Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Kynurenine as a potential biomarker for classification of reduced muscle endurance: Metabolomic profiling of patients with heart failure and exercise intolerance
T. Bekfani1, M. Bekhite2, S. Neugebauer3, S. Derlien4, A. Hamadanchi2, J. Nisser4, M. S. Hilse2, D. Haase2, T. Kretzschmar2, M. F. WU2, M. Lichtenauer5, M. Kiehntopf3, S. von Haehling6, P. Schlattmann7, M. Franz2, S. Möbius-Winkler2, C. Schulze2
1Klinik für Kardiologie, Angiologie und Pneumologie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg; 2Klinik für Innere Medizin I - Kardiologie, Universitätsklinikum Jena, Jena; 3Department of Clinical Chemistry and Laboratory Diagnostics, Universitätsklinikum Jena, Jena; 4Institute of Physiotherapy, Universitätsklinikum Jena, Jena; 5Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, AT; 6Herzzentrum, Klinik für Kardiologie und Pneumologie, Universitätsmedizin Göttingen, Göttingen; 7Institute for Medical Statistics, Computer Science and Data Science (IMSID), Universitätsklinikum Jena, Jena;

Aims: Reduced muscle endurance (RME) in patients with HFpEF and HFrEF is associated with structural and metabolic changes in skeletal muscle. We investigated the role of kynurenine (Kyn) as a potential marker in detecting RME. Additionally, we described the distorted metabolic profiles in serum in patients with RME and both preserved (HFpEF) and reduced (HFrEF) ejection fraction. 

Methods: Fifty-five participants were prospectively recruited (17 HFpEF, 18 HFrEF outpatients and 20 healthy controls, HC). All participants underwent echocardiography, CPET, isokinetic muscle function tests. Quantification of metabolites in serum was performed using liquid chromatography tandem mass spectrometry. RME was defined as muscle endurance of quadriceps below the mean value of the cohort.

Results: Compared to HC, patients with HFpEF and HFrEF had reduced amino acid (AA)-concentrations except for branched-chain and aromatic AAs, and higher concentrations of acylcarnitines (ACs) and Kyn (p<0.05). Patients with RME and HFpEF showed reduced levels of long-chain-, medium-chain-, medium-/long-chain-ACs ratios and alanine (p<0.05). In patients with RME and HFrEF we observed reduced concentrations of AAs (p<0.05) (figure 1 showing different heart maps in patients with HFpEF, HFrEF, HC and RME). In a linear regression, Kyn was an independent predictor for RME after adjusting for alanine, glutamate, ornithine, spermine and short-chain- ACs (B: -8.2 per 1µM increase, 95% CI: -13.01, -3.30, p=0.001). Kyn showed 83% sensitivity and 70% specificity (area under the curve 0.83) in detecting RME (figure 2). 

Conclusions: RME was associated with impaired fatty acid oxidation rates in HFpEF patients and with reduced concentrations of AAs in those with HFrEF. Kyn shows high potential as a biomarker for classifying RME. 


Figure 1
HC: Healthy controls, HFpEF: Heart failure with preserved ejection fraction, HFrEF: Heart failure with reduced ejection fraction, PME: preserved muscle endurance (muscle endurance of quadriceps above the mean value of the cohort) RME: reduced muscle endurance (muscle endurance of quadriceps below the mean value of the cohort).




Figure 2


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