Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction

Abstract

insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (nAfLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with nAfLD among patients with heart failure with preserved ejection fraction (Hfpef). Adults with Hfpef were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or icD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29-8.88) and BMI (OR 1.11, 95% CI 1.04-1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a twofold higher prevalence in HFpEF compared to the general population and is independently associated with BMi and diabetes. patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in Hfpef patients.

Non‐alcoholic fatty liver disease and heart failure with preserved ejection fraction: from pathophysiology to practical issues

“…Binding to its up-regulated soluble form ST2 receptor, in response to stretch myocyte, inflammation, and myocardial fibrosis, leads to hypertrophy of cardiomyocytes and heart fibrosis similarly to the action of galectin 3,38 A prospective real-life study of HFpEF patients with NAFDL found an important association between more advanced HF and hepatic fibrosis stage, and that patients with advanced fibrosis had an increase in left atrial diameter and ≥grade 2 diastolic dysfunction. 10 A similar relationship was observed in HF patients hospitalized for the treatment of decompensated HFpEF. 11 Impact of co-existing non-alcoholic steatohepatitis on heart diseases…”

“…The high degree of uncertainty about the involvement of some of the incriminated mechanisms makes evaluating and developing specific therapies difficult. However, given the high proportion of advanced cirrhosis in HFpEF patients with NAFLD, 10 the current challenge for cardiologists is to detect NAFLD early so it can be managed with approved non-specific pharmacologic or non-pharmacologic strategies associated with heart disease treatment. In the absence of validated biomarkers, cardiologists must be aware of risk factors like T2DM or metabolic syndrome, two conditions that warrant a detection primarily based on liver enzymes measurements ( Figure 2).…”

“…For instance, pro‐inflammatory macrophages (M1) release cytokines such as TNF‐A and IL‐6 that contribute to hepatocyte injuries and NAFLD, while damaged hepatocytes release IL‐33 that promotes profibrogenic effect via the IL‐33 receptor (ST2) and galectin 3,37 In the heart, IL‐33 is released in response to the stretching of myocardial fibres. Binding to its up‐regulated soluble form ST2 receptor, in response to stretch myocyte, inflammation, and myocardial fibrosis, leads to hypertrophy of cardiomyocytes and heart fibrosis similarly to the action of galectin 3,38 A prospective real‐life study of HFpEF patients with NAFDL found an important association between more advanced HF and hepatic fibrosis stage, and that patients with advanced fibrosis had an increase in left atrial diameter and ≥grade 2 diastolic dysfunction 10 . A similar relationship was observed in HF patients hospitalized for the treatment of decompensated HFpEF 11 …”

“…Conversely, NAFLD is frequently found in patients with HFpEF 9 . A recent prospective study in outpatients with HFpEF undergoing abdominal imaging indicates that the prevalence of NAFLD could reach 50% and that half of the NAFLD patients could have a NAFLD fibrosis score (NFS) indicative of advanced fibrosis 10 . A high NFS has been found to be associated with a higher risk of all‐cause mortality for symptomatic patients hospitalized for decompensated HFpEF 11 .…”

The Natural History of NAFLD, a Community-Based Study at a Large Health Care Delivery System in the United States

“…An increased risk of heart failure with increasing stage of fibrosis due to NAFLD has also been reported in other recent studies. ( 22,34 ) Progression from no cirrhosis to compensated cirrhosis over a time period of about 3 years in the total population with NAFLD and in the subpopulation with diabetes is 2.5% and 4.1%, respectively. This is in line with the findings of Alexander et al ( 20 ) in their large matched cohort study, which showed that 0.6% of patients with a coded diagnosis of NAFLD/NASH acquire a diagnosis of cirrhosis and/or liver cancer within 3 years, and that diabetes at baseline was the strongest association with incident liver outcomes.…”