Incidence and Outcomes of Atrial Fibrillation and Systolic Dysfunction in Patients Receiving Mavacamten for Obstructive Hypertrophic Cardiomyopathy: A Multicenter Study.

Mavacamten is highly effective in treating symptomatic obstructive hypertrophic cardiomyopathy (oHCM) and was approved for commercial use with a risk mitigation program (REMS) to monitor the impact on left ventricular systolic function (LVSD). The impact of mavacamten on atrial fibrillation (AF) occurrence is not well characterized. Determine the real-world incidence of new-onset and recurrent AF among patients with HCM treated with commercial mavacamten. Secondary objectives included assessing the incidences of LVSD, heart failure (HF), and cardiogenic shock. A multicenter cohort study. Center-level data were aggregated for patients who received mavacamten from May 2022 through December 2024. Twenty-one outpatient HCM centers in the United States. Consecutive patients ≥18 years of age with oHCM were included; those with permanent AF were excluded. At least one dose of commercial mavacamten. Incidence of new-onset and recurrent AF, LVSD, HF, and cardiogenic shock. Among 1,538 patients (median age, 66 years [95% CI, 65.9-66.1]; 57% female [95% CI, 54-59%]), 25% [95% CI, 22-27%] had prior AF. Median mavacamten exposure was 13.4 months [95% CI, 11.8-15.0].Overall AF incidence was 13% [95% CI, 10-17%], including 5% [95% CI, 4-7%] new-onset and 39% [95% CI, 27-51%] recurrent AF in those with history of AF prior to mavacamten initiation. LVEF <50% occurred in 8% [95% CI, 6-9%], of whom 70% had AF. Symptomatic HF occurred in 1.5% [95% CI, 0.8-2.2%], cardiogenic shock in 0.6% [95% CI, 0.1-1.0%], and an overall permanent discontinuation of mavacamten in 7% [95% CI, 4-10%]. In this multicenter cohort receiving commercial mavacamten, we identified an annual incidence of 5% new-onset AF and 39% recurrent AF, while 70% of patients who developed LVEF<50% had concurrent AF. Given this association and the morbidity that can be associated with AF, protocols for LVEF assessment and aggressive rhythm management following AF detection may be warranted to improve patient care. Further studies are needed to improve understanding of the impact of mavacamten on AF and patient outcomes. Question: What are the real-world burden and consequences of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy treated with commercial mavacamten?Findings: In a multicenter cohort of more than 1,500 patients, 5% experienced new-onset AF, while 39% of those with pre-existing AF experienced recurrence after mavacamten initiation. Left ventricular ejection fraction (LVEF) fell below 50% in 8% of patients, 70% of whom had concurrent AF.Meaning: Real-world experience with mavacamten emphasizes that regular surveillance for AF is an important aspect of managing patients with HCM. Additionally, the identification of AF should prompt LVEF assessment and aggressive rhythm management, given the potential association between AF and decrease in LVEF. The observed incidence of AF on mavacamten highlights the need for further studies on potential mechanisms and for proactive surveillance and management strategies.