Evidence map›Paper›PMID 35251005›Full record

ArticleFrontiers in immunology2022

Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients - A Proof-of-Concept Study.

Megan Kamath, Grigoriy Shekhtman, Tristan Grogan, Michelle J Hickey, Irina Silacheva, Karishma S Shah, Kishan S Shah, Adrian Hairapetian, Diego Gonzalez, Giovanny Godoy and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.1field-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

9 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Megan KamathDivison of Cardiology, Department of Medicine, Ronald Reagan University of California, Los Angeles (UCLA) Medical Center, Los Angeles, CA, United States.
Grigoriy ShekhtmanDepartment of Medical Affairs, CareDx Inc., Brisbane, CA, United States.
Tristan GroganDepartment of Medicine Statistics Core, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Michelle J HickeyUniversity of California, Los Angeles (UCLA) Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Irina SilachevaDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Karishma S ShahDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Kishan S ShahDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Adrian HairapetianDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Diego GonzalezDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Giovanny GodoyDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Elaine F ReedUniversity of California, Los Angeles (UCLA) Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
David ElashoffDepartment of Medicine Statistics Core, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Galyna BondarDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Mario C DengDeng Advanced Heart Failure Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
University of California, Los Angeles · USPAX Scientific (United States) · US

Funding

Project 3: Mapping the Evolution of Chronic Transplant Injury in the Context of CMV InfectionU19AI128913 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELASHOFF, DAVID · 2017 to 2021
$11.2M
The role of HLA and its coreceptors in endothelial cell activation and leukocyte recruitment in antibody-mediated transplant rejectionR01AI135201 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert L Fairchild, ELAINE F REED · 2018 to 2026
$5.3M
Multi-omic Biomarker Discovery and Validation in Heart Transplant Patient PopulationsR01AI144522 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DENG, MARIO C., KEATING, BRENDAN JAMES · 2020 to 2024
$4.0M
Targeting YAP with statins to prevent antibody-mediated transplant rejectionR21AI156592 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F, ROZENGURT, JUAN ENRIQUE · 2021 to 2022
$444k
Multidimensional Molecular Biomarkers of MultiOrgan Dysfunction after MCS TherapyR21HL120040 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENG, MARIO C. · 2014 to 2015
$421k
NHLBI NIH HHS R21 HL120040NIAID NIH HHS R01 AI135201NIAID NIH HHS R01 AI144522NIAID NIH HHS R21 AI156592NIAID NIH HHS U19 AI128913
6 · The paper itself

Abstract

backgroundOver the last decade, expanding use of molecular diagnostics in heart transplantation has allowed implementation of non-invasive surveillance strategies for monitoring allograft health. The commercially available HeartCare platform combines the AlloMap gene expression profiling assay and the AlloSure donor-derived cell-free DNA test (dd-cfDNA). Beyond their established use for assessment of rejection, evidence is building for predictive utility, with the longitudinal AlloMap Variability score previously shown to correlate with the risk of future rejection, graft dysfunction, re-transplantation, or death. In this single-center, retrospective pilot study, we evaluated the performance of a novel AlloSure Variability metric in predicting mortality in a cohort of heart transplant recipients.

methodsSeventy-two adult heart transplant recipients with at least 3 concurrent AlloMap/AlloSure results were included. Demographic, clinical, imaging, and laboratory parameters were captured. Variability was defined as the standard deviation of longitudinal AlloMap/AlloSure results. A Cox multivariable adjusted proportional hazards model was used to evaluate the variability metrics as predictors of mortality. Associations between AlloMap/AlloSure variability and donor specific antibody (DSA) status were also assessed.

resultsA total of 5 patients (6.9%) died during a median follow-up of 480 days. In a univariate Cox proportional hazards model, higher AlloSure variability (HR 1.66, 95%CI 1.14 - 2.41), but not AlloMap variability or the cross-sectional AlloSure/AlloMap results was associated with increased mortality risk. Longitudinal AlloSure variability was also higher among patients with both preformed DSA and those developing

conclusionOur results suggest that increased variability of dd-cfDNA in heart transplant patients is associated with both mortality risk and the presence of donor specific antibodies. These findings highlight the added value of longitudinal data in the interpretation of AlloMap/AlloSure scores in this population and open the door to larger studies investigating the utility of these metrics in shaping post-transplant clinical care paradigms.

Indexed as

Cell-Free Nucleic AcidsHeart TransplantationAdultAntibodiesCross-Sectional StudiesGraft RejectionHumansPilot ProjectsRetrospective StudiesAntibodiesCell-Free Nucleic AcidsAlloMap VariabilityAlloSure Variabilitydonor-derived cell-free DNA (dd-cfDNA)donor specific antibody (DSA)gene expression profiling (GEP)heart transplantationmortalityrisk prediction

Identifiers

PMID35251005
PMCPMC8895247
OpenAlexW4212950454

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.