AHJ Accepted.pdf (1.77 MB)
Association of gut-related metabolites with outcome in acute heart failure
journal contributionposted on 2021-01-21, 11:35 authored by Muhammad Zubair Israr, Dennis Bernieh, Andrea Salzano, Shabana Cassambai, Yoshiyuki Yazaki, Liam HeaneyLiam Heaney, Donald JL Jones, Leong L Ng, Toru Suzuki
Trimethylamine N-oxide (TMAO), a gut-related metabolite, is associated with heart failure (HF) outcomes. However, TMAO is the final product of a complex metabolic pathway (i.e. choline/carnitine) that has never been entirely investigated in HF. The present study investigates a panel of metabolites involved in the TMAO-choline/carnitine metabolic pathway for their associations with outcome in acute HF patients.
In total, 806 plasma samples from acute HF patients were analysed for TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, γ-butyrobetaine, crotonobetaine, trimethylamine, betaine aldehyde, choline, and betaine using a developed liquid chromatography-tandem mass spectrometry method. Associations with outcome of all-cause mortality (death) and a composite of all-cause mortality and/or rehospitalization due to HF (death/HF) at 30 days and 1 year were investigated.
TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, and γ-butyrobetaine were associated with death and death/HF at 30 days (short-term) (HR 1.30-1.49, p≤0.021) and at 1 year (long-term) (HR 1.15-1.25, p≤0.026) when adjusted for cardiac risk factors. L-carnitine and acetyl-L-carnitine were superior for short-term outcomes whereas TMAO was the superior metabolite for association with long-term outcomes. Furthermore, acetyl-L-carnitine and L-carnitine were superior for in-hospital mortality and improved risk stratification when combined with current clinical risk scores (i.e. ADHERE, OPTIMIZE-HF, GWTG-HF) (OR≥1.52, p≤0.020).
Carnitine-related metabolites show associations with adverse outcomes in acute HF, in particular L-carnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes. Further studies are warranted to investigate the role and implications of carnitine metabolites including intervention in the pathogenesis of HF.
Japan Heart Foundation
National Institute for Health Research (Leicester Biomedical Research Centre)
British Heart Foundation (BHF)
Medical Research Council (MRC) UK Consortium on MetAbolic Phenotyping (MAP/UK)
- Sport, Exercise and Health Sciences
Published inAmerican Heart Journal
Pages71 - 80
- AM (Accepted Manuscript)
Rights holder© Elsevier
Publisher statementThis paper was accepted for publication in the journal American Heart Journal and the definitive published version is available at https://doi.org/10.1016/j.ahj.2021.01.006.