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    Impact of Carvedilol on QT Interval Dispersion in Patients with Chronic Heart Failure
    (Journal of Cardiac Failure, 2003) Albuquerque, Denilson C.; Paola, Angelo A.V. de; Rocha, Ricardo M.; Tura, Bernardo; Albanesi Filho, Francisco M.; Veloso, Henrique H.
    Background: The role of QT interval dispersion (QTD) in heart failure (HF) remains poorly defined and controversial. Our objective was to evaluate the impact of QTD in the clinical evolution of chronic HF patients under control due to the use of carvedilol (CVD). Methods: We selected 108 patients (22-82 years), 65.7% were male, 72.2% caucasians, with stable chronic HF and NYHA functional class (FC) II, III and IV on optimized treatment, with an left ventricle ejection fraction (LVEF) of 0.40 for therapy with CVD. All patients had complete history taken and physical exam performed, as well as, laboratorial evaluation, electrocardiogram, echocardiogram and followed-up at the HF clinic for an average period of 38.2 months. All used CVD at the maximum tolerated dose. The evaluated parameters were: general characteristics of the population, cardiopathy etiology, concomitant medication used, NYHA’s FC, maximum CVD dose, LVEF and QTD before and 6 months after CVD and deaths. Results: A QTD reduction (109ms to 72ms) and an increase in the LVEF (0.27 to 0.35) was found after 6 months of therapy with CVD (p 0.001). The general characteristics of the population (p 0.05), concomitant medications (p 0.05), CVD dose (p 0.80), cardiopathy etiology (p 0.959) did not influence in the QTD reduction. This reduction was related to the patients with worse NYHA FC pre-CVD (p 0.007) and with NYHA FC improvement (p 0.028). The ROC curve analysis post-CVD determined that QTD 90ms was a mortality predictor (p 0.034; OR 3.912) (AUC 0.061; sensibility 29.2%; specificity 90.5%; positive likelihood ratio 3.06; negative likelihood ratio 0.78). The multivariate analysis showed that the QTD reduction was an independent survival predictor (p 0.004; OR 5.48). Conclusions: CVD reduced the QTD and increased the LVEF in patients with chronic HF. We did not observe interaction among QTD reduction and population characteristics. The QTD reduction was not influenced by concomitant medications, cardiopathy etiology and CVD dose. The largest QTD reduction occurred specially in worst patients (NYHA FC III and IV). The presence of QTD reduction was an independent predictor of survival and the QTD 90ms post-CVD was predictor of mortality.
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    Como o ecocardiograma pode ser útil em predizer a morte em crianças com cardiomiopatia dilatada idiopática?
    (Arquivos Brasileiros de Cardiologia, 2004) Azevedo, Vitor Manuel Pereira; Albanesi Filho, Francisco Manes; Santos, Marco Aurélio; Castier, Márcia Bueno; Tura, Bernardo Rangel
    OBJETIVO: Determinar os fatores preditores ecocardiográficos de morte em crianças com cardiomiopatia dilatada idiopática. MÉTODOS: Estudo retrospectivo de 148 crianças com cardiomiopatia dilatada idiopática diagnosticadas entre setembro/1979 a março/2003. Critérios para inclusão: insuficiência cardíaca e redução da contratilidade no ecocardiograma, na ausência de cardiopatia congênita ou secundária. Foram analisados 470 exames, durante 244,8 meses de evolução. Parâmetros analisados: dimensão do átrio esquerdo (DAE), relação átrio esquerdo/aorta (DAE/Ao), dimensão sistólica (DSVE) e diastólica (DDVE) do VE, massa do VE (massa), dimensão do ventrículo direito (DVD), fração de ejeção do VE (FE), percentagem de encurtamento do VE (%EC), gravidade da insuficiência das valvas atrioventriculares e da valva pulmonar e medida da pressão sistólica (PsVD) e diastólica (PdVD) do VD. Foi considerado significativo erro alfa <0,05. RESULTADOS: Idade média de 2,37 anos, ocorridos 35 óbitos (23,7% - IC95=17,1% a 31,2%). ANOVA demonstrou: DAE (p<0,0001), DAE/Ao (p<0,0001), DSVE (p=0,0061), DDVE (p=0,0086), massa (p<0,0001), FE (p=0,0074), %EC (p=0,0072) e DVD (p<0,0001). O agravamento da insuficiência mitral (IM) (p=0,0113) e tricúspide (IT) (p=0,0044) foram marcadores de óbito e a presença de IM, IT e insuficiência pulmonar moderada/grave foram deletérias à sobrevida. A análise de Cox demonstrou como preditores independentes da morte: DAE/Ao (p=0,0487), FE (<0,0001) e presença de IM moderada/grave (p=0,0419). CONCLUSÃO: Os pacientes com aumento progressivo da DAE/Ao, redução da FE e agravamento progressivo da IM, a despeito do tratamento clínico, devem ser considerados precocemente em programa de transplante cardíaco.
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    Macrophage migration inhibitory factor is associated with positive cultures in patients with sepsis after cardiac surgery
    (Shock, 2005) Mendonça-Filho, Hugo Tannus Furtado de; Gomes, Gleice Silva; Nogueira, Pedro Miguel Mattos; Fernandes, Marco Aurelio de Oliveira; Tura, Bernardo Rangel; Santos, Marisa; Castro-Faria-Neto, Hugo Caire
    This prospective consecutive observational study describes the blood levels of macrophage migration inhibitory factor (MIF), other cytokines, and markers of acute-phase response in 49 consecutive patients who developed the clinical syndrome of sepsis after cardiac surgery. Before starting antimicrobial treatment, all patients underwent microbiologic screening, and blood samples were collected. These samples subsequently were assayed for MIF, macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and -10, procalcitonin (PCT), and C-reactive protein (CRP). Patients with positive cultures (n = 25) had a higher mortality (P = 0.046) and higher levels of MIF (P < 0.001) than those with negative cultures (n = 24). We could not detect significant difference between the groups concerning the levels of CRP, PCT, IL6, IL10, MCP-1, or TNF-alpha. MIF levels showed an area under receiver operator curve of 0.823 for the prediction of culture-proven bacterial infection, with the best cut-off value at 988.5 pg/mL. In conclusion, circulating levels of MIF could be indicated as a valuable marker of microbiologically documented sepsis in patients after cardiac surgery, which suggests that MIF may be prospectively explored as a useful diagnostic tool in this setting.
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    Sintomas depressivos e óbito em síndromes coronarianas isquêmicas agudas
    (Revista Brasileira de Psiquiatria. 2005;27(2):163-7, 2005) Lougon, Mauricio; Mattos, Marco Antonio de; Tura, Bernardo
    Carta aos editores da Revista Brasileira de Psiquiatria
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    Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study
    (Trials, 2007) Tura, Bernardo R; Martino, Helena F; Gowdak, Luis H; Santos, Ricardo Ribeiro dos; Dohmann, Hans F; Krieger, José E; Feitosa, Gilson; Vilas-Boas, Fabio; Oliveira, Sergio A; Silva, Suzana A; Bozza, Augusto Z; Borojevic, Radovan; Carvalho, Antonio C Campos de
    Background: Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/design: We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion: Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).
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    Is myocardial performance index an independent echocardiographic marker of death in children with idiopathic dilated cardiomyopathy?
    (Clinical Cardiology, 2008) Azevedo, Vitor Manuel P; Albanesi Filho, Francisco M; Santos, Marco Aurélio; Castier, Márcia B; Tura, Bernardo R; Amino, José Geraldo; Cunha, Maria Ourinda Mesquita da
    Background: Myocardial performance index (MPI) was reported as a parameter of ventricular systolic and diastolic function, as well as a useful tool to predict the outcome in patients with ventricular dysfunction. Hypothesis: To compare MPI with classical echocardiographic parameters as an independent marker of death in children with idiopathic dilated cardiomyopathy (IDCM). Methods: Fifty-five children (13 deaths) underwent 104 echocardiograms from January 1996 to May 2005. Right ventricle (RV) MPI and left ventricle (LV) MPI, and 9 classical echocardiographic parameters (left atrium [LA]/body surface area [BSA], distance between mitral E point and ventricular septum, LV mass/body surface area, RV shortening fraction, LV end-systolic and end-diastolic dimensions/body surface area, LV ejection fraction, fiber circumferential shortening velocity, and mitral deceleration time) were compared. Statistical analysis was performed by chi-square, Pearson's correlation and Student t-test, Kaplan-Meier method, Cox's method, and receiver operating curve (ROC). Statistical significance was considered with alpha<0.05 and p=0.80]. Results: Univariate analysis showed that all studied parameters were markers of death. There was a high correlation between RVMPI and LVMPI (r=0.847]-p=0.0001]); therefore, to avoid bias, RVMPI was discharged from multivariate analysis. In the deceased group, moderate/severe mitral regurgitation was frequent (76.9%; confidence interval [CI[ 95%=46.2%- 94.9%) and it was considered in multivariate analysis. In Cox's multivariate analysis, LVMPI was the only independent marker of death (p=0.0213]). The ideal cut-off was 0.63 with 92.3% sensitivity, 66.7% specificity, and fitted ROC area=0.918]. Conclusions: In children with IDCM, LVMPI is an independent marker of death.
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    Influência da Terapia com Espironolactona sobre Níveis Sangüíneos de Tiamina em Pacientes com Insuficiência Cardíaca
    (Arquivos Brasileiros de Cardiologia, 2008) Rocha, Ricardo Mourilhe; Silva, Guilherme Vianna e; Albuquerque, Denilson Campos de; Tura, Bernardo Rangel; Albanesi Filho, Francisco Manes
    FUNDAMENTO: Estudos do manejo não-farmacológico da insuficiência cardíaca (IC) têm sido muito escassos. A importância de micronutrientes como tiamina há muito é conhecida, uma vez que sua deficiência está associada com o desenvolvimento de IC de alto débito. OBJETIVO: Nós estudamos a relação entre adicionar à inibição da ECA uma supressão adicional da aldosterona com espironolactona e níveis sangüíneos de tiamina (pmol/ml). MÉTODOS: Um total de 22 pacientes (pc) com IC (classes III/IV da NYHA) foi dividido em dois grupos [grupo I - espironolactona 25mg/dia (n=11) e grupo II - sem espironolactona (n=11)]. Determinamos os níveis de tiamina pelo uso da atividade da transcetolase eritrocitária. Os grupos foram comparados com relação à ingesta alimentar, demografia, doses de furosemida e níveis sangüíneos de tiamina, usando os testes de Mann-Whitney e t de Student. Analisamos as proporções com testes de qui-quadrado e de Kruskal-Wallis para associarmos a tiamina com fatores demográficos e usamos as doses de furosemida como variáveis dependentes. RESULTADOS: Os grupos I e II eram similares em relação à ingesta alimentar, doses diárias de furosemida (110,9±30,2 e 105,5±26,9 mg, respectivamente; p>0,05), demografia (etiologia, idade, hipertensão, diabete, tabagismo, abuso de álcool, dislipidemia e tratamento adjuvante da IC com drogas). Os pacientes do grupo I mostraram níveis de tiamina significativamente superiores, comparados com aqueles do grupo II (277,2±89,8 e 154,7±35,7, respectivamente) (p<0,001). Nenhuma das variáveis dependentes citadas acima estava associada com a tiamina. CONCLUSÃO: Em uma coorte de pacientes ambulatoriais com IC tratados com alta dose de diuréticos de alça, o uso de espironolactona está associado com níveis sangüíneos superiores de tiamina. A importância deste achado ainda deverá ser estabelecida por estudos futuros com desenho prospectivo e amostras maiores.
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    Custo-efetividade da trombólise pré-hospitalar vs intra-hospitalar no infarto agudo do miocárdio
    (Arquivos Brasileiros de Cardiologia, 2008) Araújo, Denizar Vianna; Tura, Bernardo Rangel; Brasileiro, Antonio Luiz; Luz Neto, Heitor; Pavão, Ana Luiza Braz; Teich, Vanessa
    FUNDAMENTO: Existe evidência de que a trombólise pré-hospitalar melhora os desfechos no infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST. OBJETIVO: Comparar as relações de custo-efetividade entre trombólise pré-hospitalar e trombólise intra-hospitalar para o IAM com supradesnivelamento do segmento ST, pela perspectiva do Sistema Único de Saúde. MÉTODOS: Modelo analítico de decisão foi utilizado para comparar as duas estratégias. O desfecho do estudo foi "anos de vida ganhos". O uso de recursos e os custos foram estimados pela perspectiva do Sistema Único de Saúde. Árvore de decisão e modelo de Markov foram construídos com resultados de ensaios clínicos publicados. Os custos foram valorados em real (R$), para o ano de 2005. RESULTADOS: Para um horizonte de tempo de vinte anos, a expectativa de vida média com a trombólise pré-hospitalar foi de 11,48 anos e a trombólise intra-hospitalar proporcionou expectativa de vida média de 11,32 anos. Os custos foram de R$ 5.640,00 para a trombólise pré-hospitalar e de R$ 5.816,00 para a trombólise intra-hospitalar. Houve custo adicional de R$ 176,00 por paciente com a trombólise intra-hospitalar. A trombólise pré-hospitalar proporcionou adicional de 0,15 ano de expectativa de vida comparado à trombólise intra-hospitalar. CONCLUSÃO: Esse modelo sugere que, pela perspectiva do Sistema Único de Saúde, implementar a trombólise pré-hospitalar para o IAM com supradesnivelamento do segmento ST pode representar sobrevida extra e menor custo que comparativamente à trombólise intra-hospitalar.
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    Práticas cirúrgicas baseadas em evidências: tomografia computadorizada helicoidal no diagnóstico da apendicite aguda
    (Revista do Colégio Brasileiro de Cirurgiões, 2008) Guimarães, Carlos Alberto; Santos, Bráulio dos
    Os cirurgiões são instados a não somente ler os artigos dos periódicos, mas também a compreendê-los e analisá-los criticamente quanto à validade. Eles cuidam melhor dos seus pacientes se são capazes de analisar criticamente a literatura e aplicar os resultados a sua prática. Este é o segundo artigo de uma série - Práticas Cirúrgicas Baseadas em Evidência - que tem por objetivo apresentar a avaliação crítica de um teste diagnóstico.
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    Evolução para hipertensão arterial em pacientes com diabetes tipo 1
    (Arquivos Brasileiros de Endocrinologia & Metabologia, 2008) Cobas, Roberta; Santos, Bráulio; Braga, Luiza; Cunha, Edna Ferreira; Gomes, Marilia de Brito
    Purpose: Check the evolution of type 1(T1) diabetic patients to hypertension and prehypertension and baseline factors related to final blood pressure levels (BP). Methods: Observational study involving 127 T1 diabetic patients submitted to clinical and laboratory evaluation and followed by for 5 (2.4-9.2) years. Results: From the initially normotensive patients, 21.7% developed prehypertension, 4.7% developed hypertension and 73.6% remained with normal BP. From the prehypertensive patients, 35% returned to normal BP, 50% remained prehypertensive and 15% developed hypertension. The relative risk for hypertension development was 3.2 (0.8-12.3) in the prehypertensive compared to the normotensive group. The prevalence of prehypertension and hypertension increased from 15.7% to 26% and 0.8% to 7% respectively. Levels of serum creatinine predicted final levels of systolic and diastolic BP. Conclusion: It is emphasized the importance of renal function and BP evaluation even when they are in normal range to minimize the deleterious effects of hypertension in the development of nephropathy and cardiovascular disease.
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    Embolia pulmonar: registro multicêntrico da prática clínica em hospitais terciários
    (Revista Brasileira de Terapia Intensiva, 2009) Volschan, André; Albuquerque, Denilson Campos de; Tura, Bernardo Rangel; Knibel, Marcos de Freitas; Souza, Paulo César Pereira da Silva e; Toscano, Maria Luiza
    INTRODUÇÃO: O perfil clínico e as estratégias diagnósticas e terapêuticas nos pacientes com embolia pulmonar demonstram a prática clínica na abordagem da doença. Essas informações, escassas nos estudos nacionais, possibilitam melhor conhecimento da embolia pulmonar. MÉTODOS: Estudo multicêntrico de 727 pacientes admitidos em unidades de emergência ou terapia intensiva, com o diagnóstico de embolia pulmonar confirmado por um ou mais dos seguintes exames: arteriografia pulmonar angiotomografia computadorizada helicoidal angioressonância magnética, ecodopplercardiograma, cintilografia pulmonar ou duplex-scan venoso. Dados demográficos, comorbidades, manifestações clínicas e métodos complementares foram analisados. RESULTADOS: A média de idade foi 68 anos, sendo 42% homens. Os fatores de risco mais prevalentes foram: idade > 40 anos, repouso no leito e neoplasia. A dispnéia, taquipnéia, taquicardia, dor torácica, foram as manifestações clínicas mais frequentes. O eletrocardiograma apresentou alterações em 30%, a radiografia de tórax em 45%, o duplex-scan venoso em 69% e o ecodopplercardiograma em 37%. O D-dímero a troponina e a CKMB foram positivos em respectivamente 93, 9 e 8%. Os métodos mais utilizados para o diagnóstico foram: tomografia computadorizada: 47%, duplex-scan venoso: 14% e cintilografia pulmonar: 14%. As formas mais freqüentes de tratamento foram: heparina não fracionada 50%, heparina de baixo peso molecular 30% e trombolítico 12%. A mortalidade intra-hospitalar foi de 19,5%. CONCLUSÕES: Observou-se que a idade > 40 anos, imobilização prolongada e neoplasia foram os fatores de risco de maior prevalência e a dispnéia a apresentação clínica mais freqüente. A angiotomografia computadorizada helicoidal foi o método mais utilizado para o diagnóstico e a heparina não fracionada a principal forma de tratamento.
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    Rationale, design, and baseline characteristics of the Acetylcystein for Contrast-Induced nephropaThy (ACT) Trial: a pragmatic randomized controlled trial to evaluate the efficacy of acetylcysteine for the prevention of contrast-induced nephropathy
    (Trials, 2009) ACT Trial Investigators; Tura, Bernardo R; Cramer, Helena; Santos Jr., Bráulio
    Background: Aceltylcysteine has been evaluated in several small trials as a means of reducing the risk of contrast-induced nephropathy (CIN), however systematic reviews of these studies do not provide conclusive answers. Therefore, a large randomized controlled trial (RCT) is needed to provide a reliable answer as to whether acetylcysteine is effective in decreasing the risk of CIN in high-risk patients undergoing angiographic procedures. Methods: ACT is a RCT of acetylcysteine versus placebo in 2,300 patients at-risk for CIN undergoing an intravascular angiographic procedure. The randomization list will be concealed. Participants, health care staff, investigators and outcome assessors will be blinded to whether patients receive acetylcysteine or placebo. All analysis will follow the intention-to-treat principle. The study drugs (acetylcysteine 1200 mg or placebo) will be administered orally twice daily for two doses before and two doses after the procedure. The primary outcome is the occurrence of CIN, defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography. Discussion: The first patient entered the trial on September, 2008. Up to April 7, 2009, 810 patients had been included in 35 centers. The mean age was 69 (Standard deviation: 10), 18% had a baseline serum creatinine >1.5 mg/dL, 57% were diabetics and 13% had a history of heart failure. The ongoing ACT Trial is the largest multicentre RCT that will determine whether acetylcysteine is effective in decreasing the risk of CIN in patients at risk undergoing angiography. Trial registration: Clinicaltrials.gov NCT00736866.
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    Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats
    (BMC Veterinary Research, 2010) Lessa, Andréia S; Paredes, Bruno D; Dias, Juliana V; Carvalho, Adriana B; Quintanilha, Luiz Fernando; Takiya, Christina M; Tura, Bernardo R; Rezende, Guilherme F M; Carvalho, Antonio C Campos de; Resende, Célia M C; Goldenberg, Regina C S
    Background: Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results: Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion: The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies.
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    A risk score based on spectral turbulence analysis of the signal averaged ECG for predicting cardiac death in subjects with chronic chagas heart disease
    (Heart Rhythm, 2010) Barbosa, Paulo R.; Tura, Bernardo R.; Barbosa, Eduardo C.; Barbosa-Filho, José; Kantharia, Bharat K.
    Introduction: Cardiac involvement is the main cause of death in chronic Chagas disease (CCD). This study prospectively investigated signal-averaged ECG (SAECG), 24h-ambulatory ECG and echocardiogram parameters in CCD aiming at developing a predictive score for death. Methods: Clinically stable outpatients with CCD (34 to 74 y.o, 38 males) staged according to Los Andes (Class I: N=28; II: N=48; III: N=24) were enrolled. Deaths were ascertained by review of medical records. SAECG was acquired on admission. Spectral turbulence analysis (STA) was carried out on XYZ leads after short-time Fourier transform mapping of ventricular activation, and applying intersegment spectral correlation technique. Results: During a follow-up of (mean±SEM) 95.3 ± 3.1 months, 20 patients died (rate: 26.4 ± 1.4/year). In multivariate Cox proportional hazard model, NSVT/24h (p=0.006), LVEF<50% (p<0.001), and positive STA (p=0.001) were independent predictors of death (Table inset). A prognostic score was developed by calculating weighted points proportional to beta coefficient in Cox model (Table inset). ROC analysis showed optimal cut-off value at 5 (Figure A). KM curves of novel score for deaths are presented in Figure B (proportional hazard test: rho=-0.5; p=0.06). In 1,000 bootstraps, ROC c-statistic of novel score was superior to Rassi score (Figure C). Conclusions: In CCD, NSVT, LVEF<50% and high SAECG spectral turbulence are independent predictors of death. A novel risk score improves predictive accuracy in this population.
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    A novel risk score for predicting new-onset atrial fibrillation in subjects with chronic chagas heart disease
    (Heart Rhythm, 2010) Barbosa, Paulo R.; Tura, Bernardo R.; Barbosa-Filho, José; Kantharia, Bharat K.
    Introduction: Atrial fibrillation affects about 20% of subjects with chronic Chagas disease (CCD) and heralds poor prognosis. This study prospectively investigated echocardiographic and electrocardiographic parameters aiming at creating a risk score for new-onset AF (NOAF) in CCD and to compare its performance to Rassi score. Methods: Clinically stable outpatients with CCD (34 to 74 y.o, 38 males) staged according to Los Andes (Class I: N=28; II: N=48; III: N=24) were enrolled. Patients were assessed by 12-lead ECG, 24h ambulatory ECG and 1D/2D echocardiogram. NOAF lasting >24h was tracked at three to six-month intervals. Results: During a follow-up of (mean±SEM) 91.2 ± 3.2 months, 18 developed NOAF (incidence: 30.2 ± 2.6 /year), and 20 died (rate: 26.4 ± 1.4 /year). Relative risk of NOAF for cardiac death was 3.6 (p=0.001). In multivariate Cox proportional hazard model, PVC>3,000/24h (p=0.02), LAD>3.3cm (p=0.001), and PAP>30mmHg (p=0.004) were independent predictors for NOAF (Table inset). A prognostic score for NOAF was developed by calculating weighted points proportional to beta coefficient in Cox model (table inset). ROC analysis of novel score showed optimal cut-off value at 2 (Figure A). KM curves of novel score for NOAF is presented in Figure B (proportional hazard test: rho=0.1; p=0.6). In 1,000 bootstraps, ROC c-statistic of novel score was significantly superior to Rassi score (Figure C). Conclusions: In CCD, high grade PVC, LAD>3.3cm and PAP>30mmHg are independent predictors for NOAF. Novel risk score improves NOAF predictive accuracy in this population.
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    Cortisol levels and adrenal response in severe community-acquired pneumonia: A systematic review of the literature
    (Journal of Critical Care, 2010) Salluh, Jorge I.F.; Shinotsuka, Cássia Righy; Soares, Márcio; Bozza, Fernando A.; Silva, José Roberto Lapa e; Tura, Bernardo Rangel; Bozza, Patrícia T.; Vidal, Carolina Garcia
    Objectives: Our aim was to review the literature on the prevalence and impact of critical-illness related corticosteroid insufficiency (CIRCI) on the outcomes of patients with severe community-acquired pneumonia (CAP). Methods: We reviewed Cochrane, Medline, and CINAHL databases (through July 2008) to identify studies evaluating the adrenal function in severe CAP. Main data collected were prevalence of CIRCI and its mortality. Results: We screened 152 articles and identified 7 valid studies. Evaluation of adrenal function varied, and most studies used baseline total cortisol levels. The prevalence of CIRCI in severe CAP ranged from 0% to 48%. Among 533 patients, 56 (10.7%) had cortisol levels of 10 μg/dL or less and 121 patients (21.2%) had cortisol levels of 15 μg/dL or less. In a raw analysis, there was no significant difference in mortality when patients with cortisol levels less than 10 μg/dL (8.6 vs 15.5%; P = .55) or less than 15 μg/dL (12.4 vs 16%; P = .38) were compared with those with cortisol above these levels. In the meta-analysis, relative risk for mortality were 0.81 (confidence interval, 0.39-1.7; P = .59; χ2 = 1.04) for cortisol levels less than 10 μg/dL and relative risk was 0.67 (confidence interval, 0.4-1.14; P = .84; χ2 = 1.4) for cortisol levels less than 15 μg/dL. Conclusions: A significant proportion of patients with severe CAP fulfilled criteria for CIRCI. However, CIRCI does not seem to affect the outcomes. Noteworthy, the presence of elevated cortisol levels is associated with increased mortality and may be useful as a prognostic marker in patients with severe CAP.
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    Análise em longo prazo na síndrome coronariana aguda: existem diferenças na morbimortalidade?
    (Arquivos Brasileiros de Cardiologia, 2010) Aguiar, Adolfo Alexandre Farah de; Mourilhe-Rocha, Ricardo; Esporcatte, Roberto; Amorim, Liana Correa; Tura, Bernardo Rangel; Albuquerque, Denilson Campos de
    FUNDAMENTO: A insuficiência cardíaca (IC) tem grande importância como preditor de morbimortalidade em pacientes com síndrome coronariana aguda (SCA). OBJETIVO: Avaliar os preditores de morbimortalidade na SCA em longo prazo. MÉTODOS: Foi um estudo de coorte de 403 pacientes consecutivos com queixas de dor torácica. Descreveram-se dados demográficos, clínicos, laboratoriais e terapêuticos, sendo avaliados durante a internação e até oito anos após alta, em relação à presença ou ausência de eventos cardiovasculares e óbitos. RESULTADOS: Foram 403 pacientes com queixas de dor torácica, em que 65,8% apresentavam diagnóstico de SCA sem supra de ST, 27,8% SCA com supra de ST e 6,5% sem SCA. Destes, foram avaliados os 377 pacientes com SCA, em que 37,9% eram do sexo feminino, e a média de idade foi de 62,2 ± 11,6 anos. A presença de IC antes ou durante a hospitalização influenciou a mortalidade. Dos fatores prognósticos, a creatinina inicial merece destaque, sendo o ponto de corte de 1,4 mg/dl (acurácia = 62,1%; HR = 3,27; p < 0,001). Notamos pior prognóstico para cada acréscimo de dez anos de idade (HR = 1,37; p < 0,001) e para cada incremento de 10 bpm na frequência cardíaca (HR = 1,22 p < 0,001). Quanto às terapias utilizadas antes e após 2002, houve aumento de uso de betabloqueadores, inibidores da enzima conversora da angiotensina (IECAs), estatinas e antiplaquetários, tendo impacto na mortalidade. CONCLUSÃO: Presença de IC admissional, creatinina, idade e FC foram preditores independentes de mortalidade. Observou-se que pacientes com IC atendidos antes de 2002 apresentaram pior sobrevida em relação aos atendidos após 2002 e que a mudança na terapia foi a responsável por isso.
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    Prevalence of potential bacterial respiratory pathogens in the oral cavity of hospitalised individuals
    (Archives of Oral Biology, 2010) Zuanazzi, David; Souto, Renata; Mattos, Marcelo Barbosa Accioly; Zuanazzi, Maura Rodrigues; Tura, Bernardo Rangel; Sansone, Carmelo; Colombo, Ana Paula Vieira
    Objective: To assess the prevalence of oral colonisation by bacterial respiratory pathogens in hospitalised patients. Methods: Thirty patients undergoing myocardium revascularisation surgery were evalu ated. At baseline (pre-operative phase), full-mouth clinical periodontal assessment was performed. Saliva and biofilm samples were obtained from subjects at baseline and at the post-operative phase, after orotracheal extubation. DNA was extracted from samples and species of Acinetobacter, Pseudomonas, Staphylococcus aureus and Dialister pneumosintes were detected by PCR or culture (for staphylococci isolates). Results: Most of the subjects were males, with history of hypertension and smoking. Thirteen were edentulous (ED) and 17 were dentate (DE), with moderate chronic period ontitis. The most prevalent bacteria in saliva were Staphylococcus spp. (85.7%), Pseudomonas spp. (83.8%), and Acinetobacter spp. (53.3%). There was a trend for D. pneumosintes to be more frequently detected in DE (43.7%) than ED (11.5%) patients. In plaque samples, DE with >14 teeth showed a higher prevalence of Pseudomonas spp. (100%) than individuals with 14 teeth (69.1%; p = 0.048). Conversely, P. aeruginosa was more prevalent in subjects with fewer teeth (35.5%) than with >14 teeth (5.7%; p = 0.037). All staphylococci isolates were coagulase negative, and about 11% were positive for the mecA gene. These mecA-positive isolates showed a tendency to increase in all samples, whereas P. aeruginosa reduced after surgery. A strong correlation between the presence of Acinetobacter spp. and Pseudomonas spp. was observed (rho = 0.886, p < 0.05). Conclusions: The oral cavity of hospitalised patients harbours high frequencies of bacterial respiratory pathogens, supporting its potential role as a reservoir for these species.
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    Análise de custo-efetividade da Sinvastatina versus Atorvastatina na prevenção secundária de eventos cardiovasculares no Sistema Único de Saúde brasileiro
    (Value in Health, 2011) Araujo, Denizar Vianna; Souza, Camila Pepe Ribeiro de; Bahia, Luciana Ribeiro; Rey, Helena Cramer Veiga; Santos Junior, Braulio; Tura, Bernardo Rangel; Berwanger, Otavio; Buehler, Anna Maria; Silva, Marcus Tolentino
    Objective The objective of this study is to perform an economic evaluation analyzing the treatment with atorvastatin and simvastatin in comparison to placebo treatment, within the Brazilian Public Healthcare System (SUS) scenario, for patients with high risk of cardiovascular disease; analyzing if the additional cost related to statin treatment is justified by the clinical benefits expected, in terms of cardiovascular event and mortality reduction. Methods Cardiovascular event risk and mortality risk were used as outcomes. Statin efficacy at LDL-c and cardiovascular events levels lowering data was obtained from a systematic review of literature. A decision analytic model was developed to perform a cost-effectiveness analysis comparing atorvastatin 10mg/day and simvastatin 40mg/day to placebo treatment in patients with dyslipidemia in Brazil. The target population of this study was a hypothetic cohort of men and women with a mean age of 50 years old and high risk of cardiovascular disease. The model includes only direct costs obtained from Ambulatory and Hospital Information System and Price Database of Brazilian Ministry of Health. The comparative cost-effectiveness analysis itself was done through Excel spreadsheets covering a 5 -years time horizon. Results The result shows that atorvastatin 10mg/day in comparison to placebo has higher cost with higher effectiveness in the time horizon of 5 years (Incremental Cost Effectiveness Ratio of R$ 433.065,05 per life year gained). In this scenario atorvastatin is not cost effective in comparison to placebo. The simvastatin 40mg/day appears to be a strategy with lower cost and higher effectiveness in comparison to placebo, in the time horizon analyzed (5 years). In the multivariate probabilistic sensitivity analysis, simvastatin showed 53% of the results in the quadrant with greater effectiveness and lower cost. Conclusions This study is an important tool for public decision makers. The study can be used in the decision process of increasing cardiovascular disease treatment access with budgetary sustainability for Ministry of Health. In comparison to placebo, the results show that sinvastatin is a cost saving strategy while atorvastatin is not cost effective.
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    Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia
    (NeuroImage, 2011) Moll, Jorge; Zahn, Roland; Oliveira-Souza, Ricardo de; Bramati, Ivanei E.; Krueger, Frank; Tura, Bernardo; Cavanagh, Alyson L.; Grafman, Jordan
    Poets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care about others and to be concerned about our mistakes. Functional imaging studies have implicated frontopolar, ventromedial frontal and basal forebrain regions in the experience of prosocial sentiments. Patients with lesions of the frontopolar and ventromedial frontal areas were observed to behave inappropriately and less prosocially, which could be attributed to a generalized emotional blunting. Direct experimental evidence for brain regions distinctively associated with moral sentiment impairments is lacking, however. We investigated this issue in patients with the behavioral variant of frontotemporal dementia, a disorder in which early and selective impairments of social conduct are consistently observed. Using a novel moral sentiment task, we show that the degree of impairment of prosocial sentiments is associated with the degree of damage to frontopolar cortex and septal area, as assessed with 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an established measure of neurodegenerative damage. This effect was dissociable from impairment of other-critical feelings (anger and disgust), which was in turn associated with dorsomedial prefrontal and amygdala dysfunction. Our findings suggest a critical role of the frontopolar cortex and septal region in enabling prosocial sentiments, a fundamental component of moral conscience