Disertacijos objektas yra koronarine širdies liga ir ryškiai sumažinta kairiojo skilvelio sistoline funkcija sergančių ligonių klinikinės būklės pokyčiai ir išgyvenimas vėlyvuoju pooperaciniu laikotarpiu po izoliuotų aorto-vainikinių arterijų apeinamųjų jungčių suformavimo operacijų (AVAJSO), bei kairio skilvelio tūrio ir formos atkūrimo operacijų (TFAO). Tai retrospektyvinis tyrimas. Analizuoti 216 ligonių sergančių koronarine širdies liga, kuriems atliktos AVAJSO ir 139 ligonių, kuriems kartu su revaskuliarizacija atliktos kairio skilvelio TFAO, duomenys. Nustatyta, kad ligonių, sergančių IŠL su KS sistoline disfunkcija, išgyvenimas vėlyvuoju – iki 7 metų laikotarpiu po AVAJSO bei 6 metų laikotarpiu po KS TFAO, yra geras. Nustatėme, kad operacijų, kurias nuspręsta atlikti ligoniams, turintiems krūtinės anginos simptomus, be miokardo gyvybingumo požymių įrodymo echokardiografiniu mažų dozių dobutamino krūvio mėginiu, pirmųjų 30 parų mirties rizika nebuvo didesnė. Rasta, kad ligonių, kurių funkcinė klasė vienerių metų laikotarpiu po AVAJSO buvo blogesnė, iki operacijos buvo EKG ilgesnė QRS komplekso trukmė, didesni KS galiniai diastoliniai dydžiai ir operacijos metu jiems buvo suformuota mažiau AVA jungčių. Išaiškinta, kad KS tūrio ir formos atkūrimo operacijos ligoniams su toli pažengusia KS remodeliacija atliekamos saugiai, su ne didesne pirmųjų 30 parų mirties rizika nei atliekant vien AVAJSO. Išaiškinta, kad tų ligonių, kurių funkcinė būklė nepagerėjo vienerių metų... [toliau žr. visą tekstą] / ANNOTATION OF DISERTATION Subject of disertation: Surgical treatment of patients suffering from ischemic heart disease with significantly decreased left ventricle systolic function: clinical evaluation. Objective - evaluation of clinical status and long-term postoperative survival of patients suffering from ischemic heart disease and decreased left ventricle systolic function (LV EF ≤ 35%) after isolated coronary by-pass grafting and left ventricle volume and shape surgical restoration operations. Retrospective study. The study group included 216 patients for whom coronary artery bypass grafting (CABG) and 139 patients who underwent surgical ventricular restoration (SVR). It was postulated that the long-term survival (up to 7 years) in patients after CABG and long-term survival (6 years) in patients after SVR is good. It was found out that the risk of fatal outcome during the first 30 days after CABG in patients 0suffering from ischemic LV dysfunction and symptoms of angina pectoris with viable myocardium, statistically reliably did not differ from patients with nonviable myocardium. It was stated that patients with greater functional class during one year after CABG, preoperatively had longer duration of ECG QRS complex, higher end-diastolic findings and had lower number of by-passes during the operation. We also demonstrated that LV shape and volume restoration operations were being performed for patients with highly advanced LV remodeling safely and postoperative risk... [to full text]

The general purpose of this thesis is to establish the ability of Speckle Tracking Echocardiography (STE) in assessing left atrial (LA) response to pressure and volume overload respectively in aortic stenosis (AS) and mitral regurgitation (MR), and to evaluate its accuracy in predicting LA and right ventricular (RV) fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx). I demonstrated that assessment of left ventricular (LV) long axis systolic velocity and amplitude of excursion is more sensitive than simple determination of ejection fraction (EF) for revealing the beneficial impact of MR surgery on overall LV systolic performance. Severe symptomatic AS is associated with LA enlargement and compromised mechanical function with a high incidence of peri-operative atrial fibrillation (AF). Valve replacement reverses these abnormalities and regains normal atrial function, a behaviour which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size and function disturbances, as shown by myocardial strain measurements might contribute to better patient’s recruitment for a safe valve replacement. In late stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate function measure that correlates with the extent of RV myocardial fibrosis and functional capacity. In patients with preserved EF, severe MR masks LV and LA myocardial dysfunction and correlates with symptoms and post-operative cavity function instability. Three months after MVR, the underlying myocardial disturbances are unmasked suggesting that most pre-operative measurements are subject to loading conditions. Finally LA volume and PALS remain the main predictors of post-operative AF, thus should be used for stratifying surgical risk. STE has been shown to accurately determine the severity of impairment of LA myocardial function shown by suppressed PALS which was the strongest predictor of the presence and extent of fibrosis, over and above other structure and function parameters. These findings may assist in better stratifying patients with end stage HF and identifying particularly those requiring HTx.

Contexte : Les maladies valvulaires dégénératives (MVD) représentent la pathologie cardiaque acquise la plus fréquente chez le chien. Malgré une recherche active, à l’heure actuelle aucun traitement étudié ne s’est avéré efficace dans le traitement du stade asymptomatique de la condition. Le pimobendane est un nouvel agent inodilatateur, qui s’est montré prometteur dans le traitement des stades avancés des MVD, mais peu est connu sur ses effets hémodynamiques et son impact sur le volume de régurgitation dans les MVD naturelles asymptomatiques. Hypothèses : L’introduction du pimobendane réduit la fraction de régurgitation (FR) chez les chiens atteints de MVD asymptomatiques. Sujets étudiés : Vingt-quatre chiens de compagnie, appartenant à la clientèle du Centre Hospitalier Universitaire Vétérinaire (CHUV) de l’université de Montréal et affectés par une MVD de classe ISACHC 1b. Méthode: Étude prospective, contrôlée et conduite à l’aveugle. Les chiens ont été assignés à un groupe traitement (n=19) recevant du pimobendane (0,2-0,3 mg/Kg q12h) ou à un groupe contrôle (n=5). Les évaluations échocardiographiques ont été effectuées sur une période de 6 mois. Résultats : L’introduction du pimobendane n’a pas été associée à une diminution de la FR chez les chiens affectés par une MVD asymptomatique de classe ISACHC 1b au cours de l’étude (p=0,85). Une augmentation significative de la fraction d’éjection (80,8 +/- 1,42 vs. 69,0 +/- 2,76, p=0,0064) ainsi qu’une baisse du diamètre ventriculaire gauche télé systolique (p=0.011) ont été observées chez le groupe pimobendane au jour 30. Toutefois, cet effet sur la fonction systolique n’a pas persisté au cours des 6 mois d’évaluation. / Background: Mitral Valve disease (MVD) is the most common acquired cardiac affectation of the dog, and is therefore associated with an undeniable clinical and economical importance for veterinarians and pet owners. Despite active research, at this time no known treatment has been proven to delay the onset of congestive heart failure. Pimobendan is a novel inodilator that has shown promising results in the treatment of advanced MVD, but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring asymptomatic MVD. Hypothesis: Administration of pimobendan decreases the regurgitant fraction (RF) of dogs with asymptomatic MVD. Animals: Twenty-four client-owned dogs affected by ISACHC class Ib MVD. Methods: Prospective, blinded, controlled clinical trial. Dogs were assigned to a pimobendan (0.2-0.3 mg/Kg q12h) treatment group (n=19) or a control group (n=5). Echocardiographic evaluations were performed over a 6 month study period. Results: Administration of pimobendan to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (p=0.85). There was a significant increase in the ejection fraction of the pimobendan treated dogs at day (80.8 +/- 1.42 vs. 69.0 +/- 2.76, p=0.0064), and a decrease in systolic left ventricular diameter (p=0.011). However, this improvement in systolic function was not sustained over the 6 month trial period.

Ce travail reprend les études d’évaluation d’une plateforme instrumentale dédiée à la chirurgie mitrale mini-invasive vidéo-assistée, et du télémanipulateur Da Vinci pour la réalisation d’anastomose mammaire interne / IVA à thorax fermé.) Evaluation du Portaclamp. Cette étude clinique a porté sur 20 patients opérés de chirurgie cardiaque sous CEC et a confirmé la simplicité d’utilisation du système, son efficacité et l’absence de morbidité ou complication induite. L’étude chez le porc des effets histologiques sur la paroi de l’aorte des trois clamps (l’endo-clamp, le clamp Chitwood et le Portaclamp) a révélé une atteinte majeure de l’endothélium aortique induite par l’endo-clamp . 2) Evaluation du Portapleg. Le Portapleg est un dispositif auto-suturant de cardioplégie antérograde constitué d’un clip en Nitinol restant implanté sur l’aorte. Une étude sur 20 patients a été rapportée avec comme critère principal le temps de saignement du site de ponction après injection de protamine. Le système a montré son efficacité hémostatique dans tous les cas sans événement secondaire. 3) Evaluation du Mitrax’s. C’est un cône en plastique polymère auto ajustable et auto expansible, qui repousse de façon symétrique et concentrique les parois de l’oreillette. Une étude prospective de son efficacité a été réalisée chez 62 patients opérés de chirurgie mitrale vidéo-assistée de façon consécutive. L’indice de satisfaction a été en moyenne 4.6, témoin d’une exposition optimale de la valve mitrale avec une vision endoscopique ou directe de la valve mitrale jugée excellente. 4) Analyse comparative des techniques mini-invasives de revascularisation de l’IVA par pontage mammaire (Port Access, MIDCAB, TECAB). Cette étude prospective a porté sur 160 patients ; à trois mois, le taux de réintervention sur l’IVA était : PA-CABG, 0% ; MIDCAB, 1.8% ; TECAB, 10% ; p<0.01. A trois ans, les taux actuariels de survie sans réintervention étaient : PA-CABG, 100% ; MIDCAB, 98±5 % ; TECAB, 88±8 % ; p<0.05. / This thesis is based on the evaluation studies of an instrumental platform dedicated to video assisted minimally invasive mitral valve surgery, and of the robotic Da Vinci system in LAD bypass with mammary artery in a closed chest approach. 1) Evaluation of Portaclamp. In 20 patients who underwent cardiac surgery with Portaclamp, a clinical study showed that the clamping system is safe, fast and easy and does not generate undue morbidity. In a pig model, severe lesions of the intima were observed on the clamping spot with the endoclamp, in comparison with Portaclamp and Chitwood clamp. 2) Evaluation of Portapleg. Portapleg is an auto-suturing system dedicated to antegrade cardioplegia delivery, and based on a Nitinol clip left implanted on the aorta. In 20 patients, the closure of the puncture aortic hole and the haemostasis after protamine were obtained in all cases. The procedure did not generate undue morbidity and there was no device-related adverse event. 3) Evaluation of Mitrax’s. The Mitrax’s retractor is a pattern cut polymer sheet, self-expanding and auto-adjusting. The effectiveness of Mitrax’s was evaluated in 62 patients who consecutively underwent a video-assisted mitral valve procedure. The global satisfaction index was 4.6±0.5, demonstrating the effectiveness of the device which provides optimal exposure and excellent direct vision. 4) Comparative analysis of minimally invasive techniques for LAD revascularization with mammary artery graft (Port Access, MIDCAB, TECAB). In a prospective study, 160 patients were included. At 3-month postoperatively, the end-point of LAD reintervention were PA-CABG, 0%; MIDCAB, 1.8%; TECAB, 10%; p=0.01. At 3-year, reintervention-free survival was significantly lower in the TECAB group: PA-CABG, 100% ; MIDCAB, 98±5 % ; TECAB, 88±8 % ; p<0.05.

Contexte : Les maladies valvulaires dégénératives (MVD) représentent la pathologie cardiaque acquise la plus fréquente chez le chien. Malgré une recherche active, à l’heure actuelle aucun traitement étudié ne s’est avéré efficace dans le traitement du stade asymptomatique de la condition. Le pimobendane est un nouvel agent inodilatateur, qui s’est montré prometteur dans le traitement des stades avancés des MVD, mais peu est connu sur ses effets hémodynamiques et son impact sur le volume de régurgitation dans les MVD naturelles asymptomatiques. Hypothèses : L’introduction du pimobendane réduit la fraction de régurgitation (FR) chez les chiens atteints de MVD asymptomatiques. Sujets étudiés : Vingt-quatre chiens de compagnie, appartenant à la clientèle du Centre Hospitalier Universitaire Vétérinaire (CHUV) de l’université de Montréal et affectés par une MVD de classe ISACHC 1b. Méthode: Étude prospective, contrôlée et conduite à l’aveugle. Les chiens ont été assignés à un groupe traitement (n=19) recevant du pimobendane (0,2-0,3 mg/Kg q12h) ou à un groupe contrôle (n=5). Les évaluations échocardiographiques ont été effectuées sur une période de 6 mois. Résultats : L’introduction du pimobendane n’a pas été associée à une diminution de la FR chez les chiens affectés par une MVD asymptomatique de classe ISACHC 1b au cours de l’étude (p=0,85). Une augmentation significative de la fraction d’éjection (80,8 +/- 1,42 vs. 69,0 +/- 2,76, p=0,0064) ainsi qu’une baisse du diamètre ventriculaire gauche télé systolique (p=0.011) ont été observées chez le groupe pimobendane au jour 30. Toutefois, cet effet sur la fonction systolique n’a pas persisté au cours des 6 mois d’évaluation. / Background: Mitral Valve disease (MVD) is the most common acquired cardiac affectation of the dog, and is therefore associated with an undeniable clinical and economical importance for veterinarians and pet owners. Despite active research, at this time no known treatment has been proven to delay the onset of congestive heart failure. Pimobendan is a novel inodilator that has shown promising results in the treatment of advanced MVD, but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring asymptomatic MVD. Hypothesis: Administration of pimobendan decreases the regurgitant fraction (RF) of dogs with asymptomatic MVD. Animals: Twenty-four client-owned dogs affected by ISACHC class Ib MVD. Methods: Prospective, blinded, controlled clinical trial. Dogs were assigned to a pimobendan (0.2-0.3 mg/Kg q12h) treatment group (n=19) or a control group (n=5). Echocardiographic evaluations were performed over a 6 month study period. Results: Administration of pimobendan to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (p=0.85). There was a significant increase in the ejection fraction of the pimobendan treated dogs at day (80.8 +/- 1.42 vs. 69.0 +/- 2.76, p=0.0064), and a decrease in systolic left ventricular diameter (p=0.011). However, this improvement in systolic function was not sustained over the 6 month trial period.

The objectives of this thesis are: a) To examine racial/ethnic differences in coronary artery calcification (CAC) and CAD, between symptomatic South Asians and Caucasians, matched for age, gender and conventional cardiovascular risk factors, b) To assess, using a meta-analysis model, the natural history of and stability of measurements of coronary artery calcium scoring (CACs) based on data collected from two large published trials: St Francis and EBEAT, c) To investigate the prevalence of coronary artery calcification in individuals with CT evidence for AVC, mitral valve calcification (MAC) or of both of them (AVC+MAC), d) To assess any potential association between premature CAD (&lt;55 years in first-degree male relatives and &lt;65 years in first-degree female relatives) and CAC in a large cohort of asymptomatic individuals. We found that coronary artery calcification is more extensive and diffuse in symptomatic patients of South Asian ethnic origin as compared to Caucasians, despite similar conventional risk factors for CAD. This is more evident in those &gt;50 years of age, suggesting potential genetic or other risk factors yet to be determined. The natural history of coronary artery calcification was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA brances are influenced by the branch allocation of the CACs. Valve calcification is not isolated but involve also and the coronary arteries. The presence of calcification in the aortic valve or combined aortic and mitral valves predicted coronary artery calcification. Additionally patients in whom both valves have become calcified tend to have severe coronary artery calcification. And finally, there is no relationship between the prevalence and extent of coronary artery calcification and the presence of family history of coronary heart disease in asymptomatic individuals with none of the conventional risk factors for atherosclerosis.

Made available in DSpace on 2014-06-12T18:05:57Z (GMT). No. of bitstreams: 2 arquivo7699_1.pdf: 4692354 bytes, checksum: 3063b3c29a68321b0fdc334da3fab5a0 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2007 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / No campo da neurociência computacional, a atividade elétrica dos neurônios é tradicionalmente modelada por equações diferenciais não-lineares acopladas, representando a evolução do potencial de membrana e certas variáveis relacionadas às condutâncias iônicas presentes no sistema. Uma tendência recente consiste na extensão desta estratégia de modelagem, detalhando as árvores dendríticas neuronais através da abordagem compartimental. Essa modelagem fina visa examinar a possibilidade de que essas extensas regiões neuronais em forma de árvores ramificadas desempenhem funções importantes, ou seja, sejam palco de uma complexa "computação dendrítica". Nesta dissertação, estudamos analiticamente e através de simulações um modelo cuja dinâmica da transmissão de estímulos dos elementos excitáveis é simples, porém a estrutura da árvore dendrítica é modelada em detalhe na forma de uma árvore de Cayley com um grande número de compartimentos. Resolvemos a equação mestra do problema, primeiro pela aproximação de campo médio simples, que apresenta fracos resultados. Em seguida, estudamos um cálculo da aproximação de pares, com resultados mais promissores. Os resultados de nossas simulações computacionais sugerem que a estrutura da árvore dendrítica da célula mitral é fundamental para o aumento da faixa dinâmica observado no glomérulo olfatório. Constatamos também o aparecimento de retropropagação de excitações, um fato já observado experimentalmente. Nossos resultados sugerem que a estrutura física em forma de árvore extensa com várias camadas poderia implementar importantes computações dendríticas, em especial uma função compressora de sinais com faixa dinâmica de mais de 50 dB. Fazemos também uma aplicação deste sistema ao glomérulo olfatório dos mamíferos, que contém dezenas de dendritos primários de células mitrais entrelaçados e conectados por junções comunicantes, modelado por árvores dendríticas com elementos conectados por uma rede bidirecional quase-aleatória. Um resultado notável nesta arquitetura é que a razão de ramificação das excitações não é dada simplesmente pela soma das razões dos casos isolados previamente conhecidos (rede aleatória e árvore isolada). No nosso modelo as árvores conectam-se por junçoes bidirecionais sorteadas aleatoriamente. Dependendo do número de junções comunicantes e de sua eficiência, o sistema passa a ter laços, possibilitando o aparecimento de atividade autosustentada na forma de transição de fase de não-equilíbrio. Deste forma, foi possível determinar numericamente as linhas críticas desta transição de fase. Neste caso, através de simulações, obtemos na criticalidade valores de faixa dinâmica similares aos observados experimentalmente para o glomérulo olfatório. Este resultado sugere uma possível função fisiológica para junções comunicantes nos circuitos neuronais do bulbo olfatório

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Made available in DSpace on 2014-07-22T13:16:48Z (GMT). No. of bitstreams: 2 Regina Elizabeth Müller.pdf: 4161979 bytes, checksum: 5df884fdb04b617145c35c1741e9b502 (MD5) license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil. / Introdução: A cardiopatia reumática persiste como a principal doença cardiovascular adquirida em crianças e adultos jovens em todo o mundo, sendo responsável por altas taxas de morbimortalidade e evoluindo com frequência para a necessidade de cirurgia cardíaca valvar em pacientes na fase aguda ou crônica da doença. Objetivo: Estimar os fatores associados e o tempo desde o diagnóstico até a cirurgia cardíaca valvar em crianças e adolescentes portadores de cardiopatia reumática, em um centro cardiológico de referência terciária no Rio de Janeiro. Material e Métodos: estudo observacional longitudinal de base hospitalar, utilizando metodologia de análise de sobrevivência, para estimativa do tempo até a cirurgia, e modelo de regressão de Cox, para avaliar as razões de risco associadas segundo as covariáveis. A coorte foi composta por pacientes com 3 a 20 anos, cadastrados no Instituto Nacional de Cardiologia no Rio de Janeiro entre julho de 1986 e junho de 2006 e acompanhados até setembro de 2011. O diagnóstico da lesão valvar foi confirmado pelo exame Doppler-ecocardiográfico. As covariáveis, avaliadas no início do acompanhamento, foram reunidas em três dimensões: sociodemográfica (sexo, grupo etário, cor da pele, região de moradia e década do diagnóstico); clínica (apresentação clínica, classe funcional, número de surtos anteriores, profilaxia secundária, endocardite infecciosa e fibrilação atrial); e ecocardiográfica (lesão valvar por tipo e gravidade; diâmetro do átrio esquerdo, diâmetro sistólico do ventrículo esquerdo, função ventricular esquerda, hipertensão arterial pulmonar, e ruptura de cordoalha mitral). O banco de dados foi elaborado com o programa ACCESS 2000 e a análise estatística foi realizada pelo programa R versão 2.13.1. Foi considerado significativo o valor de - 0,05. Resultados: a coorte foi composta por 348 pacientes, 58% do sexo feminino, com idade mediana ao cadastro de 12,5 anos, e de 21,5 anos ao final do acompanhamento. O tempo médio de seguimento foi de 9,0 anos (2-21 anos). O evento cirurgia cardíaca ocorreu em 39% da amostra, com tempo mediano até a cirurgia de 22,3 anos. Na análise univariada todas as covariáveis das três dimensões (socioedemográfica, clínica e ecocardiográfica) apresentaram significância estatística e risco para realização de cirurgia cardíaca (hazard ratio>1), com exceção apenas da covariável região de moradia (p>0,5). Na análise multivariada, o modelo final incluiu as variáveis: década do diagnóstico, classe funcional, número de surtos anteriores, endocardite infecciosa, lesão valvar por tipo e gravidade, diâmetro do átrio esquerdo, diâmetro sistólico do ventrículo esquerdo e ruptura de cordoalha mitral. Conclusões: A realização da cirurgia cardíaca em pacientes com cardiopatia reumática está associada a fatores sociodemográficos, clínicos e ecocardiográficos. / Introduction: Rheumatic heart disease remains as the most common acquired heart disease in children and young adults all over the world, being responsible for high mortality and morbidity rates and often demanding valve surgery in the acute or chronic phase of the disease. Objective: To estimate the time from diagnosis until valve operation and the associated factors in children and young adults with rheumatic heart disease followed up in a tertiary center for cardiovascular care in Rio de Janeiro. Methods – It is a longitudinal observational study of a hospital based population, using survival analysis methodology for time estimation and Cox regression model for hazard risk evaluation of associated variables. Cohort was composed by 3 to 20 years old patients, registered in the National Institute of Cardiology (Instituto Nacional de Cardiologia), in Rio de Janeiro, between July 1986 and June 2006, and followed up until September 2011. Valve disease diagnosis was confirmed through Doppler echocardiography examination. Variables were evaluated at the patient´s first visit and separated in three dimensions: socio demographic (gender, age group, skin color, residence region, decade of diagnosis); clinic (disease status at presentation, functional class, number of previous rheumatic episodes, secondary prophylaxis, infectious endocarditis, atrial fibrillation); echocardiographic (valve lesion and severity, left atrium diameter, systolic left ventricle diameter, left ventricle function, pulmonary hypertension, rupture of mitral chordae). The database wasbased on the program ACCESS 2000 and statistical analysis was performed using the R Program version 2.13.1. For statistical analysis was considered as significant values for  value 0.05. Results – 348 patients were included in the cohort, 58% female. Median age at the register was 12.5 years, and 21.5 years at the end of follow up. Median follow-up time was 9.0 years (2 to 21 years). 39% underwent valve operation and the median time until surgery was 22.3 years. In the univariate analysis all the variables from the three dimensions (socio demographic, clinic and echocardiographic) presented statistical significance as hazard risk in predicting valve operation (hazard ratio>1), with only one exception, that was residence region (p>0.5). In the multivariate analysis the final model included the following variables: decade of diagnosis, functional class, number of anterior rheumatic episodes, infectious endocarditis, valve lesion and severity, left atrium diameter, systolic left ventricle diameter and rupture of mitral chordate. Conclusions: Valve surgery in patients with rheumatic heart disease is associated with socio demographic, clinic and echocardiographic factors.

Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our ability to prevent or cure the disease. Ex vivo investigations, however, have provided evidence that the aortic valve's biological response is sensitive to mechanical forces, including fluid shear stresses, leading to the hypothesis that adverse fluid shear stress environment play a role in leading to valve calcification. This thesis seeks to investigate this hypothesis. A method for performing experimental measurement of time-varying shear stress on aortic valve leaflets under physiologic flow conditions was first developed, based on the Laser Doppler Velocimetry technique, and was systematically validated. This method was then applied to both the aortic surface and the ventricular surface of a normal tricuspid the aortic valve, and then on a congenital bicuspid aortic valve, using suitable in vitro valve models and an in vitro pulsatile flow loop. It was found that in the tricuspid valve, the peak shear stress on the aortic surface under adult resting condition was approximately 15-19 dyn/cm². Aortic surface shear stresses were elevated during mid- to late-systole, with the development of the sinus vortex, and were low during all other instances. Aortic surface shear stresses were observed to increase with increasing stroke volume and with decreasing heart rate. On the ventricular surface, shear stresses had a systolic peak of approximately 64-71 dyn/cm² under adult resting conditions. During late systole, due to the Womersley effect, shear stresses were observed to reverse in direction to a substantial magnitude for a substantial period of time. Further, it was found that a moderately stenotic bicuspid aortic valve can experience excessive unsteadiness in shear stress experienced by its leaflets, most likely due to the turbulent forward flow resulting from the stenosis, and due to the skewed forward flow. To demonstrate that the measured shear stresses can have an effect on the aortic valve biology, ex vivo experiments were performed in specific to determine the effects of these various shear stress characteristics on the biological response of porcine aortic valve leaflets, using the cone and plate bioreactor. It was found that unsteady shear stress measured in the bicuspid valve resulted in increased calcium accumulation. Further, it was found that low shear stresses and high frequency shear stresses resulted in increased calcium accumulation. Thus, shear stress was found to affect aortic valve pathology, and low and unsteady fluid shear stresses can enhance pathology.