Correspondence

Implantable Cardioverter–Defibrillators

N Engl J Med 2009; 360:937-938February 26, 2009

Article

To the Editor:

In his article on implantable cardioverter–defibrillators (ICDs) after myocardial infarction, Myerburg (Nov. 20 issue)1 summarizes the major ICD trials and makes recommendations regarding primary prevention. Unfortunately, he does not mention background medical therapy for the treatment of patients with heart failure, a previous myocardial infarction, and a low ejection fraction. This omission is especially worrisome since optimal medical therapy can promote reverse remodeling, can have a beneficial effect on the ejection fraction, and can reduce morbidity and mortality. Medical therapy was typically required before eligibility for the trials described in this review. For example, the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II)2 entry criteria stated that the “appropriate use of beta-blockers, angiotensin-converting–enzyme [ACE] inhibitors, and lipid-lowering drugs was strongly encouraged in both groups.” A total of 70% of the patients received ACE inhibitors and 70% received beta-blockers. Similarly, in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),3 in which the use of these drugs was an entry requirement, 85% of the patients received ACE inhibitors, 96% ACE inhibitors or angiotensin-receptor blockers, and 80% beta-blockers. Myerburg does state concern that “ICDs may be used too broadly,” but if patients are not receiving appropriate evidence-based medical therapy, the overuse of these devices, as well as their effectiveness, will be even more worrisome.

Marrick L. Kukin, M.D.
St. Luke's–Roosevelt Hospital, New York, NY 10019
mkukin@chpnet.org

3 References

1. 1

   Myerburg RJ. Implantable cardioverter-defibrillators after myocardial infarction. N Engl J Med 2008;359:2245-2253
   Full Text | Web of Science | Medline

2. 2

   Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883
   Full Text | Web of Science | Medline

3. 3

   Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237[Erratum, N Engl J Med 2005;352:2146.]
   Full Text | Web of Science | Medline

To the Editor:

ICD therapy decreases mortality among high-risk patients with a depressed ejection fraction (<35%) and symptoms of New York Heart Association (NYHA) class II or III heart failure. Myerburg points out that “patients with NYHA class IV heart failure are not considered candidates for ICD therapy.” However, it is notable that the indication for ICD therapy in patients with class IV heart failure has expanded from mere use as a bridge to transplantation to include as potential candidates those patients who are also receiving cardiac-resynchronization therapy (CRT).1 In one trial involving patients with advanced heart failure, the risk of the combined end point of death or hospitalization for heart failure was significantly reduced in the CRT-defibrillator group.2 In patients with class IV heart failure, the time to sudden death was significantly reduced in the CRT-defibrillator group.3 A significant reduction in the time to death or hospitalization was also seen in a large trial involving 813 patients (P<0.001).4 Thus, ICD therapy is contraindicated in patients with class IV heart failure except as a bridge to transplantation or if they are receiving CRT.1

Roger Kapoor, M.D., M.B.A.
University of Chicago, Chicago, IL 60637

John R. Kapoor, M.D., Ph.D.
Stanford University, Stanford, CA 94305

4 References

1. 1

   Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary. Heart Rhythm 2008;5:934-955
   CrossRef | Web of Science | Medline

2. 2

   Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150
   Full Text | Web of Science | Medline

3. 3

   Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation 2007;115:204-212
   CrossRef | Web of Science | Medline

4. 4

   Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549
   Full Text | Web of Science | Medline

Author/Editor Response

Kukin's point that accepted medical therapy is important for ICD candidates is valid, but self-evident. The ICD trial outcomes reflect protocols (and enrollment realities) that included these therapies. However, we know little about the interactions between multiple, independently tested, commonly used interventions1,2 (Figure 1Figure 1Effects of Multiple Interventions on Cardiovascular Mortality and Sudden Cardiac Death.). Designs of clinical trials limit our ability to determine whether multiple strategies have effects that are additive, synergistic, neutral, or less than the sum of the individual benefits.2 Thus, even though they are appropriately recommended, we cannot easily measure the cumulative effects of multiple therapies, and we can only speculate about variations in benefit according to whether or not ICD recipients actually receive evidence-based medical therapies.

Kapoor and Kapoor suggest that in addition to the use of ICDs as a bridge to transplantation, there should be a formal indication for ICD in patients with class IV heart failure who are candidates for CRT. Although there is reasonable support for combined CRT–ICDs in patients with class III heart failure, the trials cited provide limited scientific guidance regarding the use of these devices in patients with class IV heart failure. Class IV was underrepresented in the studies, and it is associated with a poor prognosis without transplantation. Both studies used composite primary end points of death or first hospitalization, with the censoring events dominated by hospitalizations and nonsudden deaths, and similar benefits shown with the use of CRT and CRT–ICD. As Epstein et al. noted in the 2008 updated guidelines cited by Kapoor and Kapoor, the use of CRT–ICDs should be considered on the basis of clinical judgment in individual patients with class IV heart failure, rather than as an evidence-based guideline.

Robert J. Myerburg, M.D.
University of Miami Miller School of Medicine, Miami, FL 33101
rmyerbur@med.miami.edu

5 References

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   Myerburg RJ, Mitrani R, Interian A Jr, Castellanos A. Interpretation of outcomes of antiarrhythmic clinical trials: design features and population impact. Circulation 1998;97:1514-1521
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   Califf RM, DeMets DL. Principles from clinical trials relevant to clinical practice. Circulation 2002;106:1015-1021
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   Beta-Blocker Heart Attack (BHAT) Investigators. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA 1982;247:1707-1714
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   Domanski MJ, Exner DV, Borkowf CB, Geller NL, Rosenberg Y, Pfeffer MA. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarctions: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999;33:598-604
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   Hallstrom AP, Cobb LA, Ray R. Smoking as a risk factor for recurrence of sudden cardiac arrest. N Engl J Med 1986;314:271-275
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