Surrogate markers of gut dysfunction are related to heart failure severity and outcome - from the BIOSTAT-CHF consortium

Israr, M. Z. et al. (2022) Surrogate markers of gut dysfunction are related to heart failure severity and outcome - from the BIOSTAT-CHF consortium. American Heart Journal, 248, pp. 108-119. (doi: 10.1016/j.ahj.2022.03.002) (PMID:35278373)

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Background: The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (e.g., severity, adverse outcomes) and risk stratification. Methods: A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway [acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide (TMAO)] and the gut peptide, Trefoil Factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed. Results: Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalisation or all-cause mortality at 3 years [HR 2.04-2.93 (95% CI 1.30-4.71) p≤0.002]. Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (p<0.001), higher plasma concentrations of B-type natriuretic peptide (p<0.001), and worse outcome [HR 1.90-4.58 (95% CI 1.19-6.74) p≤0.008]. Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome [C-statistics p≤0.011, NRI 13.5-21.1 (95% CI 2.7-31.9) p≤0.014]. Conclusions: A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.

Item Type:Articles
Additional Information:BIOSTAT-CHF was supported by the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010- 020808-29]. The present analysis was supported by the following funding to TS: the Japan Heart Foundation, National Institute for Health Research (Leicester Biomedical Research Centre), the British Heart Foundation (BHF) and the Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK).
Glasgow Author(s) Enlighten ID:Cleland, Professor John
Authors: Israr, M. Z., Zhan, H., Salzano, A., Voors, A. A., Cleland, J. G.F., Anker, S. D., Metra, M., van Veldhuisen, D. J., Lang, C. C., Zannad, F., Samani, N. J., Ng, L. L., and Suzuki, T.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:American Heart Journal
ISSN (Online):1097-6744
Published Online:09 March 2022
Copyright Holders:Copyright © 2022 Elsevier Inc.
First Published:First published in American Heart Journal 248: 108-119
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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