Die Diagnostik von angeborenen Herzfehlern, und vor allem die häufig lebenslange postoperative Verlaufskontrolle dieser Patienten, verlangt nach einem möglichst schonenden und dennoch zuverlässigen bildgebenden Verfahren. In der Regel wird hierzu die Echokardiographie eingesetzt, die jedoch insbesondere bei älteren Patienten aufgrund eines unzureichenden Schallfensters Schwierigkeiten bereitet. Für diese Patienten bietet sich die Magnetresonanztomographie (MRT) als alternatives bildgebendes Verfahren an. Ziel dieser Untersuchung war es, nach der Evaluation zweier funktioneller MRT-Methoden, der Flussmessung im Phantomversuch und der Ventrikelfunktionsanalyse im Vergleich zur 3D-Echokardiographie, verschiedene MR-Methoden an 6 verschiedenen Patientenkollektiven mit verschiedenen angeborenen Herzfehlern unkorrigiert und operativ korrigiert anzuwenden. 1. Bei Patienten mit Aortenisthmusstenose zeigte sich, dass neben der guten Korrelation der Abschätzung des Druckgradienten über einer Stenose oder Re-Stenose mit Hilfe der MR-Flussmessung, auch die drei-dimensionale Rekonstruktion aus der MR-Angiographie (MRA) zusätzliche Informationen liefert. 2. In der postoperativen Verlaufskontrolle von Patienten mit Fallott´scher Tetralogie ergab die Analyse der mit der MRT ermittelten Funktionsparameter Regurgitationsfraktion über der Pulmonalklappe und rechtsventrikulärer Volumina eine Korrelation zwischen der QRS-Dauer und dem rechtsventrikulären enddiastolischen Volumen (RV-EDV), was auf eine mechanoelektrische Interaktion bei der Genese ventrikulärer Arrhythmien hinweist. 3. Die MRT war in der Lage bei Patienten mit kongenital korrigierter Transposition der grossen Gefässe alleine aufgrund der Analyse der Morphologie die Diagnose dieser Fehlbildung zu stellen und in der Mehrzahl der Fälle Begleitfehlbildungen aufzudecken. 4. Mit Hilfe der MR-Flussmessung konnten bei Patienten nach arterieller und atrialer switch Operation zur Korrektur einer kompletten Transposition der grossen Gefässe sowohl Stenosen im Vergleich zur invasiven Herzkatheteruntersuchung sicher quantifiziert werden als auch unphysiologische Flussverhältnisse, die möglicherweise das Auftreten von Stenosen in den Pulmonalarterien oder dem venösen "baffle" begünstigen, erkannt werden. 5. Bei der seltenen Ebsteinanomalie erwies sich die MRT als zuverlässige Methode insbesondere die pathologische Anatomie der Trikuspidalklappe zu detektieren, als auch die Ventrikelfunktion zu quantifizieren. 6. Nach Fontanoperation erwies sich die MRT mit der Ventrikelfunktionsanalyse und Flussmessung ebenfalls als geeignete Methode, um pathologische Flussverhältnisse im Operationsgebiet zu detektieren und ihren möglichen Einfluss auf die ventrikuläre Funktion zu analysieren. In der Primärdiagnostik und insbesondere in der postoperativen Verlaufskontrolle von angeborenen Herzfehlern stellt die MRT somit unter Einsatz der MR-Flussmessung und Ventrikelfunktionsanalyse eine zuverlässige nicht-invasive Methode dar, die auch im Vergleich zur Herzkatheteruntersuchung einige Vorteile aufweist. / The diagnostics of congenital heart disease, and especially the need for frequent lifelong postoperative follow-up examinations, require an imaging modality as gentle and reliable as possible. The method commonly used for this purpose ? echocardiography - is associated with some disadvantages, especially in older patients with an insufficient acoustic window. For these patients magnetic resonance imaging (MRI) is an alternative imaging modality. The aim of this study was to evaluate two functional MR methods, flow measurement with a flow phantom and ventricular function analysis in comparison to 3D echocardiography. These methods were performed in 6 different groups of patients with uncorrected or surgically corrected congenital heart diseases. 1. Beside a good correlation between the estimated pressure gradients in the area of stenoses and re-stenoses in patients with coarctation with the aid of MR flow measurements, three-dimensional reconstruction from MR angiography (MRA) data supplies additional information. 2. The analysis of parameters such as regurgitant fraction over the pulmonary valve and right ventricular volumes derived by MRI in the postoperative follow-up of patients with tetralogy of Fallot showed a correlation to QRS duration which indicates a mechanoelectrical interaction as one etiology of arrhythmias in these patients. 3. The diagnosis of a congenitally corrected transposition of the great arteries could be made only by anatomical evaluation of the MR images. In the majority of patients all additional anomalies could be detected by MRI. 4. With the use of MR flow measurements as compared to gradients measured invasively by cardiac catheterization it was possible to reliably quantify stenoses. Furthermore, unphysiologic flow patterns, which could favor the development of pulmonary artery or "baffle" stenoses, could be detected. 5. MRI could be reliably used to detect the abnormal morphology of the tricuspid valve in patients with Ebstein anomaly and to quantify ventricular function in these patients. 6. Furthermore, after Fontan operation MRI was a suitable method to detect pathologic flow patterns at the operation site and to analyze their potential effects on ventricular function. MRI using the techniques of flow measurements and ventricular function analysis is a reliable non-invasive tool in the primary diagnostic procedure and especially in the postoperative follow-up of congenital heart disease. It has advantages even in comparison with the invasive method of cardiac catheterization.

Diese Arbeit befasst sich tierexperimentell und klinisch mit Aspekten der Nierenfunktion bei der Behandlung angeborener Herzfehler. Von Patientenseite sind das Neonatal- und Säuglingsalter und ab der Adoleszenz eine chronische Zyanose, von Behandlungsseite Röntgenkontrastmittelgaben, Dauer, Blutviskositätsänderungen und Kreislaufstillstand am kardiopulmonalen Bypass Risikofaktoren. Cortikosteroidgaben, Optimierung von Blutviskosität und Hydratation sowie eine prophylaktische Peritonealdialyse sind Ansätze zur Behandlung eines Nierenschadens. Die Ergebnisse zeigen, dass Verbesserungen der Plasmaviskosität Nierenschäden am hypothermen kardiopulmonalen Bypass vermindern während eine Cortikosteroidgabe vor Kreislaufstillstand bei Ferkeln nicht nephroprotektiv wirkt. Bei Risikopatienten erweist sich der prophylaktische Einsatz einer Peritonealdialyse als günstig. Bei chronisch zyanotischen Patienten mit einer Glomerulopathie und einem erhöhtem Risiko für Röntgenkontrastmittelexposition und kardiopulmonale Byppassoperationen muss der Nierenstatus die Operationsplanung und postoperative Therapie beeinflussen. Nephroprotektion und Verbesserungsmöglichkeiten der Blutviskosität am kardiopulmonalen Bypass müssen weiter untersucht werden. / This work focusses on clinical aspects of kidney function in the treatment of congenital heart disease. Neonates and infants as well as adolescents with cyanosis may be especially at risk. Contrast agents, duration, blood viscosity changes, and circulatory arrest in cardiopulmonary bypass may be risk factors. Corticosteroids, optimized blood viscosity and hydration, and early onset of peritoneal dialysis are considerations of treatment. Our results demonstrate a reduction of renal damage with optimized plasma viscosity during hypothermia in cardiopulmonary bypass, while corticosteroids have no advantage in young pigs after circulatory arrest. Prophylactic treatment with peritoneal dialysis has advantages in patients at risk. In chronicly cyanotic patients with glomerulopathy the risk of contrast agents and cardiopulmonary bypass is elevated. Thus, renal status should influence operative procedures and postoperative treatment. The possibilities of nephroprotection and improvement of blood viscosity should be further evaluated.

A hipóxia é capaz de alterar muitos mecanismos bioquímicos nas células endoteliais. Dentre eles, a indução da expressão endotelial de moléculas de adesão, como o fator de von Willebrand (FVW) que, em resposta ao estímulo, é secretado em sua forma mais ativa na interação com as plaquetas, o que pode resultar em trombose. Nas condições fisiológicas, o padrão multimérico do FVW no plasma é essencialmente determinado pela ADAMTS-13 (uma desintegrina e metaloproteinase com domínios trombospondina). Este estudo teve como objetivo verificar se a atividade da enzima ADAMTS-13, assim como as características do FVW relacionáveis a ela, poderiam estar alteradas na presença de hipoxemia comparativamente à condição de oxigenação normal. Este estudo longitudinal envolveu 56 pacientes portadores de cardiopatias congênitas cianogênicas, em idades entre um e sete anos, candidatos ao tratamento cirúrgico. Os pacientes foram avaliados no pré-cirúrgico (basal), no pós-operatório imediato (pós 48 horas) e após 30 dias de cirurgia, e foram divididos em dois grupos (A e B) baseado na saturação periférica de oxigênio (SpO2) no momento pós 30 dias. Foram determinados o antígeno do FVW e a análise das suas subunidades, a atividade da ADAMTS-13 e a presença de inibidores da ADAMTS-13. Os pacientes de ambos os grupos apresentaram aumento significante da SpO2, da concentração antigênica do FVW e da atividade da ADAMTS-13 nos momentos pós 48 horas e pós 30 dias em comparação com o momento pré (basal). As densidades normalizadas da subunidade principal do FVW (225 kDa) e do fragmento de 176 kDa apresentaram tendência ao aumento nos momentos pós 48 horas e pós 30 dias nos dois grupos. A razão entre a atividade da ADAMTS-13 e o FVW estava menor do que 1 no momento pós 48 horas, indicando consumo da enzima; entretanto, no momento pós 30 dias a razão fica 1:1, e o FVW se aproxima dos valores de referência. Verificamos ainda que 29% destes pacientes apresentaram inibidores contra a ADAMTS-13 no momento pré-operatório. Ainda explorando as variáveis SpO2, FVW:Ag, atividade da ADAMTS-13 e a composição das subunidades do FVW, foi feito um estudo de correlação linear entre estas variáveis. Observamos uma baixa correlação entre a enzima ADAMTS-13 e o FVW:Ag, e da enzima com os fragmentos do FVW de 176 e 140 kDa, principalmente no grupo B. No grupo A, esta correlação no momento pós 48 horas mostrou tendência a ser negativa. A maioria dos pacientes apresentou melhoras na saturação periférica de oxigênio. O aumento das variáveis estudadas no pós-operatório imediato pode ter ocorrido em função da cirurgia, que provavelmente ocasionou um quadro de lesão endotelial com inflamação, indicando que pode existir um equilíbrio entre o FVW e a ADAMTS-13 em níveis fisiológicos. Entretanto, este equilíbrio pode ser quebrado quando ocorre aumento do FVW, provavelmente por consumo da enzima. Parece-nos, portanto, que a ADAMTS-13 pode funcionar como um mecanismo de proteção a estes pacientes com tendência à trombose / Hypoxia has been shown to alter several biochemical mechanisms in endothelial cells. In addition, hypoxia induces the endothelial expression of adhesion molecules, including von Willebrand factor (VWF). Increased release of high-molecular-weight VWF multimers is associated with higher risk for thrombotic events. In physiological conditions, the multimeric pattern of plasma VWF is essentially determined by the action of ADAMTS-13 (a desintegrin and metalloprotease with thrombospondin type 1 domains). The aim of this study was to investigate if ADAMTS-13 activity and VWF subunit fragments were altered by hypoxia in cyanotic congenital heart disease. Fiftysix patients (age 1 to 7 years) with cyanotic congenital heart disease admitted to the Heart Institute for heart surgery were included in this longitudinal study. Patients were evaluated before (baseline) corrective surgery, postoperative 48 hours and postoperative 30 days. Patients were classified in two groups (A and B) based on the peripheral oxygen saturation after 30 days surgery. VWF antigenic concentration, VWF subunit composition, ADAMTS-13 activity and presence of ADAMTS-13 inhibitors were determined. Peripheral oxygen saturation, VWF:Ag and ADAMTS-13 activity were all increased significantly in both groups, in postoperative 48 hours and postoperative 30 days in comparison with baseline moment. Normalized density of VWF main subunit (225 kDa) and proteolytic fragment with 176 kDa tended to increase in postoperative 48 hours and postoperative 30 days in both groups. The rate between ADAMTS-13 activity and VWF:Ag was lower than 1 in postoperative 48 hours, an indicating of enzyme consumption; however, in the postoperative 30 days the rate was 1:1 and VWF:Ag values were near those of reference. 29% of patients presented ADAMTS-13 inhibitors at the baseline moment. A study of correlation among variables as peripheral oxygen saturation, VWF:Ag, VWF subunit composition and ADAMTS-13 was done. It was observed that ADAMTS-13 correlated slightly positively with VWF:Ag and with VWF fragments 176 and 140 kDa, mainly in group B; in group A, the correlation at postoperative 48 hours tended to be negative. Most of the patients improved their peripheral oxygen saturation. The increased value of variables observed in postoperative 48 hours can be explained by the endothelial injury and inflammation caused by the surgery itself. This indicates an equilibrium between VWF:Ag and ADAMTS-13 in physiological conditions. However, this equilibrium could disappear when VWF is increased, probably by enzyme consumption. We conclude that ADAMTS-13 can act as a protective mechanism in these patients with thrombotic tendency

In der vorliegenden Arbeit werden die Ergebnisse von Stent Implantationen bei Kindern mit angeborenen Herzfehlern an der Humboldt Universität zu Berlin, Charité vorgestellt. Zwischen 1994 und 2001 wurden bei 103 Patienten 146/149 Stents erfolgreich in 115 Gefäßstenosen oder Ductus arteriosus implantiert. Das Alter der Patienten bei der Implantation lag zwischen einem Tag und 34 Jahren (ein erwachsener Patient), im Mittel 4 Jahre, Median 1,1 Jahre; das Körpergewicht lag zwischen 1,75 kg und 75 kg, im Mittel 14,4 kg bei einem Median von 7,5 kg. Von den 149 Stents wurden 39,5% in periphere Pulmonalarterienstenosen, 17,5% in Aortenisthmusstenosen, 28,5% in den Ductus arteriosus, 8,5% in Systemvenenstenosen und 6% in Pulmonalvenenstenosen. 40% der 146 erfolgreich implantierten Stents wurden palliativ, 60% kurativ implantiert. Während eines Nachbeobachtungszeitraumes von einem Monat bis 7,5 Jahren, im Mittel 2,14 Jahren, wurden 60 der implantierten Stents insgesamt 79 mal redilatiert. 15 dieser Stents zweimal und 4 dreimal. Der häufigste Grund für eine Redilatation war das Körperwachstum der Patienten (58%). In-Stent Restenosen aufgrund von Intima-Proliferation führten in 25,5% zu einer Redilatation, die übrigen 16,5% Restenosen wurden durch Kompression von außen verursacht. Bei der vorliegenden Studie zeigte sich, dass die Stent-Implantation nicht nur eine effektive Methode zur Behandlung von Gefäßstenosen bei Patienten mit angeborenen Herzfehlern ist. Vielmehr gilt sie bei dem vorgestellten Patientengut als: 1. Vorbereitung, Erleichterung oder Ermöglichung von korrigierenden Operationen bei Neugeborenen durch palliativen Stent Einsatz in den Ductus arteriosus, Aortenisthmusstenosen oder in interventionell eröffnete rechtsventrikuläre Ausflußtrakte; 2. Vermeidung komplexer chirurgischer Eingriffe durch Stent Implantationen in native Aortenisthmusstenosen oder in den Ductus arteriosus bei Patienten mit kritischer Pulmonalstenose oder- atresie mit intaktem Ventrikelseptum; 3. Verbesserung post-operativer Ergebnisse und damit Verbesserung der langfristigen Prognose durch Beseitigung post-operativer Restenosen, zum Beispiel peripherer Pulmonalstenosen nach operativer Korrektur einer Fallotschen Tetralogie. Darüber hinaus lassen sich mit Hilfe von Stents komplexe chirurgisch/interventionelle Therapiestrategien, zum Beispiel dem Etablieren einer Fontanzirkulation, verwirklichen. Da in den meisten Fällen ein lebenslanger Verbleib der Stents geplant war wurden ausschließlich ballonexpandierbare Stents implantiert. Diese können, dem Alter und dem Körperwachstum der Patienten entsprechend durch Redilatation angepaßt werden. Diese limitierten Langzeit-Ergebnisse erscheinen diesbezüglich vielversprechend. Dagegen sind die Ursachen der In-Stent Restenosen aufgrund von Intima-Proliferation, die bei einigen Kindern gefunden wurden, noch nicht verstanden und bedürfen weiterer Untersuchungen. Eine Limitation der vorgestellten Methode besteht in der Stent-Technologie. Derzeit stehen keine Stents zur Verfügung, die im Neugeborenenalter implantiert werden können und bis zum Abschluß des Größenwachstums der Patienten eine gefäßstützende Funktion gewährleisten. Neue Stent-Technologien sind daher für den kurativen Einsatz bei Neugeborenen und kleinen Säuglingen erforderlich und werden in dieser Arbeit im Tiermodel vorgestellt. Zwei unterschiedliche neu Stents, die von zwei unabhängigen Herstellern entwickelt wurden, können durch eine Miniaturisierung der Einführungssysteme im Neugeborenenalter eingesetzt werden und ermöglichen eine Erweiterung der gestenteten Gefäßdurchmesser von minimal 4 Millimeter auf über 20 Millimeter. Weitere chronische Untersuchungen im Tiermodel sind notwendig bevor diese neuen Stent-Technologien in die klinische Erprobung bei Neugeborenen mit angeborenen Herzfehlern eingeführt werden können. / This study reports on stent implantation in paediatric patients with congenital heart disease at the department of paediatric cardiology, Humboldt university of Berlin, Charité. Between 1994 and 2001 146/149 stents were successfully implanted in 115 lesions or arterial ducts of 103 patients. The age of the patients ranged between 1 day and 34 years (one adult patient), mean 4 years, median 1.1 years; the bodyweight was measured between 1.75 kg and 75 kg, mean 14.4 kg, median 7.5 kg. The stent were implanted into different lesions: 39.5% in peripheral pulmonary artery stenoses, 17.5% in coarctation, 28.5% in the arterial duct, 8.5% in systemic vein stenoses and 6% in pulmonary vein stenoses. The implantations were performed for palliativ reasons in 40% or as a definite treatment in 60%. During a follow up period between 1 months and 7.5 years, mean 2.14 years 79 repeat dilations were performed on 60 stents, 15 stents twice and 4 stents three times. The most common reason for repeat intervention were dilation according to patients growth (58%). In-stent restenoses due to intimal hyperplasia were noted in 25.5% and 16.5% restenoses occurred due to compression from surrounding structures. The results of this study demonstrated stent-implantation not only as an effective method for treatment of vessel stenosis in young patients with congenital heart diseases. In addition 1. palliative stenting of the arterial duct, critical coarctation or right ventricular outflow tract obstruction in neonates improves surgical outcome or increases operability. 2. stent implantation can be an attractive alternative to complex surgery i.e. the establishment of Fontan circulation as part of a combined surgical/interventional concept 3. postoperative stenting of restenosis improves surgical results and reduces mortality and morbidity by reduction of the individual number of surgical procedures. Balloon expandable stents were used exclusively as the vast majority were considered to treat vessel stenosis for a lifelong period. The limited experiences on long-term follow-up are encouraging concerning the possibility of repeat dilation according to patients growth. However, the mechanisms of in-stent restenosis are not fully understand. For long-term treatment of vessel stenosis in neonates and small infants the conventional stent technology was found as a major limitation. New stent-designs are necessary. The report encloses two different new stent-technologies in animal studies. Miniaturised stents and delivery systems developed by two different companies are demonstrated. An additional advantage of the new stent designs is the broad variability of the stent diameters. After the initial implantation with a minimum diameter of 4 millimetres those stents can be dilated to a maximum diameter of more than 20 millimetres. Further investigations are necessary to demonstrate the efficacy of the new stent designs in different lesions of human neonates.

Congenital heart disease is the most common congenital anomaly, affecting approximately 1% of all live births each year. Although clinical interventions are improving, many affected infants do not survive to adulthood. Congenital cardiac defects originate from disturbances during development, making the study of mammalian cardiogenesis critical to improving outcomes for infants with congenital heart disease. Development of the mammalian heart involves epigenetically-driven specification and commitment of a diverse landscape of cardiac progenitors. Recent studies determined that chromatin modifying enzymes play a previously underappreciated role in the pathogenesis of congenital heart defects. This thesis investigates the functions of Hdac1 and Hdac2, highly homologous Class I histone deacetylases, during early murine cardiac development. We establish that Hdac1 and Hdac2 cooperatively regulate cardiogenesis in distinct cardiac progenitor populations during development. Together, our findings demonstrate that Hdac1 and Hdac2 are critical mediators of the earliest stages of mammalian cardiogenesis through a variety of spatiotemporally specific, redundant, and dose-sensitive roles and indicate they may play important roles in the pathogenesis of human congenital cardiac defects.

INTRODUÇÃO: Crianças portadoras de cardiopatia congênita cianogênica com hipofluxo pulmonar (CCCHP) necessitam de tratamento odontológico com frequência. Não encontramos estudos na literatura sobre o impacto na oxigenação dessas crianças durante os procedimentos odontológicos. A hipótese inicial era de que essas crianças submetidas a tratamento odontológico em consultório, poderiam apresentar alterações de saturação periférica de oxigênio (SpO2), pressão arterial sistêmica (PA) e frequência cardíaca (FC). OBJETIVOS: O objetivo principal da pesquisa foi avaliar a ocorrência e magnitude de variações na SpO2, FC e PA em crianças portadoras CCCHP durante exodontia de dente decíduo. Os objetivos secundários foram avaliar o risco potencial de submeter a criança portadora de CCCHP ao tratamento odontológico em consultório e instituir protocolo de atendimento odontológico à criança portadora de cardiopatia congênita do tipo cianogênica. MÉTODOS: Foram estudados 44 pacientes, sendo 20 do grupo de estudo (GE) e 24 do grupo controle (GC), com idade entre 6 e 12 anos submetidos à exodontia de dente decíduo superior. O estudo foi dividido em três períodos: lúdico (PL); anamnese, exame clínico e radiográfico (PAER) e período de procedimento odontológico (PPO), sendo esse último dividido em quatro subperíodos: pré-procedimento (PPR), anestesia (PAN); procedimento (PP) e pós-procedimento (PPP). Durante os períodos foram realizados registros da SpO2, da FC e da PA e aplicada escala de ansiedade facial image scale para avaliação do estresse. RESULTADOS: Os valores da SpO2 , FC e PA sistólica, no GE, durante o protocolo de tratamento variaram, discreta mas significativamente (p<0.05), de 80,5 (±7,6)% a 82,8 (±7,8)%, de 98,7 (±11,0) bpm a 101,3 (±9,8) bpm e de 93,6 a 108,5 mmHg, respectivamente. O GC também apresentou variação significativa durante o procedimento. DISCUSSÃO e CONCLUSÃO: Embora tenham sido observadas alterações significantes nos marcadores estudados durante os períodos, eles foram considerados pelos autores discretos e sem relevância clínica, sendo desnecessários a interrupção do tratamento odontológico ou suporte terapêutico às crianças contrariando a hipótese inicial com base na literatura, pois, ocorreu aumento de SpO2 durante o PPO quando comparado aos períodos de menor estresse. O tratamento odontológico de crianças com cardiopatia cianogênica, com uso de um protocolo padronizado, envolvendo preparo das crianças revelou ser um procedimento seguro, o que permite sua implantação em serviços, sem suporte de centro cirúrgico, facilitando assim a abordagem destas crianças em serviços descentralizados. Os resultados encontrados sugerem que o protocolo estabelecido para o atendimento a crianças portadoras de CCCHP foi adequado / INTRODUCTION: Children with cyanotic congenital heart disease with decreased pulmonary blood flow (CCHHP) often require dental treatment. We didnt find studies about the impact of the oxygenation in those children during dental procedures. The initial hypothesis was that these children undergoing dental treatment in the clinic could present a peripheral oxygen saturation (SpO2), systolic blood pressure (BP) and heart rate (HR). OBJECTIVES: The main objective of this research was to evaluate the occurrence and magnitude of changes in SpO2, HR and BP in children with CCHHP during extraction of primary deciduous. Secondary objectives were to evaluate the potential risk in subjecting the child with CCHHP to dental treatment in the office and establish protocol for dental care to children with congenital cyanotic type. METHODS: We studied 44 patients, 20 out of the study group (SG) and 24 from control group (CG), aged between 6 and 12 years who underwent upper primary tooth extraction. The study was divided into three periods: leisure time (LT), anamnesis, clinical and radiographic examination period (ACER) and period of dental procedure (PDP), the latter being divided into four sub-periods: pre-procedure (PPR), anesthesia (PAN); procedure (PP) and post-procedure (PPP). During periods of SpO2 records were made of HR and BP and applied an anxiety facial image scale to evaluate the stress. RESULTS: The values of SpO2, HR and systolic BP at SG during the treatment protocol varied, quite but significantly (p <0.05), 80.5 (± 7.6) to 82.8% (± 7, 8)%, 98.7 (± 11.0) to 101.3 bpm (± 9.8) bpm and 93.6 to 108.5 mmHg, respectively. The CG also varied significantly during the procedure. DISCUSSION and CONCLUSION: Although significant changes were observed during the periods studied, they were considered, by the authors, discrete and without clinical relevance, and unnecessary interruption of dental treatment or therapeutic support to children contradicts the initial hypothesis based on the literature because of an increase of SpO2 during the PPO compared to periods of lower stress. The dental treatment of children with cyanotic heart disease using a standardized protocol involving the preparation of children proved to be a safe procedure, which allows its implementation in services supported by surgical centers, thus facilitating the approach of those children in local services. The results suggest that the established protocol for the care of children with CCHHP was adequate

Conotruncal anomalies are the leading causes of cyanotic congenital heart disease. We attempted to use live xPlane imaging of ductal arch view and in-plane view of IVS to screen the fetal conotruncal anomalies in 200 fetuses. There were 152 normal cases, 25 conotruncal anomalies and 23 other types of fetal CHDs were involved in this study. The visualization rate of the normal ductal arch view and in-plane view of IVS with live xPlane imaging was 100% (152/152), 100% (152/152) in normal cases, 8% (2/25), 12% (3/25) in conotruncal anomalies and 69.7% (16/23), 73.9% (17/23) in non-conotruncal CHDs, respectively. The visualization rate of abnormal ductal arch and in-plane view in conotruncal anomalies was much higher than that in non-conotruncal anomalies (P&lt;0.001). Therefore, it may be a useful tool for the assessment and diagnosis of fetal conotruncal anomalies. / In conclusion, real-time 3DE is a novel and promising technique to perform the prenatal examination, both the fetal heart and other system. It represents the future of 3D ultrasound and will become a useful tool for prenatal screening and diagnosis. / This thesis summarized real-time 3D ultrasound in obstetric application. With the introduction of matrix transducer, 3D scanning the fetus in real time became available. / We attempted to use real-time 3D ultrasound in obstetrics outside the fetal heart. We evaluated the feasibility of using real-time 3D ultrasound to assist in obtaining a true midsagittal view in first trimester. Eight sonographers, including FMF-certified and non FMF-certified operators, were asked to perform ultrasound examinations on five patients and forty patients were examined in total. It showed that the deviation from true midsagittal view was reduced greatly with the guidance of live xPlane imaging. Real-time 3D ultrasound can improve the accuracy of acquisition of a defined sonographic plane, and reduce the difference in performance between operators who are formally certified or not. / We demonstrated a novel method to visualize the aortic and ductal arch with live xPlane imaging. The visualization rate is 100%. Ductal arch view can be visualized by placing the reference line through pulmonary artery and descending aorta and aortic arch view can be acquired by putting the reference line along the transverse view of aortic arch and descending aorta on the 3VT view with live xPlane imaging. Therefore, live xPlane imaging is an easy and feasible method for real-time imaging of the ductal and aortic arch. / We explored the feasibility to perform the fetal heart screening using real-time 3DE with live xPlane imaging. We developed and reported the methodology of acquiring and examining the screening planes of the fetal heart with live xPlane imaging. The procedure was simple and straight. When performing the fetal heart screening with live xPlane imaging, we just need display the apical four-chamber view and mid-sagittal view of fetal upper thorax and other thing could be done by moving the reference line. The overall detection of four cardiac screen planes can reach 100%. / We explored to evaluate the entire fetal IVS with both live xPlane imaging and live 3D imaging. We can successfully assess the entire IVS in most fetuses (153/154). We also compared the images acquired by real-time 3DE and STIC in this thesis. It showed that less motion artifact encounters with real-time 3DE and the image quality of real-time 3DE is similar to STIC volume acquired from the sagittal view (P>0.05) and superior to STIC volume from the four-chamber view (P&lt;0.05). Therefore, real-time 3DE can be used to display the lateral view of the fetal IVS, and potentially may be a useful tool for the assessment and diagnosis of fetal VSDs. / Xiong, Yi. / Adviser: Tzekin Lau. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 116-138). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

INTRODUÇÃO: A hipertensão arterial pulmonar associada a cardiopatias congênitas (HAP-CCg) é um tipo específico de doença vascular pulmonar com várias complicações. Os pacientes com HAP-CCg avançada são considerados inoperáveis e podem apresentar hipoxemia crônica e eritrocitose secundária devido ao desvio de sangue da direita para a esquerda através das comunicações cardíacas. O presente estudo teve como objetivo analisar a resposta a dois inibidores de fosfodiesterase 5 (iPDE 5), a saber, sildenafila e tadalafila, administrados por seis meses. Os fármacos haviam sido previamente aprovados para uso na HAP em geral. No entanto, a literatura é escassa no que diz respeito à sua utilização especificamente na HAP-CCg. Propusemo-nos a investigar potenciais efeitos destes fármacos além de suas ações como vasodilatadores. MÉTODOS: Foram incluídos 31 pacientes com HAP-CCg avançada (idade entre 10 e 54 anos). A maioria apresentava redução na saturação sistêmica de oxigênio, com hematócrito elevado. A sildenafila e a tadalafila foram administradas por via oral (respectivamente, 20 mg três vezes ao dia e dose única diária de 40 mg). A capacidade física foi avaliada pela distância percorrida em 6 minutos (teste de caminhada de 6 minutos, protocolo American Thoracic Society). A qualidade de vida relacionada à saúde foi avaliada utilizando-se o questionário genérico SF-36. Níveis circulantes de marcadores de disfunção microvascular foram analisados por ensaios imunoenzimáticos. Todas as medidas foram realizadas na condição basal, e aos três e seis meses de tratamento com iPDE 5. Utilizando casuística ampliada com análise de dados tanto de forma retrospectiva como prospectiva, investigamos variáveis com possível valor prognóstico. RESULTADOS: Os tratamentos com ambos os fármacos foram associados à melhora da capacidade física (classe funcional e distância percorrida em 6 minutos, p < 0,05), hematócrito e nível de hemoglobina (p < 0,05), e qualidade de vida relacionada à saúde (componentes físico e mental, p < 0,05). Comparados ao grupo controle, na condição basal, os pacientes apresentaram níveis plasmáticos elevados de beta-tromboglobulina (beta-TG, p=0,002), selectina P (p=0,018), ativador do plasminogênio tipo tecidual (t-PA, p=0,005) e do antígeno do fator de von Willebrand (VWF:Ag, p=0,005); a trombomodulina mostrou-se significantemente reduzida (TM, p < 0,001). A administração de tadalafila foi seguida de melhora no nível de beta-TG (p=0,004), t-PA (p=0,003) e TM (p=0,046), enquanto a selectina P modificou-se apenas com a sildenafila (p=0,034). O VWF:Ag mostrou-se com melhora significante, porém transitória, no grupo tratado com sildenafila (p=0,019). Usando casuística ampliada que incluiu pacientes de estudos anteriores de nosso grupo (coorte estendida de 75 indivíduos), analisamos dados coletados no início do seguimento para todos eles, assim como outros relacionados ao tratamento. Uma série de variáveis clínicas e laboratoriais foram testadas quanto à sua possível correlação com a sobrevida livre de evento (seguimento de nove anos). Nesta parte do estudo, os pacientes receberam não apenas iPDE 5 como tratamento para HAP. Alguns deles receberam antagonistas dos receptores de endotelina isoladamente, enquanto outros receberam estes medicamentos (bosentana, ambrisentana) em combinação com iPDE 5. Após realização de análises univariada, bivariada e multivariada foi possível a identificação de quatro preditores de prognóstico desfavorável: 1, menor tempo de exposição a fármacos específicos para HAP (p < 0,001); 2, classe funcional avançada na admissão (p=0,010); 3, função sistólica ventricular direita deprimida (p=0,010); e 4, níveis circulantes elevados de VWF:Ag (p=0,013). Menor tempo de exposição aos medicamentos específicos para HAP foi caracterizado como preditor independente de desfechos. CONCLUSÕES E COMENTÁRIOS: Com base nestas observações, concluímos que os iPDE 5 são importantes no manejo da HAP-CCg avançada. Os efeitos foram observados não apenas na capacidade física e na qualidade de vida, mas também em marcadores biológicos de disfunção microvascular, potencialmente relacionados à progressão e/ou complicações da doença. Além disso, as observações em longo prazo sugeriram que maior tempo de exposição aos fármacos para HAP (incluindo iPDE 5) foi benéfico, enfatizando a necessidade de instituição precoce das terapias. O fato de o estudo ter sido realizado apenas com fármacos de administração oral torna os resultados relevantes no que diz respeito a regiões onde o acesso a tratamentos específicos para HAP é limitado a tais modalidades / INTRODUCTION: Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is a particular form of pulmonary vascular disease with a number of complications. Patients with advanced CHD-PAH are deemed inoperable, and may present with chronic hypoxemia and secondary erythrocytosis due to right-to-left shunting across the cardiac communications. The present study was aimed at analyzing the response to 2 phosphodiesterase type 5 inhibitors (PDE5is), namely sildenafil and tadalafil, which were administered for 6 months. The drugs had been previously approved for management of PAH in general. However, there has been scarce literature on their use in the specific setting of CHD-PAH. We wished to investigate potential effects beyond their actions as vasodilators. METHODS: Thirty-one patients with advanced CHD-PAH were enrolled (age 10 to 54 years). Most of them had systemic oxygen desaturation with elevated hematocrit. Sildenafil and tadalafil were administered orally (respectively, 20 mg t.i.d and single daily dose of 40 mg). The physical capacity was assessed by registering the 6-minute walked distance (6-minute walk test, American Thoracic Society protocol). Health-related quality of life was assessed using the SF-36 generic questionnaire. Circulating levels of microvascular dysfunction markers were analyzed by enzyme-linked immunoassays. All measurements were performed at baseline, 3 months and 6 months of PDE5i administration. Using a larger patient population with retrospective as well as prospective data analysis, we looked for potential predictors of prognosis. RESULTS: Both therapies were associated with improvement of the physical capacity (functional class and 6-minute walked distance, p < 0.05), hematocrit and hemoglobin level (p < 0.05), and health-related quality of life (physical and mental components, p < 0.05). Compared to controls, patients had elevated baseline plasma levels of beta-thromboglobulin (beta-TG, p=0.002), P-selectin (p=0.018), tissue-type plasminogen activator (t-PA, p=0.005) and von Willebrand factor antigen (VWF:Ag, p=0.005), while thrombomodulin was importantly reduced (TM, p < 0.001). Tadalafil administration was followed by improvement of beta-TG (p=0.004), t-PA (p=0.003) and TM level (p=0.046), while P-selectin was improved by sildenafil only (p=0.034). VWF:Ag improved significantly, but only transiently in the sildenafil group (p=0.019). Using an extended population which included additional patients from previous studies of ours (the extended cohort consisted of 75 individuals), we analyzed data collected at the beginning of follow-up for all subjects, and treatment-related data as well. A number of clinical and laboratory parameters were tested for their possible correlation with event-free survival (9-year survival analysis). In this part of the study, patients were on monotherapy or combination therapy with PDE5is (sildenafil or tadalafil) and endothelin receptor antagonists (bosentan or ambrisentan). Univariate, bivariate and multivariate analyses were used to identify four predictors of a more worrisome prognosis: 1, a shorter time of exposure to specific PAH therapies (p < 0.001); 2, an advanced functional class at entry (p=0.010); 3, a depressed right ventricular systolic function (p=0.010); and 4, high circulating levels of VWF:Ag (p=0.013). A shorter exposure to PAH therapies was characterized as an independent predictor of poor outcome. CONCLUSIONS AND COMMENTS: Our observations point towards beneficial effects of PDE5is in advanced CHD-PAH. Importantly, the observed effects were not only on the physical capacity, and quality of life, but also biological markers of microvascular injury potentially related to disease progression and/or complications. Furthermore, long-term patient observation showed that a longer exposure to PAH drugs (including PDE5is) was beneficial, thus emphasizing the need for early initiation of therapies. Because only oral drugs were used, results may be relevant for countries and regions with limited access to PAH-specific medications

INTRODUÇÃO: Crianças portadoras de cardiopatia congênita cianogênica com hipofluxo pulmonar (CCCHP) necessitam de tratamento odontológico com frequência. Não encontramos estudos na literatura sobre o impacto na oxigenação dessas crianças durante os procedimentos odontológicos. A hipótese inicial era de que essas crianças submetidas a tratamento odontológico em consultório, poderiam apresentar alterações de saturação periférica de oxigênio (SpO2), pressão arterial sistêmica (PA) e frequência cardíaca (FC). OBJETIVOS: O objetivo principal da pesquisa foi avaliar a ocorrência e magnitude de variações na SpO2, FC e PA em crianças portadoras CCCHP durante exodontia de dente decíduo. Os objetivos secundários foram avaliar o risco potencial de submeter a criança portadora de CCCHP ao tratamento odontológico em consultório e instituir protocolo de atendimento odontológico à criança portadora de cardiopatia congênita do tipo cianogênica. MÉTODOS: Foram estudados 44 pacientes, sendo 20 do grupo de estudo (GE) e 24 do grupo controle (GC), com idade entre 6 e 12 anos submetidos à exodontia de dente decíduo superior. O estudo foi dividido em três períodos: lúdico (PL); anamnese, exame clínico e radiográfico (PAER) e período de procedimento odontológico (PPO), sendo esse último dividido em quatro subperíodos: pré-procedimento (PPR), anestesia (PAN); procedimento (PP) e pós-procedimento (PPP). Durante os períodos foram realizados registros da SpO2, da FC e da PA e aplicada escala de ansiedade facial image scale para avaliação do estresse. RESULTADOS: Os valores da SpO2 , FC e PA sistólica, no GE, durante o protocolo de tratamento variaram, discreta mas significativamente (p<0.05), de 80,5 (±7,6)% a 82,8 (±7,8)%, de 98,7 (±11,0) bpm a 101,3 (±9,8) bpm e de 93,6 a 108,5 mmHg, respectivamente. O GC também apresentou variação significativa durante o procedimento. DISCUSSÃO e CONCLUSÃO: Embora tenham sido observadas alterações significantes nos marcadores estudados durante os períodos, eles foram considerados pelos autores discretos e sem relevância clínica, sendo desnecessários a interrupção do tratamento odontológico ou suporte terapêutico às crianças contrariando a hipótese inicial com base na literatura, pois, ocorreu aumento de SpO2 durante o PPO quando comparado aos períodos de menor estresse. O tratamento odontológico de crianças com cardiopatia cianogênica, com uso de um protocolo padronizado, envolvendo preparo das crianças revelou ser um procedimento seguro, o que permite sua implantação em serviços, sem suporte de centro cirúrgico, facilitando assim a abordagem destas crianças em serviços descentralizados. Os resultados encontrados sugerem que o protocolo estabelecido para o atendimento a crianças portadoras de CCCHP foi adequado / INTRODUCTION: Children with cyanotic congenital heart disease with decreased pulmonary blood flow (CCHHP) often require dental treatment. We didnt find studies about the impact of the oxygenation in those children during dental procedures. The initial hypothesis was that these children undergoing dental treatment in the clinic could present a peripheral oxygen saturation (SpO2), systolic blood pressure (BP) and heart rate (HR). OBJECTIVES: The main objective of this research was to evaluate the occurrence and magnitude of changes in SpO2, HR and BP in children with CCHHP during extraction of primary deciduous. Secondary objectives were to evaluate the potential risk in subjecting the child with CCHHP to dental treatment in the office and establish protocol for dental care to children with congenital cyanotic type. METHODS: We studied 44 patients, 20 out of the study group (SG) and 24 from control group (CG), aged between 6 and 12 years who underwent upper primary tooth extraction. The study was divided into three periods: leisure time (LT), anamnesis, clinical and radiographic examination period (ACER) and period of dental procedure (PDP), the latter being divided into four sub-periods: pre-procedure (PPR), anesthesia (PAN); procedure (PP) and post-procedure (PPP). During periods of SpO2 records were made of HR and BP and applied an anxiety facial image scale to evaluate the stress. RESULTS: The values of SpO2, HR and systolic BP at SG during the treatment protocol varied, quite but significantly (p <0.05), 80.5 (± 7.6) to 82.8% (± 7, 8)%, 98.7 (± 11.0) to 101.3 bpm (± 9.8) bpm and 93.6 to 108.5 mmHg, respectively. The CG also varied significantly during the procedure. DISCUSSION and CONCLUSION: Although significant changes were observed during the periods studied, they were considered, by the authors, discrete and without clinical relevance, and unnecessary interruption of dental treatment or therapeutic support to children contradicts the initial hypothesis based on the literature because of an increase of SpO2 during the PPO compared to periods of lower stress. The dental treatment of children with cyanotic heart disease using a standardized protocol involving the preparation of children proved to be a safe procedure, which allows its implementation in services supported by surgical centers, thus facilitating the approach of those children in local services. The results suggest that the established protocol for the care of children with CCHHP was adequate

Single ventricle congenital heart defects afflict 2 per every 1000 births. They are characterized by cyanotic mixing between the de-oxygenated blood coming back from the systemic circulation and the oxygenated blood from the pulmonary circulation. Prior to introduction of the Fontan procedure in 1971, surgical options for single ventricle patients were limited. The Fontan operation involves a series of three palliative procedures aimed at the separation of systemic and pulmonary circulations and reducing the long term effects of chronic hypoxia and ventricular volume overload. The total cavopulmonary connection (TCPC) is completed in the final stage of the surgery with the anastomosis of the inferior vena cava (IVC) and superior vena cava to the pulmonary arteries. Improved quantification and visualization of flow structures within the TCPC has the potential to aid in the planning and design of the Fontan operation. Despite significant development of phase contrast magnetic resonance imaging (PC MRI) for in vivo flow measurements, it is not routinely applied in children with single ventricle congenital heart disease. Limited technologies available for post-processing of PC MRI data has prevented clinicians and scientists from conducting the detailed hemodynamic analyses necessary to better understand the physiology of the single ventricle circulation. This thesis attempts to bridge the gap between PC MRI and fluid dynamics, by developing the necessary post-processing technologies for PC MRI, and then applying these techniques for characterizing single ventricle hemodynamics.