Institute of Cardiovascular Science, University College London, London, UK.
Department of Surgery, University of Minnesota, 8195B, MMC 195 Mayo, Minneapolis, MN, 55455, USA.
Cardiovasc Eng Technol. 2022 Jun;13(3):363-372. doi: 10.1007/s13239-021-00585-0. Epub 2021 Nov 24.
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.
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.
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.
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.
人们对应用基因工程降低抗原性动物组织制造生物假体心脏瓣膜（BHV）越来越感兴趣，以减少抗体诱导的组织钙化和加速结构性瓣膜退化（SVD）。本研究测试了经过 90 天绵羊二尖瓣植入后，Gal 敲除（GalKO）和标准猪心包制成的瓣膜的生物学等效性。
GalKO（n=5）和标准（n=5）猪心包 BHV 以随机和盲法方式植入绵羊体内 90 天。每隔 30 天测量一次瓣膜血流动力学功能。取出后，检查瓣膜有无赘生物、植物、炎症、血栓和组织钙化。
10 名受者中有 9 名完成了研究。两组在血流动力学性能方面无差异，也没有不良的瓣膜相关事件。取出的 BHV 显示轻度赘生物整合和最小的血栓，两组之间无差异。X 射线检测到有限的局部矿物质沉积。原子光谱分析检测到 GalKO BHV 的组织钙水平为 1.0µg/mg±0.2，标准组织 BHV 为 1.9µg/mg±0.9（p=0.4），均认为较低且等效。
这是首次证明 GalKO 和标准猪心包之间具有生物学等效性。GalKO 突变既不会对 BHV 性能产生内在的有害生物学影响，也不会产生功能影响。GalKO 组织在外科或经导管 BHV 的商业应用将消除产生抗 Gal 抗体的患者与含有 Gal 抗原的 BHV 之间的临床差异。GalKO BHV 可能减少加速的组织钙化和 SVD，增强患者的选择，特别是对年轻患者。
