Chewing the Fat on Atrial Fibrillation

See also the article by Gunasekaran et al in this issue.

Arthur E. Stillman, MD, PhD, is the William & Kay Casarella Professor of Radiology and Imaging Sciences at Emory University. He is a past president of the North American Society for Cardiovascular Imaging and chair of the Cardiovascular Radiology and Intervention Council of the American Heart Association. He is a distinguished investigator of the Academy for Radiology & Biomedical Imaging Research and is an honorary member of the European Society of Cardiac Radiology.

Gunasekaran et al utilized an arrhythmia-insensitive cardiac T1 mapping pulse sequence to evaluate whether left ventricular fibrosis as assessed by extracellular volume is a feature of patients with atrial fibrillation (1). They found no such association, even for patients with left ventricular dysfunction. They postulated that even though atrial fibrosis is known to be present with atrial fibrillation, given the improvement of left ventricular dysfunction seen following catheter ablation, no significant ventricular fibrosis should be present. While the novelty of this work is the use of an arrhythmia-insensitive pulse sequence so not to confound their results, as was a potential issue for other studies, the results raise the issue of the cause of the atrial fibrosis and the question of why the ventricle is not involved.

Inflammation has been implicated in atrial fibrillation development (2). Inflammation and fibrosis are linked (3). Epicardial adipose tissue (EAT) is in intimate contact with both the left atrium and the ventricles. When dysfunctional, EAT secretes a variety of adipokines, which in turn can result in fibrosis and promote arrhythmias (4,5). Subepicardial atrial fibrosis has been observed in patients with atrial fibrillation (6) in support of the concept of EAT paracrine involvement. EAT also has been shown to overlie the ganglionated plexi of the pulmonary veins and areas with complex fractionated atrial electrograms (7) that are involved in atrial fibrillation. It is possible that dysfunctional EAT alters their function. Low left atrial radiodensity is seen in dysfunctional EAT and is associated with the presence of a low-voltage zone in patients with atrial fibrillation which is a surrogate for atrial fibrosis (8).

EAT has also been implicated in heart failure (9). A recent study showed increased EAT volume index and insulin resistance were associated with increased myocardial fat accumulation and interstitial myocardial fibrosis. Moreover, increased EAT volume index was associated with a reduction in left ventricular global strain (10).

Healthy EAT has properties of brown fat. The brown fat is thought to be cardioprotective. When EAT becomes dysfunctional, there is loss of browning. EAT is found to be adjacent to both the atria and ventricles. If dysfunctional EAT is responsible for atrial and ventricular fibrosis, how might we explain that fibrosis is only seen in the left atrium and not the left ventricle in patients with atrial fibrillation?

It is possible that the phenotypes of EAT are different in heart failure and atrial fibrillation. It has been shown that the transcriptomic signatures of EAT differ depending on its anatomic location (11). It is also possible that the periatrial adipose tissue differs from other EAT depending on the distance from the atrial wall in very much the same way perivascular EAT differs from other EAT.

Antonopoulos et al showed in a very elegant study that perivascular inflammation affects the size of adipocytes (12). There is a gradient of adipocyte size adjacent to the vessel wall. The smaller adipocytes adjacent to the vessel wall are associated with higher radiodensity in perivascular adipose tissue seen with inflammation and atherosclerosis. It is possible that a similar process occurs in EAT adjacent to the myocardium of the atria and ventricles.

The study of Gunasekaran et al (1) should serve as a stimulus for further research to improve our understanding of the pathophysiology underlying atrial fibrillation. The insights gained may provide for more targeted treatments and prevention.