View clinical trials related to Cardiac Allograft Vasculopathy.
Filter by:Hypothesis: CAV is associated with fibrotic changes on cardiac MRI, altered levels of pathogenetically-related biomarkers, and specific RNA expression changes in the blood
Hypothesis 1: Treatment of heart transplant recipients with sildenafil, a PDE-5 inhibitor, will improve small artery elasticity (SAE) when compared to placebo. Hypothesis 2: PDE-5 inhibition will improve endothelial function, resulting in increased production of nitric oxide, reduced activation of circulating endothelial cells, and increased endothelial progenitor cells.
Post transplant vasculopathy is a major negative outcome in heart transplantation. Current methods of detection are highly invasive and pose a risk to transplant recipients. Noninvasive markers of endothelial function can be used to detect transplant vasculopathy. Endothelial biomarkers such as: endothelial nitric oxide synthase, vascular cellular adhesion molecules, intracellular adhesion molecules, endothelin-1, thromboplastin, circulating endothelial cells, uric acid, and C-reactive play a role in the pathophysiologic mechanism of vasculopathy. Therefore, the investigators would like to assess the association between various endothelial biomarkers and the presence or absence of transplant vasculopathy.
1. Early initiation of sirolimus will prevent or delay the development of intimal thickening and subsequent graft failure. 2. Treatment guided by the development of cardiac allograft vasculopathy (CAV) on intravascular ultrasound (IVUS) will be more effective in delaying progression of CAV compared to treatment guided by angiography. 3. Prevention of the development and progression of intimal thickness on IVUS will prevent the development of heart failure, graft dysfunction, and cardiovascular death related to CAV. 4. Small artery elasticity predicts progression of cardiac allograft vasculopathy and is modified by sirolimus 5. Patients who have no progression of CAV will have favorable improvement in biomarkers and endothelial cells compared to patients who have progression of CAV
Abnormal peripheral endothelial function and alterations in circulating biomarkers that are associated with endothelial activation and inflammation correlate with angiographic evidence of cardiac allograft vasculopathy, defined as greater than 25% stenosis in a major coronary artery.
The purpose of this study is to test the hypothesis that administering Thymoglobulin® induction therapy early after transplant prevents the development of cardiac allograft vasculopathy (CAV). CAV accounts for a significant number of deaths in cardiac recipients after the first year of transplant. At 5 years post-transplant 30% of the deaths are due to CAV. With the exception of re-transplantation the available treatments for CAV are only effective at inhibiting its progression. CAV involves only the allograft and spares the native arteries, suggesting an immunologic basis for the disease. However, both immunological and non-immunological factors contribute to the development of CAV. The established immunological risk factors are recurrent rejection and humoral/antibody-mediated rejection (AMR). Non-immunological risk factors identified include preservation injury, the cause of donor death, donor graft ischemic time, and cytomegalovirus infection1. It is hypothesized that these factors increase the risk of developing CAV by causing early endothelial damage to the graft, which then could promote increased lymphocyte-endothelial interactions and the production of anti-endothelial antibodies2. The investigators hypothesized that Thymoglobulin induction therapy would prevent the development of CAV because its polyclonal nature allows Thymoglobulin to target all the potential mechanisms that contribute to the development of CAV—T-cell activation, B-cell activation, antibody formation, induction of tolerance, and modulation of lymphocyte-endothelium interactions3. Because the mechanism by which Thymoglobulin affects the immune system are still poorly understood, the investigators will also study how Thymoglobulin changes the immune system over time in the heart transplant recipient as a secondary objective.