Mavacamten's Dose-Time Dynamics and Predictive Factors in Hypertrophic Obstructive Cardiomyopathy Cardiac Remodeling

Area of Science:

• Cardiology
• Pharmacology
• Medical Imaging

Background:

• Hypertrophic obstructive cardiomyopathy (HOCM) presents significant challenges due to dynamic left ventricular outflow tract (LVOT) obstruction and disabling symptoms.
• Many HOCM patients exhibit poor response to conventional pharmacotherapies.
• Mavacamten, a novel cardiac myosin inhibitor, shows promise in improving LVOT gradients, but its real-world dose-response profile requires further elucidation.

Purpose of the Study:

• To assess longitudinal changes in echocardiographic parameters, biomarkers, and safety profiles in symptomatic HOCM patients treated with clinically guided mavacamten.
• To compare these outcomes against conventional pharmacotherapy in a real-world clinical setting.

Main Methods:

• A single-center, prospective comparative cohort study involving 95 symptomatic HOCM patients (48 mavacamten, 47 conventional therapy).
• Mavacamten initiated at 2.5 mg/day, titrated based on resting LVOT gradient (LVOTG) and ejection fraction (LVEF) up to 10 mg/day.
• Longitudinal assessments at baseline, 3, 6, and 9 months; analysis of observed mean changes and inverse probability weighting for baseline imbalances.

Main Results:

• Mavacamten group demonstrated a significant reduction in resting LVOTG, while the control group remained stable.
• Brain natriuretic peptide (BNP) levels decreased significantly in the mavacamten group but not in the control group.
• The predefined LVOTG response endpoint (≥30 mmHg reduction) was achieved by 18.8% of mavacamten patients versus 2.4% of controls (p=0.0175).

Conclusions:

• Clinically guided mavacamten therapy effectively reduces LVOT gradients and BNP levels in symptomatic HOCM patients with preserved LVEF during short-term follow-up.
• Findings support individualized mavacamten dosing strategies guided by echocardiographic monitoring.
• Caution is advised in interpreting subgroup analyses due to limited sample sizes.