title: Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support.
abstract: BACKGROUND
  Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear.
  
  
  OBJECTIVE
  This study sought to describe the metabolomic profiles of patients along the spectrum of systolic HF, determine their association with adverse outcomes in a clinical trial of HF, and evaluate whether identified metabolites change with treatment for end-stage systolic HF.
  
  
  METHODS
  To assess association of metabolites with clinical outcomes, we evaluated a population of 453 chronic systolic HF patients who had been randomized to exercise training versus usual care. To assess change in metabolites with mechanical circulatory support, 41 patients with end-stage HF who underwent left ventricular assist device (LVAD) placement were studied. Targeted, quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization, as well as prior to and ≥90 days post-placement in the LVAD group. Principal components analysis was used for data reduction.
  
  
  RESULTS
  Five principal components analysis-derived factors were significantly associated with peak Vo2 levels at baseline in fully adjusted models. Of these, factor 5 (composed of long-chain acylcarnitines) was associated with increased risk of all 3 pre-specified clinical trial outcomes: all-cause mortality/all-cause hospitalization, all cause-hospitalization, and cardiovascular death or cardiovascular hospitalization. Individual components of factor 5 were significantly higher in patients with end-stage HF prior to LVAD placement and decreased significantly post-implantation.
  
  
  CONCLUSIONS
  In chronic HF patients, circulating long-chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long-term mechanical circulatory support. These metabolites may serve as potential targets for new diagnostics or therapeutic interventions. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).
authors.affiliation: Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut; Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina. Electronic address: tariq.ahmad@yale.edu.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Kelly
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McGarrah
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Testani
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Amanda
authors.initials: A
authors.lastname: Verma
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Samsky
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Donahue
authors.affiliation: Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.
authors.forename: Olga R
authors.initials: OR
authors.lastname: Ilkayeva
authors.affiliation: Division of Cardiac Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Bowles
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Chetan B
authors.initials: CB
authors.lastname: Patel
authors.affiliation: Division of Cardiac Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Carmelo A
authors.initials: CA
authors.lastname: Milano
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rogers
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina; Inova Heart and Vascular Institute, Falls Church, Virginia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000368:Aged; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D018450:Disease Progression; D004734:Energy Metabolism / Q000502:physiology; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006353:Heart-Assist Devices / Q000706:statistics & numerical data*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D009657:North Carolina; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: C116917:acylcarnitine; D002331:Carnitine
keywords: metabolomics; phenotypes; prognosis