O pericárdio bovino é um tecido biológico utilizado na fabricação de vários produtos para a saúde e também em válvulas cardíacas desde o início da década de setenta, porém, ainda requer estudos mais aprofundados no que diz respeito às mudanças que os tratamentos químicos utilizados para confecção das válvulas ocasionam. Atualmente a engenharia de tecidos estuda a descelularização do pericárdio bovino como um processo para retirar os componentes celulares, mantendo intacta a matriz extracelular (MEC), preservando a integridade do colágeno e também pode atuar como anticalcificante. Porém, é necessário saber qual o impacto que o tratamento químico trará nas propriedades mecânicas do tecido, como tensão máxima, deformação específica e alongamento. Nos trabalhos observados, os testes mecânicos realizados nos pericárdios bovinos descelularizados foram feitos no tecido sem serem submetidos a uma pré-tensão, a qual é necessária na maioria das vezes, para formação das cúspides durante a confecção das válvulas cardíacas ou outro dispositivo médico. Por essa razão, foi realizado um estudo do efeito na propriedade mecânica que uma determinada pressão exerce sobre o pericárdio bovino, que passou pelo processo de descelularização. Em paralelo também foi feito uma avaliação histológica do tecido para verificar a ausência de células e a preservação das fibras de colágeno no tecido descelularizado. Foram preparados quatro grupos diferentes para a realização dos testes. O grupo I chamado de grupo controle. O grupo II, onde os pericárdios foram descelularizados com o método PUC I. O grupo III foi tratado como o grupo I, porém sob pressão de 240 mmHg. Já o grupo IV, os pericárdios foram descelularizados e em seguida submetidos à mesma pressão utilizando solução de glutaraldeído 0,2% e 0,5%. Após os tratamentos dos grupos, todas as amostras foram tingidas em solução de azul de metileno 0,03% para melhor visualização das fibras do tecido. Em seguida os tecidos foram cortados a laser para obtenção dos corpos de prova e submetidos ao ensaio de tração. Obteve-se a partir do ensaio, a tensão máxima das amostras, a deformação específica e o alongamento na ruptura. Foi observado que nos grupos onde foram submetidos à pressão tiveram uma tensão máxima menor do que os grupos sem pressão e um maior alongamento. Verificou-se que o efeito da pressão diminuiu a espessura dos tecidos. O processo de descelularização se mostrou eficaz uma vez que foi demonstrada a ausência de células e a preservação das fibras de colágeno após técnica utilizada. / The pericardium is a biological tissue used in the manufacture of various products for medical advices and manufacture of heart valves since the early seventies, however, it still requires further study with regard to the changes that the chemical treatments used to manufacture the valves cause. Several studies show that the tissue often undergoes a process of calcification generated by mechanical stress of opening and closing of the leaflets, damaging the hydrodynamics making valvular replacement necessary. Currently tissue engineering study decellularization process of the bovine pericardium to remove cellular components while preserving the extracellular the matrix (ECM), preserving the integrity of collagen it and can also act as anti-calcification. However, one must know the impact that chemical treatment will bring on the mechanical properties of the tissue, such as tensile strength, strain and elongation percentage. In examined studies, the mechanical tests performed on bovine pericardium decellularized tissue was made without being subjected to a pre-tension which is necessary in most cases for formation of the leaflets during the manufacturing of heart valves. For this reason, a study of the effect on mechanical property that a certain pressure exerts on the pericardium, which passed the decellularization process was made. In parallel it was also made a histological evaluation of the tissue to verify the absence of cells and preservation of collagen fibers in decellularized tissue. Four different groups were prepared for test. The group I was called a control group. In group II, the pericardia were decellularized with the PUC method I. Group III was treated as group I, but under pressure of 240 mmHg. The group IV, the pericardia were decellularized and then subjected to pressure using glutaraldehyde 0.2% and 0.5%. After treatment of the groups, all samples were stained in a solution of blue methylene 0.03% for better visualization of the fibers of the tissue. Then the tissues were cut by laser to obtain the specimens and subjected to tensile test. It was obtained from the test, the tensile strength of the samples, the strain and elongation percentage at break. It is observed that the groups which underwent pressure had a lower tensile strength than those without pressure and on the other hand showed a greater elongation percentage. Thus, it can be verified that the effect of the pressure decreased the thickness of the tissues. The decellularization process has show efficient since it has demonstrated the absence of cells and preservation of collagen fibers after technique.

O pericárdio bovino tratado com glutaraldeído (GTA) e armazenado em formaldeído tem sido utilizado para confecção de biopróteses cardíacas ao longo das últimas décadas, já se tendo acumulado grande experiência com seu manuseio. Sabemos, no entanto, que o uso do GTA associadamente à presença de restos celulares existentes em meio às fibras de colágeno e elastina do pericárdio, são fatores indutores de resposta inflamatória e de enucleação de cristais de cálcio, o que compromete a durabilidade da bioprótese in vivo a longo prazo. No presente trabalho, tivemos como objetivo comparar a resistência mecânica do pericárdio decelularizado com o pericárdio convencional, assim como avaliar sua capacidade de induzir resposta inflamatória em modelo experimental com ratos. Para estudar as duas técnicas, dividimos os pericárdios em dois grupos: Grupo I - pericárdio submetido a tratamento convencional com GTA e Grupo II - pericárdio submetido a tratamento de decelularização previamente ao tratamento convencional com GTA. Após o processamento químico dos pericárdios, as amostras do Grupo II foram histologicamente avaliadas para confirmar a eficácia da decelularização. A seguir, analisamos a resistência mecânica nos dois grupos de pericárdio através dos testes de tração e de desnaturação térmica. Em nossa casuística, os dois grupos tiveram desempenho semelhante. A capacidade de induzir resposta inflamatória foi avaliada em estudo experimental em 50 ratos Wistar, machos, com 3 meses de idade, os quais foram submetidos a implante subcutâneo no abdome de fragmentos de pericárdio dos dois grupos. Igualmente, não evidenciamos diferença significativa. Nossa terceira etapa de avaliação consistiu em confeccionar 3 biopróteses (mitral n. 29) com o pericárdio decelularizado e que foram submetidas a avaliação hidrodinâmica juntamente com uma bioprótese convencional de teste. As biopróteses decelularizadas mostraram ter desempenho hidrodinâmico semelhante à prótese de teste e ao padrão de avaliação de próteses já conhecido da Braile Biomédica (S.J.Rio Preto-SP), todas atingindo a marca de 150 milhões de ciclos. A avaliação histológica do pericárdio das próteses ao fim da ciclagem mostrou padrão microscópico habitual, não tendo havido ruptura ou fragmentação anormal induzida por estresse mecânico. Temos como conclusão que a técnica de decelularização mantém a resistência física do pericárdio em comparação àquele convencionalmente preparado, não levando à fragmentação da matriz de colágeno e elastina e nem à perda de sua resistência mecânica tanto estática quanto dinâmica, além de não ter induzido resposta inflamatória diferente daquela habitualmente encontrada no pericárdio convencional / The bovine pericardium treated with glutaraldehyde (GTA) and stored in formaldehyde has been used in the manufacturing of cardiac bioprosthesis through the past decades, and a great knowledge has been acquired in this field. We know however that the use of the GTA and the presence of cell debris among the collagen and elastin fibers are triggers to induce inflammatory response and calcium deposition in the tissue, what compromises the long term durability of bioprosthesis in vivo. In this paper, our objective was to compare the decellularized and the conventional pericardium mechanical resistance and also its capability of inducing inflammatory response in an animal experimental model. In order to study these two techniques, we divided the pericardia into two groups: Group I- pericardia conventionally treated with GTA and Group II - pericardia previously decellularized and then conventionally treated with GTA. At first, after the pericardia chemical treatment, we performed histological analysis of Group II to certify the efficacy of the decellularization process. Afterwards, we analyzed the mechanical resistance in both groups using the stretching and shrinkage tests. In our samples, both groups had the same performance. The capacity of inducing inflammatory response was evaluated in an experimental study with 50 Wistar rats, male, 3 months old, which were operated to receive the pericardia patches of both groups underneath the dermal layer in the abdomen. We also did not find any difference between the groups. The third step of evaluation was to manufacture three decellularized bioprosthesis and one no decellularized one that were submitted to hydrodynamic tests. The decellularized and the test prosthesis showed the same performance and there was also no difference when compared with the known performance of the Braile Biomédica\'s (S.J.R. Preto-SP) bioprosthesis. They all reached 150 million cicles. The histological avaluation of the bioprosthesis showed the usual microscopic pattern, and there was no abnormal rupture or fragmentation caused by mechanical stress. We have therefore reached to the conclusion that the decellularization technique keeps the physical resistance of the pericardium when compared with the conventionally prepared. It does not cause damage or fragmentation of the collagen and elastin fibers and does not lead to loss of the mechanical resistance. And also, there was no difference in both groups regarding to inflammatory response studied in the animal model

A review of the literature revealed that 1) all prosthetic heart valves to date are plagued by certain problems, 2) all prosthetic valves in current clinical use are central-occlusion valves which do not effectively simulate natural valve action, and 3) the development of a true central-flow valve with the potential benefits of reduced pressure drop, turbulence, hemolysis, and thromboembolism could be a significant contribution. A central-flow, double-leaflet valve was developed. The wear, pressure drop, turbulence, and regurgitation associated with the new valve were evaluated. The wear test results indicated the need for additional testing using more wear resistant pin-bearing combinations. The flow tests revealed that the new valve with a 65 degree opening angle produced less pressure drop than other prostheses, but the new valve did not reduce turbulence as compared to other prostheses. In addition, the backflow and mean leak associated with the new valve were too high. Details of the testing procedures are presented and recommendations for future valve modifications and testing are included. / M.S.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--Stellenbosch University, 2008. / Aortic valve replacements are frequently performed during heart surgery. However, since this is quite a stressful procedure, many patients are turned down for medical reasons. Stented valves, designed and manufactured for percutaneous insertion, eliminate many of the risks involved in open-heart surgery, thus providing a solution to patients not deemed strong enough for open-chest aortic valve replacements. The aortic valve is a complex structure, and therefore numerical simulation is necessary to obtain flow and stress data to support the design of a prosthetic heart valve in the absence of viable physical measuring methods. To aid in the design of a prosthetic heart valve, various finite element valve models were created, and the fluid structure interaction (FSI) between the valves and the blood was simulated using commercial finite element software. The effect of the geometry of the leaflets on the haemodynamic behaviour over the cardiac cycle was investigated. It was found that leaflet dimensions should be chosen judiciously, because of their considerable effect on the stress distribution and performance of the valve. A simple leaflet geometry optimisation was done for a 20 mm and 26 mm valve, respectively, by means of existing geometry relationships found in the literature. Simulations were done to obtain the maximum leaflet attachment forces that can be used by a stent designer for fatigue loading, or to investigate the structural strength of the stent. These simulations were numerically validated. The effect of leaflet thickness and stiffness on resistance to opening, stress distribution and strain were investigated. Results showed that leaflet thickness has a greater effect on the performance of the valve than leaflet stiffness, and thereby validated the results of similar tests contained in the literature. After simulating over-, as well as under-dilation of a stented valve, it was found that problems associated with over-dilation can be minimised to a certain extent by increasing the coaptation1 region of the leaflets. A simple pulse duplicator was designed based on a four-element Windkessel model. The pulse duplicator was used to study the performance of the prototype valves by means of high-speed photography, the results of which were fed into one of the numerical finite element models and compared to real valve performance. Some of the prototype valves showed efficiencies of 88%.

Com o aumento da expectativa de vida nas últimas décadas, tem ocorrido aumento concomitante da prevalência da estenose aórtica degenerativa e da doença aterosclerótica arterial coronária. O presente estudo visa avaliar a influência da doença ateroslerótica arterial coronária crítica na mortalidade hospitalar de pacientes portadores de estenose aórtica submetidos à substituição valvar isolada ou combinada à revascularização do miocárdio. No período de janeiro de 2001 a março de 2006, no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram analisados 448 pacientes submetidos à substituição valvar aórtica isolada (grupo GI) e 167 pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio (grupo GII). Os dados pré-operatórios eleitos para análise foram: sexo, idade, índice de massa corpórea, antecedentes de: acidente vascular cerebral, diabete melito, doença pulmonar obstrutiva crônica, febre reumática, hipertensão arterial sistêmica, endocardite, infarto agudo do miocárdio, tabagismo, fração de ejeção do ventrículo esquerdo, doença aterosclerótica arterial coronária crítica, fibrilação atrial crônica; operação valvar aórtica prévia (conservadora), classe funcional de insuficiência cardíaca congestiva, valor sérico de creatinina e de colesterol total, tamanho da prótese utilizada, extensão (completa ou incompleta) e número de anastomoses distais da revascularização do miocárdio, tempo de circulação extracorpórea e tempo de pinçamento aórtico. No estudo estatístico empregou-se análise univariada (teste Qui-Quadrado e teste t de Student) e multivariada (regressão logística) para avaliação da influência da doença aerosclerótica arterial coronária crítica na mortalidade hospitalar dos dois grupos estudados. No grupo GI (substituição valvar aórtica isolada), a mortalidade hospitalar foi 14,3% (64 óbitos), sendo 14,5% (58 óbitos) nos pacientes sem doença aterosclerótica arterial coronária crítica associada (grupo GIB) e 12,8% (6 óbitos) nos que apresentavam essa associação (grupo GIA). No grupo GII (substituição valvar aórtica combinada à revascularização do miocárdio), a mortalidade hospitalar foi 17,6% (29 óbitos), sendo 16,1% (20 óbitos) nos pacientes submetidos à substituição valvar aórtica combinada à revascularização completa do miocárdio (grupo GIIA) e 20,9% (9 óbitos) nos com revascularização incompleta do miocárdio (grupo GIIB). Nos pacientes submetidos à substituição valvar aórtica isolada, a presença de doença aterosclerótica arterial coronária crítica associada, em pelo menos duas artérias, influenciou a mortalidade hospitalar (p= 0,016). Nos pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio, o número de artérias coronárias com doença aterosclerótica crítica e a extensão da revascularização do miocárdio realizada não influenciaram a mortalidade hospitalar (p>0,05), mas a realização de mais de três anastomoses distais influenciou (p= 0,03). / With the increase in life expectancy in recent decades has occurred concomitant increase in the prevalence of degenerative aortic stenosis and atherosclerotic coronary artery disease. This study aim to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of patients with aortic stenosis underwent isolated valve replacement or combined coronary artery bypass grafting. In the period of january 2001 to March 2006, at the Heart Institute University of Sao Paulo Medical Center were examined 448 patients underwent isolated aortic valve replacement (GI group) and 167 patients underwent combined aortic valve replacement and coronary artery bypass grafting (GII group). Preoperative data analised were: sex, age, body mass index, history of stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, myocardial infarction, smoking, chronic atrial fibrillation. Left ventricular ejection fraction, concomitant critical atherosclerotic coronary artery disease, previous surgical aortic valvuloplasty, congestive heart failure functional class, serum creatinine and cholesterol level, aortic valve prosthesis size, concomitant complete or incomplete coronary artery bypass grafting and number of bypass grafts, cardiopulmonary bypass and aortic cross clamping time. Univariate statistical analysis (Chi-square and Student\'s t test) and multivariate (logistic regression) were used to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of two groups. GI group (isolated aortic valve replacement) hospital mortality was 14.3% (64 deaths), and 14.5% (58 deaths) in patients without associated critical atherosclerotic coronary artery disease (GIB group) and 12.8% (6 deaths) in patients with that association (GIA group). GII group (combined aortic valve replacement and coronary artery bypass grafting) hospital mortality was 17.6% (29 deaths), and 16.1% (20 deaths) in patients underwent combined aortic valve replacement and complete coronary artery bypass grafting (GIIA group) and 20.9% (9 deaths) in patients with combined incomplete coronary artery bypass grafting (GIIB group). In patients underwent isolated aortic valve replacement, associated critical atherosclerotic coronary artery disease, of at least two arteries, influenced hospital mortality (p = 0016). In patients underwent combined aortic valve replacement and coronary artery bypass grafting, the number of coronary arteries with critical atherosclerotic disease and coronary artery bypass grafting extension didnt influenced hospital mortality (p> 0.05), but more than three coronary distal anastomoses influenced the hospital mortality (p = 0.03).

Com o aumento da expectativa de vida nas últimas décadas, tem ocorrido aumento concomitante da prevalência da estenose aórtica degenerativa e da doença aterosclerótica arterial coronária. O presente estudo visa avaliar a influência da doença ateroslerótica arterial coronária crítica na mortalidade hospitalar de pacientes portadores de estenose aórtica submetidos à substituição valvar isolada ou combinada à revascularização do miocárdio. No período de janeiro de 2001 a março de 2006, no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram analisados 448 pacientes submetidos à substituição valvar aórtica isolada (grupo GI) e 167 pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio (grupo GII). Os dados pré-operatórios eleitos para análise foram: sexo, idade, índice de massa corpórea, antecedentes de: acidente vascular cerebral, diabete melito, doença pulmonar obstrutiva crônica, febre reumática, hipertensão arterial sistêmica, endocardite, infarto agudo do miocárdio, tabagismo, fração de ejeção do ventrículo esquerdo, doença aterosclerótica arterial coronária crítica, fibrilação atrial crônica; operação valvar aórtica prévia (conservadora), classe funcional de insuficiência cardíaca congestiva, valor sérico de creatinina e de colesterol total, tamanho da prótese utilizada, extensão (completa ou incompleta) e número de anastomoses distais da revascularização do miocárdio, tempo de circulação extracorpórea e tempo de pinçamento aórtico. No estudo estatístico empregou-se análise univariada (teste Qui-Quadrado e teste t de Student) e multivariada (regressão logística) para avaliação da influência da doença aerosclerótica arterial coronária crítica na mortalidade hospitalar dos dois grupos estudados. No grupo GI (substituição valvar aórtica isolada), a mortalidade hospitalar foi 14,3% (64 óbitos), sendo 14,5% (58 óbitos) nos pacientes sem doença aterosclerótica arterial coronária crítica associada (grupo GIB) e 12,8% (6 óbitos) nos que apresentavam essa associação (grupo GIA). No grupo GII (substituição valvar aórtica combinada à revascularização do miocárdio), a mortalidade hospitalar foi 17,6% (29 óbitos), sendo 16,1% (20 óbitos) nos pacientes submetidos à substituição valvar aórtica combinada à revascularização completa do miocárdio (grupo GIIA) e 20,9% (9 óbitos) nos com revascularização incompleta do miocárdio (grupo GIIB). Nos pacientes submetidos à substituição valvar aórtica isolada, a presença de doença aterosclerótica arterial coronária crítica associada, em pelo menos duas artérias, influenciou a mortalidade hospitalar (p= 0,016). Nos pacientes submetidos à substituição valvar aórtica combinada à revascularização do miocárdio, o número de artérias coronárias com doença aterosclerótica crítica e a extensão da revascularização do miocárdio realizada não influenciaram a mortalidade hospitalar (p>0,05), mas a realização de mais de três anastomoses distais influenciou (p= 0,03). / With the increase in life expectancy in recent decades has occurred concomitant increase in the prevalence of degenerative aortic stenosis and atherosclerotic coronary artery disease. This study aim to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of patients with aortic stenosis underwent isolated valve replacement or combined coronary artery bypass grafting. In the period of january 2001 to March 2006, at the Heart Institute University of Sao Paulo Medical Center were examined 448 patients underwent isolated aortic valve replacement (GI group) and 167 patients underwent combined aortic valve replacement and coronary artery bypass grafting (GII group). Preoperative data analised were: sex, age, body mass index, history of stroke, diabetes mellitus, chronic obstructive pulmonary disease, rheumatic fever, hypertension, endocarditis, myocardial infarction, smoking, chronic atrial fibrillation. Left ventricular ejection fraction, concomitant critical atherosclerotic coronary artery disease, previous surgical aortic valvuloplasty, congestive heart failure functional class, serum creatinine and cholesterol level, aortic valve prosthesis size, concomitant complete or incomplete coronary artery bypass grafting and number of bypass grafts, cardiopulmonary bypass and aortic cross clamping time. Univariate statistical analysis (Chi-square and Student\'s t test) and multivariate (logistic regression) were used to evaluate the influence of critical atherosclerotic coronary artery disease in hospital mortality of two groups. GI group (isolated aortic valve replacement) hospital mortality was 14.3% (64 deaths), and 14.5% (58 deaths) in patients without associated critical atherosclerotic coronary artery disease (GIB group) and 12.8% (6 deaths) in patients with that association (GIA group). GII group (combined aortic valve replacement and coronary artery bypass grafting) hospital mortality was 17.6% (29 deaths), and 16.1% (20 deaths) in patients underwent combined aortic valve replacement and complete coronary artery bypass grafting (GIIA group) and 20.9% (9 deaths) in patients with combined incomplete coronary artery bypass grafting (GIIB group). In patients underwent isolated aortic valve replacement, associated critical atherosclerotic coronary artery disease, of at least two arteries, influenced hospital mortality (p = 0016). In patients underwent combined aortic valve replacement and coronary artery bypass grafting, the number of coronary arteries with critical atherosclerotic disease and coronary artery bypass grafting extension didnt influenced hospital mortality (p> 0.05), but more than three coronary distal anastomoses influenced the hospital mortality (p = 0.03).

The field of structural design optimization is one with great breadth and depth in many engineering applications. From the perspective of a designer, three distinct numerical methodologies may be employed. These include size, shape, and topology optimization, in which the ordering typically (but not always) corresponds to the order of increasing complexity and computational expense. This, of course, depends on the particular problem of interest and the selected numerical methods. The primary focus of this research employs density-based topology optimization with the goal of improving structural resistance to failure. Beginning with brittle fracture, two topology optimization based formulations are proposed in which low weight designs are achieved with substantially increased fracture resistance. In contrast to the majority of the current relevant literature which favors stress constraints with linear elastic physics, we explicitly simulate brittle fracture using the phase field method during the topology optimization procedure. In the second formulation, a direct comparison is made against results obtained using conventional stress-constrained topology optimization and the improved performance is numerically demonstrated. Multiple enhancements are proposed including a numerical efficiency gain based on the Schur-complement during the analytical sensitivity analysis and a new function which provides additional path information to the optimizer, making the gradient-based optimization problem more tractable in the presence of brittle fracture physics. Subsequently, design for ductile failure and buckling resistance is addressed and a numerically efficient topology optimization formulation is proposed which may provide significant design improvements when ductile materials are used and extreme loading situations are anticipated. The proposed scheme is examined regarding its impact on both the peak load carrying capacity of the structure and the amount of external work required to achieve this peak load, past which the structure may no longer be able to support any increase in the external force. The optimized structures are also subjected to a post-optimization verification step in which a large deformation phase field fracture model is used to numerically compare the performance of each design. Significant gains in structural strength and toughness are demonstrated using the proposed framework. Additionally, the failure behavior of 3D-printed polymer composites is investigated, both numerically and experimentally. A large deformation phase field fracture model is derived under the assumption of plane-stress for numerical efficiency. Experimental results are compared to numerical simulations for a composite system consisting of three stiff circular inclusions embedded into a soft matrix. In particular, we examine how geometric parameters, such as the distances between inclusions and the length of initial notches affect the failure pattern in the soft composites. It is shown that the mechanical performance of the system (e.g. strength and toughness) can be tuned through selection of the inclusion positions which offers useful insight for material design. Finally, a size optimization technique for a cardiovascular stent is proposed with application to a balloon expandable prosthetic heart valve intended for the pediatric population born with Congenital Heart Disease (CHD). Multiple open heart surgical procedures are typically required in order to replace the original diseased valve and subsequent prosthetic valves with those of larger diameter as the patient grows. Most expandable prosthetic heart valves currently in development to resolve this issue do not incorporate a corresponding expandable conduit that is typically required in a neonate without a sufficiently long Right Ventricular Outflow Tract (RVOT). Within the context of a particular design, a numerical methodology is proposed for designing a metallic stent incorporated into the conduit between layers of polymeric glue. A multiobjective optimization problem is solved, not only to resist the retractive forces of the glue layers, but also to ensure the durability of the stent both during expansion and while subject to the anticipated high cycle fatigue loading. It is demonstrated that the surrogate-based optimization strategy is effective for understanding the trade-offs between each performance metric and ultimately efficiently arriving at a single optimized design candidate. Finally, it is shown that the desired expandability of the device from 12mm to 16mm inner diameter is achievable, effectively eliminating at least one open heart surgical procedure for certain children born with CHD.

Le nombre d’adultes porteurs d’une tétralogie de Fallot opérée dans l’enfance est en constante augmentation. Initialement, ces patients étaient considérés comme guéris. A l’âge adulte, ils présentent en fait des complications d’ordre rythmique, responsables de morts subites, et des complications d’ordre mécanique : dilatation du ventricule droit (VD) liée à l’insuffisance pulmonaire chronique, séquellaire de la première chirurgie de réparation de la cardiopathie. Les mécanismes de l’arythmie ainsi qu’une éventuelle interaction entre la dysfonction VD et la survenue de ces arythmies ne restent que partiellement élucidés. Dans ce travail, en couplant les données d’études cliniques et les données expérimentales issues d’un modèle animal (MA) mimant une tétralogie de Fallot réparée, nous avons montré que 1) l’échocardiographie ne pouvait pas se substituer à l’IRM pour la surveillance des patients avec tétralogie de Fallot réparée 2) la valvulation pulmonaire restait une intervention à risque de mortalité 3) une bioprothèse non stentée était une bonne solution pour effectuer cette valvulation 4) en cas de fuite tricuspidienne sévère lors de cette valvulation, une plastie était indispensable 5) plusieurs gènes participaient au remodelage ventriculaire droit (analyse génétique effectuée sur le MA) 6) le remodelage électrophysiologique du VD (MA) s’accompagnait de propriétés pro-arythmogènes. Les mécanismes de décompensation sont intriqués : un lien entre dysfonction VD et arythmie paraît bien établi. D’autres analyses électrophysiologiques sont en cours au niveau du ventricule gauche (MA), pour rechercher d’autres mécanismes pro-arythmogènes. / The number of adults with a repaired tetralogy of Fallot is increasing. In the past, those patients were considered healed. Nonetheless, they present arrhythmogenic issues, with frequent sudden death, and mechanical complications: right ventricular dilation due to long lasting pulmonary valve regurgitation, secondary to surgical repair. The origin of arrhythmia and its interaction with right ventricular dysfunction is only partially understood. In this study, combining clinical with experimental data, we pointed out: 1) concerning the follow-up of this population, echocardiography is not a substitute to MRI 2) operative mortality of pulmonary valve replacement (PVR) still exists 3) a stentless bioprosthesis represents a valid solution for PVR 4) a valve repair is mandatory for severe tricuspid valve regurgitation at PVR 5) the genetic analysis carried out in an animal model of repaired tetralogy of Fallot, demonstrated the involvement of numerous genes in right ventricular remodeling 6) remodeling of the right ventricle in this animal model generates pro-arrhythmic substrate. Heart failure mechanisms in repaired tetralogy of Fallot are complex: a link between right ventricular dysfunction and arrhythmias is demonstrated. Further studies are needed to investigate other pro-arrhythmic mechanisms involving the left ventricle.