Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy.

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• Obstructive hypertrophic cardiomyopathy (oHCM) patients with severe symptoms often require septal reduction therapy (SRT), a procedure with associated risks.
• Current guidelines recommend SRT for patients with intractable symptoms despite maximal medical therapy.

Purpose of the Study:

• To evaluate if mavacamten, an oral myosin inhibitor, can improve oHCM patients' condition to the point where they no longer meet criteria for SRT.
• To assess if mavacamten allows patients to avoid undergoing SRT.

Main Methods:

• A randomized, double-blind study enrolled 112 oHCM patients with a left ventricular outflow tract (LVOT) gradient ≥50 mm Hg.
• Patients received either mavacamten (titrated up to 15 mg) or placebo for 16 weeks.
• The primary endpoint was the proportion of patients proceeding with or remaining eligible for SRT after 16 weeks.

Main Results:

• Significantly fewer mavacamten patients (17.9%) met SRT criteria compared to placebo patients (76.8%) after 16 weeks (P < 0.001).
• Mavacamten demonstrated significant improvements in secondary outcomes, including reduced LVOT gradient, improved NYHA functional class, and enhanced patient-reported outcomes.
• Biomarkers such as NT-proBNP and cardiac troponin I were also favorably affected by mavacamten treatment.

Conclusions:

• Mavacamten effectively reduced the proportion of symptomatic oHCM patients meeting SRT criteria after 16 weeks.
• Further long-term studies are needed to determine sustained freedom from SRT with mavacamten treatment.