title: Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction.
abstract: OBJECTIVE
  The potential diagnostic utility of circulating microRNAs in heart failure (HF) or in distinguishing HF with reduced vs. preserved left ventricular ejection fraction (HFREF and HFPEF, respectively) is unclear. We sought to identify microRNAs suitable for diagnosis of HF and for distinguishing both HFREF and HFPEF from non-HF controls and HFREF from HFPEF.
  
  
  RESULTS
  MicroRNA profiling performed on whole blood and corresponding plasma samples of 28 controls, 39 HFREF and 19 HFPEF identified 344 microRNAs to be dysregulated among the three groups. Further analysis using an independent cohort of 30 controls, 30 HFREF and 30 HFPEF, presented 12 microRNAs with diagnostic potential for one or both HF phenotypes. Of these, miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, -211-5p, -494, and -671-5p distinguished HF from controls. Altered levels of miR-125a-5p, -183-3p, -193b-3p, -211-5p, -494, -638, and -671-5p were found in HFREF while levels of miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, and -545-5p distinguished HFPEF from controls. Four microRNAs (miR-125a-5p, -190a, -550a-5p, and -638) distinguished HFREF from HFPEF. Selective microRNA panels showed stronger discriminative power than N-terminal pro-brain natriuretic peptide (NT-proBNP). In addition, individual or multiple microRNAs used in combination with NT-proBNP increased NT-proBNP's discriminative performance, achieving perfect intergroup distinction. Pathway analysis revealed that the altered microRNAs expression was associated with several mechanisms of potential significance in HF.
  
  
  CONCLUSIONS
  We report specific microRNAs as potential biomarkers in distinguishing HF from non-HF controls and in differentiating between HFREF and HFPEF.
authors.affiliation: Cardiovascular Research Institute, Singapore; Department of Medicine, Singapore.
authors.forename: Lee Lee
authors.initials: LL
authors.lastname: Wong
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.forename: Sugunavathi
authors.initials: S
authors.lastname: Sepramaniam
authors.forename: Dwi Setyowati
authors.initials: DS
authors.lastname: Karolina
authors.forename: Kai Ying
authors.initials: KY
authors.lastname: Lim
authors.forename: Jia Yuen
authors.initials: JY
authors.lastname: Lim
authors.forename: Jenny P C
authors.initials: JP
authors.lastname: Chong
authors.forename: Jessica Y X
authors.initials: JY
authors.lastname: Ng
authors.forename: Yei-Tsung
authors.initials: YT
authors.lastname: Chen
authors.forename: Michelle M Y
authors.initials: MM
authors.lastname: Chan
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Chen
authors.forename: Poh Shuan D
authors.initials: PS
authors.lastname: Yeo
authors.forename: Tze P
authors.initials: TP
authors.lastname: Ng
authors.forename: Lieng H
authors.initials: LH
authors.lastname: Ling
authors.forename: David
authors.initials: D
authors.lastname: Sim
authors.forename: Kui Toh G
authors.initials: KT
authors.lastname: Leong
authors.forename: Hean Y
authors.initials: HY
authors.lastname: Ong
authors.forename: Fazlur
authors.initials: F
authors.lastname: Jaufeerally
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.forename: Ping
authors.initials: P
authors.lastname: Chai
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Low
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarkers; Diagnosis; Heart failure; MicroRNAs