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Randomized Controlled Trial
. 2022 Apr 26;79(16):1565-1575.
doi: 10.1016/j.jacc.2022.02.024.

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy

Anne M Dybro  1 , Torsten B Rasmussen  2 , Roni R Nielsen  2 , Bertil T Ladefoged  2 , Mads J Andersen  3 , Morten K Jensen  3 , Steen H Poulsen  2
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Free article
Randomized Controlled Trial

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy

Anne M Dybro et al. J Am Coll Cardiol. .
Free article

Abstract

Background: The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.

Objectives: This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.

Methods: This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest.

Results: No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008).

Conclusions: In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

Keywords: invasive hemodynamics; metoprolol; obstructive hypertrophic cardiomyopathy; pulmonary capillary wedge pressure; stroke volume.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the Novo Nordic Foundation (grant number NNF18OC0052289) and by Skibsreder Per Henriksen, R. og hustrus Foundation. The foundations had no part in the design of the study, the data collection, statistical analysis, data interpretation, or drafting of the manuscript and had no say in the decision to submit the results. The manufacturer of metoprololsuccinate (Hexal) was neither involved in nor funded the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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