Treatment Shows Promise for Patients With Obstructive Hypertrophic Cardiomyopathy

In patients with highly symptomatic obstructive hypertrophic cardiomyopathy (HCM), mavacamten significantly reduced the need for septal reduction therapy after 16 weeks, according to a study published in the Journal of the American College of Cardiology.

“Currently, septal reduction therapy (surgical septal myectomy or alcohol ablation) is recommended for obstructive HCM patients with severe symptoms despite maximal medical therapy and left ventricular outflow tract (LVOT) gradient ≥50 mm Hg,” wrote corresponding author Steven E. Nissen, of the Cleveland Clinic Department of Cardiovascular Medicine, Heart, Vascular & Thoracic Institute, and coauthors. “However, these procedures entail a high risk of morbidity and mortality, particularly in low-volume centers.”

The phase 3, double-blind trial investigated whether mavacamten, an oral myosin inhibitor, helped patients improve enough to no longer meet guideline criteria for, or choose to not undergo, septal reduction therapy.

The trial randomized 112 patients with obstructive HCM to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and left ventricular ejection fraction. Participants had a mean age of 60 ± 12 years and a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg, and 93% were New York Heart Association (NYHA) functional class III or higher.

After 16 weeks, 76.8% of patients who received placebo met guideline criteria or underwent septal reduction therapy compared with 17.9% of patients who received mavacamten, reported researchers.

Secondary outcomes also favored mavacamten. Among them, researchers reported a 39 mm Hg greater reduction in post-exercise LVOT gradient, a larger proportion of patients with ≥1 class improvement in NYHA functional classification, and a 9.4 point higher clinical summary score on the patient-reported Kansas City Cardiomyopathy Questionnaire with mavacamten.

“In obstructive HCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks,” researchers concluded. “Long-term freedom from septal reduction therapy remains to be determined.”

Reference:
Desai MY, Owens A, Geske JB, et al. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy. J Am Coll Cardiol. 2022;80(2):95-108. doi:10.1016/j.jacc.2022.04.048