HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials.

Abstract

HomeCirculationVol. 130, No. 1HRS/ACC/AHA Expert Consensus Statement on the Use of Implantable Cardioverter-Defibrillator Therapy in Patients Who Are Not Included or Not Well Represented in Clinical Trials Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBHRS/ACC/AHA Expert Consensus Statement on the Use of Implantable Cardioverter-Defibrillator Therapy in Patients Who Are Not Included or Not Well Represented in Clinical Trials Fred M. Kusumoto, MD, FHRS, Hugh Calkins, MD, FHRS, John Boehmer, MD, Alfred E. Buxton, MD, Mina K. Chung, MD, FHRS, Michael R. Gold, MD, PhD, FHRS, Stefan H. Hohnloser, MD, FHRS, Julia Indik, MD, PhD, FHRS, Richard Lee, MD, MBA, Mandeep R. Mehra, MD, Venu Menon, MD, Richard L. Page, MD, FHRS, Win-Kuang Shen, MD, David J. Slotwiner, MD, Lynne Warner Stevenson, MD, Paul D. Varosy, MD, FHRS and Lisa Welikovitch, MD Fred M. KusumotoFred M. Kusumoto 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Hugh CalkinsHugh Calkins 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , John BoehmerJohn Boehmer 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 §Representative for the Heart Failure Society of America (HFSA). Search for more papers by this author , Alfred E. BuxtonAlfred E. Buxton 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 *Representative for the American Heart Association (AHA). Search for more papers by this author , Mina K. ChungMina K. Chung 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Michael R. GoldMichael R. Gold 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Stefan H. HohnloserStefan H. Hohnloser 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Julia IndikJulia Indik 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Richard LeeRichard Lee 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 †Representative for the American College of Cardiology (ACC). Search for more papers by this author , Mandeep R. MehraMandeep R. Mehra 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 *Representative for the American Heart Association (AHA). Search for more papers by this author , Venu MenonVenu Menon 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 ‡Representative for the Society of Thoracic Surgeons (STS). Search for more papers by this author , Richard L. PageRichard L. Page 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 ‡Representative for the Society of Thoracic Surgeons (STS). Search for more papers by this author , Win-Kuang ShenWin-Kuang Shen 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 *Representative for the American Heart Association (AHA). Search for more papers by this author , David J. SlotwinerDavid J. Slotwiner 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author , Lynne Warner StevensonLynne Warner Stevenson 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 ‡Representative for the Society of Thoracic Surgeons (STS). Search for more papers by this author , Paul D. VarosyPaul D. Varosy 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author and Lisa WelikovitchLisa Welikovitch 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Search for more papers by this author Originally published9 May 2014https://doi.org/10.1161/CIR.0000000000000056Circulation. 2014;130:94–125Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2014: Previous Version 1 Table of ContentsIntroduction 95Current Guidelines that Address ICD Use 95Randomized Controlled Trials of ICD Therapy for Primary Prevention of Sudden Cardiac Death 96ICD Implantation in the Context of an Abnormal Troponin that Is Not Due to a Myocardial Infarction 100ICD Implantation Within 40 Days of a Myocardial Infarction 101ICD Implantation Within 90 Days of Revascularization 105ICD Implantation < 9 Months from the Initial Diagnosis of Nonischemic Cardiomyopathy 110Dual-Chamber vs Single-Chamber ICD Recommendations 1148.1. Randomized Trial Evidence from the Major Efficacy Trials of ICD Therapy 1158.2. Benefits of Dual-Chamber ICDs 1158.3. Potential Risks of Dual-chamber Device Selection 1158.4. Real-World Practice Patterns with Regard to Selection of Single-Chamber and Dual-Chamber ICDs 1168.5. Device Selection in the Era of Modern Programming Strategies 116Documentation of Clinical Decisions 116Future Research and Directions 1171. IntroductionThe implantable cardioverter defibrillator (ICD) has emerged as an important treatment option for selected patients who are at risk of sudden cardiac death. Randomized trials have consistently shown that ICD implantation reduces mortality in patients with heart failure and reduced left ventricular function, as well as in patients who have suffered a cardiac arrest.1–3 Recommendations on the use of the ICD in clinical practice have been provided in four important guideline documents sponsored by the American College of Cardiology (ACC), the American Heart Association (AHA), Heart Rhythm Society (HRS), and the European Society of Cardiology (ESC).4–7 For each indication for ICD therapy, both a Class of indication (I, II, or III) and level of evidence for the indication (A, B, or C) are provided. To ensure that recommendations are evidence-based, Class I recommendations are typically based on the results of prospective randomized clinical trials. For example, in the ACC/AHA/HRS 2012 Focused Update of the ACC/AHA/HRS 2008 Guidelines on Device-Based Therapy, no new recommendations on the indications for ICD therapy were made, with the important exception of ICDs that also provide cardiac resynchronization therapy (CRT-D).8 The lack of new recommendations reflects the fact that clinical trials over this period of time have focused on studying the effectiveness of ICDs that provide CRT therapy and not on the outcomes of non-CRT defibrillators. Randomized clinical trials study the effects of a particular treatment on a carefully selected and relatively homogeneous group of patients who meet specific inclusion and exclusion criteria for a particular clinical trial. Consistent with this approach, the indications for ICD therapy developed in the various guideline statements are limited to the specific populations of patients who participated in these clinical trials. Although the resulting guidelines are of great value, clinicians are often asked to make decisions regarding ICD therapy in patient populations who were not included or who were poorly represented in prior clinical trials. For these patients, there are no specific indications for ICD therapy. The purpose of this consensus statement is to provide clinicians with guidance on the use of ICD therapy in the management of some common populations of patients who are not represented in clinical trials and who therefore are not specifically included in the various guidelines that provide indications for ICD therapy. However, recommendations made in this document cannot account for all the nuances of clinical medicine and cannot replace careful clinical judgment for the care of an individual patient.This document is not meant to be a comprehensive guideline on a specific clinical subject. Recommendations are not given a Class recommendation; instead, phrases such as “is recommended,” “can be useful,” “can be considered,” and “is not recommended” are used. In addition, no levels of evidence are provided because there are no randomized controlled trials that have been specifically designed to address the clinical conditions posed by this document. The recommendations are largely based on subgroup analysis of randomized clinical trials, retrospective studies, analyses of large registries, and expert opinion. Similarly, this document does not use the same methodology as an Appropriate Use Criteria document.9For this consensus document, the writing group evaluated the available data on four important situations for which ICD therapy might be beneficial in selected populations that were not consistently included in randomized clinical trials: (1) use of an ICD in patients with an abnormal troponin that is not due to a myocardial infarction (MI), (2) use of an ICD within 40 days after a myocardial infarction, (3) use of an ICD within the first 90 days after revascularization, and (4) use of an ICD in the first 9 months after initial diagnosis of nonischemic cardiomyopathy. In addition, the writing group evaluated the utility of an atrial lead in a patient requiring ICD therapy without cardiac resynchronization therapy. The members of the writing group performed a comprehensive literature search, and then developed a series of recommendations with an explanation of the reasoning and research used to make each recommendation. Initial recommendations and alternatives were discussed and edited by the entire group. Final recommendations were sent to the entire group for anonymous voting. All recommendations presented in this document were agreed upon by at least 80% of the members of the writing group. The writing group members were selected by the following societies: Heart Rhythm Society, American College of Cardiology, American Heart Association, Heart Failure Society of America, and the Society of Thoracic Surgeons. Members of the writing group are from the United States, Canada, and Europe, and were selected as leaders in their fields with the majority of the writing group having no significant relationships with the medical device industry. All members of the writing committee were allowed to vote unless a significant relationship with industry was identified by the individual or the co-chairs.2. Current Guidelines that Address ICD UseSeveral Guidelines have been published that evaluate the use of ICDs in various clinical situations (Table 1).4–7 Although generally similar, there are some differences among the various documents because each group evaluated ICD implantation from a slightly different perspective. For example, three of the guidelines, the ACC/AHA/ESC 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death, the ACC/AHA/HRS 2008 Guidelines on Device-Based Therapy, and the 2009 ACC/AHA Focused Update of the 2005 Heart Failure Guidelines, addressed the use of non-CRT ICD therapy in patients with heart failure.4–6 The 2008 Guidelines on Device-Based Therapy and the 2009 Focused Update of the 2005 Heart Failure Guidelines provide specific ejection fraction cut-offs that parallel the values used in randomized clinical trials.4,5 In the text discussing the basis for the recommendations, the 2008 Guidelines on Device-Based Therapies noted that ejection fraction determination could be variable and suggested that clinicians rely on the most clinically accurate modality at their specific institution.5 Using a slightly different approach, the 2006 Guidelines on Ventricular Arrhythmias acknowledged the variability of many measures for ejection fraction and provided a range in the actual recommendations that provides increased flexibility at the cost of potential overuse.7 Clearly, the trend has been an emphasis on the incorporation of results from randomized clinical trials into the recommendations made by Guidelines documents.Table 1. Published Guideline Statements from Professional Societies that Make Recommendations on Implantation of ICDs without Cardiac Resynchronization Capabilities“Secondary Prevention”“Primary Prevention”2006 ACC/AHA/ESC Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac DeathICD therapy is recommended for secondary prevention of SCD in patients who survived VF or hemodynamically unstable VT, or VT with syncope and who have an LVEF ≤40%, who are receiving chronic optimal medical therapy, and who have a reasonable expectation of survival with good functional status for more than 1 year.An ICD should be implanted in patients with nonischemic DCM and significant LV dysfunction who have sustained VT or VF, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with good functional status for more than 1 year.Coronary revascularization is indicated to reduce the risk of SCD in patients with VF when direct, clear evidence of acute myocardial ischemia is documented to immediately precede the onset of VF.If coronary revascularization cannot be carried out and there is evidence of prior MI and significant LV dysfunction, the primary therapy of patients resuscitated from VF should be the ICD in patients who are receiving chronic optimal medical therapy, and who have a reasonable expectation of survival with a good functional status for more than 1 year.Patients presenting with sustained VT in whom low-level elevations in cardiac biomarkers of myocyte injury/necrosis are documented should be treated similarly to patients who have sustained ventricular tachycardia and in whom no biomarker rise is documented.ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF ≤30%–40%, are NYHA Class II or III receiving chronic optimal medical therapy, and have a reasonable expectation of survival with a good functional status for more than 1 year.ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with nonischemic heart disease who have an LVEF ≤30%–35%, are NYHA Class II or III, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with good functional status for more than 1 year.2008 ACC/AHA/HRS Guidelines for Device-Based TherapyICD therapy is indicated in patients who are survivors of cardiac arrest due to VF or hemodynamically unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes.ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable.ICD therapy is indicated in patients with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiologic study.ICD therapy is indicated in patients with LVEF <35% due to prior MI who are at least 40 days post-MI and are NYHA functional Class II or III.ICD therapy is indicated in patients with nonischemic DCM who have an LVEF ≤35% and who are NYHA Class II or III.ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF <30%, and are NYHA functional Class I.ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF <40%, and inducible sustained VT at electrophysiologic study.2013 ACC/AHA Guideline for the Management of Heart FailureICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with LVEF of 35% or less and NYHA Class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for more than 1 year.ICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients at least 40 days post-MI with LVEF of 30% or less, NYHA Class I symptoms while receiving GDMT, who have a reasonable expectation of meaningful survival for more than 1 year.2013 ACC/AHA Guideline for the Management of ST-Elevation Myocardial InfarctionICD therapy is indicated before discharge in patients who develop sustained VT/VF more than 48 hours after STEMI, provided the arrhythmia is not due to transient or reversible ischemia, reinfarction, or metabolic abnormalities.ACC = American College of Cardiology; ACC = American College of Cardiology Foundation; AHA = American Heart Association; DCM = dilated cardiomyopathy; ESC = European Society of Cardiology; GDMT = guideline-directed medical therapy; HRS = Heart Rhythm Society; ICD = implantable cardioverter-defibrillator; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; SCD = sudden cardiac death; STEMI = ST segment elevation myocardial infarction; VF = ventricular fibrillation; VT = ventricular tachycardia.3. Randomized Controlled Trials of ICD Therapy for Primary Prevention of Sudden Cardiac DeathSeven large randomized trials have evaluated the use of ICDs in patients at risk of sudden cardiac death due to heart failure or left ventricular dysfunction in the setting of prior MI (Table 2 and Figure 1).1,2,10–12 Each of the trials evaluated slightly different patient groups, and all of the trials, with the exception of the Coronary Artery Bypass Graft (CABG)-Patch trial, identified a patient population in whom the ICD conferred a survival benefit or reduced death from arrhythmia. Of the randomized trials, the CABG-Patch was unique in that all patients received revascularization with CABG at the time of randomization. In CABG-Patch, 900 patients with an ejection fraction (EF) <0.36 and an abnormal signal-averaged ECG who were undergoing bypass surgery were randomized to receive an ICD using epicardial patches or not.12 After an average follow-up of 32 months, the hazard ratio (HR) for death from any cause was 1.07 (95% confidence interval [CI]: 0.81–1.42, P=.64). ICD implantation was associated with a higher rate of postoperative infections (ICD: 12.3% vs control: 5.9%; P<.05) and deep sternal wound infections (ICD: 2.7% vs 0.4%, P<.05). Patients were excluded if they had prior significant ventricular arrhythmias or poorly controlled diabetes. The Multicenter Unsustained Tachycardia Trial (MUSTT) enrolled 2202 patients with coronary artery disease, an EF ≤0.40, and nonsustained ventricular tachycardia (NSVT) ≥3 beats, of whom 704 had sustained ventricular tachycardia (VT) inducible by programmed electrical stimulation.10 The patients with inducible sustained VT were randomized to no antiarrhythmic therapy or antiarrhythmic therapy guided by electrophysiologic (EP) study. After a median follow-up of 39 months, the 5-year estimates for overall mortality were 42% and 48%, respectively (relative risk: 0.80; 95% CI: 0.64–1.01). Within the EP-guided therapy group, 161 patients received an ICD (after one or more failed antiarrhythmic drug trials), and in this group, the adjusted relative risk of mortality was 0.40 (95% CI: 0.27–0.59). In the Multicenter Automatic Defibrillator Trial (MADIT), 196 patients with prior myocardial infarction, EF ≤0.35, and inducible nonsuppressible ventricular arrhythmias at electrophysiologic testing were randomized to receive an ICD or medical therapy alone.11 After an average follow-up of 27 months, the ICD was associated with a significant reduction in mortality (HR: 0.46; 95% CI: 0.26–0.82; P=.009). In the Multicenter Automatic Defibrillator Trial II (MADIT-II) 1232 patients with an EF ≤0.30 due to prior myocardial infarction were randomized to ICD therapy or medical therapy alone.2 During an average follow-up of 20 months, the ICD was associated with a significant reduction in mortality (HR: 0.69; 95% CI: 0.51–0.93; P=.016). Finally, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) randomized 2521 patients with an ejection fraction ≤0.35 and Class II or III heart failure symptoms to ICD therapy, placebo, or amiodarone. In SCD-HeFT slightly more than 50% of patients had cardiac dysfunction and heart failure due to coronary artery disease. After a median follow-up of 45 months, ICD therapy was associated with a significant reduction in mortality (HR: 0.77; 97.5% CI: 0.62–0.96; P=.007).1Table 2. Randomized Primary Prevention Trials of ICD therapy: Inclusion Criteria, Enrolled Patients, and Principal FindingsStudyInclusion CriteriaEnrolled PatientsFindingsIschemic Cardiomyopathy Multicenter Automatic Defibrillator Implantation Trial (MADIT)11Prior MI, LVEF ≤0.35; NSVTInducible nonsuppressible sustained VT/VF at EPS>3 weeks post-MI>2 months post-CABG>3 months post-PTCA196 patients enrolled, 95 in ICD armMean age: 63 years92% maleMean LVEF: 0.2690 with prior CABG, 44 with prior PTCA, 53 with ≥2 prior MIs100% NSVTReduced mortality with ICD (HR: 0.46; P=.009)Coronary Artery Bypass Graft (CABG) Patch Trial12LVEF ≤0.35, abnormal SAECG, undergoing CABG900 patients enrolled, 446 randomized to epicardial ICD implantation at time of CABGMean age: 64 years84% maleMean LVEF: 0.27100% CABGNo difference in survival with ICD (HR: 1.07; 95% CI: 0.81–1.42; P=.64)Arrhythmic mortality at 42 months: control 6.9%, ICD 4.0% (P=.057) – 45% reduction in arrhythmic death71% of deaths were nonarrhythmic: nonarrhythmic cardiac mortality at 42 months: control 12.4%, ICD 13.0% (P=.275)Multicenter Unsustained Tachycardia Trial (MUSTT)10EF ≤0.40NSVT within the last 6 months≥4 days post-MI or revascularization2202 patients enrolled, 704 patients with inducible VT, 161 received ICDsMedian age: 67 years90% maleMedian EF: 0.3056% prior CABG16% within 30 days of an MI100% NSVTNYHA Class (I/II/II/IV): 37/39/24/0Risk of sudden death reduced in patients with ICDs (HR: 0.24; 95% CI: 0.13–0.45; P<.001)Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)2>21 years oldEF ≤0.30>1 month after MI>3 months after revascularization1232 patients enrolled, 742 in ICD armMedian age: 64 years84% maleEF: 0.2357% prior CABGNYHA Class (I/II/II/IV): 35/35/25/5After average f/u of 20 months, ICD group had lower mortality (HR: 0.69; 95% CI: 0.51–0.93; P=.016)ICD associated with an absolute 5.6% decrease in mortalityNonischemic CardiomyopathyDefibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)16EF <36% due to NICMNYHA Class I–IIINSVT or PVCs458 patients enrolled, 229 received ICDsMean age: 58 years71% maleEF: 21%NYHA Class (I/II/III): 22/57/21216 patients (47%) with a recent diagnosis of NICM (≤9 months)After mean f/u of 29 months, trend for reduced mortality in the ICD group (HR: 0.65; 95% CI: 0.40–1.06; P=.08) and a significant decrease in sudden death due to arrhythmias (HR: 0.20; 95% CI: 0.06–0.71; P=.006)Subanalysis showed similar ICD benefit in patients with recently identified NICM (<9 months) compared with remote diagnosisBoth Ischemic and Nonischemic CardiomyopathySudden Cardiac Death in Heart Failure Trial (SCD-HeFT)118 years oldEF <35%NYHA Class II or III2521 patients enrolled, 829 received ICDsMedian age: 60 years76% maleEF: 0.2533 patients within 30 days of an MI23% NSVTNYHA Class (I/II/II/IV): 0/70/30/0After median f/u of 46 months, ICD group had lower mortality (HR: 0.77; 97.5% CI: 0.62–0.96; P=.007) compared with placebo or amiodarone groupsICD associated with an absolute 7.2% decrease in mortalityAcute Coronary Artery DiseaseDefibrillator in Acute Myocardial Infarction Trial (DINAMIT)1418–80 years oldMI past 6–40 daysEF <0.35Abnormal HRV674 patients enrolled, 332 received ICDsAverage age: 61 years76% maleEF: 0.28Index MI:72% Anterior72% new Q wavePeak CK: 2300 U/LReperfusion: 63%26% PCI27% thrombolysis10% bothAfter mean f/u of 30 months, no difference in mortality between ICD and no ICD groups (HR: 1.08; 95% CI: 0.76–1.55; P=.66)ICD group had a significant decrease in risk of death due to arrhythmia (HR: 0.42; 95% CI: 0.22–0.83; P=.009) but a significant increase in risk of nonarrhythmic death (HR: 1.75; 95% CI: 1.11–2.76; P=.02)Immediate Risk Stratification Improves Survival Study (IRIS)15MI in the past 5–31 days and either:EF ≤40% and initial HR >90 bpmNSVT >150 bpm898 enrolled, 445 received ICDsAverage age: 63 years77% maleEF: 0.35Index MI:64% anterior77% STEMIReperfusion: 77%72% PCI16% thrombolysis (+/– PCI)After mean f/u of 37 months, no difference in mortality between the ICD and no ICD groups (HR: 1.04; 95%CI: 0.81–1.35; P=.78)ICD group had a significant decrease in sudden cardiac death (HR: 0.55; 95% CI: 0.31–1.00; P=.049) but a significant increase in risk of nonsudden cardiac death (HR: 1.92; 95% CI: 1.29–2.84; P=.001)MI = myocardial infarction; LVEF = left ventricular ejection fraction; VT= Ventricular tachycardia; VF = Ventricular fibrillation; NSVT = Nonsustained ventricular tachycardia; CABG = Coronary artery bypass grafting; PCI = Percutaneous coronary intervention; ICD = Implantable cardioverter defibrillator; NYHA = New York Heart Association; HR = Hazard ratio; NICM = Nonischemic cardiomyopathy; PVCs = Premature ventricular contractions; HRV = Heart rate variability; STEMI = ST segment elevation myocardial infarctionDownload figureDownload PowerPointFigure 1. Survival curves for the ICD-only primary prevention trials in patients with cardiomyopathy (CM) due to coronary artery disease (CAD) or acute myocardial infarction (MI), heart failure, or nonischemic CM. All curves represent mortality/survival. MADIT = Multicenter Automatic Defibrillator Trial; MUSTT = Multicenter Unsustained Tachycardia Trial; CABG-Patch = Coronary Artery Bypass Graft-Patch; DINAMIT = Defibrillator in Acute Myocardial Infarction Trial; IRIS = Immediate Risk Stratification Improves Survival Study; SCD-HeFT = Sudden Cardiac Death in Heart Failure Trial; DEFINITE = Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation Trial. (With Permission New England Journal of Medicine.1,2,10-12,14-16)It is instructive to examine the clinical characteristics of patients who were actually enrolled in the trials (Table 2).1,2,10–12 The median age of enrolled patients was 63–67 years, and patients >75 years accounted for 554 (11%) of the patients enrolled in MUSTT, MADIT-I, MADIT-II, and SCD-HeFT.13 The trials predominantly studied men, with women accounting for only 8%–24% of enrollees. Ethnic background was identified in the MUSTT and SCD-HeFT trials. Nonwhite patients accounted for 9% of patients in MUSTT and 24% of patients in SCD-HeFT. The baseline cardiovascular characteristics varied between the trials. Although EF was similar for all five trials, ranging from 0.23–0.30, 80% of patients in MUSTT had Class I or II heart failure symptoms, 70% of patients in MADIT II had Class I or II heart failure symptoms, and 67% of patients in MADIT and 100% of patients in SCD-HeFT had Class II or III heart failure symptoms. Prior revascularization with CABG also varied among the three studies, at approximately 50% of patients with ischemic cardiomyopathy in SCD-HeFT, 45% in MADIT, 56% in MUSTT, 57% in MADIT-II, and of course 100% in CABG-Patch. NSVT was part of the inclusion criteria for MADIT and MUSTT and thus was present in all patients but was present in only 23% of patients in SCD-HeFT. The incidence of NSVT was not provided in initial or subsequent reports on the CABG-Patch or MADIT-II trials.Two trials have evaluated the use of ICDs in patients in the acute period after MI.14,15 In the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT), 674 patients were randomized between 6 to 40 days after an MI to receive an ICD or no ICD therapy.14 Additional inclusion criteria included a left ventricular ejection fraction (LVEF) ≤0.35 and impaired cardiac autonomic function. After a mean follow-up of 30 months, there was no mortality benefit associated with the ICD implant (HR: 1.08; 95% CI: 0.76–1.55; P=.66). In the Immediate Risk-Stratification Improves Survival (IRIS) trial, 898 patients were randomized between 5 to 31 days after an MI to receive an ICD or no ICD therapy.15 Unlike DINAMIT, patients could be enrolled in IRIS under two clinical scenarios, either an LVEF ≤0.40 associated with an initial sinus rate >90 bpm, or NSVT (>3 beats at a rate >150 bpm) identified by 24-hour ambulatory ECG. After a mean follow-up of 37 months, ICD therapy was not associated with a significant reduction in mortality (HR: 1.04; 95% CI: 0.81–1.35; P=.78). Similar to the primary prevention trials discussed previously, both studies predominantly enrolled men (76%–77%) who were in their early 60s (average age 61–63 years). As expected, the average LVEF was higher in IRIS (0.35) when compared with DINAMIT (0.28) because 23% of patients were enrolled in IRIS based on the presence of NSVT. In both studies, anterior wall MIs accounted for two-thirds of the index MIs. Reperfusion therapy in DINAMIT was performed in approximately 60% of patients, evenly split between thrombolysis and percutaneous coronary intervention (PCI). Reperfusion therapy was attempted in 77% of patients in IRIS, with three-fourths of these patients receiving PCI.Two large studies on ICD therapy in patients with nonischemic cardiomyopathy have been completed.1,16 In SCD-HeFT, 1211 patients (slightly less than 50% of the total group) had heart failure due to nonischemic cardiomyopathy.1 In a prespecified analysis of this patient group, ICD therapy conferred a trend toward a survival advantage (HR: 0.73; 97.5% CI: 0.50–1.07; P=.06). The apparent decrease in the magnitude of benefit conferred by the ICD is in part explained by the lower event rate observed in patients with nonischemic cardiomyopathy when compared with patients with ischemic cardiomyopathy (5-year event rate with ICD therapy: ischemic 0.359 vs nonischemic 0.214). The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial evaluated only patients with nonischemic cardiomyopathy.16 A total of 458 patients with nonischemic cardiomyopathy, LVEF <0.36, and frequent pre