Roddy Hiram, Montreal University, Canada

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia. With 70% of AF patients aged 65 and above, pathological aging stands as the major risk factor for AF. Conditions such as pulmonary hypertension, obesity, or myocardial infarction, and environmental factors such as pollutants and pesticides, also promote atrial remodeling and AF.

Inflammation is the common denominator of most AF risk factors. Clinical studies have shown significantly increased circulating levels of interleukin-(IL)-6 and IL-18 in AF compared to no-AF patients. However, classical anti-inflammatory medications are not efficient in curing AF.

Interestingly, mounting evidence suggests that termination of inflammation is an active process called ‘resolution’ impaired by endogenous molecules, including resolvin-(Rv)-D1, lipoxin-(LX)-A4, or IL-37.

Using experimental models of right and left heart disease, healthy aging, or pesticide exposure, we have evaluated the impact of the ‘resolution machinery’ in promoting the prevention of cardiac inflammation, atrial fibrosis, and AF in male and female subjects.

Our results show that preventive pro-resolution therapeutic strategies may help to attenuate atrial inflammation and atrial fibrosis in AF management. However, when the inflammation-induced atrial fibrosis is already installed, the efficacy of anti-inflammatory approaches is mitigated.

In perspective, it is suggested that the elaboration and development of future anti-AF treatments might consider the complex kinetic of inflammation to 1) tackle the upstream events involved in chronic inflammation and 2) curb inflammation-induced arrhythmogenic fibrosis.