Role of epicardial adipose tissue in atrial cardiomyopathy: focus on fibrosis, amyloid deposition, and arrhythmogenesis

Abstract Background Atrial cardiomyopathy (AC) is defined as any complex of structural, contractile, or electrophysiological changes of the atrium (1). Hallmark histopathological features include fibrosis, cardiomyocyte hypertrophy, fatty infiltration, inflammatory cell infiltration, and amyloid deposition—even in the presence of sinus rhythm—resulting in impaired atrial contractility (2). Epicardial adipose tissue (EAT) has emerged as a key modulator of atrial remodeling. EAT promotes a pro-inflammatory and pro-fibrotic phenotype and has been associated with atrial fibrillation presence (5,6), severity, and recurrence (3,4). A recent study highlighted a direct correlation between EAT thickness and postoperative AF (POAF), a complication affecting 20–40% of cardiac surgerieswith a long-term bad prognosis (7,8). The molecular pathways through which EAT contributes to atrial remodeling and arrhythmogenesis remain to be elucidated. Purpose We hypothesized that EAT may mediate structural and electrical atrial remodeling, contributing to the development of AC. This study aimed to evaluate the role of EAT in atrial fibrosis, amyloid deposition, and arrhythmogenic potential. Methods A retrospective cohort of 2,466 patients undergoing transthoracic echocardiography was analyzed to assess associations between EAT thickness (measured in end-systole between RV free wall and pericardium), atrial volume, strain, and chronic AF. In a prospective substudy, 40 patients undergoing coronary surgery were evaluated echocardiographically (atrial strain, size, LV and RV function, pulmonary pressure). EAT and right atrial biopsies were collected intraoperatively. Histological staining (H five stained positive for SAA, indicating inflammatory amyloidogenesis . Elevated IL-1β levels were identified in EAT secretome of POAF patients. In vitro, IL-1β promoted fibroblast proliferation and collagen synthesis . Conclusions EAT appears to contribute to atrial remodeling via inflammatory pathways, promoting fibrosis and amyloid deposition, and increasing arrhythmic susceptibility. IL-1β may serve as a key mediator linking EAT and atrial structural remodeling, offering a potential target for preventive strategies in AC and POAF.