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Olof Gidlöf

Research project participant

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HEARTBiT : A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients

Author

  • Casey P. Shannon
  • Zsuzsanna Hollander
  • Darlene L.Y. Dai
  • Virginia Chen
  • Sara Assadian
  • Karen K. Lam
  • Janet E. McManus
  • Marek Zarzycki
  • Young Woong Kim
  • Ji Young V. Kim
  • Robert Balshaw
  • Olof Gidlöf
  • Jenny Öhman
  • J. Gustav Smith
  • Mustafa Toma
  • Andrew Ignaszewski
  • Ross A. Davies
  • Diego Delgado
  • Haissam Haddad
  • Debra Isaac
  • Daniel Kim
  • Alice Mui
  • Miroslaw Rajda
  • Lori West
  • Michel White
  • Shelley Zieroth
  • Scott J. Tebbutt
  • Paul A. Keown
  • W. Robert McMaster
  • Raymond T. Ng
  • Bruce M. McManus

Summary, in English

Background: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT. Methods: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014. All adult cardiac transplant patients were invited to participate (median age = 56 [17 to 71]). The reference standard for rejection status was histopathology grading of tissue from endomyocardial biopsy (EMB). All locally graded ISHLT ≥ 2R rejection samples were selected for analysis (n = 36). ISHLT 1R (n = 38) and 0R (n = 86) samples were randomly selected to create a cohort approximately matched for site, age, sex, and days post-transplantation, with a focus on early time points (median days post-transplant = 42 [7 to 506]). Results: ISHLT ≥ 2R rejection was confirmed by EMB in 18 and excluded in 92 samples in the test set. HEARTBiT achieved 47% specificity (95% confidence interval [CI], 36%-57%) given ≥ 90% sensitivity, with a corresponding area under the receiver operating characteristic curve of 0.69 (95% CI, 0.56-0.81). Conclusions: HEARTBiT's diagnostic performance compares favourably to the only currently approved minimally invasive diagnostic test to rule out ACR, AlloMap (CareDx, Brisbane, CA) and may be used to inform care decisions in the first 2 months post-transplantation, when AlloMap is not approved, and most ACR episodes occur.

Department/s

  • Cardiovascular Epigenetics
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiology
  • EpiHealth: Epidemiology for Health

Publishing year

2020-08

Language

English

Pages

1217-1227

Publication/Series

Canadian Journal of Cardiology

Volume

36

Issue

8

Document type

Journal article

Publisher

Elsevier Inc.

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Epigenetics

ISBN/ISSN/Other

  • ISSN: 0828-282X