Bundle branch block (BBB) adversely impacts heart failure outcomes in heart failure (HF) with preserved ejection fraction (pEF): A TOPCAT substudy

Abstract Background Ventricular dyssynchrony induced by BBB can lead to adverse cardiovascular (CV) outcomes in HF with reduced EF, BBB is known to occur in HFpEF, but its impact on its outcomes is unclear. Methods We studied the impact of BBB in HFpEF utilizing propensity score (PS) matched cohorts without and with BBB from the TOPCAT Americas trial to account for confounding by other co-morbidities. Outcomes analyzed included the TOPCAT primary outcome, CV death & hospitalization (CVH), sudden death, pump failure death (PFD), HF hospitalizations(H), and progression of HF. The impact of concomitant AF on these outcomes with BBB was analyzed. Results 329 pts with HFpEF & BBB were PS matched for 24 demographic & disease state variables, BNP strata and AF status with a cohort of 329 pts with HFpEF without BBB. BBB was associated with increased risk of the TOPCAT primary outcome (Hazard ratio{ HR} 1.44, 95% confidence intervals {CI} 1.10-1.89, p=0.008), increased risk of HF hospitalizations by 41%(HR 1.41 95% CI 1.04-1.91 p=0.026) but not CVH (HR 1.18, 95% CI 0.93-1.49, p=0.169), or sudden death (HR 1.40, 95% CI 0.70-2.82, p=0.342) or CV death (HR 1.26, 95% CI 0.84-1.89, p=0.257). Risk of pump failure death (PFD) was higher in HFpEF subjects without a history of AF (Figure, Kaplan Meier Log Rank p=0.0478, HR: 4.22, 95% CI: 0.89 to 19.87, p=0.0689) but not in AF (p=0.138). PFD risk was markedly higher in AF subjects without BBB (Figure Kaplan Meier Log Rank p=.0012, HR:7.99, 95% CI:1.80 to 35.41,p = 0.0063) but not in subjects with BBB (p=0.91) Conclusion Ventricular dysynchrony induced by BBB in an independent risk factor increasing HFH risk in HFpEF subjects. This risk is most significant in HFpEF subjects without AF. Increase in PFD risk with AF in HFpEF subjects is most prominent in those with normal intraventricular conduction. Mechanical dyssynchrony induced by BBB may have a role in HFpEF subgroups with preserved AV filling in sinus rhythm, leading to adverse HF outcomes.