Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy

• DOI: 10.7326/m18-3016
• Publication Date: 2019-04-30T10:47:45Z
• Authors: Stephen B. Heitner; Daniel Jacoby; Steven J. Lester; Anjali Owens; Andrew Wang; David Zhang; Joseph Lambing; June Lee; Marc Semigran; Amy J. Sehnert
• Keywords: Ventricular outflow tract

Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those B β-blockers allowed. Measurements: The primary end point was change postexercise LVOT gradient at 12 weeks. Secondary points included changes peak oxygen consumption (pVO2), resting and Valsalva gradients, ejection fraction (LVEF), numerical rating scale dyspnea score. Results: In A, reduced mean from 103 mm Hg (SD, 50) baseline 19 13) weeks (mean change, −89.5 [95% CI, −138.3 −40.7 Hg]; P = 0.008). Resting LVEF also −15% [CI, −23% −6%]). Peak VO2 increased by a 3.5 mL/kg/min (CI, 1.2 5.9 mL/kg/min). B, decreased 86 43) 64 26) −25.0 −47.1 −3.0 0.020), −6% −10% −1%). 1.7 2.3) 0.03 3.3 Dyspnea scores improved both cohorts. Mavacamten well tolerated, mostly mild (80%), moderate (19%), unrelated (79%) adverse events. most common events definitely or possibly related were higher plasma concentrations atrial fibrillation. Limitation: Small size; open-label design. Conclusion: can reduce obstruction improve exercise capacity symptoms Primary Funding Source: MyoKardia.