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Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts

Emmert, Maximilian Y. ; Weber, Benedikt ; Behr, Luc ; Sammut, Sebastien ; Frauenfelder, Thomas ; Wolint, Petra ; Scherman, Jacques ; Bettex, Dominique ; Grünenfelder, Jürg ; Falk, Volkmar ; Hoerstrup, Simon P.

In: European Journal of Cardio-Thoracic Surgery, 2014, vol. 45, no. 1, p. 61-68

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    Titre
    • Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts
    Auteur
    • Emmert, Maximilian Y.. Swiss Center for Regenerative Medicine, Zurich, Switzerland
    • Weber, Benedikt. Swiss Center for Regenerative Medicine, Zurich, Switzerland
    • Behr, Luc. IMM RECHERCHE, Institut Mutualiste Montsouris, Paris, France
    • Sammut, Sebastien. IMM RECHERCHE, Institut Mutualiste Montsouris, Paris, France
    • Frauenfelder, Thomas. Department of Radiology, University Hospital Zurich, Zurich, Switzerland
    • Wolint, Petra. Swiss Center for Regenerative Medicine, Zurich, Switzerland
    • Scherman, Jacques. Clinic for Cardiovascular Surgery, University Hospital of Zurich, Zurich, Switzerland
    • Bettex, Dominique. Institute for Anesthesiology, University Hospital Zurich, Zurich, Switzerland
    • Grünenfelder, Jürg. Department of Surgical Research, University Hospital of Zurich, Zurich, Switzerland
    • Falk, Volkmar. Clinic for Cardiovascular Surgery, University Hospital of Zurich, Zurich, Switzerland
    • Hoerstrup, Simon P.. Swiss Center for Regenerative Medicine, Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Cardio-Thoracic Surgery, 2014, vol. 45, no. 1, p. 61-68. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:298421
    Summary
    OBJECTIVES While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation. METHODS Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem. RESULTS Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm². Paravalvular leakage was present in two animals, and central aortic regurgitation due to a single-leaflet prolapse was detected in two, which was primarily related to the leaflet design. No stent dislocation, migration or affection of the mitral valve was observed. CONCLUSIONS For the first time, we demonstrate the technical feasibility of a transapical TEHV delivery into the aortic valve position using a commercially available and clinically applied transapical implantation system that allows for exact anatomical positioning. Our data indicate that the combination of TEHV and a state-of-the-art transapical delivery system is feasible, representing an important step towards translational, transcatheter-based TEHV concepts