Fig. 1. Putative biological mechanisms linking NAFLD and risk of cardiac arrhythmias (i.e. atrial fibrillation, QTc interval prolongation and ventricular arrhythmias).

The pathophysiological mechanisms linking NAFLD to cardiac arrhythmias are complex and not completely understood. In the presence of NAFLD (or NASH), several alterations occur in the liver, resulting in an increased production of atherogenic lipids (e.g., very-low-density lipoproteins, small and dense low-density lipoproteins, and non-esterified fatty acids) and in an increased release of many pro-inflammatory (e.g., c-reactive protein, tumor necrosis factor-alpha, and interleukin-6), pro-fibrinogen (transforming growth factor-beta), pro-oxidant, vasoactive and thrombogenic (e.g., factor VIII, plasminogen activator inhibitor-1, and endotelin-1) molecules. These NAFLD-related alterations might have adverse effects on the risk of cardiac arrhythmias. In particular, it is well known that pro-inflammatory and pro-oxidant mediators are able to alter electrophysiology and structural substrates of myocardium, leading to increased vulnerability to cardiac arrhythmias. For instance, many inflammatory cytokines (i.e. tumor necrosis factor-alpha, interleukin-1, and interleukin-6) can modulate calcium homeostasis and connexins, that are associated with modifications in fiber continuity and possible circuit re-entry, and also promote myolysis, cardiomyocyte apoptosis and myocardial fibrogenesis.