Cardiac resynchronization therapy in patients with mild heart failure: A systematic review and meta-analysis

Purpose: Cardiac resynchronization therapy (CRT) reduces symptoms and improves survival in patients with advanced heart failure (New York Heart Association (NYHA) functional class III-IV), reduced ejection fraction, and wide QRS complex. Whether CRT has the same benefit also in asymptomatic or mildly symptomatic heart failure patients is controversial. Our objective is to summarize the available evidence on the effects of CRT in asymptomatic or mildly symptomatic (NYHA I-II) heart failure patients. Methods: We searched major web databases for randomized controlled trials of CRT in patients with mild heart failure (NYHA functional class I-II). Data regarding all-cause mortality, heart failure events, left ventricular (LV) volumes and ejection fraction, and worsening of NYHA functional class were extracted. Results: We identified five trials (CONTAK-CD, MIRACLE ICD-II, REVERSE, MADIT-CRT, and RAFT) that enrolled 4,213 patients (91% with NYHA II functional class). Primary analysis excluded the CONTAK-CD, which was not specifically conducted on patients with mild heart failure. At pooled analysis, CRT decreased mortality (odds ratio (OR), 0.78 [95% confidence interval (CI)], 0.63 to 0.97; p=0.024) and heart failure events (OR, 0.63 [95% CI, 0.52 to 0.76], p<0.001), induced a significant LV reverse remodeling (weighted mean difference (WMD) of LV ejection fraction =+4.8%[95% CI, + 0.9 to+ 8.7%], p=0.015 and WMD of LV end-systolic volume index = -19.4mL/m ²[95%CI, - 18.2 to - 20.7mL/m ²], p<0.001) and prevented the progression of heart failure symptoms (OR for worsening of NYHA functional class= 0.54 [95% CI, 0.31 to 0.93], p=0.026). Inclusion of the CONTAK-CD did not change the results. Conclusions: Among patients with mild (NYHA II) heart failure, CRT reduces mortality and the risk of heart failure events, induces a favorable LV reverse remodeling and slows the progression of heart failure symptoms.