Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure. Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation. Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy. The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters.
The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation.
The final aim i s to determine the impact of ramipril on coronary physiology early after transplantation.
Heart transplantation remains an important treatment option for patients with heart failure. Unfortunately, many patients who undergo heart transplantation suffer and die because of the development of narrowings in the arteries supplying blood to the transplanted heart. The goal of this project is to investigate the ability of a drug called ramipril to prevent this significant complication.
|Okada, Kozo; Fearon, William F; Luikart, Helen et al. (2016) Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After HeartÂ Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy. J Am Coll Cardiol 68:382-92|
|Yang, Hyoung-Mo; Khush, Kiran; Luikart, Helen et al. (2016) Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation. Circulation 133:1945-50|
|Chiu, Peter; Fearon, William F; Raleigh, Lindsay A et al. (2016) Salvage Extracorporeal Membrane Oxygenation Prior to "Bridge" Transcatheter Aortic Valve Replacement. J Card Surg 31:403-5|
|Okada, Kozo; Kitahara, Hideki; Yang, Hyoung-Mo et al. (2015) Paradoxical Vessel Remodeling ofÂ theÂ Proximal Segment of the LeftÂ AnteriorÂ Descending Artery PredictsÂ Long-Term Mortality AfterÂ HeartÂ Transplantation. JACC Heart Fail 3:942-52|
|Fearon, William F (2015) Invasive coronary physiology for assessing intermediate lesions. Circ Cardiovasc Interv 8:e001942|
|Fearon, William F (2014) Percutaneous coronary intervention should be guided by fractional flow reserve measurement. Circulation 129:1860-70|
|Fearon, William F; Low, Adrian F; Yong, Andy S et al. (2013) Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation 127:2436-41|