Research Project
9843079
ABSTRACT Trans-catheter pulmonary valve implantation (TPVI) is becoming the treatment of choice in most congenital heart disease (CHD) patients with degeneration of a previous right ventricular outflow tract (RVOT) repair. Since the life expectancy of these patients is improving, there is an increased demand for these procedures. Early efficacy and safety have been demonstrated for the Medtronic Melody and the Edwards Sapien valves, although there are no consistent procedural recommendations. There are also concerns with regards to the risk of endocarditis in the Melody transcatheter valve implants. Requirements for valve substitutes include features such as a lower introducer profile (<16Fr), low inflammatory response, long durability, low opening resistance with maximal valve area, fast and reliable closure, and non-thrombogenicity. Furthermore, structural valve failure is also caused by calcification which is histologically evident within 3 years of valve implantation. To address some of these shortcomings, we have identified a new type of heart valve leaflet tissue that promises greater longevity than the conventional glutaraldehyde fixed bovine pericardium (BP). This tissue, obtained from porcine pulmonary visceral pleura (PVP), is highly elastic and yet thinner (~1/3 of the thickness) than BP of similar strength. The PVP has been tested in venous prosthetic valve application, but because of its significant strength and elasticity, it has the potential to make TPVI more durable. In this Phase I project, the objective is to investigate the durability of the PVP tissue in animals, in pulmonary artery environment. In order to accomplish this goal, we set the following two Specific Aims: 1) To create smaller profile (13 Fr.) transcatheter pulmonary valve from PVP. We have already developed a percutaneous prosthetic venous valve which will be upscaled to the size of pulmonary artery in sheep. Since 40% of the profile of the transcatheter valve is taken up by the leaflet tissue, a 1/3 reduction of thickness of tissue will allow a significant reduction of overall delivery system. 2) To assess chronic in vivo performance of PVP TPVI into juvenile sheep for up to 4 months. The juvenile sheep model is the recognized gold standard for prosthetic valve testing. Good valves last for 4 months without tears and mineralization while bad valves start to fail within 3 months and show heavy mineral deposits. In this Phase I proof of concept study, we will demonstrate that TPVI valves incorporating PVP will be more resistant to calcification and thus offer better long-term durability than the current bioprosthetic valves using BP at smaller delivery system profile. If PVP is truly more tolerant of cyclic stresses and calcifies to a lesser degree as its composition may suggest, it would increase the longevity and durability of transcatheter valves, and potentially expand the use of transcatheter valves in younger patients with a greater life expectancy. This would deliver the benefits of transcatheter valves to the bulk of the patient population in need of bioprosthetic valve implants which would substantially impact healthcare and associated costs. Specific to the current application, this technology may offer better outcome for CHD patients which are generally underrepresented and understudied.
