Next-generation transcatheter aortic valve implantation

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) procedures are increasing rapidly, but the durability of tissue valve and periprocedural complications are not satisfactory. Immune reaction to the galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal) and conventional processing protocols of cardiac xenografts lead to calcification. Next-generation TAVI needs to be made with α-Gal–free xenografts by multiple anticalcification therapies to avoid immune rejection and enhance durability, and three-dimensional (3D) printing technology to improve the procedural safety. METHODS: Porcine pericardia were decellularized and immunologically modified with α-galactosidase. The pericardia were treated by space filler, crosslinked with glutaraldehyde in organic solvent, and detoxified. The sheep-specific nitinol (nickel–titanium memory alloy) wire backbone was made from a 3D-printed model for ovine aortic root. After it passed the fitting test, we manufactured a self-expandable stented valve with the porcine pericardia mounted on the customized nitinol wire–based stent. After in vitro circulation using customized silicone aortic root, we performed TAVI in 9 sheep and obtained hemodynamic, radiological, immunohistopathological, and biochemical results. RESULTS: The valve functioned well, with excellent stent fitting and good coronary flow under in vitro circulation. Sheep were sequentially scheduled to be humanely killed until 238 days after TAVI. Echocardiography and cardiac catheterization demonstrated good hemodynamic status and function of the aortic valve. The xenografts were well preserved without α-Gal immune reaction or calcification based on the immunological, radiographic, microscopic, and biochemical examinations. CONCLUSIONS: We proved preclinical safety and efficacy for next-generation α-Gal–free TAVI with multiple anticalcification therapies and 3D-printing technology. A future clinical study is warranted based on these promising preclinical results.