Biomarkers for Diagnosis, Prognosis, and Targeted Therapy After Heart Transplantation

Study Overview
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Brief Summary
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The objective of this prospective observational single center study is to investigate donor-derived cell-free DNA (ddcfDNA), peripheral blood platelet mRNA, peripheral blood extracellular vesicle mRNA, and peripheral blood leukocyte mRNA expression in recognition of clinically significant endomyocardial biopsy (EMB) proven acute rejection in human heart transplant recipients. In detail, the objective is to develop novel biomarkers and liquid biopsies for diagnosis, prognosis, and targeted molecular therapy for primary graft failure, ischemia-reperfusion injury, acute rejection, and development of late graft failure and cardiac allograft vasculopathy, and for monitoring immunosuppression after heart transplantation.

Official Title
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Biomarkers for Diagnosis, Prognosis, and Targeted Therapy After Heart Transplantation

Conditions
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Heart Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Cell-free DNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient age > 18 years heart transplant recipient has signed informed consent Exclusion Criteria: foreign residency no signed informed consent collected

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac transplant recipients<br>The group consist of all recruited cardiac transplant recipients operated in Helsinki University Hospital | Diagnostic Test: Cell-free DNA<br>* Donor-derived cell-free DNA relation to recipient-derived cell-free DNA is compared to histopathological rejection grade from the same time frame.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma donor-derived cell-free DNA (dd-cfDNA) for routine surveillance of acute rejection after heart transplantation | To compare plasma dd-cfDNA to endomyocardial biopsy data | 5 years | 
| Allograft educated platelet-derived mRNA for gene expression profiling of acute rejection after heart transplantation | To compare gene expression profile of allograft-educated platelets to endomyocardial biopsy data | 5 years | 
| Plasma extracellular vesicle (EV) derived mRNA for gene expression profiling of acute rejection after heart transplantation | To compare gene expression profile of EV-derived mRNA to endomyocardial biopsy data | 5 years | 
| Plasma glycoproteins for routine surveillance of acute rejection after heart transplantation | To compare plasma glycoproteome profile to endomyocardial biopsy data | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma metabolomics changes during acute rejection after heart transplantation | Plasma metabolic changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation to investigate if there are any plasma metabolomics changes during different grades of acute rejection. | 1 year | 
| Plasma proteomics changes during acute rejection after heart transplantation | Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation to investigate if there are any plasma proteomics changes during different grades of acute rejection during the first year. | 1 year | 
| Peripheral blood mononuclear cell mRNA expression for gene expression profiling of acute rejection after heart transplantation | To compare gene expression profile of peripheral blood mononuclear cells to endomyocardial biopsy data | 1 year | 
| Plasma metabolomics changes during the first year after heart transplantation and their relationship to the development of cardiac allograft vasculopathy | Plasma metabolomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to the development of cardiac allograft vasculopathy in coronary angiogram will be investigated at 1, 3, and 5 years. | 5 years | 
| Plasma metabolomics changes during the first year after heart transplantation and their relationship to patient survival at 1, 3, and 5 years | Plasma metabolomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to patient survival will be investigated at 1, 3, and 5 years. | 5 years | 
| Plasma proteomics changes during the first year after heart transplantation and their relationship to the development of cardiac allograft vasculopathy | Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to the development of cardiac allograft vasculopathy in coronary angiogram will be investigated at 1, 3, and 5 years. | 5 years | 
| Plasma proteomics changes during the first year after heart transplantation and their relationship to patient survival at 1, 3, and 5 years | Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and and their relationship to patient survival will be investigated at 1, 3, and 5 years. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor-derived Cell-Free DNA, Platelet, Endomyocardial biopsy, Liquid biopsy, Transcriptome, Proteomics, Metabolomics, Glycoproteins, Surveillance, Extracellular Vesicles