Predictive modeling of acute rejection in pediatric heart transplant recipients

Active Project Grant Awarded Last action

Award ID
R01HL164995
Recipient
Awarding agency
Obligated
$4,704,415

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 86% complete
Place of performance
Forest Hills, TN 37215, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

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.

Transactions

Action Obligated Date
Amendment $619,026
Amendment $678,800
Amendment $658,355
Amendment $666,158
Amendment $666,158
Amendment $5,372
Amendment $5,372
Amendment $5,372
Amendment $699,901
Original award $699,901

Subawards

Subrecipient Amount Awarded
The Medical College Of Wisconsin, Inc. Predictive modeling of acute rejection in pediatric heart transplant recipients $393,168
University Of Wisconsin System $11,000
The Carle Foundation Hospital $62,991
Childrens Hospital Medical Center $26,000
The Medical College Of Wisconsin, Inc. $258,158
University Of California, LOS Angeles $31,000
Icahn School Of Medicine At Mount Sinai $31,000
The Children's Hospital Of Philadelphia $31,000
The Washington University $31,000
Trustees Of Indiana University $15,000
University Of Texas Health Science Center At Houston $31,000
The Children's Hospital Corporation $22,000
Seattle Children's Hospital $6,000
The Carle Foundation Hospital $56,855
ANN & Robert H Lurie Childrens Hospital Of Chicago $15,000
The Carle Foundation Hospital $61,780
The Medical College Of Wisconsin, Inc. $169,001
The Leland Stanford Junior University $39,000
The Regents Of The University Of Colorado $30,000
Baylor College Of Medicine $31,000
University Of California, San Diego $0
Emory University $31,000
University Of California, San Diego $31,000
The Carle Foundation Hospital $19,817
The Trustees Of Columbia University In The City Of New York $31,000
The Carle Foundation Hospital $59,349
Show all 26

Quick answers

Who received award R01HL164995?

R01HL164995 was awarded to Vanderbilt University Medical Center by National Heart Lung and Blood Institute (National Institutes of Health) on July 15, 2022.

How much is award R01HL164995 worth?

$4,704,415 has been obligated on R01HL164995.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login