Role of epicardial adipose tissue in human atrial fibrillation

A recent meta‐analysis among which four reports were conducted in Japan demonstrated that epicardial adipose tissue (EAT) is closely associated with an increased risk of atrial fibrillation (AF) recurrence after catheter ablation. We previously investigated the role of EAT in AF in humans. Left atrial (LA) appendage samples were obtained from AF patients during cardiovascular surgery. Histologically, the severity of fibrotic EAT remodeling was associated with LA myocardial fibrosis. Total collagen in the LA myocardium (i.e., LA myocardial fibrosis) was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin‐6, monocyte chemoattractant protein‐1, and tumor necrosis factor‐α, in EAT. Human peri‐LA EAT and abdominal subcutaneous adipose tissue (SAT) were obtained by autopsy. EAT‐ or SAT‐derived conditioned medium was applied to the rat LA epicardial surface using an organo‐culture system. EAT‐conditioned medium induced atrial fibrosis in organo‐cultured rat atrium. The profibrotic effect of EAT was greater than that of SAT. The fibrotic area of the organo‐cultured rat atrium treated with EAT from patients with AF was greater than in patients without AF. Treatment with human recombinant angiopoietin‐like protein 2 (Angptl2) induced fibrosis in organo‐cultured rat atrium, which was suppressed by concomitant treatment with anti‐Angptl2 antibody. Finally, we attempted to detect fibrotic EAT remodeling on computed tomography (CT) images, which demonstrated that the percent change in EAT fat attenuation was positively correlated with EAT fibrosis. Based on these findings, we conclude that the percent change in EAT fat attenuation determined using CT non‐invasively detects EAT remodeling.