TY - JOUR
T1 - Pediatric and adult dilated cardiomyopathy are distinguished by distinct biomarker profiles
AU - Gropler, Melanie R.F.
AU - Lipshultz, Steven E.
AU - Wilkinson, James D.
AU - Towbin, Jeffrey A.
AU - Colan, Steven D.
AU - Canter, Charles E.
AU - Lavine, Kory J.
AU - Simpson, Kathleen E.
N1 - Funding Information:
We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.
Funding Information:
This study was supported by a research grant from the Children’s Cardiomyopathy Foundation. K.E.S. is the primary investigator for the research grant from the Children’s Cardiomyopathy Foundation. The research was done in collaboration with the Pediatric Cardiomyopathy Registry (PCMR), which is supported by the National Heart, Lung, and Blood Institute to S.E.L. (HL53392, HL111459, and HL109090) and the Children’s Cardiomyopathy Foundation. K.J.L. is supported by funding from NIH (R01 HL138466, R01 HL139714), Burroughs Welcome Fund (1014782), Foundation of Barnes-Jewish Hospital (8038–88), and the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (PM-LI-2019-829). K.J.L. serves on the Medtronic: DT-PAS/APOGEE trial advisory board and receives funding and unrelated sponsored research agreements from Amgen.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2022/7
Y1 - 2022/7
N2 - Background: Emerging evidence suggests that pediatric and adult dilated cardiomyopathy (DCM) represent distinct diseases. Few diagnostic tools exist for pediatric cardiologists to assess clinical status and prognosis. We hypothesized that pediatric DCM would have a unique biomarker profile compared to adult DCM and controls. Methods: We utilized a DNA aptamer array (SOMAScan) to compare biomarker profiles between pediatric and adult DCM. We simultaneously measured 1310 plasma proteins and peptides from 39 healthy children (mean age 3 years, interquartile range (IQR) 1–14), 39 ambulatory subjects with pediatric DCM (mean age 2.7 years, IQR 1–13), and 40 ambulatory adults with DCM (mean age 53 years, IQR 46–63). Results: Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics. We identified 20 plasma peptides and proteins that were increased in pediatric DCM compared to age- and sex-matched controls. Unbiased multidimensionality reduction analysis suggested previously unrecognized heterogeneity among pediatric DCM subjects. Biomarker profile analysis identified four subgroups of pediatric DCM with distinguishing clinical characteristics. Conclusions: These findings support the emerging concept that pediatric and adult DCM are distinct disease entities, signify the need to develop pediatric-specific biomarkers for disease prognostication, and challenge the paradigm that pediatric DCM should be viewed as a single disease. Impact: Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics and outcomes.Our findings suggest that pediatric DCM may be a heterogeneous disease with various sub-phenotypes, including differing biomarker profiles and clinical findings.These data provide prerequisite information for future prospective studies that validate the identified pediatric DCM biomarkers, address their diagnostic accuracy and prognostic significance, and explore the full extent of heterogeneity amongst pediatric DCM patients.
AB - Background: Emerging evidence suggests that pediatric and adult dilated cardiomyopathy (DCM) represent distinct diseases. Few diagnostic tools exist for pediatric cardiologists to assess clinical status and prognosis. We hypothesized that pediatric DCM would have a unique biomarker profile compared to adult DCM and controls. Methods: We utilized a DNA aptamer array (SOMAScan) to compare biomarker profiles between pediatric and adult DCM. We simultaneously measured 1310 plasma proteins and peptides from 39 healthy children (mean age 3 years, interquartile range (IQR) 1–14), 39 ambulatory subjects with pediatric DCM (mean age 2.7 years, IQR 1–13), and 40 ambulatory adults with DCM (mean age 53 years, IQR 46–63). Results: Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics. We identified 20 plasma peptides and proteins that were increased in pediatric DCM compared to age- and sex-matched controls. Unbiased multidimensionality reduction analysis suggested previously unrecognized heterogeneity among pediatric DCM subjects. Biomarker profile analysis identified four subgroups of pediatric DCM with distinguishing clinical characteristics. Conclusions: These findings support the emerging concept that pediatric and adult DCM are distinct disease entities, signify the need to develop pediatric-specific biomarkers for disease prognostication, and challenge the paradigm that pediatric DCM should be viewed as a single disease. Impact: Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics and outcomes.Our findings suggest that pediatric DCM may be a heterogeneous disease with various sub-phenotypes, including differing biomarker profiles and clinical findings.These data provide prerequisite information for future prospective studies that validate the identified pediatric DCM biomarkers, address their diagnostic accuracy and prognostic significance, and explore the full extent of heterogeneity amongst pediatric DCM patients.
UR - http://www.scopus.com/inward/record.url?scp=85112688191&partnerID=8YFLogxK
U2 - 10.1038/s41390-021-01698-x
DO - 10.1038/s41390-021-01698-x
M3 - Article
C2 - 34404929
AN - SCOPUS:85112688191
SN - 0031-3998
VL - 92
SP - 206
EP - 215
JO - Pediatric research
JF - Pediatric research
IS - 1
ER -