title: Metabolomic fingerprint of heart failure with preserved ejection fraction.
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.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02052804.
authors.affiliation: 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.
authors.forename: Beshay N
authors.initials: BN
authors.lastname: Zordoky
authors.affiliation: 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.
authors.forename: Miranda M
authors.initials: MM
authors.lastname: Sung
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Ezekowitz
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rupasri
authors.initials: R
authors.lastname: Mandal
authors.affiliation: The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada; Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Beomsoo
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Trent C
authors.initials: TC
authors.lastname: Bjorndahl
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; The Metabolomics Innovation Centre (TMIC), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Souhaila
authors.initials: S
authors.lastname: Bouatra
authors.affiliation: Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Todd
authors.initials: T
authors.lastname: Anderson
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gavin Y
authors.initials: GY
authors.lastname: Oudit
authors.affiliation: 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.
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
authors.affiliation: 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.
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D012372:ROC Curve; D013318:Stroke Volume
chemical_list: D010446:Peptide Fragments; D010455:Peptides; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain