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Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction

1
Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany
2
DZHK (German Centre for Cardiovascular Research), partner site Greifswald, 17475 Greifswald, Germany
3
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany
4
Department of Cardiology, University of Göttingen, 37099 Göttingen, Germany
5
DZHK (German Centre for Cardiovascular Research), partner site Göttingen, 37099 Göttingen, Germany
6
Department of Cardiology, University Medicine Leipzig, 04103 Leipzig, Germany
7
Department of Prevention, Rehabilitation and Sports Medicine, Technical University Munich, 80992 Munich, Germany
8
Department of Internal Medicine and Cardiology, Charité University Hospital (Campus Virchow Klinikum), 13353 Berlin, Germany
9
DZHK (German Centre for Cardiovascular Research), partner site Berlin, 13353 Berlin, Germany
10
Berlin Insitute of Health (BIH), 10178 Berlin, Germany
11
DZHK (German Centre for Cardiovascular Research), partner site Munich, 80336 Munich, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(5), 591; https://doi.org/10.3390/jcm8050591
Received: 2 April 2019 / Revised: 15 April 2019 / Accepted: 28 April 2019 / Published: 29 April 2019
(This article belongs to the Special Issue Acute and Chronic Heart Failure)
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Abstract

The prevalence of heart failure with preserved ejection fraction (HFpEF) is constantly increasing and no evidence-based pharmacological treatment option is available. While exercise training (ET) improves diastolic function, its metabolic mechanisms in HFpEF are unclear. We assessed the metabolic response to 12 weeks of ET in patients with HFpEF by performing a post hoc analysis of the EX-DHF-P trial (ISRCTN86879094). Plasma concentrations of 188 endogenous metabolites were measured in 44 ET and 20 usual care (UC) patients at baseline and 3-months follow-up. Metabolic differences between ET and UC from baseline to follow-up were compared and differential responses to ET were examined by random forest feature selection. ET prevented the increase of acetylornithine and carnitine as well as the decrease of three glycerophospholipids. After ET, two opposite metabolic response clusters were identified. Cluster belonging was associated with perceived well-being at baseline and changes in low-density lipoprotein but not with cardiorespiratory, ventilatory or echocardiographic parameters. These two ET-induced metabolic response patterns illustrate the heterogeneity of the HFpEF patient population. Our results suggest that other biological parameters might be helpful besides clinical variables to improve HFpEF patient stratification. Whether this approach improves response prediction regarding ET and other treatments should be explored. View Full-Text
Keywords: exercise; heart failure with preserved ejection fraction; metabolomics exercise; heart failure with preserved ejection fraction; metabolomics
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Bahls, M.; Friedrich, N.; Pietzner, M.; Wachter, R.; Budde, K.; Hasenfuß, G.; Nauck, M.; Pressler, A.; Felix, S.B.; Edelmann, F.; Halle, M.; Dörr, M. Heterogeneous Metabolic Response to Exercise Training in Heart Failure with Preserved Ejection Fraction. J. Clin. Med. 2019, 8, 591.

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