Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep

Objective: There is growing interest in the application of genetically engineered reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves (BHVs) to reduce antibody induced tissue calcification and accelerated structural valve degeneration (SVD). This study tested biological equivalence of valves made from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral valve implantation in sheep. Methods: GalKO (n = 5) and standard (n = 5) porcine pericardial BHVs were implanted in a randomized and blind fashion into sheep for 90-days. Valve haemodynamic function was measured at 30-day intervals. After explantation, valves were examined for pannus, vegetation, inflammation, thrombus, and tissue calcification. Results: Nine of 10 recipients completed the study. There was no difference between study groups for haemodynamic performance and no adverse valve-related events. Explanted BHVs showed mild pannus integration and minimal thrombus, with no difference between the groups. Limited focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis detected tissue calcium levels of 1.0 µg/mg ± 0.2 for GalKO BHVs and 1.9 µg/mg ± 0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. Conclusions: This is the first demonstration of biological equivalence between GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic detrimental biological nor functional impact on BHV performance. Commercial adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the clinical disparity between patients producing anti-Gal antibody and BHVs containing the Gal antigen. GalKO BHVs may reduce accelerated tissue calcification and SVD, enhancing patient choices, especially for younger patients. Graphical Abstract: [Figure not available: see fulltext.].