Age-dependent Transcriptional Programs Distinguish Pediatric from Adult Dilated Cardiomyopathy

<b>What Is New?:</b> This comparative transcriptomic analysis demonstrates that pediatric and adult dilated cardiomyopathy possess profoundly distinct biological signatures, with only 7.4% of differentially expressed disease-associated genes shared between the two age groups.Unlike adult dilated cardiomyopathy, which is driven by metabolic dysfunction and extensive remodeling of the β1-adrenergic receptor gene signaling network, pediatric disease is uniquely characterized by the activation of developmental pathways such as WNT/β-catenin and Notch signaling without significant pathological β1-adrenergic remodeling.<b>What Are the Clinical Implications?:</b> The absence of pathological β-adrenergic remodeling in pediatric hearts provides a molecular explanation for the limited clinical efficacy of β-blocker therapy in this population, underscoring the critical need to develop age-specific precision medicine strategies rather than continuing to extrapolate guideline-directed medical therapies from adult heart failure.