Non-invasive Prediction of EArly Cardiac rEjection
Purpose
Acute rejection remains a major cause of morbidity and mortality in pediatric patients after heart transplant. In order to screen for rejection, most centers perform heart catheterizations with endomyocardial biopsies frequently in the first year post transplant and then every 1-2 years thereafter; these biopsies are associated with complications, can cause significant anxiety in patients and family members, and are a significant cost for the healthcare system. This project will evaluate non-invasive methods of detecting rejection using cardiac magnetic resonance imaging and blood testing with a goal to reduce the required number of cardiac catheterizations.
Conditions
- Heart Transplant
- Pediatric Heart Transplant
- Rejection
- Cardiac MRI
- Cell Free DNA
Eligibility
- Eligible Ages
- Between 6 Years and 25 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Received heart transplant at age < 21 years old - > 2 months from transplant - ≥6 years old and ≤ 25 years old and able to undergo cardiac MRI (CMR) - CMR can be scheduled within 5 days from heart biopsy* - Heart catheterization with biopsy is scheduled "for cause" to confirm suspected AR or Heart catheterization with biopsy is scheduled for surveillance
Exclusion Criteria
- No endomyocardial biopsy scheduled - Other illness or disease process that could potentially lead to myocardial edema or fibrosis - Contraindication to CMR with contrast - Previously enrolled in this study, UNLESS previous enrollment was heart biopsy scheduled for surveillance with no suspicion of AR AND final study status was documented as "no AR" AND current enrollment is heart biopsy is scheduled "for cause" to confirm suspected AR - Multiple transplanted organs - Requires anesthesia for CMR
Study Design
- Phase
- Study Type
- Observational
- Observational Model
- Case-Control
- Time Perspective
- Cross-Sectional
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
| Healthy pediatric heart transplant recipients | Pediatric heart transplant recipients not having rejection | |
| Pediatric heart transplant recipients with acute rejection | Pediatric heart transplant recipients with acute rejection (ACR or AMR) as defined by the the core pathologist. | |
| Healthy controls | Healthy control patients retrospectively enrolled at each site to standardize parametric mapping. |
Recruiting Locations
Nashville, Tennessee 37232
Little Rock, Arkansas 72202
Palo Alto, California 94304
San Diego, California 92123
Denver, Colorado 13123
Gainesville, Florida 32608
Hollywood, Florida 33021
Atlanta, Georgia 30322
Chicago, Illinois 02115
Indianapolis, Indiana 46202
Boston, Massachusetts 02115
Ann Arbor, Michigan 48109
St Louis, Missouri 63110
New York, New York 10029
Columbus, Ohio 43205
Houston, Texas 77030
Seattle, Washington 98105
Milwaukee, Wisconsin 53226
More Details
- Status
- Recruiting
- Sponsor
- Vanderbilt University Medical Center
Detailed Description
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.