Epicardial fat and atrial fibrillation: the perils of atrial failure

Abstract

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.

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

“…The issue that adipose tissue distribution affects cardiovascular disease has been widely discussed ( 8 – 10 ). The present study found that systemic redistribution of body adipose tissue occurred in AF patients, where the accumulation of total EAT surrounding the heart had a closer correlation with the LA remodeling and dysfunction in AF patients than the adipose tissue in other parts of the body, including subcutaneous, extraperitoneal, and intra-abdominal ones.…”

“…The latest view considers that AF is the last stage of atrial remodeling, and the main pathological mechanisms include cardiac structural and electrophysiological disorders ( 10 ). The present study found that EAT, especially LA-EAT, may contribute to cardiac structural and electrical remodeling and dysfunction, leading to the occurrence of AF.…”

“…Over the past decades, a growing data from epidemiological, clinical and translational studies have demonstrated that EAT is associated with the presence, severity, and recurrence of AF (8)(9)(10). Poggi et al suggested that a tight paracrine crosstalk existed between EAT and myocardium due to their anatomical and functional features, and the dysfunctional EAT can determine a pro-inflammatory environment in the surrounding myocardial tissue (10). Batal et al found that increased posterior LA fat thickness appears to be associated with AF burden independent of age, body mass index, or LA area (8).…”

Browning Epicardial Adipose Tissue: Friend or Foe?

“…EAT-secreted adipokines could contribute to structural remodeling of the atrial myocardium that promotes fibrosis. This remodeling could enhance the loss of cells connection, altering the propagation of the depolarizing wave and leading to conduction defects: formation of microcircuits and breakthrough of electrical impulses [88,89]. The amount of EAT could also exercise a mechanical effect on left ventricle (LV) and right ventricle (RV) filling and lead to an atria enlargement, which is one of the risk factors for AF [90].…”

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study

“…There are multiple physiological functions of EAT in relation to AF, and there seems to be a dichotomy in the physiological effects of EAT [ 6 , 7 ]. It is believed to provide both thermoregulation and mechanical protection to the heart and coronary arteries in healthy human beings [ 8 , 9 ], but the role of EAT in the development and severity of AF has been investigated and suggests deleterious effects of EAT.…”