A Novel Polymeric Trileaflet Heart Valve Prosthesis

DESCRIPTION (provided by applicant): The goal of this proposal is to produce a fully characterized polyurethane heart valve prosthesis that will be ready for clinical evaluation. Existing replacement valves suffer from several shortcomings. Specifically, biological tissue fixation and methods used to mount the tissue to the supporting stent of bioprostheses cause time dependent structural changes such as calcification and leaflet wear, which lead to valve failure. The flow disturbances created by mechanical valves include high velocity jets, turbulence and areas of stagnation, which cause blood cell damage, lead to thrombus formation and necessitate the use of anticoagulation for the rest of the patient's life. The trileaflet polyurethane valve, originally developed in the design of the AbioCor replacement heart has demonstrated excellent durability and hemocompatibility in clinical evaluation. This type of valve has the potential to address both the blood compatibility problem of mechanical valves and the durability problem of bioprostheses. The changes necessary for adapting the AbioCor trileaflet valve design to the requirements of a prosthetic replacement valve was the focus of the Phase I project. The novel methods for reducing the forward flow pressure loss ensure superior hemodynamic performance without compromising valve efficiency, durability and fluid flow patterns through the valve. Phase II studies will be primarily concerned with optimizing the design of the polyurethane replacement valve, and completing the necessary requirements to support a submission for clinical trials. We will be also be evaluating valves made from bisphosphonate-modified polyurethanes, which have displayed substantial resistance to calcification. The valve design will be optimized to address potential issues with calcification and blood compatibility. A novel dynamic in vitro calcification model and an in vitro blood compatibility model will also be used to compare polyurethane valves with tissue valves. In depth fluid dynamic studies on critical areas are planned to quantify any potential for thrombus formation (stagnation) and red blood cell damage (high shear regions). Finally, in vivo animal experiments are planned to verify both hemocompatibility and calcification resistance provided by the polyurethane valve design. Existing replacement valves suffer from several shortcomings. We anticipate that the anticoagulation therapy requirements of mechanical valves can be substantially reduced by using a polyurethane trileaflet valve. We further anticipate that a polyurethane valve design can potentially mitigate the calcification and durability problems of bioprostheses associated with tissue fixation and leaflet mounting. Finally, a polyurethane valve can be manufactured at a substantially reduced cost compared to existing valves. In summary, the valve proposed in this research will lead to a new generation of replacement heart valves that improves upon the shortcomings of existing replacement valves, reduces the cost burden on the health care system and improves the survival rate of patients with heart valve prostheses