Evidence map›Paper›PMID 35643770›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2023

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults.

Marc E Richmond, Shriprasad R Deshpande, Steven D Zangwill, David P Bichell, Steven J Kindel, William T Mahle, Jacob N Schroder, Mark A Wigger, Kenneth R Knecht, Elfriede Pahl and 8 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.8field-weighted citation impact, top 9% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. A two-threshold algorithm using donor-derived cell-free DNA fraction and quantity to detect acute rejection after heart transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Article
  3. Article
  4. %dd-cfDNA: The New Frontier for Heart/Lung Transplant Surveillance?Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  5. Article
  6. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 10 institutions in 1 country.

Marc E RichmondDivision of Pediatric Cardiology, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. Electronic address: mr2306@cumc.columbia.edu.
Shriprasad R DeshpandeDivision of Pediatric Cardiology, Children's National Heart Institute, Children's National Hospital, Washington, DC.
Steven D ZangwillDivision of Cardiology, Phoenix Children's Hospital, Phoenix, Ariz.
David P BichellDivision of Pediatric Cardiac Surgery, Department of Surgery, Vanderbilt University, Nashville, Tenn.
Steven J KindelDivision of Pediatric Cardiology, Department of Pediatrics, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, Wis.
William T MahleDivision of Cardiology, Department of Pediatrics, Emory University, Children's Healthcare of Atlanta, Atlanta, Ga.
Jacob N SchroderDivision of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University, Durham, NC.
Mark A WiggerDivision of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, Tenn.
Kenneth R KnechtDepartment of Pediatrics, Arkansas Children's Hospital, Little Rock, Ark.
Elfriede PahlCardiology, Lurie Children's Hospital, Chicago, Ill.
Nunzio A GaglianelloDepartment of Medicine, Medical College of Wisconsin, Milwaukee, Wis.
Mary A GoetschDepartment of Surgery, Medical College of Wisconsin, Milwaukee, Wis.
Pippa SimpsonDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.
Mahua DasguptaDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.
Liyun ZhangDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.
Paula E NorthDepartment of Pathology, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, Wis.
Aoy Tomita-MitchellDivision of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Milwaukee, Wis.
Michael E MitchellDivision of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Milwaukee, Wis.
Medical College of Wisconsin · USVanderbilt University · USArkansas Children's Hospital · USChildren's Hospital of Wisconsin · USChildren's National · USColumbia University · USDuke University · USEmory University · USLurie Children's Hospital · USPhoenix Children's Hospital · US

Funding

Targeted, Highly Sensitive, Non-Invasive Cardiac Transplant Rejection MonitoringR01HL119747 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI MITCHELL, AOY TOMITA, MITCHELL, MICHAEL EDWARD · 2013 to 2017
$3.3M
NHLBI NIH HHS R01 HL119747
6 · The paper itself

Abstract

objectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.

methodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.

resultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).

conclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.

Indexed as

Cell-Free Nucleic AcidsHeart TransplantationAdultAllograftsAntibodiesBiopsyChildGraft RejectionHumansPredictive Value of TestsAntibodiesCell-Free Nucleic Acidscell-free DNAendomyocardial biopsyheart transplantationpediatric heart transplantationrejection

Identifiers

PMID35643770
PMCPMC9617812
OpenAlexW4225255804

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.