Development and testing of a transcatheter heart valve with reduced calcification potential.

Introduction: Patients from developing countries who require heart valve surgery are younger and have less access to open heart surgery than those from developed countries. Transcatheter heart valves (THVs) may be an alternative but are currently unsuitable for young patients because of their inadequate durability. We developed and tested a THV utilizing two new types of decellularized bovine pericardial leaflets in an ovine model. Methods: The two decellularized tissues [one with a very low dose (0.05%) of monomeric glutaraldehyde (GA) fixation and detoxification (DF) and the other without glutaraldehyde (DE)] were compared to an industry standard [Glycar-fixed with the standard dose (0.625%) of glutaraldehyde]. THVs were manufactured with the three tissue types and implanted in the pulmonary position of nine juvenile sheep for 180 days. Baseline and post-explantation evaluations were performed to determine the hemodynamic performance of the valves and their dynamic strength, structure, biological interaction, and calcification. Results: Heart failure occurred in one animal due to incompetence of its Glycar valve, and the animal was euthanized at 158 days. The gradients over the Glycar valves were higher at the explant than at the implant, but the DE and DF valves maintained normal hemodynamic performance throughout the study. The DF and DE tissues performed well during the mechanical testing of explanted leaflets. Glycar tissue developed thick pannus and calcification. Compared to Glycar, the DF tissue exhibited reduced pannus overgrowth and calcification and the DE tissue exhibited no pannus formation and calcification. All tissues were endothelialized adequately. There was a striking absence of host ingrowth in the DE tissue leaflets, yet these leaflets maintained integrity and mechanical function. Conclusion: In the juvenile sheep THV model, Glycar tissue developed significant pannus, calcification, and hemodynamic deterioration. Using a very low dose of monomeric GA to fix the decellularized bovine pericardium yielded less pannus formation, less calcification, and better hemodynamic function. We postulate that the limited pannus formation in the DF group results from GA. Bovine pericardium decellularized with our proprietary method resulted in inert tissue, which is a unique finding. These results justify further development and evaluation of the two decellularized tissue types in THVs for use in younger patients.