Predictive modeling of acute rejection in pediatric heart transplant recipients

儿童心脏移植受者急性排斥反应的预测模型

• 批准号: 10503263
• 负责人: BRUCE M. DAMON
• 金额: $ 70.53万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503263
• 关键词: Acute; Address; Adoption; Algorithms; Anxiety; Biological Markers; Biopsy; Blood; Blood Tests; Blood Vessels; Cardiac; Cardiac Catheterization Procedures; Cardiomyopathies; Cardiovascular system; Caring; Catheterization; Cause of Death; Cell Fraction; Childhood; Clinical; Clinical Trials; Collaborations; Complication; Cost Analysis; Data; Diagnosis; Disease; Edema; Eligibility Determination; Ensure; Family member; Frequencies; Goals; Grant; Health Care Costs; Healthcare Systems; Heart Transplantation; Histologic; Image; Image Analysis; Immunosuppression; Impairment; Inflammation; Injury; Left; Magnetic Resonance; Measurement; Measures; Methods; MicroRNAs; Modeling; Morbidity - disease rate; Multicenter Studies; Myocardial; Myocardium; Non-Invasive Cancer Detection; Pathologic; Patients; Pattern; Pediatric Research; Perforation; Physiological; Population; Predictive Value; Preparation; Probability; Property; Quality of life; Radiation; Resolution; Risk; Sampling; Sedation procedure; Sensitivity and Specificity; Severities; Societies; System; Testing; Texture; Tissues; Transplant Recipients; United States; Ventricular; Work; anesthesia complication; base; cardiac magnetic resonance imaging; cell free DNA; clinical decision-making; clinical practice; coronary fibrosis; cost; cost efficient; extracellular; graft dysfunction; imaging scientist; imaging study; improved; innovation; insight; interest; magnetic resonance imaging biomarker; mortality; parametric imaging; pediatric patients; post-transplant; predictive modeling; prospective; screening; standard of care

PROJECT SUMMARY/ABSTRACT Despite significant advances in the care of pediatric heart transplant (PHTx) patients, acute rejection (AR) remains one of the leading causes of death. Cardiac catheterization with endomyocardial biopsy (biopsy) is the standard of care for diagnosing AR and is performed when there is a clinical suspicion for AR or during routine surveillance. Unfortunately, biopsy is invasive and associated with potential risks, including: complications from anesthesia or sedation, valve damage, injury to the conduction system, vascular damage or occlusion, and cardiac perforation. These potential complications are magnified in the pediatric population. Non-invasive methods of detecting AR, such as blood biomarkers and cardiac magnetic resonance imaging (CMR), could decrease the frequency of biopsy. Blood biomarkers, such has donor fraction cell-free DNA and microRNA, have shown potential for diagnosis of AR but have not yet gained widespread adoption in PHTx. Advanced CMR parametric mapping sequences quantify myocardial fibrosis and edema, and our preliminary data suggest a potential for these sequences to diagnose AR. While CMR parametric mapping has significant promise, focusing simply on the average properties across an entire left ventricular plane or region ignores the spatial patterns of disease, resulting in a loss of information and an impaired ability to use the imaging data to direct care. Here we propose advanced image analysis methods that are more granular than plane analysis, including texture analysis, as a means for objectively analyzing different patterns of myocardial disease and developing predictive models that would allow improved clinical decision making. The central hypothesis of this grant is that non-invasive cardiac magnetic resonance and blood biomarkers can detect myocardial abnormalities consistent with acute rejection in pediatric heart transplant recipients and can predict the need for endomyocardial biopsy. To address this hypothesis, Aim 1 will develop and validate a comprehensive predictive model for identifying PHTx recipients having suspected AR and requiring cardiac catheterization. Aim 2 will evaluate whether blood biomarkers improve the CMR model developed in Aim 1. SubAims will include assessment of cost to determine the most cost-efficient screening protocol. Aim 3 will expand modeling to determine severity of AR as defined histologically. This multi-PI proposal is a prospective, multicenter study to perform CMR in PHTx with and without AR who are also undergoing clinical biopsy. The innovation of this study is the use of advanced CMR, texture analysis, and blood biomarkers for the non-invasive detection of AR. This proposal leverages the support of the Congenital/Pediatric Research Committee within the Society of Cardiovascular Magnetic Resonance (SCMR). Application of these data to clinical practice could improve quality of life and decrease associated morbidity by ensuring that only patients with a high probability of rejection undergo biopsy.

项目摘要/摘要 尽管小儿心脏移植（PHTX）患者的护理显着进步，但急性排斥（AR） 仍然是死亡的主要原因之一。心内膜活检（活检）的心脏导管插入术是 诊断AR的护理标准，并在AR临床怀疑或常规期间执行 监视。不幸的是，活检是侵入性的，并且与潜在风险有关，包括： 麻醉或镇静，阀门损坏，导电系统伤害，血管损伤或阻塞，以及 心脏穿孔。这些潜在的并发症在小儿种群中被放大。非侵入性 检测AR的方法，例如血液生物标志物和心脏磁共振成像（CMR），可以 减少活检的频率。血液生物标志物，这样的供体分数不含细胞的DNA和microRNA， 已经显示出诊断AR的潜力，但尚未在PHTX中获得广泛采用。先进的 CMR参数映射序列量化心肌纤维化和水肿，以及我们的初步数据 提出了这些序列诊断AR的潜力。虽然CMR参数映射具有重要的 承诺，仅关注整个左心平面或区域的平均特性忽略 疾病的空间模式，导致信息损失和使用成像数据的能力受损 直接护理。在这里，我们提出的高级图像分析方法比平面分析更颗粒状， 包括纹理分析，作为客观分析心肌疾病不同模式的一种手段 开发预测模型，可以改善临床决策。中心假设 格兰特是非侵入性心脏磁共振和血液生物标志物可以检测到心肌 异常与小儿心脏移植受者的急性排斥一致，并且可以预测需求 内膜活检。为了解决这一假设，AIM 1将开发并验证全面 用于识别具有怀疑AR并需要心脏导管插入的PHTX受体的预测模型。 AIM 2将评估血液生物标志物是否改善了AIM 1中开发的CMR模型。 包括评估成本以确定最具成本效益的筛查协议。 AIM 3将扩展建模 确定AR的严重程度为组织学上的定义。该多PI提案是一项前瞻性的多中心研究 在有和没有AR的PHTX中执行CMR，他们也正在进行临床活检。这个创新 研究是使用高级CMR，纹理分析和血液生物标志物的使用 ar。该提案利用了先天/儿科研究委员会的支持 心血管磁共振（SCMR）。将这些数据应用于临床实践可以改善 通过确保只有高可能性的患者，生活质量和减少相关的发病率 拒绝进行活检。