Physicians' Academy for Cardiovascular Education

Effects of cardiac myosin inhibitor on exercise performance in obstructive HCM

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial

Literature - Wheeler MT, Olivotto I, Elliott PM, et al. - JAMA Cardiol. 2023 Jan 18;e225099 [Online ahead of print]. doi: 10.1001/jamacardio.2022.5099

Introduction and methods


Previously, the EXPLORER-HCM study investigated the efficacy and safety of the cardiac myosin inhibitor mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). This RCT showed that treatment with mavacamten reduced symptoms and improved the peak oxygen uptake (pVO2) compared with placebo [1]. However, mavacamten’s effects on additional maximal and submaximal parameters of exercise performance in this population remain unclear.

Aim of the study

The study aim was to investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET) in patients with symptomatic obstructive HCM and thereby expand knowledge of this disease.


This was a prespecified exploratory analysis of the EXPLORER-HCM (Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy) trial. In this multinational, double-blind, placebo-controlled, phase 3 RCT, 251 patients with symptomatic obstructive HCM were randomized to mavacamten (starting dose of 5 mg) or matching placebo for 30 weeks. CPET was performed using a standardized treadmill or bicycle ergometer test protocol at baseline and week 30.


In addition to pVO2 (which was a component of the composite primary endpoint and a prespecified secondary efficacy endpoint), the following prespecified exploratory CV and performance parameters were assessed: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power (pVO2 × peak systolic blood pressure), ventilatory power (peak systolic blood pressure/VE/VCO2 slope), peak metabolic equivalents (METs), partial pressure of end-tidal CO2 (PETCO2), peak exercise time, ventilatory threshold, and VO2/workload slope.

Main results


In this prespecified exploratory analysis of the EXPLORER-HCM trial, mavacamten improved the exercise capacity of patients with symptomatic obstructive HCM over a range of (maximal and submaximal) CPET parameters beyond pVO2. The authors believe that their “findings suggest that mavacamten may potentially be associated with improvements in the ability of patients [with obstructive HCM] to perform physical activities.”


Show references

Find this article online at JAMA Cardiol.

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