First ex vivo and preliminary sheep model results of the new TRIBIO aortic valve bioprosthesis in small aortic annuli

Abstract Background Failure of a small surgical aortic bioprosthesis represents a challenging clinical scenario with valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) often resulting in patient-prosthesis mismatch. Bioprosthetic valve fracture (BVF) performed as a part of the ViV TAVI has recently emerged as an alternative approach with certain types of surgical bioprostheses. Case summary An 81-year-old woman with a history of three surgical aortic valve procedures presented with heart failure. Aortic bioprosthesis degeneration with severe stenosis and moderate regurgitation was found. The patient was deemed a high-risk surgical candidate and the heart team decided that ViV TAVI was the preferred treatment option. Due to the very small 19 mm stented surgical aortic bioprosthesis Mitroflow 19 mm (Sorin Group, Italy) we decided to perform BVF as a part of ViV TAVI to prevent patient-prosthesis mismatch. Since this was the first BVF procedure in our centre, an ex vivo BVF of the same kind of bioprosthetic valve was performed first. Subsequently, successful BVF with implantation of Evolut R 23 mm (Medtronic, USA) self-expandable transcatheter valve was performed. Excellent haemodynamic result was achieved and no periprocedural complications were present. The patient had an immediate major improvement in clinical status and remains asymptomatic after 6 months. Discussion Bioprosthetic valve fracture together with ViV TAVI is a safe and effective emerging technique for treatment of small surgical aortic bioprosthesis failure. Bioprosthetic valve fracture allows marked oversizing of implanted self-expandable transcatheter aortic valves, leading to excellent haemodynamic and clinical results. An ex vivo BVF can serve as an important preparatory step when introducing the new method.

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Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model

Biomaterials ◽

10.1016/j.biomaterials.2009.07.068 ◽

2009 ◽

Vol 30 (31) ◽

pp. 6240-6246 ◽

Cited By ~ 82

Author(s):

Hassina Baraki ◽

Igor Tudorache ◽

Maike Braun ◽

Klaus Höffler ◽

Adelheid Görler ◽

...

Keyword(s):

Aortic Valve ◽

Sheep Model

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Ozaki procedure: Ex vivo simulation

10.1510/mmcts.2021.075 ◽

2021 ◽

Keyword(s):

Aortic Valve ◽

Ex Vivo ◽

Aortic Valves ◽

Autologous Pericardium ◽

Video Tutorial ◽

Novel Technique ◽

Valve Reconstruction

Replacements for diseased aortic valves are limited. Repair of the aortic valve is performed by only a few surgeons. A novel technique of aortic valve reconstruction using autologous pericardium shows promising results. In this video tutorial, we demonstrate the Ozaki procedure using an ex vivo low fidelity simulation.

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Abstract 295: Hemodynamic Shear Stress Alterations Contribute to Calcific Aortic Valve Disease in a Frequency- and Magnitude-Dependent Manner

Circulation Research ◽

10.1161/res.111.suppl_1.a295 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Ling Sun ◽

John LeCluyse ◽

Brian Robillard ◽

Philippe Sucosky

Keyword(s):

Shear Stress ◽

Aortic Valve ◽

Aortic Valve Disease ◽

Ex Vivo ◽

Fold Increase ◽

Endothelial Activation ◽

Valve Disease ◽

Dependent Manner ◽

Molecular Signaling ◽

Calcific Aortic Valve Disease

INTRODUCTION: Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between atherogenic risk factors, molecular signaling networks and hemodynamic cues. While our earlier work demonstrated that progressive alterations in fluid wall-shear stress (WSS) on the fibrosa could trigger leaflet inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific WSS abnormalities are poorly understood. HYPOTHESIS: Supported by our previous studies, we hypothesize that valve leaflets are sensitive to both WSS magnitude and pulsatility and that abnormalities in either promote CAVD development. OBJECTIVE: This study aims at elucidating ex vivo the contribution of isolated and combined alterations in WSS magnitude and pulsatility to valvular calcification. METHODS: The fibrosa and ventricularis of porcine leaflets were subjected simultaneously to different combinations of WSS magnitude and pulsatility (i.e., physiologic, sub- and supra-physiologic levels) for 48 hours in a double-sided shear stress bioreactor. Endothelial activation (ICAM-1, VCAM-1), paracrine expression (TGF-β and BMP-4), and proteinase/collagenase expression (MMP-2, cathepsin L) were detected by immunohistochemistry, while osteogenic differentiation (α-SMA) was assessed via western blot. RESULTS: Regardless of the magnitude or frequency, non-physiologic WSS conditions did not result in endothelial activation. Tissue exposure to either supra-physiologic WSS magnitude or pulsatility significantly upregulated paracrine (74-fold increase), proteinase (4-fold increase), collagenase (5-fold increase) and α-SMA (23-fold increase) expressions relative to the levels measured under physiologic WSS. In contrast, combined alterations in WSS magnitude and pulsatility downregulated those responses. CONCLUSION: This study demonstrates the sensitivity of aortic valve leaflets to both WSS magnitude and pulsatility and the ability of supra-physiologic WSS magnitude or pulsatility to trigger events involved in early CAVD pathogenesis. The results provide new potential insights into the mechanisms of CAVD secondary to hypertension and Paget’s disease, which are associated with abnormal blood flow and leaflet WSS.

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Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease

Journal of Clinical Medicine ◽

10.3390/jcm9010029 ◽

2019 ◽

Vol 9 (1) ◽

pp. 29

Author(s):

Guillermo Solache-Berrocal ◽

Ana María Barral-Varela ◽

Sheila Areces-Rodríguez ◽

Alejandro Junco-Vicente ◽

Aitana Vallina-Álvarez ◽

...

Keyword(s):

Computed Tomography ◽

Aortic Valve ◽

Molecular Mechanisms ◽

Soft Tissues ◽

Ex Vivo ◽

Developed Countries ◽

Macrophage Infiltration ◽

Micro Computed Tomography ◽

Calcific Aortic Valve Disease ◽

Calcium Deposits

Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the extent of mineralisation in soft tissues and some methods require the destruction of the sample. Micro-computed tomography (µCT), a non-destructive technique, was used to quantify the density and volume of calcium deposits on cusps from 57 explanted aortic valves. Conventional and immunostaining techniques were used to characterise valve tissue degeneration and the inflammatory and osteogenic stage with several markers. Although most of the analysed cusps came from severe stenosis patients, the µCT parameter bone volume/tissue volume ratio distinguished several degrees of mineralisation that correlated with the degree of structural change in the tissue and the amount of macrophage infiltration as determined by CD68 immunohistochemistry. Interestingly, exosomal markers CD63 and Alix co-localised with macrophage infiltration surrounding calcium deposits, suggesting that those vesicles could be produced at least in part by these immune cells. In conclusion, we have shown that the ex vivo assessment of aortic valve mineralisation with µCT reflects the molecular and cellular changes in pathological valves during progression towards stenosis. Thus, our results give additional validity to quantitative μCT as a convenient laboratory tool for basic research on this type of cardiovascular calcification.

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Novel bicuspid aortic valve model with aortic regurgitation for hemodynamic status analysis using an ex vivo simulator

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2020.06.028 ◽

2020 ◽

Cited By ~ 2

Author(s):

Yuanjia Zhu ◽

Annabel M. Imbrie-Moore ◽

Michael J. Paulsen ◽

Bryant Priromprintr ◽

Hanjay Wang ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Regurgitation ◽

Bicuspid Aortic Valve ◽

Ex Vivo ◽

Hemodynamic Status ◽

Status Analysis ◽

Valve Model

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Truly stentless molded autologous pericardial aortic valve prosthesis with single point attached commissures in a sheep model☆

European Journal of Cardio-Thoracic Surgery ◽

10.1016/j.ejcts.2007.12.044 ◽

2008 ◽

Vol 33 (4) ◽

pp. 548-553 ◽

Cited By ~ 6

Author(s):

Wolfgang A. Goetz ◽

Teing Ee Tan ◽

Khee Hiang Lim ◽

Sidney Le Hung Salgues ◽

Nil Grousson ◽

...

Keyword(s):

Aortic Valve ◽

Single Point ◽

Valve Prosthesis ◽

Sheep Model ◽

Aortic Valve Prosthesis

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A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report

Frontiers in Pharmacology ◽

10.3389/fphar.2020.568764 ◽

2020 ◽

Vol 11 ◽

Author(s):

Arsenii Zabirnyk ◽

Maria del Mar Perez ◽

Marc Blasco ◽

Kåre-Olav Stensløkken ◽

Miguel D. Ferrer ◽

...

Keyword(s):

Aortic Valve ◽

Growth Medium ◽

Ex Vivo ◽

Growth Media ◽

Dependent Manner ◽

Ex Vivo Model ◽

Aortic Valves ◽

Valve Calcification ◽

Calcium Accumulation ◽

Aortic Valve Leaflets

Background: No pharmacological treatment exists to prevent or stop the calcification process of aortic valves causing aortic stenosis. The aim of this study was to develop a robust model of induced calcification in whole aortic valve leaflets which could be suitable for studies of the basic mechanisms and for testing potentially inhibitory drugs.Methods: Pig hearts were obtained from a commercial abattoir. The aortic valve leaflets were dissected free and randomized between experimental groups. Whole leaflets were cultured in individual wells. Two growth media were used for cultivation: standard growth medium and an antimyofibroblastic growth medium. The latter was employed to inhibit contraction of the leaflet into a ball-like structure. Calcification was induced in the growth medium by supplementation with an osteogenic medium. Leaflets were cultivated for four weeks and medium was changed every third day. To block calcification, the inhibitor SNF472 (a formulation of the hexasodium salt of myo-inositol hexaphosphate hexasodium salt) was used at concentrations between 1 and 100 µM. After cultivation for four weeks the leaflets were snap frozen in liquid nitrogen and kept at −80 °C until blind assessment of the calcium amount in leaflets by inductively coupled plasma optical emission spectroscopy. For statistical analysis, a Kruskal–Wallis test with Dunn’s post-test was applied.Results: Osteodifferentiation with calcium accumulation was in principle absent when standard medium was used. However, when the antimyofibroblastic medium was used, a strong calcium accumulation was induced (p = 0.006 compared to controls), and this was blocked in a dose-dependent manner by the calcification inhibitor SNF472 (p = 0.008), with an EC50 of 3.3 µM.Conclusion: A model of experimentally induced calcification in cultured whole leaflets from porcine aortic valves was developed. This model can be useful for studying the basic mechanisms of valve calcification and to test pharmacological approaches to inhibit calcification.

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