Abstract 4358635: Atrial Fibrillation in Genotyped Dilated Cardiomyopathy: Epidemiology and Associated Risk Factors - Insights from the SHaRe Consortium

Background: Atrial fibrillation (AF) is the most common arrhythmia in dilated cardiomyopathy (DCM) and is associated with adverse outcomes. Characterization of AF in DCM by genotype and clinical features remains limited. Aims: To describe AF prevalence and incidence in DCM stratified by genotype and disease gene, and to identify clinical and genetic predictors of incident AF. Methods: Using the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), we included 3117 DCM patients who had genetic testing. AF prevalence, incidence, clinical characteristics and genotype (genotype-positive [G+], defined by the presence of a pathogenic/likely pathogenic [P/LP] variant in a DCM gene or genotype-negative [G-]) were assessed and further stratified by disease gene. Predictors of incident AF were identified with uni- and multivariable analyses. Covariates for the multivariable model were selected based on clinical relevance and discriminative performance (C-index 0.74), and included age at first site visit, sex, genotype, prior heart failure (HF) hospitalization and left atrial (LA) diameter. Results: Of 3117 patients with DCM (mean age 48±15 years, 39% female, 35% G+), 12.3% (n=384) had prevalent AF. Among 2491 patients without prevalent AF, 12.5% (n=312) developed incident AF during a median follow-up of 4.5 years (IQR 1.6-9.0). AF burden varied by disease gene (Figure 1). Patients with P/LP LMNA variants had the highest AF prevalence (56.7%) and incidence (7.6/100 patient-years), with AF typically preceding left ventricular systolic dysfunction, and LMNA was the only gene independently associated with incident AF in multivariable analysis (HR 7.10, 95% CI 4.44-11.36; p<0.001). In contrast, those with P/LP TTN variants had lower AF burden (prevalence 24.4%, incidence 2.1/100 patient-years), comparable to G- patients, despite having the largest LA diameter (41±7mm). Patients with P/LP DSP variants were the 3 rd largest gene group (n=156) but had the lowest AF prevalence (7.4%) and incidence (0.8/100 patient-years). Additional independent predictors of incident AF included male sex, prior HF hospitalization, older age at first visit, and larger LA diameter (Table 1). Conclusion: In this multicenter cohort study of genotyped patients with DCM, LMNA had the strongest genetic association with AF, while TTN had lower AF rates despite larger LA diameter. Genotype-based risk stratification may help guide AF surveillance and management in DCM patients.