Left Bundle Branch Area Pacing Compared to Biventricular Pacing for Cardiac Resynchronization Therapy in Patients with Left Ventricular Ejection Fraction ≤50%: Results from the International Collaborative LBBAP Study (I-CLAS).

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment for heart failure with reduced ejection fraction (HFrEF) and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes.

Objective: The aim of the study was to compare the clinical outcomes between BVP and LBBAP among patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT.

Methods: This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June 2023. The primary outcome was a composite of all-cause mortality or first heart failure hospitalization (HFH). Secondary outcomes included separate analyses of HFH and all-cause mortality. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves, Cox proportional hazards models, and competing risk analyses were performed.

Results: A total of 2,579 patients were included (BVP 1118, LBBAP 1461). In the propensity-matched cohort (BVP 780, LBBAP 780), LBBAP demonstrated shorter paced QRS duration (129±19 ms vs. 143±22 ms, p<0.001). LBBAP was associated with a significantly lower risk of the composite primary outcome (HR: 0.81; 95% CI: 0.66-0.99; p=0.048) and reduced HFH (HR: 0.63; 95% CI: 0.49-0.82; p<0.001). No significant difference in all-cause mortality was observed (HR: 0.82; 95% CI: 0.63-1.07; p=0.156). Procedural complications were lower with LBBAP (3.5% vs. 6.5%, p=0.004).

Conclusions: LBBAP was associated with superior electrical resynchronization, fewer HFH and lower procedural complications compared to BVP in patients with LVEF <50% requiring CRT. Randomized trials are needed to confirm long-term benefits.