The Role of Epicardial Adipose Tissue in the Development of Atrial Fibrillation, Coronary Artery Disease and Chronic Heart Failure in the Context of Obesity and Type 2 Diabetes Mellitus: A Narrative Review

Abstract

Cardiovascular diseases (CVDs) are a significant burden globally and are especially prevalent in obese and/or diabetic populations. Epicardial adipose tissue (EAT) surrounding the heart has been implicated in the development of CVDs as EAT can shift from a protective to a maladaptive phenotype in diseased states. In diabetic and obese patients, an elevated EAT mass both secretes pro-fibrotic/pro-inflammatory adipokines and forms intramyocardial fibrofatty infiltrates. This narrative review considers the proposed pathophysiological roles of EAT in CVDs. Diabetes is associated with a disordered energy utilization in the heart, which promotes intramyocardial fat and structural remodeling. Fibrofatty infiltrates are associated with abnormal cardiomyocyte calcium handling and repolarization, increasing the probability of afterdepolarizations. The inflammatory phenotype also promotes lateralization of connexin (Cx) proteins, undermining unidirectional conduction. These changes are associated with conduction heterogeneity, together creating a substrate for atrial fibrillation (AF). EAT is also strongly implicated in coronary artery disease (CAD); inflammatory adipokines from peri-vascular fat can modulate intra-luminal homeostasis through an “outside-to-inside” mechanism. EAT is also a significant source of sympathetic neurotransmitters, which promote progressive diastolic dysfunction with eventual cardiac failure. Further investigations on the behavior of EAT in diabetic/obese patients with CVD could help elucidate the pathogenesis and uncover potential therapeutic targets.

Determinants of Arterial Stiffness in Patients with Morbid Obesity. The Role of Echocardiography and Carotid Ultrasound Imaging

“…Epicardial adipose tissue modulates the secretion of adipokines, molecules with an active role in the development of atherosclerosis [ 7 , 31 , 32 ]. In our study, we did not find statistically significant correlations between serum adipokine levels and epicardial adipose tissue thickness, but we attribute this result to the analysis of a small group of patients.…”

The role of epicardial adipose tissue dysfunction in cardiovascular diseases: an overview of pathophysiology, evaluation, and management

“…The former is located directly around or on the coronary artery adventitia; the latter is located just over the myocardium and is in direct contact with the myocardium ( 9 ). Vascular supply by coronary arteries in EAT forms part of the perivascular adventitia ( 10 ). It is thought to play a protective mechanical role against the tension and twist of an arterial pulse ( 11 , 12 ).…”

Association of epicardial fat with cardiac structure and function and cardiovascular outcomes: A protocol for systematic review and meta-analysis

“…Many observational studies have reported that increased epicardial is associated with adverse metabolic profile, cardiovascular risk factors, and coronary atherosclerosis in patients with cardiovascular diseases and in general population [1]. We and others have previously reported the independent association of increased epicardial fat with left ventricular (LV) hypertrophy and diastolic dysfunction as well as the development of heart failure (HF) and coronary artery disease in these populations [2][3][4][5][6][7][8]. In some studies, however, the association did not reach statistical significance [9,10].…”