Antibody Mediated Rejection, Cardiac Allograft Vasculopathy
Conditions
Keywords
Optical Coherence Tomography, OCT, Coronary Allograft Vasculopathy, Donor Specific Antibodies, Acetylcholine, Coronary endothelial function, Brachial Artery Flow Mediated Dilation, Heart transplantation
Brief summary
Coronary allograft vasculopathy (CAV) is the leading cause of late graft failure and second leading cause of late mortality after heart transplantation. CAV has been associated with a variety of traditional risk factors for atherosclerosis; however, immune mediated injury from development of de-novo donor-specific antibodies after transplantation also likely plays an important role. Similar to the progression of traditional atherosclerosis, it is likely that endothelial dysfunction is the precursor to the development of intimal thickening and CAV. The investigators hypothesize that coronary allograft vasculopathy after heart transplantation as defined by progressive neointimal hyperplasia is preceded by endothelial dysfunction, which in turn is at least partly mediated by donor specific antibodies. The investigators are proposing a prospective study in humans to test the above hypothesis and further mechanistically understand how CAV progresses. In this study the investigators will test for coronary endothelial function by infusing acetylcholine into the coronary artery and measure intimal hyperplasia by optical coherence tomography (OCT) and compare findings in patients with and without donor specific antibodies.
Interventions
DEVICEOptical Coherence Tomography
OCT imaging of the LAD coronary artery
DRUGAcetylcholine
Infusion in the coronary artery to study endothelial function
PROCEDUREBrachial Artery Flow Mediated Dilation
Assess peripheral brachial artery endothelial function
Sponsors
Gladwin, Mark, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who are 1 year post heart transplantation * Subjects will include both male and females * Be at least 18 years of age
Exclusion criteria
* Known coronary artery disease after transplantation * Evidence of strong or moderate antibodies already present at the time of the transplant * Severe renal dysfunction defined as creatinine clearance of \<30 or on hemodialysis. * 3 or more episodes of acute cellular rejection * Females who are pregnant * Patients requiring endomyocardial biopsy at the time of catheterization * Patients unable to tolerate heparin or systemic anticoagulation * History of multi-organ transplant * Patients unable to give consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be a comparison of intimal thickness in the coronary artery by Optical Coherence Tomography with presence or absence of donor specific antibodies. | baseline (year 1 post transplant) and annually for 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening. | baseline (year 1 post transplant) and annually for 2 years |
| Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness. | baseline (year 1 post transplant) and annually for 2 years |
| Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function. | baseline (year 1 post transplant) and annually for 2 years |
| Natural progression of coronary allograft vasculopathy over first 2 years after transplantation | baseline (year 1 post transplant) and annually for 2 years |
| Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies. | baseline (year 1 post transplant) and annually for 2 years |
| Plaque characterization in coronary artery by OCT | baseline (year 1 post transplant) and annually for 2 years |
Countries
United States
Outcome results
None listed