Abstract Body (Do not enter title and authors here): Background: By causing systemic venous congestion and hypoperfusion, heart failure can lead to liver dysfunction and these processes along with neurohumoral activation, inflammation, and metabolic dysfunction may lead to liver fibrosis. The fibrosis-5 (FIB-5) index, which incorporates serum albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, is a marker of possible liver fibrosis. We evaluated the prevalence of an abnormal FIB-5 index in heart failure with reduced ejection fraction (HFrEF), compared with (HFpEF), and the association between FIB-5 index and outcomes in these two types of HF.

Research Questions: What is the prognostic value of the FIB-5 index in patients with HF across the range of left ventricular ejection fraction (LVEF)?

Methods: The PARADIGM-HF and PARAGON-HF trials were randomized, double-blind, active treatment-controlled trials which included 8442 HFrEF patients and 4822 HFpEF patients, respectively. The primary endpoint examined in this analysis was the composite of HF hospitalization or cardiovascular (CV) death. We compared outcomes according to quartiles of FIB-5 index. A low FIB-5 index is associated with hepatic fibrosis.

Results: Overall, 44% of HFrEF patients and 42% of HFpEF patients had possible liver fibrosis as identified by a FIB-5 index <0 (which is reported to have a high specificity, positive predictive value, and negative predictive value for liver fibrosis in other diseases). Lower FIB-5 index was associated with adverse outcomes in both HF phenotypes (Figures). Comparing Quartile 1 to Quartile 4 of the FIB-5 index, gave a hazard ratio (HR) for the primary endpoint of 1.87 (95% CI 1.64-2.13) in PARADIGM-HF and 1.55 (95% CI 1.32-1.83) in PARAGON-HF. The corresponding HRs for CV death were 1.90 (95% CI 1.61–2.23) in PARADIGM-HF and 1.70 (95% CI 1.23-2.3) in PARAGON-HF. The benefit of sacubitril/valsartan was not modified by FIB-5 index.

Conclusion: The FIB-5 index suggests liver fibrosis is common in both HFrEF and HFpEF and is prognostically important, regardless of ejection fraction phenotype.