Anterior mitral valve leaflet length and response to mavacamten in obstructive hypertrophic cardiomyopathy

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Abstract Objectives This study examines whether anterior mitral valve leaflet (AMVL) length is associated with response to mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM). Aims Obstruction of the left-ventricular outflow tract (LVOT) in HCM has been associated with asymmetric septal hypertrophy and abnormalities of the mitral valve and sub-valvular apparatus. Mavacamten is a myosin-inhibitor shown to decrease LVOT gradient and improve functional status in patients with obstructive HCM. Methods and results Measurements of cardiac structural elements were obtained from magnetic resonance imaging and echocardiography data among patients with obstructive HCM treated with mavacamten. Endpoints were effective mavacamten dose, defined as the dose required to achieve a Valsalva LVOT gradient <30 mmHg, and rapid response to mavacamten therapy, defined as achieved Valsalva LVOT gradient <20 mmHg within 8 weeks of initiation. Among 33 patients, patients with an effective dose of 5 mg (n = 13) had a shorter AMVL length [20.00 (18.50, 20.80) mm] compared with patients with a dose of 10 mg (n = 12) [23.30 (22.45, 26.10) mm] and 15 mg (n = 8) [25.45 (24.20, 26.85) mm] (P < 0.001). After adjusting for age and sex, the 5 mg dose was associated with a shorter AMVL length (P = 0.003). AMVL length was shorter in rapid responders [20.9 (19.9, 22.5) mm] compared with patients without a rapid response [24.9 (23.3, 26.5) mm] (P = 0.006). Conclusion Shorter AMVL length is associated with a lower effective dose and a rapid response to mavacamten. If confirmed in larger studies, AMVL length may inform optimal dosing of myosin inhibitors in obstructive HCM.

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