The Lost Immunological Innocence of Biological Scaffolds for TAVI

Background: Transcatheter aortic valve implantation (TAVI) is rapidly replacing cardiac surgery due to its minimal invasiveness and practicability. Midterm immunological studies on the biocompatibility of galactose-alpha-1,3-galactose (α - Gal)-carrying bioprosthetic heart valves (BHVs) for TAVI are not available. In this study we investigated whether BHVs employed for TAVI augment an α - Gal-specific antibody-dependent and antibody-independent immune response 3 months post TAVI. Methods: This prospective observational study included 27 patients with severe aortic valve stenosis undergoing TAVI and 10 patients with severe mitral valve regurgitation treated with a transcatheter MitraClip procedure. Serum samples were collected before and 90 days after treatment and analyzed for concentrations of α - Gal-specific IgG, IgG subclasses and IgE, complement C3a, NETosis specific CitH3, and the systemic inflammation markers sST2 and IL-33 via ELISA. Findings: Three months after TAVI we found significantly increased serum concentrations of α - Gal-specific IgG3, C3a, citH3 levels, and sST2 (p=0·002, p=0·001, p=0·025, and p=0·039, respectively). Sensitization of α - Gal-specific IgE antibodies occurred in 55% of all patients after TAVI. Interpretation: Our results indicate that TAVI elicits a specific humoral immune response against α - Gal and causes an unspecific humoral inflammation compared with patients undergoing MitraClip implantation. This observation will lead to a better understanding of post intervention morbidity and the long-term durability of bioprostheses and indicates that caution is appropriate when designing implantation strategies for younger patients. Funding Statement: This work was supported by the institutional surgical research facility ARGE Ankersmit (FOLAB Chirurgie) Declaration of Interests: None of the authors have any conflict of interest to declare. Ethics Approval Statement: Ethics approval was obtained from the Institutional Ethics Committee of the Medical University of Vienna (EK 2218/2016). All experiments were performed in accordance with the approved ethical guidelines. Written informed consent was obtained from all study participants.