Pediatric and adult dilated cardiomyopathy represent distinct pathological entities

Meghna D. Patel, Jayaram Mohan, Caralin Schneider, Geetika Bajpai, Enkhsaikhan Purevjav, Charles E. Canter, Jeffrey Towbin, Andrea Bredemeyer, Kory J. Lavine

Research output: Contribution to journalArticle

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Abstract

Pediatric dilated cardiomyopathy (DCM) is the most common indication for heart transplantation in children. Despite similar genetic etiologies, medications routinely used in adult heart failure patients do not improve outcomes in the pediatric population. The mechanistic basis for these observations is unknown. We hypothesized that pediatric and adult DCM comprise distinct pathological entities, in that children do not undergo adverse remodeling, the target of adult heart failure therapies. To test this hypothesis, we examined LV specimens obtained from pediatric and adult donor controls and DCM patients. Consistent with the established pathophysiology of adult heart failure, adults with DCM displayed marked cardiomyocyte hypertrophy and myocardial fibrosis compared with donor controls. In contrast, pediatric DCM specimens demonstrated minimal cardiomyocyte hypertrophy and myocardial fibrosis compared with both age-matched controls and adults with DCM. Strikingly, RNA sequencing uncovered divergent gene expression profiles in pediatric and adult patients, including enrichment of transcripts associated with adverse remodeling and innate immune activation in adult DCM specimens. Collectively, these findings reveal that pediatric and adult DCM represent distinct pathological entities, provide a mechanistic basis to explain why children fail to respond to adult heart failure therapies, and suggest the need to develop new approaches for pediatric DCM.

Original languageEnglish (US)
JournalJCI insight
Volume2
Issue number14
DOIs
StatePublished - Jul 20 2017

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Dilated Cardiomyopathy
Pediatrics
Heart Failure
Cardiac Myocytes
Hypertrophy
Fibrosis
Tissue Donors
RNA Sequence Analysis
Heart Transplantation
Transcriptome
Therapeutics

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Patel, M. D., Mohan, J., Schneider, C., Bajpai, G., Purevjav, E., Canter, C. E., ... Lavine, K. J. (2017). Pediatric and adult dilated cardiomyopathy represent distinct pathological entities. JCI insight, 2(14). https://doi.org/10.1172/jci.insight.94382

Pediatric and adult dilated cardiomyopathy represent distinct pathological entities. / Patel, Meghna D.; Mohan, Jayaram; Schneider, Caralin; Bajpai, Geetika; Purevjav, Enkhsaikhan; Canter, Charles E.; Towbin, Jeffrey; Bredemeyer, Andrea; Lavine, Kory J.

In: JCI insight, Vol. 2, No. 14, 20.07.2017.

Research output: Contribution to journalArticle

Patel, MD, Mohan, J, Schneider, C, Bajpai, G, Purevjav, E, Canter, CE, Towbin, J, Bredemeyer, A & Lavine, KJ 2017, 'Pediatric and adult dilated cardiomyopathy represent distinct pathological entities', JCI insight, vol. 2, no. 14. https://doi.org/10.1172/jci.insight.94382
Patel, Meghna D. ; Mohan, Jayaram ; Schneider, Caralin ; Bajpai, Geetika ; Purevjav, Enkhsaikhan ; Canter, Charles E. ; Towbin, Jeffrey ; Bredemeyer, Andrea ; Lavine, Kory J. / Pediatric and adult dilated cardiomyopathy represent distinct pathological entities. In: JCI insight. 2017 ; Vol. 2, No. 14.
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