title: Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.
abstract: BACKGROUND
  Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF.
  
  
  OBJECTIVE
  This study sought to assess the diagnostic and prognostic values of metabolomics in HF.
  
  
  METHODS
  Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group.
  
  
  RESULTS
  A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study.
  
  
  CONCLUSIONS
  Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers.
authors.affiliation: Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan; Metabolomics Core Laboratory, Chang Gung University, Tao-Yuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, and Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: bearty54@gmail.com.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan; Metabolomics Core Laboratory, Chang Gung University, Tao-Yuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Shiao
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, and Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Nursing, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Yu-Yen
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chun-Tai
authors.initials: CT
authors.lastname: Mao
authors.affiliation: Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jui-Fen
authors.initials: JF
authors.lastname: Lin
authors.affiliation: Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Hung-Yao
authors.initials: HY
authors.lastname: Ho
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ning-I
authors.initials: NI
authors.lastname: Yang
mesh_terms: D000601:Amino Acids, Essential / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010359:Patient Readmission / Q000706:statistics & numerical data; D010713:Phosphatidylcholines / Q000097:blood; D011379:Prognosis; D013095:Spermidine / Q000097:blood; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000601:Amino Acids, Essential; D015415:Biomarkers; D010713:Phosphatidylcholines; D020097:Natriuretic Peptide, Brain; C427065:butyrylcarnitine; D002331:Carnitine; D013095:Spermidine
keywords: B-type natriuretic peptide; diagnosis; liquid chromatography-mass spectrometry; prognosis