Adiposity-associated atrial fibrillation: molecular determinants, mechanisms, and clinical significance

Abstract

Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered haemodynamic, increased sympathetic tone, and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits with discrete composition and localization that show distinct functions. Fatty tissue differentially affects the evolution of AF, with highly secretory active visceral fat surrounding the heart generally having a more potent influence than the rather inert subcutaneous fat. A variety of proinflammatory, profibrotic, and vasoconstrictive mediators are secreted by adipose tissue, particularly originating from cardiac fat, that promote atrial remodelling and increase the susceptibility to AF. In this review, we address the role of obesity-related factors and in particular specific adipose tissue depots in driving AF risk. We discuss the distinct effects of key secreted adipokines from different adipose tissue depots and their participation in cardiac remodelling. The possible mechanistic basis and molecular determinants of adiposity-related AF are discussed, and finally, we highlight important gaps in current knowledge, areas requiring future investigation, and implications for clinical management.

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

“…The cellular mechanisms by which EAT modulates cardiomyocyte calcium handling, indirectly by adipokines or directly by structural changes, are not as well studied. The reader is referred to Antonopoulos and Antoniades [ 11 ] for a detailed review of the current understanding of cellular mechanisms within EAT, cardiomyocytes, and fibroblasts within the myocardium and Gawałko et al [ 77 ] for a detailed review of the mechanistic changes underlying AF in obese patients.…”

“…Other studies have also reported the paracrine mediators secreted from EAT had similar effects of conduction slowing and AP prolongation [76], suggesting more pathogenic mechanisms than purely mechanical. However, other reports suggest that AP duration is reduced, which is considered a more common pathological change in the development of AF [58,59,77]. For example, Martinez-Mateu et al reported that in the atria of obese guinea pigs fed a high-fat diet, rapid pacing was associated with reduced voltage-gated potassium and L-type calcium current, with shortened AP duration and increased incident of afterdepolarizations [78].…”

Management of Atrial Fibrillation Using Immunoglobulin Free Light Chains, Novel Biomarkers of Inflammation

“…AF is a common cardiac arrhythmia, and inflammatory mechanisms play an important role in its pathogenesis. [1][2][3][4][5][6][7] AF is commonly found in older individuals, and type 2 diabetes, high blood pressure, obesity and genetics are important predisposing factors (Figure 1). [2][3][4] AF increases the risk of heart failure, stroke and thromboembolism, and increases morbidity and mortality in patients with cardiovascular diseases (CVDs).…”

“…[1][2][3][4][5][6][7] AF is commonly found in older individuals, and type 2 diabetes, high blood pressure, obesity and genetics are important predisposing factors (Figure 1). [2][3][4] AF increases the risk of heart failure, stroke and thromboembolism, and increases morbidity and mortality in patients with cardiovascular diseases (CVDs). 5 Inflammation is perhaps the most important determinant of AF and subsequent fibrosis in MI.…”

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation

“…As the body’s largest endocrine organ, adipose tissue is considered as a crucial regulator of AF, which may affect the occurrence, progression, and prognosis of AF ( 4 ). However, due to the broad dispersion of adipose tissue throughout the body and intra-organ location, the visceral fat with high secretory activity around the heart usually has a more practical effect than fat in other parts, promoting atrial remodeling and increasing the susceptibility to AF ( 5 ). As a kind of organ-specific adipose tissue in direct contact with the surface of the heart, epicardial adipose tissue (EAT) can secrete paracrine or endocrine inflammatory cytokines, adipokines, or other factors that influence the health or diseases of the heart ( 6 ).…”