Background: The Framingham Study from 1991 showed a clear correlation between atrial fibrillation (AF) and ischemic stroke, where patients with AF had an almost fivefold increase in risk of stroke compared with patients without AF. Since then, several trials have evaluated different antithrombotic treatments to reduce the risk of stroke in patients with AF. Other trials have investigated factors that increase the risk of stroke in patients with AF and risk score systems have been developed to categorize patients into low or increased risk of stroke to help clinicians to decide which patients benefit from antithrombotic treatment and in whom it can be abstained, not to expose patients with low stroke risk to an increased risk of bleeding conferred by antithrombotic treatment. The aims of this thesis were: [1] to evaluate if a warfarin dosing algorithm can increase hit rate and decrease mean error compared with manually changed doses; [2] to assess the prevalence and net clinical benefit of aspirin as monotherapy for stroke prevention in AF; [3] to investigate the risk of thromboembolic and haemorrhagic complications within 30 days after electrical cardioversion (ECV) of AF in patients with and without oral anticoagulation (OAC) pre-treatment; and [4] to assess the proportion of patients discontinuing OAC after pulmonary vein isolation (PVI), identify factors predicting stroke after PVI and to investigate risk of complications after PVI with and without OAC. Materials and methods: All studies are retrospective and based on data from Swedish national quality registries. In paper I, data from Auricula was used to compare the resulting INR values after algorithmic warfarin dose suggestions and manually changed doses. In paper II data was extracted from the Swedish National Patient Register, the Dispensed Drugs Register and the Cause of Death Register. Patients with aspirin treatment were compared with patients without any antithrombotic treatment regarding risk of thromboembolic and haemorrhagic complications. In paper III data was collected from the Swedish National Patient Register and the Dispensed Drugs Register to examine risk of complications (thromboembolic and haemorrhagic events) within 30 days after cardioversion, comparing patients with and without oral anticoagulation pre-treatment. In paper IV data from six different Swedish national quality registries were used (Swedish Catheter Ablation Register, Auricula, Swedish National Patient Register, Dispensed Drugs Register, Cause of Death Register and Riksstroke). Patients undergoing pulmonary vein isolation (PVI) were investigated for adherence to guidelines regarding oral anticoagulation, predictors for stroke after PVI, as well as risk of ischemic stroke or intracranial haemorrhage after PVI in patients with and without treatment. Results: Paper I showed that a computerized dosing algorithm for warfarin in most cases perform as well or better compared with doses that have been changed manually, with a better hit-rate (0.72 vs. 0.67) and a lower mean error (0.44 vs. 0.48). Paper II showed that 32% of 182.678 patients with a diagnosis of AF were on monotherapy with aspirin for stroke prevention. A total of 115.185 patients were included, 58.671 with aspirin treatment and 56.514 without antithrombotic treatment at baseline. After stratification after CHA2DS2-VASc score and after multivariable adjustment, aspirin treatment did not confer a decrease in thromboembolic events. After propensity score mathcing, rate of ischemic stroke was 7.4%/year (95% CI 7.1-7.6) in aspirin treated patients and 6.6%/year (95% CI 6.4-6.9) in patients without antithrombotic treatment. In paper III 22.874 patients undergoing electrical cardioversion were included, 10.722 with and 12.152 without OAC pre-treatment. In patients with low stroke risk (CHA2DS2-VASc 0-1), no thromboembolic complication was seen within 30 days after cardioversion. In patients with CHA2DS2-VASc ≥2, the risk of thromboembolic complications was increased when no oral anticoagulation pre-treatment was used, results that remained after propensity score matching. No difference regarding haemorrhagic complications was seen. Paper IV included a total of 1585 patients undergoing PVI with a mean follow up of 2.6 years. Adherence to current guidelines regarding oral anticoagulation was good in patients with CHA2DS2-VASc ≥2. Previous ischemic stroke was a predictor for a new stroke after PVI. In patients with CHA2DS2-VASc ≥2 stroke risk was increased in patients discontinuing OAC compared to those continuing OAC (1,60%/year vs. 0.34%/year). Conclusion: Oral anticoagulation is still underutilized for prevention of stroke and systemic embolism in patients with atrial fibrillation. Patients with risk factors for stroke (CHA2DS2-VASc ≥2p) benefit from continuous oral anticoagulation treatment to prevent stroke, also in conjunction with electrical cardioversion and after pulmonary vein isolation. If warfarin is chosen, a computerised dosing algorithm can facilitate and standardize warfarin dosing and lead to better resulting INR values than manually changed doses. Aspirin should not be used for stroke prevention in patients with atrial fibrillation.

O uso de anticoagulantes orais (ACO) esta indicado para a prevenção e tratamento de eventos tromboembólicos decorrentes de várias doenças, principalmente, as cardiovasculares. O uso de ACO representa mudanças na percepção da vida pelo individuo sob constante risco de complicações, sendo a redução desses riscos associadas à melhora da qualidade de vida relacionada à saúde (QVRS) e resultados clínicos satisfatórios. Este estudo de delineamento metodológico teve como objetivos realizar e testar as propriedades psicomtéricas do instrumento Duke Anticoagulation Satisfaction Scale (DASS) para brasileiros em uso de ACO. A DASS possui 25 itens distribuídos em três domínios, Limitação, Tarefa/Sobrecarga e Impacto Psicológico, com respostas de um (1) nada a sete (7) muitíssimo, com um intervalo possível para o total da medida de 25 a 175, no qual menores valores refletem melhor QVRS e maior satisfação com o uso do ACO. O processo de adaptação seguiu os passos preconizados pela literatura. Os dados foram coletados no ambulatório de um hospital público e de ensino do interior do Estado de São Paulo, por meio de entrevistas e consultas aos prontuários, no período de março a agosto de 2008, tendo participado do estudo 180 sujeitos abordados aleatoriamente. As propriedades psicométricas analisadas foram: a validade de face e de conteúdo (comitê de juízes); a validade de constructo (análise fatorial); a validade de constructo convergente (testes de correlação de Pearson entre os domínios da DASS e do SF-36); validade de constructo divergente (testes de correlação de Pearson entre a DASS e idade e tempo de uso do ACO); a confiabilidade (consistência interna-alfa de Cronbach). O nível de significância adotado foi de 0,05. Os resultados demonstraram que a maioria dos participantes era do sexo feminino (65,6%), com idade média de 55 anos, em uso de varfarina (83,3%) há mais de 6,9 anos, em média, sendo a prótese cardíaca metálica a principal indicação para anticoagulação (50%). Apesar de 72,8% terem recebido algum tipo de informação sobre o uso do ACO, 41,7% tiveram complicações, principalmente do tipo hemorrágica (94,6%), com necessidade de internações (15,6%). Na avaliação das propriedades psicométricas, a validade de constructo convergente teve a maioria das correlações negativas, de pouco valor para a prática e estatisticamente significantes. Em relação à validade de constructo divergente, as correlações foram positivas, de pouco valor para prática e não estatisticamente significantes A análise fatorial indicou a presença de três componentes, conforme preconizado pelo autor. A confiabilidade demonstrou um valor adequado para a consistência interna da versão adaptada da DASS ( de Cronbach=0,79). Assim, podemos concluir que a versão adaptada da DASS para o português mostrou-se válida e confiável na amostra estudada. / The therapy with oral anticoagulant (OAC) is indicated in the prevention and treatment of tromboembolic events due to many different clinical conditions, specially the cardiovascular ones. The use of OAC represents changes in the way an individual under constant risk of complications bares life, and the reduction of the risks is associated to improvement in quality of life related to health (QLRH) and satisfactory clinical studies. This methodological study aims at performing and testing the psychometrics properties of the instrument Duke Anticoagulation Satisfaction Scale (DASS) for brazilian patients undergoing OAC therapy. The instrument DASS has 25 items distributed in three domains: Limitation, Task/Overload and Psychological Impact, and responses from one (1) none to seven (7) great, with a possible interval from 25 to 175 for the total measure in which the smallest values reflect better QLRH and greater satisfaction with the use of OAC. The adaptation process followed the steps recommended in specialized literature. Data has been collected in the ambulatory of a public hospital school in the countryside of the state of São Paulo, through interviews to 180 subjects chosen randomly and through consultation to medical records from March to August, 2008. The analysis of the psychometric properties were: face and content validity (judges committee); construct validity (factor analysis); convergent construct validity (Pearsons correlation analysis among the DASS and the SF-36); divergent construct validity (Pearsons correlation analysis among the DASS and age and the time of use of OAC); reliability (Cronbach\'s alpha and internal consistency). The adopted significance level was 0,05. The results show that most participants were female (65,6%), average age of 55 years old, in therapy with warpharine over 6,9 years, having the metallic cardiac prosthesis as the main indication for anticoagulation (50%). Despite 72,8% having received some information about the use of OAC, 41,7% had complications, specially hemorrhage (94,6%) and hospital inpatient (15,6%). Evaluating the psychometric properties, the convergent construct validity had mostly negative correlations, of little value to the practice and statistically significant. Regarding the divergent construct validity, there were mainly positive correlations, of little value to the practice and not statistically significant. The factor analysis indicated three components according to what had been recommended by the author. The reliability showed an adequate value for the internal consistency of the DASS adapted version (Cronbach=0,79). Thus, it shall be concluded that the adapted version of the DASS into portugues is authentic and reliable in the studied sample.

Introdução: O tromboembolismo é uma grave complicação da fibrilação atrial (FA), particularmente em pacientes que vão se submeter à cardioversão, química ou elétrica. Para reduzir esse risco, os pacientes submetem-se à anticoagulação clássica, que vem sendo praticada há várias décadas. Apesar desta abordagem, em pacientes plenamente anticoagulados, não se conhece a prevalência de trombo ou contraste espontâneo no átrio esquerdo (AE). Por essa razão, alguns autores sugerem a realização do ecotransesofágico (ECOTEE) para confirmar o sucesso do tratamento e reduzir o risco de complicações tromboembólicas após a reversão. Os objetivos deste estudo foram: a) avaliar a prevalência de trombos e contraste espontâneo ao ECOTEE em pacientes que vão ser submetidos à cardioversão sob regime de anticoagulação plena; b) avaliar a incidência de tromboembolismo até 30 dias após o procedimento; c) avaliar a influência das variáveis clínicas (doenças associadas) e do ECOTEE (tamanho e volume indexado do AE, fração de ejeção ventricular; velocidade de fluxo no apêndice atrial esquerdo), além do escore CHA2DS2VASc e níveis de pró-BNP plasmático sobre a formação de trombo/contraste espontâneo. Métodos: Foram incluídos 85 pacientes (62 homens; média de idade 61±12 anos) com FA não valvar com indicação para cardioversão. Todos receberam varfarina com controle da taxa de INR. Quando se considerava o paciente plenamente anticoagulado (INR ente 2 e 3 por três semanas consecutivas), era prescrito um fármaco antiarrítmico (propafenona, sotalol ou amiodarona) cuja escolha se baseou em critérios clínicos. Na ausência de normalização do ritmo, eram encaminhados para cardioversão elétrica (CVE). No dia da CVE, os pacientes submetiam-se ao ECOTEE cujo resultado só era conhecido no dia seguinte após a cardioversão. Os pacientes recebiam alta com anticoagulante e retornavam ao ambulatório após 30 dias quando realizavam outro ECOTEE. Resultados: Todos os pacientes foram cardiovertidos com INR na faixa terapêutica (2,9±0,7). A reversão com fármacos ocorreu em 9/85 pacientes (10,6%); 67/76 pacientes submeteram-se à CVE e, destes, 58/67 (86%) reverteram ao ritmo sinusal. O ECOTEE antes da CVE evidenciou trombo no AE em 8/85 pacientes (9,4%) e contraste espontâneo em 36/85 pacientes (42,3%). Nenhuma variável clínica, escore CHA2DS2VASc, níveis plasmáticos de pró-BNP ou variáveis ecocardiográficas identificou pacientes com maior probabilidade de apresentar trombo/contraste espontâneo no AE. Após 30 dias, houve normalização das variáveis do ECOTEE. Em 5/8 (62,5%) pacientes, os trombos desapareceram e surgiu em outros dois pacientes (2,3%). O contraste espontâneo desapareceu em 24/38 (63%) pacientes. Não houve registro de nenhum caso de tromboembolismo sistêmico em 30 dias. A taxa de recorrência de FA foi de 21%. Conclusões: a) trombo atrial/contraste espontâneo foi detectado em 9,4% da população e nenhuma variável clínica ou ecocardiográfica identificou pacientes de risco; b) houve melhora das variáveis do ECOTEE após a reversão ao ritmo sinusal; d) o sucesso global da cardioversão foi de 88% e a taxa de recorrência de FA de 21% em 30 dias; c) não houve registro de tromboembolismo sistêmico em 30 dias, em ritmo sinusal ou em FA. / Introduction: Thromboembolism is a serious complication of atrial fibrillation (AF), particularly in patients who will undergo chemical or electrical cardioversion. To reduce this risk patients receive classic anticoagulant therapy, which has been practiced for several decades. Despite this approach, it is not known the prevalence of thrombus or spontaneous contrast in the left atrium (LA) in patients fully anticoagulated. For this reason, some authors have recommended the transesophageal echocardiogram (TEECHO) to reduce the risk of thromboembolic complications after cardioversion. The objectives of this study were: a) to evaluate the prevalence of thrombus and spontaneous contrast by TEECHO in patients about to undergo cardioversion under full anticoagulation regime; b) evaluate the incidence of thromboembolism within 30 days after the procedure; c) evaluate the influence of clinical variables (associated diseases) and TEECHO parameters (LA size and LA indexed volume, ventricular ejection fraction, flow velocity in the left atrial appendage), CHA2DS2VASc score and plasma pro-BNP levels on thrombus/spontaneous contrast formation. Methods: We included 85 patients (62 men; mean age 61 ± 12 years) with non-valvular AF referred for cardioversion. All received warfarin with INR control. When considering the patient fully anticoagulated (INR in the range of 2 to 3 for three weeks) it was prescribed an anti-arrhythmic drug (propafenone, sotalol or amiodarone) whose choice was based on clinical criteria. In the absence of normal rhythm, patients were referred for electrical cardioversion (ECV). On the day of ECV, all patients were submitted to the ECOTEE whose result was known only the next day after cardioversion. The patients were discharged with anticoagulant and returned to the clinic after 30 days when another ECOTEE was performed. Results: All patients were cardioverted with INR in the therapeutic range (2.9±0.7). Sinus rhythm was restored with drugs in 9/85 patients (10.6%); 67/76 patients underwent ECV and 58/67 (86%) reverted to sinus rhythm. The TEECHO before cardioversion showed a thrombus in LA in 8/85 patients (9.4%) and spontaneous contrast in 36/85 patients (42.3%). No clinical variable, CHA2DS2VASc score, pro-BNP plasma levels or echocardiography variables identified patients with an increased likelihood of thrombus/spontaneous contrast in LA. After 30 days, there was normalization of TEECHO variables. In 5/8 (62.5%) patients thrombi disappeared and appeared in two patients (2.3%). Spontaneous contrast disappeared in 24/38 (63%) patients. There were no reports of any case of systemic thromboembolism in 30 days. The AF recurrence rate was 21%. Conclusions: a) LA thrombus/ spontaneous contrast were detected in 9.4% of the population and no clinical or echocardiography variable identified patients at risk; b) there was an improvement of TEECHO variables after reversion to sinus rhythm; d) the overall success of cardioversion was 88% and the AF recurrence rate was 21% in 30 days; c) there was no systemic thromboembolism in 30 days, in patients in sinus rhythm or AF.

An intracranial aneurysm is a local dilation of an artery in the cerebral circulation. While the etiology of intracranial aneurysms is unknown, they likely result from a combination of factors including the weakening and degeneration of the collagen fibers and the internal elastic lamina comprising the arterial wall, as well as hemodynamic-associated stress resulting from blood pulsation inside the aneurysm sac. Intracranial aneurysm rupture leads to a devastating sequela, as 50% of patients die. In the U.S. alone there are approximately 30,000 cases of subarachnoid hemorrhage annually, a prevalence which has pushed practitioners to aggressively treat the aneurysm disease. Traditionally, intracranial aneurysms were managed with open craniotomy and microsurgical clipping; however, these treatment modalities carry relatively high morbidity and mortality depending upon the aneurysm location and surgical experience. In 2002 the International Subarachnoid Hemorrhage Aneurysm Trial established the superiority of the endovascular coiling of intracranial aneurysms compared to microsurgical clipping. This trial led to a paradigm shift in treating intracranial aneurysms with marked use of intracranial stenting, including devices used to assist endovascular coiling and stand-alone flow diverting devices. However, the placement of intracranial devices in the cerebral circulation mandates the adjunctive application of dual anti-platelet pharmaceuticals to minimize thromboembolic events, despite being associated with increased patient risk. This dissertation proposes a novel multilayer, nanometer-scale coating technology suitable for commercially available intracranial stents and flow diverting devices to minimize the use of dual anti-platelet therapy in the elective setting and expand the use of intracranial devices in the acute setting of ruptured intracranial aneurysms. A combination of qualitative and quantitative chemical characterization techniques was used to assess the composition, uniformity, and thickness of each coating layer on commercially available flow diverting devices; overall the coating was found to be relatively uniform and conformal to the device wires. Furthermore, in-vitro and in-vivo testing on commercially available intracranial devices suggest some hemocompatible and antithrombotic properties. Finally, the proposed coating technology can be modified for use as a platform for the attachment of FDA-approved molecules. With further optimization and testing this technology has the potential to minimize the adjunctive use of dual-antiplatelet therapy in the endovascular treatment of intracranial aneurysms.

Orientador: Silméia Garcia Zanati Bazan / Resumo: Fundamento: A fibrilação atrial (FA) é uma arritmia supraventricular caracterizada por uma completa desorganização na atividade elétrica atrial, fazendo com que os átrios percam sua capacidade de contração, não gerando sístole atrial. Sua prevalência aumenta com a idade e geralmente está associada a doenças estruturais cardíacas, trazendo prejuízos hemodinâmicos e complicações tromboembólicas. A anticoagulação oral (ACO) é capaz de prevenir os eventos tromboembólicos e sua monitorização é realizada através do INR (International Normalized Ratio). Objetivos: 1-avaliar a estabilidade do INR dos pacientes anticoagulados portadores de fibrilação atrial (FA) não valvar; 2- avaliar as complicações tromboembólicas ou hemorrágicas nestes pacientes; 3- identificar o subgrupo de maior risco para eventos tromboembólicos ou hemorrágicos. Casuística e Métodos: Foram revisados os prontuários médicos de 203 pacientes atendidos no ambulatório de anticoagulação da Disciplina de Cardiologia do Hospital das Clínicas da Faculdade de Medicina de Botucatu – UNESP (HC-FMB-UNESP) no período de janeiro de 2009 a janeiro de 2015, e calculado o tempo de permanência na faixa terapêutica (Time in Therapeutic Range – TTR), utilizando-se o método consagrado na literatura descrito por Rosendaal, uma interpolação linear para atribuir um valor de INR a cada dia do intervalo entre as aferições registradas. Resultados: O valor de TTR mediano foi de 53(10-88) e médio de 52,21%. Foram analisados os fatores que in... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Atrial fibrillation (AF) is a supraventricular arrhythmia characterized by complete disorganization of atrial electrical activity, causing the atriums to lose their contractile capacity, thereby not generating atrial systole. Its prevalence increases with age and may be associated with cardiac structural diseases, provoking hemodynamic damage and thromboembolic complications. Oral anticoagulation (OAC) is capable of preventing thromboembolic events and is monitored through the INR (International Normalized Ratio). Objectives: 1- to evaluate INR stability in anticoagulated patients with non-valvular Atrial Fibrillation (AF); 2- to evaluate thromboembolic and hemorrhagic complications in these patients; 3- to identify the subgroup of higher risk for thromboembolic or hemorrhagic events. Methods: The medical charts of 203 patients attended at the anticoagulation ambulatory unit in the Cardiology Department at HC-FMB-UNESP in the period from January 2009 to January 2015 were reviewed; the Time in Therapeutic Range (TTR) was calculated by the method esteemed in the literature described by Rosendaal, a linear interpolation to attribute an INR value to each day of the interval between the recorded measurements. Results: The median TTR value was 53 (10-88) and the mean 52.21%. The factors that influenced the TTR value were analyzed in this population, showing that the patients presenting INR instability in the adaptation phase had a lower mean TTR (46.83%) than those with... (Complete abstract click electronic access below) / Mestre

O uso de anticoagulantes orais (ACO) esta indicado para a prevenção e tratamento de eventos tromboembólicos decorrentes de várias doenças, principalmente, as cardiovasculares. O uso de ACO representa mudanças na percepção da vida pelo individuo sob constante risco de complicações, sendo a redução desses riscos associadas à melhora da qualidade de vida relacionada à saúde (QVRS) e resultados clínicos satisfatórios. Este estudo de delineamento metodológico teve como objetivos realizar e testar as propriedades psicomtéricas do instrumento Duke Anticoagulation Satisfaction Scale (DASS) para brasileiros em uso de ACO. A DASS possui 25 itens distribuídos em três domínios, Limitação, Tarefa/Sobrecarga e Impacto Psicológico, com respostas de um (1) nada a sete (7) muitíssimo, com um intervalo possível para o total da medida de 25 a 175, no qual menores valores refletem melhor QVRS e maior satisfação com o uso do ACO. O processo de adaptação seguiu os passos preconizados pela literatura. Os dados foram coletados no ambulatório de um hospital público e de ensino do interior do Estado de São Paulo, por meio de entrevistas e consultas aos prontuários, no período de março a agosto de 2008, tendo participado do estudo 180 sujeitos abordados aleatoriamente. As propriedades psicométricas analisadas foram: a validade de face e de conteúdo (comitê de juízes); a validade de constructo (análise fatorial); a validade de constructo convergente (testes de correlação de Pearson entre os domínios da DASS e do SF-36); validade de constructo divergente (testes de correlação de Pearson entre a DASS e idade e tempo de uso do ACO); a confiabilidade (consistência interna-alfa de Cronbach). O nível de significância adotado foi de 0,05. Os resultados demonstraram que a maioria dos participantes era do sexo feminino (65,6%), com idade média de 55 anos, em uso de varfarina (83,3%) há mais de 6,9 anos, em média, sendo a prótese cardíaca metálica a principal indicação para anticoagulação (50%). Apesar de 72,8% terem recebido algum tipo de informação sobre o uso do ACO, 41,7% tiveram complicações, principalmente do tipo hemorrágica (94,6%), com necessidade de internações (15,6%). Na avaliação das propriedades psicométricas, a validade de constructo convergente teve a maioria das correlações negativas, de pouco valor para a prática e estatisticamente significantes. Em relação à validade de constructo divergente, as correlações foram positivas, de pouco valor para prática e não estatisticamente significantes A análise fatorial indicou a presença de três componentes, conforme preconizado pelo autor. A confiabilidade demonstrou um valor adequado para a consistência interna da versão adaptada da DASS ( de Cronbach=0,79). Assim, podemos concluir que a versão adaptada da DASS para o português mostrou-se válida e confiável na amostra estudada. / The therapy with oral anticoagulant (OAC) is indicated in the prevention and treatment of tromboembolic events due to many different clinical conditions, specially the cardiovascular ones. The use of OAC represents changes in the way an individual under constant risk of complications bares life, and the reduction of the risks is associated to improvement in quality of life related to health (QLRH) and satisfactory clinical studies. This methodological study aims at performing and testing the psychometrics properties of the instrument Duke Anticoagulation Satisfaction Scale (DASS) for brazilian patients undergoing OAC therapy. The instrument DASS has 25 items distributed in three domains: Limitation, Task/Overload and Psychological Impact, and responses from one (1) none to seven (7) great, with a possible interval from 25 to 175 for the total measure in which the smallest values reflect better QLRH and greater satisfaction with the use of OAC. The adaptation process followed the steps recommended in specialized literature. Data has been collected in the ambulatory of a public hospital school in the countryside of the state of São Paulo, through interviews to 180 subjects chosen randomly and through consultation to medical records from March to August, 2008. The analysis of the psychometric properties were: face and content validity (judges committee); construct validity (factor analysis); convergent construct validity (Pearsons correlation analysis among the DASS and the SF-36); divergent construct validity (Pearsons correlation analysis among the DASS and age and the time of use of OAC); reliability (Cronbach\'s alpha and internal consistency). The adopted significance level was 0,05. The results show that most participants were female (65,6%), average age of 55 years old, in therapy with warpharine over 6,9 years, having the metallic cardiac prosthesis as the main indication for anticoagulation (50%). Despite 72,8% having received some information about the use of OAC, 41,7% had complications, specially hemorrhage (94,6%) and hospital inpatient (15,6%). Evaluating the psychometric properties, the convergent construct validity had mostly negative correlations, of little value to the practice and statistically significant. Regarding the divergent construct validity, there were mainly positive correlations, of little value to the practice and not statistically significant. The factor analysis indicated three components according to what had been recommended by the author. The reliability showed an adequate value for the internal consistency of the DASS adapted version (Cronbach=0,79). Thus, it shall be concluded that the adapted version of the DASS into portugues is authentic and reliable in the studied sample.

Introdução: O tromboembolismo é uma grave complicação da fibrilação atrial (FA), particularmente em pacientes que vão se submeter à cardioversão, química ou elétrica. Para reduzir esse risco, os pacientes submetem-se à anticoagulação clássica, que vem sendo praticada há várias décadas. Apesar desta abordagem, em pacientes plenamente anticoagulados, não se conhece a prevalência de trombo ou contraste espontâneo no átrio esquerdo (AE). Por essa razão, alguns autores sugerem a realização do ecotransesofágico (ECOTEE) para confirmar o sucesso do tratamento e reduzir o risco de complicações tromboembólicas após a reversão. Os objetivos deste estudo foram: a) avaliar a prevalência de trombos e contraste espontâneo ao ECOTEE em pacientes que vão ser submetidos à cardioversão sob regime de anticoagulação plena; b) avaliar a incidência de tromboembolismo até 30 dias após o procedimento; c) avaliar a influência das variáveis clínicas (doenças associadas) e do ECOTEE (tamanho e volume indexado do AE, fração de ejeção ventricular; velocidade de fluxo no apêndice atrial esquerdo), além do escore CHA2DS2VASc e níveis de pró-BNP plasmático sobre a formação de trombo/contraste espontâneo. Métodos: Foram incluídos 85 pacientes (62 homens; média de idade 61±12 anos) com FA não valvar com indicação para cardioversão. Todos receberam varfarina com controle da taxa de INR. Quando se considerava o paciente plenamente anticoagulado (INR ente 2 e 3 por três semanas consecutivas), era prescrito um fármaco antiarrítmico (propafenona, sotalol ou amiodarona) cuja escolha se baseou em critérios clínicos. Na ausência de normalização do ritmo, eram encaminhados para cardioversão elétrica (CVE). No dia da CVE, os pacientes submetiam-se ao ECOTEE cujo resultado só era conhecido no dia seguinte após a cardioversão. Os pacientes recebiam alta com anticoagulante e retornavam ao ambulatório após 30 dias quando realizavam outro ECOTEE. Resultados: Todos os pacientes foram cardiovertidos com INR na faixa terapêutica (2,9±0,7). A reversão com fármacos ocorreu em 9/85 pacientes (10,6%); 67/76 pacientes submeteram-se à CVE e, destes, 58/67 (86%) reverteram ao ritmo sinusal. O ECOTEE antes da CVE evidenciou trombo no AE em 8/85 pacientes (9,4%) e contraste espontâneo em 36/85 pacientes (42,3%). Nenhuma variável clínica, escore CHA2DS2VASc, níveis plasmáticos de pró-BNP ou variáveis ecocardiográficas identificou pacientes com maior probabilidade de apresentar trombo/contraste espontâneo no AE. Após 30 dias, houve normalização das variáveis do ECOTEE. Em 5/8 (62,5%) pacientes, os trombos desapareceram e surgiu em outros dois pacientes (2,3%). O contraste espontâneo desapareceu em 24/38 (63%) pacientes. Não houve registro de nenhum caso de tromboembolismo sistêmico em 30 dias. A taxa de recorrência de FA foi de 21%. Conclusões: a) trombo atrial/contraste espontâneo foi detectado em 9,4% da população e nenhuma variável clínica ou ecocardiográfica identificou pacientes de risco; b) houve melhora das variáveis do ECOTEE após a reversão ao ritmo sinusal; d) o sucesso global da cardioversão foi de 88% e a taxa de recorrência de FA de 21% em 30 dias; c) não houve registro de tromboembolismo sistêmico em 30 dias, em ritmo sinusal ou em FA. / Introduction: Thromboembolism is a serious complication of atrial fibrillation (AF), particularly in patients who will undergo chemical or electrical cardioversion. To reduce this risk patients receive classic anticoagulant therapy, which has been practiced for several decades. Despite this approach, it is not known the prevalence of thrombus or spontaneous contrast in the left atrium (LA) in patients fully anticoagulated. For this reason, some authors have recommended the transesophageal echocardiogram (TEECHO) to reduce the risk of thromboembolic complications after cardioversion. The objectives of this study were: a) to evaluate the prevalence of thrombus and spontaneous contrast by TEECHO in patients about to undergo cardioversion under full anticoagulation regime; b) evaluate the incidence of thromboembolism within 30 days after the procedure; c) evaluate the influence of clinical variables (associated diseases) and TEECHO parameters (LA size and LA indexed volume, ventricular ejection fraction, flow velocity in the left atrial appendage), CHA2DS2VASc score and plasma pro-BNP levels on thrombus/spontaneous contrast formation. Methods: We included 85 patients (62 men; mean age 61 ± 12 years) with non-valvular AF referred for cardioversion. All received warfarin with INR control. When considering the patient fully anticoagulated (INR in the range of 2 to 3 for three weeks) it was prescribed an anti-arrhythmic drug (propafenone, sotalol or amiodarone) whose choice was based on clinical criteria. In the absence of normal rhythm, patients were referred for electrical cardioversion (ECV). On the day of ECV, all patients were submitted to the ECOTEE whose result was known only the next day after cardioversion. The patients were discharged with anticoagulant and returned to the clinic after 30 days when another ECOTEE was performed. Results: All patients were cardioverted with INR in the therapeutic range (2.9±0.7). Sinus rhythm was restored with drugs in 9/85 patients (10.6%); 67/76 patients underwent ECV and 58/67 (86%) reverted to sinus rhythm. The TEECHO before cardioversion showed a thrombus in LA in 8/85 patients (9.4%) and spontaneous contrast in 36/85 patients (42.3%). No clinical variable, CHA2DS2VASc score, pro-BNP plasma levels or echocardiography variables identified patients with an increased likelihood of thrombus/spontaneous contrast in LA. After 30 days, there was normalization of TEECHO variables. In 5/8 (62.5%) patients thrombi disappeared and appeared in two patients (2.3%). Spontaneous contrast disappeared in 24/38 (63%) patients. There were no reports of any case of systemic thromboembolism in 30 days. The AF recurrence rate was 21%. Conclusions: a) LA thrombus/ spontaneous contrast were detected in 9.4% of the population and no clinical or echocardiography variable identified patients at risk; b) there was an improvement of TEECHO variables after reversion to sinus rhythm; d) the overall success of cardioversion was 88% and the AF recurrence rate was 21% in 30 days; c) there was no systemic thromboembolism in 30 days, in patients in sinus rhythm or AF.

Thrombosis and colorectal cancer have a bi-directional relationship. The presence of a colorectal malignancy results in an increased risk of developing a thrombosis and the presence of a thrombosis results in a worse cancer prognosis. The physiology causing this is at present unclear but it is proposed that proteins from the tissue factor (TF) pathway may be the instigator of this bi-directional relationship. The in-vitro studies have shown that in colorectal cancer TF impairs that action of colorectal cancer stem cells as demonstrated by reduced cancer sphere formation and also lower expression of the stem cell marker ALDH. The ability for a colorectal cell to avoid anoikis is impaired by a reduced TF level. Proliferation is affected by the level of expression of TF with a significant increase in proliferation with additional expression of TF. The increase in proliferation is further increased by the presence of TF’s ligand factor VIIa. Paradoxically reduced expression of TF also increases colorectal cancer expression. The ERK1/2 pathway offers a possible method by which TF and factor VIIa may exert their proliferative effects. In the prospective clinical cohort study (CHAMPion) abnormal expression of TF pathway proteins (TF, PAR1, PAR2 and thrombin) by both malignant epithelial and cancer associated stromal cells has been demonstrated. The stromal expression was independent of the epithelial expression and was only in stroma in close contact (0.1mm) with epithelial cells suggesting that the TF pathway proteins may have a role in stromal/epithelial communication. There was no link between the expression of TF pathway proteins and clinicopathological markers of a poor prognosis. The plasma expression of markers of TF pathway activation did not demonstrate any role as a biomarker for colorectal cancer or prognosis. The CHAMPion study has demonstrated that 7% of patients undergoing surgery for colorectal cancer have asymptomatic pre-operative DVTs present. A further 6% who were DVT free pre-operatively developed a DVT in the peri-operative period despite receiving venous thromboprophylaxis in line with current national guidelines. Pre-operative d-dimer may have the potential to identify those patients at risk of a post-operative VTE.This thesis establishes the role that TF has in promoting proliferation and anoikis resistance. It also confirms the abnormal expression of TF pathway proteins by colorectal cancer epithelial cells and for the first time demonstrates abnormal expression by the cancer associated stroma. The interaction between the stroma and epithelial cells, combined with the cellular effects of TF suggests that targeting this interaction may have a therapeutic role. The incidence of DVTs pre-operatively suggests that screening patients for the asymptomatic presence of a DVT may have an impact on their clinical outcome. The development of DVTs despite prophylaxis suggests that the level of anticoagulation is insufficient and current guidelines need to be revisited.

Patients with inflammatory bowel disease (IBD) are known to have an increased propensity for thromboembolic events. Like any patient with a high risk of event recurrence, most of these patients can be managed successfully with long-term warfarin therapy. We present the case of a 66-year-old woman with Crohn's disease who, despite careful attention to the management of her international normalized ratio, developed a new deep vein thrombosis and required inferior vena cava filter placement in addition to ongoing warfarin therapy to prevent recurrent pulmonary emboli. This report serves as a reminder to physicians to have a low threshold for diagnosing thromboembolic events in patients with IBD, even if they are presumed to be adequately anticoagulated. Known and theoretical contributing factors to this increased clotting tendency are also reviewed.

Anticoagulation risks in older adult, long-term care patients are known to be high, especially in those with frequent transitions between care environments. Introduction of collaborative practice agreements (CPA) in specific settings is encouraged in the United States and has provided an additional option for the care of medically challenging patients. The aim of this study was to investigate the time in therapeutic range (TTR) in a Medicare Part A sponsored long-term care environment managed by pharmacists through a collaborative practice agreement in South-Central Appalachia. A retrospective review of all warfarin patient admissions from a large long-term care pharmacy’s anticoagulant clinic was conducted for residents over an 18-month period. For all patients (n = 104), the overall TTR was 46.7% (INR 43% in range). Average management duration was 19.5 days per patient. Further studies are required to optimize CPA and transition strategies for complex, advanced age warfarin patients.