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Age-dependent Transcriptional Programs Distinguish Pediatric from Adult Dilated Cardiomyopathy

Zoe Leroux1, Obed O Nyarko1,2, Anis Karimpour-Fard3

  • 1Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Medrxiv : the Preprint Server for Health Sciences
|March 27, 2026
PubMed

Insights

Pediatric dilated cardiomyopathy (DCM) shows distinct gene expression from adult DCM, activating developmental pathways instead of the metabolic dysfunction seen in adults. This difference explains why standard heart failure treatments are less effective in children, necessitating tailored therapies.

Area of Science:

  • Cardiology
  • Genomics
  • Transcriptomics

Background:

  • Current pediatric dilated cardiomyopathy (DCM) management uses adult guidelines, but lacks proven efficacy due to limited pediatric trials.
  • Fundamental differences in disease mechanisms between pediatric and adult DCM are suspected, driving the need for age-specific research.

Purpose of the Study:

  • To investigate age-dependent transcriptional programs in pediatric versus adult DCM.
  • To identify distinct molecular pathways underlying therapeutic discordance in pediatric DCM.

Main Methods:

  • Comparative transcriptomic profiling using bulk RNA sequencing on pediatric and adult DCM explanted heart tissue.
  • Analysis of differential gene expression, pathway enrichment, and the β1-adrenergic receptor gene signaling network (β1-GSN).

Main Results:

  • Pediatric and adult DCM share only 7.4% of differentially expressed genes, indicating distinct disease signatures.
  • Pediatric DCM activates developmental pathways (WNT/β-catenin, Notch), while adult DCM shows metabolic dysfunction and inflammation.
  • The β1-GSN remains activated in pediatric DCM, unlike the desensitized state in adults.

Conclusions:

  • Pediatric DCM is a biologically distinct entity, not merely an early form of adult heart failure.
  • The lack of pathological β-adrenergic remodeling in children explains the limited efficacy of β-blockers.
  • Future therapies must target pediatric-specific pathways, moving beyond adult-based extrapolations.
Abstract

Keywords:
Adult heart failureCardiac remodelingDilated cardiomyopathy (DCM)Gene expression profilingPediatric heart failureβ-adrenergic signaling

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