# Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $695,340

## Abstract

SUMMARY / ABSTRACT
Heart transplant (HTx) is a well-established life-saving procedure but is associated with severe complications.
Current clinical monitoring algorithms rely on frequent invasive procedures including endomyocardial biopsies
and catheter angiography. To address these limitations, the PIs have developed non-invasive comprehensive
cardiac MRI, which can quantify regional changes in myocardial tissue and function. Our efforts have focused
on the 2 major complications of HTx: 1) acute cardiac rejection (ACR), the leading cause of death in the first
year after transplant; and 2) cardiac allograft vasculopathy (CAV), the greatest risk factor for 5-year mortality
beyond the first post-Tx year. Our cardiac MRI studies have identified new imaging biomarkers in HTx. We
were the first to establish a physiologic link between abnormal cardiac MRI measures and potential allograft
failure: myocardial T2 and extracellular volume fraction (ECV) as non-invasive tissue biomarkers for ACR. We
demonstrated that the natural history of myocardial scarring, T2, and ECV predicts adverse clinical events in
HTx recipients. In addition, our studies showed that donor and recipient mismatch (age, sex, weight, etc.) was
significantly associated with cardiac MRI-derived measures of myocardial edema/inflammation, fibrosis, and
systolic and diastolic dysfunction. Over the past five years, the PIs have assembled a unique study database
with over >450 comprehensive cardiac MRI exams comprising >110,000 annotated cardiac MRI images.
For this renewal application, we identified the need to conduct further long-term follow-up studies tailored to the
slow disease progression in HTx to identify changes over time in multiparametric MRI measures and predictors
of HTx outcome. Second, data on graft tissue and function in the pediatric HTx population are scarce and
improved strategies for donor-recipient matching in this vulnerable population are needed to make most
efficient use of the limited availability of donor hearts in children. Thus, cardiac MRI needs to better account for
age and sex related differences in patient habitus and physiology, critical for the wide age range in HTx from
pediatric to adult. The renewal application for this study aims to 1) develop multiparametric cardiac MRI for the
assessment of graft tissue (T2, T1, ECV), and dysfunction (myocardial velocities, strain) from pediatric to adult,
2) leverage the existing large cardiac MRI database (110,000 labeled cardiac MRI images) to establish deep
learning based analysis pipelines for automated cardiac MRI analysis with improved efficiency and reduced
inter-rater variability, 3) to identify predictors of adverse outcomes and to evaluate the impact of donor-recipient
mismatch on graft tissue, function, and flow in a prospective study with pediatric HTx patients, and 4) to identify
cardiac metrics predictive of long-term (> 5 years) HTx patient outcome by leveraging our HTx database (>145
HTx recipients wi...

## Key facts

- **NIH application ID:** 10208494
- **Project number:** 2R01HL117888-06A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** James Carr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $695,340
- **Award type:** 2
- **Project period:** 2014-02-04 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208494

## Citation

> US National Institutes of Health, RePORTER application 10208494, Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation (2R01HL117888-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10208494. Licensed CC0.

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