Dissertations / Theses on the topic 'Valve tricuspide'

Orientador: Domingo Marcolino Braile<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas<br>Made available in DSpace on 2018-08-07T03:55:43Z (GMT). No. of bitstreams: 1 Antoniali_Fernando_M.pdf: 4775200 bytes, checksum: 8361f227d501574e0c98c3965065c58b (MD5) Previous issue date: 2006<br>Resumo: Objetivo: Determinar a proporção existente entre os segmentos do anel da valva tricúspide normal em humanos. Método: Foram estudados 30 corações de cadáveres humanos não formolizados, com menos de 6h de período ¿post-mortem¿, sem lesões congênitas ou adquiridas e com valvas tricúspides sem deformidades e continentes. A continência desta valva foi confirmada por injeção de água sob pressão no interior do ventrículo direito estando a valva pulmonar fechada. Foram realizadas fotos digitais da valva tricúspide com o anel valvar íntegro e após secção na comissura póstero-septal e retificação do anel valvar. Estas fotos contendo escalas milimetradas foram avaliadas por programa específico de computador. Foram feitas medidas computadorizadas do perímetro, segmento septal e segmento ântero-posterior do anel valvar íntegro. Nesta condição também foram feitas medidas da distância linear entre as comissuras ântero-septal e póstero-septal. Na condição de anel valvar retificado, foram realizadas medidas computadorizadas e manuais do perímetro e dos segmentos septal, anterior e posterior do anel valvar tricuspídeo. Compararam-se as medidas médias e as razões entre elas nas condições de anel íntegro e retificado. Compararam-se, também, a forma computadorizada e manual de mensuração do anel. Resultados: Nas medidas computadorizadas realizadas com imagens digitais do anel valvar íntegro, os valores médios do perímetro, segmento septal e ântero-posterior foram 105mm (±12,7), 30,6mm (±3,7) e 74mm (±9,4), respectivamente. A distância linear média entre as comissuras ântero-septal e póstero-septal foi de 28,9mm (±3,4). Nas medidas computadorizadas realizadas com imagens digitais do anel valvar retificado, os valores médios foram 117,5mm (±13,3), 32mm (±3,7), 46,3mm (±8,3) e 39,1mm (±8,5), respectivamente para perímetro, segmento septal, anterior e posterior. A razão média entre o segmento ântero-posterior e o septal foi 2,43 (±0,212) e 2,67 (±0,304) respectivamente em anéis íntegros e retificados. Houve diferenças significantes entre as medidas do perímetro (p<0,0001), do segmento septal (p=0,003) e do segmento ântero-posterior (p<0,0001) quando realizadas em anéis íntegros e retificados. As razões entre segmento ântero-posterior e septal também apresentaram diferença significante (p=0,0005). As medidas manuais do anel valvar retificado apresentaram os valores médios de 118,5mm (±12,7), 32,6mm (±3,4), 46,6mm (±7,7) e 39,3mm (±7,9), respectivamente para perímetro, segmento septal, anterior e posterior. Não houve diferenças significantes entre medidas manuais e computadorizadas. Conclusões: A proporção existente entre os segmento septal e o segmento ântero-posterior, do anel da valva tricúspide normal em humanos, é igual a 1 : 2,43. A secção e retificação do anel tricuspídeo altera as medidas de seus segmentos e suas relações<br>Abstract: Objective: The purpose of this study was to determine the proportion among the segments of the human tricuspid valve annulus. Methods: Descriptive autopsy study of 30 human hearts, without fixation, with less than six hours of post-mortem period, without congenital or acquired lesions and without tricuspid regurgitation. The tricuspid valve insufficiency was excluded by infusion of pressured water in the right ventricle with closed pulmonary valve. Digital images of the tricuspid ring on anatomical position and on flattened state were analyzed by specific software. Computerized measurements of the perimeter, septal segment, anteroposterior segment and the linear distance between the anteroseptal and posteroseptal commissures were obtained on anatomical position. Computerized and manual measurements of the perimeter, septal, anterior and posterior segments were obtained on flattened state. The measurements were demonstrated and compared on the two different situations, anatomical position and flattened. The computerized measurements were compared with the manual ones. Results: The mean values of the perimeter, septal and anteroposterior segments of the tricuspid ring, obtained by computerized measurements on anatomical position were: 105mm (±12.7), 30.6mm (±3.7) e 74mm (±9.4), respectively. The mean linear distance between the anteroseptal and posteroseptal commissures was 28.9mm (±3.4). On the flattened state and by computerized measurements, the mean value of the perimeter was 117.5mm (±13.3) and of the septal, anterior e posterior segments were respectively: 32mm (±3.7), 46.3mm (±8.3) e 39.1mm (±8.5). The mean ratio between the antero-posterior and septal segments was 2.43 (±0.212) on the anatomical position and on flattened state was 2.67 (±0.304). Statistical differences were observed in the measurements of perimeter (p<0.0001), septal segment (p=0.003) e antero-posterior segment (p<0.0001) on the two situations. Statistical difference also occurred on the ratios between the antero-posterior and septal segments (p=0.0005). The mean values obtained by manual measurements of the tricuspid ring on flattened state were: 118.5mm (±12.7), 32.6mm (±3.4), 46.6mm (±7.7) e 39.3mm (±7.9), respectively for perimeter, septal, anterior and posterior segments. There weren¿t statistical differences on computerized and manual measurements. Conclusions: The proportion between the septal and antero-posterior segments of the normal human tricuspid valve is 1 : 2.43. The attitude of flatting the tricuspid ring to measure the segments, changes their values and the ratios between them<br>Mestrado<br>Cirurgia<br>Mestre em Cirurgia

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<br>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

Tricuspid regurgitation (TR), back flow of blood from the right ventricle to the right atrium, has been reported in approximately 85% of the population, with 16% having mild or severe TR. Patients with untreated moderate to severe TR are likely to experience decreased exercise capacity and have increased morbidity and mortality, thus affecting the patient's quality of life. Current methods of repair offer limited rates of success, and many patients require further operations to correct returning levels of TR. Incomplete repair may be due to incomplete understanding of the functional anatomy and mechanics of the TV and the underlying causes of TR. It was hypothesized that alterations in the geometry of tricuspid valve annular and subvalvular apparatus induced by ventricular dilatation determine the severity of TR. In vivo measurements of papillary muscle (PM) position in patients with single or biventricular dilatation revealed PM displacement away from the center of the annulus as compared to control patients. Additionally, pulmonary arterial pressure, annulus area, ventricular size and apical displacement of the anterior PM were highly correlated with the severity of TR. An in vitro right-heart simulator was developed to investigate isolated mechanics of TR. Through these in vitro studies it was demonstrated that the tricuspid valve begins to leak at only 40% dilation, much lower than the mitral valve. Additionally, it was shown that isolated PM displacement resulted in significant TR. The highest levels of TR were achieved with a combination of annular dilatation and PM displacement. Alterations in leaflet coaptation, as quantified by measuring the amount of leaflet available for coaptation and leaflet mobility were observed with annular dilatation and PM displacement, both isolated and combined. The changes in leaflet coaptation resulted in redistribution of the forces on the chords originating from the anterior PM and inserting into the anterior and posterior leaflets. The findings herein provide the clinical and scientific community with a mechanistic understanding of the tricuspid valve to further improve intervention and repair of TV disease.

Introdução: As principais operações para correção da anomalia de Ebstein baseiam-se na reconstrução da valva atrioventricular direita (AVD) em formato monovalvular, tendo resultados comprometidos pela necessidade de substituição ou alta reincidência de insuficiência valvar. Uma nova técnica foi desenvolvida, diferenciado-se das anteriores, pela correção anatômica da valva AVD, resultando na coaptação plena das válvulas no fechamento valvar. O objetivo deste estudo é avaliar a aplicabilidade dessa técnica, estudando os seus efeitos na evolução clínica, função da valva, restauração do ventrículo direito funcional e remodelamento reverso do coração no pós-operatório imediato (POI) e no pós-operatório em longo prazo (POL). Métodos: Estudo retrospectivo de 52 pacientes consecutivos, com idade média de 18,5±13,8anos, submetidos técnica do cone para correção da anomalia de Ebstein, entre novembro 1993 e dezembro de 2006, cujos principais detalhes cirúrgicos são: as válvulas anterior e posterior da valva AV direita são mobilizadas das suas implantações anômalas no ventrículo direito (VD), a borda livre desse conjunto é rodada no sentido horário para ser suturada à, previamente mobilizada, borda septal da válvula anterior, formando um cone cujo vértice permanece fixo ao ápice do VD e a base é suturada no nível do anel atrioventricular verdadeiro, reduzido ao mesmo tamanho da base do cone. A válvula septal, sempre que possível, é incorporada à parede do cone. A porção atrializada do VD é reduzida por plicatura longitudinal. Os dados clínicos, ecocardiográficos e os índices cardiotorácicos, obtidos nos períodos pré-operatório (PREOP) e pós-operatório, foram analisados. Resultados: Houve dois óbitos hospitalares (3,8 %) e dois óbitos no seguimento em longo prazo A melhora clínica foi significante, sendo a distribuição dos pacientes em classes funcionais de insuficiência cardíaca (NYHA), IV = 4, III = 27, II = 11 e I = 5 no PREOP, modificada para IV = 0, III = 1, II = 2 e I = 44 no pós-operatório em longo prazo (POL) (p<0,0001), com seguimento médio de 57 meses. Quatro pacientes foram reoperados, sendo realizada nova plastia valvar. O índice cardiotorácico de 0,66±0,09 no PREOP diminuiu para 0,54±0,06 no POL (p<0,0001). Os ecocardiogramas mostraram redução dos graus de insuficiência da valva AV direita (p<0,001), sendo a distribuição dos pacientes no pré-operatório, grau 1 = 0, grau 2 = 1, grau 3 = 15, grau 4 = 24, modificada para grau 1 = 19, grau 2 = 17, grau 3 = 4, grau 4 = 0 no POI, com pequena alteração no POL (grau 1 = 11, grau 2 = 22, grau 3 = 7, grau 4 = 0). A cavidade funcional do VD foi restaurada pela operação, ocorrendo aumento da área do VD funcional indexada de 8,53± 7,02 cm2/m2 no PREOP para 21,01±6,87 cm2/m2 no POI (p<0,001), e ficando inalterada em 20,28±5,26 cm2/m2 no POL (p>0,05). Conclusões: Esta técnica foi aplicável com baixa mortalidade hospitalar e sem necessidade de substituição valvar. Houve melhora clínica pós-operatória e baixa incidência de reoperações em longo prazo. A correção da insuficiência valvar foi eficaz e duradoura na maioria dos pacientes. Houve restauração da área funcional do VD e remodelamento reverso do coração.<br>Background: The main operations for Ebsteins anomaly repair are conceived to reconstruct the tricuspid valve (TV) in a monocusp format, but their results are restricted either by the need for valve replacement or by high incidence of postoperative valve regurgitation. A new surgical technique was developed, that performs an anatomical reconstruction of the tricuspid valve, realizing a leaflet-to-leaflet coaptation at the TV closure. The objective of this study is to access the feasibility of this technique, evaluating its effects in clinical outcome, tricuspid valve function, right ventricle (RV) morphology and reverse remodeling of the heart.Methods: Retrospective study on 52 consecutive patients, mean age of 18,5+- 13,8 years, treated with a new surgical technique for Ebsteins anomaly repair (the cone technique), between November 1993 and December 2006, which principal details are: a) the anterior and posterior tricuspid valve leaflets re mobilizedfrom their anomalous attachments in the RV, the free edge of this complex is rotated clockwise to be sutured to the septal border of anterior leaflet, creatind a cone which vertex remains fixed at RV apex and whose base is the sutured to a true tricuspid annulus, plicated to match it to base of said cone. The septal leaflet is incorporated into the cone wall ewhenever possible. The atrialized chamber is reduced by longitudinal placation. The clinical and echocardiographic data and the patients cardiothoracic ratios, collected at the preoperative, early and late postoperative periods, were analyzed. Results: There were two hospital deaths (3.8 %) and two more deaths in the long term followup. The significant clinical improvement was evident by the change of patients functional class of heart failure (NYHA) from IV=4, III=27, II=11 and I=5, in the preoperative to IV =0, III = 1, II = 2 e I = 44 at 57 months mean long term follow-up (p<0,0001). Four patients required late TV re-repair. Atrioventricular block did not occur and there was no need for tricuspid valve replacement at any time. The cardiothoracic ratio decreased from 0,66+-0,09, preoperatively, to 0,54+-0,06 in long term follow-up (p<0,001). Echocardiographic studies showed significant TV insufficiency reduction from the preoperative patient distribution of: grade 1 = 0, grade 2 = 1, grade 3 = 15, grade 4 = 24, modified to: grade 1 = 19, grade 2 = 17, grade 3 = 4, grade 4 = 0 on early postoperative period (p<0.001), with little change afterwards (grade 1 = 11, grade 2 = 22, grade 3 = 7, grade 4 = 0). The normal RV morphology was surgically restored, indicated by the enlargement of RV indexed area from 8.53+-7.02 cm2/m2, preoperatively to 21.01+-6.87 cm2/m2 in the early perioperative period (p<0.001), remaining unchanged, 20.28+-5.26 cm2/m2 in long term echocardiogram (p>0,05). Conclusions: This operative technique was feasible with low hospital mortality and no need for TV replacement. There was improvement in the patients clinical status and low incidence of reoperations in long term follow-up. The TV repair was efficacious and durable for the great marjority of patients and there was immediate RV morphology restoration and reverse remodeling of heart in long term follow-up

The development of a clinical case of a canine breed Bulldog ingles, 3.5 months old male having difficulty breathing, impaired physical activity as well as an abdominal protuberance described. To a breath chest auscultation with an intensity of 6/6, arrhyth- mias and death rattles perceived. A radiographic study was conducted as an adjunct to physical examination, by which, generalized cardiomegaly, dorsal displacement of the trachea, lung radiopacity with alveolar pattern is observed, plus an echocardiogram in which ventricular septal defect was observed, volume overload, artery dilated pulmonary among other hallazgos and an electrocar- diogram which is interpreted during disease management, advanced deterioration of the patient’s health is evident, the cualle death occurred.

Background: The etiology of congenital heart valve defects is not well understood; little is known about the risk factors that contribute to the survival and mortality outcomes of children with these defects. Methods: Using data from the Texas Birth Defects Registry (TBDR) we conducted a retrospective cohort study of 2070 singleton infants with congenital aortic, pulmonary, or tricuspid valve atresia or stenosis born in Texas between January 1, 1996 and December 31, 2007 to Hispanic, Non-Hispanic (NH) black, and NH white women. TBDR data were death-to-birth matched by the Texas Vital Statistics Unit for deaths between January 1, 1996 and December 31, 2008. Using Kaplan-Meier survival estimates with log rank tests and Cox proportional hazards regression model hazard ratios (HR) with 95% confidence intervals (CI), we examined whether infant sex and maternal race/ethnicity affected early childhood survival or risk of mortality for children with congenital heart valve defects. Covariates included birth weight and gestational age, maternal age, maternal education, and number of co-occurring birth defects. Results: In children with aortic valve atresia and aortic valve stenosis, we found males had higher early childhood survival than females (55.0% vs. 41.5%, P=0.0451 and 91.6% vs. 82.5%, P=0.0492, respectively). Early childhood survival for males (94.9%) with pulmonary valve stenosis was slightly lower than females (97.1%, P=0.0116), and was also lower for NH black (94.1%) and Hispanic (95.3%) children than NH white children (97.8%, P=0.0340). After adjusting for covariates, early childhood mortality in children with pulmonary valve atresia with hypoplastic right ventricle was greater in NH black than NH white children (HR=2.93, CI 1.09-7.85, P=0.0329) and greater in NH black males than NH white males (HR=4.63, CI 1.12-19.19, P=0.0349). For children with tricuspid valve atresia, early childhood survival was lower in NH black males (35.7%) and Hispanic males (64.0%) than NH white males (81.0%, P=0.0269); after adjusting for covariates, risk for early childhood mortality was higher in NH black than NH white children (HR=3.39, CI 1.41-8.13, P=0.0062), and higher in NH black males than NH white males (HR=5.23, CI 133-20.58, P=0.0179). Conclusions: Our findings demonstrate there are disparities in early childhood survival and risk of mortality by infant sex and maternal race/ethnicity for children with congenital heart valve defects. These findings provide a foundation for further investigation to better understand why these disparities exist and what can be done to improve the outcomes for children with these defects.

Background. Thoracic aortic aneurysm (TAA) is a degenerative disease of the aortic wall and is associated with an increased risk of aortic rupture. TAA is a more prevalent complication in patients with bicuspid aortic valve (BAV) compared to those with tricuspid aortic valve (TAV). Objectives. We aimed to investigate first, changes in intracellular proteins by comparing BAV and TAV patients with aneurysm, and second, regional changes in extracellular matrix (ECM) proteins by comparing the lesser (concavity) and the greater (convexity) aortic curvatures of BAV patients with and without aneurysm. The findings obtained in human patients were followed up by mechanistic studies in mice. Methods. Human and murine aortic specimens were analysed by mass spectrometry (MS) after extraction of intracellular and ECM proteins. Immunoblotting and gene expression analysis were used to validate the proteomics findings. An ECM protease knockout mouse model was used to better characterise proteolytic processing of ECM large proteoglycan. Similar techniques were used as above. Results. To compare the intracellular proteome of aneurysmal BAV and TAV patients we used two-dimensional fluorescence difference in-gel electrophoresis. This approach revealed regulation of 24 proteins. BAV aneurysms were associated with up-regulation of smooth muscle cell related proteins and down­regulation of glycolytic and oxidative stress related proteins. Next, we focused on alterations in ECM proteins and compared the concave and convex areas in aortas of BAV patients with and without TAA using liquid chromatography and tandem MS. In aortas of aneurysmal BAV patients, versican, a large proteoglycan important for tissue integrity, was up-regulated in the concave area; conversely, versican was down-regulated in the same area of non-aneurysmal BAV samples. Gene expression analysis showed no differences in versican levels between concavity and convexity of aneurysmal patients, suggesting that regulation of versican protein levels may be related to proteolytic processing. ADAMTSs (a disintegrin and metalloproteases with thrombospondin motifs) are the main proteases cleaving versican. Notably, in aneurysmal BAV patients there was an inverse association between the abundance of versican and gene expression levels of members of the ADAMTS family. To study the role of ADAMTS in the remodelling of the ECM in aorta, we used ADAMTS-5 knockout mice. After angiotensin II infusion to induce aortic dilatation, versican levels were higher in aortas of ADAMTS-5 knockout mice activity compared to wild-type controls. Conclusion. Our results suggest that ADAMTS proteases may be important for versican regulation during aortic ECM remodelling, as supported by proteomics changes in the ECM of aneurysmal BAV patients and ADAMTS-5 knockout mice.

Objetivou-se, neste trabalho, estudar a morfologia e vascularização do aparelho valvar das valvas mitral e tricúspide em corações humanos, comparando os resultados com aqueles obtidos em cães. A estereologia foi usada como ferramenta que permitiu avaliar os volumes entre as cúspides valvares, cordas tendíneas e mm. papilares, para o conhecimento das relações anatômicas desta estrutura. Foram analisados 15 corações humanos (10 homens e cinco mulheres, com idades variando de 9 a 77 anos) e 15 corações caninos (Canis familiaris - SRD 10 machos e cinco fêmeas, adultos). Os corações, sem alterações macroscópicas, foram dissecados, pesados e seu volume aferido com vistas a análise da morfologia. O estudo da irrigação e drenagem foi realizado por meio de moldes vasculares, em 10 corações de cada espécime. Fundamentados nos resultados obtidos, concluiu-se que as estruturas do aparelho valvar do coração canino e humano apresentam semelhanças tanto morfológicas como em relação a vascularização.<br>In this study we performed a comparative analysis of the morphology and vascularization of the valvar apparatus of the mitral and tricuspid valve of the human and canine heart. The volumes of the heart and valvar structures (valvar cuspids, chordae tendineae and papillary muscle) were investigated using stereological method. Fifteen human (10 men and 5 women) and 15 canine (mongrel dogs, 10 males and 5 females) hearts of different ages were studied. Ten hearts of each specimen were perfused with vascular cast material to assess and describe the vascularization. Our findings indicate that human and canine valvar apparatus of the mitral and tricuspid valves and its vascularization are similar.

Introdução: A insuficiência cardíaca congestiva (ICC) ocasionada pela cardiomiopatia dilatada idiopática (CMDId) constitui-se em quadro causador de grande impacto na saúde pública, apresentando morbidade e mortalidade significativas, porém muitos aspectos referentes à sua fisiopatologia ainda permanecem desconhecidos, de modo que trabalhos que estudem tais aspectos poderão contribuir para melhor entendimento desta entidade. Objetivos: Avaliar aspectos anatômicos e histológicos de corações com CMDId e compará-los a um grupo controle de corações normais, obtendo-se as medidas dos perímetros dos anéis atrioventriculares direito (AVD) e esquerdo (AVE) e dos ventrículos direito (VD) e esquerdo (VE) bem como a porcentagem por área de fibras colágenas e elásticas dos anéis atrioventriculares direito e esquerdo. Métodos: Foram analisados 13 corações de pacientes que faleceram vítimas de CMDId e 13 corações normais de pacientes que faleceram por causas não relacionadas à doenças cardiovasculares. Os corações foram fixados em formol, dissecados de forma a manter-se apenas os anéis atrioventriculares e a massa ventricular, com posterior laminação desta em segmentos transversais correspondentes a 20%, 50% e 80% da distância compreendida entre o sulco atrioventricular e o ápice ventricular esquerdo. Os cortes assim obtidos foram submetidos à digitalização fotográfica, que permitiu a aferição de ambos os perímetros ventriculares por meio de software específico, tornando possível a comparação de tais medidas entre os grupos e os segmentos. Os anéis atrioventriculares foram posteriormente dissecados, fotografados e medidos digitalmente para aferição das medidas perimetrais a direita e a esquerda, sendo posteriormente enviados ao laboratório de anatomia patológica, sendo realizadas colorações por meio de hematoxilinaeosina, picrossírius e resorcina fuccina oxidada, permitindo estudo das fibras colágenas e elásticas. Resultados: Com relação aos segmentos ventriculares, notou-se que no grupo CMDId ocorre dilatação nos segmentos apical, equatorial e basal, tanto a direita quanto a esquerda A medida do AVD foi maior no grupo CMDId , não havendo diferença estatisticamente significante com relação ao AVE entre os dois grupos. Com relação ao percentual por área de fibras colágenas, tanto o AVE quanto o AVD apresentaram percentagem de fibras menor no grupo CMDId em relação ao grupo normal. Com relação ao percentual por área de fibras elásticas, não houve diferença entre os grupos. Conclusões: Ocorre alteração da geometria ventricular com dilatação tanto a direita quanto a esquerda no grupo CMDId, porém com comportamento distinto entre o VE e o VD. O anel atrioventricular esquerdo não se dilata, ao contrário do direito, a despeito do fato de em ambos ocorrer diminuição da área total de colágeno, sugerindo que o mecanismo de dilatação possa apresentar particularidades oriundas de diferenças estruturais e pressóricas em ambos os ventrículos<br>Introduction: Congestive heart failure caused by idiopathic dilated cardiomyopathy causes great impact on public health, with significant morbidity and mortality, but many aspects related to its pathophysiology remain unknown, so further studies can contribute to better understanding of this entity. Objectives: To evaluate anatomical and histological aspects of hearts from patients who died victims of idiopathic dilated cardiomyopathy and compare them to a control group, to evaluate the behavior of the perimeters of the right and left atrioventricular rings and left and right ventricles and to compare the percentage area of collagen and elastic fibers of the right and left atrioventricular rings in both groups. Methods: We analyzed 13 hearts of patients who died from idiopathic dilated cardiomyopathy and 13 normal hearts from patients who died of causes not related to cardiovascular disease. The hearts were fixed in formalin, dissected in order to keep only the ventricular mass and atrioventricular rings, with subsequent lamination of segments corresponding to 20%, 50% and 80% of the distance between the atrioventricular groove and the left ventricular apex . The sections obtained were subjected to photo scanning, which allowed the measurement of ventricular perimeters by means of specific software, making it possible to compare these measures between groups and segments. The atrioventricular rings were then dissected, photographed and measured digitally to evaluate the right and left perimeters, later being sent to the pathology laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin, enabling study of collagen and elastic fibers. Results: Regarding to ventricular segments, it was noted that in the idiopathic dilated cardiomyopathy group dilation occurs in the apical, equatorial and basal segments, at both sides, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no statistically significant difference in the left side between the two groups. With respect to the percentage by area of collagen fibers, both the left and the right sides had lower percentage of fibers in the idiopathic dilated cardiomyopathy group compared to the normal group. With respect to the percentage by area of elastic fibers, there was no difference between the groups. Conclusions: There is a change in ventricular geometry in idiopathic dilated cardiomyopathy group, but with different behavior between the left and right ventricles. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of the total area of collagen, suggesting that the mechanism of dilation may present peculiarities arising from structural differences and pressure load in both ventricles

Objetivo: Determinar os valores dopplervelocimétricos normais do fluxo através da valva tricúspide em gestações únicas, entre 11 e 13 semanas e seis dias. Examinar a reprodutibilidade dos parâmetros avaliados e sua correlação com variáveis clínicas maternas e obstétricas. Métodos: Estudo prospectivo envolvendo 166 gestações únicas, com desfecho normal, examinadas entre 11 e 13 semanas e seis dias, no período de fevereiro de 2006 a agosto de 2008. Foram aferidas as velocidades máximas das ondas E e A, duração do ciclo cardíaco completo e sua fase diastólica e calculadas as relações onda E/onda A e diástole/ciclo. Os valores normais foram descritos pelas respectivas médias e desvio-padrão. Para análise da reprodutibilidade desses parâmetros foi calculado o coeficiente de correlação intra-classes em 12 casos examinados por dois examinadores. Regressão linear simples e multivariada foram empregadas para examinar a correlação dos parâmetros dopplervelocimétricos entre si e com a idade gestacional, a medida da translucência nucal e variáveis maternas. Resultados: Neste intervalo gestacional, os valores normais encontrados foram: onda E, 25 (± 4,6) cm/s; onda A, 42,9 (± 5,9) cm/s; relação E/A, 0,58 (± 0,07); ciclo cardíaco, 390 (± 21,1) ms; diástole, 147 (± 18) ms; relação diástole/ciclo, 0,38 (± 0,04). Entre as variáveis dopplervelocimétricas, foi observada correlação significativa entre o ciclo cardíaco e diástole (r=0,53; p<0,0001), diástole e onda A (r=-0,15; p=0,05), ondas E e A (r=0,77; p<0,0001), onda E e relação D/C (r=0,16; p=0,04), onda A e relação diástole/ciclo (r=-0,17; p=0,03). Todas as variáveis, exceto a velocidade da onda A, correlacionaram-se positivamente com a idade gestacional. Não foi observada correlação significativa das variáveis com a medida da translucência nucal, e, na comparação com as variáveis maternas, apenas a onda E e a idade materna apresentaram correlação significativa (r=-0,18, p=0,04). Os coeficientes de correlação intra-classes para a avaliação interobservador e intra-observador (examinadores um e dois) foram: onda E = 0,53 (0,53 e 0,64); onda A = 0,45 (0,46 e 0,49); ciclo cardíaco = 0,70 (0,79 e 0,84) e diástole = 0,63 (0,85 e 0,82). Conclusão: O presente estudo estabeleceu os valores normais dos parâmetros dopplervelocimétricos do fluxo através da valva tricúspide e demonstrou que tais parâmetros, com exceção da onda A, correlacionaram-se de forma positiva com a idade gestacional, e apresentaram reprodutibilidade boa/moderada.<br>Objective: To establish the measurements of normal tricuspid valve flow velocities at 11 to 13 weeks and 6 days to determine E-wave, A-wave, E/A ratio, cardiac cycle length, diastole length, diastole/cardiac cycle ratio, and their relationship with gestational age, nuchal translucency thickness, the characteristics of the study population, and to assess the reproducibility of flow measurements. Methods: Between February, 2006, and August, 2008, a total of 166 women with a singleton normal pregnancy between 11 and 13 + 6 weeks of gestation consented to participate in the study. Analysis of the waveforms consisted of calculation of peak velocity (cm/s) of the E-wave and A-wave, E-wave/A-wave ratio, cardiac cycle length (ms), diastole length (ms) and diastole/cardiac cycle ratio. To evaluate the intraobserver and interobserver agreement, a subgroup of 12 patients, chosen randomly, was examined twice by each examiner. For descriptive analysis of the results were calculated average and standard deviation. Simple and multivariate linear regression was used to establish the correlation between dopplervelocimetry among parameters and with gestational age, nuchal translucency thickness and the characteristics of the study population. Results: The average (± standard deviation) for transtricuspid flow-velocities waveforms parameters were: E-wave 25 (± 4.6) cm/s; A-wave 42.9 (± 5.9) cm/s; E/A ratio 0.58 (± 0.07); cardiac cycle length 390 (± 21.1) ms; diastole length 147 (± 18) ms; diastole/cardiac cycle length 0,38 (± 0.04). A statistically significant linear increase relative to gestational age was established for all parameters, except A-wave. Nuchal translucency thickness was not correlated with any parameter. A statistically significant negative regression coefficient was established for E-wave to maternal age (r=-0,18, p=0,04). A statistically significant relationship was established between: cardiac cycle length and diastole length (r=0.53; p<0.0001); diastole length and A-wave velocity (r=-0.15; p=0.05); E-wave and A-wave velocities (r=0.77; p<0.0001); E-wave velocity and D/C ratio (r=0.16; p=0.04); A-wave velocity and D/C ratio (r=-0.17; p=0.03). The intraclass correlation coeficients of interobserver and intraobsever evaluations (examiners 1 and 2) were: Ewave = 0.53 (0.53 and 0.64); A-wave = 0.45 (0.46 and 0.49); cardiac cycle = 0.70 (0.79 and 0.84) and diastole= 0.63 (0.85 and 0.82). Conclusions: These data determine normal parameters for tricuspid valve dopplervelocimetry and shows that these parameters, except A-wave, have positive correlation with gestational age, and good/moderate reproducibility.

122 pacientes fueron intervenidos realizándose una doble reparación mitral y tricúspide por una enfermedad orgánica reumática. La reparación de la válvula mitral consistió en una anuloplastia con anillo flexible de Durán asociada a comisurotomía en 98 pacientes (80.3%) y anuloplastia flexible aislada en 24 pacientes (19.7%). La reparación valvular tricúspide se realizó en 78 pacientes (63.9%) mediante anuloplastia con anillo flexible y comisorotomía, y en 44 (36.1%) una anuloplastia con anillo flexible de Durán® aislada. La comisurotomia mitral cerrada previa y el tiempo postclampaje constituyeron los principales factores predictivos de riesgo. La mortalidad tardía ha sido de 94 pacientes (77.1%). La causa cardiaca (60.7%) ha sido el motivo más frecuente. Un total de 46 (37.7%) pacientes han precisado de una reoperación. La reparación simultanea mitral y tricúspide en la enfermedad reumática orgánica con anuloplastia de Durán® presenta unos resultados precoces satisfactorios. No obstante, la progresión de la enfermedad valvular es determinante en los resultados a largo plazo.<br>Between 1974 and 1999, 122 consecutive patients (mean age, 45.1 ± 12.5 years) underwent combined mitral and tricuspid valve annuloplasty with a flexible ring for rheumatic disease. Mitral repair included commissurotomy associated with a flexible annuloplasty in 98 (80.3%), and isolated flexible annuloplasty in 24 (19.7%). Tricuspid valve repair included flexible annuloplasty in 44 patients (36.1%) and annuloplasty combined with tricuspid commissurotomy in 78 patients (63.9%). Predictors of early mortality were previous mitral closed commisurotomy and postclamping time. Late mortality was 94 patients (77.1%) and the main cause was cardiac failure. Forty-six (37.7%) patients required valve reoperation, of which 31 (67.4%) has been for a progression of rheumatic valvular disease. Simultaneous mitral and tricuspid valve repair in rheumatic valve disease with Duran® flexible annuloplasty shows a satisfactory thirty-day mortality. However, progression of valvular disease is determinant of long-term results.

L'objectif de cette thèse est l'élaboration et l'application de traitements d'images pour permettre une étude objective et fiable des sinus de Valsalva, importantes cavités de la base de l'aorte. Les méthodes proposées s'appliquent aux séquences ciné-IRM et aux examens de scanner sans qu'il n'y ait à modifier le paramétrage entre deux examens. Pour cela, nous avons d'abord étudié la morphologie de cette zone anatomique puis détaillé les différentes propriétés communes à toutes les images de sinus. Ceux-ci font en l'occurrence partie des principaux organes clairs et peu mobiles. Nous avons donc développé un algorithme qui détecte ces éléments et caractérise chacun d'entre eux par une trajectoire unique. Divers outils de morphologie mathématique ont été utilisés à cette occasion, tout comme pour l'extraction du contour des sinus dans chaque image. L'étape de segmentation repose elle sur la reconstruction géodésique, qui s'avère plus efficace et surtout plus robuste que l'usage de contours actifs usuels. L'intérieur des sinus forme un domaine simplement connexe et étoilé. Grâce à ce postulat, nous avons conçu une nouvelle reconstruction, nommée transformée en aurore, qui limite la propagation des intensités aux supports radiaux et présente les résultats dans un repère polaire pour une meilleure lecture des contours.Les points caractéristiques des sinus ont également été détectés, par étude de rayons et détermination de points dominants. Ces points fournissent les éléments nécessaires à une mesure automatique des sinus, mesure cohérente avec les mesures actuellement réalisées manuellement et les variations intra et inter-observateurs de celles-ci. D'autres outils sont enfin esquissés pour modéliser le contour par coniques, classer les images d'examens cinétiques en fonction du moment du cycle et suivre le mouvement des valves dans ces mêmes examens.L'ensemble de ces travaux ont amené à la réalisation d'un logiciel d'aide au diagnostic qui intègre nos méthodes et dont l'interface est également présentée dans le présent mémoire.

Dissertação de Mestrado Integrado em Medicina Veterinária<br>A doença mixomatosa da válvula mitral é a doença cardíaca adquirida mais comum em cães, estando associada a um aumento da pressão no átrio esquerdo com possível ocorrência de transmissão passiva retrógrada de pressão para as veias e capilares pulmonares. Na hipertensão pulmonar venosa crónica pode ocorrer vasoconstrição e remodelação vascular, originando hipertensão pulmonar arterial. Esta pode levar a hipertrofia e dilatação do ventrículo direito e eventualmente insuficiência cardíaca congestiva direita. Em Medicina Veterinária, o diagnóstico da hipertensão pulmonar é maioritariamente realizado através de ecocardiografia, com base no valor de velocidade da regurgitação da tricúspide. Os objectivos do presente trabalho foram determinar a prevalência de hipertensão pulmonar em canídeos com doença mixomatosa da válvula mitral; avaliar se o rácio átrio esquerdo:aorta e se a classificação da insuficiência cardíaca estão associados à presença de hipertensão pulmonar e avaliar a função diastólica do ventrículo direito (através do rácio E:A transtricúspide) em canídeos com doença mixomatosa da válvula mitral. A amostra total foi composta por quarenta e seis canídeos, trinta e um com doença mixomatosa da válvula mitral e os restantes quinze utilizados como grupo controlo, tendo sido realizada uma ecocardiografia transtorácica a todos os animais. A prevalência de hipertensão pulmonar em canídeos com doença mixomatosa da válvula mitral foi de 9,7%, existindo uma associação estatisticamente significativa entre as classes de insuficiência cardíaca presentes e os grupos de canídeos com doença mixomatosa da válvula mitral com e sem hipertensão pulmonar. Esta significância não se verificou em relação ao rácio átrio esquerdo:aorta. Foi encontrada diferença estatisticamente significativa do rácio E:A transtricúspide entre o grupo de canídeos com doença mixomatosa da válvula mitral e o grupo controlo. É sugerido que a evidência ecocardiográfica de hipertensão pulmonar não é um achado raro em cães com doença mixomatosa da válvula mitral e que deve ser suspeita, principalmente nos casos de insuficiência cardíaca congestiva direita. Os resultados foram também sugestivos de que canídeos com doença mixomatosa da válvula mitral podem apresentar alteração da função diastólica do ventrículo direito.<br>ABSTRACT - Contribution to the assessment of pulmonary hypertension in dogs with myxomatous mitral valve disease - Myxomatous mitral valve disease is an acquired heart disease common in dogs. This disease is associated with an increase of the left atrial pressure with the possibility of passive transmission of pressure to pulmonary veins and capillaries. In chronic pulmonary venous hypertension, vasoconstriction and vascular remodeling may occur, resulting in pulmonary arterial hypertension. This can lead to right ventricle hypertrophy/dilatation and eventually, right-side congestive heart failure may occur. In veterinary medicine, pulmonary hypertension diagnosis are mainly done through echocardiography, based on tricuspid regurgitation velocity value. The objectives of this study were to determine the prevalence of pulmonary hypertension in dogs with myxomatous mitral valve disease; to evaluate the relationship of the left atrial diameter to the aortic root ratio and heart failure classification with pulmonary hypertension; to assess the right ventricular diastolic function (transtricuspid E:A ratio) in dogs with myxomatous mitral valve disease. The study included forty six dogs, all submitted to a transthoracic echocardiography. Thirty one had myxomatous mitral valve disease and the last fifteen dogs were in group control. The prevalence of pulmonary hypertension in dogs with myxomatous mitral valve disease was 9,7%, with a significantly statistic association between the heart failure classifications and the dogs with and without pulmonary hypertension associated with myxomatous mitral valve disease. Regarding the left atrial diameter to the aortic ration, no significantly relation was observed. Respecting the transtricuspid E:A ratio, a significantly statistic difference was registered between dogs with myxomatous mitral valve disease and the control group. It is suggested that echocardiographic evidence of pulmonary hypertension is not rare in dogs with myxomatous mitral valve disease and therefore it should be under suspicion, especially in dogs with right-side congestive heart failure. The results also revealed that dogs with myxomatous mitral valve disease may have impaired right ventricular diastolic function.

Résumé - Les données concernant la prise en charge chirurgicale de la maladie tricuspidienne reposent sur des études de cohortes à petite échelle et peu d’entre elles se sont intéressées aux résultats échocardiographiques et aux facteurs de risque de mortalité et de morbidité. Une étude de cohorte rétrospective descriptive et analytique fut effectuée pour analyser l’expérience de l’Institut de Cardiologie de Montréal concernant la chirurgie de la VT. Les données ont été récoltées à l’aide des dossiers médicaux. Durant la période 1977-2008, 792 PVT et 134 RVT furent effectués (âge médian : 62 ans). La mortalité opératoire était de 13,8%. Les taux de survie actuarielle à 5, à 10 et à 15 ans étaient respectivement de 67±2%, de 47±2% et de 29±2%. Au dernier suivi, de l’IT ≥3/4 était présente chez 31% des patients du groupe PVT et chez 12% des patients du groupe RVT (p<0,001). La classe fonctionnelle NYHA s’est améliorée significativement au dernier suivi par rapport à la période pré-opératoire (p<0,001). L’analyse de propension montre que par rapport à une PVT, un RVT est associé significativement à des taux de mortalité opératoire et tardive accrus, mais à moins d’IT ≥2/4 ou ≥3/4 lors du suivi. Cette étude montre que malgré le risque chirurgical substantiel associé à la chirurgie de la VT, les patients bénéficient d’une amélioration fonctionnelle significative. Les facteurs de risque de mortalité et de morbidité sont décrits et des études de sous-groupes sur la chirurgie tri-valvulaire et la chirurgie isolée de la VT sont exposées.<br>Abstract - Data regarding surgical management of tricuspid valve disease are based on small cohort studies, and only few of them report echocardiographic results or risk factors for mortality and morbidity. A retrospective descriptive and analytic cohort study was performed in order to analyze the Montreal Heart Institute experience regarding tricuspid valve surgery. Data was extracted from the medical files of patients. During the 1977-2008 period, 792 tricuspid valve repairs and 134 tricuspid valve replacements were performed (median age of patients: 62 years). Operative mortality was 13.8%. Actuarial survival rates at 5, 10, and 15 years were 67±2%, 47±2%, and 29±2%, respectively. At last follow-up, 31% of patients who underwent repair and 12% of patients who underwent replacement had tricuspid regurgitation ≥3/4 (p<0,001). NYHA functional class improved significantly at last follow-up compared to baseline (p<0,001). Propensity score analysis showed that a replacement was associated with increased operative and late mortality rates compared to repair, but with less tricuspid regurgitation ≥2/4 or ≥3/4 at follow-up. The study shows that despite substantial mortality rates, patients experience a significant functional improvement following tricuspid valve surgery. Risk factors for mortality and morbidity are described, and sub-group analyses for triple valve surgery and for isolated tricuspid valve surgery are exposed.

This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. Of the 234 patients who received LVAD therapy in the Heart Center Leipzig during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7–28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283–848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). We concluded that preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.:Inhaltsverzeichnis Abkürzungsverzeichnis 3 1. Einführung 4 2. Formatierte Publikation 12 3. Zusammenfassung der Arbeit 19 4. Literaturverzeichnis 23 5. Anlagen 28 5.1. Statistical analysis of echocardiographic parameters in follow-up 28 5.2. Statistical Models Used 30 Darstellung des eignen wissenschaftlichen Beitrages 32 Erklärung über die eigenständige Abfassung der Arbeit 33 Lebenslauf 34 Publikationen 37 Danksagung 38

Indiana University-Purdue University Indianapolis (IUPUI)<br>The heart is a complex organ that is composed of numerous cell types, which must integrate their programs for proper specification, differentiation, and cardiac morphogenesis. During cardiac development the basic helix-loop-helix transcription factor Hand2 is dynamically expressed within the endocardium and extra-cardiac lineages such as the epicardium, cardiac neural crest cells (cNCCs), and NCC derived components of the autonomic nervous system. To investigate Hand2 function within these populations we utilized multiple murine Hand2 Conditional Knockout (H2CKO) genetic models. These studies establish for the first time a functional requirement for Hand2 within the endocardium, as several distinct phenotypes including hypotrabeculation, tricuspid atresia, aberrant septation, and precocious coronary development are observed in endocardial H2CKOs. Molecular analyses reveal that endocardial Hand2 functions within the Notch signaling pathway to regulate expression of Nrg1, which encodes a crucial secreted growth factor. Furthermore, we demonstrate that Notch signaling regulates coronary angiogenesis via Hand2 mediated modulation of Vegf signaling. Hand2 is strongly expressed within midgestation NCC and endocardium derived cardiac cushion mesenchyme. To ascertain the function of Hand2 within these cells we employed the Periostin Cre (Postn-Cre), which marks cushion mesenchyme, a small subset of the epicardium, and components of the autonomic nervous system, to conditionally ablate Hand2. We find that Postn-Cre H2CKOs die shortly after birth despite a lack of cardiac structural defects. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla, causing downregulation of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit significantly slower heart rates than control littermates. In conjunction with the aforementioned gene expression analyses, these results indicate that loss of Hand2 function within the adrenal medulla results in a catecholamine deficiency and subsequent heart failure.

Indiana University-Purdue University Indianapolis (IUPUI)<br>The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.