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: 10666409
• 负责人: BRUCE M. DAMON
• 金额: $ 66.62万
• 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/10666409
• 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; Exclusion; Family member; Frequencies; Goals; Grant; Health Care Costs; Healthcare Systems; Heart Transplantation; Histologic; Image; Image Analysis; Immunosuppression; Impairment; Inflammation; Injury; Left; Magnetic Resonance; Maps; Measurement; Measures; Methods; MicroRNAs; Modeling; Morbidity - disease rate; Multicenter Studies; Myocardial; Myocardium; Non-Invasive Detection; Pathologic; Patients; Pattern; Pediatric Research; Perforation; Physiological; Population; Predictive Value; Preparation; Probability; Property; Quality of life; Radiation; Resolution; Risk; Risk Reduction; Sampling; Sedation procedure; Severities; Societies; Specificity; System; Testing; Texture; Tissues; Transplant Recipients; United States; Ventricular; Work; anesthesia complication; cardiac magnetic resonance imaging; cell free DNA; clinical decision-making; clinical practice; coronary fibrosis; cost; cost efficient; detection method; 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.

项目概要/摘要 尽管小儿心脏移植 (PHTx) 患者的护理取得了重大进展，但急性排斥反应 (AR) 仍然是导致死亡的主要原因之一。心导管插入术联合心内膜心肌活检（活检）是 诊断 AR 的护理标准，在临床怀疑 AR 时或在常规治疗期间进行 监视。不幸的是，活检是侵入性的，并存在潜在风险，包括： 麻醉或镇静、瓣膜损伤、传导系统损伤、血管损伤或闭塞，以及 心脏穿孔。这些潜在的并发症在儿科人群中会被放大。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 减少活检频率。血液生物标志物，例如供体部分的无细胞 DNA 和 microRNA， 已显示出诊断 AR 的潜力，但尚未在 PHTx 中得到广泛采用。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 表明这些序列具有诊断 AR 的潜力。虽然 CMR 参数映射具有重要意义 承诺，仅仅关注整个左心室平面或区域的平均特性会忽略 疾病的空间模式，导致信息丢失和使用成像数据的能力受损 直接护理。在这里，我们提出了比平面分析更精细的高级图像分析方法， 包括纹理分析，作为客观分析心肌疾病不同模式的手段， 开发预测模型以改进临床决策。本研究的中心假设 授予的是非侵入性心脏磁共振和血液生物标志物可以检测心肌 与儿童心脏移植受者的急性排斥反应一致的异常，可以预测需要 用于心内膜心肌活检。为了解决这一假设，目标 1 将开发并验证一个全面的 用于识别疑似 AR 并需要心导管插入术的 PHTx 接受者的预测模型。 目标 2 将评估血液生物标志物是否改善目标 1 中开发的 CMR 模型。子目标将 包括成本评估以确定最具成本效益的筛查方案。目标 3 将扩展建模 确定组织学定义的 AR 严重程度。这项多 PI 提案是一项前瞻性、多中心研究 对患有或不患有 AR 并同时接受临床活检的 PHTx 进行 CMR。本次的创新 研究是利用先进的 CMR、纹理分析和血液生物标志物进行非侵入性检测 AR。该提案利用了先天性/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 通过确保只有高概率的患者才能获得生活质量并降低相关发病率 排斥反应进行活检。

项目成果

ACR Appropriateness Criteria® Congenital or Acquired Heart Disease.

ACR 适当性标准® 先天性或后天性心脏病。

• DOI: 10.1016/j.jacr.2023.08.018
• 发表时间: 2023
• 期刊: Journal of the American College of Radiology : JACR
• 作者: ExpertPanelsonCardiacImagingandPediatricImaging;Krishnamurthy,Rajesh;Suman,Garima;Chan,SherwinS;Kirsch,Jacobo;Iyer,RameshS;Bolen,MichaelA;Brown,RichardKJ;El-Sherief,AhmedH;Galizia,MauricioS;Hanneman,Kate;Hsu,JoeY;deR
• 通讯作者: deR