Evidence map›Paper›PMID 34622662›Full record

ArticleJournal of the American Heart Association2021

Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease-Associated Pulmonary Hypertension.

Caroline M Daly, Megan Griffiths, Catherine E Simpson, Jun Yang, Rachel L Damico, R Dhananjay Vaidya, Monica Williams, Stephanie Brandal, Pei-Ni Jone, Cassandra Polsen and 10 more

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2021. 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
1.2field-weighted citation impact, top 20% 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, 10 citations in OpenAlex.

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  7. ERJ open research · 2022
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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

20 authors at 6 institutions in 1 country.

Caroline M DalyJohns Hopkins University School of Medicine Baltimore MD.
Megan GriffithsDivision of Pediatric Cardiology Department of Pediatrics Johns Hopkins University Baltimore MD.ORCID 0000-0002-8598-9078
Catherine E SimpsonDivision of Pulmonary and Critical Care Medicine Johns Hopkins University Baltimore MD.
Jun YangDivision of Pediatric Cardiology Department of Pediatrics Johns Hopkins University Baltimore MD.
Rachel L DamicoDivision of Pulmonary and Critical Care Medicine Johns Hopkins University Baltimore MD.ORCID 0000-0002-2584-1557
R Dhananjay VaidyaDepartment of Internal Medicine Johns Hopkins University Baltimore MD.ORCID 0000-0002-7164-1601
Monica WilliamsDepartment of Anesthesia and Critical Care Medicine Johns Hopkins University Baltimore MD.
Stephanie BrandalDivision of Pediatric Cardiology Department of Pediatrics Johns Hopkins University Baltimore MD.
Pei-Ni JoneDepartment of Pediatric Cardiology Children's Hospital ColoradoUniversity of Colorado Aurora CO.
Cassandra PolsenDepartment of Pediatric Cardiology Children's Hospital ColoradoUniversity of Colorado Aurora CO.ORCID 0000-0001-8665-1944
D Dunbar IvyDepartment of Pediatric Cardiology Children's Hospital ColoradoUniversity of Colorado Aurora CO.ORCID 0000-0003-2541-3402
Eric D AustinDivision of Allergy, Immunology, and Pulmonary Medicine Department of Pediatrics Vanderbilt University Medical Center Nashville TN.
William C NicholsDivision of Human Genetics Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH.
Michael W PauciuloDivision of Human Genetics Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH.
Katie LutzDivision of Human Genetics Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH.ORCID 0000-0002-9554-7679
Melanie K NiesDivision of Pediatric Cardiology Department of Pediatrics Johns Hopkins University Baltimore MD.ORCID 0000-0001-5453-425X
Erika B RosenzweigDivision of Pediatric Cardiology Department of Pediatrics Columbia University New York City NY.
Russel HirschDivision of Pediatric Cardiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH.
Delphine YungDivision of Pediatric Cardiology Department of Pediatrics University of Washington Seattle WA.
Allen D EverettDivision of Pediatric Cardiology Department of Pediatrics Johns Hopkins University Baltimore MD.ORCID 0000-0002-5559-6708
Johns Hopkins University · USUniversity of Cincinnati Medical Center · USChildren's Hospital Colorado · USColumbia University · USUniversity of Washington · USVanderbilt University Medical Center · US

Funding

NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
National Biological Sample and Data Repository for PAHR24HL105333 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI NICHOLS, WILLIAM C · 2012 to 2016
$10.1M
Clinical and mechanistic role of HDGF in pulmonary hypertensionR01HL135114 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI EVERETT, ALLEN D · 2017 to 2020
$2.9M
Role of IGF axis in pulmonary hypertensionR01HL150070 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI EVERETT, ALLEN D, YANG, JUN · 2020 to 2023
$2.8M
The role of xanthine oxidoreductase activity and altered metabolism in scleroderma-associated pulmonary arterial hypertensionK23HL153781 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SIMPSON, CATHERINE · 2020 to 2024
$883k
NCATS NIH HHS UL1 TR002535NHLBI NIH HHS K23 HL153781NHLBI NIH HHS R01 HL135114NHLBI NIH HHS R01 HL150070NHLBI NIH HHS R24 HL105333NHLBI NIH HHS R24 HL123767NICHD NIH HHS K12 HD000850
6 · The paper itself

Abstract

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross-sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH-CHD, N=185). Outcomes, assessed by regression and Kaplan-Meier analysis, included hemodynamics, change in endostatin over time, and transplant-free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH-CHD. In APAH-CHD, endostatin was associated with a shorter 6-minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant-free survival. Addition of endostatin to an NT-proBNP (N-terminal pro-B-type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH-CHD. Endostatin with NT-proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH-CHD.

Indexed as

Angiostatic ProteinsHeart Defects, CongenitalHypertension, PulmonaryPulmonary Arterial HypertensionBiomarkersChildCross-Sectional StudiesEndostatinsEndothelial CellsFamilial Primary Pulmonary HypertensionHumansAngiostatic ProteinsBiomarkersEndostatinsangiogenesisbiomarkerschildrenproteomicspulmonary vascular disease

Identifiers

PMID34622662
PMCPMC8751905
OpenAlexW3204426827

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.