Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy

• Published in: Journal of the American College of Cardiology 2021-12, Vol.78 (25), p.2505-2517
• Main Authors: Dybro, Anne M, Rasmussen, Torsten B, Nielsen, Roni R, Andersen, Mads J, Jensen, Morten K, Poulsen, Steen H
• Format: Article
• Language: English
• Subjects: Adrenergic beta-1 Receptor Antagonists - pharmacology; Adrenergic beta-1 Receptor Antagonists - therapeutic use; Aged; Cardiomyopathy, Hypertrophic - complications; Cardiomyopathy, Hypertrophic - drug therapy; Cross-Over Studies; Double-Blind Method; Exercise Tolerance - drug effects; Female; Humans; Male; Metoprolol - pharmacology; Metoprolol - therapeutic use; Middle Aged; Ventricular Outflow Obstruction - drug therapy; Ventricular Outflow Obstruction - etiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2021.07.065

The use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies. This study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM. This double-blind, placebo-controlled, randomized crossover trial enrolled 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020. Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing. Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg [interquartile range (IQR): 15-58 mm Hg] vs 72 mm Hg [IQR: 28-87 mm Hg]; P = 0.007), at peak exercise (28 mm Hg [IQR: 18-40 mm Hg] vs 62 mm Hg [IQR: 31-113 mm Hg]; P < 0.001), and postexercise (45 mm Hg [IQR: 24-100 mm Hg] vs 115 mm Hg [IQR: 55-171 mm Hg]; P < 0.0001). During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide did not differ between the study arms. Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged. (The Effect of Metoprolol in Patients with Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).