Association of liver fibrosis risk scores with clinical outcomes in patients with heart failure with preserved ejection fraction: findings from TOPCAT

Abstract

Aims Non-alcoholic fatty liver disease leads to progressive liver fibrosis and appears to be a frequent co-morbid disease in heart failure with preserved ejection fraction (HFpEF). It is well known that liver fibrosis severity predicts future liver-related morbidity and mortality, but its impact on outcomes in patients with HFpEF remains unknown. This analysis aimed to describe the prevalence of liver fibrosis, as assessed using surrogate biomarkers, in patients with HFpEF and the association of such biomarkers in predicting clinical outcomes in these patients. Methods and results Patients with HFpEF from TOPCAT Americas were included in the analysis. The non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) scores were calculated using a combination of clinical characteristics and laboratory parameters. Risk of advanced fibrosis was classified as low, intermediate, and high. For the 1423 with sufficient data, we used Cox regression analysis to test the association between the risk of fibrosis severity and the combined primary endpoint of all cardiovascular death, aborted cardiac arrest, and hospitalization for heart failure. Advanced fibrosis, as determined by high fibrosis scores, was present in 37.57% by the NFS and 8.02% by the FIB-4. Higher risk of advanced hepatic fibrosis was associated with older age. In unadjusted models, the risk of advanced fibrosis was associated with the primary cardiovascular outcome [NFS high vs. low, hazard ratio (HR) 1.709 (95% confidence interval, CI 1.238-2.358, P = 0.0011) and FIB-4 high vs. low, HR 1.561 (95% CI 1.139-2.140, P = 0.0056)]. After multivariable adjustment, this association was diminished [NFS high vs. low, HR 1.349 (95% CI 0.938-1.939, P = 0.1064) and FIB-4 high vs. low, HR 1.415 (95% CI 0.995-2.010, P = 0.0531)]. Conclusions Our study suggests that advanced liver fibrosis, as estimated by fibrosis risk scores, may not be uncommon in patients with HFpEF, and there appears to be a limited independent association between liver fibrosis risk scores and clinical outcomes related to heart failure events.

Prognostic value of the liver fibrosis marker fibrosis‐5 index in patients with acute heart failure

“…22 However, a post-hoc analysis of the TOPCAT trial, which included only heart failure patients with preserved LVEF, reported that FIB-4 was not a significant risk factor for cardiac events. 23 Although several studies have evaluated the prognostic significance of FIB-4, there have been no reports evaluating the association between FIB-5 and prognosis in patients with heart failure. FIB-5 was first reported as an index to differentiate between a cirrhotic and a non-cirrhotic liver in patients with HCV in 2006.…”

Non‐alcoholic fatty liver disease‐related risk of cardiovascular disease and other cardiac complications

“…Similarly, it has been reported that there was a high prevalence of NAFLD with increased fibrosis scores in patients with chronic HF, especially amongst those with a preserved LV ejection fraction 44‐47 . In addition, patients with HF and coexisting NAFLD had a higher long‐term risk of CVD outcomes, compared to their counterparts without coexisting liver disease 44‐47 …”

“…Interestingly, some longitudinal studies have also shown that imaging‐defined NAFLD and its severity (assessed by non‐invasive fibrosis scores) were independently associated with an increased risk of both in‐hospital and post‐discharge, all‐cause mortality in patients admitted with acute HF 41‐43 . Similarly, it has been reported that there was a high prevalence of NAFLD with increased fibrosis scores in patients with chronic HF, especially amongst those with a preserved LV ejection fraction 44‐47 . In addition, patients with HF and coexisting NAFLD had a higher long‐term risk of CVD outcomes, compared to their counterparts without coexisting liver disease 44‐47 …”

Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction

“…The prevalence of NAFLD is higher in patients with HFpEF than in those with HFrEF, reaching up to 50% ( 16 ). In a post hoc analysis of patients with HFpEF from the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial, Peters et al ( 17 ) showed that advanced liver fibrosis may be present in up to 37.5% of patients. The presence of fibrosis in patients with HFpEF carries a negative prognostic value; the degree of fibrosis on the basis of fibrosis-4 is independently associated with hospitalization for HF ( 17 ).…”

“…In a post hoc analysis of patients with HFpEF from the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial, Peters et al ( 17 ) showed that advanced liver fibrosis may be present in up to 37.5% of patients. The presence of fibrosis in patients with HFpEF carries a negative prognostic value; the degree of fibrosis on the basis of fibrosis-4 is independently associated with hospitalization for HF ( 17 ). Also, in a prospective observational study, NAFLD fibrosis score was an independent predictor of all-cause mortality in patients with HFpEF ( 18 ).…”