Conduction System Versus Biventricular Pacing in Heart Failure With Reduced Ejection Fraction

Introduction: Conduction system pacing (CSP) has emerged as a more physiological alternative to biventricular pacing (BiVP) in HFrEF and wide QRS. However, recent randomized controlled trials (RCTs) have yielded discordant results, warranting an updated meta-analysis. Research question: What is the comparative efficacy of CSP versus BiVP on clinical events and functional outcomes in patients with HFrEF and wide QRS? Methods: MEDLINE, Embase, and Cochrane Library were searched for RCTs through April 15, 2026. Random-effects meta-analyses and Trial Sequential analyses were performed. Primary outcomes were all-cause mortality (ACM) and heart failure hospitalization (HFH) at mid-term (6-12 months) and long-term (>12 months) follow-up. Secondary outcomes included functional recovery and procedural and safety outcomes, analyzed at 6 and 12 months when available. Effect sizes were reported as RR, MD, or SMD with 95% CI, as appropriate. Heterogeneity was assessed using I 2 , and prespecified subgroup analyses were performed by CSP modality (left bundle branch area pacing (LBBAP) vs. His bundle pacing (HBP)). Analyses were performed in R v4.5.2 and TSA software (Copenhagen Trial Unit). Results: Of 7,093 screened studies, 11 RCTs comprising 12 reports and 1,073 patients were included. Risk of bias assessed by RoB2 ranged from some concerns to low. CSP showed no difference in mid-term ACM (RR 0.72; 95% CI 0.21 to 2.49; p = 0.605) or HFH (RR 0.97; 95% CI 0.52 to 1.81; p = 0.918). At long-term follow-up, CSP showed a trend toward ACM reduction (RR 0.34; 95% CI 0.11 to 1.06; p = 0.063) and a significant reduction in HFH (RR 0.30; 95% CI 0.16 to 0.58; p < 0.001). TSA confirmed long-term HFH reduction with the Z-curve crossing the monitoring boundary (required information size = 149 patients); for ACM, boundaries were not crossed, hence non-significance may not indicate a true absence of effect. At 6 months, CSP improved LVEF (MD 2.84%; 95% CI 0.74 to 4.93; p = 0.008) and reduced QRS duration (MD –9.97 ms; 95% CI –18.57 to –1.37; p = 0.023), with a trend toward lower LVESV (SMD –0.21; 95% CI –0.43 to 0.00; p = 0.054). Change in QRS duration from baseline remained significantly greater with CSP at 12 months (MD –5.00 ms; 95% CI –8.68 to –1.31; p = 0.008). NYHA class improved at 12 months (MD –0.31; 95% CI –0.50 to –0.11; p = 0.002). Periprocedural complication rates were comparable between groups (RR 0.80; 95% CI 0.48 to 1.32; p = 0.378). Subgroup analysis by CSP modality revealed that at 6 months, LBBAP drove lower pacing thresholds versus BiVP, whereas HBP showed higher thresholds, with longer procedure duration at implant (p interaction <0.001 for both). Conclusions: CSP may reduce long-term HFH and showed a trend toward ACM benefit over BiVP in HFrEF with wide QRS. Improvements in LVEF, QRS duration, and NYHA class, alongside procedural advantages of LBBAP, further support its role. Larger RCTs are needed to confirm these findings.