Background: Children with complex congenital heart disease (CHD) are exposed to cyanosis from birth until their surgical repair and are often not expected to participate in physical activities to the same extent as healthy peers because of a limited maximal exercise capacity (V̇O2max). Despite limitations in V̇O2max, these children may still have the capacity to perform most daily physical activity because it requires only a submaximal effort. The purpose of this research was to examine the relationships between submaximal exercise capacity, daily physical activity and cyanosis exposure, in children with complex CHD. Methods: Children with a single functioning ventricle (Fontan), tetralogy of Fallot or transposition of the great arteries, 10 to 17 years old were deemed eligible. The Bruce treadmill protocol with breath-by-breath analysis of oxygen consumption was used to assess submaximal exercise capacity. Five measures of submaximal exercise capacity were evaluated: energy consumption (V̇O2) at the ventilatory threshold, V̇O2 at a heart rate of 130 beats per minute (bpm), metabolic equivalents (METs) at ventilatory threshold, METs at 130 bpm and heart rate at stage 1 of the Bruce protocol. Moderate-to vigorous physical activity (MVPA) was measured (Actical accelerometer with 15 second epochs) for 7 consecutive days. Exposure to cyanosis was calculated by subtracting the child’s date of birth from the date of surgical repair. Results: Participants were children with a Fontan single ventricle (n=5), tetralogy of Fallot (n=4) or transposition of the great arteries (n=7). Daily physical activity was positively associated with V̇O2 at ventilatory threshold (r = 0.78, n = 16, p = < 0.01) and V̇O2 at a heart rate of 130 bpm (r = 0.61, n = 16, p = 0.01). Children who did more than 60 minutes of physical activity per day (n=4) achieved significantly higher energy expenditure before reaching ventilatory threshold, (95% CI of the difference [8.23, 24.85], t(14) = 4.27, p = < 0.01) and at a heart rate of 130 bpm (95% CI of the difference [1.61, 14.33], t(14) = 2.69, p = 0.02). Lastly, V̇O2 at ventilatory threshold was negatively associated with days spent in cyanosis (r = .55, n = 16, p = 0.03), Conclusion: Higher V̇O2 at ventilatory threshold and V̇O2 at a heart rate of 130 bpm was associated with more daily minutes spent in moderate-to-vigorous physical activity. These results suggest that children who meet the recommended 60 minutes of MVPA would have a higher submaximal exercise capacity (V̇O2 at ventilatory threshold or a heart rate of 130 bpm), than children who did not meet the MVPA guidelines. Lastly, children who were exposed to cyanosis for a longer period of time had a lower submaximal V̇O2 at ventilatory threshold, than children who were exposed to cyanosis for a shorter period of time.

BACKGROUND: Understanding the hemodynamics of the total cavopulmonary connection (TCPC) may lead to further optimization of the connection design and surgical planning, which in turn may lead to improved surgical outcome. While most experimental and numerical investigations have mainly focused on somewhat simplified geometries, the investigation of the flow field of true TCPC configurations is necessary for a true understanding. METHODS: This study details a manufacturing methodology yielding more accurate in vitro models that would provide a better understanding of the TCPC hemodynamics and adequate data for the validation of anatomical CFD simulations. This approach is illustrated on two different TCPC templates: an intra-atrial TCPC with a single superior vena cava (SVC) and a bilateral SVC with an extra-cardiac conduit. Power loss, flow visualization, digital particle image velocimetry (DPIV) flow measurements as well as computational fluid dynamics simulations are performed to characterize the anatomic flow structure. Additional parametric glass models of the TCPC were manufactured to help understand the fluid dynamics of the anatomical models and support the computational model validation effort. RESULTS/CONCLUSIONS: Both anatomic configurations revealed very different fluid dynamics underlining once again the need for at least one comprehensive experimental campaign per TCPC template for a good understanding of the flow phenomena. The absence of caval offset in the anatomical intra-atrial model resulted in important flow turbulence, which was enhanced by the large connection area and yielded high pressure drops and power losses. On the other hand, the bilateral SVC, which featured a smooth extra-cardiac conduit and wider vessels, led to power losses that were one order of magnitude lower than those of the anatomic intra-atrial model and a smooth flow field with lower levels of instability. The simplified glass models demonstrated that the diameter of the connecting vessels and of the pulmonary arteries in particular, was a parameter of prime importance. Finally, this study also reports on a combined experimental and numerical validation methodology, suggesting a cautious approach for the straightforward use of available CFD tools and pointing out the need for developing high resolution CFD techniques specifically tailored to tackle the complexities of cardiovascular flows.

No description available.

Les cœurs univentriculaires sont des cardiopathies congénitales, non compatibles avec la vie. Fontan a transformé le pronostic de ces patients en restaurant une circulation pulmonaire passive. Malheureusement, le pronostic à long terme reste péjoratif. Pour diminuer la morbi-mortalité de ces patients, nous avons développé un protocole chirurgical de pré-conditionnement, permettant une totalisation de Fontan percutanée adaptative aux résistances pulmonaires et aux capacités de travail du ventricule. Nous avons pu observer que les chaînes respiratoires mitochondriales n’ont pas la possibilité d’adapter leur production énergétique face au travail. Le déséquilibre de la balance Nitroso-Redox engendrera le mitohormésis et l’hormésis, puis inéluctablement surviendra un remodelage myocardique mal adaptatif. La seule possibilité pour améliorer le pronostic à long terme de ces patients sera d’augmenter les capacités oxydatives myocardiques du ventricule unique ou de créer une pompe pulmonaire. / Univentricular hearts are congenital heart diseases, not compatible with life. Fontan transformed the prognosis of these patients by restoring a passive pulmonary circulation. Unfortunately, the long-term prognosis remains pejorative. To reduce the morbidity and mortality of these patients, we developed a surgical preconditioning protocol, allowing a percutaneous Fontan totalization, adaptive to pulmonary resistance and to the working capacity of the ventricle. We observed that the mitochondrial respiratory chains do not have the ability to adapt their energy production toward work. The desequilibrium of the Nitroso-redox balance will generate mitohormesis and hormesis, then will inevitably occur a poorly adaptive myocardial remodeling. The only way to improve the long-term prognosis of these patients is to increase the myocardial oxidative capacities of the single ventricle or to create a pulmonary pump.

Estudo prospectivo e randomizado de 30 pacientes, submetidos a derivação cavopulmonar total com tubo extracardíaco. Os dados refletem o período de 2008 a 2011, com seguimento de dois anos, por meio de avaliação clínica, laboratorial, ecocardiográfica, angiotomográfica e cintilográfica. Neste estudo, procuramos comparar a eficácia do ácido acetil salicílico (AAS) e da Varfarina na profilaxia da trombose na população estudada. Para tanto, analisamos alterações nos fatores de coagulação (VII, VIII e Proteína C ); ou nos dados clínicos que predispusessem a ocorrência de trombo no pós-operatório. Além disso, no pós-operatório, após a randomização (15 pacientes randomizados para receber Varfarina, Grupo I, e 15 pacientes randomizados para receber AAS, Grupo II), estudamos a interferência da fenestração na ocorrência de trombo; alterações hemodinâmicas que pudessem contribuir com a ocorrência de trombo (fluxo lento pelo tubo extracardíaco), por meio de ecocardiograma transesofágico realizado com até 10 dias de pós operatório, 3, 6, 12 e 24 meses de pós operatório. A presença do fenômeno tromboembólico era pesquisada, além dos ecocardiogramas acima citados, por meio de consultas clínicas realizadas com a mesma periodicidade e que avaliavam, ainda, efeitos colaterais ou complicações no uso de cada uma das drogas. Avaliamos também a viabilidade e aderência ao uso de cada uma delas. O seguimento contou igualmente com a realização de angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo, bem como trombos e cintilografia pulmonar, ventilação-perfusão para avaliar possível tromboembolismo pulmonar. Durante o seguimento, ocorreram dois óbitos, ambos no grupo em uso de Varfarina. Ao todo, durante os dois anos de seguimento, 33,3% dos pacientes apresentaram fenômeno tromboembólico. Sendo que, entre os paciente em uso de AAS, 46,7% apresentaram tal complicação e 20% entre os pacientes em uso de Varfarina (p=0,121). Com relação a avaliação pré-operatória, a ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo de sobrevida livre de trombo, com valores de p de 0,035 e 0,047 respectivamente. Ao final de dois anos de seguimento, na avaliação angiotomográfica, 35,7% dos pacientes em uso de AAS tinham material hiper-refringente depositado em tubo extracardíaco com espessura superior a 2mm ( p= 0,082). Já na avaliação por cintilografia de ventilação-perfusão, dois pacientes apresentaram sinais de tromboembolismo pulmonar, ambos em uso de AAS (p=0,483), e um deles com evolução desfavorável do circuito tipo Fontan. Com relação a segurança e aderência ao tratamento, cinco pacientes tiveram dificuldade de aderência (só viabilizada por tratar-se de protocolo de estudo), entre eles, quatro em uso de Varfarina e apresentando INR variando de 1 a 6,4. Para comprovação numérica, com força estatística dos dados encontrados, uma força tarefa deve ocorrer para que se consiga um grupo maior de pacientes incluídos neste estudo. No entanto, a diferença entre os dois grupos na evolução livre de trombo nos dois primeiros anos de pós-operatório não pode, e nem deve, ser ignorada / Prospective randomized trial of 30 patients who had undergone total cavopulmonary anastomosis via an extracardiac conduit. The data reflect the period between 2008 and 2011, with two-year follow-up, through clinical, laboratorial, echocardiographic, angiotomographic, and scintigraphic assessment. In this study, we aimed to compare the efficiency of ASA (Aspirin) and Warfarin in the preventive treatment of thrombosis in the tried population. For such, we\'ve analyzed changes in coagulation factors (VII, VIII and Protein C) or in the clinical data which would predispose the occurrence of postoperative thrombus. Moreover, during postoperative care, after randomization (15 patients randomly selected to be trated with Warfarin, referred to as Group I, and 15 patients randomly selected to be treated with ASA, referred to as Group II), we also studied the influence of fenestration in the occurrence of thrombus; hemodynamic variations which could contribute to the occurrence of thrombus (slow blood flow in the extracardiac conduit), with postoperative transesophageal echocardiogram being performed within 10 days, and thereafter 3, 6, 12 and 24 months. Besides the echocardiograms aforementioned, the presence of thromboembolic events was sought after by clinical appointments taking place with the same frequency, which evaluated, apart from thromboembolism, side effects or complications from the usage of each of the drugs. We\'ve also evaluated the compliance to and feasibility of each of them. Postoperative angiotomography was also performed during the follow-up, within 6, 12 and 24 months, for the evaluation of changes on the inside wall of the extracardiac conduit, as well as thrombi, and pulmonary ventilation/perfusion scintigraphy for assessment of pulmonary thromboembolism possibility. During the follow-up, two deaths were registered, both in the group being treated with Warfarin. Overall, in the two-year follow-up, 33,3% of the patients presented thromboembolic events. Among the group being treated with ASA, 46,7% presented such complication, whereas in the group being treated with Warfarin, 20% had the same complication (p=0,121). Regarding the preoperative evaluation, prior occurrence of thrombus and low levels of coagulation factor Protein C were the only variables which influenced living time without thrombus, with p-values of 0,035 and 0,047. At the end of the two-year follow-up, in the angiotomographic evaluation, 35,7% of patients treated with ASA presented material accumulation inside the extracardiac conduit, with over 2mm of thickness (p=0,082). As for the ventilation/perfusion scintigraphy, two patients presented traces of pulmonary thromboembolism, both treated with ASA (p=0,483), one of whom with unfavorable development of the Fontan circuit. Concerning safety and compliance to the treatment, five patients had difficulty to comply with the treatment (only viable for its trial nature), among those, four under treatment with Warfarin and presenting INR values ranging from 1 to 6,4. For quantitative verification, providing statistic value to the data, an effort must be made for a larger number of patients to be gathered and tried with this treatment. However, the difference in results concerning thrombus-free recovery between the two groups during the two years following surgery cannot, and must not, be ignored

INTRODUCÃO: A cirurgia de Fontan ou conexão cavo-pulmonar total é o último procedimento de uma estratégia estadiada, empregada no tratamento de cardiopatias congênitas complexas com ventrículo único anatômico ou funcional (também chamada de cardiopatia congênita com coração univentricular). Pacientes com um único ventrículo, situação incompatível com a vida, passaram a sobreviver até a idade adulta após a realização dessa cirurgia. A conexão direta da cavas com as artérias pulmonares, exclui do sistema circulatório o ventrículo subpulmonar, criando nesses indivíduos uma circulação do tipo univentricular. A falta do ventrículo subpulmonar e a subsequente ausência de fluxo sanguíneo pulsátil no pulmão, reduz o volume de enchimento do ventrículo único e consequentemente, o débito cardíaco. Mecanismos adaptativos do sistema periférico são desencadeados para garantir uma adequada redistribuição do fluxo sanguíneo para órgãos vitais, porém não são suficientes para garantir uma capacidade funcional adequada nesses indivíduos. Acreditamos que, uma análise detalhada dessas alterações e seus respectivos mecanismos adaptativos, possam contribuir na avaliação e entendimento dessa complexa fisiologia. A interferência nos componentes relacionados a baixa capacidade física, poderiam em teoria, modificar a história natural da doença nesses indivíduos, submetidos a cirurgia de Fontan. OBJETIVOS: 1. Comparar variáveis do sistema cardiovascular, pulmonar e músculo esquelético de pacientes com idade entre 12 e 30 anos, submetidos a cirurgia de Fontan com 5 anos ou mais de evolução pós-operatória com indivíduos saudáveis. 2. Correlacionar variáveis do sistema cardiovascular, pulmonar e músculo esquelético com a capacidade funcional no grupo de pacientes com cirurgia de Fontan. 3. Identificar as variáveis preditoras de baixa capacidade funcional nesta população. MÉTODOS: Estudo transversal, tipo caso-controle. Foram incluídos 30 pacientes no Grupo Fontan (GF) e 27 indivíduos saudáveis, que compuseram o grupo controle (GC). Os indivíduos foram submetidos à ressonância magnética cardiovascular, ecodopplercardiografia, teste de esforço cardiopulmonar, prova de função pulmonar completa, microneurografia direta no nervo fibular, pletismografia de oclusão venosa, dosagem plasmática de catecolaminas e peptídeo natriurético cerebral, teste de caminhada de seis minutos, espectroscopia de fósforo por ressonância magnética do quadríceps femoral, imagem musculoesquelética por ressonância magnética da musculatura da coxa e avaliação da qualidade de vida pelo questionário SF-36 (Short-Form Health Survey). Foram realizadas análises comparativas entre os grupos nos diferentes sistemas e posteriormente, testes para identificar os preditores de baixa capacidade funcional no GF. RESULTADOS: O consumo máximo de oxigênio (VO2 pico) no GF foi menor comparada ao GC, em valores absolutos, relativo ao peso corpóreo e em porcentagem do predito para sexo e idade. [1,65 (±0,54) vs 2,81 (±0,77) L/min p < 0,001]; [29,3 (±6,0) vs 41,5 (±9,2) mL/kg/min p < 0,001] e [70 (±14) vs 100% do predito (±20) p < 0,001] respectivamente. Os volumes e capacidades pulmonares foram significativamente menores no GF comparados ao GC, e demonstraram correlação positiva com o VO2 absoluto [capacidade vital forçada (CVF) r=0,836 p < 0,001; capacidade pulmonar total (CPT) r=0,730 p < 0,001 e capacidade de difusão do monóxido de carbono (DLCO) r=0,539 p=0,002], mas foram preditores de baixa capacidade funcional, a CVF (Constante= -0,306; B=0,393; IC=0,272-0,513 e p<0,001) e a DLCO (Constante= - 0,306; B=0,042; IC= 0,018-0,067; e p=0,002). O diâmetro da artéria pulmonar esquerda, também foi identificado como preditor de baixo VO2 (Constante=0,274; B=0,111; IC=0,061-0,161 e p < 0,001). E pela análise de periférica, a área seccional transversa da musculatura da coxa foi significativamente menor no GF, demonstrando ser mais um preditor de baixa capacidade funcional nesta população (Constante: 0,380; B=0,024; IC=0,018-0,030; p < 0,001). A atividade nervosa simpática muscular foi maior no GF [30 (±4) vs 22 (±3) disparos/min p < 0,001] e o fluxo sanguíneo muscular menor [1,59 (±0,3) vs 2,17 (±0,5) mL/min/100mL p < 0,001] comparados ao GC, porém estas variáveis não foram preditoras de baixa capacidade funcional. Em relação ao metabolismo oxidativo muscular, o GF apresentou menor amplitude de pico da fosfocreatina comparado ao GC [0,43 (0,41-0,45) vs 0,45 (0,42-0,50) p=0,023]. Porém essas alterações não se correlacionaram com o VO2 pico. CONCLUSÕES: Concluímos que a função pulmonar, o controle neurovascular e a capacidade funcional de pacientes com ventrículo único funcional, clinicamente estáveis, encontram-se comprometidas quando comparadas com indivíduos saudáveis. O menor diâmetro da artéria pulmonar esquerda, a capacidade vital forçada diminuída, a capacidade de difusão do monóxido de carbono comprometida e a área seccional transversa da musculatura da coxa reduzida foram os preditores de baixa capacidade funcional na população estudada / BACKGROUND: The Fontan operation or total cavo-pulmonary connection is the last procedure of a staged strategy, performed to treat complex congenital heart diseases in patients with a functional or anatomic single ventricle, also known as a univentricular heart. After the inception of the Fontan procedure, patients are surviving to adulthood due this remarkable technique. This operation, creates a direct connection of the superior and inferior vena cava with the pulmonary arteries, excluding the subpulmonary ventricle of the circulatory system an univentricular circulation. The lack of a subpulmonary ventricle and subsequent absence of pulsatile blood flow in the lungs, reduce the filling volume of the single ventricle and consequently the cardiac output. Although some adaptive mechanisms at the peripheral system are triggered to ensure an adequade blood flow to vital organs, they are not enough for an adequate functional capacity in these patients. A detailed analysis and evaluation of these changes and their respective mechanisms may contribute to understand this complex physiology. Hopefully, it might be possible to modify and improve the long term outcomes of these individuals. The aims of the study were: 1. To compare the variables of the cardiovascular, pulmonary and musculoskeletal systems in clinically stable Fontan patients with a control group. 2. To correlate the variables of the cardiovascular, pulmonary and skeletal muscle with the functional capacity in Fontan patients. 3. To identify predictors of low functional capacity in this population. METHODS: A prospective cross-sectional study of 30 FP of (20 +/- 6 years) and 10 (8-15) years of follow-up and 27 healthy controls (HC) (22 +/- 5years) was performed. They underwent cardiovascular magnetic resonance, echocardiography, cardiopulmonary exercise test, complete lung function, catecholamine and B-type natriuretic peptide (BNP) plasmatic levels, microneurography, venous occlusion plethismography, six-minute walk test, phosphorus magnetic resonance spectroscopy (31P MRS) and magnetic resonance imaging (MRI) of skeletal muscle and quality of life (QoL) using the Short Form Health Survey (SF36). Comparative analyzes of the different systems of two groups were done as well as tests to identify the predictors of low functional capacity in Fontan groups (FG). RESULTS: The maximal oxygen consumption (VO2) in the FG was lower compared to control group (CG), in absolute values, relative to body weight and percentage predicted for gender and age [1,65 (±0,54) vs 2,81 (±0,77) L/min p < 0,001]; [29,3 (±6,0) vs 41,5 (±9,2) mL/kg/min p < 0,001] e [70 (±14) vs 100% of the predicted value (±20) p < 0,001] respectively. Pulmonary volumes and capacities were also significantly lower in FG compared to CG, and demonstrated a positive correlation with absolute peak VO2 [Forced vital capacity (FVC) r=0,836 p < 0,001; total lung capacity (TLC) r=0,730 p < 0,001 and carbon monoxide diffusion capacity (DLCO) r=0,539 p=0,002]. But, the FVC and DLCO were predictors of reduced VO2 (Constant= -0,306; B=0,393; CI=0,272-0,513 e p < 0,001) and (Constant= -0,306; B=0,042; CI=0,018-0,067; e p=0,002) respectively. The diameter of the left pulmonary artery was also other of the predictors of low functional capacity (Constant=0,274; B=0,111; CI=0,061-0,161 e p < 0,001). Analyzing the volume of the thigh muscles, a significant difference between the groups was found, and the transversal sectional area of this muscle was a predictor of low functional capacity (Constant: 0,380; B=0,024; CI=0,018-0,030; p < 0,001). Muscle sympathetic nerve activity was higher in FG [30 (±4) vs 22 (±3) burst/min p < 0,001] and forearm blood flow was lower [1,59 (±0,3) vs 2,17 (±0,5) mL/min/100mL p < 0,001] compared with CG, however, these variables were not predictive of low functional capacity. Muscle oxidative metabolism showed difference in the intracellular pH value and the peak amplitude of phosphocreatine between the groups. The peak amplitude of phosphocreatine was lower in FG compared CG [0,43 (0,41-0,45) vs 0,45 (0,42-0,50) p=0,023] however, there were no correlation with the functional capacity. CONCLUSIONS: Pulmonary function, neurovascular control and functional capacity of clinically stable Fontan patients were impaired when compared to healthy subjects. Lower diameter of the left pulmonary artery, decreased forced vital capacity, impaired carbon monoxide diffusion capacity, and reduced transverse sectional area of the thigh musculature were the predictors of low functional capacity in the study population

INTRODUCÃO: A cirurgia de Fontan ou conexão cavo-pulmonar total é o último procedimento de uma estratégia estadiada, empregada no tratamento de cardiopatias congênitas complexas com ventrículo único anatômico ou funcional (também chamada de cardiopatia congênita com coração univentricular). Pacientes com um único ventrículo, situação incompatível com a vida, passaram a sobreviver até a idade adulta após a realização dessa cirurgia. A conexão direta da cavas com as artérias pulmonares, exclui do sistema circulatório o ventrículo subpulmonar, criando nesses indivíduos uma circulação do tipo univentricular. A falta do ventrículo subpulmonar e a subsequente ausência de fluxo sanguíneo pulsátil no pulmão, reduz o volume de enchimento do ventrículo único e consequentemente, o débito cardíaco. Mecanismos adaptativos do sistema periférico são desencadeados para garantir uma adequada redistribuição do fluxo sanguíneo para órgãos vitais, porém não são suficientes para garantir uma capacidade funcional adequada nesses indivíduos. Acreditamos que, uma análise detalhada dessas alterações e seus respectivos mecanismos adaptativos, possam contribuir na avaliação e entendimento dessa complexa fisiologia. A interferência nos componentes relacionados a baixa capacidade física, poderiam em teoria, modificar a história natural da doença nesses indivíduos, submetidos a cirurgia de Fontan. OBJETIVOS: 1. Comparar variáveis do sistema cardiovascular, pulmonar e músculo esquelético de pacientes com idade entre 12 e 30 anos, submetidos a cirurgia de Fontan com 5 anos ou mais de evolução pós-operatória com indivíduos saudáveis. 2. Correlacionar variáveis do sistema cardiovascular, pulmonar e músculo esquelético com a capacidade funcional no grupo de pacientes com cirurgia de Fontan. 3. Identificar as variáveis preditoras de baixa capacidade funcional nesta população. MÉTODOS: Estudo transversal, tipo caso-controle. Foram incluídos 30 pacientes no Grupo Fontan (GF) e 27 indivíduos saudáveis, que compuseram o grupo controle (GC). Os indivíduos foram submetidos à ressonância magnética cardiovascular, ecodopplercardiografia, teste de esforço cardiopulmonar, prova de função pulmonar completa, microneurografia direta no nervo fibular, pletismografia de oclusão venosa, dosagem plasmática de catecolaminas e peptídeo natriurético cerebral, teste de caminhada de seis minutos, espectroscopia de fósforo por ressonância magnética do quadríceps femoral, imagem musculoesquelética por ressonância magnética da musculatura da coxa e avaliação da qualidade de vida pelo questionário SF-36 (Short-Form Health Survey). Foram realizadas análises comparativas entre os grupos nos diferentes sistemas e posteriormente, testes para identificar os preditores de baixa capacidade funcional no GF. RESULTADOS: O consumo máximo de oxigênio (VO2 pico) no GF foi menor comparada ao GC, em valores absolutos, relativo ao peso corpóreo e em porcentagem do predito para sexo e idade. [1,65 (±0,54) vs 2,81 (±0,77) L/min p < 0,001]; [29,3 (±6,0) vs 41,5 (±9,2) mL/kg/min p < 0,001] e [70 (±14) vs 100% do predito (±20) p < 0,001] respectivamente. Os volumes e capacidades pulmonares foram significativamente menores no GF comparados ao GC, e demonstraram correlação positiva com o VO2 absoluto [capacidade vital forçada (CVF) r=0,836 p < 0,001; capacidade pulmonar total (CPT) r=0,730 p < 0,001 e capacidade de difusão do monóxido de carbono (DLCO) r=0,539 p=0,002], mas foram preditores de baixa capacidade funcional, a CVF (Constante= -0,306; B=0,393; IC=0,272-0,513 e p<0,001) e a DLCO (Constante= - 0,306; B=0,042; IC= 0,018-0,067; e p=0,002). O diâmetro da artéria pulmonar esquerda, também foi identificado como preditor de baixo VO2 (Constante=0,274; B=0,111; IC=0,061-0,161 e p < 0,001). E pela análise de periférica, a área seccional transversa da musculatura da coxa foi significativamente menor no GF, demonstrando ser mais um preditor de baixa capacidade funcional nesta população (Constante: 0,380; B=0,024; IC=0,018-0,030; p < 0,001). A atividade nervosa simpática muscular foi maior no GF [30 (±4) vs 22 (±3) disparos/min p < 0,001] e o fluxo sanguíneo muscular menor [1,59 (±0,3) vs 2,17 (±0,5) mL/min/100mL p < 0,001] comparados ao GC, porém estas variáveis não foram preditoras de baixa capacidade funcional. Em relação ao metabolismo oxidativo muscular, o GF apresentou menor amplitude de pico da fosfocreatina comparado ao GC [0,43 (0,41-0,45) vs 0,45 (0,42-0,50) p=0,023]. Porém essas alterações não se correlacionaram com o VO2 pico. CONCLUSÕES: Concluímos que a função pulmonar, o controle neurovascular e a capacidade funcional de pacientes com ventrículo único funcional, clinicamente estáveis, encontram-se comprometidas quando comparadas com indivíduos saudáveis. O menor diâmetro da artéria pulmonar esquerda, a capacidade vital forçada diminuída, a capacidade de difusão do monóxido de carbono comprometida e a área seccional transversa da musculatura da coxa reduzida foram os preditores de baixa capacidade funcional na população estudada / BACKGROUND: The Fontan operation or total cavo-pulmonary connection is the last procedure of a staged strategy, performed to treat complex congenital heart diseases in patients with a functional or anatomic single ventricle, also known as a univentricular heart. After the inception of the Fontan procedure, patients are surviving to adulthood due this remarkable technique. This operation, creates a direct connection of the superior and inferior vena cava with the pulmonary arteries, excluding the subpulmonary ventricle of the circulatory system an univentricular circulation. The lack of a subpulmonary ventricle and subsequent absence of pulsatile blood flow in the lungs, reduce the filling volume of the single ventricle and consequently the cardiac output. Although some adaptive mechanisms at the peripheral system are triggered to ensure an adequade blood flow to vital organs, they are not enough for an adequate functional capacity in these patients. A detailed analysis and evaluation of these changes and their respective mechanisms may contribute to understand this complex physiology. Hopefully, it might be possible to modify and improve the long term outcomes of these individuals. The aims of the study were: 1. To compare the variables of the cardiovascular, pulmonary and musculoskeletal systems in clinically stable Fontan patients with a control group. 2. To correlate the variables of the cardiovascular, pulmonary and skeletal muscle with the functional capacity in Fontan patients. 3. To identify predictors of low functional capacity in this population. METHODS: A prospective cross-sectional study of 30 FP of (20 +/- 6 years) and 10 (8-15) years of follow-up and 27 healthy controls (HC) (22 +/- 5years) was performed. They underwent cardiovascular magnetic resonance, echocardiography, cardiopulmonary exercise test, complete lung function, catecholamine and B-type natriuretic peptide (BNP) plasmatic levels, microneurography, venous occlusion plethismography, six-minute walk test, phosphorus magnetic resonance spectroscopy (31P MRS) and magnetic resonance imaging (MRI) of skeletal muscle and quality of life (QoL) using the Short Form Health Survey (SF36). Comparative analyzes of the different systems of two groups were done as well as tests to identify the predictors of low functional capacity in Fontan groups (FG). RESULTS: The maximal oxygen consumption (VO2) in the FG was lower compared to control group (CG), in absolute values, relative to body weight and percentage predicted for gender and age [1,65 (±0,54) vs 2,81 (±0,77) L/min p < 0,001]; [29,3 (±6,0) vs 41,5 (±9,2) mL/kg/min p < 0,001] e [70 (±14) vs 100% of the predicted value (±20) p < 0,001] respectively. Pulmonary volumes and capacities were also significantly lower in FG compared to CG, and demonstrated a positive correlation with absolute peak VO2 [Forced vital capacity (FVC) r=0,836 p < 0,001; total lung capacity (TLC) r=0,730 p < 0,001 and carbon monoxide diffusion capacity (DLCO) r=0,539 p=0,002]. But, the FVC and DLCO were predictors of reduced VO2 (Constant= -0,306; B=0,393; CI=0,272-0,513 e p < 0,001) and (Constant= -0,306; B=0,042; CI=0,018-0,067; e p=0,002) respectively. The diameter of the left pulmonary artery was also other of the predictors of low functional capacity (Constant=0,274; B=0,111; CI=0,061-0,161 e p < 0,001). Analyzing the volume of the thigh muscles, a significant difference between the groups was found, and the transversal sectional area of this muscle was a predictor of low functional capacity (Constant: 0,380; B=0,024; CI=0,018-0,030; p < 0,001). Muscle sympathetic nerve activity was higher in FG [30 (±4) vs 22 (±3) burst/min p < 0,001] and forearm blood flow was lower [1,59 (±0,3) vs 2,17 (±0,5) mL/min/100mL p < 0,001] compared with CG, however, these variables were not predictive of low functional capacity. Muscle oxidative metabolism showed difference in the intracellular pH value and the peak amplitude of phosphocreatine between the groups. The peak amplitude of phosphocreatine was lower in FG compared CG [0,43 (0,41-0,45) vs 0,45 (0,42-0,50) p=0,023] however, there were no correlation with the functional capacity. CONCLUSIONS: Pulmonary function, neurovascular control and functional capacity of clinically stable Fontan patients were impaired when compared to healthy subjects. Lower diameter of the left pulmonary artery, decreased forced vital capacity, impaired carbon monoxide diffusion capacity, and reduced transverse sectional area of the thigh musculature were the predictors of low functional capacity in the study population

Estudo prospectivo e randomizado de 30 pacientes, submetidos a derivação cavopulmonar total com tubo extracardíaco. Os dados refletem o período de 2008 a 2011, com seguimento de dois anos, por meio de avaliação clínica, laboratorial, ecocardiográfica, angiotomográfica e cintilográfica. Neste estudo, procuramos comparar a eficácia do ácido acetil salicílico (AAS) e da Varfarina na profilaxia da trombose na população estudada. Para tanto, analisamos alterações nos fatores de coagulação (VII, VIII e Proteína C ); ou nos dados clínicos que predispusessem a ocorrência de trombo no pós-operatório. Além disso, no pós-operatório, após a randomização (15 pacientes randomizados para receber Varfarina, Grupo I, e 15 pacientes randomizados para receber AAS, Grupo II), estudamos a interferência da fenestração na ocorrência de trombo; alterações hemodinâmicas que pudessem contribuir com a ocorrência de trombo (fluxo lento pelo tubo extracardíaco), por meio de ecocardiograma transesofágico realizado com até 10 dias de pós operatório, 3, 6, 12 e 24 meses de pós operatório. A presença do fenômeno tromboembólico era pesquisada, além dos ecocardiogramas acima citados, por meio de consultas clínicas realizadas com a mesma periodicidade e que avaliavam, ainda, efeitos colaterais ou complicações no uso de cada uma das drogas. Avaliamos também a viabilidade e aderência ao uso de cada uma delas. O seguimento contou igualmente com a realização de angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo, bem como trombos e cintilografia pulmonar, ventilação-perfusão para avaliar possível tromboembolismo pulmonar. Durante o seguimento, ocorreram dois óbitos, ambos no grupo em uso de Varfarina. Ao todo, durante os dois anos de seguimento, 33,3% dos pacientes apresentaram fenômeno tromboembólico. Sendo que, entre os paciente em uso de AAS, 46,7% apresentaram tal complicação e 20% entre os pacientes em uso de Varfarina (p=0,121). Com relação a avaliação pré-operatória, a ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo de sobrevida livre de trombo, com valores de p de 0,035 e 0,047 respectivamente. Ao final de dois anos de seguimento, na avaliação angiotomográfica, 35,7% dos pacientes em uso de AAS tinham material hiper-refringente depositado em tubo extracardíaco com espessura superior a 2mm ( p= 0,082). Já na avaliação por cintilografia de ventilação-perfusão, dois pacientes apresentaram sinais de tromboembolismo pulmonar, ambos em uso de AAS (p=0,483), e um deles com evolução desfavorável do circuito tipo Fontan. Com relação a segurança e aderência ao tratamento, cinco pacientes tiveram dificuldade de aderência (só viabilizada por tratar-se de protocolo de estudo), entre eles, quatro em uso de Varfarina e apresentando INR variando de 1 a 6,4. Para comprovação numérica, com força estatística dos dados encontrados, uma força tarefa deve ocorrer para que se consiga um grupo maior de pacientes incluídos neste estudo. No entanto, a diferença entre os dois grupos na evolução livre de trombo nos dois primeiros anos de pós-operatório não pode, e nem deve, ser ignorada / Prospective randomized trial of 30 patients who had undergone total cavopulmonary anastomosis via an extracardiac conduit. The data reflect the period between 2008 and 2011, with two-year follow-up, through clinical, laboratorial, echocardiographic, angiotomographic, and scintigraphic assessment. In this study, we aimed to compare the efficiency of ASA (Aspirin) and Warfarin in the preventive treatment of thrombosis in the tried population. For such, we\'ve analyzed changes in coagulation factors (VII, VIII and Protein C) or in the clinical data which would predispose the occurrence of postoperative thrombus. Moreover, during postoperative care, after randomization (15 patients randomly selected to be trated with Warfarin, referred to as Group I, and 15 patients randomly selected to be treated with ASA, referred to as Group II), we also studied the influence of fenestration in the occurrence of thrombus; hemodynamic variations which could contribute to the occurrence of thrombus (slow blood flow in the extracardiac conduit), with postoperative transesophageal echocardiogram being performed within 10 days, and thereafter 3, 6, 12 and 24 months. Besides the echocardiograms aforementioned, the presence of thromboembolic events was sought after by clinical appointments taking place with the same frequency, which evaluated, apart from thromboembolism, side effects or complications from the usage of each of the drugs. We\'ve also evaluated the compliance to and feasibility of each of them. Postoperative angiotomography was also performed during the follow-up, within 6, 12 and 24 months, for the evaluation of changes on the inside wall of the extracardiac conduit, as well as thrombi, and pulmonary ventilation/perfusion scintigraphy for assessment of pulmonary thromboembolism possibility. During the follow-up, two deaths were registered, both in the group being treated with Warfarin. Overall, in the two-year follow-up, 33,3% of the patients presented thromboembolic events. Among the group being treated with ASA, 46,7% presented such complication, whereas in the group being treated with Warfarin, 20% had the same complication (p=0,121). Regarding the preoperative evaluation, prior occurrence of thrombus and low levels of coagulation factor Protein C were the only variables which influenced living time without thrombus, with p-values of 0,035 and 0,047. At the end of the two-year follow-up, in the angiotomographic evaluation, 35,7% of patients treated with ASA presented material accumulation inside the extracardiac conduit, with over 2mm of thickness (p=0,082). As for the ventilation/perfusion scintigraphy, two patients presented traces of pulmonary thromboembolism, both treated with ASA (p=0,483), one of whom with unfavorable development of the Fontan circuit. Concerning safety and compliance to the treatment, five patients had difficulty to comply with the treatment (only viable for its trial nature), among those, four under treatment with Warfarin and presenting INR values ranging from 1 to 6,4. For quantitative verification, providing statistic value to the data, an effort must be made for a larger number of patients to be gathered and tried with this treatment. However, the difference in results concerning thrombus-free recovery between the two groups during the two years following surgery cannot, and must not, be ignored

This research utilizes CFD to analyze blood flow through pathways representative of central shunts, commonly used as part of the Fontan procedure to treat cyanotic heart disease. In the first part of this research, a parametric study of steady, Newtonian blood flow through parabolic pathways was performed to demonstrate the effect that flow pathway curvature has on wall shear stress distribution and flow energy losses. In the second part, blood flow through two shunts obtained via biplane angiograms is simulated. Pressure boundary conditions were obtained via catheterization. Results showed that wall shear stresses were of sufficient magnitude to initiate platelet activation, a precursor for thrombus formation. Steady results utilizing time-averaged boundary conditions showed excellent agreement with the time-averaged results obtained from pulsatile simulations. For the points of interest in this research, namely wall shear stress distribution and flow energy loss, the Newtonian viscosity model was found to yield acceptable results.

Single Ventricle congenital heart defects with cyanotic mixing between systemic and pulmonary circulations afflict 2 per 1000 live births. The total cavo-pulmonary connection (TCPC), where the superior and inferior vena cavae are sutured to the left and right pulmonary arteries, is the current procedure of choice. It is believed that reducing the fluid mechanical power losses in the TCPC will relieve strain on the single functional ventricle. It is hypothesized that a proposed idealized TCPC design, decreases power losses to a level below that of any other TCPC designs, while providing other advantages and increased flexibility. Physical models with slightly different geometries of the proposed design were created, and in vitro experiments carried out with particle image velocimetry (PIV), phase contrast magnetic resonance imaging (PC-MRI), and control volume flow analysis at physiological flow rates. Computational fluid dynamics (CFD) was used for numerical studies of the same geometries as in the physical models. Power losses were calculated using the control volume method and the viscous power dissipation function. The latter method incorporated registration of high-resolution PC-MRI velocity vectors to tetrahedral meshes followed by inverse interpolation of the vectors onto the meshes. Detailed flow structures were analyzed. Results show that the new design is more energy efficient than any other idealized models. Furthermore, a tool was developed to extract flow and vessel information from PC-MRI datasets obtained from patients with Fontan connections. The tool utilized a display algorithm, which was developed for optimal noise detection in PC-MRI images. This enabled accurate segmentation. Comparing PC-MRI images before and after this accurate segmentation showed that the standard deviations of the pixels at the perimeter of the segmented vessel were statistically significantly smaller after the segmentation in 94.1% of the datasets investigated. The developed tool was able to extract flow, flow in the quadrants of vessels, area of the segmented vessel, velocities and pulsatility indices. The velocity vectors were exported for use as CFD boundary conditions in models reconstructed from patient anatomies. A database was created with patient PC-MRI data from approximately 140 patients, which is probably the largest database in the world.