Epicardial adipose tissue as a mediator of cardiac arrhythmias

Abstract

Obesity is associated with higher risks of cardiac arrhythmias. Although this may be partly explained by concurrent cardiometabolic ill-health, growing evidence suggests that increasing adiposity independently confers risk for arrhythmias. Amongst fat depots, epicardial adipose tissue (EAT) exhibits a proinflammatory secretome, and given the lack of fascial separation, has been implicated as a transducer of inflammation to the underlying myocardium. The present review explores the mechanisms underpinning adverse electrophysiological remodelling as a consequence of EAT accumulation and the consequent inflammation. We first describe the physiological and pathophysiological function of EAT and its unique secretome, and subsequently discuss the evidence for ionic channel and connexin expression modulation as well as fibrotic remodelling induced by cytokines and free fatty acids that are secreted by EAT. Finally, we highlight how weight reduction and regression of EAT volume may cause reverse remodelling to ameliorate arrhythmic risk.

Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD

“…Moreover, we simultaneously evaluated EAT which is considered an earlier subrogate marker of CVD, mediator of cardiac arrhythmias 12 and left ventricular diastolic dysfunction 13 . In 2013, Mahabadi et al 27 determine that EAT predicted MACE in the general population in participants from the prospective population-based Heinz Nixdorf Recall cohort (n = 4093 participants, age 59.4 years, 47% male) during a follow-up period of 8.0 ± 1.5 years.…”

“…Systemic inflammation and oxidative stress support subclinical organ dysfunction and gradually contributes to the development and progression of atherosclerosis 32 , 32 . Furthermore, the secretion of proinflammatory cytokines from EAT reinforces the prevailing systemic proinflammatory activity, which in turn results in pathological changes of the coronary arteries 10 , 10 and/or structural changes of the contiguous myocardium which can eventually lead to the development of cardiac arrhythmias 12 and left ventricular diastolic dysfunction 13 . In summary, AT dysfunction 39 and IR 34 are important mechanisms linking both entities, although, additional mechanisms, like dysbiosis and genetic susceptibilities, may interplay a role in the pathophysiology of NAFLD and CVD 32 , 32 .…”

“…Coronary artery calcium (CAC) 8 , 8 and epicardial adipose tissue (EAT) 10 , 10 are considered surrogate markers of coronary artery disease and have significantly improved the cardiovascular risk classification in asymptomatic individuals 8 – 11 . EAT is a novel clinical biomarker not only associated with accelerated progression of subclinical coronary atherosclerosis 10 , 10 , but also mediator of cardiac arrhythmias 12 , left ventricular diastolic dysfunction 13 , and stroke 14 . EAT has important physiological functions 15 , nonetheless, excessive EAT leads to a proinflammatory state with adverse effects on the myocardium.…”

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

“…Furthermore, NAFLD favours epicardial fat accumulation resulting in cardiac lipotoxicity, fatty infiltration, fibrosis, and yet more secretion of inflammatory mediators. That creates a vicious cycle of increasing metabolic perturbation to cause structural, electrical, and autonomic remodelling ( 33 , 34 ).…”

Septal summit: A narrow epicardial region above the left ventricular summit. Implications for electrophysiological procedures

“…The contents within this region include arteries, veins, and epicardial fibers of the intrinsic cardiac autonomic plexus [7]. All are covered by various amounts of epicardial adipose tissue [8]. Arteries are represented by small septal perforating arteries exiting from the left main trunk or proximal aspect of the left anterior descending artery [4].…”