Meta-Analysis: Cardiac Resynchronization Therapy for Patients With Less Symptomatic Heart Failure

Study Questions:

Do patients with systolic heart failure benefit from cardiac resynchronization therapy (CRT) regardless of New York Heart Association (NYHA) class at the time of implant?


This was a meta-analysis of trials enrolling ≥25 patients that assessed the impact of CRT versus control (inactive pacing, right ventricular pacing alone, left ventricular pacing alone, or implantable cardioverter-defibrillator alone) in patients with a left ventricular ejection fraction ≤40%. No restriction on NYHA class was made. The primary outcome was all-cause mortality with secondary outcomes of heart failure hospitalization, and changes in quality of life and 6-minute walk test (6MWT) distance. The efficacy of CRT with respect to the above outcomes was assessed in patients with NYHA class I/II versus III/IV symptoms.


Twenty-five trials with 9,082 total patients were included in the meta-analysis, only three of which were nonblinded. Of these, 24 included only patients with a QRS ≥120 msec, three enrolled patients (n = 2,616 total) exclusively with NYHA class I or II symptoms, and 11 enrolled patients (n = 3,445) exclusively with NYHA class III or IV symptoms. Overall, CRT reduced all-cause mortality by 19% (relative risk [RR], 0.81; 95% confidence interval [CI], 0.72-0.90), and this mortality benefit was mostly driven by reductions in heart failure death (RR, 0.64; 95% CI, 0.49-0.83), with no significant impact on sudden cardiac death. In those trials that exclusively enrolled NYHA class I/II patients, the RR for all-cause mortality with CRT was 0.80 (95% CI, 0.67-0.96) compared with RR, 0.80 (95% CI, 0.70-0.92) in those trials exclusively enrolling NYHA class III/IV patients. CRT reduced heart failure hospitalization by 31% (RR, 0.69; 95% CI, 0.58-0.82), and the risk was similar between trials exclusively enrolling NYHA class I/II patients (RR, 0.71) and class III/IV (RR, 0.65). In contrast to NYHA class III/IV patients, trials exclusively enrolling NYHA class I/II patients did not demonstrate significant improvements in 6MWT or quality-of-life scores.


The authors concluded that CRT benefits patients with reduced left ventricular ejection fraction and a prolonged QRS interval regardless of NYHA class.


This meta-analysis provided very important information regarding the benefit of CRT in patients with less severe heart failure symptomatology. Interestingly, while CRT did not provide a marked improvement in functional status or quality of life in NYHA class I/II patients, it did reduce mortality by 17% and hospitalization by 29%. However, the generalizability of benefit from CRT for asymptomatic heart failure patients remains in question, since only 15% of patients were class I. Further, one can hypothesize that the survival benefit of CRT will extend to those with atrial fibrillation, but more data are needed. We are gleaning information on CRT in the less ill, but more studies are needed. Further, VO2 testing would help identify those patients who are truly class I.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Risk, Heart Failure, Stroke Volume, Atrial Fibrillation, New York, Heart Ventricles, Hospitalization, Cardiac Resynchronization Therapy

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