Left bundle branch vs biventricular pacing: mechanistic insights from a canine model

Abstract

Background and Aims: Left bundle branch pacing (LBBP) for cardiac resynchronization therapy is emerging as an alternative pacing strategy to biventricular pacing (BiVP) in dyssynchronous heart failure (DHF). This study aimed to explore the differences in treatment effects between the two pacing modalities using electrocardiographic, echocardiographic, and molecular measurements. Methods: Adult canines underwent left bundle branch ablation, then either followed by 6 weeks of atrial tachypacing (DHF group, n = 8), or 3 weeks of atrial tachypacing followed by another 3 weeks of BiVP (n = 8) or LBBP (n = 8) tachypacing. Non-intervened canines constituted the control group (n = 7). Electrocardiographic, echocardiographic, and molecular features were compared between BiVP-treated and LBBP-treated DHF canines. Results: BiVP- and LBBP-treated canines achieved equivalent reduction in QRS duration (32 ± 6 ms vs 35 ± 5 ms, P = .276). Both BiVP and LBBP increased left ventricular ejection fraction (9 ± 5% and 10 ± 4%, respectively; P = .390) while LBBP significantly outperformed BiVP in improving left ventricular global longitudinal strain (−3.7 ± 1.2% vs −2.3 ± 1.0%, P = .019). Both BiVP and LBBP reversed biomarkers of heart failure, while LBBP more significantly modulated cytoskeleton proteins, TGF-β signalling pathways and SERCA2a expression. Moreover, LBBP contributed to a more comprehensive improvement in myocardial energy metabolism compared to BiVP. Conclusions: This study in a DHF animal model indicates that LBBP results in electrocardiographic, echocardiographic, and molecular recovery at least as good as that during BiVP. The superiority of LBBP is especially reflected in more pronounced normalization of cardiac cytoskeleton, calcium handling and energy metabolism.