surgery; CMP: cardiomyopathy; CRT: cardiac resynchronization therapy; HF: heart failure; ECG: electrocardiogram; EPS: electrophysiologic study; ICD: implantable cardioverter-defibrillator; LVEF: left ventricular ejection fraction; MI: myocardial infarction; MRA: mineralocorticoid receptor antagonist; NR: not reported (likely near zero given early date of trial); NSVT: nonsustained ventricular tachycardia; NYHA: New York Heart Association; PVC: premature ventricular contraction; SAECG: signal averaged electrocardiogram; SCA: sudden cardiac arrest; VT: ventricular tachycardia. Epicardial ICDs were predominantly used in the CABG Patch trial, as patients were all undergoing CABG. This is not consistent with contemporary practice. Some patients with NYHA class IV functional status were enrolled in MADIT-II, but the requirement was to be NYHA class I/II/III at the time of enrollment. Graphic 98261 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 35/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate NYHA and other classifications of cardiovascular disability Canadian NYHA functional [1] Cardiovascular Specific activity Class [3] classification Society functional scale [2] classification I Patients with cardiac Ordinary physical Patients can perform to disease but without activity, such as completion any activity requiring 7 metabolic equivalents (ie, can resulting limitations of physical activity. walking and climbing stairs, does not cause Ordinary physical activity does not cause angina. Angina with strenuous or rapid carry 24 lb up 8 steps; do outdoor work undue fatigue, palpitation, dyspnea, or prolonged exertion at work or recreation. [shovel snow, spade soil]; do recreational anginal pain. activities [skiing, basketball, squash, handball, jog/walk 5 mph]). II Patients with cardiac disease resulting in Slight limitation of ordinary activity. Patients can perform to completion any activity requiring 5 metabolic equivalents (eg, have sexual intercourse without stopping, garden, rake, weed, roller skate, dance foxtrot, walk at 4 mph slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal Walking or climbing stairs rapidly, walking uphill, walking or stair- climbing after meals, in cold, in wind, or when under emotional stress, or only during pain. the few hours after awakening. Walking more than 2 blocks on on level ground) but cannot and do not perform to completion activities requiring 7 metabolic equivalents. the level and climbing more than 1 flight of ordinary stairs at a normal pace and in normal conditions. III Patients with cardiac disease resulting in Marked limitation of ordinary physical Patients can perform to completion any activity requiring 2 metabolic equivalents (eg, shower without stopping, strip marked limitation of activity. Walking 1 to 2 physical activity. They are comfortable at rest. blocks on the level and climbing 1 flight in Less-than-ordinary physical activity causes normal conditions. and make bed, clean windows, walk 2.5 fatigue, palpitation, mph, bowl, play golf, https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 36/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate dyspnea, or anginal dress without stopping) pain. but cannot and do not perform to completion any activities requiring >5 metabolic equivalents. IV Patients with cardiac Inability to carry on any Patients cannot or do disease resulting in physical activity not perform to inability to carry on any physical activity without discomfort. Anginal syndrome may completion activities requiring >2 metabolic without discomfort. Symptoms of cardiac be present at rest. equivalents. Cannot carry out activities insufficiency or of the anginal syndrome may listed above (specific activity scale III). be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA: New York Heart Association. References: 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the th Heart and Great Vessels, 9 ed, Little, Brown & Co, Boston 1994. p.253. 2. Campeau L. Grading of angina pectoris. Circulation 1976 54:522. 3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: Advantages of a new speci c activity scale. Circulation 1981; 64:1227. Graphic 52683 Version 19.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 37/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Pacing leads for cardiac resynchronization therapy Two leads (right atrial and right ventricular leads) permit pacing of the right atrium and right ventricle. The third lead (coronary sinus lead), which is advanced through the coronary sinus into a venous branch that runs along the free wall of the left ventricle, paces the lateral wall and enables synchronized left ventricular contraction. Graphic 79450 Version 5.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 38/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Implantable defibrillator versus conventional drug therapy Kaplan-Meier cumulative survival curves in the MADIT trial showing that selected high-risk patients (prior infarction, left ventricular ejection fraction 35 percent, nonsustained ventricular tachycardia, and an inducible sustained ventricular tachyarrhythmia not supressible with procainamide) have a better survival rate with an implantable defibrillator compared with conventional therapy with antiarrhythmic drugs (p = 0.009). The number of patients at each time period is noted at the bottom. Data from: Moss AJ, Hall WJ, Cannom DS, et al for the Multicenter Automatic De brillator Implantation Trial Investigators, N Engl J Med 1996; 335:1933. Graphic 76854 Version 2.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 39/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate ICD reduces sudden death in MUSTT The MUSTT trial enrolled 704 patients with coronary artery disease, nonsustained ventricular tachycardia (VT), and a left ventricular ejection fraction 40 percent who had sustained VT induced during electrophysiologic (EP) study. Kaplan-Meier estimates show that the incidence of cardiac arrest or death from arrhythmia is significantly lower in those receiving an implantable cardioverter-defibrillator (ICD) compared with those receiving no therapy or those with EP-guided (EPG) antiarrhythmic drug (AAD) therapy. Data from: Buxton AE, Lee KL, Fisher JD, et al. N Engl J Med 1999; 341:1882. Graphic 68247 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 40/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Prophylactic ICD does not improve survival in high- risk patients after CABG The CABG-Patch trial randomized 900 patients with a low ejection fraction and a positive signal-averaged electrocardiogram to an implantable cardioverter-defibrillator or no defibrillator after coronary artery bypass graft surgery. There was no difference in mortality at a mean follow-up of 32 months. Data from: Bigger JT, for the Coronary Artery Bypass Graft (CABG) Patch Trial Investigators, N Engl J Med 1997; 337:1569. Graphic 78888 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 41/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate ICD improves survival in MADIT II Kaplan-Meier estimates of the probability of survival in the MADIT II trial in 1232 patients who had a myocardial infarction more than 30 days prior to enrollment (and more than three months if bypass surgery was performed) and an LVEF 30 percent. The patients were randomly assigned to a prophylactic ICD or conventional medical therapy. The study was prematurely terminated after an average follow-up of 20 months because the ICD significantly reduced all- cause mortality (14.2 versus 19.8 percent for conventional therapy, hazard ratio 0.65, 95% CI 0.51-0.93). The survival benefit was largely due to a reduction in sudden death. LVEF: left ventricular ejection fraction; ICD: implantable cardioverter- defibrillator. Data from: Moss AJ, Zareba W, Hall WJ, et al. N Engl J Med 2002; 346:877. Graphic 63529 Version 4.0 https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 42/43 7/6/23, 3:35 PM Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF - UpToDate Contributor Disclosures Joseph E Marine, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Andrea M Russo, MD, FACC, FHRS Grant/Research/Clinical Trial Support: BMS/Pfizer [Anticoagulant]; Boston Scientific [Arrhythmia]; Kestra [Arrhythmia]; Medilynx [Arrhythmia]; Medtronic [Arrhythmia]. Consultant/Advisory Boards: Abbott [Arrhythmia]; Atricure [Arrhythmia]; Biosense Webster [Arrhythmia]; Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]; PaceMate [Arrhythmia]. Speaker's Bureau: Biotronik [Arrhythmia]; Medtronic [Arrhythmia]. Other Financial Interest: ABIM [Cardiovascular board]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/primary-prevention-of-sudden-cardiac-death-in-patients-with-cardiomyopathy-and-heart-failure-with-reduced-lvef 43/43