Leaflet replacement in aortic valve repair (AVr) is associated with increased long-term repair failure. Hemodynamic performance and mechanical stress levels were investigated after porcine AVr with 5 types of clinically relevant replacement materials to ascertain which material(s) would be best suited for repair. Porcine aortic roots with intact aortic valves were placed in a left-heart simulator mounted with a high-speed camera for baseline valve assessment. Then, the non-coronary leaflet was excised and replaced with autologous porcine pericardium (APP), glutaraldehyde-fixed bovine pericardial patch (BPP; Synovis™), extracellular matrix scaffold (CorMatrix™), or collagen-impregnated Dacron (HEMASHIELD™). Hemodynamic parameters were measured over a range of cardiac outputs (2.5–6.5L/min) post-repair. Material properties of the above materials along with St. Jude Medical™ Pericardial Patch with EnCapTM Technology (SJM) were determined using pressurization experiments. Finite element models of the aortic valve and root complex were then constructed to verify the hemodynamic characteristics and determine leaflet stress levels. This study demonstrates that APP and SJM have the closest profiles to normal aortic valves; therefore, use of either replacement material may be best suited. Increased stresses found in BPP, HEMASHIELD™, and CorMatrix™ groups may be associated with late repair failure.

Thesis (MScEng)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Bioprosthetic heart valves (BHVs) for transcatheter aortic valve implantation (TAVI) have been rapidly developing over the last decade since the first valve replacement using the TAVI technique. TAVI is a minimally invasive valve replacement procedure offering lifesaving treatment to patients who are denied open heart surgery. The biomedical engineering research group at Stellenbosch University designed a 19 mm balloon expandable BHV for TAVI in 2007/8 for testing in animal trials. In the current study the valve was enlarged to 23 mm and 26 mm diameters. A finite element analysis was performed to aid in the design of the stents. New stencils were designed and manufactured for the leaflets using Thubrikar‟s equations as a guide. The 23 mm valve was manufactured and successfully implanted into two sheep. Fluid structure interaction (FSI) simulations constitute a large portion of this thesis and are being recognized as an important tool in the design of BHVs. Furthermore, they provide insight into the interaction of the blood with the valve, the leaflet dynamics and valve hemodynamic performance. The complex material properties, pulsating flow, large deformations and coupling of the fluid and the physical structure make this one of the most complicated and difficult research areas within the body. The FSI simulations, of the current valve design, were performed using a commercial programme called MSC.Dytran. A validation study was performed using data collected from a cardiac pulse duplicator. The FSI model was validated using leaflet dynamics visualisation and transvalvular pressure gradient comparison. Further comparison studies were performed to determine the material model to be used and the effect of leaflet free edge length and valve diameter on valve performance. The results from the validation study correlated well, considering the limitations that were experienced. However, further research is required to achieve a thorough validation. The comparative studies indicated that the linear isotropic material model was the most stable material model which could be used to simulate the leaflet behaviour. The free edge length of the leaflet affects the leaflet dynamics but does not greatly hinder its performance. The hemodynamic performance of the valve improves with an increase in diameter and the leaflet dynamics perform well considering the increased surface area and length. Many limitations in the software prevented more accurate material models and flow initiation to be implemented. These limitations significantly restricted the research and confidence in the results. Further investigation regarding the implementation of FSI simulations of a heart valve using the commercial software is recommended. / AFRIKAANSE OPSOMMING: Bio-prostetiese hartkleppe (Bioprosthetic Heart Valves - BHVs) wat gebruik word vir transkateter aortaklep-inplantings (Transcatheter Aortic Valve Implantation - TAVI) het geweldig vinnige ontwikkeling getoon in die afgelope tien jaar sedert die eerste klepvervanging wat van die TAVI prosedure gebruik gemaak het. TAVI is ʼn minimaal indringende klepvervangingsprosedure wat lewensreddende behandeling bied aan pasiënte wat ope-hart sjirurgie geweier word. Die Biomediese Ingenieurswese Navorsingsgroep (BERG) by Stellenbosch Universiteit het in 2007/8 ʼn 19 mm ballon-uitsetbare BHV vir TAVI ontwerp vir eksperimente met diere, en hierdie tesis volg op die vorige projekte. In die huidige studie is die klep vergroot na 23 mm en 26 mm in deursnee. ʼn Eindige element analise is gedoen om by te dra tot die ontwerp van die rekspalke vir die klep. Nuwe stensils is ontwerp en vervaardig vir die klepsuile, deur gebruik te maak van Thubrikar se vergelykings. Die 23 mm klep is vervaardig en suksesvol in twee skape ingeplant. Vloeistruktuur interaksie (Fluid Structure Interaction (FSI)) simulasies vorm ‟n groot deel van die tesis en word gesien as ʼn noodsaaklike hulpmiddel in die ontwerp van BHVs. Die simulasies verskaf ook insig in die interaksie van die bloed met die klep, die klepsuil-dinamika en die klep se hemodinamiese werkverrigting. Die komplekse materiaal eienskappe, polsende vloei, grootskaalse vervorming, die verbinding van die vloeistof en die fisiese struktuur maak van hierdie een van die mees gekompliseerde voorwerpe om te simuleer. Die FSI simulasies van die huidige ontwerp, is uitgevoer deur van kommersiële sagteware, MSC.Dytran, gebruik te maak. ʼn Geldigheidstudie wat data gebruik het vanaf die hartklop-nabootser, is uitgevoer. Die FSI model word geverifieer deur klepsuil dinamika visualisering en ʼn vergelyking van die drukgradiënt gebruik te maak. Verdere vergelykende studies is uitgevoer om te bepaal watter materiaal model om te gebruik, asook die uitwerking van die klepsuil-vrye rand en klepdeursnee op die klep se werkverrigting. Die resultate van die studie korreleer goed, in ag genome die beperkings wat ervaar is. Verdere navorsing is egter nodig vir ʼn volledige geldigheidstudie. Vergelykende studies het getoon dat die liniêre isotropiese materiaalmodel die meer stabiele materiaalmodel is wat kan gebruik word om klepsuilgedrag te simuleer. Die vrye-rand lengte van die klepsuil affekteer die dinamika van die klepsuil, maar belemmer nie die werkverrigting grootliks nie. Die hemodinamiese werkverrigting van die klep verbeter met die toename in deursnee en die klepsuil-dinamika vertoon goed in ag genome die verhoogde oppervlak area en lengte. Die vele beperkings in die sagteware het die implementering van meer akkurate materiaalmodelle verhoed. Hierdie beperkings het ʼn verminderde vertroue in die resultate tot gevolg gehad. Verdere ondersoek rakende die implementering van die FSI simulasies van ʼn hartklep deur kommersieel beskikbare sagteware te gebruik, word aanbevel.

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.

(v AJ) Introduction to the topic and importance of the topic: Aortic valve disease is the third most frequent cardiovascular disease and also the most frequently operated valvular disease in adulthood. The natural process of the disease is unfavorable, almost half of the patients suffer from symptoms of heart failure (Branny et al. 2012). This is the reason why I focused my thesis on the assessment of the quality of life of patients diagnosed of aortic stenosis. Aim of the thesis and research questions: The aim of my thesis is to evaluate the quality of life patients with diagnosed aortic valve disease, within one month before the planned surgery and in the postoperative period when patients will be checked at a cardiac surgery clinic. The partial objective at the same time was to compare the quality of life and health status of patients with aortic valve disease who have completed a spa therapy with those who have rejected it. Methodology (method, research sample): The research work will be carried out as a quantitative research in a group of 29 respondents. The HRQoL construct it means questionnaire SF-36 were used to obtain the data. The questionnaire was anonymous. For the completed questionnaires, a closed box was set up, which I didn't open until the poll was complete. The survey was...

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.

Einleitung: Die Implantation kryokonservierter allogener Aortenklappen stellt heutzutage eine effektive operative Technik dar, um in schweren Fällen einer floriden Aortenklappenendokarditis exzellente postoperative Ergebnisse zu erzielen. Diese Studie demonstriert die Langzeitergebnisse im Deutschen Herzzentrum Berlin über einen Zeitraum von 17 Jahren. Material und Methoden: Zwischen dem 1.Januar 1987 und 31.Dezember 2003 wurden bei 203 Patienten mit florider Aortenklappenendokarditis kryokonservierte Aortenklappenallografts implantiert (in subkoronarer Implantationstechnik n=107 und durch totalen Aortenwurzelersatz n=96). Das mittlere Alter der Patienten betrug 51,3 Jahre (2-82 Jahre). Darunter waren 42 Frauen und 161 Männer. 161 Patienten zeigten präoperativ eine anuläre Aortenwurzelabszeßbildung. Ergebnisse: Die 30-Tage-Mortalität (mit Anulusabszeß) betrug insgesamt 21,1% (23,6%): bei nativer Aortenklappenendokarditis 14,9% (17,5%) und bei Prothesen-endokarditis 29,2% (29,6%). Nach 17 Jahren waren 70,4+3,6% und 78,6+6,3% (p=0,24) der Patienten mit und ohne präoperativem Anulusabszeß am Leben. Bei 12 Patienten mit Anulusabszeß trat eine Allograft-Re-Infektion auf, die aktualisierte Freiheit von Reinfektion betrug 91,6+2,4% nach 17 Jahren. Insgesamt wurden 37 Patienten reoperiert, die aktualisierte Freiheit von Reoperation betrug 75,0+3,7% nach 17 Jahren. Die aktualisierte Freiheit von Explantation der Allografts wegen Strukturalteration betrug bei den Patienten mit Anulusabszeß nach 17 Jahren 96,0+2,0%. Thrombembolische Ereignisse traten nicht auf. Die Univarianzanalyse identifizierte die Allograft-Re-Infektion (p=0,0001) und zu klein bemessene Allografts (p=0,001) als Risikofaktoren für eine Reoperation sowohl bei nativer als auch Prothesenendokarditis. Schlußfolgerung: Aortenklappenallografts zeigen bei florider Aortenklappenendokarditis mit Anulusabszeß exzellente Langzeitresultate. Die 30-Tage–Mortalität wird hinsichtlich der Schwere der Erkrankung akzeptiert und Re-Infektionen sind selten. Zu klein bemessene Allografts und Re-Infektionen sind Risikofaktoren für Reoperationen. / Objective: Cryopreserved aortic valve homografts have become an accepted valve substitute in acute aortic valve endocarditis, but long-term studies of valve function are largely unavailable. This survey represents our observations over a period of 17 years. Material and methods: Between February 9, 1987 and October 30, 2003, 203 patients with infective aortic valve endocarditis underwent allograft replacement of the aortic valve (free-hand subcoronary technique, n=107 and root replacement, n=96). The patients’ age ranged between 2 and 82 years with a mean age of 51.3 years. The survey included 42 females and 161 males. 161 had infected aortic root with ring abscesses. Results: The hospital mortality of patients with native and prosthetic endocarditis complicated by periannular abscess was 14.9% (17.5%) and 29.2 % (29.6%) respectively making an overall hospital mortality of 21.2% (23.6%). 17 years patient survival in patients with and without periannular abscess was 70.4+3.6% and 78.6+6.3% (p=0,24) respectively. There were 12 events of recurrent endocarditis in patients with periannular abscess, giving an actuarial freedom of 91.6+2.4% at 17 years. Reoperation was performed in 37 patients for a variety of reasons, and overall freedom from reoperation was 75.0+3.7% at 17 years. Freedom from explantation for structural valve deterioration was 96.0+2.0% at 17 years for patients with periannular abcess. No thrombembolic event was evident. Univariable analysis identified recurrent endocarditis (p=0.0001) and undersized allograft (p=0.001) as risk factors for reoperation for both native and prosthetic aortic valve endocarditis. No risk factors for hospital mortality were found. Conclusion: Aortic allograft offers an excellent long-term clinical result in patients with infective aortic valve endocarditis with associated periannular abscess. Operative mortality is acceptable based on the severity of aortic pathology, with low evidence of recurrent endocarditis and no thrombembolic events. Undersized allograft and recurrent infection are risk factors for reoperation.

A necessidade de cirurgia para substituição da aorta ascendente e valva aórtica com reimplante coronariano em grupos especiais de pacientes onde a anticoagulação é indesejável, como nos idosos, é crescente nos últimos anos. Este estudo objetiva desenvolver e avaliar em modelo animal o comportamento de um conduto valvado aórtico feito com pericárdio bovino tratado pelo glutaraldeído (CVAP). Para tanto, CVAPs foram implantados em 8 ovinos jovens e explantados após serem sacrificados com 150 dias de pós-operatório. Realizou-se estudo angiográfico e hemodinâmico no préoperatório e antes do explante. Ecodopplercardiogramas foram realizados nos dias 30 e 150 de pós-operatório (teste) e também em 5 ovinos não operados (controle). Após explantados, submetemos os CVAPs à avaliação macroscópica, radiológica e histológica por microscopia óptica e eletrônica de transmissão. A análise estatística foi feita com teste não-paramétrico de Mann-Whitney, teste não-paramétrico de Wilcoxon e teste exato de Fisher. O nível de significância utilizado foi 5%. Na análise hemodinâmica houve acréscimo (p>0,05) das pressões arterial e capilar pulmonar entre os dias 0 e 150. Na análise ecodopplercardiográfica, o grupo teste apresentou valores maiores (p>0,05) dos diâmetros diastólicos e sistólicos do ventrículo esquerdo. No grupo teste entre os dias 30 e 150 houve acréscimo (p>0,05) de: peso, espessura das paredes do ventrículo esquerdo, gradiente transvalvar máximo, gradiente transvalvar médio, diâmetro diastólico do ventrículo esquerdo e decréscimo da fração de ejeção. Dois animais com endocardite podem explicar essas diferenças. A macroscopia demonstrou calcificação de grau variável, além de abaulamento na região dos seios em todos os CVAPs, sem aumento de diâmetro. A microscopia óptica revelou dados similares ao da literatura com o uso do pericárdio bovino tratado pelo glutaraldeído. A quantificação realizada com a microscopia eletrônica de transmissão mostrou percentual maior (p>0,05) de colágeno nos seios e nas cúspides e maior conteúdo hídrico na porção mais distal do CVAP. Estes dados indicam que a bioprótese aqui estudada permite a realização desse tipo de experimento no modelo proposto e que os resultados hemodinâmicos encontrados se assemelham aos parâmetros fisiológicos. / The need for replacement surgery of the ascending aorta and aortic valve with coronary reimplantation in special patient groups where anti-coagulation in undesirable, such as elderly, is increasing in the past years. This study aims to develop and evaluate the performance of an aortic valved conduit made with glutaraldehyde treated bovine pericardium (AVCP) in an animal model. Therefore, AVCPs were implanted in 8 young ovine and explanted after being euthanized at 150 days of the post-operative period. An angiographic and hemodynamic study was performed at pre-operative and prior the explant. EchoDoppercardiograms were performed at day 30 and 150 of post-operative (test) as well as in 5 non-operated on ovines (control). Following the explant, AVCPs were submitted to a macroscopical, radiological and histological evaluation by optic and electronic transmission microscopy. A statistics analysis was performed with a Mann-Whitneys nonparametric test, Wilcoxons non-parametric test and Fishers exact test. The significance level used was 5%. In the hemodynamic analysis an increase (p>0,05) of arterial and pulmonary capillary pressure occurred between day 0 and 150. In the echoDoppercardiographic analysis, the test group presented higher values (p>0,05) in the diastolic and systolic diameters of the left ventricle. In the test group, between day 30 and 150, occurred an increase (p>0,05) of weight, thickness of the left ventricle walls, maximum transvalvar gradient, medium transvalvar gradient, left ventricle diastolic diameter and a decrease in the ejection function. Two animals with endocarditis could explain those differences. Macroscopy showed a calcification in variable degrees besides a bulging of the sinus region in all AVCPs, without an increase of diameter. Optic microscopy revealed data similar to literature with the use of glutaraldehyde treated bovine pericadium. The quantification performed by electronic transmission microscopy showed a higher percentage (p>0,05) of collagen in sinus and cusps, and a higher watery content in the most distal portion of the AVCP. These data indicate that the bioprosthesis hereby studied allows the performance of this kind of experiment in the proposed model and that the hemodynamic outcomes found are similar to physiological parameters.

Introdução: as mucopolissacaridoses (MPSs) são doenças lisossômicas de depósito, caracterizadas pela degradação enzimática deficiente dos glicosaminoglicanos (GAGs): ácido hialurônico, condroitin sulfato, dermatan sulfato, heparan sulfato e queratan sulfato. A classificação baseia-se na enzima comprometida, tendo sido descritos sete tipos com manifestações clínicas heterogêneas: MPS tipo I, II, III, IV, VI, VII e IX. O comprometimento cardiovascular é variável, porém a falência cardiopulmonar contribui significativamente para a morbidade e mortalidade. Lesões valvares esquerdas e a hipertrofia do ventrículo esquerdo são os achados mais citados, ainda que não haja concordância quanto à relação entre o comprometimento cardíaco e o tipo de MPS. Especula-se que o acometimento é mais grave em pacientes cujo defeito enzimático traz acúmulo do dermatan sulfato (MPS tipos I, II, VI e VII), visto que esse GAG predomina naturalmente em válvulas e vasos sanguíneos. Frente à perspectiva de tratamento específico dessas patologias através de reposição enzimática, torna-se fundamental conhecer o comprometimento cardiovascular inicial, para determinar com segurança o impacto destas terapêuticas sobre as crianças a elas submetidas. O propósito deste estudo foi caracterizar as alterações ecocardiográficas de pacientes pediátricos com MPSs, além de testar a associação entre o acúmulo de dermatan sulfato e a gravidade das lesões cardiovasculares. Métodos: foram analisados retrospectivamente os prontuários e os ecocardiogramas de 28 pacientes (15M: 13F) entre 2 e 14 anos (9 ± 3 anos), acompanhados no Ambulatório de Genética do Instituto da Criança de setembro de 2003 a novembro de 2005: 6 com MPS tipo I, 2 com tipo II, 7 com tipo III, 6 com tipo IV, 5 com tipo VI e 2 com tipo VII. No período estudado nenhum paciente realizava terapia de reposição enzimática. Um único ecocardiografista executou 53 avaliações, visto que 17 indivíduos submeteram-se a múltiplos exames, com intervalo de 10,3 ± 5,6 meses. Todos os ecocardiogramas foram realizados segundo as normas da Sociedade Americana de Ecocardiografia. Os pacientes foram analisados quanto aos aspectos clínicos e parâmetros xvi ecocardiográficos, sendo realizada em seguida a comparação entre o grupo que acumula (D+) e o que não acumula dermatan sulfato (D-). O grupo D+ incluiu os tipos I, II, VI e VII e o grupo D-, os tipos III e IV. O programa estatístico utilizado foi o Statistical Package for Social Sciency e os testes aplicados foram o Exato de Fisher e o de Correlação de Spearman, com um valor de p significativo 0,05. Resultados: 26 (93%) pacientes exibiram alterações ecocardiográficas ao exame final. No entanto, em apenas 16 (57%) havia registro de ausculta anormal e em 6 (21%) alguma queixa cardiovascular. Hipertrofia de septo e de parede posterior foram detectadas em 12 pacientes (43%) e em 5 (18%) ocorreu hipertrofia septal isolada. Somente 2 (7%) apresentaram dilatação ventricular. Em 22 casos foi possível avaliar a função diastólica de ventrículo esquerdo. Destes, 6 (27%) apresentaram disfunção de grau leve. Todos apresentaram função sistólica preservada. Detectou-se hipertensão pulmonar em 10 pacientes (36%). Quatro foram admitidos à Unidade de Terapia Intensiva e dois evoluíram a óbito, todos por agravamento de hipertensão pulmonar. Valva mitral normal foi o achado em 5 (17,8%) e espessamento sem disfunção em 6 (21,4%). Espessamento valvar com disfunção ocorreu em 17 pacientes (60,8%): 12 (42,8%) com insuficiência, 2 (7,2%) com estenose e 3 (10,8%) com dupla lesão. A valva aórtica foi normal em 5 (17,8%) e espessada sem disfunção em 13 (46,4%). Espessamento com disfunção ocorreu em 10 pacientes (35,8%): todos com insuficiência de grau leve ou moderado. Verificou-se forte associação entre o acúmulo de dermatan sulfato e a presença de: disfunção valvar mitral (p = 0,0003), disfunção valvar aórtica (p = 0,006) e hipertensão pulmonar (p = 0,006). Entre os 17 indivíduos com múltiplos exames, 14 (82%) mostraram piora ecocardiográfica justificada por: surgimento (4/14) ou agravamento (6/14) de lesões valvares, surgimento (5/14) ou progressão (6/14) da hipertrofia ventricular, desenvolvimento de disfunção diastólica (1/14) e de hipertensão pulmonar (4/14). Conclusões: as alterações ecocardiográficas em pacientes pediátricos com mucopolissacaridoses são freqüentes e têm caráter progressivo, enquanto os sinais e sintomas são escassos. Lesões valvares esquerdas, hipertrofia ventricular e hipertensão pulmonar foram os achados mais comuns, havendo associação significativa entre o acúmulo de dermatan sulfato e o comprometimento cardiovascular. Diferentemente do que é descrito em adultos, a hipertensão pulmonar foi a causa mais importante de óbito e não a disfunção sistólica de ventrículo esquerdo. / Introduction: mucopolysaccharidosis (MPSs) are lysosomal storage diseases, characterized by deficient enzymatic degradation of glycosaminoglycanes (GAGs): hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate and keratan sulfate. The classification is based on the defective enzyme and seven types with heterogeneous clinical manifestations have been described: MPS type I, II, III, IV, VI, VII and IX. The cardiovascular involvement is variable, but the cardiopulmonary failure contributes significantly towards the morbidity and mortality. Left valve lesions and left ventricle hypertrophy are the most commented findings, although there is still no agreement about the relationship between the heart involvement and the type of MPS. It is speculated that the lesions are more severe in patients whose enzymatic defect lead to the accumulation of dermatan sulfate (MPS types I, II, VI and VII), because this GAG prevails naturally in valves and blood vessels. Due to the perspective of specific treatment for the pathology through enzymatic replacement, it is essential to know the initial cardiovascular abnormalities to determine the impact of this therapeutics on pediatric patient. The purpose of this study was to characterize the echocardiographic alterations of the pediatric patients with MPSs, besides testing the association between the accumulation of dermatan sulfate and the severity of the cardiovascular lesions. Methods: the medical records and echocardiograms of 28 patients (15M: 13F) aged 2 to 14 (9 ± 3 years), seen at the Genetic Clinic between September 2003 and November 2005, were retrospectively analyzed: 6 with MPS type I, 2 with type II, 6 with type III, 7 with type IV, 5 with type VI and 2 with type VII. During the period of study no patient had enzymatic replacement. A single pediatric cardiologist executed 53 echocardiograms, since 17 individuals underwent multiple exams, with an interval of 10.3 ± 5.6 months. All the echocardiograms were performed according to the recommendations of the American Society of Echocardiography. Patients were analyzed according to both clinical and echocardiographic parameters, and then a comparison was made among the group that accumulates (D+) and the one that does not xviii accumulate dermatan sulfate (D-). The group D+ included the types I, II, VI and VII and the group D included types III and IV. The statistical program used was the Statistical Package for Social Science and the applied tests were the Fisher\'s exact test and the Spearman correlation, where a p-value < 0.05 was considered significant. Results: echocardiographic alterations were detected in 26 patients (93%), whereas 16 (57%) had abnormal auscultation, and only 6 (21%) presented cardiovascular complaint. Septum and posterior wall hypertrophy were diagnosed in 12 patients (43%) and five (18%) showed signs of isolated septal hypertrophy. Only 2 (7%) presented ventricular dilation. In 22 patients it was possible to evaluate the diastolic function of the left ventricle. Of these, 6 presented mild dysfunction. However, all patients had preserved systolic function. Pulmonary hypertension was detected in 10 patients (36%). 4 patients were admitted in the Intensive Care Unit and 2 died, due to aggravation of pulmonary hypertension. Normal mitral valve was found in 5 (17.8%) and thickening without dysfunction in 6 cases (21.4%). Valve thickening with dysfunction occurred in 17 (60.8%): 12 (42.8%) with regurgitation, 2 (7.2%) with stenosis and 3 (10.8%) with double lesion. The aortic valve was normal in 5 (17.8%) and thickened without dysfunction in 13 cases (46.4%). Thickening with dysfunction happened in 10 patients (35.8%): all with mild or moderate aortic regurgitation. A strong association was observed between accumulation of dermatan sulfate and presence of mitral valve dysfunction (p = 0.0003), aortic valve dysfunction (p = 0.006) and pulmonary hypertension (p = 0.006). Among 17 individuals with multiple exams, 14 (82%) had a worsening evolution justified by the appearance (4/14) or aggravation (6/14) of valve lesions, appearance (5/14) or progression (6/14) of ventricular hypertrophy, development of left ventricle diastolic dysfunction (1/14) and of pulmonary hypertension (4/14). Conclusions: echocardiographic alterations in pediatric patients with Mucopolysaccharidosis are frequent and have a progressive character. Left valve lesions, ventricular hypertrophy and pulmonary hypertension were the most common findings and there was association between accumulation of dermatan sulfate and cardiovascular involvement. Unlike in adults, pulmonary hypertension was the main cause of death, not left ventricle systolic dysfunction.

INTRODUÇÃO: Avaliação da função diastólica de pacientes portadores de estenose ou insuficiência aórtica submetidos à troca valvar. OBJETIVOS: Avaliação da função diastólica através da análise do NTpró-BNP como método não invasivo para caracterização da insuficiência cardíaca diastólica, comparando com os dados ecocardiográficos através do Doppler Pulsado em Fluxo Mitral, Doppler Pulsado em Veias Pulmonares e Doppler Tecidual em portadores de IAO e EAO. MÉTODOS: Foram avaliados 63 pacientes, 32 pacientes com IAO (25 pacientes do sexo masculino e 7 do sexo feminino), 31 pacientes com EAO (11 pacientes do sexo masculino e 20 pacientes do sexo feminino). As variáveis foram comparadas na média entre os pacientes portador de IAO e EAO no pré e pós-operatório. RESULTADOS: A idade dos pacientes variou de 21 a 81 com média de 55 anos. Observa-se diferença quanto à média de idades entre as diferentes patologias (t-Student p< 0,0001). Os pacientes com IAO apresentam uma média de idade igual a 45,7±14,3 com variação entre 21 e 79 anos e os pacientes com EAO apresentam uma média de idade igual a 61,5±14,7 com variação entre 21 e 81 anos. Na IAO em relação à disfunção diastólica tivemos os seguintes dados com significância estatística do pré para o pós-operatório (6 meses): TRIV (p=0,0011), diferença entre Tempo de onda A mitral e onda A pulmonar (p=0,0097), Vol. Sistólico de AE (p=0,0019), Vol Sistólico de AE Indexado (0,0011), Vol. Diastólico de AE (p=0,0110), DDVE (p<0,0001), DSVE (p<0,0001), VSF (p<0,0001), VDF (p<0,0001), Massa Indexada de VE (p<0,0001) e Relação Volume/Massa do VE (p<0,0001). Na EAO em relação à disfunção diastólica tivemos os seguintes dados com significância estatística do pré para o pós-operatório (6 meses): E/E (p=0,0379), TRIV (p=0,0072), diferença entre o tempo de onda A mitral e tempo de onda A pulmonar (p=0,0176), Vol sistólico de AE(p=0,0242), Vol. Sistólico de AE indexado (p=0,0237), FEdeAE (p=0,0339), DDVE (p=0,0002), DSVE (p=0,0085), VDF (p=0,0194), Massa Indexada de VE (p<0,0001) e Relação Volume/Massa de VE(p<0,0001). O NTpró-BNP se correlacionou positivamente com os diversos graus de disfunção diastólica tanto no pré como pós-operatório CONCLUSÃO: Foram verificados no estudo da função diastólica variação com significância estatística tanto na IAO como na EAO na comparação do pré e o pós-operatório. Da mesma forma notamos variação do NT-proBNP com correlação com as variáveis ecocardiográficas que caracterizam a disfunção diastólica. / INTRODUCTION: Assessment of diastolic function in patients with aortic stenosis or aortic regurgitation waiting for aortic valve replacement. OBJECTIVE: Assesment of diastolic function with Doppler methods:Doppler signals from transvalvar mitral inflow, tissue Doppler imaging (TDI) and Doppler in pulmonary veins(DPV) correlating with serum brain peptide natriuretic (NTproNP) before and 6 months after aortic valve replacement (AVR). METHODS: We have analyzed 63 patients, 32 with AR (25 males and 7 females), 31 AS (11 males and 20 females).The indices were compared with AS and AR before and after AVR. RESULTS: The ages of patients ranged from 21 to 81 mean age was 55 years old.We have seen difference between mean age of AS and AR (t-Student-p<0.0001). Patients with AR have had mean age 45.67 plus/minus 14.28, range 21 to 79 years old and patients with AS have had mean age 61.50 plus/minus 14.72, range 21 to 81 years old. The patients who had AR the indices showed differences: Isovolumetric Relaxation Time IRT(p=0.0011), Diference between the pulmonary A wave duration and mitral A duration (p=0.0097), Left Atrial Systolic Volume (p=0.0019), Left Atrial Systolic Volume Index(p=0.0011), Left Atrial Diastolic Volume (p=0.0110), Left Ventricular Diastolic Diameter (p<0.0001), Left Ventricular Systolic Diameter (p<0.0001), End Systolic Volume (p<0.0001), End Diastolic Volume (p<0.0001), Left Ventricular Mass Index (p<0.0001) and Left Ventricular Volume and Left Ventricular Mass Index ratio (p<0.0001). Analyzing patients with AS the indices who showed differences: (The ratio of mitral velocity to early diastolic velocity of the mitral annulus) E/E (p=0.0379)(Isovolumetric Relaxation Time)(p=0.0072) IRT, Diference between the pulmonary A wave duration and mitral A duration (p=0.0176), Left Atrial Sistolic Volume (p=0.0242), Left Atrial Systolic Volume Index (p=0.0237), Left Atrial Ejection Fraction (p=0.0339) Left Ventricular Diastolic Diameter (p=0.0002), Left Ventricular Systolic Diameter (p=0.0085), End Diastolic Volume (LVEDV) (p=0.0194), Left ventricular Mass Index(p<0.0001), Left Ventricular Volume and Mass Index Ratio (p<0.0001). CONCLUSIONS: As we studied diastolic function we have verified significant statistic variation in aortic regurgitation and aortic stenosis comparing before and after aortic valve replacement. Likewise we have seen there is correlation between NTproBNP and echocardiographic variables that show diastolic dysfunction.

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