Abstract 4359878: Effect of mavacamten treatment by duration of obstructive hypertrophic cardiomyopathy diagnosis: Results from the EXPLORER cohort of MAVA-Long-Term Extension study

Introduction: Interim analyses from MAVA-LTE (NCT03723655) demonstrated that mavacamten is efficacious and well tolerated in patients with obstructive hypertrophic cardiomyopathy (oHCM). The relationship between the duration of oHCM diagnosis at mavacamten initiation and the effects of mavacamten are unknown. Research Questions: To assess the effects of mavacamten in patients from the EXPLORER cohort of MAVA-LTE by duration of oHCM diagnosis. Methods: All patients in MAVA-LTE received mavacamten. The effects of mavacamten on echocardiographic parameters and disease biomarker levels by duration of oHCM diagnosis were assessed (data cut-off: April 5, 2024). Results: In total, 231 patients were categorized into 4 subgroups based on duration of oHCM diagnosis at mavacamten initiation: 0–2.5 years (n=61), 2.5–5 years (n=49), 5–10 years (n=64) and >10 years (n=57) ( Table 1 ). At MAVA-LTE baseline, patients in the 0–2.5 years group had lower resting and Valsalva left ventricular outflow tract (LVOT) gradients, left atrial volume index (LAVI), interventricular septum (IVS) thickness, ratio of early diastolic mitral inflow velocity to mitral annular velocity (E/e’), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels than patients in other subgroups, while a higher proportion were New York Heart Association Class I ( Table 1 and 2 ). By week 204, improvements in LAVI ( Figure 1 ) were observed in all groups with abnormal baseline values ( Table 2 ). For resting and Valsalva LVOT gradients, E/e’, LVMI, and NT-proBNP levels, values improved from baseline in all subgroups by week 204 ( Table 2 ). IVS thickness improved from baseline in all subgroups by week 204 but remained elevated. Exposure adjusted incidence rates for serious treatment emergent adverse events per 100 patient-years of exposure were generally similar across subgroups (0–2.5 yrs: 9.30; 2.5–5 yrs: 7.04; 5–10 yrs: 12.33; >10 yrs: 11.53). Conclusion: Patients in MAVA-LTE who had a shorter duration from diagnosis of oHCM to mavacamten initiation had lower values for key echocardiographic parameters and disease biomarker levels at baseline than those with a longer duration. Mavacamten treatment trended towards improvement in echocardiographic parameters and disease biomarker levels regardless of the duration of oHCM diagnosis.