Background: We reviewed our experience using the Amplatzer septal occluder (AGA Medical, Golden Valley, MN) to close large, secundum-type atrial septal defects (ASDs) in children. Methods: Between June 2002 and December 2005, 52 patients (mean age 13.5 ¡Ó 8.7 years) underwent transcatheter closure of large (≥25 mm), secundum ASDs by using the Amplatzer septal occluder (ASO). Groups 1 and 2 included patients with a retroaortic rim of <5 mm (n = 39) or ≥5 mm(n = 13), respectively. All procedures were performed with general anesthesia and transesophageal echocardiographic guidance except for 10 patients, which involved local anesthesia and 3-dimensional transthoracic echocardiography. Successful device implantations, device sizes, approaches, complications, and closure rates were assessed. Results: Device implantation was successful in 50 patients (96.1%), with no difference between groups (95% vs 100%, P > 0.05). In 2 patients, implantation failed because of embolism or deployment failure. Devices were larger in group 1 than in group 2 (29.7 ¡Ó 3.9 vs 26.7 ¡Ó 3.0 mm, P =0.04). The right upper pulmonary-vein approach was more common in group 1 than in group 2 (P = .0001). Complications and closure rates did not differ between the groups (P > .05). Conclusions: Transcatheter closure of large, secundum ASD by using the ASO device was feasible, and complication rates were low. A deficient retroaortic rim did not preclude successful device implantation; however, a large device may be needed to close large ASD. Close long-term follow-up is necessary to determine the safety of transcatheter closure of large ASDs in children.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成4年10月19日 狩野良雄氏の博士論文として提出された

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 ¡Ó 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; R&#x00B2;=0.9861 ), and between TTE size and ASO size ( y = 1.3412x-1.2864; R&#x00B2;=0.9929 ) in group 1. In group 2, statistical correlation between TTE and ASO ( y=1.3419x-0.1172; R&#x00B2;=0.9934 ) was also found. Good linear regression between TTE size and ASO chosen size was noted in group 1 and group 2 (R&#x00B2;=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.

No description available.

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.

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.

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.

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.

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.