<p>Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. </p><p>Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.</p><p>Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.</p><p>A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.</p><p>Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.</p>

Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease. Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor. A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions. Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

Acute occlusion of the superior mesenteric artery (SMA) is a condition associated with high mortality and morbidity. The aim of this thesis is to evaluate diagnostic and therapeutic approaches for acute SMA occlusion. In a prospective study of patients with suspected intestinal ischemia, no biomarker was sufficiently accurate to detect this condition. In a second retrospective study, pancreatic amylase and troponin-I were elevated in a substantial proportion of patients with verified SMA occlusion. In an experimental animal model of acute SMA occlusion, microarray studies of ischemic small bowel wall were used to characterize the mRNA response to ischemia. Thrombospondin, Monocyte Chemoattractant Protein 1 and Gap Junction Alpha 1 were consistently up-regulated in all pigs with intestinal ischemia. Genes encoding previously proposed biomarkers for intestinal ischemia were either up-regulated, such as lactate dehydrogenase and creatine kinase, or down-regulated, such as intestinal fatty acid binding protein and glutathione S-transferase. In a study of the role of computed tomography in the diagnosis of SMA occlusion, it was shown that computed tomography with intravenous contrast was associated with improved survival. A retrospective analysis of all acute SMA revascularizations in Sweden 1999-2006 revealed that D-dimer was elevated in all 35 measured cases.  Endovascular surgery was associated with better outcome than open surgery, both in short and in long term. The presence of postoperative short bowel syndrome was a strong independent risk-factor for decreased long-term survival. Conclusions: Data affirm that D-dimer may serve as an exclusion test for acute SMA occlusion, whereas elevated troponin-I and pancreatic amylase are potential diagnostic pitfalls. Contrast-enhanced computed tomography of the visceral arteries seems to be the best diagnostic method. Endovascular surgery is an option to open surgery in selected cases, and was associated with favourable outcome.

Introdução: O miocárdio não compactado (MNC) é uma cardiomiopatia rara, cujas principais manifestações clínicas são insuficiência cardíaca, embolias e arritmias. A evolução desses pacientes é pouco conhecida. Dessa forma, o objetivo desse estudo é analisar o seguimento tardio de pacientes com MNC isolado ou associado a outras doenças, adultos e crianças com a doença, e de seus familiares, que foram acompanhados em hospital universitário de cardiologia, bem como avaliar os desfechos clínicos e de exames de imagem em cardiologia nesses pacientes. Métodos: Pacientes com diagnóstico de MNC confirmado por critérios ecocardiográficos e/ou ressonância magnética cardíaca (RMC) foram selecionados. Durante seu acompanhamento, foram convocados familiares de primeiro, segundo e terceiro graus para rastreamento da doença. Foram avaliados os seguintes desfechos: óbito, transplante cardíaco, eventos embólicos como acidente vascular cerebral (AVC) isquêmico, tromboembolismo pulmonar, embolia arterial periférica, internações hospitalares por insuficiência cardíaca (IC), ocorrência arritmias ventriculares complexas, e índices de exame de imagem como eletrocardiograma, Holter 24 horas, ecocardiograma transtorácico e RMC, que poderiam apresentar valor prognóstico nesses pacientes. Crianças (idade inferior a 12 anos) foram analisadas separadamente. Resultados: Foram acompanhados 215 pacientes com MNC, idade de 36,96 + 17,6 anos, 108 (50,2%) homens, que foram seguidos por 5,9 + 4,47 anos. Os pacientes foram divididos em 2 grupos: 193 com MNC isolado (Grupo 1) e 22 com MNC misto (associado a doenças genéticas, congênitas, doença de Chagas, coronariopatia, cardiomiopatia hipertrófica e miocardite de células gigantes; Grupo 2). A palpitação foi o sintoma clínico mais frequente, estando presente em 42,8% deles. A sobrevida foi menor nos pacientes do Grupo 2, nos que apresentaram FE do ventrículo esquerdo (VE) menor que 50% (p= 0,004), naqueles com aumento dos diâmetro e volume diastólicos finais do VE (p=0,018 e 0,017, respectivamente), com aumento do diâmetro do átrio esquerdo (p < 0,001), com disfunção diastólica do VE (p= 0,049), com disfunção sistólica do ventrículo direito (p= 0,003), nos que apresentaram internações hospitalares (p < 0,001), nos com eventos embólicos (p= 0,022), com arritmias ventriculares complexas (p= 0,010), com hipertensão arterial pulmonar pelo ecocardiograma (p < 0,001) . A ocorrência de FA foi estatisticamente significativa entre os pacientes com disfunção sistólica do VE (p= 0,0485) e todos os que apresentaram FA, tinham FEVE inferior a 40% (p= 0,048). Vinte e três pacientes eram crianças, seguidos por 4,41 ± 4,91 anos, idade média de 5,52 ± 3,62 anos, 12 (52,2%) do sexo masculino. A proporção de óbitos ou transplante cardíaco foi 3 vezes maior do que na população adulta (34,8%) e a IC foi o resultado mais comum. As arritmias cardíacas foram raras e os eventos embólicos não foram encontrados neste grupo. O rastreio familiar diagnosticou MNC em 36,7% dos pacientes. Na análise multivariada, a precocidade dos sintomas e a ocorrência de acidente vascular cerebral ou acidente isquêmico transitório foram os fatores mais importantes no prognóstico dos pacientes e capazes de predizer sobrevida (p < 0,001 e p= 0,008, respectivamente). Conclusão: O seguimento clínico e por métodos de imagens cardíacas por longo período de pacientes com MNC permite traçar um perfil dessa população e estimar o risco de complicações, reforçando a necessidade de diagnóstico e tratamento precoces. Em crianças, o MNC geralmente evolui de forma mais agressiva, com maior morbi-mortalidade. O rastreamento familiar consiste em uma ferramenta muito importante nesse contexto, permitindo a identificação de pacientes na fase subclínica da doença / Background: Non-compaction cardiomyopathy (NCC) is a rare disease, which main clinical manifestations are heart failure, arrhythmias and embolic events. The evolution of these patients is poorly known. Thus, the aims of this study was to analyze the late follow-up of patients with isolated NCC or associated with other diseases, adult and children with the disease and their relatives, which were followed at a university cardiology hospital, and to evaluate the clinical and the cardiology imaging outcomes in these patients. Methods: Patients with NCC confirmed by echocardiographic (echo) and / or cardiac magnetic resonance imaging (CMRI) criteria were selected. During their follow-up, their first, second and third degree relatives were recruited to perform screening of the disease using echo. The following variables were included: death, cardiac transplantation, embolic events such as stroke, pulmonary embolism, peripheral arterial embolism, hospital admissions for heart failure, complex ventricular arrhythmias, and imaging indexes of imaging exams such as electrocardiogram, Holter 24 hours, echocardiogram and CMRI, which could have prognostic value in these patients. Children (under 12 years old) were analyzed separately. Results: Two hundred and fifteen patients with NCC were followed for 5.9 ± 4.47 years, mean age of 36,96 ±17,6 years, 108 (50.2%) males. Patients were divided into 2 groups: 193 with isolated NCC (Group 1) and 22 with mixed NCC (associated with genetic and congenital diseases, Chagas disease, coronary disease, hypertrophic cardiomyopathy and giant cell myocarditis; Group 2). Palpitation was the most frequent clinical symptom, present in 42,8% of them. The survival rate was lower in Group 2 patients (p < 0.05), left ventricular (LV) ejection fraction (EF) less than 50% (p= 0.004), increased LV end-diastolic diameter and volume by echo (p= 0.018 and 0.017, respectively), with LV diastolic dysfunction (p= 0.049), with increased left atrium dimensions (p < 0,001), with right ventricular systolic dysfunction (p= 0.003), hospital admissions (p < 0.001), embolic events (p= 0.022), complex ventricular arrhythmias (p = 0.010) and pulmonary hypertension by echo (p < 0.001). All patients with isolated NCC and AF presented LVEF less than 0.40, and between patients without AF, only 41.7% presented LVEF less than 0.40 (p = 0.048). Twenty-three patients was children, followed for 4.41 ± 4.91 years, mean age of 5.52 ± 3.62 years, 12 (52.2%) males. The proportion of deaths or cardiac transplantation was 3 times higher than in the adult population (34,8%) and heart failure was the most common outcome. Cardiac arrhythmias were rare, and the embolic events were not found in this group. The familiar screening diagnosed NCC in 36.7% of the patients. In the multivariate analysis, the precocity of the symptoms and the occurrence of stroke or transient ischemic attack were the most important factors in the prognosis of this patients and it is able to predict survival (p < 0.001 and p= 0.008, respectively). Conclusion: The clinical and cardiac imaging methods allows us to draw a profile of this population and to estimate the risk of complications, emphasizing the need for early diagnosis and treatment. In children, NCC used to develop more severe disease. Family screening is a very important tool, allowing the identification of patients with subclinical stage of the disease

Introdução: O miocárdio não compactado (MNC) é uma cardiomiopatia rara, cujas principais manifestações clínicas são insuficiência cardíaca, embolias e arritmias. A evolução desses pacientes é pouco conhecida. Dessa forma, o objetivo desse estudo é analisar o seguimento tardio de pacientes com MNC isolado ou associado a outras doenças, adultos e crianças com a doença, e de seus familiares, que foram acompanhados em hospital universitário de cardiologia, bem como avaliar os desfechos clínicos e de exames de imagem em cardiologia nesses pacientes. Métodos: Pacientes com diagnóstico de MNC confirmado por critérios ecocardiográficos e/ou ressonância magnética cardíaca (RMC) foram selecionados. Durante seu acompanhamento, foram convocados familiares de primeiro, segundo e terceiro graus para rastreamento da doença. Foram avaliados os seguintes desfechos: óbito, transplante cardíaco, eventos embólicos como acidente vascular cerebral (AVC) isquêmico, tromboembolismo pulmonar, embolia arterial periférica, internações hospitalares por insuficiência cardíaca (IC), ocorrência arritmias ventriculares complexas, e índices de exame de imagem como eletrocardiograma, Holter 24 horas, ecocardiograma transtorácico e RMC, que poderiam apresentar valor prognóstico nesses pacientes. Crianças (idade inferior a 12 anos) foram analisadas separadamente. Resultados: Foram acompanhados 215 pacientes com MNC, idade de 36,96 + 17,6 anos, 108 (50,2%) homens, que foram seguidos por 5,9 + 4,47 anos. Os pacientes foram divididos em 2 grupos: 193 com MNC isolado (Grupo 1) e 22 com MNC misto (associado a doenças genéticas, congênitas, doença de Chagas, coronariopatia, cardiomiopatia hipertrófica e miocardite de células gigantes; Grupo 2). A palpitação foi o sintoma clínico mais frequente, estando presente em 42,8% deles. A sobrevida foi menor nos pacientes do Grupo 2, nos que apresentaram FE do ventrículo esquerdo (VE) menor que 50% (p= 0,004), naqueles com aumento dos diâmetro e volume diastólicos finais do VE (p=0,018 e 0,017, respectivamente), com aumento do diâmetro do átrio esquerdo (p < 0,001), com disfunção diastólica do VE (p= 0,049), com disfunção sistólica do ventrículo direito (p= 0,003), nos que apresentaram internações hospitalares (p < 0,001), nos com eventos embólicos (p= 0,022), com arritmias ventriculares complexas (p= 0,010), com hipertensão arterial pulmonar pelo ecocardiograma (p < 0,001) . A ocorrência de FA foi estatisticamente significativa entre os pacientes com disfunção sistólica do VE (p= 0,0485) e todos os que apresentaram FA, tinham FEVE inferior a 40% (p= 0,048). Vinte e três pacientes eram crianças, seguidos por 4,41 ± 4,91 anos, idade média de 5,52 ± 3,62 anos, 12 (52,2%) do sexo masculino. A proporção de óbitos ou transplante cardíaco foi 3 vezes maior do que na população adulta (34,8%) e a IC foi o resultado mais comum. As arritmias cardíacas foram raras e os eventos embólicos não foram encontrados neste grupo. O rastreio familiar diagnosticou MNC em 36,7% dos pacientes. Na análise multivariada, a precocidade dos sintomas e a ocorrência de acidente vascular cerebral ou acidente isquêmico transitório foram os fatores mais importantes no prognóstico dos pacientes e capazes de predizer sobrevida (p < 0,001 e p= 0,008, respectivamente). Conclusão: O seguimento clínico e por métodos de imagens cardíacas por longo período de pacientes com MNC permite traçar um perfil dessa população e estimar o risco de complicações, reforçando a necessidade de diagnóstico e tratamento precoces. Em crianças, o MNC geralmente evolui de forma mais agressiva, com maior morbi-mortalidade. O rastreamento familiar consiste em uma ferramenta muito importante nesse contexto, permitindo a identificação de pacientes na fase subclínica da doença / Background: Non-compaction cardiomyopathy (NCC) is a rare disease, which main clinical manifestations are heart failure, arrhythmias and embolic events. The evolution of these patients is poorly known. Thus, the aims of this study was to analyze the late follow-up of patients with isolated NCC or associated with other diseases, adult and children with the disease and their relatives, which were followed at a university cardiology hospital, and to evaluate the clinical and the cardiology imaging outcomes in these patients. Methods: Patients with NCC confirmed by echocardiographic (echo) and / or cardiac magnetic resonance imaging (CMRI) criteria were selected. During their follow-up, their first, second and third degree relatives were recruited to perform screening of the disease using echo. The following variables were included: death, cardiac transplantation, embolic events such as stroke, pulmonary embolism, peripheral arterial embolism, hospital admissions for heart failure, complex ventricular arrhythmias, and imaging indexes of imaging exams such as electrocardiogram, Holter 24 hours, echocardiogram and CMRI, which could have prognostic value in these patients. Children (under 12 years old) were analyzed separately. Results: Two hundred and fifteen patients with NCC were followed for 5.9 ± 4.47 years, mean age of 36,96 ±17,6 years, 108 (50.2%) males. Patients were divided into 2 groups: 193 with isolated NCC (Group 1) and 22 with mixed NCC (associated with genetic and congenital diseases, Chagas disease, coronary disease, hypertrophic cardiomyopathy and giant cell myocarditis; Group 2). Palpitation was the most frequent clinical symptom, present in 42,8% of them. The survival rate was lower in Group 2 patients (p < 0.05), left ventricular (LV) ejection fraction (EF) less than 50% (p= 0.004), increased LV end-diastolic diameter and volume by echo (p= 0.018 and 0.017, respectively), with LV diastolic dysfunction (p= 0.049), with increased left atrium dimensions (p < 0,001), with right ventricular systolic dysfunction (p= 0.003), hospital admissions (p < 0.001), embolic events (p= 0.022), complex ventricular arrhythmias (p = 0.010) and pulmonary hypertension by echo (p < 0.001). All patients with isolated NCC and AF presented LVEF less than 0.40, and between patients without AF, only 41.7% presented LVEF less than 0.40 (p = 0.048). Twenty-three patients was children, followed for 4.41 ± 4.91 years, mean age of 5.52 ± 3.62 years, 12 (52.2%) males. The proportion of deaths or cardiac transplantation was 3 times higher than in the adult population (34,8%) and heart failure was the most common outcome. Cardiac arrhythmias were rare, and the embolic events were not found in this group. The familiar screening diagnosed NCC in 36.7% of the patients. In the multivariate analysis, the precocity of the symptoms and the occurrence of stroke or transient ischemic attack were the most important factors in the prognosis of this patients and it is able to predict survival (p < 0.001 and p= 0.008, respectively). Conclusion: The clinical and cardiac imaging methods allows us to draw a profile of this population and to estimate the risk of complications, emphasizing the need for early diagnosis and treatment. In children, NCC used to develop more severe disease. Family screening is a very important tool, allowing the identification of patients with subclinical stage of the disease

[pt] O processo de tratamento de tumores por embolização vascular é sensível ao conjunto de partículas poliméricas empregado, ditos agentes embólicos, cujos fatores como tamanho e morfologia influenciam no sucesso do procedimento e podem ocasionar complicações quando mal dimensionados. Partículas esféricas de poli(acetato de vinila-co-metacrilato de metila) apresentam a maioria das características desejadas após tratamento por hidrólise alcalina. Este material é relativamente novo, o que significa que há uma lacuna de conhecimento em relação ao estudo dos fenômenos que regem sua cinética. Dessa forma, o presente trabalho investigou a cinética de copolimerização responsável pela sua produção. No desenvolvimento matemático, o método dos momentos foi utilizado assumindo estado quase-estacionário para as espécies radicalares. Além disso, o modelo considera difusão das moléculas no meio para contabilização dos efeitos viscosos, comumente determinados empiricamente. Constatou-se que as características físicas dos monômeros, assim como os parâmetros cinéticos da homopolimerização, puderam ser utilizados na copolimerização. Entretanto, como relatado na literatura para outros sistemas, os efeitos viscosos se comportam de forma consideravelmente diferente na copolimerização, sendo necessário a reestimação de alguns parâmetros relativos aos mesmos. Assim, foi possível reproduzir de forma adequada perfis de conversão, massas molares médias e composição do copolímero. Concluiu-se que o modelo proposto é capaz de representar a cinética da copolimerização em suspensão do poli(acetato de vinila-co-metacrilato de metila), possibilitando um melhor controle das características do copolímero aplicado ao procedimento de embolização vascular. Até onde se tem conhecimento, este é o primeiro trabalho que investiga e implementa com sucesso a modelagem cinética desse sistema. / [en] The treatment of vascularized tumors through vascular embolization is sensible to the polymeric particles used during procedure. These embolic agents have attributes, like size and morphology, which play a significant role on the success of this technique and can promote complications when not well dimensioned. Among the many options available, spherical particles of poly(vinyl acetate-co-methyl methacrylate) present most desired characteristics after alkalyne hydrolysis treatment. Being relatively new, the literature lack studies related to the kinetics of production of this material. Therefore, this research investigated the copolymerization kinetics of poly(vinyl acetate-co-methyl methacrylate) production. In the mathematical development, the method of moments was used assuming quasi-steady state for the free radical species. Additionally, the model includes the viscous effects through the diffusion of the involved molecules, which is usually accounted empirically. It was possible to use the physical properties of the monomers as well as the homopolymerization kinetic parameters in the copolymerization. However, as reported in the literature, some parameters are sensible to the system and some viscous effects affect the copolymerization differently. Therefore, some parameters were reestimated. It was possible to predict the conversion, average molecular weights and composition. Consequently, the model was capable of representing the kinetics of the suspension copolymerization of poly(vinyl acetate-co-methyl methacrylate), meaning it could be used to improve the production of this polymer as an embolic agent for vascular embolization procedure. As far as known by the author, this is the first study to successfully perform the kinetic modeling of this specific system.