Roehl, Kaitlin

Background: MARVEL-HCM is a US multicenter study assessing the safety and effectiveness of mavacamten in real-world academic and community practices. Mavacamten is a first-in-class cardiac myosin inhibitor (CMI) and the only CMI currently approved in over 50 countries for use in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Modest evidence exists describing the effectiveness and safety of mavacamten monotherapy. Aims: To describe the real-world outcomes of patients using mavacamten as monotherapy for oHCM. Methods: Patient-level data from medical records at 5 sites were analyzed to describe mavacamten monotherapy, defined as monotherapy at baseline or after background HCM therapy (beta-blockers [BB], calcium channel blockers [CCB], disopyramide) discontinuation within 12 weeks(wks) of mavacamten initiation and without reinitiation, up to 60 wks. A minimum of 12 wks follow-up was required for inclusion. Patient characteristics, echocardiographic data, and safety are reported at baseline and follow-up visits. Results: The monotherapy cohort comprised 13.4% (32/239) of patients: 24 were on mavacamten monotherapy at initiation, and 8 discontinued background therapy. Baseline characteristics included: NYHA Class II (46.9%) and III (53.1%), female (66%), hypertension (50%), and atrial fibrillation (AF) (18%) (Table 1). Median follow-up and duration of mavacamten monotherapy were 48 wks (range 12-60 wks) and 57 wks (range 14-60 wks), respectively. Resting left ventricular outflow tract gradient (LVOTg) was ≤ 30 mmHg in 93%, 91% and 100% of patients at Wk 24, 36, and 60. Valsalva LVOTg was ≤ 30 mmHg in 61%, 77% and 86% of patients at Wk 24, 36, and 60 (Fig 1). No patients were in NYHA Class III at wk 60, and ~50% of patients were NYHA Class I by wk 48 (Fig 2). Mean reduction in LVEF was 4.8% over 60 wks. One patient had LVEF < 50% at Wk 20, resulting in a dose reduction (10 to 7.5 mg). Safety events included 3 hospitalizations due to AF ablation (n=1), viral gastrointestinal illness (n=1) and heart failure (n=1). Demographic, clinical characteristics, and outcomes were similar across the mavacamten monotherapy cohort, mavacamten in combination with background HCM therapy (n=207), and the overall cohort of MARVEL-HCM (N=239). Conclusions: Mavacamten monotherapy was effective, safe, and consistent with the overall MARVEL cohort, as well as previously reported monotherapy cohorts from pivotal, long-term, and real-world evidence.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving hemodynamics and reducing LVOT obstruction. However, its impact on arrhythmic burden remains unclear, with reports of early atrial fibrillation (AF) risk contrasting with long-term reductions in arrhythmias. This study assesses the temporal patterns of Holter-detected arrhythmias in HCM patients treated with mavacamten. Methods: This retrospective study included HCM patients from three Mayo Clinic sites. Baseline demographic, clinical, and echocardiographic data were collected. Holter monitoring was performed at baseline, short-term (<6 months), and long-term (>6 months) follow-up. Arrhythmic events, including premature atrial contractions (PACs), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT), were analyzed using standardized rates per 24 h. Statistical comparisons utilized the Wilcoxon signed-rank test. Results: Twenty-seven patients (56% female, median age 66 years) were included. PACs, PVCs, and SVT duration transiently but not significantly increased at short-term follow-up but returned to baseline at long-term follow-up. No sustained or high-risk ventricular arrhythmias were observed. Conclusions: Mavacamten is associated with transient arrhythmic fluctuations early in treatment, followed by stabilization. These findings support its long-term electrophysiological safety and underscore the need for early rhythm monitoring. Further research should explore its role in arrhythmic risk stratification in HCM patients.

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.