title: Effects of left ventricular assist device support on biomarkers of cardiovascular stress, fibrosis, fluid homeostasis, inflammation, and renal injury.
abstract: OBJECTIVE
  The purpose of this study was to examine changes in a broad panel of biomarkers following left ventricular assist device (LVAD) support in advanced heart failure (HF).
  
  
  BACKGROUND
  LVAD therapy mechanically unloads the failing heart and may result in reversal of certain aspects of the end-stage HF phenotype. Changes in markers of myocardial stress, fibrosis, inflammation, fluid homeostasis, and renal injury in this setting are unknown.
  
  
  METHODS
  Amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, ST2, copeptin, growth differentiation factor (GDF)-15, C-reactive protein (CRP), and neutrophil gelatinase associated lipocalin (NGAL) levels were measured in frozen plasma collected from 37 individuals prior to continuous flow LVAD implantation and a median of 136 (interquartile range: 94 to 180) days after implantation.
  
  
  RESULTS
  The median age of patients was 68 years old. LVAD therapy was associated with significant decreases in NT-proBNP (3,093 to 2,090 pg/ml; p = 0.02), ST2 (67.5 to 45.2 ng/ml, p <0.01), galectin-3 (24.7 to 22.0 ng/ml; p = 0.04), GDF-15 (3,232 to 2,613 ng/l;p <0.001), hs-CRP (22.4 to 11.9 mg/l; p = 0.01), and copeptin (103 to 94 pmol/l; p = 0.003) but not NGAL (132 to 135 ng/ml; p = 0.06). Despite improvement over time, absolute values of each biomarker remained extremely abnormal. Greater reductions in biomarkers were noted in individuals with >25% decrease in NT-proBNP concentrations but reached statistical significance only in the case of galectin-3 (p = 0.01).
  
  
  CONCLUSIONS
  The biomarker profile in patients after LVAD placement improves but nonetheless remains significantly abnormal. Our results suggest the need for targeted therapeutic interventions to mitigate such abnormalities and potentially increase rates of myocardial recovery.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Teresa
authors.initials: T
authors.lastname: Wang
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Emily C
authors.initials: EC
authors.lastname: O'Brien
authors.affiliation: Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Samsky
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Pura
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rogers
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Damian
authors.initials: D
authors.lastname: Craig
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: Division of Cardiac Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Carmelo A
authors.initials: CA
authors.lastname: Milano
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: chetan.patel@duke.edu.
authors.forename: Chetan B
authors.initials: CB
authors.lastname: Patel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy*; D006353:Heart-Assist Devices; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers
keywords: LVAD; biomarkers; heart failure; myocardial recovery