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. 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