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.
Competing Interests: J.B. reports outside the submitted work research funding from Colgate-Palmolive. J.P. reports personal fees from Bayer AG, Daiichi-Sankyo, and Sanofi-Aventis. He is an employee of Boehringer Ingelheim International GmbH, but was not employed at the time of conception and design of the study and during analysis and interpretation of data. M.B. reports research support from the Deutsche Forschungsgemeinschaft, speakers honoraria from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Novartis, Servier, and Vifor. He is or was part of the advisory board for Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Pfizer, ReCor, Servier, and Vifor. P.S.W reports outside the submitted work: consulting fees from Astra Zeneca, research grants from Bayer AG, research grants, consulting and lecturing fees from Bayer Health Care, lecturing fees from Bristol Myers Squibb, grants and consulting fees from Boehringer Ingelheim, grants, consulting and lecturing fees from Daiichi Sankyo Europe, consulting fees and non-financial support from Diasorin, non-financial support from I.E.M., grants and consulting fees from Novartis Pharma, lecturing fees from Pfizer Pharma, non-financial grants from Philips Medical Systems, and grants and consulting fees from Sanofi-Aventis. J.M.S. has acted as Consultant to Apollo Endosurgery, Albireo Pharma Inc, Bayer, Boehringer Ingelheim, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; has received research funding from Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH and Speaker Honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals. A.G. reports no potential conflict of interest.
(© 2024 The Author(s).)