Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy.

# Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy. *Original Article* # Abstract ## Background Approved pharmacologic therapies for pediatric hypertrophic cardiomyopathy are lacking, and surgical intervention may be indicated in patients with left ventricular outflow tract obstruction. The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents. ## Methods We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving symptomatic adolescents (12 to <18 years of age) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy. The patients were randomly assigned in a 1:1 ratio to receive mavacamten or placebo. The primary end point was the change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver. ## Results A total of 44 patients underwent randomization; 23 patients (8 [35%] of whom were female) were assigned to mavacamten group, and 21 (5 [24%] of whom were female) were assigned to the placebo group. The mean (±SD) age of the patients was 14.7±1.7 years in the mavacamten group and 14.6±1.7 years in the placebo group, and the mean Valsalva left ventricular outflow tract gradient at baseline was similar in the two groups (78.4±34.1 mm Hg and 80.8±47.4 mm Hg, respectively). At week 28, the least-squares mean change in the Valsalva left ventricular outflow tract gradient was -48.5 mm Hg in the mavacamten group and -0.5 mm Hg in the placebo group (difference, -48.0 mm Hg; 95% confidence interval, -67.7 to -28.3; P<0.001). The incidence of adverse events was similar in the two groups. Two patients in each group had serious adverse events; in the mavacamten group, 1 patient had two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter-defibrillator; in the placebo group, 1 patient had chest pain, and another had depression with suicidal ideation. No patient had a reduction in the left ventricular ejection fraction to less than 50%. No deaths occurred during the trial. ## Conclusions Among adolescent patients with obstructive hypertrophic cardiomyopathy, the reduction in left ventricular outflow tract obstruction was significantly greater with mavacamten than with placebo over a 28-week period. (Funded by Bristol Myers Squibb; SCOUT-HCM ClinicalTrials.gov number, NCT06253221.). --- DOI: 10.1056/NEJMoa2601103