Dissertations / Theses on the topic 'Atrial septal defects'

Congenital heart disease is the most common form of birth defect, affecting approximately 1% of liveborn babies. Secundum atrial septal defect (ASD) is the second most common form of congenital heart disease (CHD). Most cases have no known cause. Chromosomal, syndromal and teratogenic causes account for a minority of cases. The hypothesis that mutations in the ASD genes NKX2-5 and GATA4 may cause apparently sporadic ASD was tested by sequencing them in unrelated probands with ASD. In this study, 1/102 individuals with ASD had an NKX2-5 mutation, and 1/129 had a deletion of the GATA4 gene. The cardiac transcription factor TBX20 interacts with other ASD genes but had not previously been associated with human disease. Of 352 individuals with CHD, including 175 with ASD, 2 individuals, each with a family history of CHD, had pathogenic mutations in TBX20. Phenotypes included ASD, VSD, valvular abnormalities and dilated cardiomyopathy. These studies of NKX2-5, GATA4 and TBX20 indicate that dominant ASD genes account for a small minority of cases of ASD, and emphasize the considerable genetic heterogeneity in dominant ASD (also caused by mutations in MYH6 and ACTC). A new syndrome of dominant ASD and the Marcus Gunn jaw winking phenomenon is reported. Linkage to known loci was excluded, extending this heterogeneity, but a whole genome scan did not identify a candidate locus for this disorder. Previous studies of inbred laboratory mice showed an association between patent foramen ovale (PFO) and measures of atrial septal morphology, particularly septum primum length (???flap valve length??? or FVL). In humans, PFO is associated with cryptogenic stroke and migraine, and is regarded as being in a pathological contiuum with ASD. Twelve inbred strains, including 129T2/SvEms and QSi5, were studied, with generation of [129T2/SvEms x QSi5] F1, F2 and F14 mice. Studies of atrial morphology in 3017 mice confirmed the relationship between FVL and PFO but revealed considerable complexity. An F2 mapping study identified 7 significant and 6 suggestive quantitative trait loci (QTL), affecting FVL and two other traits, foramen ovale width (FOW) and crescent width (CRW). Binary analysis of PFO supported four of these.

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Objective: Balloon atrial septostomy (BAS) is a life-saving palliative procedure for some congenital heart defects and typically performed in the cardiac catheterization laboratory. The aim of this study was to evaluate BAS under echocardiographic guidance. Method: From August 1997 through January 2004, 31 children with congenital heart defects with indication of ASB were submitted to the procedure under exclusive echocardiographic guidance. Success was admitted the obtaining of atrial septal defect (ASD) with size of four millimeters (mm) or greater and torn septal tissue flapping freely. Results: Male infants predominated (83.9%). Median age was 5 days (1 - 150) and median weight was 3300g (1800 - 7500). Transposition of the Great Arteries was present in 80.6%, Tricuspid Atresia in 12.9%, Total Anomalous Pulmonary Venous Return in 3.2% and Pulmonary Atresia with intact ventricular septum in 3.2%. The procedure was successful in all cases. ASD size increased from 1.8 ± 0.8 mm to 5.8 ± 1.3 mm (P<0.0001) and arterial oxygen saturation increased from 64.5 ± 18.9% to 85.1 ± 9.2% (P<0.0001). As complications occured three balloon ruptures, one tear of right femoral vein, one case of supraventricular tachycardia and one case of atrial flutter. Conclusion: BAS under echocardiographic guidance is a safe and effective method. It can be performed at the bedside, identifies the catheter location avoiding serious complications and evaluates the immediate result of the procedure.
Atnosseptostomia com balão (ASB) é procedimento de grande valor no tratamento de cardiopatias congênitas e monitorado tradicionalmente por radioscopia. O objetivo do presente estudo foi avaliar a ASB monitorada pela ecocardiografia. Casuística e Método: Entre agosto de 1997 e janeiro de 2004, 31 crianças foram submetidas à ASB sob monitoração ecocardiográfica exclusiva. Admitiu-se sucesso a obtenção de comunicação interatrial (CIA) com diâmetro igual ou maior que quatro milímetros (mm) e com ampla mobilidade das suas margens. Dados coletados: diâmetro da CIA e saturação arterial de oxigênio (SAT) iniciais e finais e número de trações do cateter balão. Resultados: Sexo masculino predominou (83,9%). A idade mediana foi de 5 dias (1-150) e o peso teve mediana de 3300g (1800-7500). Transposição das Grandes Artérias ocorreu em 80,6%, Atresia Tricúspide em 12,9%, Drenagem Anômala Total de Veias Pulmonares em 3,2% e Atresia Pulmonar com septo Integro em 3,2%. Sucesso foi obtido em todos os casos. O tamanho da CIA aumentou de 1,8 0,8 mm para 5,8 1,3 mm (p <0,0001) e a SAT aumentou de 64,5 18,9 % para 85,1 9,2 % (p < 0,0001). Complicações ocorridas: três rupturas de balão, uma lesão de veia femoral direita, uma taquicardia supraventricular e um flutter atnal. Conclusões: ASB monitorada pela ecocardiografia é método seguro e eficaz. Possibilita a realização do procedimento à beira do leito evitando o transporte da criança, identifica o posicionamento do cateter reduzindo complicações graves e avalia o resultado imediato do procedimento.

La fermeture percutanée est le traitement de référence des communications interatriales (CIA). Après son implantation, une cicatrisation du dispositif est classiquement attendue après quelques mois ; il semble cependant qu’un recouvrement incomplet ou partiel puisse être observé dans de rares cas, sans que l’on en connaisse les mécanismes impliqués. Cette cicatrisation imparfaite du dispositif est associée à la survenue de complications retardées. Dans le cadre de cette thèse nous avons étudié la cicatrisation de ces prothèses de CIA, en nous focalisant sur les processus de recouvrement et d’endothélialisation des dispositifs, à travers une approche translationnelle incluant expérimentations in vitro, modèle animal chronique et étude clinique. A la fin de ce travail, il est possible de conclure que : 1) il existe des cas de complications au long cours après fermeture de CIA, liées à un défaut de recouvrement du dispositif, 2) sur une large cohorte pédiatrique avec un suivi allant jusqu’à 18 ans après l’implantation, l’incidence de ces complications est faible 3) les modèles animaux, utilisés seuls, ne peuvent suffire à expliquer ni à avancer dans la compréhension de ce phénomène, 4) il n’existe pas de différences significatives concernant le processus de recouvrement entre les 3 prothèses analysées au cours de ce travail, 5) une évaluation non invasive et individualisée du recouvrement prothétique , grâce aux techniques d’imagerie, est une perspective prometteuse. Ces données montrent qu’une meilleure compréhension du processus de recouvrement prothétique passe par la réalisation conjointe d’études fondamentales et cliniques. Cependant, le développement d’outils permettant une évaluation individualisée du recouvrement doit être poursuivi, du fait de leur fort potentiel de translation clinique et de leur capacité à optimiser la prise en charge du patient
The percutaneous device closure is the gold treatment of atrial septal defect (ASD). After implantation, device healing is classically expected following several months; however, an incomplete or partial covering of the device may be observed without a full knowledge of the underlying mechanisms. In this thesis we studied the healing of these intracardiac prostheses, focusing on the covering and endothelialization processes of devices, approach through a translational approach including in vitro experiments, chronic animal model and clinical study. At the end of this work, it is possible to conclude that 1) there are cases of long-term complications after closure of CIA, related to a lack of recovery of the device, 2) in a large cohort of pediatric with a follow up of up to at 18 years after implantation, the incidence of these complications is low 3) animal models, used alone, can not suffice to explain or improve the understanding of this complex process, 4) there is no significant differences in the covering process between the 3 prostheses analyzed during this work, 5) a non-invasive and individualized assessment of prosthetic recovery, using imaging techniques, is a promising perspective with significant potential for clinical translation . These data show that a better understanding of device healing process needs the joint undertake of basic and clinical studies. Moreover, the development of tools for individualized assessment of device covering should be pursued in parallel, due to their high translational potential, in order to optimize patient management

Darbe išnagrinėti mažiau invazinės įgimtų prieširdžių pertvaros defektų (PPD) ir skilvelių pertvaros defektų (SPD) ydų chirurgijos galimybės ir ypatumai. Standartinį šių ydų operavimo būdą per išilginę vidurinę sternotomiją galima pakeisti mažiau invaziniu su geresniu kosmetiniu rezultatu. Darbe parodoma, kad mažiau invazinių PPD ir SPD korekcijų rizika iš esmės nesiskiria nuo standartinės metodikos per vidurinę išilginę sternotomiją. Mažiau invazinių širdies pertvarų defektų uždarymo operacijų metodika įgalina jas saugiai atlikti su įprastiniais širdies chirurgijos instrumentais be papildomų išlaidų. Mažiau invazinių įgimtų širdies ydų operacijų indikacijos yra siauresnės.
The study defines the possibilities and peculiarities of the less invasive congenital atrial septal defect (ASD) and ventricular septal defect (VSD) surgery. A standard median sternotomy approach in some cases is possible to replace with more cosmetic friendly and less invasive access. The study demonstrates that the risk of less invasive ASD and VSD closure doesn’t differ from the standard median sternotomy surgery risk. Less invasive operations methodic used in our centre enables it with conventional instrumentary set. Indications for less invasive congenital heart defects surgery are narrower.

Doenças cardíacas congênitas são as mais frequentes entre as malformações congênitas graves, afetando de duas a três crianças por 100 nascidos vivos, sendo o defeito do septo atrioventricular (DSAV) responsável por 5% desses, e atingindo cerca de 50% dos pacientes portadores de Síndrome de Down. Caracteriza-se essencialmente por vários graus de desenvolvimento incompleto do tecido septal ao redor das valvas atrioventriculares, bem como de anormalidades na formação das mesmas. Recomenda-se a correção cirúrgica ao redor de 4 meses de vida, no intuito de prevenir o surgimento de hipertensão pulmonar (HP) irreversível devida ao hiperfluxo pulmonar, no entanto a despeito disso, identifica-se a presença de hipertensão pulmonar em pacientes já submetido ä correção do defeito cardíaco. O presente estudo teve por objetivo analisar a prevalência de hipertensão pulmonar diagnosticada através do ecocardiografia e identificar dos fatores de risco em pacientes submetidos à correção cirúrgica de DSAV nos últimos 16 anos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão preto da Universidade de São Paulo (HCFMRP - USP). Foram selecionados pacientes portadores de DSAV, submetidos à correção cirúrgica no HCFMRP - USP, no período de janeiro de 1999 a janeiro de 2016, em seguimento no Ambulatório de Cardiologia Infantil do HCFMRP-USP, considerados portadores de hipertensão pulmonar os pacientes que apresentaram à ecocardiografia valores estimados de pressão sistólica de artéria pulmonar (PSAP) superiores a 30 mmHg. Foram analisadas variáveis clínicas pré e pós-operatórias. Não foi encontrada correlação entre peso e idade na data da correção cirúrgica e presença de HP na avaliação ecocardiográfica pós-operatória; no entanto esta se relacionou com tempo prolongado de circulação extra-corpórea e ventilação mecânica. Houve aumento significativo na sobrevida nos últimos oito anos analisados, refletindo a melhoria na qualidade de atendimento clinico e cirúrgico dos pacientes. A alta perda de seguimento ambulatorial causa preocupação, porém reflete as dificuldades próprias de serviços de saúde de países em desenvolvimento.
Congenital heart diseases are the most common serious congenital malformations, affecting two of three children per 100 newborns, the atrioventricular septal defect (AVSD) is responsible for 5% of these cases, reaching almost 50% of bearers of Down\'s Syndrome. It has been characterized essentially by many incomplete development degrees of de septal tissue around the atrioventricular valves, as well as its formation abnormalities. The actual recommendation is to proceed surgical correction nearly 4 months of age, in order to prevent irreversible pulmonary hypertension (PH) due to the pulmonary overflow. Despite of the surgical correction, patients may present pulmonary hypertension. This research aimed to analyze the prevalence of pulmonary hypertension diagnosed by transthoracic echocardiogram and identify risk factors for this outcome in patients undergoing surgical correction of AVSD in the last 16 years at the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP - USP). All patients diagnosed with AVSD, submitted to surgical correction and followed at the HCFMRP - USP in the last 16 years and were selected. Those who had systolic pulmonary arterial pressure above 30 mmHg in the echocardiogram evaluation were considered to have pulmonary hypertension. Clinical variables before and after surgery were analyzed. Anthropometric and age data at the surgery had no influence in the presence of PH in the follow up. Although prolonged cardiopulmonary bypass and pulmonary mechanical ventilation had significantly affected that outcome. The survival had increased significantly in the last eight years of our study, reflecting the improvement of assistance. A high loss of follow up was detected and made us very concerned, however shows the difficulties and low investment in the public health system in developing countries.

Einleitung Der interventionelle Verschluß eines einfachen Vorhofseptumdefekts (ASD) vom Sekundumtyp und eines persistierenden Foramen ovale (PFO) ist zur Routinemethode gereift (1). Die Intervention wird unter Röntgendurchleuchtung (Strahlenexposition) durchgeführt. Sie ist wegen der geringen Invasivität auch bis ins hohe Alter mit deutlich niedrigerem Risiko als eine Operation durchführbar (2). Die hier vorgestellten Arbeiten haben systematisch untersucht, welche Möglichkeiten bestehen, bei der Intervention auf eine Strahlenexposition zu verzichten (3-6), welche interventionellen Möglichkeiten bei multiplen Defekten und Vorhofseptumaneurysmen bestehen (7,8) und welche Auswirkungen ein restriktiver linker Ventrikel auf die hämodynamische Adaptation nach Defektverschluß haben kann (9-11). Methodik Alle Untersuchungen wurden im Rahmen der klinischen Routine im Herzkatheterlabor am sedierten Patienten mit Vorhofseptumdefekt vom Sekundumtyp, persistierendem Foramen ovale, perforiertem Vorhofseptumaneurysma oder multiperforiertem Vorhofseptum durchgeführt. 1. Es wurde eine Methode zum Verschluß von Vorhofseptumdefekten unter alleiniger Ultraschallkontrolle entwickelt, d.h. unter vollständigem Verzicht auf die sonst notwendige Röntgenstrahlung. 2. Die Morphologie von Vorhofseptumaneurysmen und multiperforierten Vorhofsepten wurde analysiert und im Hinblick auf die interventionellen Verschlußmöglichkeiten klassifiziert. Dabei wurde auch die Möglichkeit der simultanen Implantation mehrerer Okkluder mit einbezogen. 3. Zur Erkennung von Patienten mit einem restriktiven linken Ventrikel, der unmittelbar nach ASD-Verschluß insuffizient werden könnte, wurde eine Methode der präinterventionellen hämodynamischen Evaluation etabliert. Dazu wird die Vorlast und die diastolische Funktion des linken Ventrikels unter temporärem Verschluß des ASD mit einem Okklusionsballon untersucht. Demaskiert sich eine linksventrikuläre Restriktion, so wird als Therapiekonzept der Ventrikel auf den interventionellen Verschluß durch eine prophylaktische 'Konditionierung' mittels Diuretika und Inotropika vorbereitet. Resultate 1. Interventioneller ASD-Verschluß ohne Strahlenexposition Wir konnten zeigen, daß der interventionelle ASD-Verschluß ohne Einsatz von Röntgenstrahlung durchführbar ist (3). Dies gilt für die präinterventionelle Diagnostik, die invasive Größenmessung (Ballonsizing) (6) und den interventionelle Verschluß selbst (4). Als einziges bildgebendes Verfahren für die Intervention dient die Echokardiographie. Im Vergleich zum Standardprocedere waren beim Verzicht auf eine Strahlenexposition gleich gute Ergebnisse zu erzielen, die Prozedurdauer war vergleichbar. Beim spontan atmenden Patienten sind für diese Methode höhere Dosen an Sedierung erforderlich, um die längere Verweilzeit der transösophagealen Echokardiographiesonde zu ermöglichen (5). Der Amplatzer Occluder ist wegen seiner guten Sichtbarkeit im transösophagealen Ultraschall, seiner Rotationssymmetrie und seiner einfachen Plazierung für diese neue Methode des ASD-Verschlusses ohne Röntgenstrahlung besonders geeignet. 2. Verschluß morphologisch komplexer Vorhofseptumdefekte Auch multiperforierte Vorhofsepten können interventionell erfolgreich verschlossen werden. Bei dicht nebeneinander liegenden Defekten ist dies mit einem Occluder, der alle Defekte abdeckt, möglich, bei weiter auseinanderliegenden Defekten ist die simultane Implantation zweier Occluder sinnvoll. Zwei Occluder führen mit größerer Sicherheit zu einem Verschluß ohne Restshunt (7). Multiple Defekte sind häufig mit einem Vorhofseptumaneurysma vergesellschaftet. Im Hinblick auf die Interventionsmöglichkeiten läßt sich diese Anomalie in vier Gruppen unterteilen: Aneurysma mit PFO (Typ A), mit ASD (Typ B), mit mehreren dicht nebeneinander liegenden Defekten (Typ C) und große Aneurysmen mit einer Vielzahl irregulär verteilter Perforationen (Typ D). Die ersten drei Formen lassen sich interventionell verschließen. Dabei gelingt zumindest eine Teilstabilisierung der Aneurysmen (8). 3. Vorhofseptumdefekte und restriktiver linker Ventrikel Wir konnten zeigen, daß insbesondere bei älteren Patienten mit ASD eine verdeckte linksventrikuläre Restriktion vorliegen kann. Ein interventioneller ASD-Verschluß kann bei diesen Patienten zur akuten kardialen Dekompensation führen (9). Als Hinweis auf eine gestörte linksventrikuläre Compliance fanden wir bei temporärer Okklusion des Defekts einen deutlichen Anstieg des linksatrialen Drucks und einen gestörten Mitralklappeneinstrom (10). Nach einer prophylaktischen 'Konditionierung' des linken Ventrikels mittels vorlastsenkenden und inotropiesteigernden Medikamenten (Diuretika, Phosphodiesterasehemmer, Katecholamine) gelang bei fast allen Patienten der interventionelle ASD-Verschluß mit guter Adaptation des Ventrikels, ohne daß es zur kardialen Dekompensation kam (11). Schlußfolgerungen Die in dieser Habilitationsschrift ausgeführten Arbeiten haben weiterführende Fragestellungen und Grenzbereiche des interventionellen Verschlusses von ASD und PFO aufgezeigt und neue interventionelle Therapiestrategien dargestellt. Dadurch ist es möglich, im klinischen Alltag weniger Röntgenstrahlung und Röntgenkontrastmittel zu verwenden, auch morphologisch komplexe Defekte standardisiert zu behandeln und selbst im hohen Alter bei Vorliegen einer linksventrikulären restriktiven Dysfunktion Defekte mit geringem Risiko zu verschließen.
Introduction Interventional closure of the simple secundum type atrial septal defect (ASD) and of persistent foramen ovale (PFO) has developed into a routine procedure (1). The intervention is carried out under X-ray monitoring (X-ray exposure). Since it is minimally invasive it can be carried out even in patients of advanced age with significantly less risk than an operation (2). The work presented here investigates systematically the possibilities of carrying out the intervention without X-ray exposure (3-6) and in the case of multiple defects and atrial aneurysms (7, 8). It also looks at the effects of a restrictive left ventricle on hemodynamic adaptation after closure of the defect (9-11). Methods All examinations were carried out as part of the clinical routine of the heart catheter laboratory in sedated patients with a secundum type atrial septal defect, persistent foramen ovale, perforated atrial aneurysms or multiply perforated atrial septum. 1. A method was developed whereby the closure of atrial septal defects can be carried out solely under echocardiographic monitoring, i.e. completely without X-ray exposure. 2. The morphology of atrial septal aneurysms and multiply perforated atrial septum was analyzed and classified with regard to the possibilities of interventional closure. The possibility of simultaneous implantation of several occluders was also considered. 3. To recognize patients with a restrictive left ventricle, which might become insufficient directly after ASD closure, a method of preinterventional hemodynamic evaluation was established. This involves examining preload and the diastolic function of the left ventricle during temporary closure of the ASD with an occlusion balloon. If this procedure reveals left ventricular restriction, the ventricle is prepared for interventional closure by prophylactic conditioning by means of diuretics and inotropes. Results 1. Interventional ASD Closure without X-Ray Exposure We were able to show that interventional ASD closure is possible without the use of X-rays (3). This applies to the preinterventional diagnostic procedures, invasive size measurement (balloon sizing) (6) and the interventional closure itself (4). The sole imaging procedure used for the intervention is echocardiography. In comparison with the standard procedure, the results are equally good and the duration of the procedure is comparable. In the spontaneously breathing patient higher sedative doses are necessary so that the transesophageal echocardiography tube can remain in place throughout (5). The Amplatzer occluder is particularly suitable for this new method because it is easily viewed in transesophageal echocardiographic imaging, rotationally symmetrical and easily positioned. 2. Closure of Morphologically Complex Atrial Septal Defects Multiple perforations of the atrial septum can also be successfully closed by intervention. If the defects are close together, one occluder can be used to cover all the defects; if they are further apart, the simultaneous implantation of two occluders is indicated. Two occluders are more likely to achieve occlusion without residual shunt (7). Multiple defects are often associated with an atrial septal aneurysm. With regard to the interventional possibilities these anomalies can be divided into four groups: aneurysm with PFO (type A), with ASD (type B), with several defects situated close together (type C) and large aneurysms with a number of irregularly distributed perforations (type D). The first three types may be closed by intervention, which mostly achieves partial stabilization of the aneurysms (8). 3. Atrial Septal Defects and Restrictive Left Ventricle We showed that, in particular in older patients with ASD, left ventricular restriction may be concealed. In these patients interventional ASD closure can lead to acute cardiac decompensation (9). A sign of disruption of left ventricular compliance was a marked rise in the left atrial pressure and disturbance of the mitral valve inflow during temporary occlusion of the defect (10). Following prophylactic 'conditioning' of the left ventricle by drugs that reduce the preload and increase inotropism (diuretics, phosphodiesterase inhibitors, catecholamines), interventional ASD closure succeeded in almost all patients with good adaptation of the ventricle and without cardiac decompensation occurring (11). Conclusion The work reported here addresses complex questions and frontier areas of the interventional closure of ASDs and PFO and presents new interventional strategies. It enables less X-ray exposure and less X-ray contrast medium to be used in clinical practice. Morphologically complex defects can be treated by standard procedures and with a small risk, even in patients with advanced age and left ventricular restrictive dysfunction.

As fístulas broncopleurais habitualmente decorrem de procedimentos cirúrgicos de ressecção pulmonar por diversas etiologias, com incidência na literatura de 0% a 28%, e mortalidade de 16% a 72%, sendo mais frequente em homens, e nos casos de pneumonectomia do que em lobectomia. As deiscências totais de coto brônquico apresentam indicação de tratamento cirúrgico, porém a condição clínica destes pacientes geralmente é precária com alto risco anestésico e cirúrgico. Os tratamentos endoscópicos de fístulas broncopleurais até então descritos foram utilizados apenas em fístulas parciais menores que 8 milímetros. Objetivo: Este estudo propõe-se a avaliar a viabilidade do tratamento endoscópico de fístulas totais de coto brônquico utilizando o dispositivo oclusor de defeitos septais cardíacos Occlutech-Fígulla®. Casuística e métodos: Foram incluídos pacientes com fistula broncopleural total secundária a ressecção pulmonar. Os pacientes foram submetidos inicialmente à broncoscopia para avaliação e medida da fístula e a uma cintilografia pulmonar de inalação para documentação do padrão inicial de vazamento. A colocação do dispositivo foi feita através da broncoscopia realizada sob sedo-analgesia com o paciente em ventilação espontânea com suplementação de oxigênio. Os pacientes foram acompanhados durante 12 meses e avaliados quanto à cobertura do dispositivo por tecido cicatricial, fechamento do trajeto fistuloso e desenvolvimento de complicações relacionadas como o deslocamento do dispositivo, lesões de estruturas adjacentes e desenvolvimento de infecção. As análises descritivas dos dados quantitativos com distribuição normal foram apresentadas através das médias acompanhadas dos respectivos desvios padrão. Os dados sem distribuição normal foram apresentados através de suas medianas com os respectivos intervalos interquartil 25-75%. A análise inferencial utilizou a Análise de Variância de Medidas Repetidas para os dados com distribuição normal e os testes não-paramétricos Anova de Friedman para os dados que não apresentavam distribuição normal. Foi considerada uma probabilidade de erro do tipo I (alfa) de 0,05. Resultados: Foram selecionados nove pacientes com predomínio do sexo masculino (77,8%), com média de idade de 45 ±11,1 anos, com ressecções motivadas em sua maioria por sequelas de doença infecciosa (78%), com predomínio de pneumonectomia direita (66,6%), com fístulas que apresentavam diâmetro de 6 a 17 mm. Do grupo de 9 pacientes tratados tivemos três casos de fechamento completo, dois casos de fechamento parcial, duas falhas sendo uma por deslocamento e retirada do dispositivo e outra por retirada ao término do período de seguimento com permanência dos sintomas e dois óbitos não relacionados. Durante o período de acompanhamento não evidenciamos complicações infecciosas ou lesão de estruturas adjacentes relacionadas à permanência do dispositivo. Conclusão: O dispositivo para tratamento de defeitos do septo atrial pode ser uma alternativa no tratamento endoscópico de fístulas totais de coto brônquico, funcionando como tratamento definitivo em alguns casos e servindo como suporte nos pacientes que aguardam melhora das condições clínicas para uma intervenção cirúrgica tardia com menor risco. Não foram detectados eventos graves como infecções ou lesão vascular relacionados à presença do dispositivo
Bronchopleural fistulas are possible complications following lung resection procedures for different etiologies. The reported incidence is 0 % to 28%, and the related mortality is 16% to 72%. More frequently in men and pneumonectomy cases than lobectomy cases. Total dehiscence of the bronchial stump should be treated by surgical interventions; however, the clinical status of these patients is generally poor with high anesthetic and surgical risks. Endoscopic treatment of bronchopleural fistulas previously described were used only in 8mm or smaller partial fistulas. Objective To evaluate the endoscopic treatment of total bronchial stump fistulas using the Occlutech - Fígulla®, a device used to close cardiac septal defects. Patients and methods: We select patients with total bronchial stump fistula. Patients underwent bronchoscopy for local fistula evaluation and an inhalation lung scintigraphy for the initial leak parameter documentation. The placement of the device was made by bronchoscopy performed under sedation - analgesia with the patient in spontaneous ventilation with oxygen supplementation. Patients were followed for 12 months and assessed for scar tissue coverage device, fistula closure and development of related complications such as displacement device, adjacent structures lesions and infection. The descriptive analysis of quantitative data with normal distribution were presented through the mean along with the related standard deviations. Non-normal distribution data were presented by their medians with their respective interquartile ranges 25-75 %. The inferential analysis used Repeated Measures Analysis of Variance for data with normal distribution and non-parametric tests of Friedman ANOVA to data with nonnormal distribution. It was considered an error probability of a type I (alfa) 0.05. Results: This study evaluated nine patients with a males predominance (77.8% ) with mean age of 45 ± 11.1 years with resections for sequelae of infectious disease (78%), predominantly right pneumonectomy (66.6% ), with fistulas diameter ranging from 6 to 17 mm. The group of 9 patients had three cases of complete closure, two cases of partial closure, two failures one per displacement and removal of the device another for withdrawal at the end of follow-up with persistence of symptoms and two unrelated death. During the follow-up period was not detect complications such as infections or injury to adjacent structures related to the device. Conclusion: The device for treatment of atrial septal defects can be an alternative to the endoscopic treatment of total fistula bronchial stump, functioning as definitive treatment in some cases and serving as a support for patients awaiting improvement of clinical conditions for a later surgical intervention with lower risk. No severe events were detected as infections or vascular injury related to the device

INTRODUCAO: A comunicação interatrial tipo \"ostium secundum\" é um defeito cardíaco congênito caracterizado pela deficiência parcial ou total da lâmina da fossa oval, também chamada de septo primo. Corresponde a 10 a 12% do total de cardiopatias congênitas, sendo a mais frequente na idade adulta. Atualmente a oclusão percutânea é o método terapêutico de escolha em defeitos com características anatômicas favoráveis para o implante de próteses na maioria dos grandes centros mundiais. A ecocardiografia transesofágica bidimensional com mapeamento de fluxo em cores é considerada a ferramenta padrão-ouro para a avaliação anatômica e monitoração durante do procedimento, sendo crucial para a ótima seleção do dispositivo. Neste sentido, um balão medidor é introduzido e insuflado através do defeito de forma a ocluí-lo temporariamente. A medida da cintura que se visualiza no balão (diâmetro estirado) é utilizada como referência para a escolha do tamanho da prótese. Recentemente a ecocardiografia tridimensional transesofágica em tempo real tem sido utilizada neste tipo de intervenção percutânea. Neste estudo avaliamos o papel da mesma na ótima seleção do dispositivo levando-se em consideração as dimensões e a geometria do defeito e a espessura das bordas do septo interatrial. METODO: Estudo observacional, prospectivo, não randomizado, de único braço, de uma coorte de 33 pacientes adultos portadores de comunicação interatrial submetidos a fechamento percutâneo utilizando dispositivo de nitinol autocentrável (Cera ®, Lifetech Scientific, Shenzhen, China). Foram analisadas as medidas do maior e menor diâmetro do defeito, sua área e as medidas do diâmetro estirado com balão medidor obtidas por meio das duas modalidades ecocardiográficas. Os defeitos foram considerados como elípticos ou circulares segundo a sua geometria; as bordas ao redor da comunicação foram consideradas espessas (>2 mm) ou finas. O dispositivo selecionado foi igual ou ate 2 mm maior que o diâmetro estirado na ecocardiografia transesofágica bidimensional (padrão-ouro). Na tentativa de identificar uma variável que pudesse substituir o diâmetro estirado do balão para a ótima escolha do dispositivo uma série de correlações lineares foram realizadas. RESULTADOS: A idade e peso médio foram de 42,1 ± 14,9 anos e 66,0 ± 9,4kg, respectivamente; sendo 22 de sexo feminino. Não houve diferenças estatísticas entre os diâmetros maior e menor ou no diâmetro estirado dos defeitos determinados por ambas as modalidades ecocardiográficas. A correlação entre as medidas obtidas com ambos os métodos foi ótima (r > 0,90). O maior diâmetro do defeito, obtido à ecoardiografia transesofágica tridimensional, foi a variável com melhor correlação com o tamanho do dispositivo selecionado no grupo como um todo (r= 0,89) e, especialmente, nos subgrupos com geometria elíptica (r= 0,96) e com bordas espessas ao redor do defeito (r= 0,96). CONCLUSÃO: Neste estudo em adultos com comunicações interatriais tipo ostium secundum submetidos à oclusão percutânea com a prótese Cera ®, a ótima seleção do dispositivo pôde ser realizada utilizando-se apenas a maior medida do defeito obtida na ecocardiografia transesofágica tridimensional em tempo real, especialmente nos pacientes com defeitos elípticos e com bordas espessas.
INTRODUCTION: The ostium secundum atrial septal defect is a congenital heart disease characterized by partial or total deficiency of the fossa ovalis, also known as the septum primum. It corresponds to 10-12% of all congenital heart defects, being the most frequently found in adulthood. Currently, percutaneous closure is the therapeutic method of choice for defects with suitable anatomic features for device implantation in most centers in the world. Bi-dimensional transesophageal echocardiography with color flow mapping is considered the gold-standard tool for anatomic assessment and procedural monitoring, being crucial for optimal device selection. In this regard, a sizing balloon is introduced and inflated across the defect with temporary occlusion. The waist measurement seen on the balloon (stretched diameter) is used as a reference for selection of device size. Recently, real time three-dimensional transesophageal echocardiography has been utilized in this type of percutaneous intervention. In this study we assessed the role of this modality in optimal device selection taking into consideration the dimensions and the geometry of the defect and the thickness of the interatrial septum rims. METHODS: Observational, prospective, non-randomized, single-arm study of a cohort of 33 adults with atrial septal defects submitted to percutaneous closure using a self-centered nitinol device (Cera (TM), Lifetech Scientific, Shenzhen, China). The largest and the smallest diameter of the defect, its area and the measurements of the stretched diameter of the sizing balloon were assessed by both echocardiographic modalities. The defects were considered as elliptical or circular according to their geometry; the rims surrounding the defect were considered thick (> 2 mm) or thin. The selected device was equal to or 2 mm larger than the stretched diameter on bi-dimensional transesophageal echocardiography (gold-standard). In an attempt to identify a variable that could replace the stretched balloon diameter, a series of linear correlations were performed. RESULTS: The mean age and weight were 42.1 ± 14.9 years and 66.0 ± 9.4 kgs, respectively; being 22 of the female gender. There were no statistical differences between the largest and smallest diameters of the defects and the stretched diameters determined by both echocardiographic modalities. The correlation between the measurements obtained by both methods was excellent (r > 0.90). The largest defect diameter obtained by three-dimensional transesophageal echocardiography was the variable that showed the best correlation with the selected device size in the entire group (r= 0.89), especially in the subgroups with elliptical geometry (r= 0.96) and with thick rims surrounding the defect (r=0.96). CONCLUSIONS: In this study in adults with ostium secundum atrial septal defects submitted to percutaneous occlusion with the Cera (TM) device, optimal device selection could be performed using solely the largest diameter of the defect obtained by real time three-dimensional transesophageal echocardiography, especially in patients with elliptical defects and thick rims.

Introdução: As comunicações interatriais do tipo ostium secundum (CIA-OS) são tratadas por fechamento percutâneo (FP) ou intervenção cirúrgica (IC). Estudos comparando ambos métodos são escassos e avaliações de custo-efetividade inexistem na literatura nacional. Objetivos: Realizar uma avaliação da segurança e eficácia (ASE) clínica seguida de uma análise de custo-efetividade (ACE) incremental comparando o FP e IC sob a perspectiva do Sistema Único de Saúde (SUS). Materiais e métodos: ASE - Estudo observacional, não randomizado de 2 coortes de crianças e adolescentes < 14 anos com CIA-OS tratadas por FP ou IC. A coleta dos dados foi prospectiva no FP e retrospectiva no IC. ACE - Realizada revisão sistemática de estudos clínicos disponíveis no MEDLINE e a Cochrane Central. Estudos com mais de 50 pacientes e com idade média abaixo de 14 anos foram incluídos. A análise foi baseada em uma árvore de decisão computando os custos e consequências no longo prazo de ambas as opções. Foi utilizado valor da prótese de R$ 16.000 e estipulado valor de honorário médico de R$ 2.355. A efetividade foi estimada em anos de vida. A avaliação utilizou uma taxa de desconto de 5% ao ano e uma disposição a pagar de 3 vezes o PIB per capita no Brasil (63.000). Análises de limiares também foram conduzidas. Resultados: ASE - De Abr/09 a Out/11 foram alocados 75 pacientes (pts) no FP e entre Jan/06 e Jan/11 105 pts na IC. A idade e o peso foram maiores no FP e o diâmetro da CIA foi semelhante entre os grupos. Sucesso técnico foi observado em todos os procedimentos e não houve óbitos. Complicações (a maioria menores) foram encontradas em 68% na IC e em 4% do FP (p<0,001). As taxas de fluxo residual não significativo ou de oclusão total do defeito foram semelhantes nos 2 grupos. A mediana de internação foi de 1,2 dias após o FP e 8,4 dias após a IC (p< 0,001). ACE - A estratégia de busca retornou 2.957 referências, das quais 34 foram incluídas. A taxa de mortalidade foi semelhante nos 2 grupos. O FP teve discreta maior efetividade, menor taxa de complicações moderadas/graves e menor tempo de internação, mas com maior probabilidade de um segundo procedimento. A relação de custo-efetividade incremental (RCEI) do tratamento percutâneo foi de R$ 230.641 por ano de vida salvo. Considerando-se este cenário, seria necessário que o custo indireto associado à cirurgia fosse de R$ 4.960, ou que o valor pago pelo dispositivo percutâneo sofresse redução de R$ 4.960 para que o FP se tornasse aceitável do ponto de vista econômico. Conclusões: Ambos tratamentos são seguros e eficazes com ótimos desfechos, porém o FP apresenta menor morbidade e tempo de internação. Usando os valores diretos estipulados neste estudo, a RCEI foi elevada limitando a incorporação do FP pelo SUS neste momento. Estudos considerando também os custos indiretos são necessários para a adequada ACE de ambas estratégias.
Introduction: Atrial septal defects of the secundum type (ASD-OS) are treated by percutaneous closure (PC) or surgical intervention (SI). Comparative studies are scarce and there is no cost-effectiveness assessment in the Brazilian literature. Objectives: To perform a clinical safety and efficacy (ASE) assessment followed by an incremental cost-effectiveness (CEE) analysis comparing PC and SI under the Brazilian Unified Health System perspective. Materials and methods: ASE - Observational, non-randomized study of two cohorts of children and adolescents under 14 years with ASD-OS treated by PC or SI. Data was collected prospectively in PC and retrospectively in SI. CEE - A systematic review of clinical studies available in MEDLINE and Cochrane Central was performed. Studies with more than 50 patients and mean age under 14 years were included. Analysis was based on a decision tree that took into account costs and consequences during long-term follow-up for both options. The cost of the device and medical honorarium were estimated at R$ 16.000 and R$ 2.355, respectively. Effectiveness was estimated in years of life. Assessment was performed using a discount tax of 5% and a willingness to pay of 3 times the GID in Brazil (63.000). Threshold analyses were also conducted. Results: ASE - From Apr/09 to Oct/11 75 patients (pts) were enrolled in PC and from Jan/06 to Jan/11 105 pts in SI. Age and weight were greater in PC and the ASD diameter was similar. Technical success was achieved in all procedures and there were no deaths. Complications (most minor) occurred in 68% of SI and 4% of PC (p<0,001). The rate of total occlusion or non-significant residual shunts was similar in both groups. Median hospitalization time was 1.2 days in PC and 8.4 days in SI (p<0,001). CEE - Search strategy returned 2957 references and 35 were included. Mortality was similar in both groups. PC was associated with slightly better effectiveness, lower rates of moderate/severe complications and reduced hospital stay despite a higher probability of a second procedure. Incremental cost-effectiveness ratio (ICER) was R$ 230.641 for life-year gained. In this scenario, PC would be acceptable from the economic point of view if the indirect costs of the SI was R$ 4.960 or the cost of the device was reduced by R$ 4.960. Conclusions: Both methods are safe and effective with excellent outcomes, however PC is associated with less morbidity and in-hospital time. Using the direct costs stipulated in this study, the ICER was high limiting the incorporation of PC by the Brazilian Unified Health System (SUS) at this moment. Studies also considering the indirect costs should be performed for better CEE assessment of both strategies.

Introdução: A comunicação interatrial tipo ostium secundum(CIA) é uma cardiopatia congênita frequente, sendo a mais comumente encontrada na população adulta. Seu tratamento está indicado quando há repercussão hemodinâmica caracterizada pelo aumento das dimensões das câmaras direitas à ecocardiografia, independente da presença de sintomas. Nas últimas 2 décadas o fechamento percutâneo da CIA emergiu como a modalidade terapêutica preferencial devido sua alta eficácia e menor morbidade que a correção cirúrgica.Tanto o tratamento cirúrgico como o percutâneo da CIA resultam em remodelamento cardíaco com redução progressiva do tamanho das câmaras direitas e aumento das esquerdas. Recentemente, novas técnicas ecocardiográficas vem sendo empregadas para avaliação das dimensões, geometria e função das câmaras cardíacas incluindo o ecocardiograma tridimensional e o rastreamento de marcadores acústicos. Hipótese e objetivos: Partiu-se da hipótese que o fechamento percutâneo da CIA, por ser um método não invasivo, levaria a rápido remodelamento cardíaco mesmo em adultos com sobrecarga volumétrica crônica das câmaras direitas. Tivemos como objetivo avaliar o comportamento temporal do remodelamento cardíaco e analisar possíveis diferenças existentes entre pacientes de diferentes faixas etárias e com tamanhos diversos de CIA. Material e métodos: Estudo observacional, prospectivo, não randomizado de um braço único de uma coorte de adultos submetidos ao fechamento percutâneo da CIA com a prótese Cera (Lifetech, Shenzheng, China) e acompanhados por um ano. Foram selecionados 29 adultos com CIA com repercussão hemodinâmica com anatomia favorável para a oclusão percutânea e sem contra-indicações para tal. O remodelamento cardíaco foi estudado por meio de várias técnicas ecocardiográficas incluindo as clássicas e outras de introdução recente. A ecocardiografia bidimensional foi usada para a medição das dimensões do átrio direito (AD), ventrículo direito (VD) e ventrículo esquerdo (VE), para determinação da área fracionada do VD (FAC) e da excursão anterior da valva tricúspide (TAPSE) e para análise volumétrica das câmaras cardíacas. A ecocardiografia tridimensional foi empregada para análise volumétrica e funcional do VD. O rastreamento de marcadores acústico foi utilizado para avaliação da função do AD, VD e VE. O teste ANOVA foi usado para avaliação das mudanças observadas nas variáveis repetidas ao longo do tempo com comparações múltiplas de Bonferroni quando aplicável. Uma análise intra e interobservador das medidas foi realizada utilizando coeficientes de concordância. Resultados: A média de idade e peso dos pacientes foi de 45,2 ± 17,0 anos e 68,8 ± 14,0 kgs, respectivamente. Nenhum paciente apresentada hipertensão pulmonar significativa. A média do tamanho da CIA foi de 20,2 ± 5,0 mm e a média do tamanho da prótese implantada foi de 22,9 ± 6,2 mm. Em todos os pacientes houve sucesso no implante. Não houve complicações relacionadas ao procedimento e em todos os pacientes foi observada oclusão do defeito. Após o procedimento, houve redução precoce (< 3 meses) das dimensões do AD (p<0,001) e do VD (p<0,001) e aumento das dimensões do VE (p<0,014). Não houve mudanças significativas na função de deformação longitudinal do AD para onda P (p=0,227) e para onda T (p=0,124). Houve redução abrupta da função do VD pelo TAPSE (p=0,032), pela deformação longitudinal (p=0,002) e pela ecocardiografia tridimensional (p=0,084). Não houve mudanças significativas da onda S\' (p=0,55) e da FAC (p=0789) do VD. Houve redução precoce do volume de ejeção do VD (p< 0,001) e aumento do volume de ejeção do VE (p=0,027). Houve redução da deformação longitudinal do VE (p=0,049) e não houve mudanças na função do VE pelo método de Simpson (p=0,462). Pacientes maiores que 60 anos (n=8) apresentaram valores iniciais maiores nas dimensões do AD e redução mais prolongada (p=0,0497). Pacientes com CIAs maiores que 20 mm (n=12) apresentavam valores iniciais maiores de TAPSE com redução mais retardada (p=0,013). Todas as mudanças observadas inicialmente nos primeiros 3 meses se sustentaram ao final do seguimento. Houve excelente concordância na análise intraobservador para todas as medidas repetidas (CCI> 0,9) com exceção da deformação do VE (CCI< 0,7). A concordância entre as medidas realizadas por diferentes observadores não foi tão boa, com apenas as variáveis TAPSE, deformação do VE e dimensões do AD possuindo CCI > 0,7. Conclusões: O fechamento percutâneo da CIA em adultos de meia idade leva a rápido remodelamento cardíaco tanto do ponto de vista anatômico como funcional com resultados sustentados dentro do primeiro ano de seguimento. Tais mudanças temporais são observadas independente do tamanho da CIA e da idade dos pacientes, denotando o efeito benéfico do procedimento sobre a geometria e o funcionamento cardíaco global em todos adultos portadores desta frequente cardiopatia congênita.
Introduction: The atrial septal defect of the secundum type (ASD) is a frequent congenital heart disease, being the most commonly encountered in the adult population. Treatment is indicated when there is hemodynamic burden characterized by increased dimensions of the right chambers on echocardiography, regardless of the presence of symptoms. In the last two decades, percutaneous closure of the ASD has emerged as the preferred therapeutic modality due to its high efficacy and lower morbidity when compared to surgical correction. Both surgical and percutaneous treatment of the ASD result in cardiac remodeling with progressive reduction in the size of the right chambers and increase in the left chambers. Recently, new echocardiographic techniques have been employed to assess the dimensions, geometry and function of the cardiac chambers including three-dimensional echocardiography (3D echo) and acoustic speckle tracking. Hypothesis and objectives: Hypothesizing that percutaneous closure, being a non-ivasive method, results in a fast cardiac remodeling even in adults with chronic volume overload of the right chambers, our aim was to assess the temporal pattern of cardiac remodeling and analyse possible differences between patients of different age groups and different ASD sizes. Material and methods: This was an observational, prospective, non randomized, single arm study of a cohort of adults submitted to percutaneous closure of the ASD with the Cera device (Lifetech, Shenzheng, China) followed along a year. Twenty nine adults with hemodynamicaly significant ASDs with suitable anatomy for percutaneous closure and no contra-indications for the procerdure were selected. Cardiac remodeling was assessed by various echocardiographic techniques including standard and new ones. Bidimensional echocardiography was used to measure the dimensions of the right atrium (RA), right ventricle (RV) and left ventricle (LV), to determine the fractional area of the RV (FAC) and the systolic anterior excursion of the tricuspid valve (TAPSE), and to analyse the volumes of the cardiac chambers. Three-D echo was employed for volumetric and functional analysis of the RV. Acoustic speckle tracking was utilized to assess the function of the RA, RV and LV. ANOVA tests were used to assess the observed changes in the repeated variables over time with multiple Boferoni comparison as applicable. An intra and interobserver analysis of the measurements was performed using concordance coefficients. Results: Mean age and weight was 45,2 ± 17,0 years and 68,8 ± 14,0 kgs, respectively. No patient had significant pulmonar arterial hypertension. The ASD dimension and the size of the device was a mean of 20,2 ± 5,0 mm and 22,9 ± 6,2 mm, respectively. In all patients the device was implanted successfully. There were no complications related to the procedure and in all patients the ASDs were successfully closed. After the procedure, there was an early (< 3 months) reduction of the RA (< 0.001) and RV (< 0.001) sizes and an increase of the LV dimensions (p< 0.014). There were no significant changes in the function of the RA as assessed by longitudinal strain (p=0.227 for the P wave and p=0.124 for the T wave). There was an abrupt reduction of the RV function assessed by TAPSE (p=0.032), longitudinal strain (p=0.002) and 3D echo (p=0.084). There were no changes in the S\' wave (p=0.55) and FAC (p=0.789) of the RV. There was an immediate decrease in the RV stroke volume (p< 0.001) and an increase in the LV srtroke volume (p=0.027). There was a reduction in LV longitudinal strain (p=0.049) and no change in LV function as assessed by the Simpson method (p=0.462). Patients older than 60 years of age (n=8) presented with larger RA dimensions, which decreased in a slower fashion (p=0.0497). Patients with ASDs larger than 20 mm (n=12) had initial higher TAPSE values, which decreased in a slower fashion (p=0.013). All changes observed earlier on endured after a year. There was excellent concordance in the intra observer analysis for all the repeated measures (CCI > 0.9) with the exception of LV strain (CCI < 0.7). The concordance between different observers was not as good with only TAPSE, LV strain, and RA dimensions variables having a CCI > 0.7. Conclusions: Percutaneous closure of the ASD in middle aged adults results in fast cardiac remodeling from both the anatomic and functional point of view with sustained results over the first year of follow up. These temporal changes are observed regardless of the ASD size and the age of the patients, which demonstrates the beneficial effect of the procedure over the cardiac geometry and global function in all adults who have this frequent congenital heart disease.

博士
中山醫學大學
醫學研究所
95
Background: Two-dimensional echocardiography (2DE) enhanced by combining with color Doppler technology has significant limitations in providing precise quantitative information, geometric assumptions to calculate chamber volume, mass, and ejection fraction. Reconstructed three-dimensional echocardiographic (3DE) systems (from multiple cross-sectional echocardiographic scans) are still cumbersome and time-consuming. Real-time 3DE (RT3DE) with shorter imaging time than with 3D reconstruction techniques can obtain qualitative and quantitative information on heart disorders. Our purpose was to estimate the patient of Atrial Septal Defect (ASD) and Ventricular Septal Defect (VSD). Transcatheter Amplatzer septal occluder (ASO) device closure of atrial septal defects (ASDs) has traditionally been guided by two-dimensional transesophageal echocardiography (2D-TEE) and intracardiac echocardiography (ICE) modalities. Real-time three-dimensional transthoracic echocardiography (RT3D-TTE) provides rotating images to define ASD and adjacent structures with potential as an alternative to 2D-TEE or ICE for guiding the device closure of ASD. There are two subjects of this study. The first subject was to assess the feasibility and effectiveness of RT3D-TTE in parasternal four-chamber views to guide ASO device closure of ASD. The second subject was to investigate the feasibility and potential value of RT3DE as a means of accurately and quantitatively estimating the size of VSD to correlate with the surgical findings. Materials and Methods: From February 2004 to August 2005, total 97 patients of septal defect were samples. Among in these patients, the 59 patients underwent transcatheter ASO device closure of ASD. The first 30 patients underwent 2D-TEE guidance under general anesthesia and the remaining 29 patients underwent RT3D-TTE guidance with local anesthesia. In addition, the 38 patients with VSD were examined with RT3DE. 3D image data-base was post-processed using TomTec echo 3D workstation. The results were compared with the results measured by 2 DE and surgical findings. Results: The first subject of atrial septal defect patients. All interventions were successfully completed without complications. The clinical characteristics and transcatheter closure variables of RT3D-TTE and 2D-TEE were compared. Echocardiographic visualization of ASD and ASO deployment was found to be adequate when using either methods. Catheterization laboratory time (39.1±5.4 vs 78.8±14.1 minutes, P < 0.001) and interventional procedure length (7.6±4.2 vs 15.3±2.9 minutes, P < 0.001) were shortened by using RT3D-TTE as compared with 2DE-TEE. There was no difference in the rate of closure following either method, assessed after a 6-month follow-up. The maximal diameter measured by RT3D-TTE and 2D-TEE was correlated well with a balloon stretched ASD size (y = 0.985x + 0.628, r = 0.924 vs y = 0.93x + 2.08, r = 0.885, respectively). The second subject of RT3DE produced novel views of VSD and improved quantification of the size of the defect. The sizes obtained from 3DE have equivalent correlation with surgical findings as diameter measured by 2-DE (r = 0.89 vs r = 0.90). Good agreement between blinded observers was achieved by little interobserver variability. Conclusion: RT3D-TTE may be a feasible, safe, and effective alternative to the standard practice of using 2D-TEE to guide ASO deployment. In addition, RT3DE offers intraoperative visualization of VSD to generate a “virtual sense of depth”without extending examining time. From an LV en face projection, the positions, sizes, and shapes of VSDs can be accurately determined to permit quantitative recording of VSD dynamics. It is a potentially valuable clinical tool to provide precise imaging for surgical and catheter-based closure of difficult perimembranous and singular or multiple muscular VSD.

博士
國立臺灣師範大學
體育學系
104
Ventricular Septal Defects (VSDs) and Atrial Septal Defects (ASDs) are the most common problems found in pediatric heart-related diseases which generally occur in 50% of all children of congenital heart disease. Physical activity, cardiopulmonary function and exercise capacity in the group of grown-up patients with ASDs or VSDs were evaluated through this study. To study the influence of ASDs or VSDs on cardiopulmonary function and exercise capacity, we have performed cardiopulmonary exercise test (CPET) in 28 patients in the ASD group, 31 patients in the VSD group, along with 24 healthy adults were recruited in the control group. Based on the finding, AT MET, AT heart rate, peak MET demonstrated statistically differences between patients with ASDs / VSDs and healthy participants. The comprehensive cardiac rehabilitation (CCR) program was addressed to a group of 29 patients (CCR group, 15 from ASD group and 14 from VSD group). After 6 weeks, CCR group underwent CPET again. Patients in the CCR group showed significantly higher AT heart rate and peak heart rate compared to the initial evaluation. And no significant differences were found in AT heart and peak heart rate compared to the healthy participants. In the presented study, the group of grown-up patients with ASDs or VSDs showed poorer cardiac function when comparing to the healthy group, while no limitation in exercise was observed and CCR program improves the physical activity and exercise capacity. Our findings support no contraindications for physical exercise in this patient group.

碩士
國立中山大學
生物醫學科學研究所
94
Abstract: Background: At present, device closure of interatrial communication has become a well established technique in order to adequately treat severe left-to-right shunt associated with ASDs. During the traditional procedure, fluoroscopy with the waist of a compliant balloon is used to determine the appropriate size of the closure device and defect sizing. Choice of adequate closure device using transthoracic echocardiography (TTE) has been hitherto unreported. Methods & Materials: Between December 2002 and October 2004, 40 patients (15 males, 25 females, mean age; 11.7 ± 7.8 years ) with secundum ASDs underwent transcatheter closure at our institution. In group 1, 30 patients had the procedure by balloon sizing and TTE sizing. In 10 patients (group 2), TTE sizing was used as the sole too l for selecting device size and the device size was chosen to be based on the Amplatzer septal occluder ( ASO ) size and TTE size ratio in group 1. The procedure was performed under continuous transoesophageal echocardiographic monitor with general anesthesia. Results: The correlation was found between TTE and stretched balloon sizing diameter SBD ( y= 1.2645x-1.4465; R²=0.9861 ), and between TTE size and ASO size ( y = 1.3412x-1.2864; R²=0.9929 ) in group 1. In group 2, statistical correlation between TTE and ASO ( y=1.3419x-0.1172; R²=0.9934 ) was also found. Good linear regression between TTE size and ASO chosen size was noted in group 1 and group 2 (R²=0.99).In group 2, successful device implantation was accomplished in all patients whose device size was chosen to be based on the ASO and TTE ratio in group 1. Conclusions: TTE sizing is a safe and ideal method to measure interatrial defect and choose the occluding device respectively. With our experience, the sizing based on the TTE is generally easier than measurement from the balloon sizing.

碩士
國立成功大學
生物醫學工程學系
101
In recent years, cardiovascular disease has become the top one cause of death in developed countries, and it is also getting more and more common in Taiwan. The traditional cardiac surgery has been gradually replaced by Interventional Catheterisation. The Interventional Catheterisation could reduce the possibility of surgical infection, general anesthesia and the time of being in hospital, it is much more economic and effective than the traditional surgery. Normally, when doctors face a new technology or surgery equipment, the most common problem for them is the lack of practice, and in traditional education, they usually use one-on-one training. In our study, “Double-catheter simulator system for atrial septal defect” can not only simulate the real situation of surgery, like the hand feel feedback of catheter and blood vessel, the system can also shows the simulated situation on the screen in order to make the surgery more real and enhance the education effect. This system is inexpensive and without any risks, users can improve their surgery skill through their practices.

碩士
國立陽明大學
急重症醫學研究所
97
This study was performed to assess changes in pulmonary function test (PFT) and pulmonary outcome after transcatheter closure of atrial septal defect (ASD) in pediatric patients. A total 55 pediatric patients undergoing transcatheter ASD closure received PFT at baseline (day before ASD closure), and at three days and six months after transcatheter procedure. Forced vital capacity (FVC), forced expired volume in one second (FEV1), FEV1 to FVC ratio (FEV1/FVC), peak expiratory flow (PEF), and mean forced expiratory flow during the middle half of FVC (FEF25-75) were measured. Individually, subjects were classified by spirometry as normal, obstructive or restrictive, to evaluate the effect of transcatheter closure on pulmonary outcome. These 55 children had significantly reduced mean PEF and FEF25-75 (84 ± 24%, p = 0.040 and 76 ± 22%, p = 0.010 respectively) at baseline, with FEF25-75 reduced significantly at three days and six months (78 ± 24%, p = 0.010 and 81 ± 24%, p = 0.040 respectively) after transcatheter closure. Six months after transcatheter closure of ASD, significant improvement was observed in mean FVC (94 ± 19% vs. 98 ± 15%, p = 0.034) and FEV1 (90 ± 20% vs. 96 ± 19%, p = 0.008). Assessed individually, better pulmonary outcome was found in patients without pulmonary hypertension (PH) (χ2 = 8.333, p = 0.044). PFT disturbance was observed in significant flow limitation in the peripheral airway of ASD patients. Improved PFT was found after transcatheter closure and better pulmonary outcome was observed in patients without PH. ASD children need monitoring pulmonary function and should receive transcatheter closure before PH develops.

碩士
國立成功大學
生物醫學工程學系
102
In recent years, with the development of cardiovascular interventional procedure, atrial septal defect (ASD) surgery has become the main way to treat type II ASD. The advantages of cardiovascular interventional procedure are: reduce the possibility of infection, general anesthesia and the time of being in hospital. However, two-dimensional X-ray images provided in the procedure could not provide surgeons the actual structure of heart and precise three-dimensional position of the defect, so it’s not so easy for a new physician to perform. In general, new doctors is led by a senior physician for procedure training, but this approach has some potential dangers, therefore, this study will design a computer simulation of double-catheter training system for atrial septal defect that provides physician a platform to practice and be familiar with the operation of various processes, including learning how to manipulate the catheter to the correct position for diagnosis and treatment. The system provides the user interface including the records of the operating parameters such as the exerted force on the catheter, the displacement and rotation angle of the double catheter, the processing time required to complete a treatment…etc. In addition, the system can be set or provide the real situation which may be encountered while doing simulations of the treatment, for example, the operating skills of passing through the specific location, if the users accidentally bump into the vessel wall, the simulating training system will generate reverse thrust force to the users so that it can make the simulation more realistic and achieve the training outcomes. In the future, we expected that the system can be applied as a teaching platform in hospital that allows users to practice repeatedly to achieve proficiency results and finally improve the success rate of treatment.

碩士
國立成功大學
醫學工程研究所碩博士班
95
It is the best way to treat the secundum type of Atrial Septal Defect (ASD) using the cardiac catheterization & interventional procedure. In the past years, the clinicians detected the location of the catheter through angiography images and measure the size of the ASD by balloon catheter test. However, the cardiac catheterization can not display the whole view of the ASD, such as the location, size, and rim of the ASD. Therefore, we utilize the transesophageal echocardiography (TEE) to observe the ASD. However, TEE needs general anesthesia with clinical risk. Intra-cardiac echocardiography (ICE) not only allows us to observe the atrium structure in the heart, but also to evaluate the device closure of ASD for guidance during the operation. This research utilized the ICE to observe the atrium structure during cardiac catheterization procedures & interventional closure of ASD. Since the heart is a three-dimensional anatomical structure and two-dimensional ICE images often needed to reconstruct to assess the three-dimensional structure of the atrium and ASD. In this study, we develop a real-time ICE converting to three-dimensional reconstruction system. The operator of transcatheter closure of ASD can realize the three-dimensional ASD and the relevance to cardiac anatomy in 3D feature. The transcatheter of ASD will be safer and easier with this new 3D Image Reconstruction of Cardio-anatomy using Intracardiac Echocardiography.

碩士
中山醫學大學
醫學研究所
95
Atrial septal defect（ASD） is one of the most frequent lesions in congenital heart disease especially in adult. Surgical repair of an ASD is a low-risk and widely accepted procedure. In near years, ASD transcatheter occlusion techniques have become an alternative to surgical procedure. Then, ASD size measurement is paramount importance for the successful deployment of a transcatheter septal occulder（ASO）. Until now, the balloon stretched diameter（BSD）has long been regarded as the gold standard for selection size of any device. Be along with echocardiography development, real-time three-dimensional echocardiography（RT-3DE）accurately defined ASD location, size, and surrounding atrial anatomy. The study aim was to compare the BSD and RT-3DE methods to measure the ASD size. Further, to use these results to get the greater method of measurement in the cardiac cycle. Population: The fifty heart failure patients referred for transcatheter closure of a secundum ASD were enrolled. Method: In all fifty patients, maximal diameter of the defect including: antero-posterior, supero-inferior, derived from circumference, and derived from area measurement were performed in each patients when the defect hole appeared mazimal in size during the cardiac cycle. Then, comparing these data and BSD measurement, and finding the best correlation in these datas of RT-3DE. Finally, in the best correlation data, to find the good measurement in the cardiac cycle. Result: After statistical analysis, RT-3DE measurement of diameter derived from circumference agreed well with the BSD （Y=0.996x+4.313, r=0.841）. In this data, the mean diameter derived from circumference agreed well with the BSD （Y=0.790x+3.59, r=0.908）. Transcatheter closure was pergormed successfully in fifty patients using the Amplatzer device closure. Conclusion: In these patients with ASD, RT-3DE measurement of diameter derived from circumference was high correlation with BSD. In the heart cycle, mean diameter derived from circumference more agreed well with the BSD than maximum and minimum diameter derived from circumference. If we will find the best measurement of the ASD size, we need have more research and clinical experience.

Le cœur des vertébrés est un organe modulaire qui requiert le " patterning " complexe des champs morphogénétiques cardiogènes et la convergence coordonnée des diverses sous-populations de progéniteurs cardiogéniques. Au moins 7 facteurs de transcription de la famille T-box coopèrent au sein de ces nombreuses sous-populations de progéniteurs cardiogéniques afin de réguler la morphogenèse et l’agencement de multiples structures le long de l’ébauche cardiaque, ce qui explique que les mutations humaines de ces gènes engendrent diverses malformations congénitales cardiaques (MCCs). L’un de ces gènes T-box, Tbx5, dont l’haploinsuffisance génère le syndrome de Holt-Oram (SHO), intervient dans une grande variété de réseaux de régulation géniques (RRGs) qui orchestrent la morphogenèse des oreillettes, du ventricule gauche, de la valve mitrale, des septums inter-auriculaire et inter-ventriculaire, ainsi que du système de conduction cardiaque. La diversité des RRGs impliqués dans la formation de ces structures cardiaques suggère que Tbx5 détient une profusion de fonctions qui ne seront identifiables qu’en répertoriant ses activités moléculaires dans chaque lignée cardiaque examinée isolément. Afin d’aborder cette problématique, une ablation génétique de Tbx5 dans l’endocarde a été réalisée. Cette expérience a démontré le rôle crucial de Tbx5 dans la survie des cellules endocardiques bordant le septum primum et des cardiomyocytes au sein de cette structure embryonnaire qui contribuera à la morphogenèse du septum inter-auriculaire. En outre, cette étude a révélé l’existence d’une communication croisée entre la sous-population de cellules endocardiques Tbx5+ et le myocarde au niveau du septum primum, afin d’assurer la survie des cardiomyocytes, et ultimement de garantir la maturation du septum inter-auriculaire. Nos résultats confirment aussi l’importance de l’interdépendance génétique (Tbx5 et Gata4 ainsi que Tbx5 et Nos3) entre différents loci dans la morphogenèse de la cloison inter-auriculaire, et particulièrement de l’influence que peut avoir l’environnement sur la pénétrance et l’expressivité des communications inter-auriculaires (CIAs) dans le SHO. En outre, puisque les fonctions d’un gène dépendent ordinairement des différents isoformes qu’il peut générer, une deuxième étude a focalisé davantage sur l’aspect transcriptionnel de Tbx5. Cette approche a mené à la découverte de 6 transcrits alternatifs exhibant des fonctions à la fois communes et divergentes. La caractérisation de 2 de ces isoformes a révélé le rôle de l’isoforme long (Tbx5_v1) dans la régulation de la croissance des cardiomyocytes durant la cardiogénèse, tandis que l’isoforme court (Tbx5_v2), préférentiellement exprimé dans le cœur mature, réprime la croissance cellulaire. Il est donc entièrement concevable que les mutations de TBX5 entraînant une troncation de la région C-terminale accroissent la concentration d’une protéine mutée qui, à l’instar de Tbx5_v2, interfère avec la croissance de certaines structures cardiaques. En revanche, la divergence de fonctions de ces isoformes, caractérisée par les disparités de localisation subcellulaire et de d’interaction avec d’autres cofacteurs cardiaques, suggère que les mutations affectant davantage un isoforme favoriseraient l’émergence d’un type particulier de MCC. Finalement, un dernier objectif était d’identifier le ou les mécanisme(s) moléculaire(s) par le(s)quel(s) Tbx5 régule son principal gène cible, Nppa, et d’en extraire les indices qui éclairciraient sa fonction transcriptionnelle. Cet objectif nécessitait dans un premier lieu d’identifier les différents modules cis-régulateurs (MCRs) coordonnant la régulation transcriptionnelle de Nppa et Nppb, deux gènes natriurétiques dont l’organisation en tandem et le profil d’expression durant la cardiogénèse sont conservés dans la majorité des vertébrés. L’approche d’empreinte phylogénétique employée pour scanner le locus Nppb/Nppa a permis d’identifier trois MCRs conservés entre diverses espèces de mammifères, dont un (US3) est spécifique aux euthériens. Cette étude a corroboré que la régulation de l’expression du tandem génique Nppb/Nppa requérait l’activité transcriptionnelle d’enhancers en complément aux promoteurs de Nppa et Nppb. La concordance quasiment parfaite entre les profils d’expression de Tbx5 et de ces deux gènes natriurétiques chez les mammifères, suggère que le gradient d’expression ventriculaire de Tbx5 est interprété par le recrutement de ce facteur au niveau des différents enhancers identifiés. En somme, les études présentées dans cette thèse ont permis de clarifier la profusion de fonctions cardiaques que possède Tbx5. Certaines de ces fonctions émanent de l’épissage alternatif de Tbx5, qui favorise la synthèse d’isoformes dotés de propriétés spécifiques. Les diverses interactions combinatoires entre ces isoformes et d’autres facteurs cardiaques au sein des diverses sous-populations de progéniteurs cardiogènes contribuent à l’émergence de RRGs cardiaques divergents.
The vertebrate heart is a modular organ, which requires the complex patterning of the morphogenetic heart fields and the coordinated convergence of the diverse subpopulations of cardiogenic progenitors. At least 7 transcription factors of the T-box family cooperate within these numerous subpopulations of cardiogenic progenitors to regulate the morphogenesis and the layout of multiple structures along the primordial heart tube, which explains that the human mutations of these genes induce various congenital heart defects (CHDs). One of these T-box genes, Tbx5, whose haploinsufficiency generates the Holt-Oram syndrome (HOS), intervenes in a wide variety of gene regulatory networks (GRNs) that orchestrate the morphogenesis of the atria, the left ventricle, the mitral valve, the inter-atrial and inter-ventricular septa, as well as the cardiac conduction system. The diversity of GRNs involved in the formation of these cardiac structures suggests that Tbx5 holds a profusion of functions which will be identifiable only by indexing its molecular activities in each separately examined cardiac lineage. To address this problem, a conditional knockout of Tbx5 in the endocardium was generated. This experiment demonstrated a crucial role of Tbx5 in the survival of the endocardial cells lining the septum primum and the cardiomyocytes within this embryonic structure, which will contribute to the morphogenesis of the inter-atrial septum. Moreover, this study revealed a crosstalk between the Tbx5-positive endocardial cells subpopulation and the myocardium at the level of the septum primum to ensure the survival of cardiomyocytes, and ultimately to guarantee the maturation of the inter-atrial septum. Our results also confirmed the importance of genetic interdependence (Tbx5 and Gata4 as well as Tbx5 and Nos3) between different loci in the morphogenesis of the inter-atrial septum, and particularly the influence that the environment can have on the penetrance and the expressivity of atrial septal defects (ASDs) in the HOS. Besides, since the functions of a gene usually depend on the different isoforms it can generate, a second study focused more on the transcriptional aspect of Tbx5. This approach led to the discovery of 6 alternative transcripts exhibiting both common and specific functions. The characterization of 2 of these isoforms revealed the role of the long isoform (Tbx5_v1) in the regulation of cardiomyocytes growth during cardiogenesis, whereas the short isoform (Tbx5_v2), preferentially expressed in the mature heart, represses cell growth. It is thus entirely conceivable that TBX5 mutations leading to a C-terminal truncation increase the concentration of a mutated protein, which, like Tbx5_v2, interferes with the growth of certain cardiac structures. On the other hand, the divergence of functions of these isoforms, characterized by the disparities of subcellular localization and interaction with other cardiac cofactors, suggests that mutations affecting more one isoform would favor the emergence of a particular type of CHD. Finally, a last objective was to identify one or several molecular mechanism(s) by which Tbx5 regulates its main target gene, Nppa, and to extract clues that might clarify its transcriptional function. This objective required in a first place to identify the various cis-regulatory modules (CRMs) coordinating the transcriptional regulation of Nppa and Nppb, two natriuretic genes whose tandem organization and expression pattern during cardiogenesis are preserved in most vertebrates. The phylogenetic footprint approach employed to scan the Nppb/Nppa locus allowed the identification of three CRMs evolutionary conserved between different mammals species, one of which (US3) is specific to eutherians. This study confirmed that the regulation of the tandem genes Nppb/Nppa required the transcriptional activity of enhancers in complement to Nppa and Nppb promoters. The almost perfect concordance between the expression profiles of Tbx5 and these two natriuretic genes in mammals, suggests that the ventricular expression gradient of Tbx5 is interpreted by the recruitment of this factor to the identified enhancers. Altogether, the studies presented in this thesis allowed clarifying the profusion of Tbx5 cardiac functions. Some of these functions emanate from the alternative splicing of Tbx5, which favors the synthesis of isoforms endowed with specific properties. The diverse combinatorial interactions between these isoforms and other cardiac factors within the various cardiogenic progenitor subpopulations contribute to the emergence of distinct cardiac RRGs.