Abstract
BACKGROUND: Biventricular pacing (BiVP) is the conventional approach for cardiac resynchronization therapy (CRT), yet approximately one-third of patients show no clinical response. Left bundle branch area pacing (LBBAP) enables more physiological ventricular activation through His-Purkinje conduction, but its impact on key clinical endpoints such as all-cause mortality and heart failure hospitalization (HFH) remains debated. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and CNKI (to May 3, 2025) identified 24 studies encompassing 6,538 patients. Study quality was assessed using Cochrane RoB 2.0 and the Newcastle-Ottawa Scale. Subgroup analyses (by follow-up duration, study design, and sex), leave-one-out sensitivity analysis, and meta-regression were performed to assess result robustness and heterogeneity sources. Trim-and-fill correction was applied to adjust for potential publication bias. RESULTS: LBBAP was associated with a markedly lower risk compared to BiVP across several clinical outcomes. Specifically, it significantly reduced the risk of the composite endpoint (HR: 0.67, 95% CI: 0.59-0.75), all-cause mortality (HR: 0.83, 95% CI: 0.71-0.96), and HFH (HR: 0.58, 95% CI: 0.50-0.67). Echocardiographic outcomes further supported LBBAP superiority, with higher rates of echocardiographic response (OR: 1.57, 95% CI: 1.36-1.81) and super-response (OR: 2.12, 95% CI: 1.62-2.76). Improvements in left ventricular ejection fraction (LVEF) were greater with LBBAP at both 3-6 months (MD: 5.31%, 95% CI: 4.63-5.99) and ≥12 months (MD: 4.43%, 95% CI: 2.27-6.60). Similarly, left ventricular end-diastolic diameter (LVEDD) reductions were more pronounced at 3-6 months (MD: -3.48 mm, 95% CI: -5.76 to -1.21) and ≥12 months (MD: -2.86 mm, 95% CI: -5.05 to -0.68). CONCLUSIONS: These findings indicate that LBBAP provides superior clinical and structural outcomes compared to BiVP in patients undergoing CRT. Large-scale, multicenter randomized controlled trials are warranted to confirm these results, assess long-term efficacy, and elucidate gender-specific variations to optimize evidence-based CRT delivery. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251055488, PROSPERO CRD420251055488.