Inflammation and Adiposity: New Frontiers in Atrial Fibrillation

Vishal Vyas; Ross J. Hunter; M. Paula Longhi; Malcolm C. Finlay


Europace. 2020;22(11):1609-1618. 

In This Article

Abstract and Introduction


The aetiology of atrial fibrillation (AF) remains poorly understood, despite its growing prevalence and associated morbidity, mortality, and healthcare costs. Obesity is implicated in myriad different disease processes and is now recognized a major risk factor in the pathogenesis of AF. Moreover, the role of distinct adipose tissue depots is a matter of intense scientific interest with the depot directly surrounding the heart—epicardial adipose tissue (EAT) appearing to have the greatest correlation with AF presence and severity. Similarly, inflammation is implicated in the pathophysiology of AF with EAT thought to act as a local depot of inflammatory mediators. These can easily diffuse into atrial tissue with the potential to alter its structural and electrical properties. Various meta-analyses have indicated that EAT size is an independent risk factor for AF with adipose tissue expansion being inevitably associated with a local inflammatory process. Here, we first briefly review adipose tissue anatomy and physiology then move on to the epidemiological data correlating EAT, inflammation, and AF. We focus particularly on discussing the mechanistic basis of how EAT inflammation may precipitate and maintain AF. Finally, we review how EAT can be utilized to help in the clinical management of AF patients and discuss future avenues for research.


Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with its prevalence only set to increase over time.[1] While in 2010, there were an estimated 8.8 million cases of AF in Europe alone, by 2060, this is estimated to rise to 17.9 million.[2] AF is frequently highly symptomatic and is far from a benign condition. It significantly worsens outcomes in heart failure,[3] contributes to cognitive decline and vascular dementia,[4] and is the single most frequent cause of stroke.[5] Moreover, these strokes secondary to AF are associated with greater morbidity and mortality.[6] The field has evolved from initial mechanistic thinking that AF arises from a single atrial ectopic focus to a self-sustaining rotor or spiral waves arising from the left-atrial pulmonary vein junction.[7,8] This notion is supported by clinical evidence from catheter ablation of AF, which is typically centred around isolating the pulmonary veins from the left atrium, which in turn can terminate AF.[9] Unfortunately, the term 'AF begets AF'[10] stands true with electroanatomical changes in the left atrium occurring following a period of time spent in AF. Electrically, there is a down-regulation of L-type calcium channels altering calcium handling and the refractory period[10] while structurally, progressive fibrosis occurs in the left atrium.[11] This deleterious atrial remodelling forges the substrate for AF to occur and persist.

Despite these significant advances in understanding the arrhythmic mechanisms of AF, the pathophysiology of the disease processes underlying AF remain poorly understood. An area of growing interest is the role of adiposity in AF pathogenesis. Obesity is well recognized as a major modifiable risk factor for a host of cardiovascular diseases with an increase in the incidence of AF coinciding with the obesity epidemic.[12] The Women's Health Study demonstrated a linear relationship between body mass index (BMI) and AF, with a 4.7% increase in AF risk for every 1 kg/m2 increase in BMI.[13] Subsequent studies[14] and a meta-analysis have indicated that a rise in BMI parallels a marked increase in AF risk.[15]

While BMI is the most commonly used marker of obesity, there are many other clinical markers of adiposity which better reflect body fat distribution (such as waist circumference[16]). Moreover, our appreciation of the relative importance of different adipose tissue depots and their associated risk is improving. Data from the Framingham Heart Study[17] demonstrated that visceral adipose tissue appears to be associated with a greater cardiovascular risk profile compared with the subcutaneous adipose tissue depot. The authors alluded to measuring/imaging of visceral adipose tissue to aid in understanding the risk profile rather than relying on anthropometric measurements alone.

The advent of sophisticated non-invasive imaging such as multidetector computed tomography (CT) and cardiac magnetic resonance (CMR) has facilitated the visceral adipose tissue surrounding the heart to be imaged directly.[18] Here, we explore the unique and specific risk associated with epicardial adipose tissue (EAT) in AF which may also be critical in unravelling the mechanism behind why obesity increases AF risk.

We first discuss the physiology of adipose tissue and the burgeoning epidemiological basis behind the AF–EAT correlation, mechanistic data and putative theories of EAT's role in AF pathophysiology. Finally, we evaluate the clinical implications of EAT in guiding AF management and future research horizons.