Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

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.

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