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

INTRODUÇÃO: O implante transcateter de prótese valvar aórtica (TAVI) surge nos dias atuais como uma opção terapêutica para os pacientes sintomáticos portadores de estenose aórtica grave. Cerca de 200 mil pacientes em todo o mundo já foram submetidos ao TAVI. Não há grandes estudos que tenham avaliado a correlação prognóstica entre parâmetros ecocardiográficos antes do TAVI e eventos cardiovasculares a longo prazo. É relevante analisar se o strain pré-procedimento e outros parâmetros se comportam como fatores preditores independentes de eventos após o procedimento. MÉTODOS: Foram avaliados, de novembro de 2009 a outubro de 2016, 86 pacientes, submetidos a avaliação ecocardiográfica antes do TAVI e 30 dias após o procedimento, com análise do strain do ventrículo esquerdo pelo speckle tracking bidimensional e outros parâmetros ecocardiográficos. Esses pacientes foram acompanhados clinicamente e avaliados quanto aos desfechos: mortalidade global, mortalidade cardiovascular, classe funcional de insuficiência cardíaca e necessidade de reinternação cardiovascular. RESULTADOS: O strain global longitudinal pré-TAVI reduzido (valor absoluto) aumentou a chance de reinternação cardiovascular (OR: 0,87; 0,77 ±0,99; P= 0,038). A redução da relação E/e´ em 30 dias após o TAVI associou-se à queda da mortalidade global (OR: 0,97; 0,95 ±0,99; P = 0,006), bem como valores elevados pré procedimento dessa relação se associaram a maiores taxas de insuficiência cardíaca classe funcional III ou IV da New York Heart Association após a intervenção (OR: 1,08; 1±1,18; P = 0,049). CONCLUSÃO: Os resultados deste trabalho indicam que o strain global longitudinal pré-procedimento demonstrou ser um preditor de reinternação cardiovascular pós-intervenção a longo prazo. A relação E/e´ pré-procedimento apresentou correlação diretamente proporcional com o desenvolvimento de insuficiência cardíaca classe funcional III ou IV a longo prazo, assim como sua queda acentuada 30 dias após o procedimento correlacionou-se com menor mortalidade global. / INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is a therapeutic option for symptomatic patients with severe aortic stenosis. Approximately 200,000 patients around the world have already undergone TAVR. No large studies have evaluated prognostic correlation between echocardiographic parameters before TAVR and long-term cardiovascular events. It is relevant to analyze strain before procedure and how other parameters work as independent predictors of events after the procedure. METHODS: A total of 86 patients were evaluated from November 2009 to October 2016. They underwent echocardiographic evaluation before TAVR and 30 days after the procedure with analysis of strain of the left ventricle by bidimensional speckle tracking and other echocardiographic parameters. Patients were followed clinically and evaluated in relation to outcomes: global mortality, cardiovascular mortality, functional class of heart failure and need for cardiovascular readmissions. RESULTS: Global longitudinal strain before reduced TAVR (absolute value) increased the chance of cardiovascular readmission (odds ratio: 0.87; 0.77 ± 0.99; p = 0.038). Reduction of E/e´ relationship 30 days after TAVI was associated with a drop in global mortality (odds ratio: 0.97; 0.95 ± 0.99; p = 0.006). In addition, high values for this relation before the procedure were associated with higher rates of New York Heart Association functional class III or IV heart failure after the intervention (odds ratio: 1.08; 1.00 ± 1.18; p = 0.049). CONCLUSIONS: Results of this study indicate that global longitudinal strain before the procedure is a predictor of cardiovascular readmission after TAVR. The E/e´relationship before the procedure presented a correlation directly proportional to the development of long-term functional class III or IV heart failure as well as its accentuated drop 30 days after the procedure was correlated with lower global mortality.

No description available.

La sténose valvulaire aortique (SVA) est une pathologie associée au vieillissement et aux facteurs de risque cardiovasculaire. Afin d’étudier la SVA et d’explorer de nouvelles thérapies, plusieurs modèles animaux ont été récemment développés, mais la plupart de ces modèles ciblent les mécanismes de développement de la SVA reliés à l’hypercholestérolémie. Le syndrome de Werner (WS) est une maladie caractérisée par un vieillissement prématuré. Récemment, il a été découvert que des souris mutantes ayant une délétion du domaine hélicase du gène Werner, responsable du WS, démontraient un profile hémodynamique typique de la SVA. De ce fait, nous avons émis l’hypothèse que ces souris pourraient développer une SVA plus rapidement que des souris de type sauvage. Nous avons donc étudié les effets cette mutation chez des souris WrnΔhel/Δhel, en comparant le taux de progression d’une SVA entre des souris WrnΔhel/Δhel (WrnΔhel) et des souris de type sauvage comme groupe contrôle. À la suite d’une diète riche en sucre et en gras sur une période de 24 semaines, les souris WrnΔhel ont démontré une diminution plus prononcée de leur aire de valve aortique (mesures échocardiographiques) que les souris contrôles, supportée par les analyses histologiques concernant la fibrose des valves aortiques. Les souris n’ont toutefois développé aucun signe évident d’athérosclérose comme l’infiltration de lipides ou l’inflammation, bien que certaines caractéristiques liées à la dysfonction endothéliale semblent être augmentées chez les souris WrnΔhel. D’autres mesures échocardiographiques indiquant une SVA, comme une hypertrophie du ventricule gauche dans le groupe WrnΔhel, ont été obtenues. Nous avons aussi observé des indices de vieillissement plus marqués quant aux analyses sanguines et de la moelle osseuse des souris WrnΔhel en comparaison avec les souris contrôles. Par conséquent, ce modèle expérimental de vieillissement pourrait être utilisé pour les études futures sur la SVA sans les principaux effets athérogéniques des autres modèles expérimentaux. / Aortic valve stenosis (AVS) is associated with aging and classical cardiovascular risk factors. Different animal models were recently developed to study AVS and explore new therapies, however, most of these models rely almost exclusively on hypercholesterolemia-related mechanisms for AVS development. Werner syndrome (WS) is a disorder characterized by premature aging. It was recently demonstrated that mutant mice with a deletion of the helicase domain of the Werner gene, the gene responsible for WS, showed hemodynamic profile typical of AVS. We therefore hypothesized that mice with the WrnΔhel deletion could develop AVS earlier than wild-type (WT) mice. We studied the effect of the WrnΔhel mutation by comparing the rate of progression of AVS in homozygous mutant versus WT mice. By twenty-four weeks on a high-fat/high-carbohydrate diet, WrnΔhel/Δhel (WrnΔhel) mice showed a stronger decrease of the aortic valve area measured by serial echocardiography than WT mice, supported by histological analyses of valve fibrosis but without developing major signs of atherosclerosis such as lipid infiltration or increased inflammation. Some features linked to endothelial dysfunction also appeared to be increased in WrnΔhel mice. Other echocardiographic measurements were typical of AVS, such as left ventricle hypertrophy in the WrnΔhel group. We also observed stronger aging properties from WrnΔhel mice bone marrow and blood analyses compared to the WT group. Consequently, this experimental aging model could be used for AVS research without the major confounding atherogenic effects of other experimental models.

INTRODUÇÃO: O implante transcateter de prótese valvar aórtica (TAVI) surge nos dias atuais como uma opção terapêutica para os pacientes sintomáticos portadores de estenose aórtica grave. Cerca de 200 mil pacientes em todo o mundo já foram submetidos ao TAVI. Não há grandes estudos que tenham avaliado a correlação prognóstica entre parâmetros ecocardiográficos antes do TAVI e eventos cardiovasculares a longo prazo. É relevante analisar se o strain pré-procedimento e outros parâmetros se comportam como fatores preditores independentes de eventos após o procedimento. MÉTODOS: Foram avaliados, de novembro de 2009 a outubro de 2016, 86 pacientes, submetidos a avaliação ecocardiográfica antes do TAVI e 30 dias após o procedimento, com análise do strain do ventrículo esquerdo pelo speckle tracking bidimensional e outros parâmetros ecocardiográficos. Esses pacientes foram acompanhados clinicamente e avaliados quanto aos desfechos: mortalidade global, mortalidade cardiovascular, classe funcional de insuficiência cardíaca e necessidade de reinternação cardiovascular. RESULTADOS: O strain global longitudinal pré-TAVI reduzido (valor absoluto) aumentou a chance de reinternação cardiovascular (OR: 0,87; 0,77 ±0,99; P= 0,038). A redução da relação E/e´ em 30 dias após o TAVI associou-se à queda da mortalidade global (OR: 0,97; 0,95 ±0,99; P = 0,006), bem como valores elevados pré procedimento dessa relação se associaram a maiores taxas de insuficiência cardíaca classe funcional III ou IV da New York Heart Association após a intervenção (OR: 1,08; 1±1,18; P = 0,049). CONCLUSÃO: Os resultados deste trabalho indicam que o strain global longitudinal pré-procedimento demonstrou ser um preditor de reinternação cardiovascular pós-intervenção a longo prazo. A relação E/e´ pré-procedimento apresentou correlação diretamente proporcional com o desenvolvimento de insuficiência cardíaca classe funcional III ou IV a longo prazo, assim como sua queda acentuada 30 dias após o procedimento correlacionou-se com menor mortalidade global. / INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is a therapeutic option for symptomatic patients with severe aortic stenosis. Approximately 200,000 patients around the world have already undergone TAVR. No large studies have evaluated prognostic correlation between echocardiographic parameters before TAVR and long-term cardiovascular events. It is relevant to analyze strain before procedure and how other parameters work as independent predictors of events after the procedure. METHODS: A total of 86 patients were evaluated from November 2009 to October 2016. They underwent echocardiographic evaluation before TAVR and 30 days after the procedure with analysis of strain of the left ventricle by bidimensional speckle tracking and other echocardiographic parameters. Patients were followed clinically and evaluated in relation to outcomes: global mortality, cardiovascular mortality, functional class of heart failure and need for cardiovascular readmissions. RESULTS: Global longitudinal strain before reduced TAVR (absolute value) increased the chance of cardiovascular readmission (odds ratio: 0.87; 0.77 ± 0.99; p = 0.038). Reduction of E/e´ relationship 30 days after TAVI was associated with a drop in global mortality (odds ratio: 0.97; 0.95 ± 0.99; p = 0.006). In addition, high values for this relation before the procedure were associated with higher rates of New York Heart Association functional class III or IV heart failure after the intervention (odds ratio: 1.08; 1.00 ± 1.18; p = 0.049). CONCLUSIONS: Results of this study indicate that global longitudinal strain before the procedure is a predictor of cardiovascular readmission after TAVR. The E/e´relationship before the procedure presented a correlation directly proportional to the development of long-term functional class III or IV heart failure as well as its accentuated drop 30 days after the procedure was correlated with lower global mortality.

Introdução: Uma nova alternativa de tratamento foi desenvolvida, o Implante por Cateter de Bioprótese Valvar Aórtica (TAVI, em inglês, Transcatheter Aortic Valve Implantation), indicado para os pacientes portadores de estenose aórtica grave com várias comorbidades, considerados inoperáveis pelo tratamento cirúrgico convencional. O TAVI ainda não foi incorporado ao rol de políticas de saúde do Brasil pelo Sistema Único de Saúde (SUS), tampouco pela Agência Nacional de Saúde Suplementar (ANS), pois há escassez de evidências científicas fundamentadas em análise econômica do procedimento que relatem os resultados e o custo a longo prazo em comparação à cirurgia convencional. Objetivo: Identificar o custo direto médio do implante por cateter de bioprótese valvar aórtica, verificar se há alteração significativa de custo nas diferentes vias de acesso utilizadas e identificar os fatores preditores que possam elevar o custo do procedimento. Método: Trata-se de uma pesquisa com abordagens quantitativa, exploratória, descritiva, transversal, retrospectiva e documental, realizada em um hospital da Secretaria de Estado de Saúde de São Paulo (SES-SP), da Administração Direta, especializado no tratamento de doenças cardiovasculares de alta complexidade. A população do estudo correspondeu aos procedimentos eletivos do TAVI, desde a inauguração da sala híbrida, em março de 2012, até agosto de 2015, totalizando 108 procedimentos, sendo 92 por via transfemoral, 8 por via transapical e 8 por via transaórtica. Resultados: O custo direto médio dos procedimentos TAVI nas três vias totalizou R$ 82.230,94. Por via transfemoral, esse custo médio foi de R$ 82.826,38; por via transaórtica, R$ 79.440,91; e por via transapical, R$ 78.173,41. O total de material e medicamento/solução representou, por via transfemoral, 91,89% do total do custo direto médio do procedimento TAVI; por via transapical, 91,81%; e por via transaórtica, 90,69%, e o custo fixo com a válvula transcateter, no valor de R$ 65 mil, representou 78,47% sobre o custo total do procedimento TAVI, por via transfemoral; 83,14%, por via transapical; e 81,82%, por via transaórtica. O Teste Kruskal-Wallis Teste das Variáveis Contínuas apresentou diferença estatisticamente significativa entre as vias de acesso. No custo total do procedimento TAVI, o Teste de Bonferroni mostrou diferença na associação entre as vias transfemoral e transapical. No entanto, na associação com a via transaórtica, não apresentou diferença estatisticamente significativa. Os fatores preditores que elevaram o custo do procedimento TAVI foram: vias de acesso, duração do procedimento, material de hemodinâmica, medicamento/solução, material de consumo, material de perfusão, total de material e medicamento/solução, recursos humanos, gases medicinais, depreciação e energia. A segunda válvula foi a única variável referente às intercorrências no Centro Cirúrgico que elevou o custo do procedimento. A média de idade dos pacientes com indicação ao TAVI foi de 81,50 ±6,96 anos. Conclusão: O TAVI é um avanço a ser discutido e acompanhado, havendo a necessidade de reforçar novas pesquisas que avaliem os benefícios do tratamento com base nos resultados e custos, a fim de auxiliar na tomada de decisão para incorporação desse tratamento para o público-alvo, melhorando a qualidade de vida dos pacientes e proporcionando a integração destes novamente às atividades diárias. / Introduction: A new treatment alternative has been developed, the Transcatheter Aortic Valve Implantation (TAVI), indicated for patients with severe aortic stenosis with various comorbidities deemed inoperable by conventional surgical treatment. TAVI has not yet been incorporated into the Brazilian health policies by the Public Health System (SUS), or by the National Supplementary Health Agency (ANS), because there is a shortage of scientific evidence based on an economic analysis of the procedure that reports the results and the long-term costs compared to conventional surgery. Objective: To identify the average direct cost of the transcatheter aortic valve implantation, to verify if there is significant change of cost in the different access routes used, and to identify predictive factors that could increase the cost of the procedure. Method: This is a study with quantitative, exploratory, descriptive, transversal, retrospective, and documentary approaches, carried out in a hospital of the State Department of Health of São Paulo (SES-SP), of the Direct Administration, specialized in the treatment of high-complexity cardiovascular diseases. The study population corresponded to TAVI elective procedures, from the inauguration of the hybrid room, in March 2012, up to August 2015, totaling 108 procedures, of which 92 were transfemoral, 8 were transapical, and 8 were transaortic. Results: The average direct cost of the TAVI procedures in the three routes totaled R$ 82,230.94. Transfemorally, this average cost was R$ 82,826.38; through the transaortic route, R$ 79,440.91; and through the transapical route, R$ 78,173.41. The total material and medication / solution represented 91.89% of the total average direct cost of the TAVI procedure through the transfemoral route; 91.81% through the transapical route; and 90.69% through the transaortic route, and the fixed cost with the transcatheter valve, in the amount of R$ 65,000.00, represented 78.47% of the total cost of the TAVI procedure through the transfemoral route; 83.14%, through the transapical route; and 81.82% through the transaortic route. The Kruskal-Wallis Test Continuous Variables Test showed a statistically significant difference among the access routes. In the total cost of the TAVI procedure, the Bonferroni Test showed a difference in the association between the transfemoral and transapical routes. However, in the association with the transaortic route, there was no statistically significant difference. Predictive factors that increased the cost of the TAVI procedure were: access routes, length of procedure, hemodynamic material, drug / solution, consumption material, infusion material, total material and medicine/solution, human resources, medical gas, depreciation and energy. The second valve was the only variable related to the complications in the or that increased the cost of the procedure. The mean age of patients with TAVI was 81.50 ± 6.96 years. Conclusion: TAVI is an advance to be discussed and monitored, and there is a need to encourage new studies that evaluate the benefits of treatment based on the results and costs, in order to assist in the decision making for the incorporation of this treatment into its population, improving the quality of life of patients and providing once again their integration into daily activities.

Introduction: La surcharge de pression ventriculaire augmente à l’exercice chez les patients avec une sténose de valve aortique (SVA). Lorsqu’il n’y a aucun symptôme apparent, il est cependant difficile d’indiquer l’intervention chirurgicale en utilisant seulement les indices de surcharge de pression ventriculaire. D’autres paramètres, tels que la dispersion de la repolarisation ventriculaire (d-QT), qui augmentent avec le gradient de pression transvalvulaire (GPT), n’ont pas été étudiés dans la SVA. L’objectif de l’étude était de déterminer le modèle de réponse du segment QT et de la d-QT à l’épreuve d’effort chez des enfants avec une SVA congénitale modérée afin d’évaluer l’impact de la surcharge de pression ventriculaire selon une perspective électrophysiologique. Matériel et méthodes: 15 patients SVA modérés ont été comparés à 15 sujets contrôles appariés pour l’âge (14.8±2.5 ans vs. 14.2±1.5 ans) et pour le sexe (66,7% de sujets mâles). Tous les sujets ont fait une épreuve d’effort avec enregistrement électrocardiographique à 12 dérivations. Le segment QT a été mesuré à partir du début du complexe QRS jusqu’à l’apex de l’onde T (QTa) au repos, à l’effort maximal ainsi qu’après 1 et 3 minutes de récupération. La longueur du segment QT a été corrigée selon l’équation de Fridericia et la d-QT a été calculée. Résultats: La longueur du segment QT corrigée (QTc) était similaire au repos entre les groupes d’étude, mais était significativement élevée chez les SVA en comparaison avec le groupe contrôle à l’effort maximal (p=0.004) ainsi qu’après 1 (p<0.001) et 3 (p<0.001) minutes de récupération. Une interaction significative a été identifiée entre les groupes pour la d-QT (p=0.034) et les tests post hoc ont révélé une différence significative seulement au repos (p=0.001). Conclusions: Les anomalies de repolarisation ventriculaire peuvent être révélées par l’évaluation de la repolarisation électrique lors de l’épreuve d’effort chez les SVA modérées asymptomatiques. L’utilisation de la réponse du QT à l’effort pourrait être bénéfique pour l’optimisation de la stratification du risque chez ces patients. / Introduction: Pressure overload increases in patients with moderate aortic valvular stenosis (AVS) during acute exercise. In the absence of symptoms, it remains difficult however, to discriminate patients for surgery based only on pressure overload. Other parameters, such as the dispersion of ventricular repolarisation (d-QT), which reportedly increases with the transvalvular pressure gradient, have not been fully studied in AVS. The aim of the study was to determine the pattern of QT and d-QT response to exercise testing in children with moderate AVS to evaluate the impact of pressure overload from an electrophysiological perspective. Materials and methods: 15 moderate AVS patients were compared to 15 controls paired for age (14.8±2.5 vs. 14.2±1.5 years old) and gender (66.7% male). All subjects underwent exercise stress testing with 12-lead ECG recording. QT was measured from the onset of QRS to the apex (QTa) at rest, peak exercise, 1 and 3 minutes of recovery. QT was corrected using the Fridericia equation and d-QT was calculated. Results: Resting QTc was similar among the study groups, but increased significantly in AVS in comparison to the control group at maximal effort (p=0.004) and after 1 (p<0.001) and 3 (p<0.001) minutes of recovery. A significant interaction was identified between groups for d-QT (p=0.034) and post-hoc tests revealed a significant difference only at rest (p=0.001). Conclusions: Ventricular repolarisation abnormalities can be unmasked and highlighted by the assessment of electrical repolarisation during exercise challenge in asymptomatic moderate AVS. Using QT response to exercise could be beneficial for better optimisation of risk stratification in these patients.

Abstract Heart failure (HF) and aortic valve stenosis (AS) are complex disorders affected by functional alterations and actively regulated remodelling of the heart and the aortic valve, respectively. In addition to structural proteins, such as collagens and elastin, the extracellular matrix (ECM) in the heart and the aortic valve comprises non-collagenous factors that are not strictly involved in the architecture but may modulate cardiac and valvular remodelling. In the present study the expression of non-collagenous fibrosis- and calcification-related ECM proteins was investigated in HF-associated cardiac remodelling from different origins as well as in fibrocalcific aortic valve disease leading to AS. The experimental models of pressure overload, myocardial infarction (MI) and chronic renal failure were used to study the cardiac expression of bone morphogenetic protein (BMP)-2, BMP-4, bone sialoprotein, matrix Gla protein (MGP), osteoactivin, osteopontin, periostin and/or pleiotrophin in vivo in cardiac remodelling. Human aortic valves, obtained from patients undergoing valve replacement, were studied to characterize the valvular expression of BMP-2, BMP-4, bone sialoprotein, MGP, osteoactivin, osteopontin, osteoprotegerin, periostin, pleiotrophin, and thrombospondins (TSPs) 1-4 in the different stages of fibrocalcific aortic valve disease. Left ventricular (LV) MGP expression was upregulated in vivo in non-uremic cardiac remodelling. In vitro results indicate that angiotensin II elevates MGP expression in cardiomyocytes and fibroblasts. Periostin gene expression was induced in cardiac but not in aortic valve remodelling and the cardiac induction in chronic renal insufficiency was associated with LV hypertrophy and blood pressure as well as the cardiac gene expression of other fibrosis-related genes. Bone sialoprotein and osteopontin were expressed in the aortic valves in parallel with calcification, and also in distinct models of cardiac remodelling. Osteoprotegerin protein expression in stenotic valves was weak regardless of a simultaneous increase in gene expression. BMPs were downregulated in AS and no change in LV gene expression was detected in uremic cardiac remodelling. All the studied TSPs were expressed in human aortic valves, and especially the expression of TSP-2 was shown to increase in fibrocalcific aortic valves simultaneously with decreased activation of the Akt/nuclear factor (NF)-κB-pathway. This study delineates distinct expression patterns of non-collagenous ECM proteins in pathological tissue remodelling in the heart and in the aortic valve, and thus emphasizes the role of ECM proteins as an important modulator of cardiac and aortic valve remodelling. / Tiivistelmä Sydämen vajaatoiminnan ja aorttastenoosin taudinkuvaan kuuluvat toiminnallisten muutosten ohella aktiivisesti säädellyt soluväliaineen muutokset sydämen ja aorttaläpän rakenteessa. Soluväliaineen rakenteen muodostavien kollageenien ja elastiinin lisäksi soluväliaineessa on rakenteeseen kuulumattomia proteiineja. Tässä väitöskirjassa tutkittiin sidekudoksen kertymiseen ja kudosten kalkkiutumiseen osallistuvia soluväliaineen proteiineja sydämen vajaatoiminnassa sekä aorttastenoosiin johtavassa kalkkiuttavassa aorttaläppäviassa. Tutkimuksessa selvitettiin sydämen soluväliaineen proteiinien ilmentymistä painekuormituksen, sydäninfarktin ja pitkäaikaisen munuaisten vajaatoiminnan koemalleissa rotalla. Tutkittavia proteiineja olivat luun morfogeneettiset proteiinit 2 ja 4, luun sialoproteiini, matriksin Gla proteiini (MGP), osteoaktiviini, osteopontiini, periostiini ja pleiotropiini. Edellä mainittujen proteiinien lisäksi osteoprotegeriinin ja trombospondiinien 1-4 ilmentymistä tutkittiin kalkkiuttavan aorttaläppävian eri kehitysvaiheissa. Aorttaläpät oli kerätty tekoläppäleikkauspotilailta. Sydämessä MGP:n ilmentyminen lisääntyi kaikissa muissa paitsi munuaisten vajaatoiminnan koemallissa. Angiotensiini II nosti MGP:n ilmentymistä sydänlihassoluissa ja sidekudossoluissa. Periostiinin ilmentyminen lisääntyi sydämen uudelleenmuovautumisessa, muttei aorttaläppäviassa. Lisäksi munuaisten vajaatoiminnan aiheuttama periostiinin ilmentymisen muutos sydämessä liittyi sekä sydämen kasvuun, verenpaineen nousuun että muiden sidekudosta muokkaavien proteiinien ilmentymiseen. Luun sialoproteiinin ja osteopontiinin ilmentymiset erosivat toisistaan erilaisissa sydämen vajaatoiminnan malleissa, mutta aorttaläpissä niiden molempien ilmentyminen oli suhteessa läpän kalkkiutumiseen. Osteoprotegeriinin geenin ilmentyminen lisääntyi kalkkiutuneissa aorttaläpissä vaikkakin proteiinin määrä pysyi vähäisenä. Luun morfogeneettisten proteiinien ilmentyminen oli alentunut sairaissa läpissä, muttei sydämessä munuaisten vajaatoiminnan aikana. Aorttaläpissä ilmennettiin kaikkia trombospondiineita, joista trombospondiini-2:n ilmentyminen kasvoi sairaissa aorttaläpissä. Kalkkiutuneissa läpissä solunsisäinen Akt/NF-κB–signaalinvälitysjärjestelmä oli vaimentunut. Tutkimus osoittaa, että soluväliaineen proteiinien ilmentymistä säädellään eri tavoin sydämen vajaatoiminnassa ja aorttastenoosissa kudoksen uudelleenmuovautumisprosessin aikana.

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

Die transfemorale Aortenklappenimplantation stellt für ältere Patienten mit einer symptomatischen, hochgradigen Aortenklappenstenose und einem erhöhten perioperativen Letalitätsrisiko eine Alternative zum konventionell-chirurgischen Aortenklappenersatz dar. In der vorliegenden Arbeit wurden die beiden aktuell in Europa zugelassenen transfemoralen Systeme in Bezug auf deren prozedurale Sicherheit, den klinischen Nutzen, die 1-Jahres-Letalitätsrate und die langfristige Klappenfunktionalität unter Anwendung der Kriterien zur standardisierten Komplikationsanalyse des Valve Academic Research Consortiums (VARC) verglichen. Jeweils 100 konsekutive Patienten, bei denen eine transfemorale Aortenklappenimplantation mit den Edwards SAPIEN™/SAPIEN XT™ Transcatheter Heart Valves bzw. dem Medtronic CoreValve ReValving™ System durchgeführt wurde, wurden in die Analyse eingeschlossen. Dies stellt das größte bisher publizierte Patientenkollektiv für den Vergleich der beiden Aortenklappenimplantationssysteme in einem Zentrum über den femoralen Zugangsweg dar. Es wurden mit beiden Systemen ähnlich gute postinterventionelle hämodynamische und klinische Ergebnisse erreicht. Ein signifikanter Unterschied bezüglich der prozeduralen Sicherheit und der 1-Jahres-Letalitätsrate zwischen den beiden Systemen konnte trotz signifikanter Unterschiede in Bezug auf bestimmte periinterventionelle Risiken nicht nachgewiesen werden. Die langfristige Klappenfunktion beider Systeme war exzellent.