Non-invasive risk assessment tool for pediatric heart failure

摘要 小儿心力衰竭（HF）是一种严重的疾病，即使在治疗过程中也难以评估。 侵入性的医院手术重要的是，对于儿科人群来说，大约25%的 小儿HF患者在诊断后1年内自发恢复正常心脏功能。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学家正确预测 的HF患者无需手术干预即可恢复正常心脏功能，迫使临床医生放置 尽管在某些情况下不需要外科手术干预，但他们仍将这些儿童列入移植名单。 最近在科罗拉多丹佛大学进行的一项研究为这个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microRNA的独特表达特征， 无需手术干预即可恢复心室功能的儿童HF患者亚群。是 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， 一种基于这些循环miRNA测量的商业测试。建议完成的工作 该项目旨在为预期的第二阶段试验提供基础。通过建立和 验证测试方案与控制样品，该项目将创建一个测试的基础，然后可以 在随后的前瞻性研究中进行了评价，该研究旨在测试新诊断的儿科HF患者， 跟踪他们的治疗结果。成功开发用于儿童HF患者的非侵入性测试 将具有重要的患者和商业价值。通过为临床医生提供非侵入性风险 对于患有HF的儿科患者的分层工具，这种测试将（1）帮助临床医生，患者和家庭 了解与健康相关的预后，以制定适当的长期计划;（2）减少侵入性 对这些受损患者进行的手术，（3）防止不必要的移植， 存活超过移植心脏当前10-20年寿命的数十年，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.