Substrate Comprising Fibrosis and Epicardial Adipose Tissue-Associated Electrophysiological Remodeling Can Sustain Atrial Fibrillation Drivers: Insights from Image-Personalized Computational Simulations

Background Computational models of atrial fibrillation (AF) help clarify arrhythmia mechanisms, but the contribution of left atrial (LA) epicardial adipose tissue (EAT) is rarely included. Objective To assess whether incorporating EAT-associated effects into fibrosis-based atrial models alters reentrant arrhythmia inducibility, and to characterize the pro-arrhythmic properties of EAT-affected tissue. Methods LA fibrosis and EAT were quantified by LGE and Dixon MRI in 19 patients with persistent AF. For each patient, three anatomically identical image-personalized models were built (fibrosis only; fibrosis plus half-epicardial EAT effects, 0.5 mm; fibrosis plus full-epicardial EAT effects, 1.0 mm), yielding 855 simulations. In EAT regions, inward rectifier K + current was reduced by 35%, intracellular K + by 50%, and conduction velocity by 25%. Results Sustained reentry occurred in 370 simulations (43.3%), of which 306 had a functional (rotor-driven) component. Functional reentry inducibility rose from 22.8% (fibrosis only) to 41.4% (half-EAT) and 43.2% (full-EAT). At least one functional reentry was inducible in 12/19 fibrosis-only models, 18/19 half-EAT models, and 19/19 full-EAT models. Median inducible simulations per patient increased from 4 to 6 (p=0.004) and 7 (p=0.003), without significant difference between half- and full-EAT (p=0.895). Fibrosis/EAT overlap regions comprised only 2.1% of the LA wall but were the most arrhythmogenic, with a median 65.5% of their volume harboring reentry versus 8.8% (non-substrate), 37.3% (fibrosis), and 42.8% (EAT) (all p<0.001). In an exploratory analysis of PVI-only ablation patients (n=13), fibrosis-EAT overlap outside the PVI region was associated with 1-year recurrence (log-rank p=0.007). Conclusion Adding EAT effects to fibrosis-based models increased sustained functional reentry, with transmural depth contributing only modestly. Reentry anchored preferentially where fibrosis and EAT effects coexisted.