Background: The number of patients with congestive heart failure is growing. Cardiac resynchronization therapy has been the focus of multiple studies. It involves pacing the right and left ventricles simultaneously to improve myocardial efficiency, and it has been shown to decrease morbidity and mortality compared with medical therapy alone. Until the Resynchronization/Defibrillation for Ambulatory Heart Failure Trial, studies had not shown improved mortality rates in patients with mild to moderate heart failure treated with cardiac resynchronization therapy and an implantable defibrillator. Wells and colleagues investigated the effect of cardiac resynchronization therapy combined with optimal medical therapy or with an implantable defibrillator in patients with symptomatic heart failure or arrhythmia.

The Study: Eligible trials evaluated the effects of cardiac resynchronization therapy compared with control therapy in patients who had arrhythmia or symptomatic heart failure with a QRS interval greater than 120 milliseconds. Comparisons were made between cardiac resynchronization therapy with optimal medical therapy versus optimal medical therapy alone, and between cardiac resynchronization therapy with an implantable defibrillator versus a standard implantable defibrillator alone. Optimal medical therapy included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, diuretics, and spironolactone (Aldactone), if indicated. The primary outcome was all-cause mortality.

The authors searched Medline, EMBASE, and the Cochrane library for randomized controlled trials from the past 30 years. The Cochrane Risk of Bias Tool was applied to screen for biases. For statistical analysis, the data were combined using the random-effects model, and treatment effect was conveyed as a relative risk. Additional analysis was performed for each New York Heart Association (NYHA) subgroup.

Results: The search results were narrowed from 3,071 studies to 12, which were the focus of the meta-analysis. Cardiac resynchronization therapy with optimal medical therapy significantly reduced mortality compared with optimal medical therapy alone (relative risk [RR] = 0.73; 95% confidence interval [CI], 0.62 to 0.85). Cardiac resynchronization therapy plus an implantable defibrillator also significantly reduced mortality when compared with an implantable defibrillator alone (RR = 0.83; 95% CI, 0.72 to 0.96). Improved mortality with the combination of cardiac resynchronization therapy and an implantable defibrillator was significant only in patients with NYHA class I or II heart failure (RR = 0.80; 95% CI, 0.67 to 0.96) and not NYHA class III or IV. The authors note that there were fewer patients with class III heart failure in the studies reviewed, which may have affected the outcomes.

Conclusion: Cardiac resynchronization therapy in combination with optimal medical therapy significantly reduced mortality in patients with heart failure, including advanced heart failure (NYHA class III and IV), which supports the 2008 guidelines from the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society. Cardiac resynchronization therapy in combination with an implantable defibrillator significantly reduced mortality in patients with mildly symptomatic heart failure (NYHA class I or II).