Evidence map›Paper›PMID 36004627›Full record

ArticleCirculation2022

Plasma Cell-Free DNA Predicts Survival and Maps Specific Sources of Injury in Pulmonary Arterial Hypertension.

Samuel B Brusca, Jason M Elinoff, Yvette Zou, Moon Kyoo Jang, Hyesik Kong, Cumhur Y Demirkale, Junfeng Sun, Fayaz Seifuddin, Mehdi Pirooznia, Hannah A Valantine and 11 more

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

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
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  7. Observational
  8. Review
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  10. Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  18. Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
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  20. Observational
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

21 authors at 9 institutions in 2 countries.

Samuel B BruscaPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0003-3762-7918
Jason M ElinoffPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-2376-6370
Yvette ZouPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-5187-3616
Moon Kyoo JangDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (M.J., H.K., F.S., M.P., S.A.-E.).ORCID 0000-0002-1657-2877
Hyesik KongDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (M.J., H.K., F.S., M.P., S.A.-E.).ORCID 0000-0001-7540-2045
Cumhur Y DemirkalePulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.
Junfeng SunPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.
Fayaz SeifuddinDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (M.J., H.K., F.S., M.P., S.A.-E.).
Mehdi PiroozniaDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (M.J., H.K., F.S., M.P., S.A.-E.).ORCID 0000-0002-4210-6458
Hannah A ValantineGenomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (M.J., H.K., H.A.V., S.A.-E.).ORCID 0000-0002-2948-9503
Carl TanbaDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, MA (C.T., I.R.P.).ORCID 0000-0003-0482-5192
Abhishek ChaturvediPauley Heart Center, Virginia Commonwealth University School of Medicine, Richmond (A.C.).
Grace M GraningerPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-2856-9747
Bonnie HarperPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-7829-6193
Li-Yuan ChenPulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-3596-4577
Justine ColeDepartment of Laboratory Medicine (J.C.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0002-0278-4094
Manreet KanwarCardiovascular Institute at Allegheny Health Network, Pittsburgh, PA (M.K.).ORCID 0000-0002-7280-5268
Raymond L BenzaDepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus (R.L.B.).ORCID 0000-0001-9627-6236
Ioana R PrestonDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts Medical Center, Boston, MA (C.T., I.R.P.).
Sean Agbor-Enoh *Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (M.J., H.K., F.S., M.P., S.A.-E.).ORCID 0000-0002-9380-9161
Michael A Solomon *Pulmonary Arterial Hypertension Section of the Critical Care Medicine Department (S.B.B., J.M.E., Y.Z., C.Y.D., J.S., G.M.G., B.H., L.-Y.C., M.A.S.), National Institutes of Health Clinical Center, Bethesda, MD.ORCID 0000-0001-7400-6614
National Institutes of Health Clinical Center · USNational Heart Lung and Blood Institute · USTufts Medical Center · USAllegheny Health Network · USJohns Hopkins University · USPalo Alto University · USThe Ohio State University Wexner Medical Center · USUniversity of California, San Francisco · 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
Clinical Translational Research Program in Pulmonary Arterial Hypertension (PAH): Disease Mechanisms, Biomarkers, and Novel Therapeutic TargetsZIACL090066 · CLC · CLINICAL CENTER · PI SOLOMON, MICHAEL · 2020 to 2025
$0k
Intramural NIH HHS ZIA CL090066
6 · The paper itself

Abstract

backgroundCell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown.

methodsPlasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using

resultsIn cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance

conclusionsCirculating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.

Indexed as

Cell-Free Nucleic AcidsPulmonary Arterial HypertensionAgedBiomarkersFamilial Primary Pulmonary HypertensionFemaleHumansMaleMiddle AgedPrognosisROC CurveBiomarkersCell-Free Nucleic Acidsbiomarkerscell-free nucleic acidsendothelium, vascularmethylationmonocytesmyocytes, cardiacpulmonary arterial hypertensionrisk assessment

Identifiers

PMID36004627
PMCPMC9529801
OpenAlexW4293102283

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Read underepoch 390

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 OpenQuestion graph.