title: Circulating biomarker responses to medical management vs. mechanical circulatory support in severe inotrope-dependent acute heart failure.
abstract: BACKGROUND
  Severe inotrope-dependent acute heart failure (AHF) is associated with poor clinical outcomes. There are currently no well-defined blood biomarkers of response to treatment that can guide management or identify recovery in this patient population. In the present study, we characterized the levels of novel and emerging circulating biomarkers of heart failure in patients with AHF over the first 30 days of medical management or mechanical circulatory support (MCS). We hypothesized a shared a plasma proteomic treatment response would be identifiable in both patient groups, representing reversal of the AHF phenotype.
  
  
  RESULTS
  Time course plasma samples of the first 30 days of therapy, obtained from patients managed medically (n= 8) or with implantable MCS (n= 5), underwent semi-targeted and candidate biomarker analyses, using multiple reaction monitoring (MRM) mass spectrometry, antibody arrays, and enzyme-linked immunosorbent assays. Differentially expressed proteins were identified using robust limma for MRM and antibody array data. Patients managed medically or with implantable MCS had a shared proteomic signature of six plasma proteins: circulating cardiotrophin 1, cardiac troponin T, clusterin, and dickopff 1 increased, while levels of C-reactive protein and growth differentiation factor 15 decreased in both groups over the 30 day time course.
  
  
  CONCLUSIONS
  We have characterized the temporal proteomic signature of clinical recovery in AHF patients managed medically or with MCS, over the first 30 days of treatment. Changes in biomarker expression over the time course of treatment may provide a basis for understanding the biological basis of AHF, potentially identifying novel markers and pathophysiologic mechanisms of recovery.
authors: Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada; PROOF Centre of ExcellenceVancouverCanada.
authors: Anna J
authors: 0000-0003-1596-2387
authors: AJ
authors: Meredith
authors: PROOF Centre of Excellence Vancouver Canada.
authors: Darlene L Y
authors: DL
authors: Dai
authors: PROOF Centre of Excellence Vancouver Canada.
authors: Virginia
authors: V
authors: Chen
authors: PROOF Centre of Excellence Vancouver Canada.
authors: Zsuzsanna
authors: Z
authors: Hollander
authors: PROOF Centre of ExcellenceVancouverCanada; Department of Computer ScienceUniversity of British ColumbiaVancouverCanada.
authors: Raymond
authors: R
authors: Ng
authors: School of Nursing University of British Columbia - Heart Centre at St Paul's Hospital Vancouver Canada.
authors: Annemarie
authors: A
authors: Kaan
authors: PROOF Centre of ExcellenceVancouverCanada; Department of MedicineUniversity of British ColumbiaVancouverCanada.
authors: Scott
authors: S
authors: Tebbutt
authors: Division of Cardiology University of British Columbia Vancouver Canada.
authors: Krishnan
authors: K
authors: Ramanathan
authors: Division of Surgery University of British Columbia Vancouver Canada.
authors: Anson
authors: A
authors: Cheung
authors: Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada; PROOF Centre of ExcellenceVancouverCanada.
authors: Bruce M
authors: BM
authors: McManus
keywords: Acute heart failure; Bioinformatics; Biomarkers; Mechanical circulatory support; Plasma proteomics; Ventricular assist device