Conduction system pacing vs. biventricular pacing for cardiac resynchronization therapy in heart failure: a systematic review and meta-analysis considering randomized controlled trials and observational studies.

AIMS: Biventricular pacing (BiVP) is the gold standard for cardiac resynchronization therapy (CRT) in heart failure with reduced ejection fraction (HFrEF), yet up to 30% of patients fail to respond. Conduction system pacing (CSP) has emerged as an alternative with potential for physiological superiority. Multiple 2026 multicentre randomized controlled trials (RCTs) reported contradictory results, necessitating an updated meta-analysis. This analysis aims to compare the safety and efficacy of CSP vs. BiVP for CRT in patients with HFrEF. METHODS AND RESULTS: PubMed, Cochrane CENTRAL, and Embase were searched (January 2010-May 2026) for RCTs and observational studies. Pooled risk ratios (RRs) and mean differences (MDs) were estimated using random-effects restricted maximum likelihood models. Twenty-five studies (11 RCTs, n = 1201; 14 observational, n = 3376) involving 4577 participants were included. In the RCT-only analysis, no significant differences were found in all-cause mortality (RR 0.96; P = 0.91), heart failure (HF) hospitalization (RR 0.67; P = 0.12), or procedural complications (RR 0.83; P = 0.44). Conduction system pacing significantly shortened paced QRS duration (MD -19.52 ms, P < 0.001) and improved New York Heart Association (NYHA) class (MD -0.19, P = 0.05). Combined analysis showed larger effect sizes, including lower all-cause mortality (RR 0.74; P = 0.004) and HF hospitalization (RR 0.64; P < 0.001) in the CSP group. CONCLUSION: Randomized evidence demonstrates no significant difference between CSP and BiVP in hard clinical endpoints, despite superior electrical resynchronization and modest functional improvement with CSP. Confirmation of any clinical superiority of CSP awaits adequately powered trials reporting objective outcomes.