In Obstructive Hypertrophic Cardiomyopathy, Mavacamten Improves CPET Outcomes

In patients with obstructive hypertrophic cardiomyopathy, mavacamten can improve multiple cardiopulmonary exercise testing outcomes.

Mavacamten is associated with improvements to multiple cardiopulmonary exercise testing (CPET) outcomes among patients with obstructive hypertrophic cardiomyopathy (HCM). These findings were published in JAMA Cardiology.

This study was a secondary exploratory analysis of data from the EXPLORER-HCM ( Identifier: NCT03470545) study, which was a phase 3, randomized, double-blind, placebo-controlled trial conducted in 13 countries in 2018 to 2019. Patients (N=251) with obstructive HCM were randomly assigned in a 1:1 ratio to receive 5 mg mavacamten (n=123) or placebo (n=128) for 30 weeks. Changes to CPET outcomes from baseline to week 30 were evaluated. Patients received CPET on either a standardized treadmill or bicycle ergometer.

The mavacamten and placebo cohorts had mean ages of 58.5 (standard deviation [SD], 12.2) and 58.5 (SD, 11.8) years, 54% and 65% were men, 76% and 74% were taking β-blockers, 20% and 13% were taking calcium channel blockers, and 28% and 26% had New York Heart Association (NYHA) functional class III, respectively.

The change from baseline among mavacamten recipients was favored over placebo for the following outcomes:

  • Peak minute ventilation (VE) and carbon dioxide output (VCO2) ratio (adjusted difference in difference [aDID], -2.2; 95% CI, -3.05 to -1.26; P <.001)
  • Peak metabolic equivalents (aDID, 0.4; 95% CI, 0.17-0.60; P <.001)
  • Peak partial pressure of end-tidal carbon dioxide (PETCO2; aDID, 2.0; 95% CI, 1.12-2.79 mm Hg; P <.001)
  • Peak circulatory power (aDID, 372.9; 95% CI, 153.12-592.61 mL/kg/min x mm Hg; P =.001)
  • Peak exercise time at peak exercise (aDID, 0.7; 95% CI, 0.13-1.24 min; P =.02)
  • Peak VE/VCO2 slope (aDID, -2.6; 95% CI, -3.58 to -1.52; P <.001)
  • Ventilatory power (aDID, 0.6; 95% CI, 0.29-0.90 mm Hg; P <.001)
  • PETCO2 at rest (aDID, 0.8; 95% CI, 0.07-1.53 mm Hg; P =.03)
  • VO2/workload slope at nonpeak exercise (aDID, 0.04; 95% CI, 0.002-0.086; P =.04)
. . . mavacamten therapy improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity.

Among mavacamten recipients, the change in log2 of N-terminal-pro hormone brain natriuretic peptide (NT-proBNP) levels at week 30 negatively correlated with the change in peak VO2 (r, -0.30; P =.002) and positively correlated with improvements in the VE/VCO2 slope (r, 0.27; P =.003).

These findings are based on an exploratory analysis and should be viewed as hypothesis generating.

 “…mavacamten therapy improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity,” the study authors wrote. “The favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial effect of mavacamten in patients with obstructive HCM.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Wheeler MT, Olivotto I, Elliot PM, et al. Effects of mavacamten on measures of cardiopulmonary exercise testing beyond peak oxygen consumption: a secondary analysis of the EXPLORER-HCM randomized trial. JAMA Cardiol. Published online January 18, 2023. doi:10.1001/jamacardio.2022.5099