Prognostic Significance of microRNA Expression in Children with Cardiomyopathy

项目摘要 小儿心肌病包括一组异质性疾病，包括扩张性，肥厚性， 以及不常见的限制性心肌病。新出现的实验证据和流行病学数据 表明儿童心力衰竭人群与成人患者明显不同。 1岁以上儿童心力衰竭的原因和心脏移植的原因是扩张性的 在这些病因中，小儿扩张型心肌病（DCM）估计有40% 五年无移植存活率，仍然是导致心脏移植的最常见诊断， 1岁以上儿童。核心假设是循环microRNAs（miRs）将是有用的， 风险分层的生物标志物，将与结果相关，并可能代表新的治疗靶点， DCM患儿本研究的目的是：1）确定一个队列中循环miR的概况， DCM和急性收缩性心力衰竭的儿童。然后将循环miR表达模式 根据1年内达到主要终点进行分层，定义为：[1]死亡或移植，[2]恢复 （心室大小和功能正常化）或[3]稳定型DCM（持续性心室扩张或功能障碍）; 2)在一个单独的慢性、稳定型DCM儿童队列中定义miR谱，以确定 在1年内进展至死亡/移植的稳定型DCM患者将与Aim的特征相似 1组急性心力衰竭儿童，他们也进展到死亡/移植;和3）分析 在儿科对照组（心脏不能存活的非衰竭供体）中， 被放置[NF]）和儿科DCM患者。这项研究的结果可以改善临床医生对预后的判断， 在诊断儿童DCM时进行评估，改善关于将儿童列为心脏病患者的决策 移植，而不是确定那些谁预计恢复心室功能，并可以提供 深入了解疾病的细胞机制，并确定未来治疗儿童DCM的新靶点。

Project Summary 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.