HEARTBiT : A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients
(2020) In Canadian Journal of Cardiology 36(8). p.1217-1227- Abstract
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... (More)
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.
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- author
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- publishing date
- 2020-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Canadian Journal of Cardiology
- volume
- 36
- issue
- 8
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85086737363
- pmid:32553820
- ISSN
- 0828-282X
- DOI
- 10.1016/j.cjca.2019.11.017
- language
- English
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- yes
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- 889726be-a0de-4887-b23f-2fb17d730952
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- 2024-04-17 12:10:34
@article{889726be-a0de-4887-b23f-2fb17d730952,
abstract = {{<p>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.</p>}},
author = {{Shannon, Casey P. and Hollander, Zsuzsanna and Dai, Darlene L.Y. and Chen, Virginia and Assadian, Sara and Lam, Karen K. and McManus, Janet E. and Zarzycki, Marek and Kim, Young Woong and Kim, Ji Young V. and Balshaw, Robert and Gidlöf, Olof and Öhman, Jenny and Smith, J. Gustav and Toma, Mustafa and Ignaszewski, Andrew and Davies, Ross A. and Delgado, Diego and Haddad, Haissam and Isaac, Debra and Kim, Daniel and Mui, Alice and Rajda, Miroslaw and West, Lori and White, Michel and Zieroth, Shelley and Tebbutt, Scott J. and Keown, Paul A. and McMaster, W. Robert and Ng, Raymond T. and McManus, Bruce M.}},
issn = {{0828-282X}},
language = {{eng}},
number = {{8}},
pages = {{1217--1227}},
publisher = {{Elsevier}},
series = {{Canadian Journal of Cardiology}},
title = {{HEARTBiT : A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients}},
url = {{http://dx.doi.org/10.1016/j.cjca.2019.11.017}},
doi = {{10.1016/j.cjca.2019.11.017}},
volume = {{36}},
year = {{2020}},
}