Left Bundle Branch Versus Biventricular Pacing for Cardiac Resynchronization Therapy in Heart...

Background: Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP) is established as a guideline-directed intervention for patients with heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). Left bundle branch pacing (LBBP) has emerged as a physiological alternative that directly recruits the native His-Purkinje conduction system, potentially delivering superior electrical and mechanical resynchronization. Despite growing observational evidence, randomized trial data comparing LBBP and BiVP remain limited. This meta-analysis synthesizes all available randomized controlled trial (RCT) evidence. Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to June 2026. Two independent reviewers screened studies and extracted data. We included prospective RCTs comparing dedicated LBBP with BiVP in adults with HFrEF and LBBB. The primary outcome was the change in left ventricular ejection fraction (LVEF) from baseline. Secondary outcomes included super-response rate, heart failure hospitalization (HFH), all-cause mortality, paced QRS duration, and safety. We used random-effects to do the analysis and assessed heterogeneity with the I 2 statistic. Results: Two RCTs met full eligibility criteria, enrolling a total of 240 patients. Both trials enrolled patients with nonischemic cardiomyopathy predominating and LBBB. Pooled analysis showed that LBBP was associated with significantly greater LVEF improvement compared with BiVP (mean difference: +6.1%; 95% CI: 1.6%-10.6%; P=0.007; I 2 =0%). Super-response rates were consistently higher with LBBP (60% vs 39%). In the long-term HeartSync-LBBP trial, LBBP significantly reduced the composite of all-cause mortality and HFH (8% vs 28%; HR 0.26; 95% CI 0.12-0.57; P<0.001) as well as a marked reduction in HFH (7% vs 28%; HR 0.23; 95% CI 0.10-0.52; P<0.001). All-cause mortality was numerically lower with LBBP (2% vs 5%; HR 0.40; P=0.25). Paced QRS duration was significantly shorter with LBBP (126.05-ms vs 136.6-137 ms). Success rates were high in both arms (94% for LBBP; 87% for BiVP). No major procedural complications were attributable to LBBP. Conclusions: In patients with HFrEF and LBBB, LBBP achieved significantly greater improvements in LVEF and super-response rates than BiVP across randomized trials, and was associated with substantially lower rates of heart failure hospitalization on long-term follow-up. These findings support LBBP as a superior alternative to BiVP for CRT in eligible patients with LBBB. Larger multicenter trials with diverse populations and longer follow-up are warranted to establish mortality benefit and generalizability.