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