Age-Dependent Role of Genetics and Renal Function for Atrial Fibrillation Development in Hypertrophic Cardiomyopathy

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate whether genetic, structural, and clinical factors were associated with atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). METHODS: Of the 212 prospectively enrolled patients in the HCM genetic registry, 33 had initial AF, and the remaining 179 (126 males, 58±13 years) were followed up for the development of new-onset AF. RESULTS: Patients with initial AF had older age, lower estimated glomerular filtration rate (eGFR), lower left ventricular (LV) global longitudinal strain, higher left atrial volume index (LAVI), and higher LV extracellular volume fraction. During a median follow-up period of 916 (400-1,327) days, AF occurred in 12 (6.7%) patients. In Cox regression analysis, lower eGFR (hazard ratio per 1 mL/min/1.73 m² increase, 0.93; p=0.007), LV ejection fraction (hazard ratio, 0.82; p=0.009), and higher LAVI (hazard ratio, 1.07; p=0.010) were associated with increased risk of future AF. The addition of eGFR to LAVI significantly increased the global χ² value (8.508 to 15.017; p=0.006). Among patients younger than 65 years (n=128), those with any sarcomere variants (pathogenic and variants of uncertain significance [VUS], n=77) had a higher prevalence of overall AF (initial and new-onset, 82.4% vs. 56.8%; p=0.045). CONCLUSIONS: In patients with HCM, decreased renal function provides an additive predictive value on LAVI for future AF. In patients younger than 65, the presence of sarcomere variants, including VUS, is related to a higher prevalence of AF.