Twenty-five RCTs (n=9,082 patients), of which 14 were newly identified trials from updated searches, met the inclusion criteria. Six trials were described as low risk of bias, six showed high risk of bias, and for 13 the risk of bias was unclear. Fourteen trials were double-blind, eight were single-blind, and three were open-label trials. Patients in 18 trials were randomly assigned after successful device implantation, but in six trials patients were randomised before device implantation. Sixteen RCTs used parallel study design and nine trials involved cross-over design. Duration of follow-up ranged from one to 40 months.
There was a significant reduction in all-cause mortality with cardiac resynchronization therapy (RR 0.81, 95% CI 0.72 to 0.90; 25 trials, n=9,082 patients). This finding did not change in any of the sensitivity analyses.
Cardiac resynchronization therapy was associated with a reduction in the risk for heart failure hospitalisation (RR 0.69, 95% CI 0.58 to 0.82; 15 trials, n=7,012 patients) and improved left ventricular ejection fraction (WMD 0.0364, 95% CI 0.0189 to 0.0539; 11 trials, n=3,202 patients).
Cardiac resynchronization therapy was associated improved functional scores on the Minnesota Living with Heart Failure Questionnaire (WMD 6.56 points, 95% CI 4.08 to 9.04; 14 trials, n=4,283 patients) and six-minute walk test (WMD 17.50 minutes, 95% CI 7.05 to 27.94; 15 trials, n=3,475 patients).
There was significant heterogeneity between trials in the outcomes assessed except for all-cause mortality.
There was no statistically significant difference in effect of cardiac resynchronization therapy between the subgroups of patients with New York Heart Association (NYHA) class I/II and NYHA class III/IV symptoms in all the outcomes assessed, except that functional outcomes did not improve appreciably in patients with milder symptoms (NYHA class I/II). Left ventricular pacing alone did did not affect any of the outcomes.
The implantation success rate for cardiac resynchronization therapy was 94.4% (95% CI 93.8% to 94.8%). The rates of complications for cardiac resynchronization therapy included mechanical complications in 3.2% (95% CI 2.8 to 3.6) of patients, device malfunction in 1.9% (95% CI 1.5% to 2.4%), lead problems in 6.2% (95% CI 5.6 to 6.8), and infections in 1.4% (95% CI 1.1 to 1.7). Peri-implantation death occurred in 0.3% (95% CI 0.2 to 0.5)of patients undergoing cardiac resynchronization therapy.
The funnel plot suggested potential publication bias for heart failure hospitalisation.