Rozprawy doktorskie na temat „Mitral valve insufficiency”

The projects of this thesis examine the complex interaction between isotonic exercise, functional capacity, exercise-induced myocardial ischaemia, severity of regurgitation and left ventricular function in patients with significant chronic mitral regurgitation. The concept of left ventricular contractile reserve, i.e. the ability of the left ventricle to increase its contractility and decrease its end systolic volume with isotonic exercise, is explored. In patients with chronic isolated mitral regurgitation without coronary disease, isotonic exercise was associated with a slight decrease in left ventricular end diastolic volume but a marked decrease in end systolic volume, resulting in a significant increase in the stroke volume and ejection fraction. Early after uncomplicated mitral valve repair surgery, there was a significant decrease in the left ventricular ejection fraction with a proportion of the patients developing left ventricular dysfunction despite a normal pre-operative ejection fraction. When different pre-operative echocardiographic indices of left ventricular function were evaluated for their ability to predict left ventricular function after mitral valve repair, the exercise indices were found to be superior to resting indices. Left ventricular end systolic volume immediately after exercise was found to be the best predictor. The optimal cut-off was at 25 ml/m2, which had a sensitivity and specificity of 83% in predicting early post-operative left ventricular dysfunction. Exercise indices appeared to be superior to resting indices in identifying patients with persistent left ventricular dysfunction <1 year after mitral valve repair. The concept of contractile reserve was further examined by estimating the left ventricular stroke work from simplified pressure-volume loops, which were constructed from non-invasively obtained parameters with geometric assumptions. Left ventricular stroke work immediately after exercise, but not at rest, was found to be significantly lower in patients with latent left ventricular dysfunction. Patients without latent ventricular dysfunction had similar increases in stroke work with exercise compared with healthy normal subjects. The ability of the left ventricle to increase its stroke work with exercise, a measure of the contractile reserve, was correlated with the left ventricular ejection fraction after mitral valve repair. A numerical model was constructed using the clinical data as input parameters. The results from the numerical model were similar to that obtained from the clinical study, testifying that the observation made in the clinical study was valid and independent of the geometric assumptions made in constructing the simplified pressure-volume loops. Left ventricular pressure-volume loops under different loading conditions were plotted from simultaneously measured left ventricular pressure and volume to measure the left ventricular end systolic elastance (Ees) and preload recruitable stroke work relationship (MSW). Despite normal or near normal haemodynamics at rest, a significant proportion of the study patients were found to have impaired left ventricular contractility, as measured by Ees, consistent with a state of latent left ventricular dysfunction. Exercise indices of left ventricular function were better correlated with Ees and MSW than resting indices. There were highly significant inverse relationships between end systolic volume index immediately after exercise and Ees and MSW. Moreover, there was a significant powered relationship between MSW and exercise left ventricular ejection fraction. There was no such relationship between Ees or MSW and any of the resting echocardiographic indices of left ventricular function. Furthermore, the optimal diagnostic cut-off level of end systolic volume index after exercise at 25 ml/m2 accurately identified those with impaired left ventricular contractility as defined by an Ees of > 2 mmHg/ml. In patients with chronic organic mitral regurgitation with ejection fraction of < 50%, objectively measured functional capacity, VO2max, was correlated with exercise cardiac output, patient age and gender but not to the severity of the mitral regurgitation or the resting left ventricular function. The VO2max of these patients were significantly lower than that of age and gender-matched healthy controls despite these patients' relative lack of subjective symptoms. There were significant individual variations in the response of the severity of the mitral regurgitation to isotonic exercise. Patients whose regurgitant stroke volume increased had a lower exercise cardiac output than those whose regurgitant stroke volume decreased. Such variability was also seen with the response of the left ventricular function to exercise. Patients whose left ventricular end systolic volume increased with exercise, i.e. patients with a limited contractile reserve, had a lower exercise cardiac output and lower VO2max than those whose end systolic volume decreased with exercise. The determinants of exercise capacity were then examined in patients with functional mitral regurgitation and left ventricular dysfunction. VO2max of these patients was correlated with exercise cardiac output and exercise left ventricular ejection fraction, a situation similar to that seen in patients with organic mitral regurgitation and normal left ventricular function. Furthermore, indices of left ventricular systolic function at rest and pulsed wave Doppler indices of diastolic function showed no significant correlations with VO2max. The determinants of VO2max remained unchanged in these patients after four weeks of supervised exercise training. The four weeks of exercise training resulted in a significant decrease in left ventricular end systolic volume, a trend towards an increase in left ventricular ejection fraction and some restoration of the contractile reserve. The total exercise time almost doubled. However, this dramatic improvement in total exercise time was accompanied only by non-significant increases in VO2max and left ventricular ejection fraction. Therefore, the benefits of exercise training in these patients may involve more than just central mechanisms. Exercise induced myocardial ischaemia may also contribute to a limited left ventricular contractile reserve in patients with mitral regurgitation. Electrocardiographic changes at rest are commonly seen in patients with mitral regurgitation due to mitral valve prolapse. These resting electrocardiographic changes make exercise electrocardiography uninterpretable for exercise-induced ischaemia. Exercise electrocardiographic changes are also commonly encountered in these patients despite the absence of coronary artery disease and a normal resting electrocardiogram, making exercise electrocardiography unreliable as a non-invasive screening test for coronary artery disease. In these patients, exercise echocardiography was slightly more sensitive but significantly more specific in diagnosing significant coronary artery disease. The overall accuracy and the positive predictive value were significantly higher for exercise echocardiography than for exercise electrocardiography. The "cost-effectiveness" of different diagnostic strategies for coronary artery disease in patients with mitral valve prolapse was examined based on the results of the clinical study. Strategies involving exercise electrocardiography as part of the screening test were costly and were associated with a high false negative rate. Strategies involving exercise echocardiography were more accurate and less costly but the initial costs of exercise echocardiography for all patients meant that the overall costs were still considerable. Assessing the pre-test probability of coronary artery disease in these patients and using exercise echocardiography as the initial test for patients with at least a moderate pre-test probability of coronary artery disease seemed to result in the best compromise between cost and effectiveness. The studies of this thesis have shown that a limited cardiac contractile reserve is a sign of latent ventricular dysfunction in patients with chronic mitral regurgitation. The presence of a limited contractile reserve can be used to predict left ventricular dysfunction after mitral valve repair. The concept of a limited contractile reserve is further supported by the finding of a limited increase in left ventricular stroke work with exercise from a theoretical as well as a numerical model of left ventricular pressure-volume loops. Exercise echocardiographic indices show better correlations to invasively measured Ees and MSW than resting indices. VO2max in these patients is determined more by their ability to increase their forward cardiac output with exercise and not by the regurgitant volumes. Exercise training in patients with left ventricular dysfunction and functional mitral regurgitation results in some restoration of contractile reserve. Exercise echocardiography is also a reliable and cost-effective test in the non-invasive screening for coronary artery disease in these patients. Based on the results of the studies in the thesis, one can incorporate exercise echocardiography as one of the important assessment tools in the management of patients with significant mitral regurgitation as it allows measurement of left ventricular volumes and assessment of contractile reserve. Further studies are needed to examine whether a policy of monitoring of contractile reserve in these patients to guide therapy and surgical referral will result in a better preservation of long term left ventricular function, an improvement in functional capacity and patient outcome.

Introdução: Embora o papel da ecocardiografia transesofágica (ETE) esteja bem estabelecido na avaliação morfológica e funcional da valva mitral e na seleção dos pacientes com prolapso da valva mitral (PVM) para a cirurgia reparadora, o impacto da ETE tridimensional (3D) no resultado cirúrgico ainda não está bem demonstrado. Os objetivos deste trabalho foram avaliar o valor diagnóstico adicional da ETE 3D em comparação com a técnica bidimensional (2D) e a associação de parâmetros anatômicos tridimensionais com o resultado cirúrgico em pacientes com PVM submetidos à valvoplastia. Métodos: Para a análise comparativa da sensibilidade, especificidade e acurácia diagnóstica entre ETE 2D e 3D, foram incluídos 62 pacientes operados por PVM com insuficiência importante, sendo a inspeção cirúrgica considerada padrão-ouro. Para a análise 3D, foram estudados 54 pacientes submetidos à plástica valvar que foram divididos em 2 grupos de acordo com o grau da insuficiência mitral pós-operatória (grupo 1, insuficiência mitral ausente ou grau I; grupo 2, insuficiência mitral grau II ou III). Foram medidos pela quantificação 3D os seguintes parâmetros anatômicos: diâmetros anteroposterior e intercomissural, altura, circunferência e área do anel mitral; comprimento, área e linha de coaptação das cúspides; volume e altura do prolapso; distância dos músculos papilares à borda da cúspide; e ângulos mitroaórtico e não planar. Para a identificação de variáveis associadas aos grupos de resultados cirúrgicos, foi realizada análise univariada (teste t de Student para as variáveis contínuas e teste qui-quadrado ou o teste de Fisher para as variáveis categóricas), análise multivariada com método de regressão logística e curva ROC para a obtenção do ponto de corte. Resultados: A ETE 2D apresentou maior sensibilidade no diagnóstico de prolapso nos segmentos A2, P1 e P3 que a ETE 3D (p = 0,019, 0,023, 0,012, respectivamente) enquanto que a ETE 3D apresentou maior especificidade no segmento P1 (p = 0,006). Não houve diferença na acurácia diagnóstica ente os dois métodos. A presença de prolapso das duas cúspides (p = 0,041) e a distância do músculo papilar posteromedial à borda da cúspide (p = 0,038) foram maiores no grupo 2. Análise multivariada identificou prolapso das duas cúspides e distância do músculo papilar posteromedial à borda da cúspide maior que 30 mm como fatores associados à insuficiência mitral pós-operatória grau II ou III (p = 0,039 e 0,015, respectivamente), e com risco de 5,3 e 6,3 vezes maior de insuficiência significativa pós-operatória, respectivamente. Conclusões: A ETE 2D e 3D apresentaram acurácia equivalente no diagnóstico de PVM, com maior sensibilidade da ETE 2D no diagnóstico de prolapso nos segmentos A2, P1 e P3, e maior especificidade da ETE 3D no segmento P1. A distância do músculo papilar posteromedial à borda da cúspide obtida pela análise quantitativa 3D e a presença de prolapso das duas cúspides mostraram associação com o grau da insuficiência mitral pós-operatória grau II e III
Background: Although the transesophageal echocardiography (TEE) is well established in the morphological and functional assessment of the mitral valve and in the choice of patients with mitral valve prolapse (MVP) eligible to valvuloplasty, the impact of tridimensional (3D) TEE on surgical results has not been well demonstrated yet. The present study aimed to evaluate the additional diagnostic value of 3D TEE in comparison with bidimensional (2D) technique, as well as the correlation between 3D anatomical parameters and the surgical results in patients with MVP submitted to valvuloplasty. Methods: In order to compare the sensitivity, specificity, and accuracy between 2D and 3D TEE, 62 patients with MVP and severe mitral regurgitation were enrolled; surgical appraisal was considered as the gold-standard. Regarding 3D analysis, 54 patients submitted to valvuloplasty were divided in two groups, according to their postoperative mitral regurgitation grades (group 1, absent or grade I mitral regurgitation; and group 2, grade II or III mitral regurgitation). The following parameters were assessed quantitatively by 3D TEE: anteroposterior diameter, commissural width, height, circumference and area of the mitral ring; anterior and posterior leaflets length, leaflets surface area, coaptation length, volume and height billow; distance from the tip of the anterolateral and posteromedial papillary muscle to leaflet border; non-planar and aortic-mitral angles. Univariate analysis (Student t test for continuous variables and Chi-square or Fischer test to the categorical ones), multivariate and ROC curve analyses were performed to identify the relationship between anatomical parameters and surgical results (p < 5%). Results: 2D TEE showed higher sensitivity to diagnose MVP in A2, P1, and P3 segments, when compared with 3D TEE (p= 0.019, 0.023, and 0.012, respectively), while 3D TEE showed greater specificity to identify P1 segment (p= 0.006). No difference was observed in the accuracy between both methods. The presence of bileaflet prolapse (p= 0.041) and the distance from posteromedial papillary muscle to leaflet border (p= 0.038) were higher in group 2. Multivariate analysis showed that bileaflet prolapse and distance of more than 30 mm from posteromedial papillary muscle to leaflet border were related to grade II or III postoperative mitral regurgitation (p= 0.039 and 0.015, respectively), representing 5.3 and 6.3 more risk of significant mitral regurgitation, respectively. Conclusions: Both 2D TEE and 3D TEE presented similar accuracy in the diagnosis of MVP; 2D TEE showed higher sensitivity to diagnose the prolapse in A2, P1 and P3 segments, while the 3D TEE presented greater specificity to identify the affected P1 segment. The distance from the tip of the posteromedial papillary muscle to the leaflet border quantitatively estimated by 3D TEE and the evidence of bileaflet prolapse showed to be associated to the degree of mitral regurgitation after valvuloplasty

INTRODUÇÃO: A plastia valvar mitral é o tratamento de escolha para a correção da insuficiência mitral mixomatosa. Estudos ecocardiográficos tridimensionais demonstram que a plastia mitral com implante de anéis protéticos altera a morfologia e a função do anel valvar mitral, porém a literatura é escassa em relação ao comportamento do anel mitral após a plastia mitral sem utilização de anéis protéticos. OBJETIVO: Analisar a morfologia e a função cardíaca de indivíduos submetidos à plastia valvar mitral pela técnica de Duplo Teflon, através da ecocardiografia tridimensional em tempo real. CASUÍSTICA: Foram incluídos 14 pacientes portadores de insuficiência mitral secundária a degeneração mixomatosa, que foram submetidos à plastia valvar mitral pela técnica de Duplo Teflon. Destes, 10 pacientes eram do sexo masculino e a idade média foi de 61,3 ± 11,2 anos. Em relação à classe funcional, 13 pacientes encontravam-se em classe III ou IV no período pré-operatório. Na análise ecocardiográfica pré-operatória, o valor médio do volume diastólico final do ventrículo esquerdo foi 156,57 ± 46,61ml, e a fração de ejeção do ventrículo esquerdo variou de 38 a 68%, com média de 57,93 ± 6,67%. O valor médio do anel mitral posterior foi 6,97 ± 0,13 cm. MÉTODOS: Os pacientes foram avaliados nos períodos pré-operatório, pós-operatório imediato (POI), 6 meses e 1 ano após a plastia mitral. A ecocardiografia tridimensional avaliou a morfologia do anel mitral através das medidas do anel anterior e posterior, dos diâmetros transversos e da área valvar. A função anular foi avaliada pela relação entre as áreas valvares internas durante a sístole e diástole. Foram avaliados os volumes e a função do átrio e do ventrículo esquerdos. Foi utilizado teste de análise de variância de medidas repetidas para o estudo estatístico, sendo considerado estatisticamente significante p < 0,05. RESULTADOS: O anel mitral posterior demonstrou uma redução significativa (p<0,001) no POI, que manteve-se estável durante o estudo. Não houve variação significativa na área valvar durante o estudo. Houve uma redução significativa nos diâmetros ântero-posterior e médio-lateral no POI (p<0,001), porém houve um aumento significativo no diâmetro médio-lateral entre POI e 1 ano. A fração de variação do anel mitral durante o ciclo cardíaco, ao longo do estudo, variou entre 30,92 e 35,75%, não havendo diferença estatisticamente significante. A análise dos volumes sistólicos, atrial e ventricular, demonstrou uma redução volumétrica significativa entre POI e 1 ano (p=0,028 e p=0,020, respectivamente). Entre o pré-operatório e 1 ano, houve uma redução média de 19,9% e 15,4% nos volumes atrial e ventricular, respectivamente. Os volumes diastólicos atrial e ventricular apresentaram uma redução significativa no POI (p<0,001 e p=0,024, respectivamente), permanecendo estáveis ao longo do estudo. Houve aumento na fração de ejeção do átrio esquerdo após 6 meses (p<0,001), porém não houve variação na função ventricular esquerda. CONCLUSÕES: A plastia mitral com a anuloplastia segmentar pela técnica do Duplo Teflon reduziu o anel posterior da valva mitral, que permaneceu estável no período de um ano. A variação da área anular mitral durante o ciclo cardíaco permaneceu estável durante o estudo. Além disso, houve um remodelamento reverso atrial e ventricular esquerdo, associado à melhora na função do átrio esquerdo
INTRODUCTION: Mitral valve repair is the treatment of choice to correct mixomatous mitral insufficiency. Tridimensional echocardiography studies demonstrate that mitral repair using prosthetic ring implant modifies mitral valve annulus morphology and function, although the literature related to mitral valve annulus behavior after mitral repair without use of prosthetic rings is scarce. OBJECTIVE: Analyze cardiac morphology and function using real time tridimensional echocardiography in individuals submitted to mitral valve repair with Double Teflon technique. CASUISTIC: Were included 14 patients with mitral valve insufficiency secondary to mixomatous degeneration that were submitted to mitral valve repair with the Double Teflon technique. Of them, 10 patients were male and the mean age was 61.3 ± 11.2 years. According to preoperatively functional class, 13 patients were in class III or IV. In preoperative echocardiographic analysis, the mean value of left ventricle end diastolic volume was 156.57 ± 46.61ml, and the left ventricle ejection fraction ranged between 38 and 68%, with average of 57.93 ± 6.67%. The mean value of the posterior annulus was 6.97 ± 0.13 cm. METHODS: Patients were evaluated in preoperative period, immediate postoperative period, 6 months and 1 year after mitral repair. Tridimensional echocardiography evaluated mitral annulus morphology by anterior and posterior measurements, transverse diameters and valve area. The annular function was evaluated through the ratio between internal valve areas during systole and diastole. Were evaluated left atrial and ventricle volumes and function. Statistic analysis was made by repeated measures ANOVA test and was considered statistically significant p < 0.05. RESULTS: Posterior mitral annulus demonstrated a significant reduction in immediate postoperative period (p<0.001), remaining stable during the study. There was no significant variation in valve area during the study. There was a significant reduction in anteroposterior and mediolateral diameters in the immediate postoperative period (p<0.001), although there was a significant increase in mediolateral diameter between immediate postoperative period and 1 year. Annular area variation over the cardiac cycle during the study ranged between 30.92 and 35.75%, without statistic significance. The analysis of systolic volumes, atrial and ventricular, demonstrated a significant volumetric reduction between immediate postoperative period and 1 year (p=0.028 and p=0.020, respectively). Between preoperative period and 1 year, there was a mean reduction in atrial and ventricle volumes of 19.9% and 15.4%, respectively. Atrial and ventricle diastolic volumes presented a significant reduction in immediate postoperative period (p<0.001 and p=0.024, respectively), remaining stable during the study. There was an increase in left atrial ejection fraction after 6 months (p<0.001), although there was no significant variation in left ventricle ejection fraction. CONCLUSIONS: Mitral valve repair with segmentar annuloplasty with the Double Teflon technique reduced the posterior mitral annulus, which remained stable in 1 year period. The variation in mitral annulus area during cardiac cycle remained stable during the study. Furthermore, there was a left atrial and ventricle reverse remodeling, associated with an improvement in left atrial function

Introdução e Objetivo: No Brasil, procedimentos valvares representam no mínimo 30% das cirurgias cardíacas realizadas no país. Em nosso meio ainda predominam as lesões valvares decorrentes da febre reumática e doenças degenerativas. Nos pacientes reumáticos, a valva mitral é a mais acometida, predominando a estenose devido à fusão comissural e lesões no plano subvalvar; porém espessamento e retração de cúspides também são comuns, determinando dupla lesão ou insuficiência desta valva. Em processos degenerativos, as cordas tendíneas podem se apresentar alongadas. Na tentativa de utilização futura do laser como método auxiliar na correção cirúrgica dessas valvopatias, iniciamos estudo experimental com o objetivo de comparar histologicamente o tecido valvar mitral de suínos (cordas tendíneas e cúspides) submetido com e sem o laser de alta potência (LAP). Métodos: Foram estudadas cordas tendíneas e cúspides mitrais de suínos jovens e saudáveis, divididos em 6 grupos: G1-Aplicação do laser em cordas tendíneas com o tempo de 15 s; G2- Aplicação do laser em cordas tendíneas com o tempo de 20 s; G3- Aplicação do laser em cordas tendíneas com o tempo de 30 s; G4- Grupo controle relacionado a G1, G2 e G3; G5- Grupo cúspide submetido a corte com lâmina de bisturi; G6- Grupo cúspide submetido a corte com laser. As cordas tendíneas dos grupos G1, G2 e G3 receberam tratamento com laser de diodo (=980 nm, P=3,0 W) e o grupo G6 com laser de diodo em outros parâmetros (=980 nm, P=9,0 W, T=12s). Termografia e tomografia por coerência óptica foram utilizadas durante o experimento. Parte da amostra foi preservada em formaldeído e glutaraldeído para análise microscópica e a outra parte foi preservada em solução fisiológica 0,9% para análise mecânica. Resultados: Houve um decréscimo significante no comprimento das cordas tendíneas após aplicação do laser quando comparado ao comprimento inicial (p=0,005 em G1 e G2 e p=0,004 em G3). À microscopia óptica, G1, G2 e G3 apresentaram áreas hialinas ocupando quase a totalidade da espessura da corda, quando coradas pela Hematoxilina-Eosina (HE), áreas vermelho-escura na região central da corda quando coradas pelo Tricrômico de Masson e áreas com birrefringência diminuída quando coradas pelo Picrosírius vermelho. Na avaliação mecânica, os grupos lasers apresentaram diminuição da rigidez do material, assim como na força máxima durante a ruptura, entretanto o deslocamento foi maior em relação ao grupo controle (p=0,005). No G5, evidenciamos ausência de qualquer alteração histológica. No G6 foram identificadas áreas de menor birrefringência do colágeno quando corado pelo Picrosírius vermelho, áreas estas que apresentavam aspecto basofilico hialino no HE e coloração vermelho-escura ao Tricrômico de Masson. Conclusão: As cordas tendíneas de valvas mitrais de suínos submetidas ao laser de alta potência apresentaram redução do seu comprimento final, diminuição na birrefringência e alteração na distribuição dos feixes de colágeno. Além disso, apresentaram queda da rigidez, maior fragilidade de rotura e maior deslocamento ao teste de tração mecânica quando comparada ao grupo controle. Com relação às cúspides, os danos térmicos encontrados no grupo corte com laser de alta potência foram maiores do que em relação ao bisturi de lâmina, quando evidenciados pela microscopia óptica
Introduction and Objective: In Brazil, valvar procedures represent at least 30% of cardiac surgeries performed in the country. It still predominate valvar lesions resulting from rheumatic fever and degenerative diseases. In rheumatic patients, the mitral valve is the most affected, predominantly stenosis due to commissural fusion and lesions in the subvalvar plane, however, thickening and retraction of the leaflets are also common, causing double lesion or mitral insufficiency. In degenerative process, the chordae tendineae may present elongated. In an attempt to further use of the laser as an auxiliary method in the surgical correction of valvar heart disease, we started experimental study with the purpose of comparing the histological swine tissue mitral valve (chordae tendineae and cusps) with and without high-power laser (HPL) application. Methods: Normal porcine mitral valve chordae and cups were studied and divided randomly into the following 6 groups: G1- Laser in the chordae tendineae with time of 15s; G2- Laser in the chordae tendineae with time of 20s; G3- Laser in the chordae tendineae with time of 30s; G4- Control Group; G5- Cusp group cut with a scalpel blade; G6- Cusp group cut with laser. Chordae tendineae from G1, G2 e G3 received diode laser (=980 nm, P=3,0 W) and G6 diode laser with other parameters (=980 nm, P=9,0 W, T=12s). Termography and optical coherence tomography were included during the procedure. Part of the sample was preserved in formaldehyde and glutaraldehyde for microscopic analysis and another part was stored in 0.9% saline for mechanical analysis. Results: There was a significant decrease in chordae length after laser application when compared to the initial length (p=0,005 to G1 and G2; p=0,004 to G3). In laser groups, histological analysis revealed a typical hyaline areas occupying almost the entire thickness of the chordae, when stained with Hematoxylin-Eosin (HE); dark red central areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius red. In mechanical analysis, we found lower stiffness, maximum rupture force decrease and larger displacement compared with the Control Group (p=0,005). In G5, was evidenced absence of any histological abnormality and a homogeneous blue appearance, typical of the cusp. However in G6, a basophilic hyaline aspect was found focally when stained with HE, dark red areas when stained with Masson Trichrome and a birefringence decrease when stained with Picrocirius Red. Conclusion: Chordae tendineae of normal porcine submitted to a high-power laser presented with reduced length, birefringence decrease and the collagen bundles organized into different orientations. Besides, presented lower stiffness, maximum rupture force decrease and larger displacement compared with the control group. Regarding cups, thermal changes were bigger in the cusp group cut with laser compared cusp group cut with scalpel blade, observed by optical microscopy

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A degeneração mixomatosa da válvula mitral (DMVM) é a enfermidade mais comum na clínica de pequenos animais no âmbito das cardiopatias, cuja evolução pode resultar em alterações hemodinâmicas importantes decorrentes dos mecanismos neuro-hormonais compensatórios. Embora seu diagnóstico seja relativamente simples, as alterações intrínsecas podem ser subestimadas pelos exames convencionais, a exemplo da disfunção sistólica e reserva miocárdica que podem passar despercebidas à ecocardiografia. Desta forma, o objetivo do presente estudo foi avaliar a ocorrência de disfunção sistólica em cães com DMVM por meio do teste de estresse farmacológico com dobutamina. Para tanto, foram utilizados três grupos de cães: G1 (n=8) grupo controle, G2 (n=7) animais com DMVM e diâmetro interno do ventrículo esquerdo em diástole indexado à aorta (DIVEd/Ao) < 2,37 e G3 (n=6) animais com DMVM e DIVEd/Ao ≥ 2,37 em um total de 21 animais. O ecocardiograma foi realizado antes (T0) e após (T1) infusão contínua com dobutamina, que foi realizada da seguinte forma: 5μg/kg/minuto por cinco minutos e 10μg/kg/minuto durante 10 minutos (T1). Os resultados foram avaliados pelo teste de Tukey com nível de significância de 5% quanto às variáveis fração de ejeção (FEJ%) (variação percentual média (VPM) de FEJ% antes e após a infusão de dobutamina), VPM de fração de encurtamento (FEC%) e diâmetros internos do ventrículo esquerdo em sístole e diástole indexados pelo diâmetro da aorta (DIVEs/Ao e DIVEd/Ao). Os resultados acerca da VPM FEC% e VPM FEJ%,demonstraram que houve diferença estatística quanto à primeira variável entre os grupos G1 com G3, bem como entre G2 e G3, enquanto em relação à segunda, apenas o G1 e G3 diferiram estatisticamente. Por outro lado não houve diferença significativa (p>0,05) para as médias obtidas pré e pós dobutamina da FEC% e FEJ% entre todos os grupos, no entanto, houve diferença significativa dentro os grupos G1 e G2 quando analisados os momentos T0 e T1. Outrossim, verificando as médias obtidas do DIVEd/Ao, conclui-se que houve diferença entre os grupos G1 e G3 como também entre G2 e G3 (p<0,05). Por sua vez, as médias obtidas do DIVEs/Ao diferiram significativamente (p<0,05) em todos os grupos pré (T0) e pós dobutamina (T1), exceto no G3. Entre os grupos, as médias no T0, têm diferença estatística significante entre os grupos G1 e G3 (p<0,05). Ademais, Em relação ao VVEs/m², dentro dos grupos houve diferença significativa apenas entre G1 e G3. Já entre os tempos, apenas o G1 houve diferença entre T0 e T1. Por fim, constatou-se significância estatística (p<0,05) quando se correlacionou DIVEd/Ao com a VPM FEC% e VPM FEJ%, demonstrando que quanto maior o DIVEd/Ao menores são estas variáveis. Desta forma, conclui-se que a dobutamina é capaz de evidenciar disfunção sistólica em animais com DMVM, principalmente naqueles que têm um remodelamento maior (G3), sendo capaz de inferir uma forte relação entre o tamanho do DIVEd/Ao e disfunção sistólica. Além disso, notou -se que em animais com menor remodelamento do ventrículo esquerdo (VE), como os do grupo G2, a resposta inotrópica ao desafio farmacológico foi satisfatória, revelando a presença de reserva contrátil nestes pacientes. Por fim, o teste de estresse com dobutamina mostrou-se eficaz, seguro e aplicável na rotina clínica.
Myxomatous mitral valve disease (MMVD) is the most common cardiopathy in small animals, which evolution may result in important hemodynamic changes due to compensatory neurohormonal mechanisms. Although its diagnosis is relatively simple, intrinsic changes may be underestimated by conventional exams, as systolic dysfunction and myocardial reserve that may go unnoticed by echocardiograph. Therefore, the objective of the present study was to evaluate the occurrence of systolic dysfunction in dogs with MMVD through pharmacological stress test with dobutamine. The dogs were distributed in three groups: G1 (n = 8) control group, G2 (n = 7) animals with MMVD and left ventricular diastolic diameter indexed to the aorta (LVIDd:Ao) < 2.37 and G3 (n = 6) animals with MMVD and LVIDd:Ao ≥ 2.37. The echocardiograph was performed before (T0) and after (T1) continuous infusion of dobutamine, as follows: 5μg/kg/minute for five minutes and 10μg/kg/minute for 10 minutes (T1). The results were evaluated by Tukey test with significance level of 5% for the following variables: ejection fraction (EF%) (mean percentage variation (MPV) of EF% before and after dobutamine infusion), MPV of shortening fraction FS% and internal diameters of left ventricle in systole and in diastole indexed by aortic diameter (LVIDs:Ao and LVIDd:Ao). The results about the MPV FS% and the MPV EF% showed that there was statistical difference between the G1 and G3 groups, as well as between G2 and G3, while the G1 and G3 differed statistically from the G1 and G3 groups. On the other hand, there was no significant difference (p> 0.05) for the averages obtained before and after dobutamine of the FS% and EF% among all groups, however, there was a significant difference between groups G1 and G2 when the T0 moments and T1. In addition, it was concluded that there were differences between the G1 and G3 groups as well as between G2 and G3 (p <0.05). Also, by means of the LVIDd:Ao means, it was concluded that there was a difference between the G1 and G3 groups as well as between G2 and G3 (p <0.05). In it’s turn, the means obtained from LVIDs:Ao differed significantly (p <0.05) in all groups before (T0) and post-dobutamine (T1), except in G3. Among the groups, the averages at T0, have significant statistical difference between the G1 and G3 groups (p <0.05). In addition, with respect to ESV/m², within the groups there was a significant difference only between G1 and G3. Among the times, only G1 showed differences between T0 and T1. Finally, statistical significance (p <0.05) was found when DIVEd / Ao correlated with MPV FS% and EF%, demonstrating that the higher the LVIDd:Ao the lower these variables. Therefore, it was determined that dobutamine can point to systolic dysfunction in animals with MMVD, especially those showing greater remodeling (G3), also inferring a strong relationship between LVIDd:Ao size and systolic dysfunction. Furthermore, in animals with less left ventricular (LV) remodeling, such as those in group G2, inotropic response to pharmacological challenge was satisfactory, revealing the presence of contractile reserve in these patients. To conclude, dobutamine stress test showed effective, safe and applicable in clinical routine.

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Introduction: One of the most often and important complications after surgical treatment of atrioventricular septal defects is the left atrioventricular valve insufficiency. So, this study was conducted to identify risk factors for moderate or severe left atrioventricular valve regurgitation within 30 days of surgical repair of atrioventricular septal defects at our center. Methods: This was a retrospective study in which we evaluated the results of 104 consecutive patients that were operated on at our practice between 2002 and 2010. The following associated factors were considered: age, weight, Down syndrome, grade of preoperative atrioventricular valve regurgitation, abnormalities on the atrioventricular valve and the use of annuloplasty. Patients were separated in two groups according to type of AVSD: group I (complete) and group II (incomplete – partial and transitional). Characteristics of the 53 patients of the group I: the median patient age at the time of repair was 6.7 months; the median weight was 5.3 Kg; 86.8% had Down syndrome; at the time of preoperative evaluation, there were 26 cases with moderate or severe atrioventricular valve regurgitation (49.1%); annuloplasty was perfored in 34%; abnormalities on the valve were found in 11.3% of the cases. Characteristics of the 51 patients of the group II: The median patient age at the time of repair was 4.1 years; the median weight was 13.4 Kg; 37.2% had Down syndrome; at the time of preoperative evaluation, there were 23 cases with moderate or grater LAVVR (45.1%); abnormalities on the AV valve were found in 17.6% of the cases; annuloplasty was performed in 21.6% of the patients. Results: Group I - At the time of post-operative evaluation, there were 21 cases with moderate or severe left atrioventricular valve regurgitation (39.6%). After performing a multivariate analysis, the only significant factor associated with these grades of insufficiency within 30 days of surgical correction of complete atrioventricular septal defect was the absence of Down syndrome (p = 0.03). Group II - At the time of postoperative evaluation, there were 12 cases with moderate or greater LAVVR (23.5%). During univariate analysis, only absence of Down syndrome was statistically significant (p = 0.02). However, after a multivariate analysis, none of the factors reached significance. Conclusion: Absence of Down syndrome proved to be associated with moderate or severe post-operative left atrioventricular valve regurgitation in patients with complete AVSD. However, none of the factors studied was determinant of a moderate or greater LAVVR within the first 30 days of repair of incomplete AVSD at our center.
Introdução: Uma das complicações mais frequentes e importantes do tratamento cirúrgico do defeito de septo atrioventricular (DSAV) é a insuficiência residual da valva atrioventricular esquerda, tanto nas formas totais, como parciais e transicionais. Dessa forma, esse estudo foi conduzido para identificar fatores de risco associados à insuficiência da valva atrioventricular esquerda (IVAVE) de grau moderado ou importante nos primeiros 30 dias após correção de defeito de DSAV. Métodos: Dados de 104 pacientes com DSAV operados entre 2002 e 2010 foram avaliados retrospectivamente, sendo estudados os seguintes fatores de risco: idade e peso no momento da correção, ausência de síndrome de Down, grau de insuficiência da valva atrioventricular (AV) antes da correção, anormalidades na valva AV e uso de anuloplastia. Os pacientes foram separados em dois grupos de acordo com o tipo de DSAV: grupo I (total) e grupo II (parcial e transicional). Características dos 53 pacientes do grupo I: a mediana da idade foi de 6,7 meses e a do peso de 5,3 Kg; 86,8% tinham síndrome de Down; antes da operação, 26 pacientes apresentavam insuficiência pelo menos moderada da valva AV (49.1%); anuloplastia foi realizada em 34% dos pacientes; anormalidades na valva AV foram encontradas em 11.3% dos casos. Características dos 51 pacientes do grupo II: a mediana da idade foi de 4,1 anos e a do peso de 13,4 Kg; 37,2% tinham síndrome de Down; antes da operação, 23 pacientes apresentavam IVAVE pelo menos moderada (45,1%); anormalidades na valva AV foram encontradas em 17,6% dos casos; anuloplastia foi realizada em 21,6% dos pacientes. Resultados: Grupo I – Após a correção cirúrgica, 21 casos apresentaram IVAVE pelo menos moderada (39,6%). Pela análise multivariada, o único fator associado com IVAVE pelo menos moderada no pós-operatório foi ausência de síndrome de Down (p = 0,03). Grupo II - Após a correção cirúrgica, 12 casos apresentaram IVAVE pelo menos moderada (23,5%). Pela análise univariada, apenas a ausência de síndrome de Down teve significância estatística (p = 0.02). Porém, após análise multivariada, nenhum dos fatores teve significância estatística. Conclusão: Ausência de síndrome de Down foi determinante de IVAVE moderada ou importante nos primeiros 30 dias após correção de DSAV total. Todavia, nenhum dos fatores estudados foi determinante para tais graus de IVAVE entre os pacientes com DSAV parcial e transicional.

L’insuffisance mitrale est la valvulopathie mondiale la plus fréquente avec une prévalence de 2%. Lorsque le patient n’est pas en mesure d’être opéré à cœur ouvert, un implant percutané est utilisé pour aider la fermeture des feuillets. Le seul implant actuellement disponible est basé sur la réparation bord à bord de la valve mitrale. Il réduit le reflux vers l’oreillette lors de la systole, mais n’est pas adapté pour les patients souffrant d’insuffisance mitrale fonctionnelle, chez qui la pathologie provient du ventricule et non des éléments de la valve. L’objectif de la thèse est de fournir une plateforme numérique permettant d’aider au développement d’un implant adapté pour ces patients. Plusieurs géométries de valve ont été réalisées au moyen d’un modèle paramétrique, en utilisant des données anatomiques. La dynamique de la valve a été modélisée avec le logiciel ADINA par des simulations éléments finis en grandes déformations. Des modèles structurels de la valve ont permis de représenter la fermeture de la valve sous une pression uniforme. Les lois de comportement de matériaux ont été développé dans le but d’obtenir une fermeture réaliste de la valve. Cela a nécessité la prise en compte de l’hyperélasticité et de l’anisotropie des tissus. Des pathologies valvulaires, telles que la dilatation de l’anneau mitrale ou la rupture des cordages tendineux ont été modélisées, et plusieurs méthodes ont été testées pour y apposer des systèmes médicaux. En utilisant une description ALE et un couplage monolithique, les interactions fluide-structure ont été simulées pour une valve mitrale bi-dimensionnelle. La fermeture hermétique de la valve pendant la systole a pu être reproduite et l’ouverture de la valve étudiée pendant la diastole. La plateforme numérique développée permet de modéliser la fonction de la valve mitrale et peut être utilisée pour aider au développement d’un implant mitral grâce au modèle paramétrique reproduisant différentes géométries de valve et aux lois matériaux anisotropes. Une perspective reste la création d’un modèle 3D des interactions fluide-structure de la valve mitrale
Mitral insufficiency is the first valvular disease worldwide, with a 2% prevalence. When open-heartsurgery is impossible for the patient, surgeons use percutaneous devices to help the mitral leaflets coapt. However, the only device currently available is based on the edge-to-edge mitral valve repair technique. This type of implant is not adapted for patients suffering from functional mitral insufficiency, where the ventricle is responsible for the lack of coaptation of the leaflets. This thesis aims to provide a numerical platform to help the development of a mitral valve implant adapted for those patients. Several mitral valve geometries were created from a parametric model using anatomical measurements. Finite element simulations of the mitral valve were performed using ADINA to determine the valve closure under constant pressure. Several material models were developed in large strain and large deformation to model the valve closure accurately. Pathological behaviour such as annulus dilatation and chordae rupture were modelled, and several methods were tested to implement medical devices. Fluid-structure interaction of a 2D mitral valve was obtained using an ALE description and a monolithic coupling approach. Both the systole and the diastole were reproduced and studied, and the hermetic seal of the valve was detailed. The numerical platform developed is suited to model mitral valve function and can be used to help the development of mitral implants. In addition, the parametric geometry model and the anisotropic material model will be useful to depict with realism the valve function. A 3D fluid-structure interaction of the mitral valve could be developed

Thesis (M.S.)--East Carolina University, 2009.
Presented to the faculty of the Department of Exercise and Sport Science. Advisor: Timothy P. Gavin. Title from PDF t.p. (viewed May 5, 2010). Includes bibliographical references.

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.

Objetivos: Avaliar a evolução e as complicações dos doentes que sobreviveram a ferimentos cardíacos, atendidos no Pronto-Socorro Municipal 28 de Agosto e Hospital Pronto-Socorro Dr. João Lúcio Pereira Machado, em Manaus, no período de janeiro de 1998 a junho de 2006. Métodos: Foi realizada uma busca de prontuários dos doentes atendidos nos dois prontossocorros, nos quais durante a toracotomia exploradora evidenciou-se o ferimento cardíaco. Os sobreviventes que retornaram ao ambulatório foram avaliados prospectivamente por meio de eletrocardiograma e ecocardiograma, para averiguar a morfologia e a funcionalidade do coração. Foi preenchido um protocolo com registro dos dados dos doentes, tais como: idade, sexo, mecanismo de trauma, complicações intra e pós-operatórias, dentre outras variáveis. Resultados: A população de referência totalizou 100 doentes, dos quais 95% eram homens, 69% entre 20 e 30 anos; 81% das lesões foram por arma branca, sendo que em 78% delas, a entrada se encontrava no precórdio; 41% das lesões acometeram o ventrículo direito (VD) e 38% acometeram o ventrículo esquerdo (VE); em 48% dos casos foi realizada toracotomia ântero-lateral esquerda. A sobrevivência foi de 72%. A população de estudo foi composta por 25 doentes que retornaram ao ambulatório e foram avaliados prospectivamente por meio de eletrocardiograma e ecocardiograma. Das 33 alterações no ecocardiograma (ECO), sete doentes (28%) tinham insuficiência mitral, enquanto nove (36%) não tinham alterações. Das 45 alterações no eletrocardiograma (ECG), oito doentes (32%) tinham taquicardia sinusal, enquanto seis (24%) não tinham alterações. Não houve efeito do tempo no resultado do ECO (p=0,5323) ou do ECG (p=0,6596). Das alterações detectadas no ECO, três (21,4%) foram devidas a lesões grau IV (em VD) e 11 (78,7%) devidas a lesões grau V (em VE) (p=0,048). Das 12 alterações detectadas no ECG, três (25%) relacionaram-se a lesões grau IV e nove (75%) relacionaram-se a lesões grau V (p=0,226). Conclusões: Aproximadamente um terço dos sobreviventes a lesões cardíacas não apresentaram alterações ao eletrocardiograma e ecocardiograma. Ventrículo esquerdo e grau de lesão V da OIS-AAST estiveram relacionados a um maior número de alterações ao eletrocardiograma e ecocardiograma. Taquicardia sinusal e insuficiência mitral foram alterações encontradas em um de cada três doentes que sobreviveram a um ferimento cardíaco.
Objectives: To evaluate the evolution and the complications of the patients that survived cardiac wounds, attended at the Pronto-Socorro Municipal 28 de Agosto and Hospital Pronto-Socorro Dr. João Lúcio Pereira Machado, in Manaus, during the period of January 1998 until June 2006. Methods: A medical records evaluation was made among the patients attended at the two emergency hospitals in which a cardiac wound was found during a exploring thoracotomy. The survivors that returned to the ambulatory were evaluated prospectively through electrocardiogram and echocardiogram, so it was possible to analyze the morphology and the function of the heart. A protocol was filled out with a registry of patients data, such as: age, sex, trauma mechanism, intra-operative and post-operative complications, and other variables. Results: The total reference population in this study was 100 patients, in which 95% were male, the majority (69%) had ages until 30; 81% of the lesions were caused by stab wounds; 78% of the orifice of entry were located at the precordium; 41% of the lesions wounded the right ventricle and 38% wounded the left ventricle; In 48% of the cases a left antero-lateral thoracotomy was executed. The survival rate was 72%. The studied population was of 25 patients that returned to the ambulatory and were prospectively evaluated with electrocardiogram and echocardiogram. Among the 33 echocardiogram alterations (ECO), seven patients (28%) had mitral insufficiency, while nine (36%) didn\'t have any alterations. Among the 45 electrocardiogram alterations (ECG), eight patients (32%) had sinusal tachicardia, while six (24%) had no alterations. Time made no difference in the results of the ECO (p=0,5323) or of the ECG (p=0,6596). Of the 14 detected ECO complications, three (21,4%) were due to IV degree lesions in the right ventricle and eleven (78,7%) were due to V degree lesions (in the left ventricle) (p=0,048). From the 12 left ventricle lesions that complicated (ECG), 9 were V degree. From the 12 alterations detected at the ECG, three (25%) were due to IV degree lesions and nine (75%) were due to V degree lesions (p=0,226). Conclusions: Approximately one third of the cardiac wound survivors did not have alterations in the electrocardiogram and echocardiogram. Left ventricle and V degree lesions from the OIS-AAST were related to a larger number of alterations in the electrocardiogram and echocardiogram. Sinusal Tachicardia and mitral insuficiency were alterations found in one third of the patients that survived a cardiac wound.

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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.

A obesidade é definida como acúmulo excessivo de gordura corpórea, derivada de um desequilíbrio crônico entre energia ingerida e gasta. Neste desequilíbrio estão relacionados fatores como estilo de vida (dieta e atividade física), alterações neuro-endócrinas e fatores hereditários (MARQUES-LOPES et al., 2004). A obesidade não acomete apenas seres humanos, tornando-se um elemento importante de estudos e pesquisas, inclusive em animais de companhia como cães e gatos. O diagnóstico da obesidade geralmente é feito por inspeção direta. Cães e gatos devem ter costelas facilmente palpáveis com configuração de ampulheta, quando vistos de cima. Incapacidade de palpar as costelas e presença de depósitos de gordura facilmente palpáveis na base da cauda, sobre os quadris ou na área inguinal sugerem obesidade. Condições ideais de gordura corporal giram em torno de 15% a 20% para cães (LEWIS et al., 1987). O tecido adiposo é conhecido como um local de armazenamento de energia e síntese de vários hormônios, dentre eles, destaca-se a adiponectina, proteína responsável pela correlação entre obesidade associada à ateroesclerose (ISHIOKA et al., 2006). Expressa exclusivamente em adipócitos, sua concentração plasmática diminui com o aumento da gordura corporal (ISHIOKA et al., 2006). Vários estudos têm sugerido também que a adiponectina tenha seus efeitos como uma molécula anti-aterogênica e anti-inflamatória, demonstrando ser um fator de proteção para doenças cardiovasculares (OUCHI et al., 1999; OUCHI et al., 2000), porém valores circulantes de adiponectina devem ser interpretados com cautela. Sabe-se que a obesidade em seres humanos está relacionada ao aumento da morbidade e da letalidade por doenças cardiovasculares (ATKINS, 1991; GRUNDY; ABATE, 2004; WOFFORD; HALL, 2004), portanto a mensuração deste polipeptídeo pode auxiliar a demonstrar se pacientes obesos e/ou cardiopatas estão expostos a um maior ou menor risco do desenvolvimento de eventos cardiovasculares. Assim, considerando que os diversos estudos com adiponectina em humanos obesos associado à doenças cardiovasculares são controversos, e os poucos relatos, relativos ao tema, publicados na medicina veterinária, objetivou-se avaliar a concentração sérica de adiponectina em cães: normais, obesos, com doença valvar crônica da mitral e em obesos com insuficiência valvar mitral concomitante, por meio de técnicas laboratoriais de radioimunoensaio (RIE) e enzyme linked immuno sorbent assay (ELISA), verificando se existe correlação entre níveis séricos diminuídos da adiponectina na obesidade e no paciente com insuficiência valvar crônica de mitral. Para isto, selecionaram-se 53 cães de raças, sexo e idades variadas, divididos nos quatro grupos de estudo. Realizou-se avaliação clínica e complementares, além da mensuração das concentrações séricas da adiponectina. O grupo de cães obesos associados à insuficiência valvar crônica mitral apresentou tendência a diminuição nas médias das concentrações circulantes da adiponectina pela técnica de radioimunoensaio, quando comparado aos outros grupos de estudo.
Obesity is defined as excessive accumulation of body fat, derived from a chronic imbalance between food intake and energy expended. This imbalance is related factors such as lifestyle (diet and physical activity), neuroendocrine disorders, and hereditary factors (MARQUES-LOPES et al., 2004). Obesity is not only affecting humans, making it an important element of studies and research, including pets such as dogs and cats. The obesity is usually done by direct inspection. Dogs and cats must be easily palpable ribs with hourglass configuration when viewed from above. Inability to palpate the ribs and the presence of fat deposits easily palpable at the base of the tail, on the hips or in the inguinal area suggest obesity. Ideally body fat are around 15% to 20% clothing (LEWIS et al., 1987). Adipose tissue is known as a local energy storage and synthesis of several hormones, among them, there is adiponectin, a protein responsible for the correlation between obesity associated with atherosclerosis (ISHIOKA et al., 2006). Exclusively expressed in adipocytes, its plasmatic concentration decreased with increase in body fat (ISHIOKA et al., 2006). Several studies have also suggested that adiponectin has its effect as a molecule anti-atherogenic and anti-inflammatory, proving to be a protective factor for cardiovascular disease (OUCHI et al., 1999, OUCHI et al., 2000), although values of circulating adiponectin should be interpreted with caution. It is known that obesity in humans is associated with increased morbidity and mortality from cardiovascular disease (ATKINS, 1991; GRUNDY, SLAUGHTER, 2004; WOFFORD; HALL, 2004), so measurement of the polypeptide can help show whether patients obese and / or heart are exposed to a greater or lesser risk of developing cardiovascular events. Thus, considering that several studies of adiponectin in obese humans associated with cardiovascular disease are controversial, and few published reports in veterinary medicine, aimed to evaluate the serum adiponectin in dogs: normal, overweight, with chronic mitral valve disease and In obese patients with concomitant mitral valve insufficiency using laboratory techniques for radioimmunoassay (RIA) and enzyme linked immuno sorbent assay (ELISA), checking whether a correlation exists between low serum adiponectin in obesity and in patients with chronic mitral valve insufficiency. For this, we selected 53 breeds, sex and ages were divided into four study groups. We carried out clinical evaluation and complementary addition to the measurement of serum adiponectin. The group of obese dogs associated with chronic mitral valve regurgitation tended to decrease in mean circulating concentrations of adiponectin by radioimmunoassay, when compared to other study groups.

Cardiac resynchronization therapy (CRT) is an established therapy for patients with advanced congestive heart failure and prolonged QRS duration, aiming at correcting dyssynchrony in the left ventricle (LV). Apart from the beneficial effects on cardiac function and LV reverse remodeling, reduction in functional MR has been observed by Doppler echocardiography after CRT. On the other hand, functional mitral regurgitation (MR) in fact varies over the cardiac cycle that a biphasic pattern has been reported, i.e. early- and late-systolic peaks with a mid-systolic decrease in regurgitant flow. Nevertheless, it remains to be explored whether (1) the improvement of MR leads to a greater extent of LV reverse remodeling; (2) the different components (i.e. early- and late-systolic) of MR improve and their predictors if any.
Despite comparable ejection fraction, higher degree of functional MR was associated with further impairment in short-axis myocardial deformation (circumferential and radial), but not with long-axis myocardial deformation. The degree of LV basal rotation was also lower in the MR patient group. Furthermore, the decrease in myocardial deformation was associated with greater extent of LV remodeling.
In conclusion, LV global mechanical dyssynchrony play a role in determining the severity of functional MR in addition to mitral leaflet tenting in patients with LV systolic dysfunction. Functional MR is associated with further impairment of myocardial deformation, but with differential change in individual component of myocardial deformation. CRT reduces functional MR in both early- and late-systolic phases, by way of improvement in LV remodeling, LV dyssynchrony and mitral leaflet tenting. Meanwhile, the improvement of MR contributes to LV reverse remodeling after CRT. (Abstract shortened by UMI.)
The improvement of functional MR was an independent predictor of LV reverse remodeling after CRT. The extent of LV reverse remodeling (reduction of LV end-systolic volume) was greatest in patients with improvement of MR, followed by those with "mild or no" MR at baseline, and was least in those without improvement of MR. CRT reduced functional MR by reducing both its early- and late-systolic components in heart failure patients. The reductions in LV end-systolic volume and dyssynchrony were related to the improvement of early-systolic MR, while the improvement of late-systolic MR was attributable to the reductions in mitral leaflet tenting and LV dyssynchrony.
The main findings were as follows: LV global systolic dyssynchrony served as an independent predictor for the presence of significant functional MR in patients with LV systolic dysfunction. Although mitral valvular tenting area was the most powerful predictor, LV global systolic dyssynchrony added incremental value to mitral valve tenting area in predicting the presence of significant functional MR.
We performed echocardiography with TDI and 2DSTE in 147 patients of both ischemic and non-ischemic etiologies with LV systolic dysfunction (defined as LV ejection fraction <50%) and 45 normal controls. MR severity, displacement of papillary muscle, mitral annular dilation and dysfunction, mitral leaflet tenting, LV remodeling and function were assessed by 2D and Doppler echocardiography. LV mechanical dyssynchrony indices were derived from TDI velocity. Myocardial strain (i.e. amount of deformation) in longitudinal, circumferential and radial directions and torsion (opposite rotational movement between apex and base of the heart) were measured by 2DTSE.
Liang, Yujia.
"October 2009."
Adviser: Cheuk man Yu.
Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: .
Thesis (Ph.D)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 169-193).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.

碩士
國立中興大學
獸醫學系暨研究所
100
Left ventricular dyssynchrony (LVD) is observed in numbers of congestive heart failure patients. Because of the difference in systolic timing, LVD may further decrease cardiac output which will enhance the severity of the clinical signs, and increase mortality. The causes of LVD include myocardial dyssynergy and electrical activation delay, only the latter could be treated effectively by cardiac resynchronization therapy (CRT). Therefore, both of dyssynchrony and dyssynergy should be taken into consideration for distinguishing the cause of LVD. Dyssynergy is typical in ischemic heart disease with scar formation and endocardium dysfunction, which could make the transmural strain gradient (TSG) decrease. Thus, considering about TSG might also constructive to recognize the impact on myocardium. Mitral valve insufficiency is a common senile disease in small dogs. The increase regurgitant flow would make left ventricle remodeling and increase wall stress, this will compromise coronary perfusion. The aim of this study is using speckle tracking (STE) to evaluate the impact on dyssynchrony between different stages in mitral valve regurgitation (MR) Maltese dogs. Twenty healthy control group and thirty-three dogs with MR are classified according to the American College of Veterinary Internal Medicine (ACVIM) to MR1(n = 15), MR2(n =10) and MR3(n = 8). All dogs underwent conventional echocardiography and STE. The results demonstrated strain, DI, DNI and TSG might be influenced by MR. MR1 and MR2 are the most dyssynchrony and lowest TSG groups, MR3 is the most dyssynergy groups. These STE indices may be influenced by strain, myocardium remodeling and compensation. Consequently, although MR cause difference between groups and severity of dyssynergy is worst in MR3 as we expected, these STE indices should be more estimated for clinical application.

Проект виконано на кафедрі біотехнічних систем Тернопільського національного технічного університету імені Івана Пулюя
Кінаш Роман Володимирович. Метод обробки фонокардіосигналу для виявлення мітральної недостатності клапанів серця людини. – Рукопис. Дипломна робота магістра за спеціальністю 163 «Біомедична інженерія», Тернопільський національний технічний університет імені Івана Пулюя, Тернопіль, 2019. Дипломну роботу магістра присвячено розробленні методу обробки фонокардіосигналу для виявлення мітральної недостатності клапанів серця людини. У роботі обґрунтовано математичну модель фонокардіосигналу у вигляді періодично корельованого випадкового процесу, яка має засоби та методи поєднання стохастичної природи та повторності сигналу, що є властивим для сигналів біологічного походження. На базі обґрунтованої математичної моделі у вигляді періодично корельованого випадкового процесу застосовано компонентний метод для обробки фонокардіосигналу, який дає змогу оперативно виявити мітральну недостатність клапанів серця людини. Розроблено програмне забезпечення в середовищі Matlab для автоматичних систем діагностики функціонального стану серцево-судинної системи на основі компонентного методу обробки фонокардіосигналу як періодично корельованої випадкової послідовності. Ключові слова: фонокардіосигнал, математична модель, періодично корельований випадковий процес, обробка, компонентний метод, виявлення мітральної недостатності клапанів серця людини, автоматизована система.
Kinash Roman. A method of phonocardiogram processing for a human heart valves mitral insufficiency detection. - Manuscript. Master's thesis on the specialty 163 "Biomedical Engineering", Ternopil Ivan Puliuj National Technical University, Ternopil, 2019. The master's thesis is devoted to the development of a method of processing the phonocardiosignal to detect the mitral insufficiency of the valves of the human heart. On the basis of a valid mathematical model in the form of a periodically correlated random process, a component method for the processing of phonocardiosignal is applied, which allows to expeditiously detect the mitral insufficiency of the valves of the human heart. The software in Matlab environment for automatic systems of diagnostics of the functional state of the cardiovascular system is developed based on the component method of processing the phonocardiosignal as a periodically correlated random sequence. Keywords: phonocardiosignal, mathematical model, periodically correlated random process, processing, component method, detection of mitral insufficiency of human heart valves, automated system.
ЗМІСТ ПЕРЕЛІК УМОВНИХ ПОЗНАЧЕНЬ 9 ВСТУП 10 РОЗДІЛ 1 ОГЛЯД СТАНУ ПРОБЛЕМИ ЗА НАПРЯМОМ НАУКОВОГО ДОСЛІДЖЕННЯ 13 1.1 Мітральна недостатність 13 1.2 Методи діагностики мітральної недостатності клапанів серця людини 14 1.2.1. Фізикальний 14 1.2.2 Аускультація 15 1.2.3. Фонокардіографія 16 1.3 Відомі математичні моделі фонокардіосигналів 21 1.3.1 Детерміновані моделі 21 1.3.2 Стохастичні моделі 21 1.4 Висновки до розділу 1 23 РОЗДІЛ 2. МАТЕМАТИЧНА МОДЕЛЬ ФОНОКАРДІОСИГНАЛУ 25 2.1 Параметри фонокардіосигналу 25 2.2 Обробка характеристик фонокардіосигналу 28 2.3 Енергетична теорія при моделюванні фонокардіосигналу 32 2.4 Математична модель фонокардіосигналу при недостатності мітральних клапанів 34 2.5 Висновки до розділу 2 38 РОЗДІЛ 3. МЕТОД ОБРОБКИ ФОНОКАРДІОСИГНАЛІВ 39 3.1 Реєстрація фонокардіосигналів 39 3.2 Методи обробки при недостатності мітральній 44 3.2.1 Когерентний метод обробки 47 3.2.2 Компонентний метод обробки 49 3.3 Алгоритм методу компонентної обробки фонокардіосигналів при виявленні мітральної недостатності клапанів серця людини 51 3.4 Висновки до розділу 3 53 7 РОЗДІЛ 4. РЕЗУЛЬТАТИ ОБРОБКИ ФОНОКАРДІОСИГНАЛУ 55 4.1 Блок-схема програмного забезпечення компонентної обробки фонокардіосигналу 55 4.2 Програмна реалізація компонентного методу аналізу 56 4.3 Блок схема програми для автоматичної обробки фонокардіосигналів 59 4.4 Реалізація програмного забезпечення автоматичної обробки фонокардіосигналів 60 4.5 Результати виявлення мітральної недостатності 66 4.6 Висновки до розділу 4 73 РОЗДІЛ 5. СПЕЦІАЛЬНА ЧАСТИНА 74 5.1 Метрологічне забезпечення медико-біологічних досліджень 74 5.2 Обґрунтування вибору УДК напряму наукового дослідження 77 5.3 Висновки до розділу 5 78 РОЗДІЛ 6. ОБГРУНТУВАННЯ ЕКОНОМІЧНОЇ ЕФЕКТИВНОСТІ 79 6.1 Розрахунок витрат на проведення науково-дослідної роботи 79 6.2 Науково-технічна ефективність науково-дослідної роботи 84 6.3 Висновки до розділу 6 88 РОЗДІЛ 7. ОХОРОНА ПРАЦІ ТА БЕЗПЕКА В НАДЗВИЧАЙНИХ СИТУАЦІЯХ 89 7.1 Охорона праці 89 7.2 Безпека в надзвичайних ситуаціях 91 7.3 Висновки до розділу 7 93 РОЗДІЛ 8. ЕКОЛОГІЯ 94 8.1 Cтатистична оцінка екологічного стану навколишнього природного середовища та закономірностей його розподілу 94 8.2 Моніторинг поверхневих вод 97 8.3 Висновки до розділу 8 100 ВИСНОВКИ 101 СПИСОК ВИКОРИСТАНИХ ДЖЕРЕЛ 102 ДОДАТКИ 106 8 ДОДАТОК А. Програмна реалізація компонентного методу обробки фонокардіосигналу 107 ДОДАТОК Б. Програмна реалізація графічного інтерфейсу програмного забезпечення обробки фонокардіосигналу 108 ДОДАТОК Д. Копія тези конференції 115