Two-Lead Versus Conventional Three-Lead Cardiac Resynchronization Therapy in Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) with reduced ejection fraction, but conventional CRT defibrillator (CRT-D) systems require 3 transvenous leads and may increase lead-related complications. Two-lead CRT systems may reduce hardware burden while preserving CRT efficacy in selected patients with intact sinus node function. We systematically searched PubMed, Embase, and Cochrane CENTRAL through May 2026 for randomized and observational studies comparing 2-lead CRT-DX or single-pass Ventricular Dual-Dual CRT with conventional 3-lead CRT-D in adults with guideline-indicated CRT. Primary outcomes were all-cause mortality, atrial lead complications, major complications, and HF hospitalization. Secondary outcomes included echocardiographic response, change in left ventricular ejection fraction, CRT pacing percentage, and procedure time. Five studies (n = 1156) were included. Compared with 3-lead CRT-D, 2-lead CRT was associated with significantly fewer atrial lead complications (odds ratio 0.31, 95% confidence interval [CI] 0.13-0.75; P = 0.009), fewer major complications overall (odds ratio 0.45, 95% CI 0.24-0.86; P = 0.015), and shorter procedure time (mean difference -13.11 minutes, 95% CI -18.71 to -7.51; P < 0.001). No significant differences were observed in all-cause mortality, HF hospitalization, echocardiographic response, change in left ventricular ejection fraction, or CRT pacing percentage. In selected CRT candidates without an atrial pacing indication, 2-lead CRT-DX appears to provide comparable clinical and echocardiographic outcomes to conventional 3-lead CRT-D, while reducing lead-related complications and procedure time. These findings support consideration of lead-sparing strategies, although larger randomized trials with longer follow-up are needed.