More than 16,000 US children need the implantation of a valved conduit to replace the right ventricular outflow tract (RVOT) annually. These children require one to four repeat open-heart surgeries to replace the valved conduit before they reach adulthood because available prostheses do not grow with the child. The long-term goal of our multidisciplinary collaborative team is to develop a biostable polymeric valved conduit that can be implanted surgically to reconstruct the RVOT and then expanded (by successive transcatheter procedures) to avoid multiple surgeries in children. Our overall objective is to design, validate and demonstrate the in vitro and in vivo proof of concept of the expandability and valvar competence of the device. Our central hypothesis is that the use and controlled processing of a biostable polymer with adequate plasticity, associated to an optimized design of the valve, can allow for successive controlled expansions while maintaining valve competence. We will test this hypothesis in the following three specific aims:
Aim1 : Characterize the growth accommodation of non-valved conduits. We will 1.1) characterize the mechanical properties of 8 ePTFE materials with varying densities and thicknesses using a uniaxial tensile tester, 1.2) develop a computational model of tube expansion from 12-24 mm based on the mechanical data, and 1.3) validate the expansion experimentally using a transcatheter balloon and measuring the expansion potential, uniaxial tensile properties and microarchitecture.
Aim 2 : Develop a valve design for competence at all diameters. Our hypothesis is that a valve design with increased height of coaptation and increased length of the free edge can be expanded from a 12-24 mm diameter while maintaining valve competence. We will use a fluid-structure interaction based computational design, prototype fabrication, and experimental validation in our heart valve pulse duplicator to iteratively examine the effects of the design on the hemodynamic performance of the valved conduit.
Aim 3 : Describe the performance and durability of the valved conduit. We will 3.1) characterize the biocompatibility using an aortic rat model; 3.2) demonstrate the acute in vivo performance in a sheep model; 3.3) assess the in vitro durability in an accelerated wear tester. Expected outcomes: to have identified the conditions of the fabrication process, optimized the valve hydrodynamics for different stages of expansion and performed the in vitro and in vivo proof of concept of the biocompatibility, expandability and maintenance of the valvar competence of the device. The innovation of the proposed research is that we will develop a valved conduit designed specifically for growth-accommodation that is durable and competent at every stage of expansion, using and developing innovative designs, computational models, manufacturing techniques and translational methodologies. Impact and significance: our results will contribute to the evidence for further development of an innovative expandable surgical valved device that will help avoid multiple repeat open-heart surgeries in children. Future studies include cytotoxicity testing and a pre-clinical study to prepare FDA approval.

Public Health Relevance

The proposed research is relevant to public health because a biostable polymeric valved conduit that can be implanted surgically to reconstruct the right ventricular outflow tract in neonates and infants and then expanded by successive transcatheter procedures to reach the adult size, would revolutionize how we treat children with heart valve diseases. Such a new generation of valved conduit would decrease the number of open-heart surgeries and reoperations, decrease the mortality, complications and healthcare costs related to these procedures and increase the life expectancy and quality of life of these patients. Thus, this proposal is relevant to the part of NIH's mission that pertains to fostering innovative research strategies as a basis for ultimately protecting health.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
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Evans, Frank
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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