Abstract 4144180: Preclinical Investigation of Integration and Tissue Response to a Novel Growth-Accommodating Transcatheter Pulmonary Valve

Background: Among 40,000 newborns with congenital heart defects, many face right ventricular outflow tract (RVOT) dysfunction, requiring pulmonary valve replacement. Existing options like the Melody™ transcatheter pulmonary valve aren't suitable for children under 20 kg, posing risks to the right ventricle (RV) as smaller children await weight gain. To avoid the detrimental effects to the RV in young children, we have developed IRIS Valve, a novel growth accommodating transcatheter pulmonary heart valve. This valve can be implanted using a 12-Fr transcatheter delivery system, catering to children weighing as little as 8 kg. As the native valve annulus expands, the IRIS Valve can be balloon-expanded up to 20mm. Hypothesis: We investigate the successful integration of the IRIS Valve into the RVOT six months after implantation. Aims: We aimed to assess the IRIS Valve's integration and chronic response over a six-month period in Yucatan mini-pigs to ensure the prosthetic valve's integrity. Methods: Derived from origami ideas, the IRIS Valve maintains its fully-coapted trileaflet design crafted from porcine pericardial tissue, in a diameter range from 12 mm to 20 mm (Fig. 1). The animal implantation studies involved seven Yucatan pigs weighing between 8 and 17 kg. The implantation was performed using a 12- or 14-Fr delivery catheter. The valves were appropriately balloon-expanded to accommodate the increasing size of the animals. Six months post-implantation, two animals were euthanized, and their hearts were harvested for histopathological analysis. The RVOT and proximal pulmonary artery, containing the IRIS Valve, were excised, stained with H&E, and embedded into MMA blocks. Results: All seven implanted IRIS Valves maintained precise positioning at the native pulmonary valve and exhibited either no or minimal regurgitation across pigs with diverse pulmonary annulus sizes (Fig. 2). Macroscopic examination post-euthanasia revealed intact valve leaflets. Histopathological examination with H&E staining demonstrated robust integration of IRIS Valve into the RVOT wall, accompanied by a variable chronic inflammatory response characterized by mixed lymphocytes and macrophages, as well as multinucleated giant cells reacting to both the ePFTE skirt and suture material (Fig. 3). Conclusions: Our findings indicate that the IRIS transcatheter pulmonary valve maintains its integrity throughout the 6-month study period and exhibits characteristic chronic inflammatory markers.