Abstract
Abstract 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 likely distorted metabolic pathways 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. Results 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. 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). 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). Conclusions Kyn shows high potential as biomarker for detecting RME. RME was associated with impaired fatty acid oxidation rates in HFpEF patients and with reduced concentrations of AAs in those with HFrEF. Funding Acknowledgement Type of funding sources: None.
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