Prognostic Implication of Liver Function Tests in Heart Failure With Preserved Ejection Fraction Without Chronic Hepatic Diseases: Insight From TOPCAT Trial

Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients. Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08–1.26; ALP: adjusted HR, 1.12; 95% CI 1.04–1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02–1.31; ALP: adjusted HR, 1.16; 95% CI 1.05–1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12–1.33; ALP: adjusted HR, 1.12; 95% CI 1.03–1.23). Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.