Randomized Trial of Left Bundle Branch Pacing vs Right Ventricular Pacing in Vulnerable Cardiac Function

BACKGROUND: Right ventricular pacing (RVP) is associated with an increased risk of pacing-induced cardiomyopathy (PICM) in high pacing burden patients. Left bundle branch pacing (LBBP), a more physiological pacing modality, may better preserve cardiac function. OBJECTIVES: This randomized trial aimed to evaluate the clinical outcomes of LBBP versus RVP in high pacing burden patients with high risk of cardiac dysfunction. METHODS: In this prospective, multicenter, randomized controlled trial, 160 high pacing burden patients with high risk of cardiac dysfunction were randomly assigned in a 1:1 ratio to either LBBP or RVP. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization (HFH), or PICM. Secondary endpoints included the individual components of the primary endpoints, echocardiographic parameters, and New York Heart Association (NYHA) functional class. RESULTS: During a median follow-up duration of 36 months, the primary endpoint occurred in 9 patients in the LBBP group and in 25 patients in the RVP group (11.6% vs. 33.9%; HR 0.310, 95% CI 0.145-0.664; P=0.001), mainly driven by PICM (6.5% vs. 18.2%; sHR 0.324, 95% CI 0.119-0.883; P=0.028). No significant differences were observed in all-cause mortality (P=0.391) and HFH (P=0.100) between two groups. LBBP showed superior improvements than RVP in left ventricular ejection fraction (LVEF) (mean difference: 5.34, 95% CI: 3.18-7.50; P <0.001), left ventricular end-diastolic diameter (LVEDD) (mean difference: -3.06, 95% CI: -4.38- -1.73; P <0.001) and left ventricular end-systolic diameter (LVESD) (mean difference: -3.74, 95% CI: -5.07- -2.41; P <0.001) from baseline to 36 months. Patients in the LBBP group also showed favored NYHA functional class compared with those in the RVP group at 36-month follow-up (1.66 ± 0.60 vs. 1.90 ± 0.56, P = 0.014). CONCLUSIONS: In high pacing burden patients with high risk of cardiac dysfunction, LBBP significantly reduced the risk of the composite outcome, driven primarily by a decreased risk of PICM, and is associated with better echocardiographic improvements and clinical function. CONDENSED ABSTRACT: This LBBP-FAVOUR randomized trial is the first multi-center, prospective, randomized controlled trials to evaluate the clinical efficacy of left bundle branch pacing (LBBP) vs right ventricular pacing (RVP) in patients with high risk of cardiac dysfunction. During a median follow-up of 36 months, LBBP significantly reduced the risk of the composite endpoint including pacing-induced cardiomyopathy (PICM), heart failure hospitalization, and all-cause mortality compared with RVP, and this benefit was mainly driven by the reduction in PICM risk. This work lays a solid foundation for future larger randomized trials in specific patient populations to further validate these findings.