Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia

Abstract

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

Mediterranean Diet: A Tool to Break the Relationship of Atrial Fibrillation with the Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

“…However, a growing body of evidence support the notion that NAFLD may elicit structural, electrical, and autonomic remodelling in the heart, representing a pro-arrhythmogenic substrate in the heart [ 20 ].…”

Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease

“…Evidence suggests that OPN plays an essential role in liver diseases [ 60 , 61 ], including fatty liver, which is linked to atherosclerotic cardiovascular pathology [ 62 ], as well as subclinical atherosclerosis [ 63 ]. Recently, this molecule has also been associated with the presence of cardiac arrhythmias [ 64 ]. On the other hand, the rs11730582 polymorphism was associated with a low risk of having hypoadiponectinemia.…”

Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes

“…Notably, both atherogenic dyslipidemia and dysglycaemia mediate CVD risk in NAFLD patients with T2DM; (b) the release into the bloodstream of several pro-inflammatory (e.g., tumour necrosis factor-a [TNF-a], interleukin-6 [IL-6]), pro-oxidant and pro-coagulant factors (e.g., fibrinogen, factor VIII, plasminogen activator inhibitor-1) as well as pro-fibrogenic mediators. In particular, the synthesis of lipids, including DAG, may also contribute to the hepatic production of inflammatory cytokines and pro-coagulant factors [13,[20][21][22]; (c) the bidirectional relationship between NAFLD and hypertension [23]. Several observational studies and some meta-analyses have reported that patients with…”

“…Notably, both atherogenic dyslipidemia and dysglycaemia mediate CVD risk in NAFLD patients with T2DM; (b) the release into the bloodstream of several pro-inflammatory (e.g., tumour necrosis factor-a [TNF-a], interleukin-6 [IL-6]), pro-oxidant and pro-coagulant factors (e.g., fibrinogen, factor VIII, plasminogen activator inhibitor-1) as well as pro-fibrogenic mediators. In particular, the synthesis of lipids, including DAG, may also contribute to the hepatic production of inflammatory cytokines and pro-coagulant factors [13,[20][21][22]; (c) the bidirectional relationship between NAFLD and hypertension [23]. Several observational studies and some meta-analyses have reported that patients with NAFLD have an increased risk of developing hypertension [24], thus suggesting that this association may partly mediate the relationship between NAFLD and cardiac complications and that that NAFLD may be a consequence, but also a cause of hypertension [23]; (d) patients with NAFLD have early changes in myocardial substrate metabolism inducing cardiac functional disturbances, probably conditioning a higher risk of heart failure [25] and arrhythmias [22,26]; (e) chronic hyperglycemia induces an inflammatory and osteoblastic phenotype in valvular interstitial cells in experimental models of aortic valve sclerosis [27].…”

“…All these factors can promote myocardial remodelling and dysfunction, thereby predisposing to the development of various cardiac complications [13,[20][21][22].…”