Les avancées technico-médicales contribuent à l’augmentation de l’espérance de vie des adultes atteints de cardiopathies congénitales (CC). Toutefois, ils sont confrontés à de multiples défis quotidiens, accompagnés d’un important fardeau de détresse émotionnelle. Des variables environnementales et sociales comme les pratiques parentales de surprotection durant l’enfance sont associées à l’anxiété dans la population générale, mais peu d’études ont été réalisées auprès de cette population. Notre étude évalue l’association entre les pratiques parentales perçues (globales ; positives : soins, structure, soutien à l’autonomie ; négative : surprotection) et la variance de la symptomatologie anxieuse, au-delà des facteurs sociodémographiques et de l’historique médico-chirurgical pédiatrique chez les adultes porteurs de cardiopathies congénitales (CC). Cette étude transversale a été menée sur 264 adultes suivis à l’Institut de Cardiologie de Montréal pour une CC. Les symptômes anxieux à l’âge adulte ont été évalués avec l’Hospital Anxiety and Depression Scale, tandis que la perception des pratiques parentales durant l’enfance a été évaluée rétrospectivement à l’aide d’auto-questionnaires validés, à savoir : Parental Bonding Instrument, Perceived Parental Autonomy Support Scale et Multidimensional Parenting Structure Scale. Les informations sociodémographiques et l’historique médico-chirurgical pédiatrique ont été recueillis dans les dossiers médicaux des patients. Des analyses de régression hiérarchique ont été effectuées et démontrent que les pratiques parentales perçues sont associées à l’explication de 9 % de la variance de l’anxiété au-delà des données sociodémographiques et l’historique médico-chirurgical pédiatrique. Les pratiques parentales constituent des cibles potentielles d’intervention visant à améliorer le profil d’anxiété des adultes atteints de CC. / Techno-medical advances are contributing to the increased life expectancy of patients with congenital heart disease. From birth, they face multiple medical, surgical, and daily challenges. This physical condition may be accompanied by a significant burden of emotional distress and poorer psychological health. Environmental and social variables such as overprotective parenting practices during childhood are associated with anxiety in the general population, but little is documented in this population. Our study assesses the association between parenting practices (global; positive: care, structure, autonomy support; negative: overprotection) and variance in anxiety symptomatology, over and above sociodemographic factors and pediatric medical-surgical history in adults with congenital heart disease (CHD). The present cross-sectional study was conducted on 264 adults followed at the Montreal Heart Institute for a diagnosis of CHD. Adult anxiety symptoms were assessed with the Hospital Anxiety and Depression Scale, while perception of childhood parenting practices were assessed retrospectively with validated self-administrated questionnaires, namely: Parental Bonding Instrument, Perceived Parental Autonomy Support Scale, and Multidimensional Parenting Structure Scale. Sociodemographic and pediatric medico-surgical history information were collected from patients' medical files. Hierarchical multiple linear regression analyses were performed, demonstrating that perceived parenting practices explained more variance in anxiety symptoms (9 %) beyond sociodemographic variables and pediatric medico-surgical history. Parenting practices are potential targets for future interventions to prevent the development and maintenance of anxiety symptoms in adults with CHD.

Les malformations cardiaques congénitales (CHM) représentent 28 % de toutes les malformations congénitales majeures et touchent 8 pour 1000 naissances à terme. Elles sont la cause de mortalité et de morbidité non infectieuse la plus fréquente chez les enfants de moins d’une année de vie. Les communications interventriculaires (VSD) forment le sous-type de CHM le plus fréquent et l’aggrégation familiale est extrêmement rare. Le but de cette étude était d’identifier les facteurs génétiques et les régions chromosomiques contribuant aux VSD. Une grande famille ségréguant diverses formes de pathologies septales, incluant des VSD, des anévrysmes du septum interventriculaire (VSA) et des communications interauriculaires (ASD), a été examinées et caractérisées cliniquement et génétiquement. Dix-huit membres de la famille, sur trois générations, ont pu être étudiés. (10 affectés : 4 VSD, 3 VSA, 2 ASD et une tétralogie de Fallot). L’analyse de liaison multipoint paramétrique démontre un logarithme des probabilités maximal (LOD) de 3.29 liant significativement le chromosome 10p15.3-10p15.2 aux traits observés dans cette famille. Le pointage LOD oriente vers une région pauvre en gènes qui a déjà été associée aux malformations du septum interventriculaire, mais qui est distincte de la région du syndrome de DiGeorge de type 2 sur le chromosome 10p. De plus, plusieurs scénarios d’analyse de liaison suggèrent que la tétralogie de Fallot est une phénocopie et qu’elle est donc génétiquement différente des autres pathologies du septum observées dans cette famille. En bref, cette étude associe une forme rare de VSD/VSA au chromosome 10p15 et permet d’étendre le spectre de l’hétérogénéité des pathologies septales. Mots-clés : Malformations cardiaques congénitales, malformations du septum, tétralogie de Fallot, analyse de liaison, chromosome 10p15, génétique moléculaire / Cardiac malformations represents 28 % of all major congenital malformation and affect 8 per 1000 live birth. They are the most frequent cause of non infectious mortality and morbidity in childen of less then 1 year of life. Although ventricular septal defects (VSD) are the most common congenital heart lesion, familial clustering has been described only in rare instances. The aim of this study was to identify genetic factors and chromosomal regions contributing to VSD. A unique, large kindred segregating various forms of septal pathologies—including VSD, ventricular septal aneurysms, and atrial septal defects (ASD)—was ascertained and characterized clinically and genetically. Eighteen family members in three generations could be studied, out of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of Fallot). Parametric multipoint LOD scores reach significance on chromosome 10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor region where deletions have been reported to associate with septal defects, but that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage analysis scenarios suggest that tetralogy of Fallot is a phenocopy and genetically distinct from the autosomal dominant form of septal pathologies observed in this family. This study maps a rare familial form of VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic heterogeneity of septal pathologies. Fine mapping, haplotype construction, and resequencing will provide a unique opportunity to study the pathogenesis of septal defects and shed light on molecular mechanisms of septal development.

Les maladies rares sont définies en Europe par une prévalence inférieure à 1/2 000 cas et représentent plus de 7000 entités différentes dont 80% sont d’origine génétique. La majorité est de début pédiatrique. J’ai réalisé l’étude de cas familiaux rares avec récurrence dans la fratrie de cardiopathies congénitales avec hétérotaxie (défaut de latéralité gauche/droite) d’une part, et de mort subite cardiaque inexpliquée chez le nourrisson ou en période néonatale d’autre part. La stratégie d’identification de gène par séquençage de l’exome au sein de ces familles dans l’hypothèse d’une transmission autosomique récessive a permis d’identifier trois gènes et d’en étudier deux sur le plan fonctionnel dans différents modèles : 1) Perte de fonction de MMP21 et malformations cardiaques congénitales par anomalie de latéralité embryonnaire. MMP21 code pour une métallopeptidase matricielle dont nous démontrons le rôle très spécifique au niveau du nœud embryonnaire sur un modèle poisson zèbre et souris. Ceci ouvre de nouvelles perspectives dans la compréhension des mécanismes moléculaires qui sous-tendent la mise en place de l’asymétrie gauche/droite chez la plupart des vertébrés. De manière intéressante, alors que tous les mammifères ont le cœur latéralisé à gauche, tous n’ont pas un gène MMP21 codant. Il existe donc plusieurs voies de signalisation de l’asymétrie gauche/droite chez les vertébrés. 2) Mutations hypomorphes de PPA2 et mort subite cardiaque chez le nourrisson. PPA2 code pour une pyrophosphatase mitochondriale et les données chez la levure ont montré que la fonction de cette enzyme était essentielle au fonctionnement mitochondrial. Nous décrivons une nouvelle présentation clinique de maladie mitochondriale responsable de décès par arrêt cardiaque inattendu chez le nourrisson. 3) Perte de fonction de PLCD3 et cardiomyopathie foudroyante par apoptose et nécrose diffuse des cardiomyocytes en période néonatale. Ce résultat nécessite encore d’être confirmé par l’identification d’autres cas mais la fonction de la protéine et des données chez la souris sont des arguments majeurs en faveur de la causalité du gène. Au total, ces travaux sont déterminants à la fois sur le plan clinique dans le cadre du conseil génétique pour les familles concernées et sur le plan fondamental en éclairant les mécanismes biologiques de mise en place de l’axe gauche-droit au cours du développement embryonnaire avec MMP21, sur le rôle essentiel de PPA2 dans la mitochondrie et sur celui de PLCD3 dans la survie des cardiomyocytes en postnatal. / Rare diseases are defined in Europe by a prevalence of less than 1/2,000 individuals and represent more than 7,000 different diseases of which 80% are genetic. Most have a paediatric onset. My project involved the study of rare cardiac disorders in familial cases with recurrence in siblings, focusing on congenital heart disease in the context of heterotaxia (laterality defects) and sudden unexpected death due to cardiac arrest in infancy and the neonatal period. Whole exome sequencing was used as a tool for disease gene discovery in these families with the hypothesis of autosomal recessive inheritance. This strategy led to the identification of 3 novel disease genes. I performed functional validation for two of these genes in different models, confirming their involvement in each disease. 1) Loss of function of MMP21 and cardiac malformations due to left-right patterning defects during embryonic development. MMP21 encodes a metallopeptidase for which I demonstrated a highly specialized role in the generation of left-right asymmetry at the node using zebrafish. This gives new insight into the molecular mechanisms at the origin of left-right asymmetry in vertebrates. Interestingly, all mammals have a left-sided heart, but some species have lost the Mmp21 gene, indicating that there are different pathways leading to left-right determination in vertebrates. 2) Hypomorphic mutations in PPA2 cause sudden cardiac arrest in infants. PPA2 is a nuclear gene encoding the mitochondrial pyrophosphatase and using a yeast model we showed that this enzyme is essential for the mitochondrial energy transducing system and biogenesis. I described a novel clinical spectrum for a mitochondrial disease responsible for unexpected cardiac arrest in infancy. 3) PLCD3 loss of function and fatal cardiomyopathy by cardiomyocyte apoptosis and necrosis in neonates. Exome sequencing in one familial case with 2 siblings presenting fatal cardiomyopathy led to the identification of compound heterozygous mutations in PLCD3, a gene previously implicated in a similar pathology in a mouse model. Identification of further cases with mutations in this gene will be needed in order to confirm the role of PLCD3 in the disease. In total, these studies are crucial from a clinical point of view for the genetic counseling of the affected families and they contribute to the elucidation of biological mechanisms of embryonic development and left-right determination (MMP21), mitochondrial function (PPA2) and post-natal cardiomyocyte survival (PLCD3).

Das mit dem kardiopulmonalen Bypass assoziierte kapilläre Leck bei Operationen am offenen Herzen führt zu einem Anstieg des totalen Wassergehalts des Körpers, wobei es vor allem zu einer pulmonalen sowie myokardialen Ödementwicklung kommt. Mit der von Naik, Knight und Elliott (1991) hinsichtlich Filterposition und Filtrationszeitpunkt beschriebenen modifizierten Form der Ultrafiltration unmittelbar nach Abgang vom Bypass konnte eine markante Reduzierung der mit dem Bypass assoziierten Flüssigkeitsakkumulation sowie eine unmittelbare Verbesserung der hämodynamischen Parameter (Herzindex, myokardiale Kontraktilität, verminderter postoperativer Verbrauch inotroper Substanzen) nachgewiesen werden. Ziel vorliegender Studie ist deshalb die Untersuchung der Auswirkung der modifizierten Ultrafiltration auf die Lungenfunktion. Für diese Studie wurden 37 Kinder (Alter 3 Tage bis 92 Monate, Gewicht 3,1 bis 21,3 kg) beobachtet, bei denen die operative Korrektur eines angeborenen Herzfehlers unter Einsatz der Herz-Lungen-Maschine (kardiopulmonaler Bypass mit extrakorporaler Membranoxygenierung) vorgenommen wurde. Bei 27 Kindern wurde nach Abgang von der Herz-Lungen-Maschine die modifizierte Hämofiltration durchgeführt, 10 Kinder dienten als Kontrollgruppe. Bei allen Patienten wurden vor Beginn sowie nach Abschluß des Einsatzes der Herz-Lungen-Maschine, nach der ca. zehn Minuten dauernden modifizierten Ultrafiltration bzw. bei der Kontrollgruppe zu einem vergleichbaren Zeitpunkt ca. zehn Minuten nach Entwöhnung vom kardiopulmonalen Bypass und nach einem weiteren Zeitraum von ca. zehn Minuten mittels dynamischer Lungenfunktionsmessung Parameter der Lungenmechanik (dynamische Compliance und Resistance) sowie Lungenfunktion (alveoloarterielle Sauerstoffdifferenz) bestimmt. Außerdem wurden hämodynamische (arterieller und zentralvenöser Blutdruck) und rheologische Veränderungen (Hämoglobin, Hämatokrit) aufgezeichnet. Bei der modifizierten Ultrafiltration zeigte sich unmittelbar nach Filtrationsende mit dem signifikanten Anstieg der Compliance um 13,9 % ein Effekt, der sich etwa 10 Minuten nach Filtrationsende noch weiter steigerte. Weiterhin konnte ein Abfall der alveoloarteriellen Sauerstoffdifferenz um insgesamt 29,2 % gemessen werden. Es ließ sich jedoch keine proportionale Abhängigkeit zwischen der Ultrafiltratmenge und der Verbesserung der Lungenfunktion nachweisen. Die von anderen Autoren unter modifizierter Ultrafiltration festgestellten Veränderungen der Hämodynamik, wie zum Beispiel der signifikante Anstieg des arteriellen Blutdruckes, oder der rheologischen Veränderungen, wie zum Beispiel ein Anstieg des Hämatokrit-Wertes, ließen sich bestätigen. Die Ergebnisse zeigen, daß durch die modifizierte Technik der Ultrafiltration eine unmittelbare Verbesserung der postoperativen Lungenfunktion erreicht werden kann. / The capillary leak, associated with cardiopulmonary bypass in open heart surgery, causes a rise of total body water resulting in tissue, especially in pulmonary and myocardial edema. The modified ultrafiltration is a new aproach to reduce these edemas, first described by Naik, Knight and Elliot in 1991. With the modification of the postition of the ultrafilter in the bypass circuit and the time of filtration in the first minutes after the patient has been weaned from bypass a significant reduction of the bypass associated fluid accumulation could be shown as well as an improvement of hemodynamics (heart index, myocardial contractility, reduced need of inotopic drugs). To investigate the influence of the modified ultrafiltration on the lung function is the objective of this study. In this study 37 children (aging from 3 days to 92 months, weighting from 3.1 to 21.3 kg) have been examined in cardiac surgery for moderate to severe congenital heart disease with the application of the cardiopulmonary bypass. The effect of modified ultrafiltration, which immediately started after being weaned from the cardiopulmonary bypass, was studied in 27 children, 10 children formed the controll population. In all patients alterations in pulmonary mechanics (dynamic compliance and resistance), in pulmonary function (alveolar-arterial difference of oxygen), in hemodynamics (arterial and central venous blood pressure, heart rate) and in blood values (hemoglobin, hematocrit) could be recorded at frequent intervals. The measurements were done before and after being weaned from bypass, after conclusion of the modified ultrafiltration respectively after a comparable intervall in the control group and about 10 minutes later before the closure of the chest was performed. After the modified ultrafiltration a significant increase of pulmonary compliance of about 13.9 % was observed, an effect, which was further amplified in the next 10 minutes. Furthermore a decrease of alveolar-arterial difference of oxygen of 29.2 % could be shown, but no correlation between the amount of ultrafiltrat and improvement of pulmonary function could be proved. Other findings like a significant increase of arterial blood pressure or an increase of the hematocrit, which were also described by other authors in previous studies, could be confirmed. The results indicate, that by using the modified technique of ultrafiltration an improvement of pulmonary function is achievable.

Hintergrund: Das akute Nierenversagen ist eine häufige Komplikation nach einer Herzoperation bei Neugeborenen, Säuglingen und Kleinkindern. Die Bedeutung der postoperativen Hämodynamik für eine Nierenschädigung ist gut bekannt, jedoch ist der Einfluß des kardiopulmonalen Bypasses und des tiefen hypothermen Kreislaufstillstandes weniger klar. Überdies gibt es Veränderungen der Blutviskosität während und nach der Herzoperation am kardiopulmonalen Bypass, welche die Nierenfunktion beeinflussen können. Aus diesem Grunde wurde der Einfluß der Blutviskosität am kardiopulmonalen Bypass und des tiefen hypothermen Kreislaufstillstandes auf die Nierenfunktion in dieser Patientengruppe untersucht. Methode: Untersucht wurden 44 Patienten mit einem Körpergewicht unter 10 kg, die am kardiopulmonalen Bypass operiert wurden. Von diesen erfolgte die Herzoperation bei 7 Patienten unter zusätzlicher Anwendung des tiefen hypothermen Kreislaufstillstandes. Bei allen Patienten wurden zu verschiedenen Zeitperioden Messungen zur Beschreibung der Nierenfunktion (Diurese, Kreatinin-Clearance und Gesamtprotein, Albumin, alpha-1-Mikroglobulin, Transferrin, IgG, N-Acetyl-beta-D-Glucosaminidase im Urin) und Bestimmungen der Blut- und Plasmaviskosität, der Erythrozytenaggregation und des kolloidosmotischen Druckes durchgeführt. Beide Gruppen wurden hinsichtlich des Einflusses des Kreislaufstillstandes auf die Nierenfunktion miteinander verglichen. Ergebnisse: Die während des kardiopulmonalen Bypasses im Zusammenhang mit einem erhöhten transglomerulären Filtrationsgradienten entstandene Polyurie und Proteinurie normalisierte sich innerhalb von 24 Stunden postoperativ. Die renale Ausscheidung von N-Acetyl-beta-D-Glucosaminidase und die erhöhte Natriumausscheidung zeigten zusätzlich eine tubuläre Schädigung an. Bei Hypothermie hatte die Plasmaviskosität einen deutlichen Einfluß auf die Blutviskosität, die während hypothermer Perfusion mit den im Urin gemessenen Werten von Albumin und N-Acetyl-beta-D-Glucosaminidase korrelierte. Die Patienten in der Kreislaufstillstandsgruppe hatten eine längere Bypasszeit und eine niedrigere minimale Körpertemperatur im Vergleich zu den Patienten ohne Kreislaufstillstand (p < 0,05). Diurese und Kreatinin-Clearance zeigten keine Differenzen zwischen beiden Gruppen. Während der Reperfusion wurde in der Kreislaufstillstandsgruppe signifikant mehr Albumin renal ausgeschieden als in der Vergleichsgruppe, ebenso Albumin und N-Acetyl-beta-D-Glucosaminidase nach dem kardiopulmonalen Bypass (p < 0,01). Schlußfolgerung: Die kardiopulmonale Bypassperfusion könnte eine Proteinurie und einen milden tubulären Schaden verursachen. Die Blutviskosität scheint dafür ein mitbestimmender Faktor zu sein und ist möglicherweise während hypothermer Perfusion wesentlich von der Plasmaviskosität abhängig. Es ist notwendig und wünschenswert anhand einer prospektiven Interventionsstudie den Einfluß der Blut- und Plasmaviskosität auf die postoperative Nierenfunktion zu untersuchen. Der tiefe hypotherme Kreislaufstillstand kann die Empfindlichkeit der Niere für einen Ischämie-Reperfusions-Schaden steigern. Obgleich die Befunde mild sind und keinen schweren ischämischen Nierenschaden anzeigen, sollte der durch den Kreislaufstillstand verursachte potentielle Nierenschaden für die Planung des chirurgischen Eingriffs bei Patienten mit angeborenen Herzfehlern als zusätzliches Risiko für ein akutes Nierenversagen mit in Betracht gezogen werden. / Background: Acute renal failure is a common complication after cardiopulmonary bypass in infants. Whereas it is well known that postoperative hemodynamics inflict acute renal failure, the influence of extracoporeal circulation on the kidney is less clear. Moreover, changes in blood viscosity occur during and after surgery, which may influence renal dysfunction. For this reason, the impact of blood viscosity during cardiopulmonary bypass and circulatory arrest on renal function was investigated. Methods: 44 patients weighting less than 10 kg operated on cardiopulmonary bypass were investigated, inclusive of 7 patients who additionally underwent circulatory arrest. In all patients analyses of renal function (diuresis, creatinine clearance, urinary total protein, albumin, alpha-1-microglobulin, transferrin, IgG, and N-acetyl-beta-D-glucosaminidase), blood, and plasma viscosity measurements, erythrocyte aggregation and colloid osmotic pressure were performed. Both groups were compared with regard to the impact of circulatory arrest on renal function. Results: Polyuria and proteinuria that appeared during cardiopulmonary bypass indicated an elevated transglomerular filtration gradient, which recovered within 24 hours. The appearance of N-acetyl-beta-D-glucosaminidase in the urine and elevated sodium excretion were additionally indicative of mild tubular damage. With hypothermia, plasma viscosity could had a major impact on the blood viscosity, which, during hypothermic perfusion, seemed to be related to proteinuria and N-acetyl-beta-D-glucosaminidase values. The patients of the circulatory arrest group had a longer bypass time and a lower body temperature in compare to the patients without circulatory arrest (p < 0.05). Diuresis and creatinine clearance revealed no differences between both groups. During reperfusion in the circulatory arrest group significantly more albumin were excreted as in the comparison group, likewise albumin and N-acetyl-beta-D-glucosaminidase after cardiopulmonary bypass (p < 0.01). Conclusions: Cardiopulmonary bypass perfusion could cause proteinuria and mild tubular damage. Blood viscosity may be one possible contributing factor, which in hypothermia may depend mainly on plasma viscosity. It is necessary and desirable to investigate the impact of blood, and plasma viscosity on postoperative renal function based on a prospective intervention study. The deep hypothermic circulatory arrest can increase the sensitivity of the kidney to an ischemia-reperfusion injury. Although the findings are mild and do not indicate severe ischemic renal damage, potential renal damage by deep hypothermic circulatory arrest should be taken into account for planning surgical procedures for congenital heart disease patients with additional risks of acute renal failure.

O presente estudo teve como objetivo avaliar se as mães de crianças com cardiopatia congênita utilizam a espiritualidade/religiosidade como estratégia de enfrentamento e se utilizam de forma negativa ou positiva. Também avaliou a qualidade de vida destas mães e suas associações com as estratégias de enfrentamento além das variáveis: idade, estado civil, profissão, primeira cirurgia e já ter realizado outras cirurgias, tempo de internação, conhecimento sobre a data da cirurgia e grau de escolaridade. Foi aplicado um questionário semi estruturado com o objetivo de obter dados referentes à religiosidade/espiritualidade, o instrumento que avalia a qualidade de vida WHOQOL-bref (World Health Organization Quality of Life - versão abreviada) e o instrumento CRE (Coping Religioso Espiritual) que avalia aspectos relacionados à: religiosidade/espiritualidade. A amostra foi composta por 48 mães de crianças portadoras de cardiopatia congênita que encontravam-se internadas aguardando procedimento cirúrgico. O presente estudo demonstrou através dos achados descritos que ser mãe de uma criança portadora de doença crônica, assim como a cardiopatia congênita, é um fato estressante devido às freqüentes internações, mudança na rotina, ansiedade com a cirurgia, medo da perda, entre outros. Estas mães diante desses eventos utilizam estratégias religiosas positivas e que estas estão correlacionadas com qualidade de vida / The present study aimed to evaluate whether mothers of children with congenital heart disease use spirituality or religiosity as a coping strategy and are used negatively or positively. We also evaluated the quality of life of these mothers and their associated coping strategies besides their variables: age, marital status, occupation, first surgery and other surgeries that were already performed, length of stay, knowledge of the date of surgery and schooling . We applied a semi-structured questionnaire in order to obtain data on religiosity or spirituality, the instrument that assesses the quality of life WHOQOL- BREF (World Health Organization Quality of Life - short version) and the instrument CRE (Religious Coping Spiritual) which evaluates aspects related to: religiosity or spirituality. The sample consisted of 48 mothers of children with congenital heart disease who were hospitalized awaiting surgery. The present study demonstrated by the findings reported to be a mother of a child with chronic illness, as well as congenital heart disease, it is a stressful fact due to frequent hospitalizations, change in routine, anxiety with surgery, fear of loss, among others. These mothers before these strategies use positive religious events and these are correlated with the quality of life

Made available in DSpace on 2016-01-26T12:51:50Z (GMT). No. of bitstreams: 1 liliangoraieb_dissert.pdf: 2524026 bytes, checksum: 35df67e734bc16baa9fa59b0adee085f (MD5) Previous issue date: 2005-12-12 / Objective: To evaluate the behavior of the pulmonary compliance and resistance of the airway passage in patients with high blood flow congenital heart disease undergoing surgical treatment with cardiopulmonary bypass. Method: The static pulmonary compliance and the airway resistance were evaluated in 35 patients during the intraoperative period, in four distinct instants: the first, before the thorax opening, with the infants being already anesthetized, under mechanical ventilation; the second, after thorax and pericardium opening, with the retractors in position; the third, five minutes after the end of cardiopulmonary bypass; the forth, after thorax closing. Pulmonary measurements were performed non-invasively by means of the airway occlusion at the end of inspiration, and the use of proper mathematical formula. In different periods, the observed and related variables with the pulmonary changes were: preoperative, the age, weight and systemic and pulmonary blood flow; intraoperative, the perfusion and the anoxia duration and the minimum body temperature; and, postoperative, duration of mechanical ventilatory support and the length of stay in the ICU. Results: At the end of the surgery, the pulmonary compliance showed a significant and immediate increase (P<0.001) in all the patients. Patients over 30-months as well as the ones with weight over 10kg showed greater increase; P=0.0004, P=0.0006, respectively. Patients with 50-minute duration of cardiopulmonary bypass delayed more to present increase of pulmonary compliance (P=0.04). The resistance of the airway passage did not present significant alteration at the end of surgical correction (P=0.393). Conclusion: All the patients presented pulmonary compliance improvement at the end of the surgery. It was influenced significantly by the age, weight and duration of cardiopulmonary bypass; however, the resistance of the airway passage has not changed. / Avaliar o comportamento da complacência pulmonar e resistência da via aérea nos pacientes portadores de cardiopatias congênitas com hiperfluxo pulmonar submetidos a tratamento cirúrgico com auxílio de circulação extracorpórea. Método: Trinta e cinco pacientes foram avaliados com medidas de complacência estática e resistência da via aérea em quatro instantes distintos durante a cirurgia: O primeiro antes da abertura do tórax, com a criança já anestesiada e sob ventilação mecânica. O segundo, após a abertura do tórax e pericárdio, com os afastadores posicionados. O terceiro, cinco minutos após a saída de circulação extracorpórea e o quarto, após o fechamento do tórax. As medidas pulmonares foram feitas de forma não invasiva com o método de oclusão da via aérea ao final da inspiração e uso de fórmulas matemáticas específicas. As variáveis observadas e relacionadas às alterações pulmonares foram: No período pré-operatório, idade, peso e a relação entre fluxo sanguíneo sistêmico e pulmonar, no intra-operatório, tempos de perfusão, de anóxia e temperatura mínima, no pós-operatório, tempo de ventilação mecânica e tempo de permanência na unidade de terapia intensiva. Resultados: A Complacência pulmonar ao final da cirurgia mostrou aumento significativo imediato (P<0,001) em todos os pacientes. Pacientes maiores de 30 meses tiveram maior aumento (P=0,0004). Os com peso superior a 10kg também apresentaram maior aumento (P=0,0006). Pacientes com tempo de circulação extracorpórea maior que 50 minutos demoraram mais para apresentar aumento da complacência pulmonar (P=0,04). A resistência da via aérea não apresentou alteração significativa ao final da correção cirúrgica (P=0,393). Conclusão: A complacência pulmonar apresentou melhora ao final da cirurgia em todos os pacientes, sendo influenciada de forma significativa pela idade, peso e tempo de circulação extracorpórea. A resistência da via aérea, entretanto, não se alterou.

A disfunção microvascular, envolvendo células endoteliais, plaquetas e leucócitos, está presente na hipertensão arterial pulmonar (HAP), associando-se a risco aumentado de trombose e menor sobrevida. Estudos sobre disfunção microvascular são escassos em outras formas da doença que não a idiopática. Os objetivos do estudo foram: caracterizar a disfunção microvascular em diferentes formas de HAP através da dosagem de marcadores bioquímicos, avaliando possíveis correlações com índices de gravidade; investigar os efeitos da administração de rosuvastatina em níveis circulantes de marcadores de disfunção microvascular nesses pacientes; e investigar possível associação entre o nível plasmático dos marcadores e prognóstico. Foram incluídos sessenta pacientes: 14 com HAP idiopática ou hereditária, e 46 com HAP associada a cardiopatia congênita (HAPCCg) sem hipoxemia (N=18) ou com hipoxemia (N=28), com idades entre 13 e 60 anos. Foram dosados os níveis plasmáticos circulantes do antígeno do fator de von Willebrand (vWF:Ag), ativador tecidual do plasminogênio (t-PA); inibidor do ativador do plasminogênio (PAI-1), fator de necrose tumoral (TNF-), proteína C reativa (PCR), selectina-P; interleucina-6 (IL-6); e interleucina-10 (IL -10), na condição basal e após 30, 60 e 180 dias de tratamento, por método imunoenzimático. Após randomização, administrouse placebo (N=30) ou dose única oral diária (10mg) de rosuvastatina (N=30), por seis meses. Dados demográficos e funcionais como idade, distância caminhada em seis minutos, saturação periférica de oxigênio em repouso e após esforço, bem como hematócrito, também foram registrados. Pacientes com HAPCCg foram acompanhados por um período de 0,7 a 4,0 anos (mediana de 3,6 anos). Na condição basal, excetuando-se TNF- e PCR, todas as proteínas apresentaram-se significantemente elevadas em relação aos controles (p<0,001), havendo correlação com índices de gravidade clínica. No estudo com rosuvastatina, houve redução significante nos níveis de selectina-P em relação ao placebo (p=0,037), ao longo do tratamento. Houve melhora na saturação periférica de oxigênio após seis minutos de caminhada, no grupo estatina, em pacientes com HAPCCg com hipoxemia, em relação ao placebo. Considerando-se o período de acompanhamento, em portadores de HAPCCg, níveis plasmáticos persistentemente elevados do vWF:Ag (média de quatro determinações), acima do nível correspondente ao percentil 95 dos controles (139 U/d/L) associaram-se maior risco de morte (razão de risco 6,56, IC 95% 1,46 a 29,4, p=0.014), sem alteração após ajustamento para variáveis demográficas, funcionais e de tratamento, à análise multivariada. Assim, a disfunção microvascular está presente em indivíduos com HAP idiopática, hereditária ou associada a cardiopatias congênitas. Na HAP, o uso crônico de rosuvastatina em dose baixa associase à redução do nível circulante de selectina-P, e propicia aumento na saturação periférica de oxigênio ao final do exercício, em indivíduos com HAPCCg e hipoxemia. Em indivíduos portadores de HAPCCg, níveis plasmáticos persistentemente elevados do vWF:Ag são indicativo de pior prognóstico / Microvascular dysfunction, involving endothelial cells, platelets and leukocytes, is present in pulmonary arterial hypertension (PAH), and is associated to higher risk to thrombotic complications and mortality. Most data about microvascular dysfunction in PAH do not include other forms of the disease beyond idiopathic PAH. The present study was planned to measure plasma levels microvascular dysfunction markers in two different forms of PAH, and investigate possible correlations with indices of severity of the disease; to investigate the effects of chronic rosuvastatin administration versus placebo on the circulating levels of these markers; and to investigate possible associations between levels of these parameters and prognosis. Sixty patients (aged 13 to 60 years) were included, 14 with idiopathic or hereditary PAH, and 46 with congenital heart disease-associated PAH (CHDPAH), in the absence (N=18) or presence (N=28) of hypoxemia. Plasma levels of von Willebrand factor antigen (vWF:Ag), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNF-), reactive C protein (RCP), P-selectin, interleukin-6 (IL- 6), and interleukin-10 (IL-10) were measured before treatment and 30, 90, and 180 days on treatment using high-sensitivity enzyme-linked immunosorbent assay kits. Patients were randomly assigned to placebo (N=30) or a single oral dose of rosuvastatin (N=30), 10mg/day, for six months. Demographic and functional data such as age, six-minute walk distance, peripheral oxygen saturation at rest and at the end of the six-minute walk, as well as the hematocrit, were recorded. Patients with CHDPAH were followed-up for 0.7 to 4.0 years (median 3.6 years). At baseline, levels of all proteins (except TNF- and RCP) were significantly increased in patients versus controls (p<0,001), and correlated significantly with indices of severity of the disease. P-selectin level was lower in the rosuvastatin group compared with placebo throughout the treatment (p = 0.037). In hypoxemic CHDPAH patients, the peripheral oxygen saturation, at the end of the six-minute walk, was higher in the rosuvastatin group, compared with placebo. During the follow-up of patients with CHDPAH, an average vWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was associated with a high risk of death (hazard ratio 6.56, 95% CI 1.46 to 29.4, p=0.014). This was not modified after adjustment for demographic, functional and treatment-related variables in multivariate analysis. In conclusion, microvascular dysfunction is present in individuals with idiopathic, hereditary and the congenital heart disease-associated PAH. The chronic use of low-dose rosuvastatin is associated to reduction of circulating levels of P-selectin. In patients with CHDPAH with hypoxemia, rosuvastatin also increases peripheral oxygen saturation during exercise. In CHDPAH patients, a sustained increase in plasma vWF:Ag is indicative of poor prognosis

Background: The vast majority of infants born with congenital heart disease (CHD) reach adulthood because of the developments in cardiology in recent decades. This thesis aims to describe the psychosocial situation of child/adolescent cardiac patients and their families, investigate the situation faced by parents and siblings initially and over time, investigate the approaches paediatric cardiologists use in encountering the family, and describe the teamwork occurring in paediatric cardiology teams (PCTs) in Sweden. Theoretical framework: The theoretical framework was based on a quality of life model applied to children, a stress-coping model, and a psychosocial approach including support, profession, and teamwork. Methods: The research combines quantitative data collection/analysis and qualitative research interviews/content analysis. Results: Complexity: The three grades of medical complexity differed regarding the number and severity of psychosocial symptoms, the children with the most complex CHD having the most severe symptoms. The most frequent symptoms in the whole patient group regarding various spheres were: healthcare and treatment-related needs in the external sphere, family symptoms in the interpersonal sphere, and mental/psychosomatic symptoms in the personal sphere. Coping: Being informed of a child’s/sibling’s heart disease has emotional consequences, so information, communication, and support are essential. Breaking the news of a child’s disease can be described as a turning point still significant after ten years. The professionalism of the doctor’s approach in breaking the news is crucial. Profession: Among paediatric cardiologists, how to break bad news to a family is an important concern, evident in findings regarding the significance of trust and confidence and the use of various emotional positions. Paediatric cardiologists commonly wish to be skilled at handling this situation, and attaining the needed skills calls for reflection, education, and sharing experience. Team: PCTs in Sweden aim and try to work in a structured way. In PCTs, there is a need for leadership, resource coordination, coaching, and a forum for joint reflection. Dependence on the physician on the team was identified in all PCTs. The challenge of managing increasing complexity at both the family and system levels requires interprofessional teams. Conclusions: These studies illustrate the psychosocial complexity and the need of psychosocial support. Emotional consequences, communication, information and support are essential both for the children, parents/families and for the professionals. To manage this complexity organizational alteration action plans are required. There is a need for a forum to stimulate dialogue and common reflection in the local PCT and at the regional and national centres.

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