Microvascular Cardiac Allograft Vasculopathy Trial

Recruiting

• Conditions: Cardiac Allograft Vasculopathy
• Interventions: 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

• Registration Number: NCT05826444
• Lead Sponsor: German Heart Institute

Brief Summary

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 (miRNA based).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-01
• Study First Submitted: 2023-03-13
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-24
• Status Verified: 2024-07
• Last Update Submitted: 2024-08-08
• Last Update Posted: 2024-08-12
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
microvascular cardiac allograft vasculopathy	Genetics	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	IMR	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	Magnetocardiography	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	Magnetic resonance imaging	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	Histology	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	calcium signaling	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	Echocardiography	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Magnetic resonance imaging	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Magnetocardiography	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	IMR	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
microvascular cardiac allograft vasculopathy	Angio-IMR	Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Genetics	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Angio-IMR	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Echocardiography	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	Histology	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.
control	calcium signaling	Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

DHZC Deutsches Herzzentrum der Charité; 🇩🇪 Berlin, Germany