The Evolution of Hypertrophic Cardiomyopathy Care With Milind Desai, MD

At the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025, Milind Desai, MD, director of clinical operations of the Tomsich Department of Cardiovascular Medicine at Cleveland Clinic, discussed recent advancements in the diagnosis and treatment of hypertrophic cardiomyopathy (HCM).

The editorial team at HCPLive sat down with Desai to discuss the disease, recent clinical and medicinal advancements, and where the pipeline may lead in 2026. Desai mentioned several current and ongoing studies investigating medical therapies, spotlighting aficamten’s progress in the pipeline and mavacamten’s reaffirmed efficacy.

“In the last few years since 2018, we’ve had a plethora of phase 3 randomized control trials using cardiac myosin inhibitors,” Desai told HCPLive. “Mavacamten being one of the first in line, and aficamten is currently undergoing review by the [US Food and Drug Administration]. And between these two, I can count about 6 randomized controlled trials across the world, all of which have shown that this class of drug, compared to placebo, improves symptoms, exercise capacity, need for septal reduction therapy, biomarkers, favorable cardiac remodeling, etc.”

Desai mentions the recent SEQUOIA-HCM trial, which investigated the efficacy of aficamten compared to placebo in patients with symptomatic obstructive HCM. The 24-week trial enrolled 182 patients; the 142 randomly assigned to aficamten saw a significant improvement in limiting symptoms (71% vs 42%; P ≤.002).1

Additionally, patients receiving aficamten were more likely to have complete hemodynamic response (68% vs 7%), demonstrate enhance exercise capacity (47% vs 24%), and show a decrease in N-terminal pro-B type natriuretic peptide (84% vs 8%; P ≤.002 for all). An improvement in ≥1 of these measures was achieved in 97% of patients receiving aficamten versus 59% in the placebo cohort.1

Mavacamten, meanwhile, had its efficacy reaffirmed during the EXPLORER-HCM trial, which enrolled 251 patients and randomly assigned them to receive either mavacamten or placebo. Investigators measured exercise performance parameters including carbon dioxide output, minute ventilation, ventilatory efficiency, peak respiratory exchange ratio, ventilatory power and threshold, and peak exercise time, among others. Investigators saw significantly greater improvements among the mavacamten cohort across every parameter during the trial.2

Desai also highlighted invasive therapies and surgeries, explaining newer and more efficient techniques coming out of various countries in recent months.

“There’s a lot of surgical myectomy which traditionally has been done through the trans-aortic route. Now there’s emerging data, a lot of it coming out of China, where they’re doing beating heart myectomy, which is where the heart continues to beat and there’s a small incision in the apex, through which the surgeon does a myectomy,” Desai said. “There’s also something called SESAME, which tries to mimic a myectomy through an interventional, catheter-based technique.”

Finally, Desai gave his advice to clinicians dealing with HCM, noting the critical importance of determining the specific type of HCM prior to treatment. In addition, Desai pushed for shared decision-making conversations if first-line background therapy fails, warning clinicians not to approach further treatment as mutually exclusive.

“I always say the following: it is not this or this, it is this plus or minus this,” Desai said. “If you go on a pathway of cardiac myosin inhibitors, it doesn’t mean that myectomy is no longer going to be an option.”

Editor’s Note: Desai reports disclosures with Bristol Myers Squibb, Cytokinetics, Tenaya, viz.AI, Edgewise, and others.

References

1. Maron MS, Masri A, Nassif ME, et al. Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024;84(19):1821-1831. doi:10.1016/j.jacc.2024.09.003

2. Wheeler MT, Olivotto I, Elliott 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. 2023;8(3):240-247. doi:10.1001/jamacardio.2022.5099