Beta-Blocker (Bisoprolol) vs Calcium Channel Blocker (Verapamil) in Non-Obstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial (JACC March 2026-1)-Article: Beta-Blocker (Bisoprolol) vs Calcium Channel Blocker (Verapamil) in Non-Obstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial

Article: Beta-Blocker (Bisoprolol) vs Calcium Channel Blocker (Verapamil) in Non-Obstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial

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This randomized, double-blind, placebo-controlled triple-crossover trial tested two standard first-line drugs—bisoprolol (beta-blocker) and verapamil (non‑dihydropyridine calcium-channel blocker)—in an exclusively nonobstructive hypertrophic cardiomyopathy (HCM) cohort, where prior randomized evidence has been lacking. Adults with nonobstructive HCM and at least one severity marker (NYHA class II/history of II, NT-proBNP ≥300 ng/L, or recent nonsustained VT) received 3 treatment periods (target: bisoprolol 7.5 mg daily, verapamil 360 mg daily, and placebo). Outcomes were assessed after 2 weeks at steady state in each period. The primary endpoint was peak oxygen consumption (pVO₂) on cardiopulmonary exercise testing.<br /><br />Thirty-two patients (mean age 54 years; 34% women) were randomized. Bisoprolol significantly reduced pVO₂ versus verapamil and placebo: mean pVO₂ was 25.7 mL/kg/min on bisoprolol, 28.2 on verapamil, and 28.7 on placebo. Adjusted differences were −1.8 mL/kg/min (bisoprolol vs verapamil; P=0.013) and −2.5 (bisoprolol vs placebo; P=0.002), while verapamil did not differ from placebo.<br /><br />Both drugs lowered resting and peak heart rate, more so with bisoprolol (−37 beats/min at peak vs placebo) than verapamil (−17). Neither drug changed oxygen consumption at anaerobic threshold or ventilatory efficiency (VE/VCO₂ slope). Verapamil improved myocardial function by increasing global longitudinal strain (~1.1% vs placebo) and reducing NT-proBNP (−177 ng/L), without worsening patient-reported health status. In contrast, bisoprolol worsened multiple signals: lower Kansas City Cardiomyopathy Questionnaire score (−6.6 points), higher NT-proBNP (+165 ng/L), increased left atrial volume index (+13 mL/m²), and higher tricuspid regurgitation pressure gradient (+4.3 mm Hg).<br /><br />Overall, in nonobstructive HCM, bisoprolol reduced functional capacity, whereas verapamil preserved pVO₂ and showed more favorable biomarker and myocardial/diastolic-function patterns, highlighting important phenotype-specific differences relevant to management.

Keywords

nonobstructive hypertrophic cardiomyopathy

randomized double-blind placebo-controlled trial

triple-crossover study

bisoprolol

verapamil

peak oxygen consumption (pVO2)

cardiopulmonary exercise testing

NT-proBNP biomarker

global longitudinal strain

Kansas City Cardiomyopathy Questionnaire (KCCQ)