Performance hémodynamique de prothèses valvulaires aortiques percutanées et stratégies d'implantation lors de procédures « valve-in-valve » : études in vitro et in vivo

"Thèse en cotutelle Doctorat en médecine expérimentale, Université Laval, Québec, Canada, Philosophiæ doctor (Ph. D.), et Aix-Marseille Université, Marseille, France"L’implantation de prothèse valvulaire aortique percutanée (TAVI), a émergé comme une alternative moins invasive que la chirurgie pour les patients avec sténose sévère et haut risque chirurgical. Les résultats prometteurs tant hémodynamiques que cliniques du TAVI pourraient conduire à étendre ce traitement à une population de plus en plus large avec anatomie plus complexe ou risque chirurgical plus bas, ainsi qu’aux patients avec bioprothèses chirurgicales (BPs) dégénérées. Cette dernière application également appelée « Valve-in-Valve » (ViV), consiste à implanter une prothèse percutanée dans une BP défaillante et permet d’éviter la réintervention chirurgicale invasive associée à un risque de mortalité augmenté. Cependant, deux complications hémodynamiques majeures limitent la généralisation de ces techniques percutanées. Dans le contexte du TAVI « classique », il s’agit des fuites périvalvulaires (PVL) dont la présence est associée à une mortalité augmentée. Ces fuites pourraient être plus sévères dans des anneaux non circulaires. L’effet du surdimensionnement de la prothèse percutanée, pour assurer son étanchéité, sur l’hémodynamie est mal connu et pourrait avoir un impact négatif. De plus, les exigences en termes de performance hémodynamique et de durabilité de la prothèse percutanée doivent être plus hautes chez une population à plus bas risque chirurgical. Il est donc important de déterminer la faisabilité du TAVI et de caractériser la performance hémodynamique dans ces situations d’implantation. Dans le contexte ViV, la présence de hauts gradients (≥ 20 mmHg) post-procéduraux est fréquente et a été associée à une mortalité augmentée. Ces gradients élevés, traduisent souvent une sténose résiduelle et sont particulièrement fréquents dans les BPs sténosées de taille nominale ≤ 21 mm. Les petites BPs et le mode de dégénérescence ont également été associés à une mortalité augmentée. Ainsi, le ViV n’est pas indiqué dans la plupart des petites BPs et par conséquent, il n’existe actuellement aucune recommandation pour leur traitement. Les facteurs que sont les petites BPs et le mode de dégénérescence actuellement mis en cause ne sont pas assez spécifiques et excluent trop de patients qui pourraient bénéficier du traitement. Par ailleurs, le bénéfice hémodynamique réel du ViV par rapport aux statuts avant ViV n’a pas été étudié. Il est donc nécessaire de préciser les facteurs associés non seulement à la performance hémodynamique post-ViV mais également à l’utilité du traitement. iv L’objectif général de ce travail doctoral est de comprendre les interactions entre la prothèse percutanée et l’anneau aortique ou la BP à traiter, impliquées dans la performance hémodynamique, en particulier dans des conditions d’implantation complexes, afin d’étendre les indications du TAVI. Dans le contexte ViV, le défi est de préciser les facteurs modifiables et non modifiables associés à la performance et à l’utilité hémodynamiques du traitement, afin d’identifier les patients susceptibles d’en bénéficier et de proposer des stratégies d’implantation pour éviter la sténose résiduelle.Transcatheter aortic valve implantation (TAVI) has emerged as a less invasive alternative to surgery for patients with severe aortic stenosis and high surgical risk. The promising hemodynamic and clinical outcomes after TAVI has led to extend indications to a larger population including patients with complex anatomy or lower surgical risk, as well as patients with degenerated surgical bioprostheses (BPs). The latter application of TAVI referred to as Valve-in-Valve (ViV) consists in implanting a transcatheter prosthesis within a failing BP in order to avoid redo surgery which is associated with an increased risk of mortality. However, generalization of transcatheter procedures remains limited by 2 major concerns. Regarding "classical" TAVI, the incidence of perivalvular leaks has been associated with increased risk of mortality and may be worsened in non circular annuli. Oversizing, which is used to secure the device, might have a negative impact on the prosthesis hemodynamics but its real effect is unknown. Moreover, the treatment of a lower risk and younger population requires excellent hemodynamic performance and valve durability. It is thus necessary to determine the feasibility of TAVI and to assess the hemodynamic performance in those complex situations. Regarding ViV implantations, the Achille's heel has been residual stenosis. Indeed, elevated post-procedural gradients are common following ViV, especially in BPs with label size ≤ 21 mm, and have been associated with increased mortality. However, there is only few experience in small BPs which are currently excluded from ViV indications and for which there is no recommendation. The factors that have been identified are not specific enough and ViV might be beneficial to a large proportion of patients which are currently excluded from indications. Besides, the actual hemodynamic benefit associated with ViV has not been evaluated (vs. pre ViV status). It is thus necessary to determine precisely the factors associated with both post-ViV hemodynamic performance and which treatment utility. The general objective of this work is to understand the interactions between the transcatheter prosthesis and the aortic annulus or the BP to be treated, which impact the hemodynamic performance, especially in complex conditions of implantation, in order to extend the indications of TAVI. In the context of ViV, the objective is to specify the modifiable and non-modifiable factors associated with the hemodynamic performance and utility of the treatment. The final aim is to identify patients who will benefit from ViV and to provide strategies of implantation in order to avoid residual stenosis

Hemodynamic performance of transcatheter aortic valve prostheses and strategie of implantation for valve-in-valve procedures : in vitro and in vivo studies

L’implantation valvulaire aortique percutanée (TAVI) a émergé comme une alternative à la chirurgie pour les patients avec sténose sévère et haut risque chirurgical. Cette technique s’étend à une population plus large (e.g. anatomie plus complexe, risque chirurgical plus bas), ainsi qu'au traitement Valve-in-Valve (ViV) des bioprothèses (BPs) chirurgicales défaillantes. Cependant, deux complications majeures en limitent la généralisation. En TAVI « classique », la présence de fuites péripothétiques a été associée à une mortalité augmentée. Les effets du surdimensionnement de la prothèse percutanée pour assurer son étanchéité, ou de la forme de l’anneau souvent non circulaire, sur la performance hémodynamique, sont mal connus. En ViV, la présence de hauts gradients est fréquente et associée à une mortalité augmentée. Les BPs de taille nominale ≤ 21 mm et le mode de dégénérescence par sténose, facteurs mis en cause dans la sténose résiduelle et associés à une mortalité augmentée, ne sont pas assez spécifiques et il n’existe actuellement aucune recommandation pour le traitement des petites BPs. Par ailleurs, le bénéfice hémodynamique réel du ViV par rapport aux statuts avant ViV n’a pas été étudié.L’objectif général de ce travail doctoral est de comprendre les interactions entre la prothèse percutanée et l’anneau aortique ou la BP à traiter, impliquées dans la performance hémodynamique, en particulier dans des conditions d’implantation complexes, afin d’étendre les indications du TAVI. En ViV, le défi est de préciser les facteurs associés à sa performance et son utilité hémodynamique et de proposer des stratégies d’implantation afin d’optimiser le succès de la procédure.Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgery for patients with severe aortic stenosis and high surgical risk. This technique is extending to a wider population (e.g. with more complex anatomy or lower surgical risk), as well as to patients with degenerated surgical bioprostheses (BPs). However, two major concerns remain limiting. Regarding “classical TAVI”, periprosthetic leaks have been associated with increased mortality. Oversizing is used to secure the device within the aortic annulus which is often non circular. The effects of oversizing and annulus shape on the hemodynamic performance are unknown. Regarding ViV implantations, elevated post-procedural gradients are common and have been associated with increased mortality. The principal factors associated with this residual stenosis as well as with increased risk of mortality, have been BPs label size ≤ 21 mm and mode of failure by stenosis. These factors are not specific enough and there is currently no recommendation for the treatment of small BPs. Besides, the actual hemodynamic benefit associated with ViV has not been evaluated (vs. pre ViV status).The general objective of this work is to understand the interactions between the transcatheter prosthesis and the aortic annulus or the BP to be treated, which impact the hemodynamic performance, especially in complex conditions of implantation, in order to extend the indications of TAVI. In the context of ViV, the objective is to specify the factors associated with the hemodynamic performance and utility of the treatment. The final aim is to provide strategies of implantation in order to optimize the success of the procedure

Elastin-like polymer coating on CoCr surfaces for cardiovascular applications

Cardiovascular diseases have emerged as a major concern since they are the first cause of death in developed countries. The advent of percutaneous transluminal coronary angioplasty consisted in an alternative to invasive surgery. Especially the introduction of cardiovascular stents has significantly meliorated the potential of angioplasty, e.g. with the use of drug eluting and bioadsorbable stents. Still, restenosis remains a major implant-related complication and can imply re intervention. Therefore, research has focused on limiting and/r avoided restenosis by investigating the field of surface treatments and drug delivery material. The rapidly developing field of material technology and engineering has enable design of molecular-specific surfaces for a new generation of vascular devices. This project has been focused on how to promote endothelialization on a bare metal CoCr alloy stent still widely used nowadays. The knowledge about biological response and interactions between extra cellular matrix proteins and cellular agents has lead to explore the potential of genetically engineered protein based polymers such as elastin-like polymers which mimic properties of the human elastin. This project has for general goal to promote endothelialization on CoCr-alloy by functionalizing the surfaces with REDV elastin-like biopolymer which contains a specific domain for endothelial cell adhesion. For that purpose different surface treatments have been performed on CoCr in order to enhance the biopolymer adhesion. First surfaces have been activated by means of O2 plasma, acid HNO3 and NaOH basic etching. Afterwards, a series has been CPTES silanized previous to biopolymer adsorption. Finally, REDV elastin-like biopolymer has been physically and/or chemically attached to the different treated surfaces. All treatments have been thoroughly physic-chemically characterized before and after all treatments steps. Finally special attention has been paid to the study of biopolymer coating stability after some thermal and/or mechanical treatments in order to determine the best surface treatment conditions of adhesion and the efficiency of previous surface treatments. REDV elastin-like biopolymer was successfully adsorbed on CoCr ASTM F-90 alloy surfaces. It was biofunctionalized CoCr ASTM F-90 alloy surfaces through CPTES silane. Silanization increased biopolymer adsorption but the efficiency was low. NaOH activated samples presented a higher CPTES silane attachment and biopolymer adhesion as observed by an increase of adhered HUVEC cells compared to other treatments. REDV elastin-like biopolymer is more sensitive to mechanical and thermal treatments probably due to a detachment and/or denaturation of the biomolecule. The increase of silanization efficiency on treated CoCr surfaces could enhance biopolymer stability as observed for NaOH treated surfaces.Incomin

Elastin-like polymer coating on CoCr surfaces for cardiovascular applications

Cardiovascular diseases have emerged as a major concern since they are the first cause of death in developed countries. The advent of percutaneous transluminal coronary angioplasty consisted in an alternative to invasive surgery. Especially the introduction of cardiovascular stents has significantly meliorated the potential of angioplasty, e.g. with the use of drug eluting and bioadsorbable stents. Still, restenosis remains a major implant-related complication and can imply re intervention. Therefore, research has focused on limiting and/r avoided restenosis by investigating the field of surface treatments and drug delivery material. The rapidly developing field of material technology and engineering has enable design of molecular-specific surfaces for a new generation of vascular devices. This project has been focused on how to promote endothelialization on a bare metal CoCr alloy stent still widely used nowadays. The knowledge about biological response and interactions between extra cellular matrix proteins and cellular agents has lead to explore the potential of genetically engineered protein based polymers such as elastin-like polymers which mimic properties of the human elastin. This project has for general goal to promote endothelialization on CoCr-alloy by functionalizing the surfaces with REDV elastin-like biopolymer which contains a specific domain for endothelial cell adhesion. For that purpose different surface treatments have been performed on CoCr in order to enhance the biopolymer adhesion. First surfaces have been activated by means of O2 plasma, acid HNO3 and NaOH basic etching. Afterwards, a series has been CPTES silanized previous to biopolymer adsorption. Finally, REDV elastin-like biopolymer has been physically and/or chemically attached to the different treated surfaces. All treatments have been thoroughly physic-chemically characterized before and after all treatments steps. Finally special attention has been paid to the study of biopolymer coating stability after some thermal and/or mechanical treatments in order to determine the best surface treatment conditions of adhesion and the efficiency of previous surface treatments. REDV elastin-like biopolymer was successfully adsorbed on CoCr ASTM F-90 alloy surfaces. It was biofunctionalized CoCr ASTM F-90 alloy surfaces through CPTES silane. Silanization increased biopolymer adsorption but the efficiency was low. NaOH activated samples presented a higher CPTES silane attachment and biopolymer adhesion as observed by an increase of adhered HUVEC cells compared to other treatments. REDV elastin-like biopolymer is more sensitive to mechanical and thermal treatments probably due to a detachment and/or denaturation of the biomolecule. The increase of silanization efficiency on treated CoCr surfaces could enhance biopolymer stability as observed for NaOH treated surfaces.Incomin

Hemodynamic performance of transcatheter aortic valve prostheses and strategie of implantation for valve-in-valve procedures : in vitro and in vivo studies

L’implantation valvulaire aortique percutanée (TAVI) a émergé comme une alternative à la chirurgie pour les patients avec sténose sévère et haut risque chirurgical. Cette technique s’étend à une population plus large (e.g. anatomie plus complexe, risque chirurgical plus bas), ainsi qu'au traitement Valve-in-Valve (ViV) des bioprothèses (BPs) chirurgicales défaillantes. Cependant, deux complications majeures en limitent la généralisation. En TAVI « classique », la présence de fuites péripothétiques a été associée à une mortalité augmentée. Les effets du surdimensionnement de la prothèse percutanée pour assurer son étanchéité, ou de la forme de l’anneau souvent non circulaire, sur la performance hémodynamique, sont mal connus. En ViV, la présence de hauts gradients est fréquente et associée à une mortalité augmentée. Les BPs de taille nominale ≤ 21 mm et le mode de dégénérescence par sténose, facteurs mis en cause dans la sténose résiduelle et associés à une mortalité augmentée, ne sont pas assez spécifiques et il n’existe actuellement aucune recommandation pour le traitement des petites BPs. Par ailleurs, le bénéfice hémodynamique réel du ViV par rapport aux statuts avant ViV n’a pas été étudié.L’objectif général de ce travail doctoral est de comprendre les interactions entre la prothèse percutanée et l’anneau aortique ou la BP à traiter, impliquées dans la performance hémodynamique, en particulier dans des conditions d’implantation complexes, afin d’étendre les indications du TAVI. En ViV, le défi est de préciser les facteurs associés à sa performance et son utilité hémodynamique et de proposer des stratégies d’implantation afin d’optimiser le succès de la procédure.Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgery for patients with severe aortic stenosis and high surgical risk. This technique is extending to a wider population (e.g. with more complex anatomy or lower surgical risk), as well as to patients with degenerated surgical bioprostheses (BPs). However, two major concerns remain limiting. Regarding “classical TAVI”, periprosthetic leaks have been associated with increased mortality. Oversizing is used to secure the device within the aortic annulus which is often non circular. The effects of oversizing and annulus shape on the hemodynamic performance are unknown. Regarding ViV implantations, elevated post-procedural gradients are common and have been associated with increased mortality. The principal factors associated with this residual stenosis as well as with increased risk of mortality, have been BPs label size ≤ 21 mm and mode of failure by stenosis. These factors are not specific enough and there is currently no recommendation for the treatment of small BPs. Besides, the actual hemodynamic benefit associated with ViV has not been evaluated (vs. pre ViV status).The general objective of this work is to understand the interactions between the transcatheter prosthesis and the aortic annulus or the BP to be treated, which impact the hemodynamic performance, especially in complex conditions of implantation, in order to extend the indications of TAVI. In the context of ViV, the objective is to specify the factors associated with the hemodynamic performance and utility of the treatment. The final aim is to provide strategies of implantation in order to optimize the success of the procedure

Mitral bileaflet mechanical heart valves dysfunction and patient/prosthesis mismatch: in vitro investigation of differential diagnosis

International audienc

Effects of Hemodynamic Conditions and Valve Sizing on Leaflet Bending Stress in Self‐Expanding Transcatheter Aortic Valve: An In‐vitro Study

International audienc

EFFECT OF VALVE OVERSIZING ON LEAFLET BENDING STRESS IN THE COREVALVE: AN IN VITRO STUDY

66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Washington, DC, MAR 17-19, 2017International audienceno abstrac

Impact of vascular hemodynamics on aortic stenosis evaluation : new insights into the pathophysiology of normal flow - small aortic valve area - low gradient pattern

Background: About 50% of normal‐flow/low‐gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and Vpeak measurements. Methods and Results: Doppler‐echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/Vpeak compared with normal stage (both P≤0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (−42%) compared with severe (−35%) AS (P˂0.0001). Comprehensive Doppler‐echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/Vpeak and aortic valve calcification divided by the cross‐sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients with normal‐flow/low‐gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal‐AC group (16% and 12% compared with 2%; P=0.03). Conclusions: Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severit

Effect of oversizing and elliptical shape of aortic annulus on transcatheter valve hemodynamics: An in vitro study

International audienceBackground: Transcatheter aortic valve implantation (TAVI) is often performed in patients with non-circular aortic annulus and in oversizing (OS) conditions. The impact of elliptical annulus shape and the consequences of oversizing/underdeployment on the hemodynamic performance are still debated. Objective: This in-vitro study aims to assess and compare the valve hemodynamic performances of the Edwards SAPIEN transcatheter heart valve (THV) in the different current conditions of use: important oversizing in small circular annuli and in elliptical annuli, moderate oversizing in circular and in elliptical annuli of various degrees of eccentricity. Methods: A pulsed cardiovascular simulator was used. Edwards SAPIEN 23 and 26 (mm) were implanted in different circular and elliptical annuli of various sizes and eccentricity. Transvalvular mean pressure gradients (TPGm), effective orifice area (EOA) after implantation of Edwards SAPIEN THV were measured by Dopplere-chocardiography and the performance index (PI - 100 x EOA / Annulus Area) was calculated. Para and transvalvular regurgitation was assessed by color-Doppler and leakage volume was quantified by flowmeter measurement. Results: For a given aortic annulus area, EOAs after implantation of Edwards SAPIEN THV were generally larger and TPGms lower with elliptical annuli compared to circular annuli. The PI was higher (p = 0.047) for elliptical (48 +/- 3%) than for circular annuli (43 +/- 5%). Paravalvular regurgitation occurred only in the case of the SAPIEN 26 implanted in the elliptical annulus with highest eccentricity. Conclusion: The results of this in-vitro study suggest that the EOAs of Edwards SAPIEN are better in elliptical than in circular annuli. No transvalvular regurgitation occurred and only one paravalvular regurgitation was observed after implantation of SAPIEN 26 in the highly eccentric annulus. (C) 2016 Elsevier Ireland Ltd. All rights reserved