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.

项目总结/文摘