Herry, Morgane

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is a genetic heart disease inherited in an autosomal dominant pattern. Studies have shown that novel first-in-class targeted myosin inhibitor-Mavacamten significantly improves LV diastolic function, systolic anterior motion measures, exercise capacity and left ventricular outflow (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). HCM primarily affects the left side of the heart, making pulmonary hypertension (PH) a common complication. However, the clinical significance and prognostic impact of PH in HCM are not yet fully understood. Purpose This study evaluated the effects of Mavacamten on echo-Doppler-derived pulmonary artery systolic pressure (PASP) in oHCM patients. Methods 70 Adult patients (53% male, mean age 60±12 years) meeting the imaging criteria for oHCM and receiving Mavacamten treatment were identified. Baseline clinical and imaging characteristics were analyzed. The impact of Mavacamten on echo-Doppler-derived PASP was assessed. Clinical and echocardiographic follow-ups were conducted at a median of 12 weeks (IQR: 7–24 weeks) and 74 weeks (IQR: 38–97 weeks) after the baseline echocardiographic assessment. Results The mean PASP of the cohort was 32 ± 10 mmHg, with 39% of patients having PASP >30 mmHg. When stratified by baseline PASP (using a 30-mmHg cut-off ), patients with elevated PASP were older and had more pronounced diastolic dysfunction. At the first follow-up, PASP decreased from 33 ± 10 mmHg to 29 ± 6 mmHg, and at the second follow-up, it further decreased to 27 ± 9 mmHg (p < 0.001). PASP decrease was more pronounced in patients with elevated PASP at baseline (Figures 1, 2). When analyzing changes in echocardiographic parameters over time according to baseline PASP levels, the group with elevated PASP at baseline demonstrated more pronounced changes. While LVOT gradient changed significantly from baseline to both follow-ups in both the elevated and normal PASP groups, certain parameters of diastolic dysfunctions including the E/e' ratio, showed significant changes only in the elevated PASP group (Figure 1). We observed that in univariate regression analysis, age was significantly associated with elevated baseline PASP along with MR and echocardiographic parameters indicative of diastolic dysfunction such as left atrial volume index (LAVI), TR velocity, and E/e. In multivariate analysis TR velocity remained significantly associated with PASP (β=23.05, 95% CI 3.17 to 167.8; p=0.002), highlighting a significant relationship between diastolic dysfunction parameters and PASP. Conclusion This study demonstrates that Mavacamten therapy significantly improves echocardiographic parameters and reduces PASP in patients with oHCM, with particularly pronounced benefits in those with elevated baseline PASP. These findings highlight the potential of Mavacamten as a targeted therapy for addressing both LVOT obstruction and associated PH in oHCM.Changes of echocardiographic parameters PASP over time in oHCM

Background: Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States. Research Questions: This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM. Methods: In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks. Results: Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of <40% and 2% experienced an LVEF of <50%. Conclusions: This is the largest observational study to date demonstrating the effectiveness and safety of mavacamten with substantial sustained reductions in resting and Valsalva LVOTg, and progressive improvements in NYHA class without considerable changes in mean LVEF up to 72 weeks.