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

BACKGROUND Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet b-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES This study aimed to evaluate the effect of b-blocker withdrawal on peak oxygen consumption (peak VO2) in patients with HFpEF and chronotropic incompetence. METHODS 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 b-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n ¼ 26) versus continuing (arm B: n ¼ 26) b-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. RESULTS 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 b-blocker withdrawal (14.3 vs 12.2 mL/kg/min [D þ2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [D þ11.7%]; P < 0.001, respectively). CONCLUSIONS b-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. b-blocker use in HFpEF deserves profound re-evaluation. (b-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39) (J Am Coll Cardiol 2021;78:2042–2056) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.