Background: Valvular heart disease (VHS) can be lethal. An auscultated murmur could be a first indication of VHS. Lately auscultation has been evaluated as non-accurate, while a murmur also can be normal/functional. The next step of verifying VHS, is a transthoracic echocardiography (TTE). The echocardiography clinic at Uppsala University Hospital has seen a lot of non-pathological referrals regarding murmur evaluation. Therefore, a fast-track screening TTE, performed by a biomedical scientist was of interest. Aim: The aim was to evaluate pathological possibility, regarding remitted patients with a new heart murmur. Material: The clinical quality work was based on remitted patients of ages 18 to 50. Sampling took place between November 2022 and Mars 2024, by Radiology Information System. Method: Type of murmur, outcomes and referring clinic was documented. Normal outcome group consisted of: absent VHS and mild VHS. Pathological outcome group consisted of: moderate and severe VHS. Probability was calculated based on systolic- and non-specified murmur. Result: Normal outcome group had 116 referrals and pathological outcome group had three referrals. Possibility of a pathological outcome became 2,5 %. Majority of the referrals came from the primary care (92 %). Conclusion: A systolic- and non-specified murmur had low possibility of a pathological outcome, which could indicate that a shorter screening TTE by a biomedical scientist is an option. A limitation was that the type of the remitted murmur could not be trusted. Majority of the referrals came from the primary care, which indicates that further clinical work at these facilities is necessary.

Made available in DSpace on 2016-08-29T15:37:24Z (GMT). No. of bitstreams: 1 tese_6105_DISSERTAÇÃO - MARCELO CHAMELETE.pdf: 666740 bytes, checksum: 2059fc425fdbafd74ebe3793f976627d (MD5) Previous issue date: 2012-03-30 / Das doenças cardíacas caninas, a degeneração valvar mixomatosa é a de maior prevalência na rotina da clínica médica, podendo levar a insuficiência cardíaca. Sabe-se que é uma doença de caráter crônico e progressivo sem cura, cujo controle depende, principalmente da inibição da ativação dos mecanismos compensatórios neuroendócrinos. A melhor estratégia da terapia depende da gravidade da doença e fatores individuais, tornando o tratamento da doença desafiador, e precipitando a necessidade de monitorização constante do paciente. Um bloqueio da ativação de mecanismos compensatórios mais amplo tem sido utilizado em insuficientes cardíacos humanos com os fármacos bloqueadores de receptores de angiotensina II (BRAs). Muitas são as pesquisas demonstrando os benefícios da utilização dos BRAs em insuficientes cardíacos humanos, porém em cães a pesquisa ainda é escassa. No presente trabalho objetivou-se revisar a degeneração valvar mixomatosa em cães e o tratamento padrão, assim como revisar a utilização dos BRAS. Objetivou-se também com essa pesquisa, avaliar os efeitos do bloqueador de receptor de angiotensina II, o valsartan em 20 semanas em cães com degeneração valvar mixomatosa. Foram obtidos dados clínicos, eletrocardiográficos, ecocardiográficos, laboratoriais antes da introdução do valsartan a 0,5 mg/kg a cada 24 horas e a cada quatro semanas até completarem-se 20 semanas. Pode-se notar que a relação Ae/Ao em nenhum momento foi maior que 1,7, apesar do constante remodelamento, não havendo diferença significativa entre o momento inicial e o final. O índice de volume sistólico se manteve aumentado durante todo o experimento, e o índice de volume diastólico aumentou no M3 mas retornou ao valor semelhante igual ao do início. A pressão arterial sistêmica sistólica não apresentou alteração estatística. Não houve alteração de valores hematológicos, porém a elevação das as enzimas hepáticas sugeriram sobrecarga hepática. A ausência de efeitos colaterais e a manutenção de fatores clínicos, eletrocardiográficos, laboratoriais e ecocardiográficos, importantes para o bom prognóstico, revela que o valsartan na dose de 0,5 mg/kg pode ser uma opção eficaz e segura em cães com insuficiência cardíaca congestiva de corrente da doença valvular crônica.

Objectives A substantial number of patients with severe tricuspid regurgitation (TR) and congestive heart failure (CHF) are medically managed without undergoing corrective surgery. We sought to assess the characteristics and outcomes of CHF patients who underwent tricuspid valve surgery (TVS), compared with those who did not. Methods Retrospective observational study involving 2556 consecutive patients with severe TR from the Cleveland Clinic Echocardiographic Database. Cardiac transplant patients or those without CHF were excluded. Survival difference between patients who were medically managed versus those who underwent TVS was compared using Kaplan-Meier survival curves. Multivariate analysis was performed to identify variables associated with poor outcomes. Results Among a total of 534 patients with severe TR and CHF, only 55 (10.3%) patients underwent TVS. Among the non-surgical patients (n=479), 30% (n=143) had an identifiable indication for TVS. At 38 months, patients who underwent TVS had better survival than those who were medically managed (62% vs 35%; p<0.001). On multivariate analysis, advancing age (HR: 1.23; 95% CI 1.12 to 1.35 per 10-year increase in age), moderate (HR: 1.39; 95% CI 1.01 to 1.90) and severe (HR: 2; 95% CI 1.40 to 2.80) right ventricular dysfunction were associated with higher mortality. TVS was associated with lower mortality (HR: 0.44; 95% CI 0.27 to 0.71). Conclusion Although corrective TVS is associated with better outcomes in patients with severe TR and CHF, a substantial number of them continue to be medically managed. However, since the reasons for patients not being referred to surgery could not be ascertained, further randomised studies are needed to validate our findings before clinicians can consider surgical referral for these patients. / Revisión por pares

Les valvulopathies cardiaques sont des maladies cardiaques fréquentes. Certaines se traduisent par un manque de coaptation des valves, on désigne ce type de pathologie sous le terme d’insuffisance. Le traitement standard de ces valvulopathies consiste à remplacer les valves malades par des valves prothétiques. L'absence de substitut valvulaire idéal et les inconvénients inhérents au matériel prothétique et à la nécessité d’un traitement anticoagulant, incitent à favoriser, chaque fois que cela est possible, les techniques de chirurgie conservatrice des valves. Actuellement, la réparation de la valve aortique demeure un défi chirurgical. En revanche en ce qui concerne la valve mitrale une réparation est plus souvent réalisable. Cependant, la faisabilité et le résultat final, dépends du mécanisme de la fuite, de l’extension des lésions ainsi que de la technique de réparation chirurgicale utilisée. C’est pour tenter de surmonter tous ces obstacles qu’est né le projet d’étude des forces magnétiques d’aimants permanents comme traitement complémentaire à une plastie ou comme traitement exclusif, pour rétablir une coaptation valvulaire efficace. Pour concrétiser cette idée, nous avons réalisé notre recherche en trois étapes essentielles : 1- La conception d’un système magnétique d’aide à la coaptation. 2- Une étude de faisabilité portant sur la vérification du fonctionnement des aimants in vitro et in vivo. 3- La vérification de l’efficacité de la force magnétique pour atteindre la coaptation nécessaire pour corriger l’insuffisance valvulaire. Cette recherche a été réalisée en étroite collaboration entre le service de Chirurgie Thoracique et Cardio-vasculaire du groupe hospitalier Pitié-Salpêtrière à Paris et le groupe de recherche électrodynamique - GREM3 - du Laboratoire LAPLACE à Toulouse. Les aimants ont été fabriqués en tenant compte des facteurs suivants : la biocompatibilité, la conservation de l'aimantation en milieu sanguin, la flexibilité mécanique des éléments implantés, et la nécessité de stérilisation. L'une des préoccupations principales était d’obtenir une force magnétique adaptée pour fermer la valve et permettre son ouverture en fonction du cycle cardiaque. Dans un deuxième temps, sur la base des concepts précédemment décrits, et après réalisation des tests in vitro, une étude expérimentale a été réalisée in vivo en vue de démontrer la faisabilité du projet. Cette phase d’expérimentation animale a consisté en l’implantation d’aimants permanents sur la valve aortique chez sept moutons gardés en vie pendant 3 mois. Les résultats ont été satisfaisants : aucun prolapsus iatrogène, parfaite bio-tolérance des aimants implantés sans nécessité de traitement anticoagulant, absence de réaction inflammatoire visible à l’autopsie après sacrifice des moutons au troisième mois postopératoire. En dernier lieu, afin d’étudier la valeur de la force magnétique nécessaire pour atteindre la coaptation souhaitée dans l’insuffisance valvulaire, trois modèles d’aimants ont été implantés chez quatre moutons. Malheureusement les résultats n’ont pas été entièrement satisfaisants. Actuellement, forts des enseignements tirés de ces expériences, nous tentons d’améliorer le problème de fabrication des aimants ; de nouveaux aimants sont en cours de réalisation. A notre connaissance, l’utilisation de la force magnétique pour corriger l'insuffisance valvulaire n'a jamais été rapportée dans la littérature. Même si la phase d’expérimentation des aimants destinés à traiter ces insuffisances valvulaires n’est pas arrivée à son terme, nous avons montré la faisabilité du concept sur valve saine. Ce champ d'investigation doit continuer à être exploré compte tenu des avantages qu’ont ces aimants. D’une part, ils sont techniquement faciles à poser et pourraient donc permettre de réaliser une réparation rapide et reproductible des valves. D’autre part, en raison de cette simplicité, on pourrait envisager une implantation par voie percutanée exclusive, ouvrant alors une voie nouvelle, en matière de chirurgie conservatrice des insuffisances valvulaires cardiaques (aortique et mitrale). / Valvular heart diseases are important cardiac pathology and valvular heart insufficiency is one of them. The standard treatment is valve replacement with prosthetic valve. Lacks of ideal prosthetic valve and the drawbacks inherent in prosthetic material and anticoagulant therapy, encourage us to develop techniques of conservative surgery of the valve. Today, repair of the aortic valve remains a surgical challenge, but mitral valve repair is frequently possible. However, the result and possibility of repair depends on the mechanism of insufficiency and the extension of the lesion of the mitral valve. For overcoming all these obstacles, we proposed the theory to study of the magnetic forces of permanent magnets as an adjuvant, or as exclusive treatment to restore effective valve coaptation. To realize this idea, we based our research on three steps: 1 - Characterization of magnets required. 2 - Feasibility study of the magnets in vitro and in vivo 3 - Verification of the effectiveness of the magnetic force to achieve the desired coaptation in valvular insufficiency. This research is done in collaboration between the department of Thoracic and Cardiovascular surgery of Pitié-Salpêtrière hospital in Paris and the research group Electrodynamics - GREM3 LAPLACE Laboratory in Toulouse. The magnets were fabricated by taking into account the following factors: lowprofile and permanency; biocompatibility; the conservation of magnetization in a blood medium; mechanical flexibility of the implanted elements; and the possibility of sterilization. One of the main concerns was to elaborate the adapted intensity of the magnetic force, such that it would be sufficiently strong to close the valve, yet be weak enough to allow valve opening during cardiac cycle. To assess the feasibility, before conducting experiments in animals, in vitro data were obtained and judged appropriate by using a circulating pig heart model with a paracorporeal pneumatic (Thoratec®) ventricular assist device. The phase of animal testing was carried out by the establishment of three permanent magnets on the aortic valve in seven sheep kept alive for 3 months and the results were satisfactory: - No iatrogenic prolepses, - Perfect bio-tolerance without the need for anticoagulation - No visible inflammatory reaction at autopsy on the third postoperative month. Finally, to study the effectiveness of the magnetic force to achieve the desired coaptation in valvular insufficiency, three models of magnets have been tested on 4 sheep, but the results were not satisfactory. Currently we try to solve the problem and new magnets are by the way of conception. To our knowledge, the use of magnetic force to correct valvular incompetence has never been reported. Even if the experimental phase of magnets for treating valvular insufficiency has not reached its conclusion, we demonstrated the feasibility of the concept of healthy valve. This field of investigation must continue to be explored because the magnets have several advantages. On the one hand, they are technically easy to perform, and could thus allow a rapid repair. On the other hand, because of this simplicity, we could consider a percutaneous implantation, which will open a new way for conservative surgery in valvular insufficiency.

According to statistics from the American Heart Association, valvular heart disease directly leads to about 20,000 deaths a year and contributes to an additional 50,000. While significant advancements have been made in the treatment options available for valvular heart disease, complications still occur. For this reason, the future of valvular heart disease treatment lies in understanding the physiology of the heart valve, and subsequently bioengineering a valve from one's own tissue to mimic native valve processes. Valvular interstitial cells (VICs) are the major cell type populating the valve matrix. In the inactive fibroblast-like state, these cells are responsible for extracellular matrix deposition. Activated VICs display a myofibroblast morphology characterized by the expression of alpha smooth muscle actin and are responsible for valve maintenance and repair. The activation of VICs is hypothesized to be stimulated by mechanical tension, which, in the presence of TGF-â1 allows the complete differentiation of VICs from the inactive to the active form. However, little is known about the potential for reversal or dedifferentiation from the active to inactive state. The purpose of this study was to determine whether substrate stiffness, the mechanical tension hypothesized to initiate VIC activation, modulates alpha smooth muscle actin expression in the presence and absence of TGF-â1. To mimic conditions found in vivo, substrates were varied from physiologic to pathological stiffness levels. Results showed that when freshly isolated VICs are cultured in the presence of serum, alpha smooth muscle actin expression increased on all substrate stiffnesses. In TGF-â-free medium, there was an apparent increase on all stiffness levels as well, but a statistical significance between groups could not be demonstrated. Immunoblots used to detect TGF-â1 showed that intracellular TGF-â1 was upregulated in VICs cultured in the presence of serum compared to those cultured in TGF-â-free medium. Taken together, these results suggest that freshly isolated VICs become activated, as indicated by increased expression of alpha smooth muscle actin, on all substrate levels in the presence of serum. It also appears as though unknown factors which are present in serum are required to stimulate significant autocrine production of TGF-â1. To determine whether VICs which had transitioned to the myofibroblast phenotype had the ability to dedifferentiate, cells were cultured on polystyrene for a minimum of four days then replated on substrates of varying stiffness. Analysis of alpha smooth muscle actin expression showed that, in the presence of serum and when replated on all of substrates used, alpha smooth muscle actin expression decreased, suggesting that these cells indeed have the potential to dedifferentiate. A change in cell morphology to a more rounded phenotype as well as the loss of visible stress fibers further supported this possibility. These studies represent a unique approach to studying phenotypic differentiation of valvular interstitial cells. Using acrylamide substrates of varying stiffness, and growth factor free media, we have shown that by altering substrate stiffness, changes in alpha smooth muscle actin expression consistent with differentiation and dedifferentiation can be induced. This potential for dedifferentiation suggests that in engineering the next generation of bioartificial valves, it may be possible to use the patient's own cells to seed the manufactured scaffold. This would avoid complications associated with current treatments, including immune rejections.

No description available.

Since living conditions have improved and antibiotics have entered routine use, valvular heart disease (VHD) in the developed world is mostly degenerative in origin, rather than rheumatic. Our population is increasing with age, and therefore the burden of VHD is likely to increase. Despite this, the epidemiology & prognostication in VHD remain poorly understood. A better understanding of the prevalence of VHD in our population, and improved methods of predicting outcomes, are essential if we are to be better equipped to meet the challenges of this new “epidemic”. This thesis aims to improve our knowledge of the prevalence of VHD in the elderly, and the potential benefits of cardiac magnetic resonance (CMR) assessment of patients with clinically significant mitral regurgitation. The prevalence of undiagnosed valvular heart disease in those aged 65 and over is examined in Chapters 2 and 3. Chapter 2 outlines a population-based screening study for VHD in primary care in Oxfordshire, which the author played a central role in establishing. The results show that VHD is extremely common in this cohort, and is strongly associated with increasing age. In chapter 4, the level of anxiety provoked by screening for VHD is looked at; this demonstrates that only a small number of patients have significant anxiety levels, but it is more likely in those with a new diagnosis of VHD, and in women. From Chapter 5 onwards, the thesis focuses on the use of CMR in patients with significant mitral regurgitation (MR). In Chapter 5, the clinical value of quantitative assessment of MR using CMR is examined, showing that it was able to predict progression to symptoms or surgery in these patients. In conclusion, this thesis offers insights into the prevalence of VHD in the elderly population, and looks at the anxiety associated with looking for VHD in this group. The potential clinical benefits of CMR in patients with MR are examined, and quantification of MR with this modality would appear to be of prognostic utility.

La endocarditis infecciosa (EI) es una enfermedad potencialmente muy grave, que puede llegar a ser mortal sin tratamiento, cuyo pronóstico ha experimentado una gran mejoría en las ultimas décadas. Este importante cambio en la historia natural de la enfermedad se ha reflejado en una progresiva disminución de la morbi-mortalidad, sobretodo gracias al uso de potentes antibióticos y al empleo de las técnicas quirúrgicas de reparación valvular. La EI es la infección del endotelio de las válvulas cardiacas por gérmenes patógenos. La elevada morbi-mortalidad de la EI se debe a la destrucción que se produce en las válvulas y los tejidos circundantes, debido a la particular anatomía valvular que impide la correcta difusión de los antibióticos al interior de las vegetaciones valvulares. La EI tenía en la era-preantibiótica una mortalidad del 100%. El gran descenso en la mortalidad se ha producido en las últimas tres décadas, con el desarrollo de la cirugía cardiaca y la posibilidad de efectuar recambios valvulares. Con la introducción de la ecocardiografía se han podido visualizar por primera vez mediante un método incruento las vegetaciones valvulares. El desarrollo de esta técnica de imagen ha sido fundamental y en la actualidad tiene un papel clave en el diagnóstico y manejo de esta entidad ya que permite estudiar con gran detalle la anatomía cardiaca. En la actualidad, la mortalidad por EI sobre válvula nativa en fase aguda oscila entre el 20% y el 30% y la supervivencia a los 10 años de seguimiento se sitúa entre el 70% y el 80%. El pronóstico de la EI depende de un gran número de variables. Las complicaciones perianulares en la endocarditis infecciosa representan la extensión de la infección más allá de las estructuras valvulares y representan una de las complicaciones más importantes en esta enfermedad. La formación de lesiones perianulares se asocia a un pronóstico desfavorable, con elevada mortalidad. La formación de fístulas aorto-cavitarias en la endocarditis sólo se ha descrito de forma ocasional en la endocarditis y, por ello, se desconocen sus características clínicas y sus factores pronósticos de mortalidad.La hipótesis del estudio es que la presencia de complicaciones graves en la EI (desarrollo de abscesos perianulares y fístulas aorto-cavitarias) detectadas por ecocardiografía se asocia a un incremento significativo de la morbi-mortalidad. El análisis de las características clínicas y pronósticas permitiría identificar los parámetros asociados a un curso desfavorable; de esta forma podrían redefinirse las líneas de actuación (fundamentalmente quirúrgicas) encaminadas a un abordaje más temprano en pacientes seleccionados, con más posibilidades de reconstrucción completa y erradicación de la infección. Identificar estas variables permitiría, en definitiva, aumentar la supervivencia a corto y medio plazo de los casos de EI complicada.Los objetivos de este estudio son: determinar las características clínicas y el pronóstico de los pacientes con abscesos perianulares íntegros y de pacientes con fistulización aorto-cavitaria en la endocarditis y determinar el impacto sobre el pronóstico de la aparición de fistulización aorto-cavitaria en la endocarditis complicada con lesiones perianulares.Se han publicado varios estudios multicéntricos con el objetivo de reclutar una gran serie de pacientes con complicaciones perianulares y poder estudiar con detalle las características clínicas de estas complicaciones y poder analizar sus factores pronósticos de mortalidad.ARTICULOS PUBLICADOSARTICULO 1:Anguera I, Quaglio G, Miró JM, Paré C, Azqueta M, Marco F, Mestres CA, Moreno A, Pomar JL, Mezzelani JL, Sanz G. Acquired aortocardiac fistulas complicating infective endocarditis. Am J Cardiol 2001;87:652-654. Impact factor (2005) : 3.14ARTICULO 2:Anguera I, Miro JM, Vilacosta I, Almirante B, Anguita M, Muñoz P, San Roman JA, de Alarcón A, Ripoll T, Navas E, Gonzalez-Juanatey C, Cabell CH, Sarriá C, Garcia-Bolao I, Fariñas MC, Leta R, Rufi G, Miralles F, Pare C, Evangelista A, Fowler Jr VG, Mestres CA, de Lazzari E, Guma JR. Aorto-cavitary fistulous tract formation in infective endocarditis. Clinical and echocardiographic features of 76 cases and risk factors for mortality. Eur Heart J 2005;26:288-297. Impact factor (2005) : 6.25ARTICULO 3: Anguera I, Miro JM, Evangelista A, Cabell CH, San Roman JA, Vilacosta, Almirante B, Ripoll T, Fariñas MC, Anguita M, Navas E, Gonzalez-Juanatey C, Garcia-Bolao I, Muñoz P, de Alarcón A, Sarriá C, Rufi G, Miralles F, Pare C, Fowler Jr VG, Mestres CA, de Lazzari E, Guma JR, Corey GR. Prognostic factors of mortality of Periannular complications in infective endocarditis. A multicenter cohort study of 351 patients with aorto-cavitary fistulae and non-ruptured periannular abscess (1992-2003). Am J Cardiol 2005 (en revisión editorial).ARTICULO 4: Anguera I, Miro JM, Cabell CH, Abrutyn E, Fowler VG, Hoen B, Olaison L, Stafford JA, Eykyn S, Habib G, Pare C, Wang A, Corey R and the ICE-MD Investigators. Characteristics of aortic periannular abscesses studied with transesophageal echocardiography. A report from the ICE-ME database. Am J Cardiol 2005;96:976-981. Impact factor (2005) : 3.14Como resultado de este estudio, puede concluirse que la fistulización aorto-cavitaria es una complicación infrecuente de la endocarditis infecciosa, que se asocia a una extensa destrucción tisular a nivel del anillo aórtico y a la presencia de abscesos perianulares. La ecocardiografía transesofágica es la técnica de elección para la detección y el estudio de las fístulas aorto-cavitarias. La aparición de insuficiencia cardiaca grave es frecuente en estos pacientes, y a pesar del tratamiento quirúrgico agresivo la mortalidad es elevada. La infección protésica, la cirugía urgente y el desarrollo de insuficiencia cardiaca son los factores pronósticos independientes de mortalidad en los pacientes con fístulas aorto-cavitarias en la endocarditis. La formación de fístulas aorto-cavitarias se asocia a un mayor grado de destrucción anular aórtica y con mayor frecuencia de desarrollo de insuficiencia cardiaca en comparación con los abscesos no fistulizados. Ambas complicaciones requieren con mucha frecuencia tratamiento quirúrgico y tienen una elevada mortalidad, pero la fistulización no constituye un factor pronóstico independiente de mortalidad, tanto a corto como a largo plazo. La formación de abscesos perianulares es frecuente en la endocarditis de localización aórtica, se asocia frecuentemente con infección estafilocócica, y tiene una elevada morbi-mortalidad. La infección estafilocócica es un factor de riesgo independiente de mortalidad en los pacientes que desarrollan abscesos perianulares a nivel aórtico. / Title: "The study of periannular complications in infective endocarditis. Analysis of clinical, microbiological, echocardiographic, therapeutic and prognostic aspects of patients with non-ruptured periannular abscesses and with aorto-cavitary fistulous tract formation in IE"Infective endocarditis (IE) is a devastating disease associated with high death rates without appropriate treatment. The prognosis of IE has changed dramatically during the last three decades due to the use of potent antibiotics and the generalization of surgical therapies of valve repair. Infective endocarditis is characterized by the infection of the endothelium of cardiac valves caused by virulent organisms, and the elevated morbidity and mortality is produced by the destruction of valvular tissue and adjacent structures. In the modern era, one-year mortality of native valve IE is in the range of 20% - 30%, and 10-year survival is in the range of 70%-80%. Spread of infection in IE from valvular structures to the surrounding perivalvular tissue results in periannular complications. Periannular complications, including periannular abscess formation and aorto-cavitary fistulous (ACF) tract formation have not been adequately studied, and may place the patient at increased risk of adverse outcomes including heart failure (HF) and death. Aorto-cavitary fistulous tract formation has only been described occasionally.The main objectives of the present investigation were to investigate the clinical characteristics and the prognosis of patients with non-ruptured periannular abscesses and with aorto-cavitary fistulous tract formation in IE and to determine the prognostic impact of fistulization in patients with periannular lesions in the setting of IE.Several manuscripts including a large number of patients with periannular lesions have been published describing the clinical characteristics and prognostic factors of mortality of patients with periannular lesions in IE.Aorto-cavitary fistula is an uncommon complication of aortic IE associated with extensive aortic root destruction and presence of periannular abscesses. Transesophageal echocardiography is the diagnostic tool of choice for the detection of aorto-cavitary fistulae in both native and prosthetic valves. Despite aggressive surgical treatment, rates of heart failure and mortality are high. Prosthetic IE, urgent surgery and the development of heart failure were associated with an increased risk of death in patients with endocarditis complicated by fistulous tract formation. ACF formation in the course of IE is associated with higher rates of aortic annulus destruction and heart failure compared to non-ruptured abscess. Surgery and mortality rates for both complications were very high; however, despite the higher complications, ACF in the current era of high rates of surgical therapy was not an independent risk factor for mortality.Periannular abscess formation occurs frequently in aortic valve IE, is associated with staphylococcal etiology, and has a high morbidity and mortality. In the current era of TEE imaging and high use of surgical treatment periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. Finally, S. aureus infection constitutes an independent prognostic factor for mortality in patients who develop an abscess.

Resumo: Foi construído um simulador de fadiga para próteses valvulares cardíaca, com osrecursos próprios do Laboratório de Máquinas Térmicas da Universidade Federal doParaná e materiais disponíveis no comércio local.Foi possível realizar ensaios com velocidades de até 2.540 ciclos por minuto.Com auxílio da estroboscopia é possível verificar o fechamento e a abertura totais,bem como as posições intermediárias.Foram obtidas, em escala, as curvas de pressão x tempo transprotéticas, obteve-setambém fotografias e filmagens em vídeo das próteses nas posições aberta,intermediárias e fechada, bem como suas nuances frente às alterações de fluxo epressão.Foi possível detectar, com a máquina em funcionamento, a ocorrência de problemasde fadiga nas referidas próteses após 42 milhões de ciclos.Os resultados obtidos foram compatíveis com as normas preconizadas e osresultados encontrados na literatura.

The aortic valve maintains unidirectional blood flow between the left ventricle and the systemic circulation. When diseased, the valve is replaced either by a mechanical or a bioprosthetic heart valve, that carry issues such as thrombogenesis, long term structural failure, and calcification, necessitating the development of more structurally and biologically sufficient long-term replacements. Tissue engineering provides a possible avenue for development, combining cells, scaffolds, and biochemical factors to regenerate tissue. The overall goal of this dissertation was to create a foundation for the rational design of a tissue engineered aortic valve. The novel approach taken in this thesis research was to view each of the three leaflets as a laminate structure. The first three aims consider the leaflet as a laminate structure comprising of layers of collagen, elastin, and glycosaminoglycans (GAGs). In the first aim, the effect of GAGs on the tensile properties and stress relaxation in the leaflet was investigated, by removing GAGs through increasing amounts of hyaluronidase. A decrease in GAGs led to significantly higher elastic moduli, maximum stresses, and hysteresis in the leaflet. In the second aim, the 3D elastic fiber network of the leaflet was characterized using immunohistochemistry and scanning electron microscopy. This structure was found to have regionally varying thicknesses and patterns. In the third aim, a novel hydrogel-fiber composite design was proposed to match the anisotropy of the leaflet. This composite composed of aligned electrospun poly(ε-caprolactone) (PCL) within a poly(ethylene glycol) diacrylate (PEGDA) matrix. Surface modification and embedding of the PCL did not significantly alter the anisotropy or strength of the underlying PCL scaffold, providing the basis for an anisotropic, biocompatible scaffold. In the last aim, a novel co-culture model was designed using magnetic levitation as a layered structure of valvular endothelial cells and interstitial cells. This technique was used to create co-culture models within hours, while maintaining cell phenotype and function, and inducing extracellular matrix formation, as shown by immunohistochemical stains and their gene expression profiling. The overall result of this dissertation is a clearer understanding of the layered structure-function relationship of the aortic valve, and its application towards heart valve tissue engineering.