Microvascular Cardiac Allograft Vasculopathy Trial

NCT05826444 | Recruiting

• 1 other identifier: mCAV
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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).

Conditions

Cardiac Allograft Vasculopathy

Keywords

heart transplantation; cardiac allograft vasculopathy

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (3)

• mCAV status influences the intrinsic cardiac magnetic field

  at study inclusion

• mCAV status influences the cellular calcium signaling

  at study inclusion

• mCAV status influences subcellular structures

  at study inclusion

Study Arms (2)

microvascular cardiac allograft vasculopathy

Heart transplant recipients with microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.

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

control

Heart transplant recipients without microvascular cardiac allograft vasculopathy defined by histopathology and invasive index of microvascular resistance.

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

Interventions

Echocardiography DIAGNOSTIC_TEST

Echocardiography with afterload change

control; microvascular cardiac allograft vasculopathy

Magnetic resonance imaging DIAGNOSTIC_TEST

Stress-MRI

control; microvascular cardiac allograft vasculopathy

Magnetocardiography DIAGNOSTIC_TEST

Magnetocardiography

control; microvascular cardiac allograft vasculopathy

Histology DIAGNOSTIC_TEST

Histological analysis

control; microvascular cardiac allograft vasculopathy

Genetics DIAGNOSTIC_TEST

miRNA sequencing

control; microvascular cardiac allograft vasculopathy

calcium signaling DIAGNOSTIC_TEST

cardiomyocyte calcium signaling

control; microvascular cardiac allograft vasculopathy

IMR DIAGNOSTIC_TEST

Index of microvascular resistance measurement

control; microvascular cardiac allograft vasculopathy

Angio-IMR DIAGNOSTIC_TEST

Angiography derived post-processing index if microvascular resistance

control; microvascular cardiac allograft vasculopathy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Heart transplant recipients

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• German Heart Institute: lead
• Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK): collaborator
• Deutsche Stiftung für Herzforschung: collaborator

Study Sites (1)

DHZC Deutsches Herzzentrum der Charité

Berlin, 13353, Germany

RECRUITING

MeSH Terms

Interventions

Echocardiography; Magnetic Resonance Imaging; Magnetocardiography; Shadowing Technique, Histology; Calcium Signaling

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Tomography; Electrodiagnosis; Magnetometry; Investigative Techniques; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Histological Techniques; Second Messenger Systems; Signal Transduction; Biochemical Phenomena; Chemical Phenomena; Ion Transport; Biological Transport; Metabolism; Cell Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 24, 2023
• Study Start: October 1, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)