Evidence map›Paper›PMID 33435695›Full record

ArticleCirculation2021

Cell-Free DNA to Detect Heart Allograft Acute Rejection.

Sean Agbor-Enoh, Palak Shah, Ilker Tunc, Steven Hsu, Stuart Russell, Erika Feller, Keyur Shah, Maria E Rodrigo, Samer S Najjar, Hyesik Kong and 13 more

2 registry-linked trialsOpen access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 132 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 3 pooled it
37.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02423070 recruitingnot on this map

Genome Transplant Dynamics

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2015 to 2034Enrolled991ConditionsThoracic Organ Transplantation
NCT06740578 completednot on this map

Evaluation of the Added Clinical Value of Donor-derived Cell-free DNA for the Monitoring of Cardiac Allograft Rejection: an Observational Prospective Longitudinal Multicenter Study.

Typeobservational_patient_registrySponsorParis Translational Research Center for Organ TransplantationRan2021 to 2023Enrolled320ConditionsHeart Transplantation, Rejection Heart Transplant
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 262 citations in OpenAlex.

  1. Pooled it
  2. Elevated Cardiac Troponin to Detect Acute Cellular Rejection After Cardiac Transplantation: A Systematic Review and Meta-Analysis.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Pooled it
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  14. JHLT open · 2026
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  15. The tissue is the issue: Going beyond histopathology in antibody-mediated rejection in heart transplant patients.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026
    Article
  16. Review
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72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 9 institutions in 3 countries.

Sean Agbor-Enoh *Genomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Palak Shah *Genomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Ilker TuncGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Steven HsuGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Stuart RussellDepartment of Medicine, Duke University School of Medicine, Durham, NC (S.R.).
Erika FellerGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Keyur ShahGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Maria E RodrigoGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Samer S NajjarGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Hyesik KongGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Mehdi PiroozniaDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (S.A.-E., I.T., H.K., M.P., U.F., A.B., A.M., K.B., Y.Y., M.K.J., H.A.V.).
Ulgen FideliGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Alfiya BikineyevaGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Argit MarishtaGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Kenneth BhattiGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Yanqin YangGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Cedric MutebiGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Kai YuNational Cancer Institute, Rockville, MD (K.Y.).
Moon Kyoo JangGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Charles MarboeGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Gerald J BerryGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
Hannah A ValantineGenomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).
GRAfT Investigators
National Heart Lung and Blood Institute · USJohns Hopkins University · USNorwegian Womens Public Health Association · NODuke University · USNational Cancer Institute · MYNewYork–Presbyterian Hospital · USPalo Alto University · USUniversity of Maryland, Baltimore · USVirginia Commonwealth University · US

Funding

Cell-free DNA to detect transplant rejectionZIAHL006268 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI AGBOR-ENOH, SEAN · 2021 to 2025
$8.8M
Bioinformatics CoreZICHL006228 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI PIROOZNIA, MEHDI · 2017 to 2021
$6.6M
MicroRNA Biomarkers of Allograft Rejection and Cardiac Allograft Vasculopathy in Cardiac TransplantationK23HL143179 · NHLBI · INOVA HEALTH CARE SERVICES · PI SHAH, PALAK · 2020 to 2024
$927k
American Heart Association-American Stroke Association 17SDG33660431NHLBI NIH HHS HHSN268201300001CNHLBI NIH HHS K23 HL143179
6 · The paper itself

Abstract

backgroundAfter heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients.

methodsThis multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis.

resultsThe study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%];

conclusionsWe found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

Indexed as

AdultAgedAllograftsCell-Free Nucleic AcidsCohort StudiesFemaleGraft RejectionHumansMaleMiddle AgedProspective StudiesYoung AdultCell-Free Nucleic Acidsallograft rejectionbiomarkerscardiac transplantationcell-free DNAgraft injury

Identifiers

PMID33435695
PMCPMC8221834
OpenAlexW3118471169

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.