Abstract 13085: Quantitation of the Alpha-Gal Epitopes Threat in Commercial Heart Valve Bioprostheses
The glutaraldehyde (GA) treatment of heart valve bioprostheses (HVBs) might be inadequate to ensure complete shielding of the xenoantigen alpha-Gal. The primary cause of failure of HVBs is due to dystrophic calcification, tentatively related to the inflammatory reaction elicited by exposed immunogenic epitopes. The aim is to detect and in case to quantify the amount of exposed alpha-Gal epitopes in currently stored pericardial HVBs as Mitroflow® and Soprano Armonia™ (Sorin Heart Valves), Perimount Magna and Sapien XT (Edwards Lifesciences). The valves were previously tested in a Sheffield pulse duplicator. The Sapien XT valve was crimped and balloon-expanded to mimic the initial conditions of implantation. The HVB leaflets were detoxified and reacted with the M86 primary monoclonal antibody to quantify the exposed alpha-Gal epitopes by an indirect ELISA assay. To evaluate the relevance of the reactive xenogeneic residues, the alpha-Gal content in HVB cusps was compared to that determined in native bovine pericardial tissue and expressed for each 10 mg of wet tissue with reference to a standardized source of alpha-Gal epitopes (rabbit red cells). All valves exhibited adequate hydrodynamic performance. Epitope binding to M86 was evidenced in all the investigated HVBs, the extent being about five times less with respect to native bovine pericardium (1.14 ± 2.2*1012). The difference between Soprano (2.01 ± 0.17*1011), Mitroflow (2.18 ± 0.13*1011) and Sapien XT (2.11 ± 0.21*1011) was not significant. The Magna bioprosthesis exhibited the greatest amount of reactive epitopes: 2.71 ± 0.32*1011 (Magna vs Soprano p=0.0006; Magna vs Mitroflow p=0.003; Magna vs Sapien p=0.001). HVBs original GA-treatment did not prevent the binding of resident alpha-Gal antigens with M86 antibodies after storage and hydrodynamic testing. The investigated HVBs exhibited a non negligible while comparable amount of reactive epitopes accounting to 19.8 % ± 2.7 of those exposed by native pericardial tissue. Future perspectives are addressed to investigate the presence and possible exposition of alpha-Gal in currently available HVBs before and after progressive wear testing, alternatives in GA-treatment (dynamic) as well as implications in calcification phenomena.
- © 2011 by American Heart Association, Inc.