Association Between age or Duration of Diagnosis in Obstructive Hypertrophic Cardiomyopathy and Response to Mavacamten Treatment: Exploratory Analysis of the EXPLORER-HCM Trial

Background and Aims: In patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM), it is unclear if response to cardiac myosin inhibition varies with older age or a longer duration of diagnosis. This study evaluated the response of these subgroups to mavacamten therapy for all primary, secondary and exploratory endpoints in the EXPLORER-HCM trial (ClinicalTrials.gov: NCT03470545). Methods: Patients were stratified by age (≤ 60 vs > 60 years) and duration of HCM diagnosis (≤ 5 vs > 5 years). To estimate treatment differences and evaluate age and diagnosis duration by treatment interaction, analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints. Results: Older patients were more commonly female (53% vs 29%), had lower prevalences of pathogenic/likely pathogenic HCM gene variants (17% vs 36%), lower mean peak oxygen consumption (pVO₂) (17.6 vs 21.1 mL/kg/min), and higher mean NT-proBNP levels (817 vs 592 ng/L) but similar NYHA classes and quality-of-life scores. Patients with longer vs shorter diagnosis duration had similar mean ages (59.0 ± 11.6 vs 57.9 ± 12.3 years) but more family histories of HCM (38% vs 16%) and higher mean NT-pro BNP levels (938 ± 118 vs 494 ± 145 ng/mL). No differences were observed in improvement in peak oxygen consumption, NYHA class or patient-reported outcomes among older patients and those with longer durations of diagnosis. Conclusions: In EXPLORER-HCM, mavacamten treatment had a similar benefit for all primary, secondary and exploratory endpoints in patients with symptomatic, obstructive HCM, regardless of age or duration of diagnosis.