Abstract
ObjectiveThere 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.MethodsGalKO (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.ResultsNine 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.ConclusionsThis 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
Highlights
Patients with heart valve disease choose between biological heart valves (BHVs), which do not generally require long-term anticoagulation therapy but have more limited durability, and mechanical heart valves (MHVs), which are highly durable but require lifetime anticoagulation, exposing the patient to chronic hemorrhagic/thromboembolic risks.[16]
The real-world practice of prosthetic heart valve implantation into adults continues to evolve, and recent AHA/ACC recommendations state that BHVs should be used for patients over 70 years of age and the choice between MHV and BHV implantation individualized for each patient aged 50-70 years.[28]
We extend the biological equivalence testing, comparing mitral valve implantation of GalKO and standard BHVs in the adolescent sheep model for 90 days
Summary
Replacement heart valves are highly effective and have been used to treat heart valve diseases for over 50 years.[6,13] Patients with heart valve disease choose between biological heart valves (BHVs), which do not generally require long-term anticoagulation therapy but have more limited durability, and mechanical heart valves (MHVs), which are highly durable but require lifetime anticoagulation, exposing the patient to chronic hemorrhagic/thromboembolic risks.[16]. BHV durability is limited by structural valve degeneration (SVD), characterized by leaflet calcification, fibrosis, inflammation, stenosis and leaflet tearing.[31]. The occurrence of SVD is strongly age-dependent and, as a consequence, the use of BHVs has largely been abandoned in children and teenagers, as reoperation due to SVD is required in over 90% of cases within 5 years.[28,31]. Despite the concerns with re-operation due to SVD, BHVs are popular with patients and physicians, and their use in the U.S has increased greatly over the last 20 years.[17]
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