these data, older United States guidelines stated that it was reasonable to consider CEA in patients with asymptomatic carotid stenosis of 60 to 99 percent with five or more years of expected life expectancy at centers where the perioperative risk of stroke or death could be reliably documented to be <3 percent [55]. However, these trials enrolled from the late 1980s through the early 2000s and used medical therapy that was suboptimal compared with contemporary standards [45]. Multiple studies have shown that intensive medical therapy has lowered the stroke risk in patients with asymptomatic carotid stenosis who are managed without carotid revascularization. Importantly, with contemporary intensive medical therapy, the risk of stroke in medically treated patients is now as low, or lower, than the stroke risk in surgically treated patients from the CEA trials, with reported stroke rates of 0.5 to 1 percent per year [7-9,28,45-47]. As a result, some experts have suggested that medical therapy alone, without carotid revascularization, is the preferred treatment for most patients with asymptomatic carotid stenosis [4,7,8]. Other experts believe that CEA remains the best approach for treating asymptomatic 70 to 99 percent carotid stenosis [56,57]. They do not agree that the available data establish the equivalence of medical therapy and CEA. As an example, they discount studies asserting that stroke risk reduction with modern medical therapy negates the benefit of CEA for patients with asymptomatic carotid stenosis, arguing that those studies were skewed by the inclusion of many patients with low-risk 50 to 69 percent carotid stenosis [56]. Unfortunately, cross-study comparisons may introduce bias, and improvements in surgical techniques in the decades since the landmark asymptomatic CEA trials were done may have reduced the risk of perioperative stroke and death associated with carotid revascularization [58]. As a result, the benefit of carotid revascularization in asymptomatic carotid stenosis is uncertain, and contemporary randomized controlled trials comparing carotid revascularization with intensive medical therapy are needed to know which approach is truly the best [59]. In this regard, the SPACE-2 trial recruited patients from 2009 to 2019 with asymptomatic internal carotid artery stenosis of 70 percent [60]. The results showed no significant difference between treatment groups for the cumulative incidence of any stroke (ischemic or hemorrhagic) or death within 30 days or any ipsilateral ischemic stroke within five years of follow-up for best medical https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 10/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate treatment alone (3.1 percent), best medical treatment plus CEA (2.5 percent), or best medical treatment plus carotid artery stenting (CAS; 4.4 percent). However, the trial was limited by stopping early due to slow recruitment (only 513 patients enrolled with initial planned enrollment of 3640 patients) and by a very low number of outcome events [60]. Our approach to patient selection In the absence of more contemporary data, we present our approach to the management of asymptomatic carotid stenosis below. Treatment decisions should account for the patient's comorbid conditions, life expectancy, and preferences, as well as the local experience of the center and surgeon. Note that the two largest trials comparing CEA and medical therapy enrolled patients with a stenosis of 60 to 99 percent. However, in practice, many ultrasound laboratories report carotid stenosis as <50 percent, 50 to 69 percent, and 70 to 99 percent stenosis, and so we will present our recommendations in these categories. Stenosis less than 50 percent Patients with asymptomatic internal carotid artery atherosclerotic disease who have <50 percent carotid stenosis do not require carotid revascularization. However, such patients should be screened for treatable risk factors for stroke and cardiovascular disease, with institution of appropriate lifestyle changes and medical therapies. Annual carotid duplex surveillance to evaluate for plaque progression may be reasonable. (See 'Intensive medical therapy and follow-up' above.) Stenosis 50 to 69 percent For patients with asymptomatic carotid atherosclerotic disease who have 50 percent to 69 percent internal carotid artery stenosis, we suggest intensive medical therapy and follow-up using all available risk reduction strategies. (See 'Intensive medical therapy and follow-up' above.) Although patients with 60 to 69 percent stenosis meet the criteria for the ACAS and ACST trials, we believe it is reasonable to forego revascularization and use intensive medical therapy based on the overall low potential benefit of carotid revascularization and evidence that carotid stenosis does not become hemodynamically or clinically significant until it is >70 percent or with a residual lumen diameter of 1.5 mm or less [18,21,24-26,61]. For these patients, we pursue carotid artery follow-up and surveillance with the goal of detecting patients with progression of stenosis to >70 percent despite compliance with intensive medical therapy. This is most easily accomplished using duplex ultrasonography performed annually by a qualified technologist in an accredited vascular laboratory [50]. (See 'Imaging surveillance' above.) Stenosis 70 to 99 percent For medically stable patients with asymptomatic carotid atherosclerotic disease at baseline who have a life expectancy of at least five years and have a severe (70 to 99 percent) internal carotid artery stenosis, either intensive medical therapy alone https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 11/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate or intensive medical therapy plus carotid revascularization is reasonable. Many vascular surgeons have adopted a more conservative approach and would only consider carotid revascularization for someone with a more severe stenosis of 80 to 99 percent. (See 'Alternative approaches' below.) If carotid revascularization is considered, the combined perioperative risk of stroke and death for carotid revascularization should be less than 3 percent for the surgeon and center (See 'Is revascularization beneficial?' above.). We advise a shared decision-making approach that incorporates the patient's values and preferences. It is critical that the patient understand that with intensive medical therapy the risk of stroke is relatively low, and the benefit of carotid revascularization is uncertain. We encourage patients with this degree of asymptomatic carotid stenosis to participate in ongoing randomized controlled trials comparing carotid revascularization with contemporary medical management, such as the CREST-2 trial [62]. Occlusion There is no role for revascularization to prevent recurrent stroke in the setting of complete carotid chronic occlusion. Intensive medical therapy is indicated. (See 'Intensive medical therapy and follow-up' above.) Alternative approaches The management of asymptomatic carotid atherosclerotic disease is controversial. The following strategies are advocated by different experts: Avoidance of carotid revascularization regardless of the degree of asymptomatic carotid stenosis, with reliance on intensive medical management as described above using statins, antiplatelet agents, treatment of hypertension and diabetes, and healthy lifestyle changes [63]. (See 'Intensive medical therapy and follow-up' above.) Intensive medical management for most patients, with carotid revascularization only for a subgroup of patients with asymptomatic carotid stenosis who have a particularly high risk of stroke [12,31]. This approach relies on the use of markers to determine high stroke risk, such as those with progression of carotid stenosis, the detection of asymptomatic carotid embolism, the presence of silent embolic infarcts, increased carotid plaque burden or high- risk plaque morphology, and reduced cerebrovascular reserve. Some vascular surgeons recommend medical therapy for stenosis <80 percent but recommend revascularization when stenosis exceeds 80 percent. (See 'Factors potentially associated with stroke risk' above.) Revascularization with CEA for most medically stable patients with asymptomatic carotid stenosis of 60 to 99 percent, rather than reserving CEA for more severe degrees of stenosis https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 12/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate (ie, 70 or 80 percent) [2,31,64]. This approach relies on prior data from randomized clinical trials, which showed a benefit in patients who were not receiving optimal medical therapy (see 'Carotid endarterectomy' below) without accounting for the uncertainty introduced by subsequent data, which show a lower risk of stroke with contemporary intensive medical therapy. For this reason, we advocate a more conservative approach. (See 'Intensive medical therapy and follow-up' above and 'Our approach to patient selection' above.) Patients unlikely to benefit from revascularization Patients unlikely to benefit from carotid revascularization include those with severe comorbidity due to other medical or surgical illnesses that increase their perioperative risk, limited life expectancy, a prior disabling ipsilateral stroke, or patients with total occlusion of the internal carotid artery (contraindication). Risk factors for morbidity and mortality associated with carotid revascularization techniques (ie, carotid endarterectomy, carotid artery stenting) should be evaluated to identify those who may face unacceptably high risk [65]. These risk factors are discussed separately. (See "Carotid endarterectomy", section on 'Preoperative evaluation' and "Overview of carotid artery stenting".) Most other asymptomatic atherosclerotic lesions affecting the inflow to the internal carotid artery or its outflow are best managed medically, including stenosis involving the brachiocephalic artery (ie, also not causing extremity symptoms or subclavian steal syndrome), the common carotid artery, or stenosis of the distal internal carotid artery beyond the bifurcation. Likewise, conditions causing asymptomatic nonatherosclerotic carotid stenosis (eg, fibromuscular dysplasia, dissection, vasculitis, or prior radiotherapy) are best managed medically. Choice of procedure The optimal carotid revascularization procedure, whether CEA or CAS, and for CAS, the optimal approach (transfemoral [TF-CAS] versus transcarotid artery revascularization [TCAR]) is controversial. However, there is agreement that the short-term (periprocedural) risk of stroke and death is generally higher with TF-CAS, while long-term outcomes are similar for CEA and CAS. The risk of stroke may be lower for TCAR compared with TF-CAS. (See 'Carotid endarterectomy' below and 'Carotid stenting' below.) Carotid endarterectomy Randomized controlled trials had found that CEA was beneficial for selected patients with asymptomatic internal carotid artery stenosis of 60 to 99 percent [51-53]. However, the absolute benefit was low. In addition, the evidence from these trials supporting CEA for asymptomatic carotid disease was less compelling for females compared with males. For those who are not already receiving antiplatelet therapy, treatment with aspirin (81 to 325 mg/day) is recommended for all patients who are having CEA. Aspirin should be started prior to https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 13/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate surgery and continued indefinitely for patients with asymptomatic atherosclerosis (see "Carotid endarterectomy", section on 'Antiplatelet therapy'). In addition, patients with atherosclerotic carotid disease, including those who undergo CEA, should receive intensive medical management that includes LDL-lower therapy and treatment of hypertension, cigarette smoking, and diabetes. (See 'Intensive medical therapy and follow-up' above and "Overview of secondary prevention of ischemic stroke".) Endarterectomy trials The efficacy of CEA, compared with no surgery, for patients with asymptomatic high-grade carotid stenosis was evaluated in three high-quality randomized controlled trials. These were the VA trial [51], ACAS [52], and ACST [53]. In a meta-analysis of these three trials, including 5268 subjects with a mean follow-up of 3.3 years per subject, CEA was associated with a 2.9 percent risk of perioperative stroke or death. CEA reduced the risk of any stroke, but the benefit was small with an overall absolute risk reduction of approximately one percent per year [54]; the corresponding number needed to treat (NNT) to prevent one stroke at three years was approximately 33. The outcome of any stroke or death was not significantly lower with CEA compared with medical therapy alone (20.5 versus 22.6 percent, relative risk [RR] 0.92, 95% CI 0.83-1.02). Findings of the individual CEA trials are as follows: The VA trial randomly assigned 444 males with 50 to 99 percent asymptomatic carotid stenosis to CEA plus aspirin or aspirin alone [51]. The mean duration of follow-up was 48 months. The incidence of stroke or TIA was significantly lower for the CEA plus aspirin group compared with the aspirin alone group (8 versus 21 percent, RR 0.38, 95% CI 0.22- 0.67) ( figure 1). The difference in incidence for ipsilateral stroke was nonsignificantly lower for the CEA plus aspirin group (4.7 versus 9.4 percent). The composite outcome of all stroke and death at 30 days and 48 months was similar (41 and 44 percent, respectively); most of the deaths were due to coronary heart disease. This trial was criticized for including TIA in the primary endpoint, since by definition TIA does not result in any persistent neurologic deficit [55]. The ACAS trial randomized 1662 adults with 60 to 99 percent asymptomatic carotid stenosis to CEA plus aspirin (325 mg/day) or aspirin alone [52]. At a median follow-up of 2.7 |
preferences. It is critical that the patient understand that with intensive medical therapy the risk of stroke is relatively low, and the benefit of carotid revascularization is uncertain. We encourage patients with this degree of asymptomatic carotid stenosis to participate in ongoing randomized controlled trials comparing carotid revascularization with contemporary medical management, such as the CREST-2 trial [62]. Occlusion There is no role for revascularization to prevent recurrent stroke in the setting of complete carotid chronic occlusion. Intensive medical therapy is indicated. (See 'Intensive medical therapy and follow-up' above.) Alternative approaches The management of asymptomatic carotid atherosclerotic disease is controversial. The following strategies are advocated by different experts: Avoidance of carotid revascularization regardless of the degree of asymptomatic carotid stenosis, with reliance on intensive medical management as described above using statins, antiplatelet agents, treatment of hypertension and diabetes, and healthy lifestyle changes [63]. (See 'Intensive medical therapy and follow-up' above.) Intensive medical management for most patients, with carotid revascularization only for a subgroup of patients with asymptomatic carotid stenosis who have a particularly high risk of stroke [12,31]. This approach relies on the use of markers to determine high stroke risk, such as those with progression of carotid stenosis, the detection of asymptomatic carotid embolism, the presence of silent embolic infarcts, increased carotid plaque burden or high- risk plaque morphology, and reduced cerebrovascular reserve. Some vascular surgeons recommend medical therapy for stenosis <80 percent but recommend revascularization when stenosis exceeds 80 percent. (See 'Factors potentially associated with stroke risk' above.) Revascularization with CEA for most medically stable patients with asymptomatic carotid stenosis of 60 to 99 percent, rather than reserving CEA for more severe degrees of stenosis https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 12/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate (ie, 70 or 80 percent) [2,31,64]. This approach relies on prior data from randomized clinical trials, which showed a benefit in patients who were not receiving optimal medical therapy (see 'Carotid endarterectomy' below) without accounting for the uncertainty introduced by subsequent data, which show a lower risk of stroke with contemporary intensive medical therapy. For this reason, we advocate a more conservative approach. (See 'Intensive medical therapy and follow-up' above and 'Our approach to patient selection' above.) Patients unlikely to benefit from revascularization Patients unlikely to benefit from carotid revascularization include those with severe comorbidity due to other medical or surgical illnesses that increase their perioperative risk, limited life expectancy, a prior disabling ipsilateral stroke, or patients with total occlusion of the internal carotid artery (contraindication). Risk factors for morbidity and mortality associated with carotid revascularization techniques (ie, carotid endarterectomy, carotid artery stenting) should be evaluated to identify those who may face unacceptably high risk [65]. These risk factors are discussed separately. (See "Carotid endarterectomy", section on 'Preoperative evaluation' and "Overview of carotid artery stenting".) Most other asymptomatic atherosclerotic lesions affecting the inflow to the internal carotid artery or its outflow are best managed medically, including stenosis involving the brachiocephalic artery (ie, also not causing extremity symptoms or subclavian steal syndrome), the common carotid artery, or stenosis of the distal internal carotid artery beyond the bifurcation. Likewise, conditions causing asymptomatic nonatherosclerotic carotid stenosis (eg, fibromuscular dysplasia, dissection, vasculitis, or prior radiotherapy) are best managed medically. Choice of procedure The optimal carotid revascularization procedure, whether CEA or CAS, and for CAS, the optimal approach (transfemoral [TF-CAS] versus transcarotid artery revascularization [TCAR]) is controversial. However, there is agreement that the short-term (periprocedural) risk of stroke and death is generally higher with TF-CAS, while long-term outcomes are similar for CEA and CAS. The risk of stroke may be lower for TCAR compared with TF-CAS. (See 'Carotid endarterectomy' below and 'Carotid stenting' below.) Carotid endarterectomy Randomized controlled trials had found that CEA was beneficial for selected patients with asymptomatic internal carotid artery stenosis of 60 to 99 percent [51-53]. However, the absolute benefit was low. In addition, the evidence from these trials supporting CEA for asymptomatic carotid disease was less compelling for females compared with males. For those who are not already receiving antiplatelet therapy, treatment with aspirin (81 to 325 mg/day) is recommended for all patients who are having CEA. Aspirin should be started prior to https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 13/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate surgery and continued indefinitely for patients with asymptomatic atherosclerosis (see "Carotid endarterectomy", section on 'Antiplatelet therapy'). In addition, patients with atherosclerotic carotid disease, including those who undergo CEA, should receive intensive medical management that includes LDL-lower therapy and treatment of hypertension, cigarette smoking, and diabetes. (See 'Intensive medical therapy and follow-up' above and "Overview of secondary prevention of ischemic stroke".) Endarterectomy trials The efficacy of CEA, compared with no surgery, for patients with asymptomatic high-grade carotid stenosis was evaluated in three high-quality randomized controlled trials. These were the VA trial [51], ACAS [52], and ACST [53]. In a meta-analysis of these three trials, including 5268 subjects with a mean follow-up of 3.3 years per subject, CEA was associated with a 2.9 percent risk of perioperative stroke or death. CEA reduced the risk of any stroke, but the benefit was small with an overall absolute risk reduction of approximately one percent per year [54]; the corresponding number needed to treat (NNT) to prevent one stroke at three years was approximately 33. The outcome of any stroke or death was not significantly lower with CEA compared with medical therapy alone (20.5 versus 22.6 percent, relative risk [RR] 0.92, 95% CI 0.83-1.02). Findings of the individual CEA trials are as follows: The VA trial randomly assigned 444 males with 50 to 99 percent asymptomatic carotid stenosis to CEA plus aspirin or aspirin alone [51]. The mean duration of follow-up was 48 months. The incidence of stroke or TIA was significantly lower for the CEA plus aspirin group compared with the aspirin alone group (8 versus 21 percent, RR 0.38, 95% CI 0.22- 0.67) ( figure 1). The difference in incidence for ipsilateral stroke was nonsignificantly lower for the CEA plus aspirin group (4.7 versus 9.4 percent). The composite outcome of all stroke and death at 30 days and 48 months was similar (41 and 44 percent, respectively); most of the deaths were due to coronary heart disease. This trial was criticized for including TIA in the primary endpoint, since by definition TIA does not result in any persistent neurologic deficit [55]. The ACAS trial randomized 1662 adults with 60 to 99 percent asymptomatic carotid stenosis to CEA plus aspirin (325 mg/day) or aspirin alone [52]. At a median follow-up of 2.7 years, the incidence of ipsilateral stroke and any perioperative stroke or death was lower for the CEA plus aspirin group compared with the aspirin group (5 versus 11 percent; RR 0.53, 95% CI 0.22-0.72). The incidence of major ipsilateral stroke, major perioperative stroke, and perioperative death was nonsignificantly lower for the CEA plus aspirin group (3.4 versus 6 percent) ( figure 2). This study was not powered to determine sex https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 14/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate differences. However, subgroup analysis suggested that CEA was less effective in females. Males had an absolute risk reduction of 8 percent, whereas the absolute risk reduction in females was only 1.4 percent, perhaps due to a higher incidence of perioperative complications in females compared with males (3.6 versus 1.7 percent). The ACST trial randomly assigned 3120 patients with 60 percent asymptomatic carotid stenosis to immediate CEA or to deferred CEA (until a definite indication occurred) [53,66]. The main analysis for ACST combined ipsilateral and contralateral strokes [67]. In the immediate CEA group, one-half were treated with CEA by one month and 88 percent by one year. In the deferred CEA group, approximately 4 percent of patients per year underwent CEA. At a mean of 3.4 years of follow-up, the five-year risk for all strokes or perioperative death in the immediate CEA group was reduced compared with deferred CEA group (6.4 versus 11.8 percent, absolute risk reduction [ARR] 5.4 percent, 95% CI 2.96-7.75) ( figure 3). Benefit with immediate CEA was also found for fatal or disabling stroke (3.5 versus 6.1 percent). Approximately one-half of the strokes in the trial were fatal or disabling ( figure 4). The CEA group had a perioperative risk of stroke or death of 3.1 percent within 30 days of surgery. The ACST subgroup analyses reported the results of risk reduction for non-perioperative stroke (ie, the benefit) separately from perioperative risk (ie, the risk) but did not report the overall balance of benefit and risk, which is of most importance to patients and clinicians [68]. While CEA was beneficial for preventing non-perioperative stroke in the entire cohort, the risk reduction over five years was significant for males (ARR 8.2 percent, 95% CI 5.64- 10.78) but not females (ARR 4.1 percent, 95% CI 0.74-7.41). The benefit of CEA was maintained at long-term follow-up (median nine years) in the ACST cohort [66]. The risk for all stroke or perioperative death in the immediate CEA group was significantly reduced compared with the deferred CEA group at five years (6.9 versus 10.9 percent) and at 10 years (13.4 versus 17.9 percent). Factors influencing outcome Delay to benefit CEA for patients with asymptomatic carotid atherosclerosis is a long- term investment [53]. The ACAS and especially the ACST trials showed that the net benefit of CEA is delayed for many months to nearly two years because of perioperative morbidity. In the ACST, the net benefit of CEA was delayed for approximately two years after surgery ( figure 3) [53,66]. (See 'Endarterectomy trials' above.) Perioperative complications CEA for patients with asymptomatic carotid atherosclerosis should be performed only at institutions in which the perioperative stroke and death rate is https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 15/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate <3 percent. Combined morbidity and mortality that exceed 3 percent could eliminate the small benefit gained from revascularization for patients with asymptomatic carotid disease [69-71]. Surgeons participating in the ACAS trial were required to have a perioperative complication rate of <3 percent in asymptomatic patients [72]. Similarly, the ACST reported a 3.1 percent perioperative complication rate [53]. (See 'Endarterectomy trials' above.) A review of Medicare recipients undergoing CEA found a higher mortality rate in hospitals that did not participate in major carotid surgery trials, particularly in those centers performing fewer procedures (2.9 percent, versus 1.4 percent in North American Symptomatic Carotid Endarterectomy Trial [NASCET] and ACAS trial hospitals) [73]. Low patient volume (less than three CEAs performed every two years) and a greater number of years since licensure of the surgeon have also been associated with worse outcomes following CEA [74]. (See 'Endarterectomy trials' above.) Sex The potential benefit of CEA may be greater for males compared with females with asymptomatic carotid disease. Nevertheless, we use the same approach for managing asymptomatic carotid stenosis regardless of sex, but include a discussion of the difference in the data when counseling female patients. A meta-analysis of data from the ACAS and ACST trials ( figure 5) found no benefit for females with respect to the five-year risk of any stroke or perioperative death (odds ratio [OR] 0.96, 95% CI 0.63-1.45) [68]. By contrast, there was significant benefit for males (OR 0.49, 95% CI 0.36-0.66). In the ACST trial, the benefit of surgery for females with asymptomatic carotid disease was reported as significant, although less robust than the benefit for males [53]. However, this analysis excluded perioperative events. The 10-year data from ACST found a similar benefit for the outcome of any stroke or perioperative death for males and females <75 years of age (males: ARR 5.5 percent, 95% CI 0.9-10.0; females: ARR 5.8 percent, 95% CI 0.1-11.4). In addition, a cohort study that included over 1.2 million patients treated primarily with CEA (but also CAS) from 2005 to 2015 reported no difference in outcome for asymptomatic carotid stenosis in males versus females [75]. Carotid stenting Although overall outcomes with CAS have improved over time, CEA remains the preferred method of revascularization for most patients with asymptomatic carotid atherosclerosis with standard surgical risk. Based upon the data from randomized trials comparing CEA with predominantly carotid artery stents placed using a transfemoral approach (ie, TF-CAS), we suggest not treating asymptomatic carotid disease with CAS unless both of the following conditions are met (see 'Stenting versus endarterectomy trials' below): https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 16/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate The patient's anatomy or risk factors suggest a prohibitively high risk for CEA The local center and operator have demonstrated a low (<3 percent) periprocedural risk The available evidence suggests that CAS and CEA provide similar long-term outcomes for patients with asymptomatic and symptomatic carotid occlusive disease, but the periprocedural risk of stroke and death has been higher with TF-CAS. An alternative to TF-CAS, TCAR uses a neck incision to deliver the stent directly into the carotid artery, which avoids passing wires and catheters across the aortic arch and possibly reduces the risk for embolism. Observational data suggest that TCAR has a lower risk of perioperative stroke or death compared with TF-CAS. However, there are no trials directly comparing these techniques. The approach to CAS, including a comparison of transfemoral and transcarotid carotid stenting and their advantages and disadvantages, is reviewed separately. (See "Overview of carotid artery stenting".) Most major guidelines note that the advantage of revascularization with CAS over intensive medical therapy alone is not well established for patients with asymptomatic carotid disease [2,31,57,64]. Nevertheless, some experts consider CAS as an alternative to CEA for the treatment of patients with asymptomatic carotid atherosclerotic disease, particularly in patients younger than age 70 years who are considered to be poor candidates for surgery due to high risks for perioperative complications. Risk factors for periprocedural complications of CAS are discussed separately. (See "Overview of carotid artery stenting".) Stenting versus endarterectomy trials Most clinical trial data regarding carotid stenting compared CEA with CAS in patients with either symptomatic or asymptomatic carotid disease. These trials suggest that the periprocedural (30-day) stroke or death rate is higher with TF-CAS compared with CEA, while the risk of stroke or death beyond 30 days is similar for both techniques [76,77]. A 2017 meta-analysis of five trials (ACT1, CREST, EVA-3S, ICSS, SAPPHIRE) compared CEA with CAS in 6526 patients with symptomatic or asymptomatic carotid disease [76]. In a subgroup analysis limited to patients with asymptomatic carotid disease, the risk of any periprocedural stroke was higher for CAS compared with CEA (2.8 versus 1.6 percent, OR 1.86, 95% CI 1.05-3.31). However, the risk of periprocedural stroke plus ipsilateral stroke during long-term follow-up was similar for CAS and CEA (5.3 versus 4.5 percent, OR 1.26, 95% CI 0.86- 1.84). The composite outcome of death, stroke, or myocardial infarction during the periprocedural period plus ipsilateral stroke during long-term follow-up was also similar for CAS and CEA (6.0 versus 8.2 percent, OR 0.92, 95% CI 0.68-1.26) [76]. No randomized trials have compared CAS (TF-CAS or TCAR) with medical therapy alone. Note that the trials discussed below have involved TF-CAS. Data regarding TCAR or other approaches https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 17/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate to CAS are reviewed separately. (See "Overview of carotid artery stenting", section on 'Approach to carotid artery stenting'.) The ACST-2 trial, conducted from 2008 to 2020, randomly assigned 3625 patients with asymptomatic carotid stenosis of 70 to 99 percent to either CAS or CEA in a 1:1 ratio [78]. The procedural (ie, 30-day) rate of death or any stroke was higher with CAS compared with CEA (3.7 versus 2.7 percent), but the difference was not statistically significant. The five- year rate of procedural death or any stroke during follow-up was also higher with CAS compared with CEA (8.6 versus 7.1 percent), but again the difference did not achieve statistical significance. These results largely reflected a slightly higher incidence of nondisabling stroke in the CAS group; the five-year rate of procedural death or any fatal or disabling stroke was similar for CAS and CEA (3.3 versus 3.5 percent). The ACT I trial, halted early due to slow recruitment, randomly assigned 1453 patients with asymptomatic carotid stenosis of 70 to 99 percent to either CAS or CEA in a 3:1 ratio [79]. For the primary composite endpoint (death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within one year), event rates for CAS and CEA were 3.8 and 3.4 percent, respectively, achieving the prespecified statistical margin for noninferiority of CAS compared with CEA. The rates of stroke or death within 30 days for CAS and CEA were 2.9 and 1.7 respectively, and the difference was not statistically significant. The CREST trial randomly assigned 2502 patients with carotid atherosclerotic disease to endarterectomy or stenting [80,81]. The proportion of enrolled patients with asymptomatic and symptomatic carotid disease was 47 and 53 percent, respectively. The overall effectiveness and safety of CAS and CEA were similar, and the benefits were equal for males and females and for patients with asymptomatic and symptomatic carotid disease. The primary endpoint for the trial, a composite of any stroke, myocardial infarction, or death within 30 days following treatment plus any ipsilateral stroke during 10-year follow- up (median 2.5 years), was similar for CAS and CEA (11.8 versus 9.9 percent, hazard ratio [HR] 1.11, 95% CI 0.83-1.44). In addition, the overall rate of ipsilateral stroke, including the periprocedural period through 10 years of follow-up, was similar for CAS and CEA (10.8 versus 7.9 percent, HR 1.33, 95% CI 0.98-1.80). However, there was a clear trade-off, with higher rates of perioperative stroke or death (and lower rates of perioperative myocardial infarction) for CAS compared with CEA. A CREST substudy found that at one year, stroke had a large detrimental impact on quality of life, while both MI and cranial nerve palsy had small impacts on quality of life that were not statistically significant [82]. Despite the higher rate of stroke with CAS, there were no differences at one year after the procedure between the CEA and CAS groups in any quality-of-life measure. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 18/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate The SAPPHIRE trial compared CAS with CEA in patients considered at high risk for surgery due to clinically significant cardiac disease, severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal nerve palsy, previous radical neck surgery, cervical radiation therapy, recurrent stenosis after CEA, and age greater than 80 years [83,84]. SAPPHIRE randomly assigned 334 patients to CAS or CEA and enrolled symptomatic patients with 50 percent carotid stenosis or asymptomatic patients with 80 percent carotid stenosis. More than 70 percent of patients had asymptomatic carotid disease. At one year, CAS was not inferior to CEA [83]. The primary endpoint was the cumulative incidence of periprocedural (30 day) death, stroke, or myocardial infarction, and/or death or ipsilateral stroke between 31 days and one year. There was near significant reduction in the primary composite endpoint for CAS compared with CEA (12.2 versus 20.1 percent, absolute difference 7.9 percent, 95% CI -0.7 to 16.4 percent). At three years, follow-up data was available for 78 percent of the subjects. The major secondary endpoint (ie, primary endpoint events plus death or ipsilateral stroke between one and three years) was similar for CAS compared with CEA (24.6 versus 26.2 percent) [85]. A number of methodologic and statistical problems with SAPPHIRE have made the conclusions problematic and controversial, with bias that favored the CAS group [65,86-89]. In addition, the periprocedural complication rates in both the CAS and CEA treatment groups were higher than the recommended rate of 3 percent [2,64], which might negate any potential advantages of CAS. Despite these shortcomings, the conclusion that CAS is not inferior to CEA in patients with asymptomatic disease is probably valid for the patient group that was studied, that is, those considered "high risk" for carotid surgery [86]. Stenting in specific subgroups Older adults appear to have worse outcomes with CAS than with CEA [90-92], even though older age was originally proposed to be a condition associated with high surgical risk and therefore a potential indication for stenting rather than endarterectomy. In the prospective CREST trial, the rate of poor outcome in patients age 70 and older was higher with stenting than with endarterectomy [90]. (See 'Stenting versus endarterectomy trials' above.) In a meta-analysis of 41 studies in patients 80 years old, the relative risks of death or myocardial infarction at 30 days were similar for patients having CAS or CEA, but the stroke rate was significantly higher for CAS (7.0 percent, versus 1.9 percent for CEA) [91]. Based upon an acceptable 3 percent stroke rate at 30 days, the pooled RR for stroke was more than threefold higher after CAS (RR 2.18 versus 0.63 with CEA). Most of the included studies were retrospective, so the results of this meta-analysis are not definitive. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 19/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate A 2022 patient-level meta-analysis, which included 2544 patients from two large randomized trials (ACT1, CREST), found that in patients younger than 80 years of age with >70 percent asymptomatic stenosis, periprocedural adverse events were similar in TF-CAS and CEA including: any stroke (2.7 and 1.5 percent); death (0.1 and 0.2 percent); and any stroke/death (2.7 and 1.6 percent) [93]. The rate of ipsilateral stroke after the periprocedural period was also similar (2.3 and 2.2 percent). These data suggest that TF-CAS may be a reasonable treatment option for patients who are younger than 80 years old. In data drawn largely from registries and case series, subgroups suggested to have tolerated CAS with relative safety included patients with prior neck irradiation, high cervical carotid bifurcations, and those with complete occlusion of the contralateral internal carotid artery. Further evidence from large controlled clinical trials is needed before drawing firm conclusions about the safety and effectiveness of CAS in these various subgroups. (See "Overview of carotid artery stenting", section on 'Risk assessment'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 20/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Basics topics (see "Patient education: Carotid artery disease (The Basics)" and "Patient education: Atherosclerosis (The Basics)") SUMMARY AND RECOMMENDATIONS Definition and implications Asymptomatic carotid atherosclerotic disease refers to the presence of atherosclerotic narrowing of the extracranial internal carotid artery in individuals without a history of ipsilateral carotid territory ischemic stroke or transient ischemic attack in the last six months. The most feared outcome of carotid atherosclerosis is ischemic stroke. The estimated risk of ipsilateral stroke in patients with asymptomatic carotid atherosclerosis (stenosis 50 percent) is approximately 0.5 to 1.0 percent annually. Asymptomatic carotid atherosclerosis is also a marker of increased risk for myocardial infarction and vascular death. (See 'Extracranial carotid atherosclerosis' above.) Intensive medical therapy for all patients All patients with carotid stenosis should receive intensive medical therapy to reduce the risk of future stroke and myocardial infarction. These interventions include antiplatelet and statin therapy and other measures to address risk factors for atherosclerosis. Specific recommendations are discussed separately. (See 'Intensive medical therapy and follow-up' above and "Overview of secondary prevention of ischemic stroke" and "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke" and "Overview of primary prevention of cardiovascular disease".) Role of revascularization The approach to asymptomatic carotid stenosis due to atherosclerosis depends upon the severity of stenosis and the comorbid conditions and life expectancy of the patient. In addition, the local experience of the center and surgeon or interventionalist is important if carotid revascularization is desired. (See 'Role of carotid revascularization' above.) Less than 50 percent stenosis Patients with asymptomatic internal carotid artery atherosclerotic disease with <50 percent carotid artery stenosis do not require carotid revascularization. (See 'Stenosis less than 50 percent' above.) Fifty to 69 percent stenosis For patients with asymptomatic carotid atherosclerotic disease with 50 to 69 percent carotid artery stenosis, we suggest no revascularization procedure (Grade 2C). Patients should be managed with intensive medical therapy alone and followed with interval surveillance carotid ultrasound imaging. (See 'Stenosis 50 to 69 percent' above.) https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 21/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Seventy to 99 percent stenosis For medically stable patients with a severe 70 to 99 percent asymptomatic carotid stenosis, either intensive medical therapy alone or intensive medical therapy plus carotid revascularization are reasonable. For patients to potentially benefit from carotid revascularization, their life expectancy should be at least five years, and the combined perioperative risk of stroke and death should be 3 percent. We advise a shared decision-making approach that incorporates the patient's values and preferences. Patients must understand both that the risk of stroke with intensive medical therapy is relatively low and that the benefits of carotid revascularization are limited. We encourage patients with asymptomatic carotid stenosis of 70 to 99 percent to participate in ongoing randomized controlled trials comparing carotid revascularization with modern medical management. (See 'Stenosis 70 to 99 percent' above and 'Carotid endarterectomy' above and 'Factors influencing outcome' above.) Endarterectomy compared with stenting Carotid artery angioplasty and stenting (CAS) and carotid endarterectomy (CEA) provide similar long-term outcomes for patients with carotid occlusive disease, but the periprocedural risk of stroke and death is higher with transfemoral carotid artery stenting (TF-CAS) compared with CEA. The periprocedural risk may be lower for transcarotid artery revascularization (TCAR) compared with TF-CAS. TF-CAS should generally be reserved for patients with unacceptably high surgical risk and performed only in centers with demonstrated low (<3 percent) periprocedural risk for combined stroke and death. (See 'Carotid stenting' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Ronald M Fairman, MD, who contributed to an earlier version of this topic review. The UpToDate editorial staff also acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. de Weerd M, Greving JP, Hedblad B, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 22/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 2010; 41:1294. 2. Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:3754. 3. Inzitari D, Eliasziw M, Gates P, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 2000; 342:1693. 4. Spence JD. Management of asymptomatic carotid stenosis. Neurol Clin 2015; 33:443. 5. Chimowitz MI, Weiss DG, Cohen SL, et al. Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167. Stroke 1994; 25:759. 6. Goessens BM, Visseren FL, Kappelle LJ, et al. Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with manifest arterial disease: the SMART study. Stroke 2007; 38:1470. 7. Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis. Stroke 2009; 40:e573. 8. Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population- based study. Stroke 2010; 41:e11. 9. Chang RW, Tucker LY, Rothenberg KA, et al. Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention. JAMA 2022; 327:1974. 10. Gaba K, Bulbulia R. Identifying asymptomatic patients at high-risk for stroke. J Cardiovasc Surg (Torino) 2019; 60:332. 11. Paraskevas KI, Veith FJ, Spence JD. How to identify which patients with asymptomatic carotid stenosis could benefit from endarterectomy or stenting. Stroke Vasc Neurol 2018; 3:92. 12. Bogiatzi C, Azarpazhooh MR, Spence JD. Choosing the right therapy for a patient with asymptomatic carotid stenosis. Expert Rev Cardiovasc Ther 2020; 18:53. 13. Howard DPJ, Gaziano L, Rothwell PM, Oxford Vascular Study. Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol 2021; 20:193. 14. Lewis RF, Abrahamowicz M, C t R, Battista RN. Predictive power of duplex ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997; 127:13. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 23/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 15. Balestrini S, Lupidi F, Balucani C, et al. One-year progression of moderate asymptomatic carotid stenosis predicts the risk of vascular events. Stroke 2013; 44:792. 16. Yang C, Bogiatzi C, Spence JD. Risk of Stroke at the Time of Carotid Occlusion. JAMA Neurol 2015; 72:1261. 17. Kakkos SK, Nicolaides AN, Charalambous I, et al. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J Vasc Surg 2014; 59:956. 18. Shanik GD, Moore DJ, Leahy A, et al. Asymptomatic carotid stenosis: a benign lesion? Eur J Vasc Surg 1992; 6:10. 19. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986; 315:860. 20. Roederer GO, Langlois YE, Jager KA, et al. The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke 1984; 15:605. 21. Norris JW, Zhu CZ. Stroke risk and critical carotid stenosis. J Neurol Neurosurg Psychiatry 1990; 53:235. 22. Bock RW, Gray-Weale AC, Mock PA, et al. The natural history of asymptomatic carotid artery disease. J Vasc Surg 1993; 17:160. 23. Hirt LS. Progression rate and ipsilateral neurological events in asymptomatic carotid stenosis. Stroke 2014; 45:702. 24. Kistler JP, Furie KL. Carotid endarterectomy revisited. N Engl J Med 2000; 342:1743. 25. Suwanwela N, Can U, Furie KL, et al. Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens. Stroke 1996; 27:1965. 26. Can U, Furie KL, Suwanwela N, et al. Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens. Stroke 1997; 28:1966. 27. Markus HS, King A, Shipley M, et al. Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study. Lancet Neurol 2010; 9:663. 28. Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol 2010; 67:180. 29. Madani A, Beletsky V, Tamayo A, et al. High-risk asymptomatic carotid stenosis: ulceration on 3D ultrasound vs TCD microemboli. Neurology 2011; 77:744. 30. Topakian R, King A, Kwon SU, et al. Ultrasonic plaque echolucency and emboli signals predict stroke in asymptomatic carotid stenosis. Neurology 2011; 77:751. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 24/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 31. Naylor R, Rantner B, Ancetti S, et al. Editor's Choice - European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease. Eur J Vasc Endovasc Surg 2023; 65:7. 32. Kakkos SK, Sabetai M, Tegos T, et al. Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis. J Vasc Surg 2009; 49:902. 33. Kamtchum-Tatuene J, Noubiap JJ, Wilman AH, et al. Prevalence of High-risk Plaques and Risk of Stroke in Patients With Asymptomatic Carotid Stenosis: A Meta-analysis. JAMA Neurol 2020; 77:1524. 34. Nicolaides AN, Kakkos SK, Kyriacou E, et al. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg 2010; 52:1486. 35. el-Barghouty N, Nicolaides A, Bahal V, et al. The identification of the high risk carotid plaque. Eur J Vasc Endovasc Surg 1996; 11:470. 36. Huibers A, de Borst GJ, Bulbulia R, et al. Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1). Eur J Vasc Endovasc Surg 2016; 51:616. 37. Gupta A, Kesavabhotla K, Baradaran H, et al. Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis. Stroke 2015; 46:91. 38. Bassiouny HS, Sakaguchi Y, Mikucki SA, et al. Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis. J Vasc Surg 1997; 26:585. 39. Kakkos SK, Griffin MB, Nicolaides AN, et al. The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke. J Vasc Surg 2013; 57:609. 40. Griffin MB, Kyriacou E, Pattichis C, et al. Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms. J Vasc Surg 2010; 52:69. 41. Schindler A, Schinner R, Altaf N, et al. Prediction of Stroke Risk by Detection of Hemorrhage in Carotid Plaques: Meta-Analysis of Individual Patient Data. JACC Cardiovasc Imaging 2020; 13:395. |
1. de Weerd M, Greving JP, Hedblad B, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 22/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 2010; 41:1294. 2. Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:3754. 3. Inzitari D, Eliasziw M, Gates P, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 2000; 342:1693. 4. Spence JD. Management of asymptomatic carotid stenosis. Neurol Clin 2015; 33:443. 5. Chimowitz MI, Weiss DG, Cohen SL, et al. Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167. Stroke 1994; 25:759. 6. Goessens BM, Visseren FL, Kappelle LJ, et al. Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with manifest arterial disease: the SMART study. Stroke 2007; 38:1470. 7. Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis. Stroke 2009; 40:e573. 8. Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population- based study. Stroke 2010; 41:e11. 9. Chang RW, Tucker LY, Rothenberg KA, et al. Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention. JAMA 2022; 327:1974. 10. Gaba K, Bulbulia R. Identifying asymptomatic patients at high-risk for stroke. J Cardiovasc Surg (Torino) 2019; 60:332. 11. Paraskevas KI, Veith FJ, Spence JD. How to identify which patients with asymptomatic carotid stenosis could benefit from endarterectomy or stenting. Stroke Vasc Neurol 2018; 3:92. 12. Bogiatzi C, Azarpazhooh MR, Spence JD. Choosing the right therapy for a patient with asymptomatic carotid stenosis. Expert Rev Cardiovasc Ther 2020; 18:53. 13. Howard DPJ, Gaziano L, Rothwell PM, Oxford Vascular Study. Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol 2021; 20:193. 14. Lewis RF, Abrahamowicz M, C t R, Battista RN. Predictive power of duplex ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997; 127:13. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 23/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 15. Balestrini S, Lupidi F, Balucani C, et al. One-year progression of moderate asymptomatic carotid stenosis predicts the risk of vascular events. Stroke 2013; 44:792. 16. Yang C, Bogiatzi C, Spence JD. Risk of Stroke at the Time of Carotid Occlusion. JAMA Neurol 2015; 72:1261. 17. Kakkos SK, Nicolaides AN, Charalambous I, et al. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J Vasc Surg 2014; 59:956. 18. Shanik GD, Moore DJ, Leahy A, et al. Asymptomatic carotid stenosis: a benign lesion? Eur J Vasc Surg 1992; 6:10. 19. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986; 315:860. 20. Roederer GO, Langlois YE, Jager KA, et al. The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke 1984; 15:605. 21. Norris JW, Zhu CZ. Stroke risk and critical carotid stenosis. J Neurol Neurosurg Psychiatry 1990; 53:235. 22. Bock RW, Gray-Weale AC, Mock PA, et al. The natural history of asymptomatic carotid artery disease. J Vasc Surg 1993; 17:160. 23. Hirt LS. Progression rate and ipsilateral neurological events in asymptomatic carotid stenosis. Stroke 2014; 45:702. 24. Kistler JP, Furie KL. Carotid endarterectomy revisited. N Engl J Med 2000; 342:1743. 25. Suwanwela N, Can U, Furie KL, et al. Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens. Stroke 1996; 27:1965. 26. Can U, Furie KL, Suwanwela N, et al. Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens. Stroke 1997; 28:1966. 27. Markus HS, King A, Shipley M, et al. Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study. Lancet Neurol 2010; 9:663. 28. Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch Neurol 2010; 67:180. 29. Madani A, Beletsky V, Tamayo A, et al. High-risk asymptomatic carotid stenosis: ulceration on 3D ultrasound vs TCD microemboli. Neurology 2011; 77:744. 30. Topakian R, King A, Kwon SU, et al. Ultrasonic plaque echolucency and emboli signals predict stroke in asymptomatic carotid stenosis. Neurology 2011; 77:751. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 24/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 31. Naylor R, Rantner B, Ancetti S, et al. Editor's Choice - European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease. Eur J Vasc Endovasc Surg 2023; 65:7. 32. Kakkos SK, Sabetai M, Tegos T, et al. Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis. J Vasc Surg 2009; 49:902. 33. Kamtchum-Tatuene J, Noubiap JJ, Wilman AH, et al. Prevalence of High-risk Plaques and Risk of Stroke in Patients With Asymptomatic Carotid Stenosis: A Meta-analysis. JAMA Neurol 2020; 77:1524. 34. Nicolaides AN, Kakkos SK, Kyriacou E, et al. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg 2010; 52:1486. 35. el-Barghouty N, Nicolaides A, Bahal V, et al. The identification of the high risk carotid plaque. Eur J Vasc Endovasc Surg 1996; 11:470. 36. Huibers A, de Borst GJ, Bulbulia R, et al. Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1). Eur J Vasc Endovasc Surg 2016; 51:616. 37. Gupta A, Kesavabhotla K, Baradaran H, et al. Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis. Stroke 2015; 46:91. 38. Bassiouny HS, Sakaguchi Y, Mikucki SA, et al. Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis. J Vasc Surg 1997; 26:585. 39. Kakkos SK, Griffin MB, Nicolaides AN, et al. The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke. J Vasc Surg 2013; 57:609. 40. Griffin MB, Kyriacou E, Pattichis C, et al. Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms. J Vasc Surg 2010; 52:69. 41. Schindler A, Schinner R, Altaf N, et al. Prediction of Stroke Risk by Detection of Hemorrhage in Carotid Plaques: Meta-Analysis of Individual Patient Data. JACC Cardiovasc Imaging 2020; 13:395. 42. van Dam-Nolen DHK, van Egmond NCM, Koudstaal PJ, et al. Sex Differences in Carotid Atherosclerosis: A Systematic Review and Meta-Analysis. Stroke 2023; 54:315. 43. Gupta A, Chazen JL, Hartman M, et al. Cerebrovascular reserve and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta-analysis. 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Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995; 273:1421. 53. Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004; 363:1491. 54. Chambers BR, Donnan GA. Carotid endarterectomy for asymptomatic carotid stenosis. Cochrane Database Syst Rev 2005; :CD001923. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 26/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 55. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005; 65:794. 56. Cambria RP, Conrad MF. Asymptomatic carotid stenosis: Revisionist history is usually wrong. J Vasc Surg 2020; 71:2. 57. AbuRahma AF, Avgerinos ED, Chang RW, et al. Society for Vascular Surgery clinical practice guidelines for management of extracranial cerebrovascular disease. J Vasc Surg 2022; 75:4S. 58. Munster AB, Franchini AJ, Qureshi MI, et al. Temporal trends in safety of carotid endarterectomy in asymptomatic patients: systematic review. Neurology 2015; 85:365. 59. Chaturvedi S, Chimowitz M, Brown RD Jr, et al. The urgent need for contemporary clinical trials in patients with asymptomatic carotid stenosis. Neurology 2016; 87:2271. 60. Reiff T, Eckstein HH, Mansmann U, et al. Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial. Lancet Neurol 2022; 21:877. 61. Shakur SF, Hrbac T, Alaraj A, et al. Effects of extracranial carotid stenosis on intracranial blood flow. Stroke 2014; 45:3427. 62. Howard VJ, Meschia JF, Lal BK, et al. Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials. Int J Stroke 2017; 12:770. 63. Brett AS, Levine JD. The case against identifying carotid stenosis in asymptomatic patients. JAMA Intern Med 2014; 174:2004. 64. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease. Stroke 2011; 42:e464. 65. Brott TG, Brown RD Jr, Meyer FB, et al. Carotid revascularization for prevention of stroke: carotid endarterectomy and carotid artery stenting. Mayo Clin Proc 2004; 79:1197. 66. Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010; 376:1074. 67. Barnett HJ. Carotid endarterectomy. Lancet 2004; 363:1486. 68. Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke 2004; 35:2425. 69. Gorelick PB. Carotid endarterectomy : where do we draw the line? Stroke 1999; 30:1745. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 27/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 70. Goldstein LB, Moore WS, Robertson JT, Chaturvedi S. Complication rates for carotid endarterectomy. A call to action. Stroke 1997; 28:889. 71. Barnett HJ. The inappropriate use of carotid endarterectomy. CMAJ 2004; 171:473. 72. Moore WS, Vescera CL, Robertson JT, et al. Selection process for surgeons in the Asymptomatic Carotid Atherosclerosis Study. Stroke 1991; 22:1353. 73. Wennberg DE, Lucas FL, Birkmeyer JD, et al. Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics. JAMA 1998; 279:1278. 74. O'Neill L, Lanska DJ, Hartz A. Surgeon characteristics associated with mortality and morbidity following carotid endarterectomy. Neurology 2000; 55:773. 75. Mayor JM, Salemi JL, Dongarwar D, et al. Sex-Based Differences in Ten-Year Nationwide Outcomes of Carotid Revascularization. J Am Coll Surg 2019; 229:38. 76. Sardar P, Chatterjee S, Aronow HD, et al. Carotid Artery Stenting Versus Endarterectomy for Stroke Prevention: A Meta-Analysis of Clinical Trials. J Am Coll Cardiol 2017; 69:2266. 77. Moresoli P, Habib B, Reynier P, et al. Carotid Stenting Versus Endarterectomy for Asymptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis. Stroke 2017; 48:2150. 78. Halliday A, Bulbulia R, Bonati LH, et al. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy. Lancet 2021; 398:1065. 79. Rosenfield K, Matsumura JS, Chaturvedi S, et al. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med 2016; 374:1011. 80. Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11. 81. Brott TG, Howard G, Roubin GS, et al. Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis. N Engl J Med 2016; 374:1021. 82. Cohen DJ, Stolker JM, Wang K, et al. Health-related quality of life after carotid stenting versus carotid endarterectomy: results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial). J Am Coll Cardiol 2011; 58:1557. 83. Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004; 351:1493. 84. Yadav JS. Carotid stenting in high-risk patients: design and rationale of the SAPPHIRE trial. Cleve Clin J Med 2004; 71 Suppl 1:S45. https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 28/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate 85. Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008; 358:1572. 86. Cambria RP. Stenting for carotid-artery stenosis. N Engl J Med 2004; 351:1565. 87. Thomas DJ. Protected carotid artery stenting versus endarterectomy in high-risk patients reflections from SAPPHIRE. Stroke 2005; 36:912. 88. LoGerfo FW. Carotid stents: unleashed, unproven. Circulation 2007; 116:1596. 89. Samuelson RM, Yamamoto J, Levy EI, et al. The argument to support broader application of extracranial carotid artery stent technology. Circulation 2007; 116:1602. 90. Voeks JH, Howard G, Roubin GS, et al. Age and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial. Stroke 2011; 42:3484. 91. Usman AA, Tang GL, Eskandari MK. Metaanalysis of procedural stroke and death among octogenarians: carotid stenting versus carotid endarterectomy. J Am Coll Surg 2009; 208:1124. 92. Antoniou GA, Georgiadis GS, Georgakarakos EI, et al. Meta-analysis and meta-regression analysis of outcomes of carotid endarterectomy and stenting in the elderly. JAMA Surg 2013; 148:1140. 93. Matsumura JS, Hanlon BM, Rosenfield K, et al. Treatment of carotid stenosis in asymptomatic, nonoctogenarian, standard risk patients with stenting versus endarterectomy trials. J Vasc Surg 2022; 75:1276. Topic 1113 Version 48.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 29/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate GRAPHICS Carotid endarterectomy reduces stroke, but not endpoint of stroke and death, in asymptomatic men Medical versus surgical (carotid endarterectomy) therapy in 444 men with asymptomatic carotid stenosis 50 percent. (Top panel) Carotid endarterectomy reduced the four-year incidence of ipsilateral stroke or TIA compared to medical therapy (8 versus 20.6 percent, p<0.001). (Bottom panel) There was no difference between the two groups in the incidence of stroke and death (41 versus 44 percent). TIA: transient ischemic attack. Data from: Hobson RW, Weiss DG, Fields WS, et al. E cacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans A airs Cooperative Study Group. N Engl J Med 1993; 328:221. Graphic 53736 Version 7.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 30/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Carotid endarterectomy in asymptomatic men In the ACAS trial, 1662 patients with an asymptomatic carotid stenosis 60 percent were randomized to medical therapy with aspirin or CEA and followed for a mean of 2.2 years. (Top panel) There was no difference between the two groups in the incidence of major stroke or death. (Bottom panel) The incidence of any ipsilateral TIA or stroke or death was lower in the surgical group (p = 0.004). CEA: carotid endarterectomy; TIA: transient ischemic attack. Data from: Executive Committee for the Asymptomatic Carotid Atherosclerosis Trial. JAMA 1995; 273:1421. Graphic 54275 Version 4.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 31/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Any type of stroke or perioperative death in the Asymptomatic Carotid Surgery Trial Risk of any stroke and perioperative death in ACST. The net five-year risk for all strokes or perioperative death in the CEA group was reduced by nearly half compared with the CEA deferral group. ACST: Asymptomatic Carotid Surgery Trial; CEA: carotid endarterectomy. Reproduced with permission from: MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004; 363:1491. Copyright 2004 Elsevier. Graphic 51041 Version 7.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 32/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Fatal or disabling stroke or perioperative death in the Asymptomatic Carotid Surgery Trial The risk of fatal or disabling stroke or perioperative death in the ACST. The net five-year risk for fatal or disabling strokes or perioperative death in the CEA group was reduced by nearly half compared with the CEA deferral group. About one-half of the strokes in the trial were fatal or disabling. ACST: Asymptomatic Carotid Surgery Trial; CEA: carotid endarterectomy. Reproduced with permission from: MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004; 363:1491. Copyright 2004 Elsevier. Graphic 64869 Version 6.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 33/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Meta-analysis of ACAS and ACST The effect of endarterectomy for asymptomatic carotid stenosis on the risk of any stroke and operative death by sex in the ACST and ACAS trials. ACST: Asymptomatic Carotid Surgery Trial; ACAS: Asymptomatic Carotid Atherosclerosis Study; CI: confidence interval; OR: odds ratio. Reproduced with permission from: Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke 2004; 35:2425. Copyright 2004 Lippincott Williams & Wilkins. Graphic 80838 Version 11.0 https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 34/35 7/5/23, 11:40 AM Management of asymptomatic extracranial carotid atherosclerotic disease - UpToDate Contributor Disclosures Michael T Mullen, MD Grant/Research/Clinical Trial Support: NINDS [Asymptomatic carotid disease]. All of the relevant financial relationships listed have been mitigated. Jeffrey Jim, MD, MPHS, FACS Consultant/Advisory Boards: Endospan [Aortic interventions]; Medtronic [Aortic interventions]; Silk Road Medical [Carotid stent]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Eidt, MD Grant/Research/Clinical Trial Support: Syntactx [Clinical events, data/safety monitoring for medical device trials]. All of the relevant financial relationships listed have been mitigated. Joseph L Mills, Sr, MD No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Kathryn A Collins, MD, PhD, FACS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/management-of-asymptomatic-extracranial-carotid-atherosclerotic-disease/print 35/35 |
7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Management of symptomatic carotid atherosclerotic disease : Michael T Mullen, MD, Jeffrey Jim, MD, MPHS, FACS : Scott E Kasner, MD, John F Eidt, MD, Joseph L Mills, Sr, MD : John F Dashe, MD, PhD, Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 03, 2023. INTRODUCTION The location most frequently affected by carotid atherosclerosis is the carotid bifurcation, often with extension into the proximal internal carotid artery (ie, the origin). Atherosclerosis of the internal carotid artery at the bifurcation accounts for 10 to 12 percent of all ischemic strokes [1,2]. This topic will review the treatment of symptomatic extracranial carotid atherosclerotic disease. The management of asymptomatic carotid disease is discussed separately. (See "Management of asymptomatic extracranial carotid atherosclerotic disease".) Other aspects of carotid occlusive disease are reviewed elsewhere. (See "Evaluation of carotid artery stenosis" and "Carotid endarterectomy" and "Overview of carotid artery stenting" and "Percutaneous carotid artery stenting" and "Transcarotid artery revascularization".) CHARACTERIZATION Definition of symptomatic disease Symptomatic extracranial carotid atherosclerotic disease is defined as neurologic symptoms that are sudden in onset and referable to the appropriate internal carotid artery distribution (ipsilateral to significant carotid atherosclerotic pathology), including one or more transient ischemic attacks (TIAs) characterized by focal neurologic dysfunction or transient monocular blindness, or one or more ischemic strokes [3]. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 1/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate The definition is contingent on the occurrence of carotid symptoms within the previous six months [3,4]. Remote carotid symptoms should not be considered as indicative of "symptomatic" carotid disease. Vertigo and syncope are not generally caused by unilateral carotid stenosis. Therefore, patients with these symptoms in isolation should be considered as asymptomatic with regard to carotid disease even if they are found to have carotid artery stenosis. Mechanism of stroke Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. This process can lead to ischemic stroke or TIA from embolization, thrombosis, or reduced brain perfusion (more likely in the setting of bilateral disease). Location and severity of stenosis Treatment of symptomatic extracranial carotid atherosclerotic disease depends upon the location and severity of the carotid lesion. Location In nearly all cases, symptomatic atherosclerosis of the extracranial internal carotid artery (ICA) occurs at its origin or just distal to the bifurcation of the common carotid artery ( figure 1) and typically involves the carotid bulb. The benefit of carotid endarterectomy and carotid stenting for this type of ICA stenosis was established by the randomized trials described below. (See 'Patients appropriate for CEA' below and 'Patients appropriate for CAS' below.) Common carotid artery stenosis located proximal to the carotid bulb is a less frequent cause of stroke or TIA and is less well studied. Atherosclerosis of the common carotid most often occurs at the origin of the artery. Common carotid artery lesions that do not involve the origin can occur as a late complication of radiation treatment. (See 'Common carotid artery lesions' below.) Lesion severity The benefit of carotid endarterectomy (CEA) for patients with symptomatic carotid disease was established by clinical trials designed in the 1980s that used conventional contrast arteriography to determine the degree of internal carotid stenosis. Lesion severity is generally graded as mild (<50 percent), moderate (50 to 69 percent), severe (70 to 99 percent), near occlusion (eg, with severe long segment luminal narrowing from bifurcation to skull base, which is sometimes referred to as a "string sign" on angiographic imaging), and occlusion. Estimates of percent stenosis differ depending upon the definition used and imaging modality. Comparison of the two major trials of endarterectomy, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST), https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 2/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate requires an understanding of how carotid artery stenosis was measured since these studies used different methodologies ( figure 2) [5]. NASCET measured the residual lumen diameter at the most stenotic portion of the vessel and compared this with the lumen diameter in the unaffected internal carotid artery segment distal to the stenosis [6]. ECST measured the lumen diameter at the most stenotic portion of the vessel, but compared this with the estimated diameter at the carotid bulb [4]. The maximum stenosis is generally in the carotid bulb, a wider portion of the artery than the distal segment. As a result, a given stenosis would be more severe using the ECST method compared with that of NASCET. ECST methodology also requires an estimation of the true bulb diameter, which increases the risk of interobserver variability. Despite these differences, the results of different methods have a nearly linear relationship to each other and provide data of similar prognostic value. A 50 percent stenosis with the NASCET method is equivalent to a 65 percent stenosis for the ECST method, while a 70 percent stenosis with the NASCET method is equivalent to an 82 percent stenosis for the ECST method. (See "Evaluation of carotid artery stenosis".) Imaging modality Catheter-based contrast digital subtraction arteriography (DSA) has been considered the gold standard for measuring the severity of internal carotid artery stenosis. However, noninvasive vascular imaging studies including carotid duplex ultrasound (CDUS), magnetic resonance (MR) angiography, and computed tomographic (CT) angiography are preferred in clinical practice because DSA is invasive and associated with a risk of stroke and other complications. (See "Neuroimaging of acute stroke", section on 'Digital subtraction angiography'.) Duplex ultrasound, CT angiography, and MR angiography can all be used to identify symptomatic carotid stenosis in patients who could benefit from carotid revascularization with CEA or carotid artery stenting (CAS). Some experts note that MR angiography is less accurate for evaluating a moderate stenosis, particularly when performed without contrast [7]. Additionally, CT and MR angiography may provide additional anatomic data that could be useful for surgical planning. For patients who undergo CAS, DSA will necessarily be performed as a part of the procedure. Comparisons of the various imaging studies for the evaluation of carotid stenosis are discussed separately. (See "Evaluation of carotid artery stenosis" and "Carotid endarterectomy", section on 'Preoperative evaluation'.) Epidemiology Atherosclerosis of the internal carotid artery at the bifurcation accounts for 10 to 12 percent of all ischemic strokes [1,2]. Evidence from population-based and hospital-based https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 3/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate studies suggests that TIA or stroke associated with ipsilateral carotid stenosis is associated with a high risk of recurrent ipsilateral stroke [8-11]. INTENSIVE MEDICAL MANAGEMENT Optimal medical management includes antithrombotic therapy, high-potency statin therapy, and risk factor modification, including blood pressure control, glucose control, weight control, and lifestyle modification with smoking cessation, exercise, and recommended dietary modifications. (See "Overview of secondary prevention of ischemic stroke", section on 'Lifestyle modification'.) Intensive medical therapy is recommended for all patients with atherosclerotic carotid artery stenosis in any location and regardless of symptoms, but particularly for those with an ipsilateral transient ischemic attack (TIA) or ischemic stroke [12]. The goal is to reduce the risk of future cardiovascular events, including stroke. Recommendations for medical treatment are provided separately. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Overview of secondary prevention of ischemic stroke" and "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) At the time when most of the major carotid endarterectomy (CEA) trials were underway (the late 1980s to mid-1990s), the best medical therapy for carotid disease was generally considered to be antiplatelet treatment with aspirin. Since the completion of these trials, medical regimens emerged that reduced the risk of stroke. These therapies include aggressive treatment with statins, antiplatelet agents, and antihypertensive agents. It is unknown if medical therapies that were introduced after the major trials would change the relative risk reduction afforded by CEA for carotid disease, but they might increase the number of patients needed to treat to prevent one stroke. CAROTID REVASCULARIZATION Treatment of symptomatic extracranial carotid atherosclerotic disease includes medical management and may or may not include carotid revascularization. A decision to offer carotid revascularization for extracranial internal carotid artery stenosis weighs the baseline risk of stroke (see 'Baseline risk of stroke' below) against the potential benefits (lowered risk of future stroke) and harms (eg, perioperative stroke or other complications) associated with the selected revascularization procedure. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 4/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Patients likely to benefit In general, for patients with severe (70 to 99 percent) or moderate (50 to 69 percent) symptomatic internal carotid stenosis, the benefits of carotid revascularization for stroke risk reduction outweigh the risks, particularly when performed within two weeks of the presenting event. However, the benefit varies based upon the degree of stenosis. The benefit for females may be less than for males. Stenosis 70 to 99 percent For patients with recently symptomatic carotid stenosis of 70 to 99 percent who have a life expectancy of at least two years, we recommend revascularization in addition to medical management. Revascularizations should occur within two weeks of symptom onset, when possible. Stenosis 50 to 69 percent For patients with recently symptomatic carotid stenosis of 50 to 69 percent who have a life expectancy of at least three years, we suggest carotid revascularization in addition to medical management, when revascularization can be done within two weeks of symptom onset. Beyond two weeks from symptom onset, the benefit is less certain overall, and females, in particular, may not benefit from revascularization beyond two weeks from symptom onset. These recommendations are in general agreement with guidelines from the American Heart Association/American Stroke Association (AHA/ASA) [12]. For patients who are candidates for revascularization, we suggest carotid endarterectomy rather than transfemoral carotid artery stenting when there is a surgically accessible carotid artery lesion; no clinically significant cardiac, pulmonary, or other disease that would greatly increase the risk of anesthesia and surgery; and no prior ipsilateral endarterectomy. (See 'Patients appropriate for CEA' below.) Patients unlikely to benefit It is important to exclude those who are unlikely to benefit from carotid revascularization. These include patients with the following conditions [13,14]: Stenosis less than 50 percent. Severe comorbidity due to other surgical or medical illness. Stroke associated with persistent, severe neurologic deficits and disability that precludes preservation of useful function. Near occlusion of the symptomatic ipsilateral internal carotid artery; note that distinguishing between a very high-grade stenosis and near occlusion is not necessarily straightforward; the management of such patients should be individualized along with expert guidance. For patients with total occlusion, revascularization is not an option. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 5/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Risk factors for morbidity and mortality associated with carotid revascularization should be identified to avoid procedures in those who may face unacceptably high surgical risk [15]. Specific factors are discussed separately. (See "Carotid endarterectomy", section on 'Preoperative evaluation' and "Carotid endarterectomy", section on 'Risk factors for poor outcome'.) CHOICE OF PROCEDURE Treatment options Carotid revascularization options include carotid endarterectomy (CEA) or carotid artery stenting (CAS). CEA is established as safe and effective by randomized controlled trials for reducing the risk of ischemic stroke in symptomatic patients with carotid artery atherosclerosis. CAS may be useful in selected patients but with risks that differ depending on the technique selected. The choice between CEA and CAS also depends upon the patient's medical comorbidities and the anatomic characteristics of the symptomatic carotid. Regardless of technique, the perioperative risk of stroke and death for the surgeon or center should be <6 percent to provide an overall benefit to the patient. Combined morbidity and mortality that exceeds 6 percent for patients with symptomatic stenosis could eliminate the benefit gained from CEA or CAS [16-18]. Thus, it is important for individual surgeons and stroke centers to track their outcomes and to be transparent about this information. Patients appropriate for CEA For patients who are candidates for carotid revascularization due to moderate (50 to 69 percent) or severe (70 to 99 percent) symptomatic carotid stenosis, we suggest CEA rather than CAS when the following conditions are met: An ipsilateral transient ischemic attack (TIA) or nondisabling ischemic stroke as the symptomatic event A surgically accessible carotid artery lesion No prior ipsilateral endarterectomy No contraindications to revascularization (see 'Patients unlikely to benefit' above) In addition, the risk of perioperative stroke and death with CEA for the surgeon or center should be <6 percent. Some patients who are appropriate candidates for carotid revascularization but who do not meet these conditions may be appropriate candidates for CAS. (See 'Patients appropriate for CAS' below.) https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 6/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate CEA is performed through a neck incision. An arteriotomy is performed at the carotid bifurcation (longitudinal or transverse depending on the technique), and the carotid plaque is then freed and removed and the arteriotomy closed either primarily (direct suture repair) or using a carotid patch. CEA can be performed using local/regional anesthesia or general anesthesia. The choice of anesthesia is generally determined by surgeon and anesthesiologist skill and preference, as well as patient characteristics and preference. The preoperative evaluation, surgical technique, and complications of CEA are reviewed in detail separately. (See "Carotid endarterectomy" and "Complications of carotid endarterectomy".) Antiplatelet treatment, generally with aspirin (81 to 325 mg/day), is recommended for all patients who are undergoing CEA. Other antiplatelet agents (eg, clopidogrel) may be selected for patients with contraindications to aspirin. Antiplatelet agents should be started prior to surgery and continued indefinitely after surgery in the absence of contraindications. (See "Carotid endarterectomy", section on 'Antiplatelet therapy'.) Randomized controlled trials have established CEA as safe and effective for reducing the risk of ischemic stroke in patients with symptomatic internal carotid artery atherosclerosis and moderate (50 to 69 percent) or severe (>70 percent) stenosis [3,4,19]. Patients appropriate for CAS Based upon the available data, we suggest CAS rather than CEA for select patients with recently symptomatic carotid stenosis of 50 to 99 percent who have one or more of the following conditions: A carotid lesion that is not suitable for surgical access Radiation-induced stenosis Carotid restenosis after endarterectomy Clinically significant cardiac, pulmonary, or other disease that greatly increases the risk of anesthesia and surgery Unfavorable neck anatomy including contralateral vocal cord paralysis, open tracheostomy, or prior radical surgery Carotid artery stenting can be performed using the following approaches, which are compared and reviewed in more detail elsewhere: (See "Overview of carotid artery stenting", section on 'Selecting an approach'.) Transfemoral carotid artery stenting (TF-CAS) TF-CAS has been the standard for endovascular carotid intervention [15]. Percutaneous vascular access is typically obtained via the right or left common femoral artery. (See "Overview of carotid artery stenting", section on 'Transfemoral carotid revascularization' and "Percutaneous carotid artery stenting".) https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 7/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Transcarotid artery revascularization (TCAR) TCAR uses a hybrid surgical approach that accesses the carotid artery through a small transverse neck incision, which avoids passing wire/catheters across the aortic arch. (See "Overview of carotid artery stenting", section on 'Transcarotid revascularization' and "Transcarotid artery revascularization".) In data drawn largely from registries and case series, subgroups suggested to have tolerated CAS with relative safety included patients with prior neck irradiation, high cervical carotid bifurcations, and those with complete occlusion of the contralateral internal carotid artery. For high-risk patients (anatomic and physiologic), TCAR may be preferable to TF-CAS and CEA [20,21]. Further evidence from large controlled clinical trials is needed before drawing firm conclusions about the safety and effectiveness of CAS in these various subgroups. Factors that may affect periprocedural outcomes of CAS are discussed elsewhere. (See "Overview of carotid artery stenting", section on 'Risk assessment'.) In the absence of the conditions listed above, CEA remains the preferred treatment for most patients with symptomatic internal carotid atherosclerosis (see 'Patients appropriate for CEA' above). This preference for CEA is in general agreement with major society guidelines [12,20]. If CAS is considered, the periprocedural risk of stroke and death with CAS for the operator or center should be <6 percent. Note that older patients have worse outcomes with transfemoral CAS compared with CEA (see 'Older age and worse outcomes with CAS' below). For patients age 70 years and older in all these subgroups, the benefit-to-risk ratio of CAS is unknown. Patients undergoing CAS are generally treated with a dual antiplatelet regimen (aspirin and clopidogrel) prior to the procedure and continued for at least 30 days after the procedure, followed by long-term single-agent antiplatelet therapy. CEA trials Several major trials evaluated CEA for patients with TIA or nondisabling ischemic stroke attributed to symptomatic internal carotid artery stenosis. All were initiated in the 1980s and first published in 1991. These were the North American Symptomatic Carotid Endarterectomy Trial (NASCET) ( figure 3 and figure 4) [6,22], the European Carotid Surgery Trial (ECST) ( figure 5) [4,19,23], and the Veterans Affairs (VA) trial [24]. In a pooled analysis of patient-level data from the ECST, NASCET, and VA trials, CEA was beneficial for patients with 70 to 99 percent symptomatic stenosis (but not near occlusion) [14,25]. Prerandomization carotid angiograms from ECST were reassessed by the NASCET method, and outcomes were standardized to achieve comparability among the trials. To prevent one event at five years for ipsilateral carotid territory ischemic stroke and operative stroke or death, the number needed to treat (NNT) was 6 (95% CI 5-9) and the absolute risk reduction (ARR) was approximately 17 percent; to prevent one event at five years for disabling or fatal https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 8/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate ipsilateral ischemic or operative stroke and operative death, the NNT was 14 (95% CI 8-35) and the ARR was approximately 7 percent. CEA was also beneficial for patients with 50 to 69 percent symptomatic stenosis. The NNT to prevent any stroke or operative death at five years was 13 (95% CI 8-28, ARR approximately 7.7 percent), while the NNT to prevent any ipsilateral carotid territory ischemic stroke or operative stroke or death at five years was 22 (95% CI 12-80, ARR approximately 4.5 percent) [14,25]. CEA was not beneficial for symptomatic carotid stenosis of 30 to 49 percent, and CEA was harmful for symptomatic patients with less than 30 percent stenosis [14,25]. As an example, patients in the ECST with mild stenosis had little risk of ipsilateral ischemic stroke; possible benefits of CEA were small and were outweighed by the early risks [4]. In NASCET, patients with stenosis of less than 50 percent did not benefit from surgery [3]. There was no benefit of CEA for patients with near occlusion of the internal carotid artery, but there were few patients in this category [14,25]. Trials comparing CAS with CEA Data from randomized controlled trials suggest that CAS and CEA achieve similar long-term benefit for patients with symptomatic carotid occlusive disease. However, the periprocedural (30-day) stroke or death rate is greater with TF-CAS than with CEA, and while the risks of CAS and CEA are similar in the postprocedural period, the combined periprocedural and postprocedural risks still favor CEA. Note that CAS trials have involved predominantly transfemoral carotid artery stenting (TF-CAS). Whether TCAR reduces the risk of complications is unknown. Comparisons of the approaches to CAS are discussed separately. (See "Overview of carotid artery stenting", section on 'TCAR versus TF-CAS'.) A 2020 meta-analysis identified seven trials comparing endovascular treatment with CEA in patients with symptomatic carotid stenosis and four trials comparing endovascular treatment with CEA in patients with both symptomatic and asymptomatic stenosis [26]. None of the trials specifically included patients considered to be at high surgical risk. The patients assigned to the endovascular arms of the included trials were treated with TF-CAS. In the analysis of patients with symptomatic carotid stenosis, the following observations were made [26]: Compared with CEA, patients assigned to endovascular treatment had a higher rate of periprocedural stroke or death at 30 days (7.2 versus 4.4 percent, odds ratio [OR] 1.7, 95% CI 1.31-2.19). In subgroup analysis, patients 70 years of age had an increased risk of periprocedural stroke or death with endovascular treatment compared with CEA (OR 2.23, 95% CI 1.61-3.08). By contrast, the risk of periprocedural stroke or death for patients <70 years of age was similar for the two treatment groups (OR 1.11, 95% CI 0.74-1.64). https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 9/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Compared with CEA, the endovascular treatment group had a higher rate of death or any stroke during the periprocedural period or ipsilateral stroke during follow-up (10.2 versus 7 percent, OR 1.51, 95% CI 1.24-1.85). Compared with CEA, endovascular treatment was associated with lower periprocedural risks of myocardial infarction (OR 0.47), cranial nerve palsy (OR 0.1), and access site hematoma (OR 0.4). The rate of ipsilateral stroke after the periprocedural period was similar for the endovascular and CEA treatment groups (3 versus 2.9 percent, OR 1.05, 95% CI 0.75-1.47). Similar findings were noted in a 2019 pooled analysis of long-term patient-level data from the four largest trials comparing TF-CAS and CEA for symptomatic carotid stenosis, with median follow-up across the trials ranging from 2 to 6.9 years [27]. Most importantly, the combined periprocedural and postprocedural composite risk of stroke or death favored CEA at 1, 3, 5, 7, and 9 years from randomization, with differences ranging between 2.8 percent (95% CI 1.1-4.4) and 4.1 percent (95% CI 2.0-6.3). FACTORS INFLUENCING BENEFIT AND RISK Recommendations for treating symptomatic carotid stenosis are largely based upon findings of major randomized trials (eg, the North American Symptomatic Carotid Endarterectomy Trial [NASCET], the European Carotid Surgery Trial [ECST]), but remain predicated on carotid endarterectomy (CEA) providing a greater benefit to the patient in terms of stroke reduction compared with the risk of performing the procedure. The baseline risk of stroke in symptomatic patients is reviewed above. (See 'Baseline risk of stroke' below.) In addition to the perioperative complication rate and the timing of surgery (see 'Timing of revascularization' below), a number of additional factors appear to impact benefit and risk of CEA in patients with symptomatic carotid stenosis. These include age, sex, retinal versus hemispheric ischemia, and the presence of contralateral carotid stenosis or occlusion. Baseline risk of stroke Since any benefit of carotid revascularization (ie, endarterectomy and stenting) is dependent upon the absolute risk of adverse outcome with or without treatment, it is useful to systematically consider the risks and benefits of revascularization based on individual patient characteristics whenever possible [28]. A risk model for patients with recently symptomatic carotid stenosis was derived from the ECST trial data and validated by showing that the predicted stroke risk for patients assigned to medical treatment in the NASCET trial was close to the observed risk [28]. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 10/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate While the model does not account for the risk and benefit of surgery, it may be useful for assessment of baseline stroke risk and patient selection for carotid revascularization. The baseline ipsilateral stroke risk for patients with recently symptomatic extracranial carotid atherosclerotic disease is calculated based upon the following factors [28]: Patient age Patient sex Degree of carotid stenosis Type of presenting symptomatic event (eg, ocular transient ischemic attack [TIA], hemispheric TIA, minor stroke, or major stroke) Time since last symptomatic event Carotid plaque morphology (eg, smooth versus ulcerated or irregular) These factors can be entered into the model to estimate the absolute risk of ipsilateral stroke for individual patients with symptomatic carotid disease who are candidates for carotid revascularization ( figure 6) [28]. As an example, a 70-year-old man who presents with an ocular TIA, a 70 to 99 percent ipsilateral carotid stenosis, an ulcerated irregular plaque, and time greater than 12 weeks since the last symptomatic event has a predicted absolute five-year stroke risk of 15 to 20 percent. However, if the same patient presents with a cerebral (hemispheric) TIA and time less than two weeks since the last symptomatic event, the predicted absolute five-year stroke risk increases to 35 to 40 percent. Retinal versus hemispheric ischemia Among patients with symptomatic carotid disease, transient retinal ischemia (ie, transient monocular blindness [TMB]; also called amaurosis fugax) portends a lower risk of ipsilateral carotid stroke than hemispheric TIA. In a subset analysis from NASCET, 198 medically treated patients with TMB had a three-year risk of ipsilateral stroke that was approximately one-half that of 417 medically treated patients with hemispheric TIA [29]. Older age and benefit with CEA Subgroup analysis of the NASCET trial found that patients who were age 75 years and older with 50 to 99 percent stenosis benefited more from CEA than younger patients [30]. Others have reported similar findings [31]. These results suggest that CEA should not be withheld from appropriately selected patients over the age of 75 years. Older age and worse outcomes with CAS Older adult patients have worse outcomes with transfemoral carotid artery stenting (TF-CAS) compared with CEA, even though older age was originally proposed to be associated with high risk for surgery and therefore a potential indication for CAS rather than CEA. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 11/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate This point is illustrated by the findings of a 2016 meta-analysis that evaluated pooled patient- level data from subjects with symptomatic carotid disease in the EVA-3S, SPACE, ICSS, and CREST trials [32]. For patients assigned to TF-CAS, the overall periprocedural risk of stroke and death increased with age. Compared with patients aged <60 years, the risk was higher for patients aged 65 to 69 years (hazard ratio [HR] 2.2, 95% CI 1.1-4.1), 70 to 74 years (HR 4, 95% CI 2.2-7.3), 75 to 79 years (HR 3.9, 95% CI 2.1-7.3), and 80 years (HR 4.2, 95% CI 2.2-7.8). For patients assigned to CEA, the periprocedural risk was similar for these age groups. Compared with CEA, the periprocedural risk of stroke and death with TF-CAS was increased for patients aged 70 to 74 years (HR 2.1, 95% CI 1.3-3.3), 75 to 79 years (HR 1.9, 95% CI 1.2-3.0), and 80 years (HR 2.4, 95% CI 1.4-4.4). Similar findings were reported in other meta-analyses of randomized trials [26,33]. The risk of stroke associated with TF-CAS appears to increase linearly with patient age [33,34]. For patients 70 years of age with stroke or TIA being considered for carotid revascularization, 2021 guidelines from the American Heart Association/American Stroke Association (AHA/ASA) stated that it is reasonable to select CEA over CAS to reduce the periprocedural stroke rate [12]. These guidelines noted that the usefulness of TCAR for prevention of recurrent stroke and TIA is uncertain. By contrast, the 2021 Society for Vascular Surgery guidelines noted that, based on the available evidence (predominantly observational data from 2017 onward), TCAR appears to be equivalent to CEA, there are no differences in outcomes with TCAR relative to older age, and the periprocedural risk of stroke may be lower with TCAR compared with TF-CAS [20]. Older age as a risk factor for periprocedural complications of CAS is reviewed in more detail separately. (See "Overview of carotid artery stenting", section on 'Risk assessment'.) Benefit of CEA varies by sex The benefit of CEA may be greater for males than for females. Results from analyses that pooled data from two or more of the major trials (ECST, NASCET, VA, and ASA and Carotid Endarterectomy [ACE] trials [31,35,36]) found that the risk of stroke ipsilateral to a symptomatic carotid stenosis in medically treated patients was lower for females compared with males, while the perioperative risk of death in patients treated with CEA was higher for females compared with males. Nevertheless, CEA was beneficial for both males and females with 70 to 99 percent symptomatic carotid stenosis, with similar five-year absolute risk reduction in stroke for males and females (17.3 and 15.1 percent, respectively). Surgical benefit in females was confined to those who had CEA within two weeks after their last event. As discussed above, for females with 50 to 69 percent symptomatic carotid stenosis, the benefit of carotid revascularization is also less certain. However, an analysis that incorporates time from ischemic event has suggested a similar benefit for males and females with moderate stenosis if https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 12/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate CEA is performed within two weeks of symptom onset (five-year ARR in males of 15.2 percent and in females 13.8 percent) [35]. Beyond two weeks, the benefit is less clear overall, and particularly in females ( figure 5). (See 'Patients likely to benefit' above and 'Timing of revascularization' below.) Contralateral carotid stenosis or occlusion CEA is likely to be beneficial for patients who have symptomatic ipsilateral carotid stenosis and coexisting severe contralateral carotid stenosis or occlusion. However, such patients are at higher perioperative risk than those without a severe contralateral carotid artery stenosis [37]. These points were illustrated in a report from the NASCET cohort that analyzed medical versus surgical therapy in 659 patients with a recent ischemic event attributed to a 70 to 99 percent stenosis of an ipsilateral carotid artery [38]. The contralateral carotid artery had a 70 to 99 percent stenosis in 8.6 percent and was totally occluded in 7 percent. After a two-year follow-up, medically treated patients with an occluded contralateral carotid were twice as likely to have an ipsilateral stroke compared with those with severe or mild to moderate contralateral carotid stenosis (HR 2.36 and 2.65, respectively). Among surgically treated patients, the perioperative risk of stroke and death was higher in those with a totally occluded or mild to moderately stenotic contralateral vessel (4 and 5 percent, respectively) compared with those without contralateral disease. Despite this increased risk, patients who had CEA still had better outcomes compared with patients treated medically. Factors associated with increased surgical risk In data from NASCET, predictors of medical complications with CEA were a history of myocardial infarction or angina and hypertension [39]. Patients with a recent history of myocardial infarction, unstable angina pectoris, or heart failure were excluded from NASCET, perhaps in part explaining the low perioperative medical complication rate. The NASCET study examined rates of perioperative stroke and death at 30 days, stroke severity at 90 days, variables that influenced perioperative risk, and the durability of CEA [40]. Five baseline variables were predictive of increased surgical risk: hemispheric (versus retinal) TIA as the qualifying event; left-sided procedure; contralateral carotid occlusion; ipsilateral ischemic lesion on CT scan; and irregular or ulcerated ipsilateral plaque. It bears repeating that combined perioperative morbidity and mortality that exceeds 6 percent could eliminate the benefit gained from CEA for patients with symptomatic stenosis [16-18]. Timing of revascularization For patients with carotid stenosis and a nondisabling stroke or transient ischemic attack (TIA), we suggest that carotid revascularization with carotid endarterectomy (CEA) or carotid artery stenting (CAS) be performed within two weeks of the last symptomatic event rather than a later time; for patients with ischemic stroke, an exception is https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 13/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate that very early CEA (within the first two days after stroke onset) may be associated with increased operative risk. However, the optimal timing of revascularization in patients with symptomatic carotid atherosclerosis has been the subject of considerable debate. No high- quality prospective, randomized trials have specifically evaluated outcomes related to the timing of CEA after a recent stroke or TIA [41], and data for outcomes related to the timing of CAS are notably lacking. Timing of revascularization has been better studied for CEA than for CAS. Below we provide the evidence and recommendations for CEA, which can generally be extrapolated to timing of CAS. However, available data show that early CAS (TF-CAS, TCAR) is associated with worse outcomes after an index event compared with CEA. After mild stroke or TIA A pooled analysis of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) trials, representing the largest experience to date, found that CEA within two weeks of a nondisabling stroke or TIA significantly improved outcomes compared with later surgery ( figure 7) [31]. In the subgroup of patients with 70 percent or greater carotid stenosis, CEA was associated with a 30.2 percent reduction in absolute risk of stroke in patients randomized within two weeks of their last event, compared with a 17.6, 11.4, and 8.9 percent absolute reduction in those randomized 2 to 4, 4 to 12, and more than 12 weeks from their last event. For patients with 50 to 69 percent stenosis, clinically important benefits from CEA were noted only in patients randomized within two weeks of their last event. Further analysis of the pooled NASCET and ECST data showed that the decline in benefit of CEA over time was more rapid in females than in males [35]. Surgical benefit in females was confined to those who had CEA within two weeks after their last event, irrespective of the degree of stenosis, while CEA within two weeks of a nondisabling hemispheric stroke was not associated with an increased operative risk. When CEA is indicated for patients with TIA or stroke, guidelines from the American Heart Association/American Stroke Association (AHA/ASA) state that it is reasonable to perform the surgery within two weeks rather than delaying surgery [12]. Very early or emergency CEA Very early CEA (eg, within two days of stroke) or emergency CEA for progressing/fluctuating stroke or crescendo TIA may have a high operative risk, as suggested by findings from a meta-analysis of 47 studies (mostly observational or registry studies) published between August 2008 and March 2015 that evaluated early carotid intervention for recently symptomatic stenosis [42]. For CEA |
uncertain. By contrast, the 2021 Society for Vascular Surgery guidelines noted that, based on the available evidence (predominantly observational data from 2017 onward), TCAR appears to be equivalent to CEA, there are no differences in outcomes with TCAR relative to older age, and the periprocedural risk of stroke may be lower with TCAR compared with TF-CAS [20]. Older age as a risk factor for periprocedural complications of CAS is reviewed in more detail separately. (See "Overview of carotid artery stenting", section on 'Risk assessment'.) Benefit of CEA varies by sex The benefit of CEA may be greater for males than for females. Results from analyses that pooled data from two or more of the major trials (ECST, NASCET, VA, and ASA and Carotid Endarterectomy [ACE] trials [31,35,36]) found that the risk of stroke ipsilateral to a symptomatic carotid stenosis in medically treated patients was lower for females compared with males, while the perioperative risk of death in patients treated with CEA was higher for females compared with males. Nevertheless, CEA was beneficial for both males and females with 70 to 99 percent symptomatic carotid stenosis, with similar five-year absolute risk reduction in stroke for males and females (17.3 and 15.1 percent, respectively). Surgical benefit in females was confined to those who had CEA within two weeks after their last event. As discussed above, for females with 50 to 69 percent symptomatic carotid stenosis, the benefit of carotid revascularization is also less certain. However, an analysis that incorporates time from ischemic event has suggested a similar benefit for males and females with moderate stenosis if https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 12/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate CEA is performed within two weeks of symptom onset (five-year ARR in males of 15.2 percent and in females 13.8 percent) [35]. Beyond two weeks, the benefit is less clear overall, and particularly in females ( figure 5). (See 'Patients likely to benefit' above and 'Timing of revascularization' below.) Contralateral carotid stenosis or occlusion CEA is likely to be beneficial for patients who have symptomatic ipsilateral carotid stenosis and coexisting severe contralateral carotid stenosis or occlusion. However, such patients are at higher perioperative risk than those without a severe contralateral carotid artery stenosis [37]. These points were illustrated in a report from the NASCET cohort that analyzed medical versus surgical therapy in 659 patients with a recent ischemic event attributed to a 70 to 99 percent stenosis of an ipsilateral carotid artery [38]. The contralateral carotid artery had a 70 to 99 percent stenosis in 8.6 percent and was totally occluded in 7 percent. After a two-year follow-up, medically treated patients with an occluded contralateral carotid were twice as likely to have an ipsilateral stroke compared with those with severe or mild to moderate contralateral carotid stenosis (HR 2.36 and 2.65, respectively). Among surgically treated patients, the perioperative risk of stroke and death was higher in those with a totally occluded or mild to moderately stenotic contralateral vessel (4 and 5 percent, respectively) compared with those without contralateral disease. Despite this increased risk, patients who had CEA still had better outcomes compared with patients treated medically. Factors associated with increased surgical risk In data from NASCET, predictors of medical complications with CEA were a history of myocardial infarction or angina and hypertension [39]. Patients with a recent history of myocardial infarction, unstable angina pectoris, or heart failure were excluded from NASCET, perhaps in part explaining the low perioperative medical complication rate. The NASCET study examined rates of perioperative stroke and death at 30 days, stroke severity at 90 days, variables that influenced perioperative risk, and the durability of CEA [40]. Five baseline variables were predictive of increased surgical risk: hemispheric (versus retinal) TIA as the qualifying event; left-sided procedure; contralateral carotid occlusion; ipsilateral ischemic lesion on CT scan; and irregular or ulcerated ipsilateral plaque. It bears repeating that combined perioperative morbidity and mortality that exceeds 6 percent could eliminate the benefit gained from CEA for patients with symptomatic stenosis [16-18]. Timing of revascularization For patients with carotid stenosis and a nondisabling stroke or transient ischemic attack (TIA), we suggest that carotid revascularization with carotid endarterectomy (CEA) or carotid artery stenting (CAS) be performed within two weeks of the last symptomatic event rather than a later time; for patients with ischemic stroke, an exception is https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 13/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate that very early CEA (within the first two days after stroke onset) may be associated with increased operative risk. However, the optimal timing of revascularization in patients with symptomatic carotid atherosclerosis has been the subject of considerable debate. No high- quality prospective, randomized trials have specifically evaluated outcomes related to the timing of CEA after a recent stroke or TIA [41], and data for outcomes related to the timing of CAS are notably lacking. Timing of revascularization has been better studied for CEA than for CAS. Below we provide the evidence and recommendations for CEA, which can generally be extrapolated to timing of CAS. However, available data show that early CAS (TF-CAS, TCAR) is associated with worse outcomes after an index event compared with CEA. After mild stroke or TIA A pooled analysis of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) trials, representing the largest experience to date, found that CEA within two weeks of a nondisabling stroke or TIA significantly improved outcomes compared with later surgery ( figure 7) [31]. In the subgroup of patients with 70 percent or greater carotid stenosis, CEA was associated with a 30.2 percent reduction in absolute risk of stroke in patients randomized within two weeks of their last event, compared with a 17.6, 11.4, and 8.9 percent absolute reduction in those randomized 2 to 4, 4 to 12, and more than 12 weeks from their last event. For patients with 50 to 69 percent stenosis, clinically important benefits from CEA were noted only in patients randomized within two weeks of their last event. Further analysis of the pooled NASCET and ECST data showed that the decline in benefit of CEA over time was more rapid in females than in males [35]. Surgical benefit in females was confined to those who had CEA within two weeks after their last event, irrespective of the degree of stenosis, while CEA within two weeks of a nondisabling hemispheric stroke was not associated with an increased operative risk. When CEA is indicated for patients with TIA or stroke, guidelines from the American Heart Association/American Stroke Association (AHA/ASA) state that it is reasonable to perform the surgery within two weeks rather than delaying surgery [12]. Very early or emergency CEA Very early CEA (eg, within two days of stroke) or emergency CEA for progressing/fluctuating stroke or crescendo TIA may have a high operative risk, as suggested by findings from a meta-analysis of 47 studies (mostly observational or registry studies) published between August 2008 and March 2015 that evaluated early carotid intervention for recently symptomatic stenosis [42]. For CEA https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 14/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate performed within 48 hours of the index event of stroke, the pooled periprocedural risk of stroke and death was 8.4 percent (95% CI 5.0-12.7); for the index event of TIA, the corresponding risk was 2.8 percent (95% CI 0.4-7.2). For CEA performed within 15 days of the index event of stroke, the pooled periprocedural risk of stroke and death was 4.9 percent (95% CI 3.4-6.7); for the index event of TIA, the corresponding risk was 1.9 percent (95% CI 0.8-3.3). A 2009 systematic review identified 18 nonrandomized studies of CEA for recently symptomatic carotid stenosis that reported data on time from presenting event to CEA and further stratified CEA into emergency (stroke-in-evolution or crescendo TIA) and nonemergency indications. The rate of perioperative stroke or death was significantly higher with emergency CEA (14 percent, versus 4 percent for nonemergency CEA, pooled relative odds 4.6, 95% CI 3.4-63) [43]. However, the rate of perioperative stroke or death for neurologically stable patients with recent TIA or nondisabling stroke was similar for early CEA (less than one week) and later CEA (one week or more). After moderate to severe stroke Intervention is often not indicated in the setting of very large infarcts with severe neurologic disability. In moderate infarcts, decision-making should be individualized, accounting for the size and severity of the index stroke, the potential for meaningful neurologic deterioration if another stroke were to occur, and the operative risk. The benefit of CEA for patients with moderate to severe ischemic stroke has not been evaluated in randomized clinical trials, as patients who had disabling strokes were not eligible for NASCET or ECST. Given that there have been no prospective trials addressing the question of timing of surgery, it is difficult to generalize observations from the NASCET and ECST trials to all patients undergoing CEA. In particular, patients who have a large infarction with brain swelling and/or significant hemorrhagic transformation have long been thought to have high perioperative risk with early CEA [44-46]. On the other hand, delay in CEA may expose the patient to an increased risk of recurrent stroke. A number of retrospective studies have evaluated the timing of CEA after moderate to severe ischemic stroke, and a 1997 review noted that patients undergoing CEA who have fixed neurologic deficits after a stroke probably represent a heterogeneous group whose risks vary according to clinical and radiological features [47]. Several included reports documented satisfactory outcomes in patients undergoing surgery within six weeks of cerebral infarction. An evidenced-based review of CEA published by the American Academy of Neurology (AAN) in 2005 identified six retrospective cohort studies comparing the timing of CEA (early versus late) in patients after stroke [48]. None of the studies found any https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 15/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate differences in outcomes of perioperative morbidity or longer-term follow-up. All six studies were limited by small size. After intravenous thrombolysis There are only limited retrospective data about the risk of complications with carotid revascularization for patients with acute ischemic stroke who were treated with intravenous thrombolysis. Most studies suggest that CEA or CAS is not associated with increased risk of complications in this setting, at least for patients with minor or moderate deficits [49-53]. However, some reports have found an association with an increased risk of poor outcomes, particularly for patients undergoing revascularization within 48 to 72 hours of intravenous thrombolysis [53,54]. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Alteplase' and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".) Higher risk with urgent CAS and TCAR compared with CEA Early CAS and TCAR are associated with worse 30-day outcomes after an index event compared with CEA. CAS and TCAR performed within the first two days after carotid symptom onset are associated with an increased risk of stroke/death compared with CEA. The safety of CAS and TCAR compared with CEA from three to seven days after symptom onset is not entirely clear, but most data suggest a higher risk with CAS and TCAR [55-58]. In a 2017 pooled analysis of individual patient data from four randomized controlled trials comparing CEA and CAS that included 513 patients treated within seven days of symptom onset, the risk of stroke or death was higher for CAS compared with CEA (8.3 versus 1.3 percent, risk ratio 6.7, 95% CI 2.1-21.9) [55]. A 2022 systematic review of 71 studies (mainly retrospective) with over 200,000 patients found that CAS within two days of symptom onset was associated with higher 30-day stroke and mortality rates compared with CEA [56]. CAS from 3 to 14 days was associated with a similar 30-day stroke rate but higher mortality (odds ratio 2.76, 95% CI 1.39 5.50) compared with CEA. Nearly all of the CAS procedures were performed via the transfemoral route. The data for TCAR are more limited. In a retrospective review of 2608 symptomatic patients treated with TCAR, the procedure was performed after symptom onset within 48 hours (5.5 percent), from days 3 through 14 (35.6 percent), and 14 days or more (58.9 percent) [57]. On adjusted analysis, treatment within 48 hours was associated with a three-fold increased risk of in-hospital stroke/death compared with treatment after 14 days. In another retrospective analysis, performing a TCAR within 48 hours after a stroke was the strongest predictor (odds ratio 5.4) of a postoperative stroke/TIA [58]. However, TCAR within 48 hours after a TIA was not associated with an increased risk. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 16/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate OTHER MANAGEMENT ISSUES Common carotid artery lesions There are limited data about the management of high-grade stenosis involving the common carotid artery (CCA). Treatment depends in part upon the severity and location of the CCA stenosis. Symptomatic stenosis localized to the distal CCA near the bifurcation or extending to the internal carotid artery (ICA) bulb can be treated much the same as proximal ICA stenosis with either carotid endarterectomy or carotid artery stenting. Isolated, proximal CCA lesions can be treated using either retrograde or antegrade stenting. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization", section on 'Endovascular repair'.) Tandem lesions involving the ICA and the CCA may be treated with endarterectomy of the ICA stenosis, followed by retrograde stenting of the proximal CCA artery lesion. However, some surgeons first treat the proximal CCA stenosis before performing endarterectomy of the ICA lesion [59]. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization", section on 'Endovascular repair'.) Carotid restenosis There is controversy about the appropriate management for patients who develop restenosis of the carotid artery following carotid endarterectomy (CEA) or carotid artery stenting (CAS). Restenosis due to intimal hyperplasia is usually benign. For patients who develop symptomatic cerebral ischemia due to recurrent carotid stenosis caused by intimal hyperplasia or atherosclerosis, multispecialty guidelines note that it is reasonable to either repeat CEA or perform CAS using the same criteria as recommended for initial revascularization [13]. There is no established benefit for revascularization of an asymptomatic restenosis [60]. Additional factors that should be considered in the decision include the degree of wound healing since surgery, the occurrence of local or cerebral perioperative complications with prior surgery, and the time since the prior surgery, since perioperative risk may change over time. In addition, patient preference is always important in such decisions. The approach to carotid restenosis is discussed in greater detail elsewhere. (See "Complications of carotid endarterectomy", section on 'Carotid restenosis' and "Overview of carotid artery stenting", section on 'Carotid thrombosis and restenosis'.) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 17/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Carotid artery disease (The Basics)" and "Patient education: Stroke (The Basics)") SUMMARY AND RECOMMENDATIONS Definition of symptomatic extracranial carotid disease Symptomatic extracranial carotid atherosclerotic disease is defined as focal neurologic symptoms that are sudden in onset and referable to the carotid artery distribution within the previous six months. These symptoms may be transient ischemic attacks (TIAs), episodes of transient monocular blindness, or ischemic strokes. (See 'Definition of symptomatic disease' above.) Importance of medical management Treatment of symptomatic extracranial carotid atherosclerotic disease includes intensive medical management and may or may not include carotid revascularization with carotid endarterectomy (CEA) or carotid artery stenting (CAS). Optimal medical therapy includes antithrombotic therapy, statin therapy, and risk factor modification. It is recommended for all patients with atherosclerotic carotid artery stenosis in any location and regardless of symptoms. (See 'Intensive medical management' above.) https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 18/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Patients likely to benefit from revascularization For patients with recently symptomatic carotid stenosis of 70 to 99 percent who have a life expectancy of at least two years, we recommend revascularization with CEA in addition to medical management (Grade 1A). (See 'Patients likely to benefit' above and 'Patients appropriate for CEA' above.) For patients with recently symptomatic moderate carotid stenosis of 50 to 69 percent who have a life expectancy of at least three years, we suggest carotid revascularization with CEA in addition to medical management (Grade 2A). Medical management alone is an appropriate alternative, especially in situations when the benefit is less certain, such as for female patients and if revascularization is delayed more than two weeks. (See 'Patients likely to benefit' above and 'Patients appropriate for CEA' above.) These recommendations apply to patients who are appropriate candidates for CEA, who meet the following conditions (see 'Patients appropriate for CEA' above): - - An ipsilateral TIA or nondisabling ischemic stroke as the symptomatic event A surgically accessible carotid artery lesion Absence of severe cardiac, pulmonary, or other disease that would greatly increase the risk of anesthesia and surgery - No prior ipsilateral endarterectomy CEA is performed by a surgeon or center where the risk of perioperative stroke and death with CEA is <6 percent Patients with symptomatic extracranial carotid atherosclerotic disease are most likely to benefit when carotid revascularization can be done within two weeks of symptom onset; for patients with ischemic stroke, an exception is that very early CEA (within the first two days after stroke onset) may be associated with increased operative risk. (See 'Timing of revascularization' above.) Patients unlikely to benefit from revascularization It is important to exclude those who are unlikely to benefit from carotid revascularization. This includes patients with severe comorbidity due to other surgical or medical illness, who may have unacceptably high risk for carotid revascularization, patients with stroke who have persistent, severe neurologic deficits and disability that precludes preservation of useful function, patients with less than 50 percent carotid stenosis, and patients with carotid occlusion or near occlusion. (See 'Patients unlikely to benefit' above.) https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 19/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate For patients with carotid stenosis that is 30 to 49 percent, we suggest against CEA or CAS (Grade 2B). There is no role for revascularization. For patients with near occlusion of the symptomatic ipsilateral internal carotid artery, there was no benefit of CEA in clinical trials, but there were few patients and events in this category. Note that distinguishing between a very high-grade stenosis and near occlusion is not necessarily straightforward; the management of such patients should be individualized along with expert guidance. For patients with total occlusion, revascularization is not an option. Conditions favoring CAS rather than CEA For most patients, CEA is preferred over CAS because of a higher periprocedural stroke risk associated with CAS. Important exceptions include (see 'Patients appropriate for CAS' above): A carotid lesion that is not suitable for surgical access Radiation-induced stenosis Severe cardiac, pulmonary, or other disease that greatly increases the risk of anesthesia and surgery For these patients, CAS may be preferred and may be the only option. The approach to CAS, whether transfemoral carotid artery stenting (TF-CAS) or transcarotid artery revascularization (TCAR), is influenced by a variety of factors. For patients age 70 years and older with symptomatic carotid disease, outcomes are worse for TF-CAS compared with CEA; for TCAR, an age-related effect on outcomes has not been seen, but data are limited. (See 'Older age and worse outcomes with CAS' above.) ACKNOWLEDGMENTS The editorial staff at UpToDate acknowledges Ronald M Fairman, MD, who contributed to an earlier version of this topic review. The editorial staff also acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 20/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 1. Touz E. 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Long-term clinical and angiographic outcomes in symptomatic patients with 70% to 99% carotid artery stenosis. Stroke 2000; 31:2037. 23. Rothwell PM, Gutnikov SA, Warlow CP, European Carotid Surgery Trialist's Collaboration. Reanalysis of the final results of the European Carotid Surgery Trial. Stroke 2003; 34:514. 24. Mayberg MR, Wilson SE, Yatsu F, et al. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group. JAMA 1991; 266:3289. 25. Orrapin S, Rerkasem K. Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database Syst Rev 2017; 6:CD001081. 26. M ller MD, Lyrer P, Brown MM, Bonati LH. Carotid artery stenting versus endarterectomy for treatment of carotid artery stenosis. Cochrane Database Syst Rev 2020; 2:CD000515. 27. Brott TG, Calvet D, Howard G, et al. Long-term outcomes of stenting and endarterectomy for symptomatic carotid stenosis: a preplanned pooled analysis of individual patient data. Lancet Neurol 2019; 18:348. 28. Rothwell PM, Mehta Z, Howard SC, et al. Treating individuals 3: from subgroups to individuals: general principles and the example of carotid endarterectomy. Lancet 2005; 365:256. 29. Benavente O, Eliasziw M, Streifler JY, et al. Prognosis after transient monocular blindness associated with carotid-artery stenosis. N Engl J Med 2001; 345:1084. 30. Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis. Lancet 2001; 357:1154. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 22/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 31. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363:915. 32. Howard G, Roubin GS, Jansen O, et al. Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials. Lancet 2016; 387:1305. 33. Carotid Stenting Trialists' Collaboration, Bonati LH, Dobson J, et al. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta- analysis of individual patient data. Lancet 2010; 376:1062. 34. Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11. 35. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke. Stroke 2004; 35:2855. 36. Alamowitch S, Eliasziw M, Barnett HJ, et al. The risk and benefit of endarterectomy in women with symptomatic internal carotid artery disease. Stroke 2005; 36:27. 37. Antoniou GA, Kuhan G, Sfyroeras GS, et al. Contralateral occlusion of the internal carotid artery increases the risk of patients undergoing carotid endarterectomy. J Vasc Surg 2013; 57:1134. 38. Gasecki AP, Eliasziw M, Ferguson GG, et al. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg 1995; 83:778. 39. Paciaroni M, Eliasziw M, Kappelle LJ, et al. Medical complications associated with carotid endarterectomy. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke 1999; 30:1759. 40. Ferguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. Stroke 1999; 30:1751. 41. Vasconcelos V, Cassola N, da Silva EM, Baptista-Silva JC. Immediate versus delayed treatment for recently symptomatic carotid artery stenosis. Cochrane Database Syst Rev 2016; 9:CD011401. 42. De Rango P, Brown MM, Chaturvedi S, et al. Summary of Evidence on Early Carotid Intervention for Recently Symptomatic Stenosis Based on Meta-Analysis of Current Risks. Stroke 2015; 46:3423. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 23/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 43. Rerkasem K, Rothwell PM. Systematic review of the operative risks of carotid endarterectomy for recently symptomatic stenosis in relation to the timing of surgery. Stroke 2009; 40:e564. 44. Blaisdell WF, Clauss RH, Galbraith JG, et al. Joint study of extracranial arterial occlusion. IV. A review of surgical considerations. JAMA 1969; 209:1889. 45. BRUETMAN ME, FIELDS WS, CRAWFORD ES, DEBAKEY ME. CEREBRAL HEMORRHAGE IN CAROTID ARTERY SURGERY. Arch Neurol 1963; 9:458. 46. Rob CG. Operation for acute completed stroke due to thrombosis of the internal carotid artery. Surgery 1969; 65:862. 47. Pritz MB. Timing of carotid endarterectomy after stroke. Stroke 1997; 28:2563. 48. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005; 65:794. 49. McPherson CM, Woo D, Cohen PL, et al. Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery. Stroke 2001; 32:2075. 50. Bartoli MA, Squarcioni C, Nicoli F, et al. Early carotid endarterectomy after intravenous thrombolysis for acute ischaemic stroke. Eur J Vasc Endovasc Surg 2009; 37:512. 51. Crozier JE, Reid J, Welch GH, et al. Early carotid endarterectomy following thrombolysis in the hyperacute treatment of stroke. Br J Surg 2011; 98:235. 52. Bazan HA, Zea N, Jennings B, et al. Urgent carotid intervention is safe after thrombolysis for minor to moderate acute ischemic stroke. J Vasc Surg 2015; 62:1529. 53. Brinster CJ, Sternbergh WC 3rd. Safety of urgent carotid endarterectomy following thrombolysis. J Cardiovasc Surg (Torino) 2020; 61:149. 54. Vellimana AK, Washington CW, Yarbrough CK, et al. Thrombolysis is an Independent Risk Factor for Poor Outcome After Carotid Revascularization. Neurosurgery 2018; 83:922. 55. Rantner B, Kollerits B, Roubin GS, et al. Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials. Stroke 2017; 48:1580. 56. Coelho A, Peixoto J, Mansilha A, et al. Editor's Choice - Timing of Carotid Intervention in Symptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis. Eur J Vasc Endovasc Surg 2022; 63:3. 57. Cui CL, Dakour-Aridi H, Eldrup-Jorgensen J, et al. Effects of timing on in-hospital and one- year outcomes after transcarotid artery revascularization. J Vasc Surg 2021; 73:1649. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 24/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 58. Elmously A, Rich N, Lazar AN, et al. Outcomes of early transcarotid artery revascularization versus carotid endarterectomy after acute neurologic events. J Vasc Surg 2022; 76:760. 59. de Borst GJ, Hazenberg CE. How should I treat a patient with a tandem carotid artery atherosclerotic stenosis involving the internal carotid artery and the innominate/proximal common carotid artery? Eur J Vasc Endovasc Surg 2015; 50:257. 60. Chung J, Valentine W, Sharath SE, et al. Percutaneous intervention for carotid in-stent restenosis does not improve outcomes compared with nonoperative management. J Vasc Surg 2016; 64:1286. Topic 1106 Version 43.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 25/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate GRAPHICS Lateral view of the internal carotid artery Lateral view of a schematic drawing of the carotid arteries, vertebral arteries, and intracranial vessels and their relationships in the neck and brain. Reproduced with permission from: U acker R. Atlas Of Vascular Anatomy: An Angiographic Approach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2007. Copyright 2007 Lippincott Williams & Wilkins. Graphic 63286 Version 1.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 26/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Methods of measuring carotid stenosis in NASCET and ECST Modi ed from Donnan, GA, Davis, SM, Chambers, BR, Gates, PC, Lancet 1998; 351:1372. NASCET: North American Symptomatic Carotid Endarterectomy Trial; ECST: European Carotid Surgery Trial; CC: Common Carotid Method. Graphic 58353 Version 2.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 27/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Benefit of carotid endarterectomy after recent ipsilateral nondisabling stroke or TIA in the NASCET trial The NASCET included 659 patients with a recent TIA or nondisabling stroke and a 70 to 99 percent carotid stenosis who were randomly assigned to carotid endarterectomy or medical therapy. After a two- year follow-up, the cumulative risk of any ipsilateral stroke was significantly lower in the endarterectomy group compared with the medical treatment group (9 versus 26 percent). The Kaplan-Meier survival curve shows the probability of event-free survival after randomization at six-month intervals. NASCET: North American Symptomatic Carotid Endarterectomy Trial; TIA: transient ischemic attack. Data from: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445. Graphic 75669 Version 7.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 28/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Carotid endarterectomy reduces major stroke and death in symptomatic patients with severe stenosis The NASCET included 659 patients with a recent TIA or nondisabling stroke and a 70 to 99 percent carotid stenosis who were randomly assigned to carotid endarterectomy or medical therapy. At two-year follow-up, the cumulative risk of a major stroke or death was significantly lower in the endarterectomy group compared with the medical treatment group (8.0 versus 19.1 percent). The Kaplan- Meier survival curve shows the probability of event-free survival after randomization at six-month intervals. NASCET: North American Symptomatic Carotid Endarterectomy Trial; TIA: transient ischemic attack. Data from: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445. Graphic 67964 Version 12.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 29/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Sex difference in the effect of time from symptoms to surgery on benefit from c endarterectomy for TIA and nondisabling stroke Pooled data from the NASCET and the ECST showing the absolute reduction with surgery in the five-year risk |
endarterectomy. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke 1999; 30:1759. 40. Ferguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. Stroke 1999; 30:1751. 41. Vasconcelos V, Cassola N, da Silva EM, Baptista-Silva JC. Immediate versus delayed treatment for recently symptomatic carotid artery stenosis. Cochrane Database Syst Rev 2016; 9:CD011401. 42. De Rango P, Brown MM, Chaturvedi S, et al. Summary of Evidence on Early Carotid Intervention for Recently Symptomatic Stenosis Based on Meta-Analysis of Current Risks. Stroke 2015; 46:3423. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 23/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 43. Rerkasem K, Rothwell PM. Systematic review of the operative risks of carotid endarterectomy for recently symptomatic stenosis in relation to the timing of surgery. Stroke 2009; 40:e564. 44. Blaisdell WF, Clauss RH, Galbraith JG, et al. Joint study of extracranial arterial occlusion. IV. A review of surgical considerations. JAMA 1969; 209:1889. 45. BRUETMAN ME, FIELDS WS, CRAWFORD ES, DEBAKEY ME. CEREBRAL HEMORRHAGE IN CAROTID ARTERY SURGERY. Arch Neurol 1963; 9:458. 46. Rob CG. Operation for acute completed stroke due to thrombosis of the internal carotid artery. Surgery 1969; 65:862. 47. Pritz MB. Timing of carotid endarterectomy after stroke. Stroke 1997; 28:2563. 48. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005; 65:794. 49. McPherson CM, Woo D, Cohen PL, et al. Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery. Stroke 2001; 32:2075. 50. Bartoli MA, Squarcioni C, Nicoli F, et al. Early carotid endarterectomy after intravenous thrombolysis for acute ischaemic stroke. Eur J Vasc Endovasc Surg 2009; 37:512. 51. Crozier JE, Reid J, Welch GH, et al. Early carotid endarterectomy following thrombolysis in the hyperacute treatment of stroke. Br J Surg 2011; 98:235. 52. Bazan HA, Zea N, Jennings B, et al. Urgent carotid intervention is safe after thrombolysis for minor to moderate acute ischemic stroke. J Vasc Surg 2015; 62:1529. 53. Brinster CJ, Sternbergh WC 3rd. Safety of urgent carotid endarterectomy following thrombolysis. J Cardiovasc Surg (Torino) 2020; 61:149. 54. Vellimana AK, Washington CW, Yarbrough CK, et al. Thrombolysis is an Independent Risk Factor for Poor Outcome After Carotid Revascularization. Neurosurgery 2018; 83:922. 55. Rantner B, Kollerits B, Roubin GS, et al. Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials. Stroke 2017; 48:1580. 56. Coelho A, Peixoto J, Mansilha A, et al. Editor's Choice - Timing of Carotid Intervention in Symptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis. Eur J Vasc Endovasc Surg 2022; 63:3. 57. Cui CL, Dakour-Aridi H, Eldrup-Jorgensen J, et al. Effects of timing on in-hospital and one- year outcomes after transcarotid artery revascularization. J Vasc Surg 2021; 73:1649. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 24/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate 58. Elmously A, Rich N, Lazar AN, et al. Outcomes of early transcarotid artery revascularization versus carotid endarterectomy after acute neurologic events. J Vasc Surg 2022; 76:760. 59. de Borst GJ, Hazenberg CE. How should I treat a patient with a tandem carotid artery atherosclerotic stenosis involving the internal carotid artery and the innominate/proximal common carotid artery? Eur J Vasc Endovasc Surg 2015; 50:257. 60. Chung J, Valentine W, Sharath SE, et al. Percutaneous intervention for carotid in-stent restenosis does not improve outcomes compared with nonoperative management. J Vasc Surg 2016; 64:1286. Topic 1106 Version 43.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 25/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate GRAPHICS Lateral view of the internal carotid artery Lateral view of a schematic drawing of the carotid arteries, vertebral arteries, and intracranial vessels and their relationships in the neck and brain. Reproduced with permission from: U acker R. Atlas Of Vascular Anatomy: An Angiographic Approach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2007. Copyright 2007 Lippincott Williams & Wilkins. Graphic 63286 Version 1.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 26/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Methods of measuring carotid stenosis in NASCET and ECST Modi ed from Donnan, GA, Davis, SM, Chambers, BR, Gates, PC, Lancet 1998; 351:1372. NASCET: North American Symptomatic Carotid Endarterectomy Trial; ECST: European Carotid Surgery Trial; CC: Common Carotid Method. Graphic 58353 Version 2.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 27/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Benefit of carotid endarterectomy after recent ipsilateral nondisabling stroke or TIA in the NASCET trial The NASCET included 659 patients with a recent TIA or nondisabling stroke and a 70 to 99 percent carotid stenosis who were randomly assigned to carotid endarterectomy or medical therapy. After a two- year follow-up, the cumulative risk of any ipsilateral stroke was significantly lower in the endarterectomy group compared with the medical treatment group (9 versus 26 percent). The Kaplan-Meier survival curve shows the probability of event-free survival after randomization at six-month intervals. NASCET: North American Symptomatic Carotid Endarterectomy Trial; TIA: transient ischemic attack. Data from: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445. Graphic 75669 Version 7.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 28/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Carotid endarterectomy reduces major stroke and death in symptomatic patients with severe stenosis The NASCET included 659 patients with a recent TIA or nondisabling stroke and a 70 to 99 percent carotid stenosis who were randomly assigned to carotid endarterectomy or medical therapy. At two-year follow-up, the cumulative risk of a major stroke or death was significantly lower in the endarterectomy group compared with the medical treatment group (8.0 versus 19.1 percent). The Kaplan- Meier survival curve shows the probability of event-free survival after randomization at six-month intervals. NASCET: North American Symptomatic Carotid Endarterectomy Trial; TIA: transient ischemic attack. Data from: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445. Graphic 67964 Version 12.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 29/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Sex difference in the effect of time from symptoms to surgery on benefit from c endarterectomy for TIA and nondisabling stroke Pooled data from the NASCET and the ECST showing the absolute reduction with surgery in the five-year risk each of the three main trial outcomes (ie, time to first ipsilateral ischemic stroke and any perioperative stroke death) in patients with 50 to 69% carotid artery stenosis (light bars) and 70% carotid artery stenosis withou occlusion (dark bars), stratified by the time from last symptomatic event to randomization and sex. The numb adjacent to the bars indicate the exact absolute risk reduction (ARR). TIA: transient ischemic attack; NASCET: North American Symptomatic Carotid Endarterectomy Trial; ECST: Eu Carotid Surgery Trial. https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 30/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate From: Rothwell PM, Eliasziw M, Gutnikov SA, et al. Sex di erence in the e ect of time from symptoms to surgery on bene t from carotid endarterectomy for transient ischemic attack and nondisabling stroke. Stroke 2004; 35:2855. DOI: 10.1161/01.STR.0000147040.20446. Copyright 2004 American Heart Association. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of material is prohibited. Graphic 131304 Version 1.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 31/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Predicted five-year risk of ipsilateral ischemic stroke in patients with recently symptomatic carotid stenosis on medical treatment Derived from Cox model based on five clinically important patient characteristics in men and women. Stroke/TIA/Ocular refers to the most severe symptomatic ipsilateral ischemic event in the past six months: Stroke> Cerebral TIA> Ocular events only. Reproduced with permission from: Rothwell, PM, Mehta, Z, Howard, SC, et al. From subgroups to individuals: general principles and the example of carotid endarterectomy. Lancet 2005; 365:256. Copyright 2005 Elsevier. Graphic 71761 Version 1.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 32/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Early carotid endarterectomy is associated with improved outcomes Shown is the absolute reduction with surgery in the five-year cumulative risk of ipsilateral carotid ischemic stroke and any stroke or death within 30 days after carotid endarterectomy (CEA) in patients with 50 to 69 percent stenosis and 70 percent stenosis without near occlusion stratified by the time from last symptomatic event to randomization. Numbers above the bars indicate actual absolute risk reduction. Vertical bars are 95 percent confidence intervals. These results suggest that CEA is likely to be of greatest benefit if performed within two weeks of the last neurologic event in patients with 70 percent carotid stenosis. For patients with 50 to 69 percent stenosis, CEA may only have benefit if performed within two weeks of the last event. Data from: Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363:915. Graphic 70338 Version 3.0 https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 33/34 7/5/23, 11:41 AM Management of symptomatic carotid atherosclerotic disease - UpToDate Contributor Disclosures Michael T Mullen, MD Grant/Research/Clinical Trial Support: NINDS [Asymptomatic carotid disease]. All of the relevant financial relationships listed have been mitigated. Jeffrey Jim, MD, MPHS, FACS Consultant/Advisory Boards: Endospan [Aortic interventions]; Medtronic [Aortic interventions]; Silk Road Medical [Carotid stent]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Eidt, MD Grant/Research/Clinical Trial Support: Syntactx [Clinical events, data/safety monitoring for medical device trials]. All of the relevant financial relationships listed have been mitigated. Joseph L Mills, Sr, MD No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Kathryn A Collins, MD, PhD, FACS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/management-of-symptomatic-carotid-atherosclerotic-disease/print 34/34 |
7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of carotid artery stenting : Jeffrey Jim, MD, MPHS, FACS : John F Eidt, MD, Joseph L Mills, Sr, MD : Kathryn A Collins, MD, PhD, FACS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 08, 2023. INTRODUCTION The proximal internal carotid artery and the carotid bifurcation are the locations most frequently affected by carotid atherosclerosis. Progression of atherosclerotic plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. This process can lead to cerebral ischemia (eg, transient ischemic attack, stroke) from arterial embolization, thrombosis, or less commonly from hemodynamic compromise. For patients with appropriate indications, options for carotid revascularization include carotid endarterectomy (CEA) or carotid angioplasty and stenting, which can be approached using several approaches, each with advantages and disadvantages. An overview of carotid artery stenting (CAS), including approaches to CAS and factors that may favor one approach over the other, and general issues surrounding periprocedural care are reviewed, including complications. CEA is reviewed elsewhere. (See "Carotid endarterectomy".) CAROTID ATHEROSCLEROTIC DISEASE The management of symptomatic or asymptomatic carotid atherosclerotic disease, including the indications for carotid revascularization and the choice between carotid endarterectomy [CEA] and CAS), is discussed in detail separately. (See "Management of symptomatic carotid atherosclerotic disease" and "Management of asymptomatic extracranial carotid atherosclerotic disease".) https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 1/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Indications for stenting CAS is an option for selected patients with contraindications to CEA due to high-risk anatomical or physiological factors for symptomatic ( 50 percent) or asymptomatic high-grade ( 80 percent) internal carotid artery stenosis. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid stenting' and "Management of symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CAS'.) Risk assessment Many of the risk factors for a worse outcome identified for CAS, such as symptomatic carotid disease, increasing degrees of carotid stenosis, parallel those identified in major trials of CEA. (See "Carotid endarterectomy", section on 'Risk factors for poor outcome'.) Other factors that may affect CAS outcomes in patients undergoing CAS include age, sex, composition and morphology of the stenotic lesion, and the presence of white matter lesions, among others. Age Data from the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial [1], Carotid Revascularization Endarterectomy versus Stent trial (CREST) [2-4], prospective series [5-7], and retrospective reports [8-10] suggest that patients 80 years old have a significantly higher risk of stroke and death at 30 days compared with younger patients following transfemoral CAS (TF-CAS). In addition, a retrospective study suggested that patients older than 80 had a higher incidence of unfavorable arterial factors that increased the technical difficulty of TF-CAS, such as aortic arch elongation, arch calcification, common carotid and innominate artery origin stenosis, common and internal carotid artery tortuosity, and a higher risk of residual stenosis post-stenting due to underlying vessel calcification [11]. It is also postulated that older patients have a lower cerebral reserve that makes them more sensitive to minor cerebral emboli, which may be one factor explaining their higher risk of stroke during TF-CAS [12]. Age does not appear to have an appreciable effect on patient outcomes after transcarotid artery revascularization (TCAR), which combines the benefits of avoiding a potentially diseased aortic arch with a low rate of distal embolization. The higher complication rates associated with age seen in those undergoing TF-CAS have not manifested among those undergoing the TCAR procedure. In a study evaluating all patients undergoing carotid procedures in the Vascular Quality Initiative between 2015 and November 2018, 10,381 TF- CAS cases (from 269 centers) and 3152 TCAR cases (from 174 centers) were evaluated [13]. The patients were divided into three different age groups: <70 years, 71 to 79 years, and >80 years. In-hospital mortality, stroke, myocardial infarction, and transient ischemic attack (TIA) were similar between the three age groups. TF-CAS was associated with an increased risk for stroke among older patients (>77 years) but TCAR was not. https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 2/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Sex Clinical studies indicate that the perioperative risk of CAS compared with CEA may be higher in females compared with males [14-18]. Studies are conflicting whether the perioperative risk associated with CAS is more prevalent in symptomatic or asymptomatic women, although data favor increased risk in symptomatic females. Sex as it may impact the choice of CAS or CEA in symptomatic and asymptomatic individuals is discussed in detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Factors influencing outcome' and "Management of symptomatic carotid atherosclerotic disease", section on 'Factors influencing benefit and risk'.) Composition and morphology of the stenotic lesion For patients with atherosclerotic disease, heavily calcified carotid plaque [19], ulcerated plaque [6], increasing degree of carotid stenosis [8], longer lesions, and presence of thrombus have been associated with an increased risk for stroke. Retrospective reviews also suggest that long carotid lesions (>10 mm) [8,20] or carotid segments with more than one lesion separated by normal vessel wall are associated with a higher stroke risk [8]. An analysis of plaque characteristics derived from the CREST trial reported that only plaque length was associated with age with respect to stroke risk; however, it was responsible for only 8 percent of the excess stroke risk [21]. Among patients with radiation-induced stenosis, a systematic review identified 27 studies including 533 patients who underwent CAS or CEA [22]. For patients who underwent TF- CAS, the pooled estimate for any cerebrovascular adverse event was 3.9 percent, which was similar to that identified for CEA. However, the rate of restenosis (long-term) >50 percent and/or occlusion was significantly higher in patients treated with CAS compared with CEA (22.5 versus 10.7 percent). An earlier meta-analysis that included 21 studies found similar results [23]. White matter lesions White matter lesions are likely a consequence of degenerative changes in the deep perforating arterioles. Risk factors for the development of white- matter lesions include age and hypertension. In the International Carotid Stenting Study (ICSS), the number of lesions identified on baseline brain imaging was correlated with stroke rates at 30 days [24]. Patients who underwent CAS with 7 age-related white matter changes had a higher risk of stroke relative to those with <7 lesions (hazard ratio [HR] 2.76, 95% CI 1.17-6.51) and relative to CEA (any stroke: HR 2.98, 95% CI 1.3-6.9; non-disabling stroke: HR 6.34, 95% CI 1.45-27.71). No differences in stroke rates were detected for those with <7 lesions. Other risk factors Other medical risk factors associated with an increased risk for periprocedural complications (mainly stroke) and worse outcome after TF-CAS have been https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 3/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate identified in uncontrolled prospective and retrospective studies. The assessment of medical risk prior to stenting and stroke risk associated with asymptomatic and symptomatic carotid stenosis are discussed in detail elsewhere. (See "Evaluation of cardiac risk prior to noncardiac surgery".) Other medical risk factors include [6,20,25-30]: Presence of aortic stenosis (may be an overall surrogate for atherosclerotic disease) Aortic arch calcification or variant aortic arch anatomy (transfemoral approach) Diabetes mellitus with inadequate glycemic control (hemoglobin A1C >7 percent) Symptomatic compared with asymptomatic ipsilateral carotid stenosis Hemispheric TIA or minor stroke compared with retinal TIA or no symptoms Chronic kidney disease Oral anticoagulant therapy Emergency admission Contraindications Contraindications to CAS can be grouped into those that contraindicate the procedure, in general, and those that contraindicate a specific approach (TF-CAS, TCAR). General contraindications are listed below. These and other specific contraindications are discussed in topics that discuss a specific approach [31] (see 'Indications for stenting' above and "Percutaneous carotid artery stenting", section on 'Contraindications for transfemoral approach' and "Transcarotid artery revascularization", section on 'Anatomic requirements and eligibility'): Absolute Visible thrombus within the lesion detected on preoperative imaging (eg, ultrasound, angiography) or intraoperative imaging Inability to gain vascular access Active infection Relative In general, relative contraindications to CAS include the following. Additional considerations depend upon the approach to carotid stenting. Severe plaque calcification, circumferential carotid plaque Severe carotid tortuosity Near occlusion of the carotid artery ( figure 1) [32,33] Small internal carotid artery (may not accommodate available commercial artery stents) Timing and other considerations The timing of intervention in patients with symptomatic carotid disease depends on the nature and severity of symptoms (eg, TIA, stroke) and is discussed separately. Although the periprocedural risks associated with CAS are similar to CEA https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 4/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate performed earlier (0 to 7 days), the stroke risk for CAS may be slightly higher [34,35]. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Timing of revascularization'.) Other considerations: Bilateral carotid stenosis For patients with severe bilateral carotid stenosis, we suggest a staged approach rather than simultaneous CAS [8,36,37]. A staged approach limits the length of the procedure and intravenous contrast load, whereas simultaneous CAS theoretically increases the risk for cerebral hyperperfusion syndrome and the risk of severe bradycardia or hypotension related to bilateral baroreceptor irritation [38]. (See 'Hyperperfusion syndrome' below.) Prophylactic carotid stenting Given that prophylactic CEA prior to another surgical procedure is generally not supported by available evidence, it may not be reasonable to offer CAS in this setting. A decision to proceed should be individualized based upon the risk of perioperative stroke weighed against the risk of bleeding associated with ongoing antiplatelet therapy (eg, clopidogrel, aspirin), which is recommended following CAS. (See "Coronary artery bypass grafting in patients with cerebrovascular disease", section on 'Method of carotid revascularization' and "Carotid endarterectomy", section on 'Carotid endarterectomy prior to other procedures' and 'Dual antiplatelet therapy' below.) APPROACH TO CAROTID ARTERY STENTING As experience using stents to treat atherosclerotic lesions at other peripheral sites increased, CAS was developed with the aim of reducing the systemic (eg, myocardial infarction [MI]) and local risks (eg, nerve injury) associated with carotid endarterectomy (CEA), which has been the established as the gold standard for carotid revascularization for atherosclerotic disease. To provide a durable benefit, the periprocedural risk of stroke and death for any carotid revascularization must be 3 percent for asymptomatic patients and 6 percent for symptomatic stenosis. (See "Management of asymptomatic extracranial carotid atherosclerotic disease" and "Management of symptomatic carotid atherosclerotic disease".) With the introduction of CAS, some outcomes improved with CAS, but stroke rates were increased in early trials, likely related to certain aspects of the stent technology, the conduct, the procedure (eg, crossing a diseased aortic arch), and possibly the nature of cerebral protection. Improvements in stent devices, differing access approaches, and differing embolic protection methods (distal filter protection, proximal flow arrest, proximal flow reversal) have all been https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 5/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate aimed at reducing the risk of stroke associated with CAS and stroke rates have improved for some, but not all patients. Alternative access approaches and technologic refinements continue. CAS can be performed percutaneously or through a small incision in the neck. Percutaneous CAS obtains vascular access through the groin (transfemoral), axillary artery (transaxillary), brachial artery (transbrachial), radial artery (transradial) [39-42], or direct puncture of the carotid (transcervical). By far the most common approach is via the right (or left) common femoral artery (ie, transfemoral CAS [TF-CAS]). Percutaneous approaches for CAS are typically performed in conjunction with a distal filter-type embolic protection device; proximal occlusion has also been used [43-45]. (See 'Transfemoral carotid revascularization' below and "Percutaneous carotid artery stenting".) Transcarotid artery revascularization (TCAR) is a specific technique that accesses the carotid through a short incision at the base of the neck over the proximal ipsilateral common carotid artery [43-61]. The TCAR procedure is performed through a short carotid sheath in conjunction with flow reversal for embolic protection using a proprietary device. (See 'Transcarotid revascularization' below and "Transcarotid artery revascularization".) Transfemoral carotid revascularization Clinical trials have compared CEA with TF-CAS in patients with either symptomatic or asymptomatic carotid disease [1,2,4,62-69]. No trials have compared CAS with medical therapy alone. Compared with CEA, the periprocedural risk for stroke, and possibly longer-term risk, following TF-CAS is higher [70-72]. Combined 30-day stroke and death rates for TF-CAS in randomized trials range from 6 to 9 percent for symptomatic and from 2 to 4 percent for asymptomatic patients [73-76]. Stroke rates have improved since the introduction of CAS, achieving long-term benefit for symptomatic and asymptomatic patients [73-76]. Clinical trials A meta-analysis of 16 trials (including CREST [2,4,68,69], ICSS [66,67], Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis [EVA- 3S] [63], Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy [SAPPHIRE] [64,65], and others) compared endovascular treatment (mainly TF-CAS) with CEA [74]. The risk of periprocedural stroke or death at 30 days was increased for CAS compared with CEA (8.2 versus 5.0 percent, odds ratio [OR] 1.72, 95% CI 1.29-2.31). In subgroup analysis, a higher risk of periprocedural stroke or death was seen for CAS patients 70 years of age compared with CEA (OR 2.20, 95% CI 1.47-3.29). By contrast, the risk of periprocedural stroke or death for patients <70 years of age was similar for CAS and CEA (OR 1.16, 95% CI 0.80-1.67). CAS had a higher rate of death or stroke during the periprocedural period or ipsilateral stroke during follow-up (10.4 versus 7.7 percent, OR 1.39, 95% CI 1.10-1.75), but a lower risk for MI (OR 0.44), https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 6/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate cranial nerve palsy (OR 0.08), and access site hematoma (OR 0.37). The randomized trials of carotid stenting in symptomatic and asymptomatic patients are discussed in more detail elsewhere. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Carotid stenting' and "Management of symptomatic carotid atherosclerotic disease", section on 'Trials comparing CAS with CEA'.) Registry data The 30-day death and stroke rate was 3.6 percent in an analysis of two multicenter postmarket surveillance registries of CAS (EXACT, CAPTURE-2) that included 6320 high-risk patients [77]. In the SAPPHIRE worldwide registry, which included 2001 patients followed for 30 days, mortality was 1.1 percent and stroke rate was 3.2 percent [78]. A similar rate was found in later large reviews [10,79-81]. Transcarotid revascularization The available clinical data on the TCAR procedure consist of safety and efficacy studies, institutional reports, and real-world outcomes found in the TCAR Surveillance Project (TSP). The updated Society for Vascular Surgery guidelines on the management of extracranial cerebrovascular disease note that TCAR procedure is at least equivalent to CEA, with some potential improvements, and compared with TF-CAS, the overall data demonstrate better outcomes [82]. TCAR may be preferable to CEA and TF-CAS for high-risk patients (anatomic and physiologic) [83]. Safety and efficacy studies The use of the TCAR procedure with internal carotid flow reversal was first described in 2004 [60,61]. However, the first report of TCAR performed with the neuroprotection system was published in 2011. The Silk Road Medical Embolic PROtectiOn System: First-In-Man (PROOF) study reported initial procedural success in 68 of 75 (91 percent) [43]. There were three device malfunctions and four artery dissections with device insertion. Of note, 9 percent had transient intolerance to flow reversal, which was managed successfully by minimizing the duration of flow reversal. At 30 days, there were no major strokes, MIs, or deaths [84]. In a subgroup of 31 patients who underwent a diffusion-weighted magnetic resonance imaging examination, 16 percent had evidence of new ischemic brain lesion without clinical sequelae. The Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) study was a prospective, single-arm, multicenter clinical trial that enrolled 208 patients considered at high risk for complications from CEA who had either symptomatic 50 percent stenosis or asymptomatic 70 percent stenosis [85]. Between 2012 and 2014, 67 patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase, and this latter group was evaluated for outcome analysis. The mean flow reversal time was 13 minutes, and there was one case (0.7 percent) of intolerance to high-flow reversal. The initial technical success rate was 99 percent and the all-stroke rate was 1.4 percent. The composite rate of https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 7/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate stroke/death was 2.8 percent, and the composite rate of stroke/death/MI was 3.5 percent. One patient (0.7 percent) had postoperative hoarseness from potential 10th cranial nerve injury, which resolved at six months. In a follow-up study, 165 patients (112 of 141 pivotal ROADSTER patients as well as 53 of 78 extended-access patients) had outcomes analyzed at one year [86]. Patients aged 75 years and older comprised 43.3 percent of the cohort; 79.9 percent were asymptomatic. In this group, the ipsilateral incidence of stroke incidence was 0.6 percent; seven patients (4.2 percent) died during follow-up, but none of the deaths were neurologic in origin. The ROADSTER 2 study was a prospective, single-arm, multicenter post-approval registry that enrolled 692 patients between 2015 and 2019. Patients were considered at high risk for complications from CEA with either symptomatic 50 percent stenosis or asymptomatic 80 percent stenosis. In the "per protocol" study population, which included 632 patients (ie, 60 protocol violations excluded), the primary endpoint of procedural success (ie, technical success plus absence of stroke/death/MI) was 97.9 percent [87,88]. In the per protocol group, the perioperative (30-day) stroke rate was 0.6 percent, the composite rate of stroke/death was 0.8 percent, and composite rate of stroke/death/MI was 1.7 percent. Observational studies Outcomes for the TCAR procedure appear to be at least equivalent to CEA in observational studies. In a multi-institutional analysis of patients undergoing TCAR and CEA at four institutions, 663 consecutive patients were identified. TCAR patients had higher prevalence of several comorbidities (diabetes, hyperlipidemia, coronary disease, and renal insufficiency). The stroke rates were similar at 30 days (1.0 percent TCAR versus 1.1 percent CEA) and one year (2.8 percent TCAR and 3.0 percent CEA) in the unmatched groups. The patients were then propensity matched based on preoperative comorbidities. In comparing 292 TCAR with 292 CEA patients, stroke (1.0 percent TCAR versus 0.3 percent CEA) and death (0.3 percent TCAR versus 0.7 percent CEA) were similar at 30 days and comparable at one year (stroke 2.8 percent TCAR versus 2.2 percent CEA and death 1.8 percent TCAR versus 4.5 percent CEA). The two groups had a similar composite endpoint of stroke/death/MI (2.1 percent TCAR versus 1.7 percent CEA), but TCAR was associated with a decreased rate of cranial nerve injury (0.3 percent TCAR versus 3.8 percent CEA) [89]. TCAR surveillance project The TSP remains the largest source of data on the clinical outcome of TCAR. Although not all CEA and TF-CAS procedures are captured within the VQI, over 95 percent of all TCAR procedures performed in the United States are recorded in this registry [90]. Several studies have used data from the TSP to compare outcomes between the different methods of carotid revascularization. TCAR versus CEA In a TSP study comparing in-hospital outcomes for patients treated between January 2016 and March 2018, 1182 TCAR patients were compared with 10,797 CEA https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 8/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate patients. TCAR patients were older, more likely symptomatic, and had more medical comorbidities (including coronary artery disease, heart failure, and lung and kidney disease). TCAR patients were more likely to undergo redo carotid intervention, given higher rates of prior ipsilateral CEA (16 versus 2 percent) [91]. TCAR patients were more often treated with local or regional anesthesia (20 versus 7 percent). On unadjusted analysis, TCAR had a similar rate of in- hospital stroke/death (1.6 versus 1.4 percent) and stroke/death/MI (2.5 versus 1.9 percent) compared with CEA. There was no difference in the rate of stroke (1.4 versus 1.2 percent), in- hospital death (0.3 versus 0.3 percent), 30-day death (0.9 versus 0.4 percent), or MI (1.1 versus 0.6 percent). TCAR on average was 33 minutes shorter than CEA, and the patients were less likely to incur a cranial nerve injury (0.6 versus 1.8 percent). On adjusted analysis, there was no difference in terms of stroke/death, stroke/death/MI, or the individual outcomes [92]. TCAR versus TF-CAS In a TSP study that compared in-hospital outcomes for 638 patients undergoing TCAR from 2016 to 2017 with 10,136 patients who underwent TF-CAS between 2005 and 2017 [93], TCAR patients were found to be significantly older, had more cardiac comorbidities, were more likely to be symptomatic, and were less likely to have recurrent stenosis. TCAR procedures were more likely to be performed under general anesthesia (79 versus 12 percent) compared with TF-CAS. TCAR was associated with overall lower rates of in- hospital transient ischemia attacks (TIA)/stroke (1.9 versus 3.3 percent) and in-hospital TIA/stroke/death (2.2 versus 3.8 percent) compared with TF-CAS. On multivariate analysis, there was a trend but no statistically significant difference in stroke or death rates. In a later TSP study using data between September 2016 and April 2019, there were 5251 TCAR procedures performed by 1035 surgeons from 319 centers [90]. Most procedures were performed by vascular surgeons (85 percent), followed by general surgeons (9 percent), neurosurgeons (2 percent), and cardiologists (1 percent). TCAR accounted for 46 percent of all carotid stenting procedures performed in 2018. There were 6640 TF-CAS patients included in the study. After propensity score matching, 3286 pairs of patients were identified. TCAR was associated with a lower risk of in-hospital stroke or death (1.6 versus 3.1 percent), stroke (1.3 versus 2.4 percent), and death (0.4 versus 1 percent). There was no statistically significant difference in the risk of perioperative MI (0.2 versus 0.3 percent). The TCAR procedure was also associated with less radiation exposure for the patient and less contrast utilized. At one year, TCAR also had a lower risk of ipsilateral stroke or death (5.1 versus 9.6 percent). Selecting an approach Anatomic evaluation The evaluation of patients who may be candidates for CAS includes preoperative vascular imaging to characterize the carotid lesion and assure its patency, evaluate https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 9/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate surrounding anatomy, and identify anatomic features that may influence the approach to CAS. (See "Evaluation of carotid artery stenosis".) The evaluation of the carotid lesion may include duplex ultrasonography, computed tomographic (CT) angiography, or magnetic resonance imaging or catheter angiography depending on the clinical presentation (symptomatic, asymptomatic). These are typically sufficient to characterize the carotid lesion and surrounding anatomy. For TCAR, ultrasound examination of the neck also confirms adequate anatomy for arterial sheath insertion. For TF-CAS, CT angiography identifies any significant aortoiliac occlusive disease. For patients with occlusive disease, a decision needs to be made whether transfemoral access is feasible, or whether adjunctive endovascular procedure (eg, iliac artery angioplasty/stenting) is needed to safely achieve access. For some patients, an alternative access route may need to be selected. For TCAR, CT angiography defines anatomic candidacy related to the length of common carotid artery, presence of aortic arch atheroma, vessel tortuosity, and calcium burden within the carotid lesion. Cross-sectional contrast-enhanced imaging from the aortic arch through to the Circle of Willis should also be performed to identify the presence of intracranial arterial disease that may affect patient outcome. Factors favoring TF-CAS For patients in whom CAS has been selected, the following factors may favor the TF-CAS. Severe radiation injury in the neck Prior neck ablative surgery (laryngectomy with tracheostomy or radical neck dissection) The degree of radiation damage to the soft tissue in a patient who has undergone prior neck irradiation should be considered when selecting an approach for CAS. The TCAR procedure may be avoided because it requires limited dissection through a neck incision. Patients with prior neck irradiation tolerate TF-CAS with relative safety [5,94-96]. However, in many [97-99], but not all, studies [100,101], the rate of late carotid restenosis and occlusion following CAS was higher in patients who had radiation-induced occlusive disease compared with those who had atherosclerotic carotid disease [98]. A systematic review identified 27 studies that included 533 patients with radiation-induced carotid stenosis who underwent CAS or CEA [22]. Among patients who underwent TF-CAS, the pooled estimate for any cerebrovascular adverse event was 3.9 percent, which was similar to that identified for CEA. However, the rate of restenosis >50 percent and/or occlusion was significantly higher in patients treated with CAS compared with https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 10/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate CEA (22.5 versus 10.7 percent). An earlier meta-analysis that included 21 studies found similar results [23]. However, carotid restenosis and occlusion in these reports was largely asymptomatic. Factors favoring TCAR For patients in whom CAS has been selected, the following factors may favor the TCAR procedure. Peripheral arterial disease with unfavorable peripheral artery (eg iliac, femoral) access Heavily calcified, severely ulcerated or thrombus-lined aortic arch Likely inability to track and deploy a distal cerebral protection device because of marked tortuosity of the proximal internal carotid artery Variations in aortic arch anatomy, such as a type III arch or bovine anatomy Patients with marked truncal obesity with groin colonization with bacteria and yeast Age >80 PERIOPERATIVE CARE Transfemoral CAS (TF-CAS) is most commonly performed using local anesthesia with sedation and close cardiopulmonary monitoring by the anesthesia provider. It is important for the patient to be able to communicate freely during the procedure with the anesthesia provider. The patient needs to be comfortable, but not so heavily sedated that they are disinhibited or unable to follow commands. Transcarotid artery revascularization (TCAR) may be more commonly performed using general anesthesia. In a study looking at 2609 patients undergoing TCAR, 82.3 percent were performed with general anesthesia and 17.7 percent under local anesthesia with no differences in clinical outcomes (eg, mortality, myocardial infarction [MI], neurologic events) [102]. General anesthesia is generally recommended for TCAR proceduralists early during their experience; however, when procedural familiarity is obtained, TCAR is well suited for use of local anesthesia as with TF-CAS. (See "Anesthesia for carotid endarterectomy and carotid stenting".) Some degree of periprocedural bradycardia or hypotension occurs in up to 68 percent of patients who undergo CAS [103-110]. Given that bradycardia or even cardiac arrest can develop during ballooning of the stent, both atropine and glycopyrrolate should be available for immediate infusion. Bradycardia is due to carotid baroreceptor stimulation during inflation of the post-stent angioplasty balloon. Following CAS, patients are typically discharged in one to two days. Outpatient CAS may become feasible, but the safety of this practice needs to be established. Reimbursement in the United States for CAS mandates an overnight hospitalization of at least one day. https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 11/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate Medication management Preoperative control of blood pressure Poorly controlled hypertension preoperatively is predictive of prolonged length of stay due to postoperative hypertension. Thus, we make an effort to have hypertension under control before proceeding with CAS [111]. (See "Anesthesia for carotid endarterectomy and carotid stenting", section on 'Hemodynamic monitoring'.) Prophyactic antibiotics Although not routinely recommended for all percutaneous interventional procedures, antibiotic prophylaxis prior to CAS is standard practice, regardless of approach. Appropriate antibiotic choices are given in the table ( table 1). Dual antiplatelet therapy Prior to CAS, we recommend pretreatment with dual antiplatelet therapy (DAPT) using aspirin and clopidogrel ( algorithm 1); however, data are limited regarding the effectiveness of DAPT; the optimal timing, dose and duration of treatment for CAS is unknown [112]. Our specific pretreatment and post-treatment dosing regimens for percutaneous CAS and TCAR are provided separately. (See "Percutaneous carotid artery stenting", section on 'Antiplatelet/statin therapy' and "Transcarotid artery revascularization", section on 'Dual antiplatelet therapy and statins'.) A systematic review identified only two small trials comparing single with dual antiplatelet therapy in patients undergoing CAS. In a meta-analysis of these two trials [113-115], the risk for transient ischemic attack (TIA) was reduced for dual compared with single antiplatelet therapy (1.3 versus 14.6 percent; risk difference -0.13; 95% CI -0.22 to -0.05). However, there were no differences in stroke, major bleeding, or hematoma formation, or incidence of MI or death. In a separate meta-analysis of these same trials, the risk for restenosis was similar [116]. In the absence of any other robust data, we initiate DAPT using aspirin and clopidogrel prior to the procedure (at least 48 hours for percutaneous CAS; the TCAR trial favored 72 hours pretreatment) and continue dual antiplatelet therapy post-procedure for at least four weeks. Thereafter, aspirin should be continued indefinitely to reduce the risk for future cardiovascular events. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Antiplatelet therapy'.) In an observational study from the Vascular Quality Initiative looking at 31,036 total CAS procedures (approximately 50/50 TCAR and TF-CAS), perioperative P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor taken within 36 hours of the procedure) markedly reduced the perioperative neurologic event rate [117]. Among patients on P2Y12 inhibitors, 92.7 percent were also taking aspirin. P2Y12 inhibitors were significantly more likely to be used in TCAR cases compared with TF-CAS cases (87.3 versus 76.8 percent). Of the patients on P2Y12 inhibitors, 77.3 https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 12/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate percent were on clopidogrel. This study demonstrated there is considerable room for improving compliance with recommended perioperative DAPT. For patients with a history of neck irradiation, we suggest long-term DAPT with aspirin and clopidogrel following CAS, provided the risk of bleeding remains low. While there are no studies available that have specifically evaluated such a protocol in this subset of patients, radiated patients are at high risk for recurrent carotid stenosis following CAS, as high as 30 percent in some series. In CAS trials, the following protocols were used: In the CREST trial, patients were treated with aspirin (325 mg twice daily) and clopidogrel (75 mg twice daily) starting at least 48 hours before the CAS procedure [4]. Those scheduled for CAS within 48 hours received aspirin 650 mg and clopidogrel 450 mg at least four hours before the CAS procedure. Following CAS, treatment included aspirin 325 mg once or twice daily and clopidogrel 75 mg daily (or ticlopidine 250 mg twice daily) for at least 30 days, with a recommendation to continue aspirin indefinitely (at least one year). In a survey of participants of the Asymptomatic Carotid Surgery Trial 2 (ACST2 trial), 82 percent of sites used dual antiplatelet therapy (DAPT) preoperatively and 86 percent postoperatively with a mean postprocedural duration of three months (range 1 to 12), while 9 percent continued DAPT lifelong [118]. For those prescribing postprocedural mono antiplatelet therapy (76 percent), aspirin was more commonly prescribed than clopidogrel (59 versus 6 percent), and 11 percent did not show a preference for either aspirin or clopidogrel. Eleven centers (16 percent) tested for antiplatelet therapy resistance. In the ROADSTER 2 study, early postoperative outcomes in the intention-to-treat population (692 patients) included stroke in 13 patients (1.9 percent), death in 3 patients (0.4 percent), and MI in 6 patients (0.9 percent) [88]. Sixty patients had major protocol deviations, and among these, 48 patients were not on dual antiplatelet and statin therapy while undergoing carotid intervention or during the periprocedural follow-up period. Among the 60 patients with protocol violations, perioperative (30-day) stroke occurred in 9 (26 percent); death in 2 (3.3 percent); MI in none. Guidelines have suggested a range of periprocedural aspirin therapy ranging from 75 mg to 325 mg daily [82,83,119,120]. Various loading doses of clopidogrel have also been used. Other doses of clopidogrel have also been investigated. In the Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting (ARMYDA-9 CAROTID) trial, 156 patients were randomly assigned to receive a loading dose of clopidogrel (600 mg or 300 mg) before stenting https://www.uptodate.com/contents/overview-of-carotid-artery-stenting/print 13/41 7/5/23, 11:42 AM Overview of carotid artery stenting - UpToDate with or without a statin reload (2 x 2 trial design) [121]. The perioperative (30-day) incidence of TIA/stroke or new ischemic lesions on magnetic resonance imaging was lowest in the 600 mg clopidogrel plus statin reload group. By contrast, in a smaller trial, no differences were seen between groups for asymptomatic patients (n = 35) undergoing CAS assigned to 300 mg or 600 mg of clopidogrel with respect to the sum of all microembolic signals on transcranial Doppler, or platelet aggregation measurements [122]. Cilostazol is a phosphodiesterase inhibitor that is commonly used in the treatment of claudication. A systematic literature review identified seven studies evaluating outcomes using cilostazol in association with CAS [123]. Major outcomes included in-stent restenosis within the observation period, revascularization rate, major/minor bleeding, and MI/stroke/death rate at 30 days and within the observation period. A significantly lower rate of in-stent stenosis was seen with cilostazol treatment after a mean follow-up of 20 months (odds ratio [OR] 0.158, 95% CI 0.072-0.349). No significant differences were found between the groups among five studies (649 patients) for periprocedural MI/stroke/death or in three studies (1076 patients) for MI/stroke/death for the entire follow-up period. Statin therapy Statin therapy is recommended for patients following TIA or ischemic stroke or in those with coronary artery disease risk equivalents. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease" and "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'.) Whether statin therapy can reduce the risk of cerebral embolization during or after CAS is debated [121,124-129]. A small study compared debris collected from embolic protection devices in 62 patients who were or were not taking statins [129]. Statin use (HMG-CoA-reductase inhibitor) was associated with significantly fewer embolic particles (16.4 versus 42.4 particles). |