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PLoS One. 2015 May 26;10(5):e0124844. doi: 10.1371/journal.pone.0124844. eCollection 2015.

Metabolomic fingerprint of heart failure with preserved ejection fraction.

Author information

1
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Cardiovascular Research Center, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
2
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
3
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada.
4
The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada; Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.
5
Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada.
6
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada; Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.

Abstract

BACKGROUND:

Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.

METHODS AND RESULTS:

Ambulatory patients with clinical diagnosis of HFpEF (n = 24), HFrEF (n = 20), and age-matched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy. Compared to non-HF control, HFpEF patients demonstrated higher serum concentrations of acylcarnitines, carnitine, creatinine, betaine, and amino acids; and lower levels of phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients. Using logistic regression, two panels of metabolites were identified that can separate HFpEF patients from both non-HF controls and HFrEF patients with area under the receiver operating characteristic (ROC) curves of 0.942 and 0.981, respectively.

CONCLUSIONS:

The metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov NCT02052804.

PMID:
26010610
PMCID:
PMC4444296
DOI:
10.1371/journal.pone.0124844
[Indexed for MEDLINE]
Free PMC Article
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