Microvascular Cardiac Allograft Vasculopathy Trial

Study Overview
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Brief Summary
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The aim of the mCAV study is a comprehensive characterization of the genetic, morphological and functional phenotype of isolated microvascular graft vasculopathy (mCAV) after orthotopic heart transplantation (OHT). The utilized methods include dynamic echocardiography, magnetic resonance imaging, invasive microvascular resistance measurements, histology, cellular calcium-signaling and magnetocardiography as well as molecular genetic expression analysis.

Official Title
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Morphological and Functional Phenotype of Isolated Microvascular Cardiac Allograft Vasculopathy in Heart Transplant Recipients

Conditions
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Cardiac Allograft Vasculopathy

Intervention / Treatment
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* Diagnostic Test: Echocardiography
* Diagnostic Test: Magnetic resonance imaging
* Diagnostic Test: Magnetocardiography
* Diagnostic Test: Histology
* Diagnostic Test: Genetics
* Diagnostic Test: calcium signaling
* Diagnostic Test: IMR
* Diagnostic Test: Angio-IMR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: able to consent Written consent of the participant after clarification and sufficient time to think about participation heart transplant recipient Indication for routine invasive diagnostics or due to symptoms Exercise tolerant in everyday life - cycling, climbing stairs at least 2 floors at a moderate speed without symptoms of exertion or dyspnea Exclusion Criteria: Addiction or other diseases that do not allow the patient to assess the nature and scope as well as possible consequences of the study Patients or their legal guardians who do not sign the declaration of consent or who cannot fully understand it due to a lack of German language skills Pregnant women, breastfeeding women Severe comorbidities affecting the miRNA profile: diabetes mellitus, malignancy, end-stage renal disease with renal replacement therapy Contraindication to the stress test: signs of cardiac decompensation, angina pectoris, dyspnea, hyperthyroidism, GFR <30 ml/min, peripheral arterial disease, pheochromocytoma, angle-closure glaucoma, prostate adenoma, paroxysmal tachycardia, tachycardia atrial fibrillation Evidence of an acute rejection or local wall motion disturbances in the resting echocardiography
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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| microvascular cardiac allograft vasculopathy<br>Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance. | Diagnostic Test: Echocardiography<br>* Echocardiography with afterload change<br>Diagnostic Test: Magnetic resonance imaging<br>* Stress-MRI<br>Diagnostic Test: Magnetocardiography<br>* Magnetocardiography<br>Diagnostic Test: Histology<br>* Histological analysis<br>Diagnostic Test: Genetics<br>* miRNA sequencing<br>Diagnostic Test: calcium signaling<br>* cardiomyocyte calcium signaling<br>Diagnostic Test: IMR<br>* Index of microvascular resistance measurement<br>Diagnostic Test: Angio-IMR<br>* Angiography derived post-processing index if microvascular resistance<br>|
| control<br>Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance. | Diagnostic Test: Echocardiography<br>* Echocardiography with afterload change<br>Diagnostic Test: Magnetic resonance imaging<br>* Stress-MRI<br>Diagnostic Test: Magnetocardiography<br>* Magnetocardiography<br>Diagnostic Test: Histology<br>* Histological analysis<br>Diagnostic Test: Genetics<br>* miRNA sequencing<br>Diagnostic Test: calcium signaling<br>* cardiomyocyte calcium signaling<br>Diagnostic Test: IMR<br>* Index of microvascular resistance measurement<br>Diagnostic Test: Angio-IMR<br>* Angiography derived post-processing index if microvascular resistance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mCAV status influences pw-doppler wall motion analysis in echocardiography | pw-doppler wall motion analysis is measured with afterload increase | at study inclusion | 
| mCAV status influences global longitudinal strain in echocardiography | global longitudinal strain is measured by speckle tracking analysis with afterload increase | at study inclusion | 
| mCAV status influences diastolic strain in echocardiography | diastolic strain is measured by speckle tracking analysis with afterload increase | at study inclusion | 
| mCAV status influences cardiac deformity | cardiac deformity analysis are performed by MRI | at study inclusion | 
| mCAV status influences grade of fibrosis | fibrosis grades are measured by MRI | at study inclusion | 
| mCAV status influences extracellular volume | extracellular volume is measured by MRI | at study inclusion | 
| mCAV status influences the circulating miRNA profile | circulating miRNA profile is measured by miRNAseq | at study inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mCAV status influences the intrinsic cardiac magnetic field | the intrinsic cardiac magnetic field is measured by magnetocardiography | at study inclusion | 
| mCAV status influences the cellular calcium signaling | the cellular calcium is visualized by confocal laser microscopy using electrical stimulation | at study inclusion | 
| mCAV status influences subcellular structures | mitochondria, T-tubuli are described after visualization by confocal laser microscopy | at study inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart transplantation, cardiac allograft vasculopathy