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

GND
1133218873
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Magdeburg, Otto von Guericke-University, 39120 Magdeburg, Germany;
Bekfani, Tarek;
GND
1139058487
ORCID
0000-0003-0346-9181
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Bekhite, Mohamed;
GND
115086740X
Affiliation
Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, 07743 Jena, Germany;(S.N.);(M.K.)
Neugebauer, Sophie;
GND
13916085X
Affiliation
Institute of Physiotherapy, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(S.D.);(J.N.)
Derlien, Steffen;
GND
1273272838
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Hamadanchi, Ali;
GND
1216427410
Affiliation
Institute of Physiotherapy, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(S.D.);(J.N.)
Nisser, Jenny;
GND
1218023724
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Hilse, Marion S.;
GND
130141534
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Haase, Daniela;
GND
1229199403
ORCID
0000-0002-5296-3955
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Kretzschmar, Tom;
GND
1229198784
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Wu, Mei-Fang;
Affiliation
Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria;
Lichtenauer, Michael;
GND
114935971
Affiliation
Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, 07743 Jena, Germany;(S.N.);(M.K.)
Kiehntopf, Michael;
Affiliation
Department of Cardiology and Pneumology, University of Göttingen Medical Center, 37075 Göttingen, Germany;
von Haehling, Stephan;
GND
138812187
ORCID
0000-0001-7420-7707
Affiliation
Institute for Medical Statistics, Computer Science and Data Science (IMSID), Jena University Hospital, 07743 Jena, Germany;
Schlattmann, Peter;
GND
14264790X
Affiliation
Department of Internal Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;
Lehmann, Gabriele;
GND
133832325
ORCID
0000-0001-6543-4684
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Franz, Marcus;
GND
136433057
ORCID
0000-0003-1319-6738
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Möbius-Winkler, Sven;
GND
121635244
Affiliation
Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, 07743 Jena, Germany;(M.B.);(A.H.);(M.S.H.);(D.H.);(T.K.);(M.-F.W.);(M.F.);(S.M.-W.)
Schulze, Christian

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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