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Cardiac Resynchronization and Death From Progressive Heart Failure: A Meta-analysis of Randomized Controlled Trials

David J. Bradley, MD, PhD; Elizabeth A. Bradley, MD; Kenneth L. Baughman, MD; Ronald D. Berger, MD, PhD; Hugh Calkins, MD; Steven N. Goodman, MD, PhD; David A. Kass, MD; Neil R. Powe, MD, MPH, MBA
JAMA. 2003;289(6):730-740. doi:10.1001/jama.289.6.730.
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Context Progressive heart failure is the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based therapy for heart failure, enhances cardiac performance and quality of life, but its effect on mortality is uncertain.

Objective To determine whether cardiac resynchronization reduces mortality from progressive heart failure.

Data Sources MEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov database, the US Food and Drug Administration Web site, and reports presented at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.

Study Selection Eligible studies were randomized controlled trials of cardiac resynchronization for the treatment of chronic symptomatic left ventricular dysfunction. Eligible studies reported death, hospitalization for heart failure, or ventricular arrhythmia as outcomes. Of the 6883 potentially relevant reports initially identified, 11 reports of 4 randomized trials with 1634 total patients were included in the meta-analysis.

Data Extraction Trial reports were reviewed independently by 2 investigators in an unblinded standardized manner.

Data Synthesis Follow-up in the included trials ranged from 3 to 6 months. Pooled data from the 4 selected studies showed that cardiac resynchronization reduced death from progressive heart failure by 51% relative to controls (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls. Cardiac resynchronization also reduced heart failure hospitalization by 29% (OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not associated with a statistically significant effect on non–heart failure mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter defibrillators, cardiac resynchronization had no clear impact on ventricular tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).

Conclusions Cardiac resynchronization reduces mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction. This finding suggests that cardiac resynchronization may have a substantial impact on the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization also reduces heart failure hospitalization and shows a trend toward reducing all-cause mortality.

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Figure 1. Reports Evaluated for Inclusion in the Meta-analysis
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FDA indicates US Food and Drug Administration.
Figure 2. Death Among Patients Randomized to Cardiac Resynchronization vs No Resynchronization
Graphic Jump Location
CI indicates confidence interval; CR, cardiac resynchronization; MIRACLE, Multicenter InSync Randomized Clinical Evaluation; MUSTIC, Multisite Stimulation in Cardiomyopathies. Odds ratio less than 1.0 favors CR. Weight refers to weight given to each trial in statistical model. Boxed area is proportional to weight. A, odds ratio refers to odds ratio of death from progressive heart failure among patients randomized to CR vs no CR. Heterogeneity χ22 = 0.34 (P = .85). B, Odds ratio refers to the odds ratio of non–heart failure death among patients randomized to CR vs no CR. Heterogeneity χ23 = 0.43 (P = .93). C, Odds ratio refers to the odds ratio of death from all causes among patients randomized to CR vs no CR. Heterogeneity χ23 = 0.90 (P = .83).
Figure 3. Heart Failure Hospitalization Among Patients Randomized to Cardiac Resynchronization vs No Cardiac Resynchronization
Graphic Jump Location
CI indicates confidence interval; CR, cardiac resynchronization; MIRACLE, Multicenter InSync Randomized Clinical Evaluation; MUSTIC, Multisite Stimulation in Cardiomyopathies. Odds ratio refers to the odds ratio of heart failure hospitalization among patients randomized to CR vs no CR. Odds ratio less than 1.0 favors CR. Weight refers to weight given to each trial in statistical model. Boxed area is proportional to weight. Heterogeneity χ22 = 0.43 (P = .93).

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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