Epicardial adipose tissue as a mediator of cardiac arrhythmias.

Kiran Haresh Kumar Patel,Fu Siong Ng,Curtis Se Liebers,Taesoon Hwang

doi:10.1152/ajpheart.00565.2021

Kiran Haresh Kumar Patel, Fu Siong Ng + Show 2 more

Open Access

https://doi.org/10.1152/ajpheart.00565.2021

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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. Among 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 remodeling 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 remodeling 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 remodeling to ameliorate arrhythmic risk.

Highlights

Atrial fibrillation is the most common arrhythmia globally and its impact on healthcare systems is forecast to increase with an aging population [1, 2]
Consistent with this, epicardial adipose tissue (EAT) has been implicated in arrhythmogenesis owing to its intimate relationship with the underlying myocardium [13, 14]
We summarize the evidence for its role as a transducer of inflammation to the underlying myocardium and outline the mechanisms by which it may induce an arrhythmogenic substrate

Summary

INTRODUCTION

Atrial fibrillation is the most common arrhythmia globally and its impact on healthcare systems is forecast to increase with an aging population [1, 2]. The current body of evidence suggests possibilities of therapeutically treating and preventing electrophysiological changes that are induced by lipotoxicity and obesity These studies provide insights into the modulation of ionic currents in a lipotoxic environment, the contrasting effects of FFA on APD may stem from differences in animal models, including atrial versus ventricular myocytes, as well as the duration of FFA exposure. FFAs modulate connexin expression with OA and arachidonic acid shown to inhibit gap junctional coupling within hours of exposure in neonatal rat cardiac myocytes [141, 142] This was rapidly reversed with washing the cells in a FFA-free solution, suggesting the effect is most likely to be due to an extracellular component activating membrane receptors [141, 142] and subsequently initiating an intracellular signaling pathway mediated by protein kinases via G protein-coupled receptors [143, 144]. Given that QT interval and QT dispersion are metrics by which ventricular arrhythmic risk is determined [171,172,173,174,175], it is plausible that the benefits of weight loss may extend to arrhythmias of ventricular origin, this remains to be determined

CONCLUSIONS

Findings

DISCLOSURES