Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common, progressive liver disease that affects up to one-quarter of the adult population worldwide. The clinical and economic burden of NAFLD is mainly due to liver-related morbidity and mortality (nonalcoholic steatohepatitis, cirrhosis or hepatocellular carcinoma) and an increased risk of developing fatal and nonfatal cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers (for example, colorectal cancer and breast cancer). Additionally, there is now accumulating evidence that NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aortic-valve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. This Review focuses on the association between NAFLD and non-ischaemia-related cardiac disease, discusses the putative pathophysiological mechanisms and briefly summarizes current treatment options for NAFLD that might also beneficially affect cardiac disease.

Key points

  • Convincing evidence now substantiates a strong association between the presence and severity of nonalcoholic fatty liver disease (NAFLD) and the risk of cardiomyopathy (mainly left ventricular dysfunction and hypertrophy, possibly leading to heart failure) and arrhythmias (mainly atrial fibrillation).

  • NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and causes the release of pro-inflammatory, profibrogenic and vasoactive mediators that can promote the development of cardiac and arrhythmic complications.

  • An accurate, patient-centred, team-based approach to the management and treatment of individuals with NAFLD, based on a careful evaluation of related cardiometabolic risk factors and monitoring for cardiovascular, cardiac and liver complications, is warranted.

  • Despite the evidence linking NAFLD to these important cardiac and arrhythmic complications, it has not been definitively proved whether a cause–effect association also exists.

  • When treating patients with NAFLD, management should address not only the risk of progressive liver disease but also cardiometabolic risk factors to control cardiovascular disease risk.

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Fig. 1: Adverse effects of NAFLD on coronary arteries and other anatomical structures of the heart.
Fig. 2: Role of low-grade systemic inflammation in the development of NAFLD-related cardiomyopathy and cardiac arrhythmias.
Fig. 3: Targeting pathophysiological processes to treat NAFLD.

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Acknowledgements

Q.M.A. is supported by the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Programme of the European Union under grant agreement 634413, the UK Medical Research Council and the UK National Institute for Health Research Newcastle Biomedical Research Centre. H.T. is supported by the excellence initiative (Competence Centres for Excellent Technologies — COMET) of the Austrian Research Promotion Agency FFG: Research Centre of Excellence in Vascular Ageing Tyrol, VASCage (K-Project number 843536) funded by the BMVIT (Austrian Ministry for Transport, Innovation and Technology), the BMWFW (Federal Ministry of Science, Research and Economy), the Wirtschaftsagentur Wien and the Standortagentur Tirol. G.T. is supported in part by grants from the University School of Medicine of Verona (Italy).

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Anstee, Q.M., Mantovani, A., Tilg, H. et al. Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 15, 425–439 (2018). https://doi.org/10.1038/s41575-018-0010-0

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