Abstract 19176: Atrial Fibrillation Prevalence With Mavacamten for Obstructive Hypertrophic Cardiomyopathy

Abstract

Introduction: Mavacamten is a first-in-class, small molecule, selective cardiac myosin inhibitor for treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). Partial reversal of hypertrophic remodelng, diastolic dysfunction, and sarcomeric calcium sensitivity have been reported. While atrial fibrillation (AF) prevalence is observed in ~10% of pre-approval study subjects, the effects of mavacamten on AF have not been reported. Hypothesis: AF prevalence remains elevated after mavacamten therapy for HCM Methods: Chart review was performed for standard of care clinical encounters, 12-lead ECG, and echocardiography (TTE) for patients treated mavacamten at a single HCM referral center. Results: Among 12 patients prescribed mavacamten, 92% had no prior AF symptoms nor diagnosis. After 6 months of mavacamten therapy, 25% had AF with 17% new-onset. TTE demonstrated resolution of LVOT gradients in 100% of AF patients at 6 months. Case 1: 60-year-old male with OSA and LVOT gradients of 31 mmHg at rest and 41 mm Hg with Valsalva was started on mavacamten for exertional fatigue and dyspnea. After 3 months, he developed new-onset, paroxysmal AF treated by TEE-guided cardioversion, amiodarone and apixiban. Case 2: 66-year-old female with LVOT gradients of 38 mmHg at rest and 74 mm Hg with Valsalva initiated mavacamten for exertional dyspnea. After mavacamten initiation, exertional symptoms improved but frequent episodes of symptomatic AF persisted despite sotalol 120mg. Case 3: 58-year-old female with LVOT gradient of 97 mm Hg at rest and no change with Valsalva and dyspnea on exertion. After unexplained syncopal events, an implantable cardiac monitor recorded AF. After 1 month of mavacamten, she experienced increased frequency of AF. Conclusions: In a single center experience with mavacamten, AF prevalence of 25% with 17% new onset AF developed despite improvement in symptoms and hypertrophic remodeling parameters. As a novel cardiac myosin inhibitor that attenuates hypertrophic remodeling, diastolic dysfunction, and calcium sensitivity that are anticipated to reduce AF susceptibility, more observation of arrhythmia incidence and burden in larger cohorts will inform arrhythmia outcomes and mechanisms in HCM.