Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction

Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence.

This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo₂) in patients with HFpEF and chronotropic incompetence.

This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo₂ and percentage of predicted peak Vo₂ (peak Vo₂%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used.

The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo₂ and peak Vo₂% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo₂ and peak Vo₂% increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively).

β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39).