Is Fatty Liver a Risk Marker for Heart Failure?

Nonalcoholic fatty liver disease (NAFLD) is a common obesity-related condition with an estimated prevalence of 10% to 30% worldwide and 70% to 90% among persons with obesity undergoing bariatric surgery (1). NAFLD is a spectrum of diseases, including isolated hepatic steatosis, nonalcoholic steatohepatitis (NASH; steatosis plus hepatocyte injury), and fibrosis/cirrhosis, that can lead to liver cancer, liver failure, and need for transplantation (1). NAFLD is an asymptomatic disease and a diagnosis of exclusion made by documenting the presence of fat on imaging after exclusion of other potential causes of liver fat (e.g., alcohol) (1). In contrast, NASH, which is the more severe form of NAFLD, requires liver biopsy for diagnosis. Cardiovascular disease is the most common cause of death in NAFLD, but whether NAFLD is a driver or merely a passenger biomarker for the development of cardiovascular disease remains to be determined (1, 2). Several small studies have demonstrated that both imaging-based and biopsy-proven NAFLD are associated with subclinical changes in myocardial structure and function in both children and adults (3-5). More recently, investigators from the Coronary Artery Risk Development in Young Adults study, a large, prospective, population-based cohort of biracial adults, demonstrated that computed tomography-diagnosed NAFLD in midlife (mean age 50) was associated with subclinical myocardial remodeling independent of traditional heart failure (HF) risk factors or adiposity measures, providing pathophysiologic insight into the potential link between NAFLD and HF (2). To date, no studies have demonstrated whether biopsy-proven NASH per se is associated with differential risk for underlying cardiac abnormalities. In the current issue, Simon et al. (6) demonstrate for the first time that histological NASH is associated with increased left atrial volume index, left ventricular concentric remodeling, and impaired diastolic function among a retrospective cohort of bariatric surgery patients. Adverse structural remodeling of the heart is a pivotal process in the progression of HF (7) and is, therefore, emerging as a therapeutic target in HF prevention (8). Better understanding of potential mediators in the developmental pathways toward abnormal myocardial geometry, such as NAFLD/NASH, may offer important potential therapeutic targets in order to prevent and treat the HF epidemic. Several limitations of the current work warrant mention and temper enthusiasm for the study findings. First, this is a very small, single-center, retrospective, cross-sectional study with only 11 patients having histologically confirmed NASH. Thus, neither temporal nor causal relationships can be inferred. Second, the authors lacked measurement of cardiac hemodynamics. Clinically, patients with obesity and HF often have high cardiac output compared with patients without obesity who have HF. The increase in cardiac output associated with obesity may be due to increased body size alone, but other causes of a high-output state, most notably subclinical liver disease, may play a role. Cirrhosis is a high-cardiac-output state (9); thus, it is plausible that subclinical hepatic dysfunction, perhaps mediated by NASH, may contribute to high cardiac output in some patients with obesity. Finally, several of the observed differences in echocardiographic parameters (e.g., an early diastole to atrial contraction [E:A] ratio of 1.03 vs. 1.16), though statistically significant, may not represent a clinically significant difference. Thus, the study findings illuminate potential pathophysiologic mechanisms of the association between NASH and HF, and they do not demonstrate a direct link to clinical HF. Future prospective studies to determine the impact of the full histological spectrum of NAFLD on a full range of echocardiographic parameters, including hemodynamic measurement, and on subsequent risk for clinical HF are needed.