Interatrial septal thickness and risk of incident atrial fibrillation

Background Obesity is associated with increased risk of atrial fibrillation (AF), yet susceptibility varies widely among individuals with obesity. Ectopic cardiac adiposity may contribute to atrial remodeling and arrhythmogenesis. Interatrial septal (IAS) thickening, an imaging finding associated with lipomatous hypertrophy of the interatrial septum, may provide a clinically accessible marker of localized atrial adiposity, but its long-term association with incident AF is not well defined. Methods We conducted a retrospective cohort study of adults who underwent clinically indicated, nonemergent diagnostic transesophageal echocardiography (TEE) between 2010 and 2017 for indications other than arrhythmia evaluation. Patients with interatrial septal (IAS) thickness >5 mm on the index TEE were included, whereas those with prior AF or TEE performed for suspected or known arrhythmia were excluded. IAS thickness was measured on the index TEE. Incident AF and all-cause mortality were ascertained from electronic health records through January 1, 2024. IAS thickness was first modeled as a continuous exposure using competing risk regression, with death treated as a competing event. Restricted cubic splines were used to assess nonlinearity and identify a potential risk threshold. We then examined categorical IAS thickening in relation to long-term incident AF using multivariable competing risk models and cumulative incidence functions and tested for interaction by obesity status (body mass index ≥30 kg/m²). All models were adjusted for age, sex, comorbidity burden (including, but not limited to, heart failure and at least moderate valvular heart disease), and mitral regurgitation. Results Among 880 patients (median follow-up 6.76 years), 236 developed incident AF. In competing risk restricted cubic spline analyses, the association between IAS thickness and AF risk was non-linear, with a threshold for increased risk at approximately 19 mm; AF risk was relatively stable below this value and increased incrementally with greater IAS thickness above the threshold. Patients with IAS thickness ≥19 mm had a higher cumulative incidence of AF over follow-up (adjusted hazard ratio [aHR] 1.58; 95% confidence interval [CI] 1.12–2.23; p=0.010). In multivariable models, the association between marked IAS thickening and incident AF was not modified by obesity (p-for-interaction= 0.860). Conclusions In patients undergoing TEE for non-arrhythmic indications, IAS thickness exhibited a threshold association with incident AF, with risk increasing above 19 mm. Marked IAS thickening was independently associated with long-term AF risk, and this association was observed irrespective of obesity status. These findings suggest that IAS thickness captures risk beyond generalized adiposity and may serve as a clinically accessible imaging marker to refine AF risk stratification.