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Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients wi...

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Autores principales: Bekfani, Tarek, Bekhite, Mohamed, Neugebauer, Sophie, Derlien, Steffen, Hamadanchi, Ali, Nisser, Jenny, Hilse, Marion S., Haase, Daniela, Kretzschmar, Tom, Wu, Mei-Fang, Lichtenauer, Michael, Kiehntopf, Michael, von Haehling, Stephan, Schlattmann, Peter, Lehmann, Gabriele, Franz, Marcus, Möbius-Winkler, Sven, Schulze, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139290/
https://www.ncbi.nlm.nih.gov/pubmed/35626711
http://dx.doi.org/10.3390/cells11101674
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author Bekfani, Tarek
Bekhite, Mohamed
Neugebauer, Sophie
Derlien, Steffen
Hamadanchi, Ali
Nisser, Jenny
Hilse, Marion S.
Haase, Daniela
Kretzschmar, Tom
Wu, Mei-Fang
Lichtenauer, Michael
Kiehntopf, Michael
von Haehling, Stephan
Schlattmann, Peter
Lehmann, Gabriele
Franz, Marcus
Möbius-Winkler, Sven
Schulze, Christian
author_facet Bekfani, Tarek
Bekhite, Mohamed
Neugebauer, Sophie
Derlien, Steffen
Hamadanchi, Ali
Nisser, Jenny
Hilse, Marion S.
Haase, Daniela
Kretzschmar, Tom
Wu, Mei-Fang
Lichtenauer, Michael
Kiehntopf, Michael
von Haehling, Stephan
Schlattmann, Peter
Lehmann, Gabriele
Franz, Marcus
Möbius-Winkler, Sven
Schulze, Christian
author_sort Bekfani, Tarek
collection PubMed
description Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.
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spelling pubmed-91392902022-05-28 Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker Bekfani, Tarek Bekhite, Mohamed Neugebauer, Sophie Derlien, Steffen Hamadanchi, Ali Nisser, Jenny Hilse, Marion S. Haase, Daniela Kretzschmar, Tom Wu, Mei-Fang Lichtenauer, Michael Kiehntopf, Michael von Haehling, Stephan Schlattmann, Peter Lehmann, Gabriele Franz, Marcus Möbius-Winkler, Sven Schulze, Christian Cells Article Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME. MDPI 2022-05-18 /pmc/articles/PMC9139290/ /pubmed/35626711 http://dx.doi.org/10.3390/cells11101674 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bekfani, Tarek
Bekhite, Mohamed
Neugebauer, Sophie
Derlien, Steffen
Hamadanchi, Ali
Nisser, Jenny
Hilse, Marion S.
Haase, Daniela
Kretzschmar, Tom
Wu, Mei-Fang
Lichtenauer, Michael
Kiehntopf, Michael
von Haehling, Stephan
Schlattmann, Peter
Lehmann, Gabriele
Franz, Marcus
Möbius-Winkler, Sven
Schulze, Christian
Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title_full Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title_fullStr Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title_full_unstemmed Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title_short Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker
title_sort metabolomic profiling in patients with heart failure and exercise intolerance: kynurenine as a potential biomarker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139290/
https://www.ncbi.nlm.nih.gov/pubmed/35626711
http://dx.doi.org/10.3390/cells11101674
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