Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation

Study Overview
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Brief Summary
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Demonstrate the impact of the Molecular Microscope Diagnostic System as the standard of care for heart transplant patients.

Detailed Description
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The current standard for biopsy-based diagnoses of rejection of heart transplants is the ISHLT classification from 2004, which represents a widely-used international consensus, based on morphological criteria of the cellular infiltrate within the myocardial specimen system with certainties and some arbitrary and blurred parameters. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces incorrect diagnoses with potential harm to patients due to inappropriate treatment. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to heart transplant endomyocardial biopsies (EMBs). The present study will develop a Reference Set of EMB, adapt the MMDx system to assess and report EMBs; and validate and refine this system in 900 unselected prospectively collected for clinical indications and a standard of care EMBs from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility. We refine now our MMDx system using a new type of analysis (see primary outcome) and the resulting MMDx report. Currently, INTERHEART recruited 1859 biopsies from 1233 patients.

Official Title
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Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation, a Multicenter Study (INTERHEART)

Conditions
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Cardiac Transplant Disorder

Intervention / Treatment
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* Procedure: Endomyocardial biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: biopsy for clinical indications Exclusion Criteria: no consent pregnant women

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Endomyocardial biopsy|One of several endomyocardial biopsy bites taken as the standard of care. We are asking now for two endomyocardial biopsy bites, to determine tissue sampling variability.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in heart transplant biopsies, in a reference set of 200 biopsies | Create a molecular classifier that predicts antibody mediated and T cell mediated rejection, based on the archetypal analysis. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assign in real time (three working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection. | The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart transplant, global gene expression, molecular diagnostics