Die bikuspide Aortenklappe gilt als Risikofaktor für das frühzeitige und häufige Auftreten von Aortenklappenvitien, Aneurysmen und Dissektionen. Das Ziel dieser Arbeit ist es, ein begründetes chirurgisches Therapiekonzept für Patienten mit bikuspider Aortenklappe und Dilatation der Aorta ascendens zu entwickeln. Wir analysierten die Daten von 555 Patienten mit bikuspider und 2015 Patienten mit trikuspider Aortenklappe, die sich in unserer Einrichtung einer Operation an der Aortenklappe und/ oder einem Eingriff im Bereich der Aorta ascendens unterzogen. Die Aorta ascendens wurde angiographisch, echokardiographisch und mittels CT auf ihre Konfiguration analysiert und histologisch und histomorphometrisch beschrieben. Auch wurden die Langzeitergebnisse nach Aorta ascendens Reduktionsplastik erfasst. Bei Patienten mit bikuspider Aortenklappe sind mit zunehmendem Durchmesser der Aorta ascendens häufiger die histologischen Zeichen einer Dilatation zu finden. Schwerere strukturelle Veränderungen, insbesondere eine höhergradige zystische Medianekrose, sind nicht zu beobachten. Die Aorta Ascendens Reduktionsplastik zeigt bei Patienten mit bikuspider Aortenklappe und Dilatation der Aorta ascendens gute Langzeitergebnisse. Nur bei Patienten mit nicht optimaler Durchmesser-Reduktion bei der Operation kommt es zu einer späteren Redilatation. / The bicuspid aortic valve is a known risk factor for the early and frequent occurrence of aortic valve defects, aneurysms and dissections. This study aims to develop an appropriate surgical therapy concept for patients with bicuspid aortic valve and dilatation of the ascending aorta. The data of 555 patients with bicuspid and 2015 patients with tricuspid aortic valve who underwent surgical treatment of the aortic valve and/or of the ascending aorta at our institution were evaluated. We analyzed the configuration of the ascending aorta by angiography, echocardiography and CT and described the aortic wall by histological and histomorphometric examination. We also analyzed the long-term results after reduction aortoplasty of the ascending aorta. Histological examination of the aortic wall specimens showed that patients with bicuspid aortic valve with increased diameter of the ascending aorta more often have histological signs of dilatation. More severe histological changes such as cystic media necrosis did not occur. Reduction aortoplasty of the ascending aorta shows good long-term results in patients with bicuspid aortic valve and dilatation of the ascending aorta. Only in patients in whom surgical reduction is less than optimal does redilatation occur later.

Ces travaux s’inscrivent dans le cadre de la navigation endovasculaire assistée par ordinateur. L’objectif principal est d’étudier et de proposer de nouvelles solutions pour la localisation et le suivi des dispositifs endovasculaires en mouvement par rapport aux structures anatomiques, considérées comme immobiles ou mobiles. Il s’agit à terme de faciliter le geste interventionnel, en maximisant la précision et la fiabilité des procédures, tout en minimisant le recours aux rayons X et au produit de contraste. Les travaux et résultats obtenus concernent : - L’étude d’approches de recalage permettant de fusionner des données 3D pré-opératoires décrivant les structures anatomiques et des données intra-opératoires de localisation 3D électromagnétique (positions d’un cathéter équipé d’un capteur magnétique en son extrémité). Dans le contexte du traitement des anévrismes aortiques abdominaux, deux méthodes de recalage ne nécessitant pas de marqueur externe et exploitant uniquement les trajectoires endovasculaires (avec hypothèse de correspondance totale ou partielle) ont été proposées. Les tests ont été réalisés sur fantôme physique. Bien que la précision de localisation des systèmes électromagnétiques soit encore limitée, ceux-ci pourraient être utilisés pour aider la navigation endovasculaire, comme par exemple, lors du cathétérisme d’artères collatérales. - L’élaboration d’une méthode de tracking des calcifications et de repères dans les séquences d’images fluoroscopiques, dans le contexte des procédures d’implantation endovasculaire de valve aortique (TAVI). Nous avons proposé une méthode de tracking par modèle d’apparence adaptatif (TMAA). L'approche a été évaluée sur 13 séquences fluoroscopiques dans le cadre des procédures TAVI valve native et 5 séquences fluoroscopiques dans le cadre des procédures TAVI valve-in-valve. Elle fournit une erreur de localisation moyenne inférieure à 1 mm et un temps de traitement de 32,23 ms/trame. L’évaluation de cette méthode et son application sur données patients ont permis de montrer la précision et la compatibilité du tracking avec une utilisation clinique. / This work is part of computer-assisted endovascular navigation. The aim of this thesis is to study and to propose new solutions for the localization and the tracking of moving endovascular devices within anatomical structures, which can be considered fixed or moving. The objective is to facilitate the endovascular intervention, by maximizing the accuracy and reliability of procedures, while minimizing the use of X-rays and contrast agents. The works concern : - The study of registration approaches to align pre-operative 3D data describing the anatomical structures and intra-operative 3D electromagnetic data (positions of a catheter equipped with a magnetic sensor at its tip). In the context of the treatment of abdominal aortic aneurysms (AAA), two fiducial-free registration methods that exploit only the endovascular trajectories (with total or partial correspondence hypothesis) have been proposed. The tests were performed on an AAA phantom. Although the localization accuracy of electromagnetic systems is still limited, these could be used to assist endovascular navigation (e.g., catheterization of collateral arteries). - The elaboration of a method to track calcifications and markers in fluoroscopic sequences, in the context of transcatheter aortic valve implantation (TAVI) procedures. We proposed a method of tracking by adaptive appearance model (TMAA). The approach was evaluated on 13 fluoroscopic sequences as part of TAVI native valve procedures and 5 fluoroscopic sequences as part of TAVI valve-in-valve procedures. The average localization error was less than 1 mm and the average processing time was 32.23 ms/frame. The evaluation of this method and its application on patient data has made it possible to show the precision and the compatibility of the tracking with a clinical use.

Heart valve tissue engineering (HVTE) stands as a potential intervention that could reduce the prevalence of congenital heart valve disease in juvenile patients. Prior studies in our laboratory have utilized mechanobiological testing to quantify the forces involved in the development of heart valve tissue, utilizing a Flow-Stretch-Flexure (FSF) bioreactor to condition bone marrow stem cells (BMSCs)-derived valve tissue. Simulations have demonstrated that certain sets of flow conditions can introduce specific levels of oscillatory shear stress (OSS)-induced stimuli, augmenting the growth of engineered valves as well as influencing collagen formation, extracellular matrix (ECM) composition and gene expression. The computational findings discussed in this thesis outline the methods in which flow conditions, when physiologically relevant, induce specific oscillatory shear stresses which could not only lead to an optimized valve tissue phenotype (at 0.18≤ OSI≤ 0.23), but could identify native valve tissue remodeling indicative of aortic valve disease.

No description available.

Introdução: O recente aperfeiçoamento da ultra-sonografia permitiu a análise estrutural e funcional do vaso. Casuística e Métodos: 36 pacientes com insuficiência aórtica e indicação de troca valvar, divididos em grupos com pressão arterial diastólica (PAD) superior e inferior a 50mmHg, avaliados antes e seis meses após a cirurgia. A função arterial compreendeu a complacência, distensibilidade e a função endotelial pela dilatação fluxo-mediada e nitrato-mediada. Conclusão: A complacência e a distensibilidade foram maiores no grupo com menor PAD e diminuíram após a cirurgia. A disfunção endotelial foi presente em insuficiência aórtica crônica independente do nível da pressão arterial diastólica / Introduction: The recent improvement of ultrasonography made possible a functional and structural analysis of the vessel. Methods: 36 patients with aortic insufficiency and valve replacement need, divided in 2 groups with diastolic blood pressure (DBP) above and below 50mmHg. Checked twice: before and 6 months after surgery. The arterial function comprised compliance, distensibility and endothelial function through flow-mediated dilatation and nitrate-mediated dilatation. Conclusion: The compliance and distensibility were higher in the group with lower DBP and decreased after surgery. Endothelial dysfunction was present in chronic aortic insufficiency no matter the level of DBP

Contexte: L'implantation valvulaire aortique par cathéter (TAVI) est une procédure relativement jeune dont l'objectif est de traiter les patients atteints de sténose aortique sévère pour qui la chirurgie cardiaque conventionnelle est considérée à haut risque ou contre-indiquée. Cette procédure a subi, au fil du temps, des améliorations sur le plan technologique (succession de différentes générations de prothèses valvulaires) ainsi que sur le plan technique (simplification des différentes étapes de la procédure). Objectif: L'objectif de ce travail est de décrire l'impact clinique d'une avancée technologique, soit le passage de la deuxième vers la troisième génération de la prothèse Edwards, et d'une avancée technique, soit l'implantation de la prothèse sans pré-dilatation de la valve native. Méthodes: Nous présentons d'abord, par le biais d'une revue et méta-analyse, les résultats cliniques du TAVI au début de son utilisation à plus grande échelle, en 2012. Ensuite, une étude monocentrique rétrospective dans un centre à haut volume décrit les résultats du passage de la deuxième vers la troisième génération de la valve Edwards chez 507 patients. Enfin, une étude rétrospective avec appariement a testé différentes stratégies de pré-dilatation durant la procédure: une pré-dilatation systématique, une pré-dilatation sélective chez des patients présentant des caractéristiques cliniques précises, et l'absence de pré-dilatation. Résultats: Dans l'article présentant les résultats cliniques au début de l'expérience TAVI, le taux de mortalité à 30 jours variait entre 5 et 18%. Le taux de décès à 1 an était estimé à 23% (méta-analyse, random effects model). Le taux d'AVC à 30 jours était entre 0 et 6.7% et le taux de complication vasculaire majeure entre 2 et 16%. L'étude sur le passage de la SAPIEN XT vers la SAPIEN 3 a montré une diminution non significative de la mortalité à 30 jours (de 8.7 à 3.5%; p=0.21) et des AVC à 30 jours (de 2.8 à 1.4%; p=0.6), ainsi qu'une diminution significative des complications vasculaires majeures à 30 jours (de 9.9 à 2.8%; p<0.0001). Cependant, il y a eu une augmentation significative du taux de pacemaker (de 9.8 à 17.3%; p=0.03). L'étude sur la pré-dilatation versus le direct TAVI a montré une absence d'effet adverse du direct TAVI en termes de décès ou complications vasculaires à 30 jours. Nous avons trouvé une tendance à la réduction des AVC avec le direct TAVI (3 vs. 1%; p=0.11), en particulier chez les patients avec une valve aortique peu ou modérément calcifiée. Cependant, chez les patients avec calcification extensive de la valve, le risque de malposition de la prothèse était numériquement plus élevé. Au cours des 3 études présentées, la mortalité à 1 an a peu évolué (entre 20 et 25%). Conclusions: Les événements adverses à court terme ont diminué après le changement de génération de valve Edwards. Le direct TAVI permet de simplifier la procédure sans augmenter les taux d'effets adverses. Cependant, les deux avancées présentent des limites qui incitent à la prudence. / Context: Transcatheter aortic valve implantation (TAVI) is a relatively young procedure intended to treat patients with severe aortic stenosis who are at high risk for conventional surgery, or inoperable. This procedure underwent multiple technological improvements (successive generations of devices) and multiple technical improvements (simplification of various steps in the procedure). Objective: We intend to describe the clinical impact of a technological improvement (the transition from the second to the third generation of the Edwards device in a high-volume center) and that of a technical improvement (TAVI without pre-dilatation, known as direct TAVI). Methods: We first describe, through a meta-analysis, the state of TAVI at the beginning of its widespread use, in 2012. Next, we describe, through a single-center retrospective study, the clinical impact of the transition from the second to the third generation of the Edwards device in 507 patients. Finally, in a retrospective study with matching, we tested three pre-dilatation strategies: systematic pre-dilatation, selective pre-dilatation, and direct TAVI. Results: In the article describing the initial TAVI experience, the 30-day mortality rate was between 5 and 18%. One-year mortality was estimated at 23% by meta-analysis (random effects model). Stroke rate at 30 days was between 0 and 6.7% and major vascular complication rate was between 2 and 16%. The transition from SAPIEN XT to SAPIEN 3 resulted in a non-significant reduction in 30-day mortality (from 8.7 to 3.5%; p=0.21) and 30-day stroke rate (from 2.8 to 1.4%; p=0.6), and a significant reduction in major vascular complications (from 9.9 to 2.8%; p<0.0001). However, there was a significant increase in permanent pacemaker rate (from 9.8 to 17.3%; p=0.03). Next, we found no adverse effect of performing direct TAVI in terms of mortality or vascular complications at 30 days. We found a trend towards a reduction in stroke rate with direct TAVI (3 vs. 1%; p=0.11), particularly in patients with mildly or moderately calcified valves. However, in those with extensive valvular calcification, the risk of device malposition was numerically higher. In all three studies presented, there was little variation in 1-year mortality (20 to 25%). Conclusions: Short-term adverse events were reduced by the transition towards the third-generation Edwards device. Direct TAVI is feasible and safe. However, both of these improvements have limitations and should be considered carefully.

No description available.

Introdução: A doença valvar aórtica grave é caracterizada por um processo de acúmulo progressivo de fibrose intersticial no tecido miocárdico. No contexto da sobrecarga mecânica crônica do VE característica dessa condição, a quantidade de fibrose intersticial pode exercer um papel importante na indesejável transição entre hipertrofia ventricular esquerda compensada e insuficiência cardíaca congestiva clinicamente manifesta. Entretanto, a avaliação quantitativa da fibrose intersticial só tem sido possível através da análise histopatológica de fragmentos miocárdicos obtidos por biopsia endomiocárdica. Objetivos: Avaliar se a ressonância magnética (RM) cardíaca com técnica do realce tardio permite a quantificação não-invasiva da fibrose miocárdica quando comparada à análise histopatológica em pacientes portadores de doença valvar aórtica grave. Adicionalmente, avaliou-se a relação entre a quantidade de fibrose miocárdica e parâmetros prognósticos importantes, tais como mortalidade e recuperação funcional do VE após cirurgia de troca valvar aórtica. Métodos: Entre Maio de 2001 e Dezembro de 2003 foram incluídos 54 pacientes com indicação de cirurgia de troca valvar aórtica. Antes da cirurgia, todos os pacientes foram submetidos a RM cardíaca com técnicas de cine-RM e realce tardio miocárdico. A quantificação da fibrose miocárdica pela RM baseou-se na análise das imagens de realce tardio utilizando um novo algoritmo semi-automático. As regiões de fibrose miocárdica foram definidas como o somatório de todos os pixels do tecido miocárdico com intensidade de sinal acima de um limiar definido como: intensidade de sinal média do miocárdio + 2 desvios padrão da intensidade de sinal média da área remota + 2 desvios padrão da intensidade de sinal média do ar. Amostras de tecido miocárdico obtidas por miectomia durante o ato cirúrgico foram submetidas a coloração pelo picrosírius para quantificação da fibrose intersticial. Os pacientes foram submetidos a um segundo exame de RM cardíaca 6 meses após a cirurgia para se avaliar as alterações evolutivas dos parâmetros funcionais do VE e todos foram acompanhados por pelo menos 24 meses quanto à sobrevida após a cirurgia de troca valvar aórtica. Resultados: O percentual de fibrose miocárdica pela RM apresentou boa correlação com os valores obtidos pela histopatologia (r=0,69; y=3,10x+13,0; p<0,0001). A quantidade de fibrose miocárdica, tanto pela histopatologia como pela RM, apresentou correlação inversa significativa com a FE ventricular esquerda basal (r=-0,63 e -0,67 respectivamente; p<0,0001). Adicionalmente, o percentual de fibrose miocárdica apresentou correlação inversa significativa com o grau de recuperação funcional do VE após a cirurgia de troca valvar (r=- 0,42, p=0,04 para a histopatologia; r=-0,47, p=0,02 para a RM). Mais importante, a análise de Kaplan-Meier revelou que o acúmulo de fibrose miocárdica associou-se a menor sobrevida 52±17 meses após a cirurgia de troca valvar (teste log-rank: 2=6,32; p=0,01 para histopatologia; 2=5,85; p=0,02 para RM). Conclusões: A RM cardíaca permite quantificar as regiões de fibrose miocárdica com boa acurácia quando comparada à análise histopatológica nos pacientes portadores de doença valvar aórtica grave. A magnitude de acúmulo de fibrose miocárdica está associada a pior recuperação funcional do VE e a menor sobrevida após a cirurgia de troca valvar aórtica. / Introduction: Severe aortic valve disease is characterized by a process of progressive accumulation of interstitial fibrosis in the myocardial tissue. It has been shown that the amount of interstitial myocardial fibrosis can play an important role in the transition from well-compensated hypertrophy to overt heart failure in the setting of chronic left ventricular mechanical overload typical of this condition. However, assessment of interstitial myocardial fibrosis has only been possible through histological analyses of myocardial fragments obtained from endomyocardial biopsies, which is a complex and invasive procedure and, therefore, with limited clinical applicability. Objectives: Determine whether delayedenhancement cardiac magnetic resonance imaging (MRI) allows for the non-invasive quantification of myocardial fibrosis when compared against histopathological analyses in patients with severe aortic valve disease. Additionally, we evaluated the relationship between the amount of myocardial fibrosis and important prognostic parameters, such as all-cause mortality and LV functional recovery after aortic valve replacement. Methods: Fifty-four patients scheduled to undergo aortic valve replacement surgery were enrolled between May 2001 and December 2003. Before surgery, all patients underwent cine and delayedenhancement MRI in a 1.5 Tesla scanner. Quantification of myocardial fibrosis by cardiac MRI was based on the assessment of the delayed-enhancement dataset using a novel semiautomatic algorithm. The regions of myocardial fibrosis were defined as the sum of pixels with signal intensity above a threshold value defined as: mean signal intensity of the myocardium + 2 standard deviations of mean signal intensity of a remote area + 2 standard deviations of mean signal intensity of air. During open-heart surgery, myectomy samples were acquired from the LV septum and later stained with picrosirius for interstitial myocardial fibrosis quantification. A second cardiac MRI study was performed 6 months after surgery to assess long-term changes in LV functional parameters, and all patients were followed for at least 24 months to evaluate survival after aortic valve replacement. Results: There was a good correlation between the values of myocardial fibrosis measured by MRI and those obtained by histopathological analyses (r=0.69; y=3.10x+13.0; p<0.0001). The amount of myocardial fibrosis, either by MRI or by histopathology, exhibited a significant inverse correlation with LV ejection fraction before surgery (r=-0.63 e -0.67 respectively; p<0.0001). Additionally, the amount of myocardial fibrosis displayed a significant inverse correlation with the degree of LV functional recovery after aortic valve replacement (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for MRI). Most importantly, Kaplan-Meier and Cox regression analyses revealed that higher degrees of myocardial fibrosis accumulation were associated with worse survival 52±17 months after aortic valve replacement surgery (log-rank test: 2=6.32; p=0.01 for histopathology; 2=5.85; p=0.02 for MRI). Conclusions: Cardiac MRI allows for the non-invasive quantification of myocardial fibrosis with good accuracy when compared with histopathological analyses in patients with severe aortic valve disease. The degree of myocardial fibrosis accumulation is associated with impaired LV functional recovery and worse survival after aortic valve replacement surgery.

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.

No description available.