Inflammatory immune response in recipients of transcatheter aortic valves

Cecilia Veraar; Matthias Koschutnik; Christian Nitsche; Maria Laggner; Dominika Polak; Barbara Bohle; Andreas Mangold; Bernhard Moser; Julia Mascherbauer; Hendrik J Ankersmit

doi:10.1016/j.xjon.2021.02.012

Inflammatory immune response in recipients of transcatheter aortic valves

JTCVS Open. 2021 Mar 12:6:85-96. doi: 10.1016/j.xjon.2021.02.012. eCollection 2021 Jun.

Authors

Cecilia Veraar^{1

2}, Matthias Koschutnik³, Christian Nitsche³, Maria Laggner^{2

4}, Dominika Polak⁵, Barbara Bohle⁵, Andreas Mangold³, Bernhard Moser⁴, Julia Mascherbauer^{3

6}, Hendrik J Ankersmit^{2

4}

Affiliations

¹ Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesiology, General Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria.
² Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Medical University of Vienna, Vienna, Austria.
³ Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
⁴ Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
⁵ Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
⁶ Department of Internal Medicine III, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, Krems, Austria.

Abstract

Objective: Transcatheter aortic valve implantation (TAVI) is rapidly replacing cardiac surgery due to its minimal invasiveness and practicality. Midterm immunological studies on the biocompatibility of galactose-alpha-1,3-galactose (α-Gal)-carrying bioprosthetic heart valves for TAVI are not available. In this study we investigated whether bioprosthetic heart valves employed for TAVI augment an α-Gal-specific antibody-dependent and antibody-independent immune response 3 months after TAVI implantation.

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 (Abbott Laboratories, Abbott Park, Ill) procedure. Blood samples were drawn before and 90 days after treatment at a routine checkup. Serum samples were analyzed using enzyme-linked immunosorbent assay. Serum concentrations of α-Gal-specific immunoglobulin (Ig) G, IgG subclasses and IgE, complement factor 3a, NETosis-specific citrullinated H3, and the systemic inflammation markers soluble suppression of tumorigenicity and interleukin 33 were evaluated.

Results: Three months after TAVI, we found significantly increased serum concentrations of α-Gal-specific IgG3, complement factor complement factor 3a, citrullinated H3 levels, and soluble suppression of tumorigenicity (P = .002, P = .001, P = .025, and P = .039, respectively). Sensitization of α-Gal-specific IgE antibodies occurred in 55% of all patients after TAVI.

Conclusions: Our results indicate that TAVI elicits a midterm, 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 postintervention morbidity and the long-term durability of bioprostheses and indicates that caution is appropriate when designing implantation strategies for younger patients.

Keywords: BHV, bioprosthetic heart valve; C3a, complement factor 3a; CitH3, citrullinated H3; DAPI, 4′,6-diamidino-2-phenylindole; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; Ig, immunoglobulin; MitraClip; NET, neutrophil extracellular traps; NETosis; NT-proBNP, N-terminal pro-brain natriuretic peptide; ST2; TAVI; TAVI, transcatheter aortic valve implantation; alpha Gal; bioprosthetic heart valves; complement activation; mAb, monoclonal antibody; sST2, soluble suppression of tumorigenicity-2; α-Gal, galactose-alpha-1,3-galactose.