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Observational Study
. 2025 Aug;22(8):2028-2037.
doi: 10.1016/j.hrthm.2025.04.005. Epub 2025 Apr 25.

Left bundle branch area pacing compared with biventricular pacing for cardiac resynchronization therapy in patients with left ventricular ejection fraction ≤50%: Results from the International Collaborative LBBAP Study (I-CLAS)

Ramez Morcos  1 , Pugazhendhi Vijayaraman  2 , Óscar Cano  3 , Francesco Zanon  4 , Shunmuga Sundaram Ponnusamy  5 , Bengt Herweg  6 , Parikshit S Sharma  7 , Marek Jastrzebski  8 , Manuel Molina-Lerma  9 , Zachary I Whinnett  10 , Kevin Vernooy  11 , Jiangang Zou  12 , Girish M Nair  13 , Rajeev K Pathak  14 , Roderick Tung  15 , Gaurav A Upadhyay  16 , Karol Curila  17 , Mihail G Chelu  18 , Kenneth A Ellenbogen  19
Affiliations
Observational Study

Left bundle branch area pacing compared with biventricular pacing for cardiac resynchronization therapy in patients with left ventricular ejection fraction ≤50%: Results from the International Collaborative LBBAP Study (I-CLAS)

Ramez Morcos et al. Heart Rhythm. 2025 Aug.

Abstract

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction 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 in 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 2579 patients were included (BVP, 1118; LBBAP, 1461). In the propensity score-matched cohort (BVP, 780; LBBAP, 780), LBBAP demonstrated shorter paced QRS duration (129 ± 19 ms vs 143 ± 22 ms; P < .001). LBBAP was associated with a significantly lower risk of the composite primary outcome (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-0.98; P = .048) and reduced HFH (HR, 0.63; 95% CI, 0.49-0.82; P < .001). No significant difference in all-cause mortality was observed (HR, 0.82; 95% CI, 0.63-1.07; P = .156). Procedural complications were lower with LBBAP (3.5% vs 6.5%, P = .004).

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

Keywords: Biventricular pacing; Cardiac resynchronization therapy; Heart failure hospitalization; Left bundle branch area pacing; Mortality.

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Conflict of interest statement

Disclosures Dr Vijayaraman: honoraria, consultant, research, fellowship support: Medtronic; consultant, honoraria: Abbott, Biotronik, Boston Scientific; patent: HBP delivery tool. Dr Cano: honoraria, consultant: Abbott, Medtronic, Biotronik, Boston Scientific, and MicroPort. Dr Zanon: honoraria: Abbott, Biotronik, Boston Scientific, Medtronic, and MicroPort. Dr Ponnusamy: honoraria: Medtronic, Abbott. Dr Herweg: speaker, consultant: Abbott; speaker, fellowship support: Medtronic. Dr Sharma: honoraria: Medtronic; consultant: Medtronic, Abbott, Biotronik. Dr Jastrzebski: honoraria, consultant: Medtronic, Abbott. Dr Vernooy: consultant: Biosense Webster, Philips, Medtronic, Abbott, Boston Scientific. Dr Whinnett: honoraria: Medtronic, Boston Scientific; consultant: Medtronic, Abbott. Dr Nair: honoraria and consulting fees: Medtronic, Biosense Webster, Boston Scientific. Dr Pathak: honoraria, consultant, research, fellowship support: Medtronic, Abbott. Dr Upadhyay: consulting or speaking from Abbott, Biotronik, Boston Scientific, GE Medical, Medtronic, Philips, Rhythm Science, and Zoll Medical. Dr Tung: honoraria from Abbott, Medtronic, Biotronik, Biosense Webster, and Boston Scientific. Dr Curila: consultant and honoraria from Medtronic, Biotronik, and Abbott. Dr Chelu: honorarium: Impulse Dynamics.