Mavacamten therapy increases functional outcome in OHCM patients: JAMA

Mavacamten enhanced a variety of cardiopulmonary exercise testing (CPET) indicators other than peak oxygen uptake (pVO2), showing consistent and wide improvements in maximum exercise capacity, says an article published in the Journal of American Medical Association.

In the EXPLORER-HCM research, the cardiac myosin inhibitor mavacamten increased peak oxygen absorption in individuals with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The complete impact of mavacamten on exercise performance is still unknown, though. Therefore, utilizing cardiopulmonary exercise testing, Matthew Wheeler and colleagues carried out this investigation to examine the impact of mavacamten on exercise physiology.

Exploratory analysis of the data from the EXPLORER-HCM project, a phase 3 trial that was performed in 68 cardiology centers across 13 nations. It was randomized, double-blind, and placebo-controlled. 251 symptomatic obstructive HCM patients in all were enrolled. Mavacamten or a placebo was randomly given to patients in a 1:1 ratio. A standardized treadmill or bicycle ergometer test protocol was used to evaluate the following predetermined exploratory cardiovascular and performance parameters at baseline and week 30: minute ventilation (VE), ventilatory efficiency (VE/VCO2 slope), peak VE/VCO2 ratio, peak circulatory power, peak respiratory exchange ratio (RER), ventilatory power, peak metabolic equivalents (METs), ventilatory threshold, peak exercise time, partial pressurization.

The key findings of this study were:

1. A total of 251 patients were signed up.

2. There were 59% male patients, with an average age of 58.5 (11.9) years.

3. Peak-exercise CPET metrics such as peak METs, peak circulatory power, and peak PETCO2 all showed a substantial improvement with mavacamten compared to placebo.

4. Comparing Mavacamten to a placebo, the peak exercise time was also improved.

5. Nonpeak-exercise CPET metrics, such as the VE/VCO2 slope and ventilatory power, significantly improved with mavacamten compared to placebo.

In addition to pVO2, mavacamten treatment increased a variety of CPET measures, demonstrating consistent and extensive advantages for maximum exercise capacity. Mavacamten has good benefits on submaximal exertional tolerance, which sheds more light on how well it works for individuals with obstructive HCM.

Reference:

Wheeler, M. T., Olivotto, I., Elliott, P. M., Saberi, S., Owens, A. T., Maurer, M. S., Masri, A., Sehnert, A. J., Edelberg, J. M., Chen, Y.-M., Florea, V., Malhotra, R., Wang, A., Oręziak, A., & Myers, J. (2023). Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption. In JAMA Cardiology. American Medical Association (AMA). https://doi.org/10.1001/jamacardio.2022.5099