Detection of Acute Graft Rejection in Heart Transplant Patients by Estimation of T2

Study Overview
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Brief Summary
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The investigators propose a simple and non-invasive method to monitor heart transplant patients with MRI. Its diagnostic and prognostic values have already been assessed in two monocentric studies. Other monocentric studies based on related methods have confirmed the investigators findings. These studies are insufficient to allow a large diffusion of the technique. Only a large multi-centric study will change medical practices. In addition, this project will spread the new method at a national level and will allow an assessment of its practical usefulness in centres not familiar with MRI T2 quantification. Furthermore, MRI seems to detect rejections at earlier stage than biopsy. A confirmation of this observation could lead to a modification of diagnostic criteria of cardiac graft rejection. The ultimate aim of the DRAGET project is to replace a strategy based solely on biopsy with one based on a first-line MRI (with biopsy only when needed) for a more efficient and earlier detection of rejection. This would constitute a major advance in patients security and comfort as well as an economic improvement.

Official Title
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Detection of Acute Rejection in Heart Transplant Patients by Mean of T2 Quantification With MRI Open Transversal Clinical Trial With Repeated Measures

Conditions
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Acute Graft Rejection, Heart Transplantation

Intervention / Treatment
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* Device: MRI T2 quantification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart transplant patient Able to realize 4 couples Biopsy/MRI within 12 months after the transplant Mandatory enrolment in a social security plan Patient having signed an informed consent. Exclusion Criteria: Contraindication to MRI: pacemaker, ferromagnetic foreign body, etc Impossibility to undergo MRI: claustrophobia, morbid obesity, hospitalisation in intensive care unit, arrhythmia Pregnancy Patients under a measure of legal protection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALL_patients<br>MRI T2 quantification : heart transplant patients will have 4-6 MRI exams for T2 quantification during their first year after transplantation. | Device: MRI T2 quantification<br>* MRI acquisitions will be performed according to the already described method based on conventional Fast Spin Echo sequences and with an additional calibration pad positioned on the patient thorax (dedicated pad made by the Nancy CIC-IT with stable and adapted T2). MRI will be performed if possible before the biopsy and otherwise the radiologist will be kept blinded of the biopsy results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of myocardial T2 assessed with MRI for the diagnosis of histological heart graft rejection (with 95% confidence interval). | endpoint = sensitivity and specificity acute rejection means presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R) | 3 years after first inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of histological or clinical rejection within months of a couple MRI/biopsy with normal biopsy (grade<2R). | endpoint = number of rejections For this purpose, rejection will be defined as: a) acute rejection documented by presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R), or b) marked decrease in left ventricle ejection fraction (>10%), reversible after subsequent increase in immunosuppressive treatment. | 3 years after first inclusion | 
| Complications with MRI and with biopsies. | endpoint = Number of adverse events due to both exams | 3 years after first inclusion | 
| Magnitude of better tolerability of MRI over biopsies for the patient. | endpoint = Physical and psychological distress assessed by questionnaire using Likert scales. This questionnaire will be completed by the patients. | 3 years after first inclusion | 
| Inter-observer reproducibility of T2 quantification with MRI and of pathological grading of the biopsies. | endpoint = 95% interobserver limit of agreement for T2 quantification and Cohen's Kappa coefficient for histological grading. | 3 years after first inclusion | 
| Level of confidence, at the end of the study, of the expert-physicians of each centre concerning the use of T2 quantification as an alternative to routine biopsies. | endpoint = Confidence assessed by questionnaire using Likert scales. This questionnaire will be completed by study investigators at the end of the study. | 3 years after first inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, T2 quantification