Association between age or duration of diagnosis in obstructive hypertrophic cardiomyopathy and response to mavacamten treatment: Exploratory analysis of the EXPLORER-HCM trial

• Published in: Journal of cardiac failure 2024-12
• Main Authors: Wang, Andrew, Lakdawala, Neal K., Abraham, Theodore P., Nilles, Ester Kim, Wojdyla, Daniel M., Owens, Anjali Tiku, Bach, Richard G., Saberi, Sara, Sehnert, Amy, Cresci, Sharon
• Format: Article
• Language: English
• Subjects: age; cardiomyopathy; diagnosis duration; hypertrophic; mavacamten; myosin
• ISSN: 1071-9164; 1532-8414; 1532-8414
• DOI: 10.1016/j.cardfail.2024.10.449

•In the EXPLORER-HCM trial, older patients with obstructive hypertrophic cardiomyopathy (HCM) and patients with a longer duration of diagnosis had similar improvements in the primary, secondary, exploratory, and other echocardiographic endpoints compared with younger patients and patients with a shorter duration of HCM diagnosis.•Mavacamten treatment led to similar, beneficial effects on exercise capacity, symptoms, quality of life, and biomarker levels in older vs. younger patients with obstructive HCM and patients with a longer vs. shorter duration of HCM diagnosis. 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). 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. Older patients were more frequently female (53% vs. 29%), with a lower prevalence 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 a higher mean NT-proBNP level (817 vs. 592 ng/L) but similar NYHA classes and quality of life scores. Patients with a longer vs. shorter diagnosis duration had similar mean ages (59.0±11.6 vs. 57.9±12.3 years) but more family history of HCM (38% vs. 16%) and a higher mean NT-pro BNP level (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 a longer duration of diagnosis. 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. Older age in obstructive HCM and response to mavacamten or placebo for 30 weeks. HCM, hypertrophic cardiomyopathy; HTN, hypertension; LVOT, left ventricular outflow tract; NYHA, New York Heart Association. [Display omitted]