Impact of Mavacamten on Disease-Related Symptoms in Patients With Obstructive Hypertrophic Cardiomyopathy: HCMSQ Outcomes in EXPLORER-HCM

BACKGROUND: The Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) is the first patient-reported outcome tool to measure cardinal symptoms of HCM. We examined the impact of mavacamten on HCM symptoms measured by the HCMSQ. METHODS AND RESULTS: EXPLORER-HCM (NCT03470545) was a phase 3, double-blind, randomized trial in 251 adults with symptomatic obstructive HCM who received mavacamten or placebo for 30 weeks. Changes in the HCMSQ shortness of breath (SoB), the tiredness, the cardiovascular symptoms domains and total scores were assessed. Responder analyses, impact of withdrawing treatment, and associations between HCMSQ scores and echocardiographic parameters were explored. A total of 217 patients completed the HCMSQ at baseline (mavacamten, n = 108; placebo, n = 109), and 171 patients completed it at week 30 (mavacamten, n = 85; placebo, n = 86). At week 30, patients receiving mavacamten experienced significantly greater improvements from baseline in HCMSQ SoB, tiredness, and cardiovascular symptoms domains and total score versus placebo (all P<0.001). Higher proportions of patients receiving mavacamten versus placebo experienced meaningful improvements in HCMSQ SoB domain (52.9% vs 18.6%), tiredness domain (23.5% vs 12.8%), cardiovascular symptoms domain (42.4% vs 22.1%), and total (36.5% vs 14.0%) scores. Therapy cessation was associated with return to baseline in HCMSQ scores by week 38. HCMSQ SoB domain score was significantly associated with echocardiographic E/e' lateral and resting and Valsalva left ventricular outflow tract gradient. CONCLUSIONS: In patients with obstructive HCM, mavacamten markedly reduced patient-reported symptom burden measured by the HCMSQ compared with placebo. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT03470545. Unique identifier: NCT03470545.