Abstract
<title>Abstract</title> <p> Background Conduction system pacing (CSP) has emerged as a potential alternative to biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). However, the relative efficacy and safety of different CSP techniques remain unclear. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) comparing CSP with BiVP. Primary outcome: composite of all‑cause death or heart failure hospitalization. Secondary outcomes: change in left ventricular ejection fraction (LVEF), change in left ventricular end‑systolic volume (LVESV), echocardiographic response (structural: LVESV reduction ≥ 15%; functional: LVEF increase ≥ 5%), QRS duration shortening, NYHA functional class improvement, and complication rate. Random‑effects meta‑analysis was used, with four pre‑specified subgroups: CSP with optimization, strict left bundle branch pacing (LBBP), His‑CRT, and left ventricular septal pacing (LVSP)‑dominant. Results Ten independent RCTs (Vinther 2021/Frandsen 2026 counted as one trial) were included, CSP significantly reduced the risk of all‑cause death or heart failure hospitalization (risk ratio RR 0.47, 95% CI 0.32–0.69, <italic>P</italic> < 0.0001 ; no subgroup interaction, <italic>P</italic> = 0.35), Overall LVEF change did not differ (MD 2.03%, 95% CI − 0.34% to 4.39%, <italic>P</italic> = 0.09, I² = 80%), but subgroup differences were significant ( <italic>P</italic> = 0.03): strict LBBP (MD 5.55%) and His‑CRT (MD 3.12%) favored CSP. Overall LVESV change showed a non‑significant trend (MD − 6.97 mL, 95% CI − 14.30 to 0.36 mL, <italic>P</italic> = 0.06, I² = 64%); strict LBBP significantly reduced LVESV (MD − 23.98 mL). Functional response favored CSP (RR 1.10, 95% CI 1.00–1.20, <italic>P</italic> = 0.05, I² = 0%), but structural response did not (RR 1.04, 95% CI 0.90–1.20, <italic>P</italic> = 0.57). CSP significantly shortened QRS duration (MD − 8.88 ms, 95% CI − 15.32 to − 2.45 ms, <italic>P</italic> = 0.007, I² = 87%), driven by the CSP‑with‑optimization subgroup (I² = 0%). NYHA class improvement favored CSP (MD − 0.21, 95% CI − 0.33 to − 0.09, <italic>P</italic> = 0.0007). Overall complication rates did not differ (RR 0.93, 95% CI 0.55–1.58, <italic>P</italic> = 0.79), but the His‑CRT subgroup had a higher risk in the long‑term Frandsen 2026 study (RR 4.00). Meta‑regression showed that each 10‑ms increase in baseline QRS duration was associated with a 4.09% reduction in LVEF benefit of CSP over BiVP ( <italic>P</italic> = 0.04). CSP technique significantly explained heterogeneity in LVEF ( <italic>P</italic> = 0.004) and LVESV ( <italic>P</italic> = 0.0003), with strict LBBP reducing LVESV by 23.98 mL more than His‑CRT. Conclusions CSP significantly reduces all‑cause death or heart failure hospitalization, improves electrical synchrony and functional class, but LVEF and LVESV improvements are seen only in specific subgroups. Significant differences in efficacy and safety exist among CSP techniques, supporting individualized CRT strategies based on technical characteristics and patient condition. </p>