Abstract and Introduction
Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside—and even without—mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.
Obesity and atrial fibrillation (AF) share a multifactorial pathogenesis—including biological, socio-economic, and environmental factors—as well as some of the heterogeneous pathways and mechanisms that contribute to adverse health outcomes. Although recently revised, the classical concept of obesity has been widely associated with cardiac diseases, including arrhythmias. Indeed, estimates suggest that obesity may account for one-fifth of total AF cases for ~60% of the recent incident cases increase.[2–4] Weight gain and a higher body mass index (BMI) are strongly correlated with incident AF so that every 5-unit increment in BMI would confer an ≈29% greater risk of incident AF, while a reduction of 1 kg/m2 can decrease by 7%. Body mass index is also associated with the risk of post-surgical and post-ablation AF as well as the likelihood of progression from paroxysmal to permanent AF as well. Even impressive, these values seem to underestimate the real impact of adiposity when body fat distribution is considered. Whereas BMI is no longer considered a reliable marker of obesity, the new term of 'adiposopathy' seems more representative of such a heterogeneous condition, characterized by different phenotypes. The shift towards visceral adipose tissue (VAT) distribution alongside insulin resistance, pro-inflammatory adipo-cytokine unbalance, and abnormal deposition of ectopic fat (e.g. within liver, pancreas, heart, kidney, and skeletal muscle) are then increasingly described as the new paradigm of obesities. As compared with subcutaneous fat depots, especially VAT is highly sensitive to the maladaptive processes induced by hypercaloric/overnourished state—mainly adipocyte hypertrophy—with subsequent adipocyte dysfunction and shift towards a pro-inflammatory phenotype.
Here, we will focus on epicardial adipose tissue (EAT), a visceral fat depot located between the myocardium and the epicardium. It should be distinguished from paracardial fat (adipose tissue located external to the parietal pericardium) and pericardial fat (often defined as paracardial fat plus epicardial fat). Epicardial adipose tissue is a complex microenvironment in which several cell types interact. We will summarize and update current knowledge of how adiposopathy might impact on AF by focusing on the mechanisms sustaining atrial remodelling. A risk gradient for AF indeed exists and progresses as fat depots are specifically defined from general adiposity (BMI) to visceral and finally EAT.[10,11]
Europace. 2022;24(8):1201-1212. © 2022 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.