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, 3:09 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. 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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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 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, 3:09 PM