Pediatric cardiomyopathies encompass a heterogeneous group of disorders including dilated, hypertrophic, and less commonly, restrictive cardiomyopathies. Emerging experimental evidence and epidemiologic data suggest that the pediatric heart failure population is distinctly different from adult patients The most common cause of heart failure and reason for cardiac transplantation in children older than 1 year is dilated cardiomyopathy (DCAmong these etiologies, pediatric dilated cardiomyopathy (DCM) has an estimated 40% five year transplant-free survival and remains the most common diagnosis leading to heart transplant in children greater than 1 year of age. The central hypothesis is that circulating microRNAs (miRs) will be useful biomarkers for risk stratification, will correlate with outcomes and may represent novel therapeutic targets in children with DCM.
The aims of this study are: 1) Determine the profile of circulating miRs in a cohort of children with DCM and acute systolic heart failure. The circulating miR expression patterns will then be stratified based on reaching a primary end-point by 1 year defined as: [1] death or transplantation, [2] recovery (normalization of ventricular size and function) or [3] stable DCM (persistent ventricular dilation or dysfunction); 2) Define the miR profile in a separate cohort of children with chronic, stable DCM to determine if those patients with stable DCM who progress to death/transplant within 1 year will be similar to the profile of the Aim 1 cohort of children with acute heart failure who also progress to death/transplant; and 3) Analyze the expression of circulating and heart tissue miRs in pediatric controls (non-failing donors whose heart could not be placed [NF]) and pediatric DCM patients. The results of this study could improve clinicians prognostic? assessment at diagnosis of DCM in children, improve decision-making regarding listing children for heart transplant as opposed to identifying those who are expected to recover ventricular function, and could provide insight into cellular mechanisms of disease and define novel targets for future treatment of DCM in children.

Public Health Relevance

Nearly half of all children with dilated cardiomyopathy and heart failure die or receive a heart transplant within 2 years of diagnosis while another 20-30% will have normal hearts in the same time period. At the time of cardiomyopathy diagnosis, doctors must make decisions about which children will likely need a heart transplant and which children will like have normal hearts in the next 2 years. The purpose of this study, ?Prognostic Significance of microRNA Expression in Children with Cardiomyopathy?, is to look at whether a blood test (microRNA) helps doctors make improved decisions about which child will need a transplant in the near future.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Kaltman, Jonathan R
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Wayne State University
Schools of Medicine
United States
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