Hemocompatibility and safety of the Carmat Total Artifical Heart hybrid membrane

Ulysse Richez; Hector De Castilla; Coralie L Guerin; Nicolas Gendron; Giulia Luraghi; Marc Grimme; Wei Wu; Myriam Taverna; Piet Jansen; Christian Latremouille; Francesco Migliavacca; Gabriele Dubini; Antoine Capel; Alain Carpentier; David M Smadja

doi:10.1016/j.heliyon.2019.e02914

Hemocompatibility and safety of the Carmat Total Artifical Heart hybrid membrane

Heliyon. 2019 Dec 8;5(12):e02914. doi: 10.1016/j.heliyon.2019.e02914. eCollection 2019 Dec.

Authors

Ulysse Richez^{1

2

3}, Hector De Castilla³, Coralie L Guerin^{4

5}, Nicolas Gendron⁶, Giulia Luraghi⁷, Marc Grimme³, Wei Wu⁷, Myriam Taverna⁸, Piet Jansen³, Christian Latremouille⁹, Francesco Migliavacca⁷, Gabriele Dubini⁷, Antoine Capel³, Alain Carpentier⁹, David M Smadja⁶

Affiliations

¹ Université de Paris, Innovative Therapies in Haemostasis, INSERM UMR-S1140, F-75006, Paris, France.
² et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), AH-HP, Georges Pompidou European Hospital, F-75015, Paris, France.
³ Carmat SA, Vélizy-Villacoublay, France.
⁴ Institut Curie, Flow Cytometry Department, F-75006, Paris, France.
⁵ National Cytometry Platform, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg.
⁶ Service D'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), AH-HP, Georges Pompidou European Hospital, F-75015, Paris, France.
⁷ Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy.
⁸ PNAS, Institut Galien de Paris-Sud, Faculté de Pharmacie, Université Paris-Sud, CNRS UMR8612, 5 Rue JB Clément, Chatenay Malabry, France.
⁹ Service Chirurgie Cardique et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), AH-HP, Georges Pompidou European Hospital, F-75015, Paris, France.

Abstract

The Carmat bioprosthetic total artificial heart (C-TAH) is a biventricular pump developed to minimize drawbacks of current mechanical assist devices and improve quality of life during support. This study aims to evaluate the safety of the hybrid membrane, which plays a pivotal role in this artificial heart. We investigated in particular its blood-contacting surface layer of bovine pericardial tissue, in terms of mechanical aging, risks of calcification, and impact of the hemodynamics shear stress inside the ventricles on blood components. Hybrid membranes were aged in a custom-designed endurance bench. Mechanical, physical and chemical properties were not significantly modified from 9 months up to 4 years of aging using a simulating process. Exploration of erosion areas did not show no risk of oil diffusion through the membrane. Blood contacting materials in the ventricular cavities were subcutaneously implanted in Wistar rats for 30 days as a model for calcification and demonstrated that the in-house anti-calcification pretreatment with Formaldehyde-Ethanol-Tween 80 was able to significantly reduce the calcium concentration from 132 μg/mg to 4.42 μg/mg (p < 0.001). Hemodynamic simulations with a computational model were used to reproduce shear stress in left and right ventricles and no significant stress was able to trigger hemolysis, platelet activation nor degradation of the von Willebrand factor multimers. Moreover, explanted hybrid membranes from patients included in the feasibility clinical study were analyzed confirming preclinical results with the absence of significant membrane calcification. At last, blood plasma bank analysis from the four patients implanted with C-TAH during the feasibility study showed no residual glutaraldehyde increase in plasma and confirmed hemodynamic simulation-based results with the absence of hemolysis and platelet activation associated with normal levels of plasma free hemoglobin and platelet microparticles after C-TAH implantation. These results on mechanical aging, calcification model and hemodynamic simulations predicted the safety of the hybrid membrane used in the C-TAH, and were confirmed in the feasibility study.

Keywords: Bioengineering; Biomedical engineering; Biophysics; Bioprosthetic; Cardiology; Carmat; Haematology; Hemocompatibility; Total artificial heart.