Orientadores: Renato Giuseppe Giovanni Terzi, Ilma Aparecida Paschoal / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T22:30:15Z (GMT). No. of bitstreams: 1 Moreira_MarcosMello_D.pdf: 18313915 bytes, checksum: db1efb99a56b2256d14393f2e951147a (MD5) Previous issue date: 2009 / Resumo: Métodos para confirmar o diagnóstico de tromboembolismo pulmonar (TEP) são relativamente invasivos, de alto custo e nem sempre disponíveis. Justifica-se a busca de métodos mais acessíveis, de baixo custo, minimamente invasivos e que possam ser realizados à beira do leito. Foi objetivo deste estudo estabelecer um protocolo de triagem diagnóstica de TEP, minimamente invasivo e de baixo custo, usando para isto a capnografia volumétrica (CV) e o Oímero-O (DO) (ELISA Rápido), para pacientes internados em diferentes unidades de um hospital terciário, atentanto para as possíveis limitações deste protocolo. Foi realizado um estudo prospectivo e observacional com 92 pacientes. Um estudo prévio de CV em 114 voluntários estabeleceu o padrão de normalidade para as variáveis analisadas. No grupo TEP, a CV foi associada à gasometria arterial para cálculo das variáveis do espaço morto e à dosagem do DO. O padrão-ouro para diagnóstico de TEP foi dado pela cintilografia de inalação/perfusão e/ou, tomografia computadorizada helicoidal e/ou, arteriografia pulmonar. Isoladamente, a variável capnográfica que apresentou melhor sensibilidade e especificidade foi a fração tardia do espaço morto alveolar (tO/ate) (91% e 98%, respectivamente). Obteve-se um resultado falso-negativo para o DO e, para a tO/ate, um falso-positivo e três falso-negativos. Quando a tO/ate ,foi associada ao DO, conseguiu-se 100% sensibilidade e 17% de especificidade. Uma outra variável capnográfica importante, por sugerir função pulmonar prévia anormal, e por esta razão, sinalizar uma possível limitação da tO/ate, foi o slope da fase III do capnograma. Por meio dos dados da CV de ambos os grupos (controle e doentes), estabeleceu-se um protocolo que ajuda a direcionar a equipe multiprofissionál quando da suspeita clínica de TEP. / Abstract :Background: Tests used to confirm a diagnosis of pulmonary embolism (PE) are relatively invasive, costly and not always available. Minimally invasive methods that are more accessible, less expensive and easily applied should be sought. Objective: To establish a low-cost, minimally invasive, PE diagnostic protocol in hospitalized patients, using capnographic variables and ELlSA D-dimer (DD) to rule out PE. Methods: A prospective observational study was conducted in 92 patients with suspected PE. The values of reference group for volumetric capnography (VCap) were used in order to compare with patterns of patients with PE. The patients were submitted to arterial blood gas analysis (to calculate the dead space variables) and had the DD values determined. The diagnosis was confirmed through ventilation/perfusion scintigraphy, spiral computed tomography, pulmonary arteriogram, or combinations of the three. Results: The capnographic variable that presented the greatest sensitivity and specificity (91 % and 98%, respectively) was the late dead space fraction (fDlate). Our findings include one false-negative DD result, as well as three false-positive and eight false-negative fDlate results. The combination of the fDlate and DD testing presented 100% sensitivity and 17% specificity. Another important capnographic variable, the phase 111 slope, indicated a possible limitation of VCap, since it interferes with the calculation of fDlate. Conclusion: The protocol established could guide multiprofessional teams in the management of clinical suspicion of PE. We were able to determine that the phase 111 slope might interfere with the calculation of fDlate, especially in patients with a history of abnormal lung function. Throught VCap variables (control group and sickness); was possible establishes a protocol that guide the multiprofissional team in cases of PE. / Doutorado / Pesquisa Experimental / Doutor em Cirurgia

O diagnóstico da tromboembolia pulmonar aguda (EPA) e a avaliação da gravidade desta condição é desafiador. Enquanto as concentrações de troponina I cardíaca (TI) já estão bem estabelecidas quanto ao risco de estratificação, não há estudos prévios que tenham examinado se há alguma relação linear entre as concentrações de TI cardíaca e a gravidade da EPA. Além disso, as metaloproteinases (MMPs) da matriz extracelular estão envolvidas na fisiopatologia da EPA. Entretanto, é desconhecido se o aumento da atividade gelatinolítica das MMPs após a EPA reflete a gravidade desta condição. Nós examinamos se as concentrações circulantes destes biomarcadores aumentam em proporção à gravidade da EPA experimental induzida em cães anestesiados. A EPA foi induzida com coágulos de sangue autólogo (salina, 1, 3 ou 5 mL/Kg) injetados no átrio direito. As avaliações hemodinâmicas foram realizadas no momento basal e 120 minutos após a EPA. Da mesma forma, foram realizadas as quantificações de troponina I no soro e a zimografia das MMPs 2 e 9 no plasma. Nossos resultados sugerem não haver aumento significativo da atividade gelatinolítica da pró-MMP-2 no plasma após a EPA, enquanto que a atividade da pró-MMP-9 aumenta em 80% apenas no grupo que recebeu 5 mL/Kg de coágulos. A TI cardíaca no soro e a atividade da pró-MMP-9 no plasma tiveram uma correlação positiva com o índice de resistência vascular pulmonar (p=0,007 e rs=0,833 para a TI, e p=0,034 e rs=0,684 para a pró-MMP-9) e com a pressão média na artéria pulmonar (p=0,005 e rs=0,610 para a TI, e p=0,022 e rs=0,720 para a pró-MMP-9). Concluímos que a TI cardíaca e a pró-MMP-9 circulantes aumentam em proporção à gravidade da EPA, embora o aumento da pró-MMP-9 não seja muito evidente em graus menos severos da EPA. Estes achados podem ser relevantes para a clínica da EPA. / Making the diagnosis of acute pulmonary thromboembolism (APT) and assessing its severity is very challenging. While cardiac troponin I (CTI) levels are promising in risk stratification, no previous study has examined whether there is a linear relation between CTI levels and the severity of APT. Moreover, matrix metalloproteinases (MMPs) are involved in the pathophysiology of APT. However, it is unknown whether the increases in MMP levels after APT reflect the severity of this condition. We examined whether the circulating levels of these biomarkers increase in proportion to the severity of experimental APT induced in anesthetized dogs. APT was induced with autologous blood clots (saline, 1, 3, or 5 mL/kg) injected into the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin zymography of MMP-2 and MMP-9 from plasma samples were performed and serum CTI levels were determined at baseline and 120 min after APT. Our results sugest that while no significant increases in pro-MMP-2 levels were found after APT, pro-MMP-9 levels increased by 80% only after 5 mL/kg of clot embolization. Serum CTI and plasma pro-MMP-9 levels correlated positively with pulmonary vascular resistance (p=0.007 and rs=0.833 for troponin I, and p=0.034 and rs=0.684 for pro-MMP-9) and with pulmonary artery pressure (p=0.005 and rs=0.610 for troponin I, and p=0.022 and rs=0.720 for pro-MMP-9). We conclude that circulating CTI and pro-MMP-9 increase in proportion to the severity of APT, although the increases in plasma pro-MMP-9 are less clear with less severe APT. These findings may be relevant for clinical APT.

Com a transição epidemiológica no Brasil, as doenças crônicas passaram a ser responsáveis pelo maior número de óbitos entre homens e mulheres. Entre os componentes que definem o estado de saúde humana, alguns do contexto geográfico, como clima local e fatores socioeconômicos, parecem influenciar na mortalidade por doenças do aparelho circulatório, tais como no acidente cerebral vascular (AVC) e na embolia pulmonar (EP). O objetivo principal deste trabalho foi verificar a influência do contexto geográfico (variáveis meteorológicas, índice climático e fatores socioeconômicos) na mortalidade por doenças do aparelho circulatório (AVC e EP) no município de São Paulo, no período de 2002 a 2011. Para analisar a associação da mortalidade com as variáveis meteorológicas foi utilizado um modelo linear generalizado empregando-se o método de Poisson e os modelos de lags distribuídos. Espacialmente a associação da mortalidade com as variáveis socioeconômicas foram testadas utilizando-se os modelos de regressão espacial OLS e GWR. Como resultado encontramos que tanto o frio quanto o calor são fatores de risco para todos os tipos de AVC e EP, com risco maior dependendo do tipo em homens e mulheres. Espacialmente os valores mais elevados do risco relativo (RR) da mortalidade por AVC estavam concentrados nas regiões periféricas do municipio de São Paulo, o que coincidiu com as áreas de menor renda per capita e vegetação e maior porcentagem de população preta. Já com relação à distribuição espacial dos altos valores de RR por EP esses estavam presentes principalmente na região central do município. Concluindo, a nossa pesquisa gerou grande quantidade de resultados que mostram que tanto as variáveis ambientais como socioeconômicas têm influência na mortalidade por algumas doenças do aparelho circulatório. Tendo em vista que o atendimento de urgência para os casos de AVC e EP pode evitar óbitos e sequelas graves, a melhor compreensão da importância do contexto geográfico pode permitir o desenvolvimento de sistemas de alertas junto aos serviços de atendimento de urgência e o direcionamento de campanhas para a prevenção dos fatores de risco evitáveis. / With the epidemiological transition in Brazil, chronic diseases are now responsible for more deaths among men and women. Among the components that define the state of human health, some geographical context, as local climate and socioeconomic factors appear to influence the mortality from circulatory diseases, such as in stroke and pulmonary embolism (PE). The main objective of this study was to investigate the influence of the geographical context (meteorological variables, climate index and socioeconomic factors) in mortality from cardiovascular diseases (stroke and PE) in São Paulo, between 2002 to 2011. In order to analyze the association of mortality with the meteorological variables we used a generalized linear model using the Poisson distribution and distributed lag non linear models. Spatially the association of mortality with socioeconomic variables were tested using the spatial regression models OLS and GWR. As a result we found that both the cold and the heat are risk factors for all types of stroke and PE with a higher risk depending on the type of men and women. Spatially the highest values of relative risk (RR) for stroke mortality were concentrated in the outskirts of the city of São Paulo, which coincided with areas of lower per capita income and vegetation and higher percentage of black population. In relation to spatial distribution of high values of RR PE by these were present mainly in the inner area. In conclusion, our research has generated a lot of results that show that both environmental and socioeconomic variables influence on mortality from some diseases of the circulatory system. In view of the urgent care for stroke and PE cases can avoid serious sequelae and deaths, a better understanding of the importance of geographic context may allow the development of warning systems at the urgent care services and targeting campaigns for the prevention of avoidable risk factors.

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.

Background: Recent studies have suggested that patients with idiopathic pulmonary fibrosis (IPF) may have a higher risk of venous thromboembolism (VTE) compared to general population even though the results were inconsistent. Objective: To investigate the risk of VTE among patients with IPF. Methods: Comprehensive literature review using MEDLINE and EMBASE database were performed to identify studies that compared the risk of VTE among patients with IPF to general population. Effect estimates from each study were combined together using random effect model, generic inverse variance method of DerSimonian and Laird. Results: Out of 510 retrieved articles, 5 studies met the inclusion criteria and were included in the meta-analysis. A significant risk of VTE in patients with IPF was observed with the pooled risk ratio of 2.11 (95% confidence interval, 1.28-3.48). The heterogeneity was moderate with I2 of 64%. Conclusion: An approximately 2-fold increased risk of VTE among patients with IPF was observed in this meta-analysis.

Relation between the reperfusion of pulmonary arteries after acute pulmonary embolism to the development of chronic thromboembolic pulmonary hypertension Incomplete resolution of thromboemboli following acute pulmonary embolism (PE) is a key factor in development of chronic thromboembolic pulmonary hypertension (CTEPH). In our study, we evaluated the incidence, risk factors and clinical impact of incomplete reperfusion after acute PE. Study population and methods: 85 patients after the first acute PE were assessed clinically and by pulmonary scintigraphy and echocardiography at month 6, 12 and 24 after an acute PE. Results: Incomplete reperfusion was detected in 23.5 % of patients after 6 months, in 24.9 % of patients after 12 months and in 18.6 % of patients after 24 months. At month 6, patients with incomplete reperfusion were more obese when compared with patients with normal reperfusion BMI 30.8 vs 28.3 kg/m2 ; p=0.012) and their initial hemoglobin levels were higher (143.0 vs 136.0 g/l; p=0.012). Similar results were observed at month 12 - patients with residual perfusion defects were more obese (BMI 31.1 vs 28.5; p=0.016) with higher initial hemoglobin levels (144.0 vs 136.0; p=0.007). Patients with incomplete reperfusion at month 24 were significantly older (67.7 vs 55.0 years; p=0.02), their...

BACKGROUND: South Africa bares a significant burden of HIV and imaging is commonly performed as part of the workup for respiratory distress. OBJECTIVES: The aim of this study was to document the prevalence of pulmonary thrombo-embolic disease (PTED) and other findings in HIV-infected patients referred for CT pulmonary angiography (CTPA) for suspected PTED. METHOD: Forty CTPA studies of documented HIV-infected individuals investigated for suspected PTED during a 1-year period were retrieved, anonymised and interpreted by three consultant radiologists. Inter-reader reliability was calculated using Free Marginal multi-rater Kappa. RESULTS: Fourteen of the forty cases (35%) were positive for PTED. In the pulmonary embolism (PE)-positive group, 57.14% had peripheral disease and 42.86% had both peripheral and central disease. Associated findings in the PE-positive cases were pulmonary infarcts (17.5%), mosaic attenuation (17.5%) and linear atelectasis (7.5%). The most common incidental findings were solid pulmonary nodules (52.5%), non-wedge-shaped consolidation (45%), cardiomegaly (52.5%) and enlarged intra-thoracic lymph nodes (52.5%). Thirty per cent of the study population had findings related directly to the presence of PTED, whilst most cases in the study (77.5%) had pulmonary findings unrelated to PTED. In the PE-negative cases, 55% reported emergent findings that warranted immediate or urgent medical attention. CONCLUSION: Computed tomography pulmonary angiography imaging is critical for diagnosing PE. However, further investigation into the judicious application of CTPA in HIV-infected patients with suspected PTED is required, as CTPA findings in most of the cases in this study were unrelated to PE.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic with an unprecedented death toll worldwide. Although it primarily affects the respiratory tract presenting as pneumonia or acute respiratory failure, it is also known to cause significant cardiovascular complications, including acute coronary syndrome (ACS), arrhythmia, myopericarditis, cardiomyopathy, venous thromboembolism, heart failure, and cardiogenic shock. Morbidity and mortality secondary to cardiovascular complications are higher in patients with preexisting cardiovascular risk factors. Here, we present a case report of a 69-year-old male who was recently diagnosed with COVID-19 illness presenting with ST-elevation myocardial infarction (STEMI) and eventually with Takotsubo cardiomyopathy (TTC), and the course was complicated by right atrial thrombus and a pulmonary embolism (PE).

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coeffcient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE.

Background: After the first COVID-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed COVID-19 was observed, but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-COVID-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion, and (4) preceding COVID-19 infection numbers in Germany. Methods: Claims data of Helios hospitals in Germany were used, and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period), were analyzed and compared to corresponding periods covering the same weeks in 2016–2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016–2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring between 14 up to 90 days with increasing window sizes before PE cases and modeled the data with Poisson regression. Results: There were 2,404 PE hospitalizations between May 6 and December 15, 2020, as opposed to 2,112–2,236 (total 8,717) in the corresponding 2016–2019 control periods (crude rate ratio [CRR] 1.10, 95% CI 1.05–1.15, P < 0.01). With the use of multivariable Poisson GLMM adjusted for age, sex, and volume depletion, PE cases were significantly associated with the number of cases with pneumonia (CRR 1.09, 95% CI 1.07–1.10, P < 0.01) and with CTPA (CRR 1.10, 95% CI 1.09–1.10, P < 0.01). The increase of PE cases in 2020 compared with the control period remained significant (CRR 1.07, 95% CI 1.02–1.12, P < 0.01) when controlling for those factors. In the 2020 cohort, the number of preceding average daily COVID-19 infections was associated with increased PE case incidence in all investigated windows, i.e., including preceding infections from 14 to 90 days. The best model (log likelihood −576) was with a window size of 4 days, i.e., average COVID-19 infections 14–17 days before PE hospitalization had a risk of 1.20 (95% CI 1.12–1.29, P < 0.01). Conclusions: There is an increase in PE cases since early May 2020 compared to corresponding periods in 2016–2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-COVID-19 pneumonia, CTPA use, and preceding COVID-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.