Congenital heart defects (CHD) represent the most common type of birth defect, and are a leading cause of childhood deaths in the developed world. Many forms of CHD require pulmonary valve (PV) replacement surgery, which is typically performed with biologic valves, such as human cadaveric donor valves, which are in short supply. Additionally, such biologically-derived valves deteriorate progressively due to a child's aggressive immune response, leading to their overall poor durability, manifested as progressive stenosis and/or insufficiency. As a result, children with CHD enter a cycle of multiple re-operations for valve replacements. The advent of percutaneous valve delivery, along with the development of stent-mounted valves (SMV), could potentially change this treatment pattern, but current SMVs are problematic because they cannot be crimped sufficiently to reach a small profile that is compatible with vessel sizes in small children, and are not available in deployed diameters that are required for application in small children. In this proposal, we describe an SMV that employs a next-generation polymer that enables the reliable production of thin leaflets, and offers significant improvements in biocompatibility and durability over previous polymeric options. Our current SMV model has excellent hydrodynamic performance and exceeds ISO 5840-3 guidelines for durability. In the present STTR proposal, Polyvascular will team with colleagues at Baylor College of Medicine/Texas Children's Hospital and Rice University to scale the SMV to sizes that are appropriate for its target pediatric population.
In Aim 1, we will adapt our current fabrication methods to manufacture pediatric-sized SMVs, assess hydrodynamic performance at pulmonary pressures as a function of leaflet thickness, and assess batch reproducibility of our fabrication method.
In Aim 2, complementary studies of these same valves will assess SMV durability under high-speed cyclic loading, with a goal of reaching ISO 5840-3 targets of 200 million cycles without failure.
In Aim 3, we will simulate the process of SMV crimping and re-expansion, which are necessary steps in product use, but which may potentially damage SMV components. We will fabricate SMVs with multiple leaflet thicknesses, and measure their minimum possible profile after crimping. After re- expansion, each SMV will be visually assessed for damage and/or radial asymmetry, and will be re-tested for hydrodynamic performance. We hypothesize that these experiments in our Phase I STTR will demonstrate the feasibility of creating functional polymeric SMVs at sizes relevant to young pediatric patients with CHD. These steps will lay the groundwork for final manufacturing of SMVs in Phase II and testing their response in an animal model. We anticipate that this SMV may offer a new therapeutic opportunity for children with CHD, with reduced numbers of surgeries and potential long-term health benefits.
Many infants and children who are born with congenital heart defects require replacement of their pulmonary valve, which allows the heart to pump to the lungs. Such valve replacements require open-heart surgery, which carries significant risk and discomfort. Small children currently have very limited options for valve replacement. Our proposal describes the development of a new heart valve that is specifically designed for small children, and can be delivered in a minimally-invasive fashion through the groin without open-heart surgery.
