Non-invasive risk assessment tool for pediatric heart failure

摘要 儿童患者的心力衰竭(HF)是一种很难评估的破坏性疾病，即使是在 侵入性的医院程序。重要的是，对于儿科人群来说，大约25%的人 儿童心衰患者在确诊后1年内可自行恢复正常心功能。不幸的是， 没有可靠的临床参数或生物标志物可以让儿科心脏病专家正确预测 的心力衰竭患者无需手术即可恢复正常的心功能，迫使临床医生 他们的这些孩子在移植名单上，尽管在某些情况下不需要手术干预。 科罗拉多大学丹佛分校最近进行的一项研究为这一问题提供了一个潜在的解决方案 确定了在循环血液中发现的与A基因相关的microRNAs的独特表达特征 未经手术干预即可恢复心功能的儿童心衰患者亚群。它是 该第一阶段项目的目标是完成与开发有关的初步概念验证实验 一种基于对这些循环中的miRNA的测量的商业测试。拟完成的工作 该项目旨在为预期的第二阶段试验提供基础。通过建立和 使用控制样本验证测试协议，该项目将为测试奠定基础，然后可以 在随后的前瞻性研究中进行评估，该研究旨在测试新诊断的儿童心衰患者和 观察他们的治疗结果。小儿心力衰竭患者无创检测方法的研制 会有很大的患者价值和商业价值。通过为临床医生提供非侵入性风险 对于心力衰竭儿童患者的分层工具，这类测试将(1)帮助临床医生、患者和家庭 了解与健康相关的预后，以便制定适当的长期计划，(2)减少侵袭性疾病的数量 对这些患者进行手术，(3)防止不必要的移植，改善 存活几十年，超过目前移植心脏10-20年的寿命，以及(4)降低健康 与心脏移植相关的护理费用。

ABSTRACT Heart Failure (HF) in pediatric patients is a devastating disease that is difficult to evaluate, even with invasive hospital procedures. Importantly, and unique to the pediatric population, approximately 25% of pediatric HF patients spontaneously recover normal heart function within 1 year of diagnosis. Unfortunately, there is no reliable clinical parameter or biomarker that allows pediatric cardiologists to correctly predict which of their HF patients will recover normal heart function without surgical intervention, forcing clinicians to place their these children on transplant lists even though surgical intervention would be unnecessary in some cases. Offering a potential solution to this problem, a recent study performed at the University of Colorado Denver has identified unique expression signatures of microRNAs found in circulating blood that correlate with a subpopulation of pediatric HF patients who recover ventricular function without surgical intervention. It is the objective of this Phase I project to complete initial proof-of-concept experiments related to the development of a commercial test based on the measurement of these circulating miRNAs. The work proposed to complete this project is designed to provide the groundwork for a prospective Phase II trial. By establishing and validating the test protocols with control samples, this project will create the basis for a test that can then be evaluated in a subsequent prospective study designed to tests newly diagnosed pediatric HF patients and follow their treatment outcomes. The successful development of a non-invasive test for pediatric HF patients would have significant patient and commercial value. By providing clinicians with a non-invasive risk stratification tool for pediatric patients with HF, a test of this kind would (1) help clinicians, patients and families understand health related prognosis for appropriate long-term planning, (2) reduce the number of invasive procedures performed on these compromised patients, (3) prevent unnecessary transplantations, improving survival for decades beyond the current 10-20 year lifespan of a transplanted heart, and (4) decrease health care expenditures associated with cardiac transplantation.