Clinical utility of the Fibrosis-4 index for predicting mortality in patients with heart failure with or without metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

Background: The liver-heart axis potentially influences the risk of mortality in patients with heart failure. We aimed to identify the clinical utility of the fibrosis-4 (FIB-4) index in patients with heart failure for predicting mortality in the context of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Patients with heart failure and a subsample of healthy participants were enrolled in the MyoVasc study (NCT04064450) and followed for nine years. Participants with excessive alcohol consumption were excluded. The Fatty Liver Index (FLI) and FIB-4 index were used to classify MASLD and hepatic fibrosis, respectively. Data were adjusted for potential confounders. The primary endpoint was all-cause mortality.

Findings: 2726 participants, including 172 healthy individuals, were included in the study. The participants had a mean age of 64.4 ± 11.2 years and a median FIB-4 index of 1.59 (interquartile range [1.17; 2.17]). There were 532 deaths. The FIB-4 index was predictive for all-cause mortality (hazard ratio (HR) 1.341, 95% confidence interval (CI) [1.273; 1.412], p < 0.0001). The HRs and 95% CIs for the FIB-4 index in FLI categories were 1.597 [1.256; 2.031] (p = 0.00013, FLI <30), 1.802 [1.519; 2.138] (p < 0.0001, FLI 30-60), and 1.292 [1.215; 1.374] (p < 0.0001, FLI ≥60). The interaction term for the FIB-4 index with FLI ≥60 (reference FLI <30) was HR 0.774 [0.617; 0.972] (p = 0.027), indicating a smaller impact of the FIB-4 index in FLI ≥60 than in FLI <30 (HR 1.664 [1.333; 2.077], p < 0.0001). Multivariable linear regressions revealed relevant independent relationships between the FIB-4 index and N-terminal pro-B-type natriuretic peptide, systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy in participants with a FLI below 60.

Interpretation: In patients with heart failure, the FIB-4 index predicts all-cause mortality and relates to cardiac functional and structural changes, especially in those without MASLD.

Funding: Johannes Gutenberg-University Mainz.