Evidence map›Paper›PMID 41001507›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Donor-Derived Cell-Free DNA Stratifies Risk of Mortality and Graft Dysfunction in Severe Acute Cardiac Allograft Rejection.

Zaid N Safiullah, Han Su, Hyesik Kong, Moon Kyoo Jang, Keyur Shah, Gerald J Berry, Palak Shah, Hannah A Valantine, Xin Tian, Sean Agbor-Enoh

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Zaid N SafiullahCritical Care Medicine Department, National Institutes of Health, Bethesda, MD.
Han SuOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Hyesik KongGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0001-7540-2045
Moon Kyoo JangGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0002-1657-2877
Keyur ShahGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.
Gerald J BerryGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0002-6176-2629
Palak ShahGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0001-8175-168X
Hannah A ValantineGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0002-2948-9503
Xin TianOffice of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.ORCID 0000-0003-1896-2462
Sean Agbor-EnohGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD.ORCID 0000-0002-9380-9161

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Cardiac acute rejection (AR) is a risk factor for poor outcomes, however there are limited risk prediction models to stratify patients for death or sustained LV dysfunction. This study assesses the prognostic utility of percentage donor-derived cell-free DNA (%dd-cfDNA) at the diagnosis of AR for poor outcomes. Methods: The prospective multicenter GRAfT study enrolled heart transplant recipients and collected serial plasma samples to quantitate %dd-cfDNA. AR was defined as acute cellular rejection (ACR), antibody-mediated rejection (AMR), as well as biopsy-negative AMR (donor-specific antibody positivity with LV dysfunction). AR was classified as mild-to-moderate (ACR grade 2 or AMR grade 1) or severe (ACR grade ≥3, AMR grade ≥2, or DSA+/LV dysfunction) and further stratified by a %dd-cfDNA threshold of 0.25%. Regression models assessed the association between AR and %dd-cfDNA levels at the AR diagnosis with the primary composite outcome of sustained LVEF decline <50% and/or death. Results: The study included 275 patients and 3,190 %dd-cfDNA assessments. Over the median of 4.6 (IQR 1.8 - 5.0) years follow-up, 51 patients experienced the composite outcome of death or prolonged EF reduction, and 75 patients developed AR, including 16.2% patients with ACR, 9.4% with pathologic AMR, and 6.6% with DSA+/LV dysfunction. Thirty-two (42.7%) patients had severe AR and 43 (57.3%) had mild-to-moderate AR. Severe-but not mild-to-moderate-AR was associated with an increased risk of the primary composite endpoint (HR = 5.17, 95% CI 2.38 - 11.3, p < 0.001). Among those with severe AR, a %dd-cfDNA level greater than 0.25% at diagnosis was associated with a higher risk of the primary outcome (HR, 6.06, 95% CI, 1.78-20.6; p = 0.004). Percent dd-cfDNA remained elevated in severe AR patients with adverse outcomes. Conclusion: Severe AR with high %dd-cfDNA levels is associated with an increased risk of poor outcomes, offering novel prognostic utility.

Indexed as

Acute RejectionCardiac TransplantationCell-free DNA

Identifiers

PMID41001507
PMCPMC12458610

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