Epicardial adipose tissue and atrial fibrillation: Possible mechanisms, potential therapies, and future directions

Abstract

Obesity plays an important role in the pathogenesis of atrial fibrillation (AF). Recently, rather than general fat distribution, epicardial adipose tissue (EAT) gains a growing concern. EAT is the local adipose deposition between myocardium and pericardium. Accumulated evidence revealed several distinguishing characteristics of EAT. It lies contiguously with the myocardium and could infiltration into myocardium, actively secrets cytokines and adipokines mediating inflammation or remodeling, and contains abundant ganglionated plexi. Clinical research also found EAT may be an independent risk factor of AF. Volume or thickness of EAT measured on CT or MRI could be applied as a predictor of presence, severity, and recurrence of AF. Some drugs, like antidiabetic drugs and lipid-lowing drugs, show ability to reduce EAT. Additional surgical ablation of EAT was also proved that it could improve outcome of pulmonary vein isolation for AF. In present review, we summarize recent epidemic, biological, and clinical findings about EAT and its possible role in AF. K E Y W O R D S atrial fibrillation, epicardial adipose tissue, mechanisms, therapies 1 2 THE LINK BETWEEN AF, OBESITY, AND ADIPOSE TISSUE Obesity and AFObesity is an already recognized risk factor of AF. 5,6 It is usually assessed by several indicators, such as body mass index (BMI), waist circumference, waist to hip ratio, and body fat rate. Compared with nonobese people, obese individuals possess higher probability (49%) of suffering AF, which may be associated with atrial enlargement, ventricular diastolic dysfunction, and ectopic fat depot increase. 5 Furthermore, previous literature showed that every 5 kg/m 2 increase in BMI could increase about 10-30% higher risks of AF, and also indicated that every 1 kg/m 2 reduction in BMI was associated with a significant 7% reduction in the risk of AF. 7 These pieces of evidence support that obesity is closely associated with AF occurrence. However, in general, the indicators to measure obesity, such as BMI, are relatively rough to reflect excess adipose; and individuals with similar BMI may have different risks of AF. More precise measurements are needed to predict the occurrence and development of AF.

Topographical anatomy of the right atrial appendage vestibule and its isthmuses

“…There were also variations within each isthmus—the adipose layer was thickest near the valve annulus and thinnest near the RAA orifice. Since the epicardial adipose tissue produces numerous mediators that may promote atrial fibrillation, its distribution within the vestibule may be important for locating arrhythmogenic substrates 24 . Moreover, it is highly probable that abundant epicardial adipose tissue, that is located at the superior isthmus area could allow the muscle bundles of accessory nonannulus pathways to cross the annulus at a greater distance than anticipated (more epicardially), thus hindering their destruction via endocardial access 10,25 …”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…Thus, due to its proximity to the heart, EAT deregulation can affect myocardial function by increasing cardiac lipid accumulation, insulin resistance, and fibrosis due to a decreased secretion of anti-inflammatory adipokines such as adiponectin and an increased secretion of pro-inflammatory adipokines like leptin, TNFα, IL-1β, IL-6, or resistin [ 12 , 19 ]. Moreover, it has been proposed that the adipokines released by EAT in pathological conditions have paracrine effects on cardiac electrical activity, affecting conductivity and promoting atrial fibrillation [ 20 ], and in coronary arteries, they cause atherosclerosis through the promotion of inflammation and immune cell infiltration [ 21 , 22 ]. Lately, EAT thickness has been considered a clinical biomarker that correlates to features of heart failure and metabolic syndrome [ 23 , 24 , 25 , 26 , 27 ].…”

The characteristics and efficacy of catheter ablation of focal atrial tachycardia arising from an epicardial site

“…The mechanism of the arrhythmogenicity associated with epicardial adipose tissue is still uncertain and considered multifactorial. A previous systematic review 4 reported the possible mechanisms: inflammation, adipose infiltration, electrical remodeling, fibrosis and structure remodeling, autonomic nervous dysfunction, oxidative stress, gene expressing, local aromatase effect, and ventricular diastolic dysfunction. Nakahara et al 10 reported that epicardial adipose tissue was adjacent to the endocardial breakthrough of an SIAT and that the most likely mechanism of the AT was considered to be a neural reflex rather than mechanical stimulation because of the long distance between the AT focus at the right superior PV antrum and esophagus.…”

“…Post ganglionic efferent fibers innervate the atrial myocardium and can provoke supraventricular arrhythmias especially atrial fibrillation 1 . Other earlier studies 2‐5 have reported the participation of chronic low‐grade inflammation, oxidative stress, and the formation of reentrant circuits from intramyocardial fat and via the muscular bundles of the LOM and/or CS. On the other hand, focal atrial tachycardias (ATs) arising from the epicardial side (Epi‐AT) are rare arrhythmias or may be underestimated or unrecognized during catheter ablation (CA), because Epi‐ATs can often be successfully treated with a similar procedure as that used in ablation of ordinary ectopic ATs, and because such ATs may be recognized as unmappable ATs during endocardial CA.…”

“…The epicardial structures in the atrium such as the coronary sinus (CS), ligament of Marshall (LOM), and epicardial adipose tissue are associated with atrial arrhythmogenicity 1‐5 . The mechanism has not been fully clarified and is considered multifactorial.…”