# Predictive modeling of acute rejection in pediatric heart transplant recipients

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $705,273

## Abstract

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 w...

## Key facts

- **NIH application ID:** 10503263
- **Project number:** 1R01HL164995-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** BRUCE M. DAMON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $705,273
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10503263

## Citation

> US National Institutes of Health, RePORTER application 10503263, Predictive modeling of acute rejection in pediatric heart transplant recipients (1R01HL164995-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10503263. Licensed CC0.

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