Conduction-System Versus Biventricular Pacing for CRT in HFrEF: Pairwise and Network Meta-Analysis

Background: Conduction-system pacing (CSP) has emerged as a physiological alternative to conventional biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT) in patients with heart failure with reduced ejection fraction (HFrEF). However, whether CSP provides superior clinical, echocardiographic, procedural, or safety outcomes compared with BiVP remains uncertain. Methods: We conducted a systematic review, pairwise meta-analysis, and frequentist network meta-analysis of randomized controlled trials comparing CSP with BiVP in adults with HFrEF undergoing CRT. PubMed/MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were searched from inception to May 5, 2026. The primary outcomes were change in left ventricular ejection fraction (LVEF), heart-failure hospitalization, and all-cause mortality. Secondary outcomes included NYHA functional class, QRS duration, ventricular volumes, procedural metrics, echocardiographic response, feasibility, device-related outcomes, and safety. Risk ratios or mean differences with 95% confidence intervals were pooled using random-effects models. Network meta-analysis compared individual pacing strategies, including His-bundle pacing (HBP), left bundle branch area/left bundle branch pacing, mixed CSP, and BiVP. Results: Nine randomized controlled trials including 976 participants were analyzed. Compared with BiVP, CSP was not associated with a statistically significant improvement in LVEF (MD, 1.90 percentage points; 95% CI, −1.05 to 4.86; p = 0.176), heart-failure hospitalization (RR, 0.83; 95% CI, 0.31 to 2.22; p = 0.660), or all-cause mortality (RR, 1.05; 95% CI, 0.40 to 2.70; p = 0.900). Network meta-analysis showed no statistically significant superiority of any individual CSP modality over BiVP for the primary outcomes. CSP was associated with a modest improvement in NYHA functional class (MD, −0.17; 95% CI, −0.34 to −0.00; p = 0.049), but no significant differences were observed in QRS duration, LVESV, LVEDV, pacing threshold, procedural time, fluoroscopy time, echocardiographic response, procedural success, complications, lead revision, infection or explantation, crossover, or ventricular arrhythmias requiring ICD therapy. Conclusions: In randomized evidence, CSP was not consistently superior to BiVP for LVEF improvement, heart-failure hospitalization, mortality, ventricular remodeling, procedural outcomes, or safety in patients with HFrEF undergoing CRT. CSP may represent a feasible physiological alternative in selected patients and experienced centers, but BiVP remains the established default strategy. Larger randomized trials with standardized CSP capture criteria, longer follow-up, and adequately powered clinical endpoints are needed.