Bisoprolol reduced peak exercise capacity compared with verapamil and placebo in patients with nonobstructive hypertrophic cardiomyopathy (HCM). In a randomized, double-blind, placebo-controlled triple-crossover trial published in the Journal of the American College of Cardiology, bisoprolol and verapamil were compared with placebo to evaluate their effects on exercise capacity, symptoms, biomarkers, and cardiac structural measures in nonobstructive HCM.

Adults with nonobstructive HCM and at least one marker of disease severity, including New York Heart Association functional class ≥II, N-terminal pro-B-type natriuretic peptide (NT-proBNP) >300 ng/L, or documented nonsustained ventricular tachycardia, were enrolled. Thirty-two patients (mean age 54 ± 15 years; 34% women) received bisoprolol (target dose 7.5 mg), verapamil (360 mg), and placebo during three treatment periods, with outcomes assessed after two weeks of steady-state therapy. The primary endpoint was peak oxygen consumption (pVO₂).

Mean pVO₂ was 25.7 ± 8.7 mL/kg/min with bisoprolol, 28.2 ± 8.6 with verapamil, and 28.7 ± 8.7 with placebo. Compared with verapamil and placebo, bisoprolol was associated with lower pVO₂ (−1.8 mL/kg/min; P = 0.013 and −2.5 mL/kg/min; P = 0.002). Peak heart rate decreased with bisoprolol (−37 beats/min; P < 0.001) and verapamil (−17 beats/min; P<0.001).
Verapamil improved global longitudinal strain (−1.1%; P = 0.001) and reduced NT-proBNP (−177 ng/L; P<0.001), whereas bisoprolol increased NT-proBNP (+165 ng/L; P = 0.006), left atrial volume index (+13.0 mL/m²; P < 0.001), tricuspid regurgitation pressure gradient (+4.3 mm Hg; P = 0.049), and reduced Kansas City Cardiomyopathy Questionnaire score (−6.6 points; P = 0.001). 

Bisoprolol reduced peak oxygen consumption, whereas exercise capacity remained unchanged with verapamil, providing new insights into the mechanisms of these treatments in nonobstructive HCM.