Genetic evaluation of early-onset atrial fibrillation: impact on patient management

Background and Aims Genetic testing is recommended for select patients with atrial fibrillation (AF). The aims of this study were to define the results of genetic evaluation and its therapeutic impact for patients referred to a dedicated AF precision medicine clinic. Methods Patients diagnosed with AF before age 60 were candidates for referral. In addition to standard evaluation with history, physical exam, and electrocardiogram (ECG), genetic evaluation included a three-generation pedigree, cardiac imaging, ambulatory monitoring, and clinical genetic testing with a cardiomyopathy/arrhythmia panel. Results Overall, 264 participants were referred: the median age was 47 years (Q1, Q3: 38, 55), 77 (29%) were female, and 236 (89%) were White. Median age at AF diagnosis was 39 years (Q1, Q3: 31, 48), and median time from AF diagnosis to evaluation was 3.7 years (Q1, Q3: 0.9, 10). A total of 242 patients (92%) underwent genetic testing, which identified a pathogenic or likely pathogenic variant in 48 (20%). The strongest predictors of positive genetic testing were history of cardiomyopathy, infranodal conduction disease, and elevated T1 or late gadolinium enhancement on cardiac magnetic resonance imaging (all P < .05). The strongest predictors of negative genetic testing were obstructive sleep apnoea and a normal 12-lead ECG (both P < .04). Overall, genetic testing changed clinical management in 52% of patients with positive genetic testing, highlighted by seven new implantable cardioverter-defibrillator placements and initiation of disease-modifying therapy in 16 patients. Conclusions Genetic testing was positive in 20% of patients with early-onset AF referred to a dedicated AF precision medicine clinic. Genetic testing results may change clinical management in genotype-positive patients.