Highlights from the IV International Symposium of Thrombosis and Anticoagulation (ISTA), October 20-21, 2011, Salvador, Bahia, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fourth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, from October 20-21, 2011. This scientific program was developed by clinicians for clinicians and was promoted by three major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, and Hospital do Coração Research Institute. Comprising 2 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Factors That Impact the Decision to Perform Left Ventriculography in Coronary Artery Disease. / Fatores que Impactam a Decisão de Realizar Ventriculografia Esquerda em Doença Arterial Coronariana.

BACKGROUND: Left ventriculography is an invasive method for assessment of left ventricular systolic function. Since the advent of noninvasive methods, its use has been questioned, as it carries some risk to the patient. OBJECTIVE: To assess which factors are independently associated with the decision to perform ventriculography in patients with coronary artery disease. METHODS: Analytical, retrospective, database review study of electronic medical records comparing 21 predefined variables of interest among patients undergoing coronary angiography. P-values <0.05 were considered significant. RESULTS: We evaluated 600 consecutive patients undergoing coronary angiography. Left ventriculography was performed in the majority of cases (54%). After multivariate analysis, patients with chronic coronary syndrome (OR 1.72; 95% CI: 1.20-2.46; p < 0.01) were more likely to undergo the procedure. Patients with known ventricular function (OR 0.58; 95% CI: 0.40-0.85; p < 0.01); those with a history of CABG (OR 0.31; 95% CI: 0.14-0.69; p < 0.01) or hypertension (OR 0.58; 95% CI: 0.36-0.94; p = 0.02); and those with higher creatinine levels (OR 0.42; 95% CI: 0.26-0.69; p < 0.01) had greater odds of not undergoing ventriculography. CONCLUSIONS: In patients undergoing coronary angiography, a diagnosis of chronic coronary syndrome was independently associated with greater likelihood of left ventriculography, while having previously determined ventricular function, a history of hypertension or CABG, and higher creatinine levels were associated with a decreased likelihood of undergoing this procedure.

FUNDAMENTO: A ventriculografia esquerda é um método invasivo para avaliar a função sistólica do ventrículo esquerdo. Depois do advento de métodos não invasivos, o seu uso tem sido questionado por resultar em algum risco para o paciente. OBJETIVOS: Avaliar quais fatores associam-se independentemente com a decisão de realizar ventriculografia em pacientes com doença arterial coronariana. MÉTODOS: Tratou-se de um estudo analítico, retrospectivo, avaliando prontuários eletrônicos e banco de dados e comparando 21 variáveis de interesse pré-definidas entre pacientes submetidos a cineangiocoronariografia. Foi considerado significante p < 0,05. RESULTADOS: Avaliamos 600 pacientes consecutivos, e a ventriculografia esquerda foi realizada na maioria dos pacientes submetidos a uma cineangiocoronariografia (54%). Depois da análise multivariada, os pacientes com síndromes coronarianas crônicas ( odds ratio [OR] 1,72; intervalo de confiança de 95% [IC 95%]: 1,20­2,46; p < 0,01) tiveram maior chance de serem submetidos ao procedimento. Os pacientes com função ventricular conhecida (OR = 0,58; IC 95%: 0,40­0,85; p < 0,01), os revascularizados (OR 0,31; IC 95% 0,14­0,69; p < 0,01), os hipertensos (OR 0,58; IC 95%: 0,36­0,94; p = 0,02) e aqueles com maiores valores de creatinina (OR 0,42; IC 95% 0,26­0,69; p < 0,01) tiveram maior chance de não realizar ventriculografia. CONCLUSÕES: Nos pacientes submetidos a cineangiocoronariografia, o diagnóstico de síndrome coronariana crônica associou-se de modo independente com uma maior realização da técnica, enquanto ter a função ventricular previamente conhecida, ser hipertenso, ter sido submetido a revascularização cirúrgica prévia e ter valores de creatinina mais elevados associaram-se a uma maior chance de não realizar o método.

Invasive and noninvasive correlations of B-type natriuretic peptide in patients with heart failure due to Chagas cardiomyopathy.

Heart failure due to Chagas cardiomyopathy (HFCC) differs from failure with other etiologies because of the occurrence of intense inflammatory infiltrate and right ventricle compromise. This article investigates correlations of B-type natriuretic peptide (BNP) levels with parameters of severity in HFCC. Twenty-eight patients and 8 normal controls underwent heart catheterization and clinical and laboratory analyses. BNP levels were higher in patients with HFCC (P<.0001) and correlated with New York Heart Association (NYHA) class; right atrial pressure; wedge pressure; cardiac output; levels of serum sodium, hemoglobin, urea, and tumor necrosis factor-alpha; and ejection fraction. Interferon-gamma and transforming growth factor-beta did not correlate with BNP level. The authors conclude that BNP levels are elevated in patients experiencing HFCC, irrespective of NYHA class, and that the occurrence of HFCC correlates with severity of disease.

Evaluation of the Bleeding Intensity of Patients Anticoagulated with Warfarin or Dabigatran Undergoing Dental Procedures.

BACKGROUND: Thrombotic disorders remain one of the leading causes of death in the Western world. Dabigatran appeared as an alternative to warfarin for anticoagulation in the treatment of atrial fibrillation (AF). The risk associated with bleeding due to its use has been documented in several randomized clinical trials, but no large study has examined in detail the risk of bleeding during dental extraction and other dental procedures involving bleeding. OBJECTIVE: To compare the intensity of bleeding in individuals taking dabigatran or vitamin K antagonist (warfarin) and undergoing dental procedures. METHODS: Prospective, single-center, controlled study with one single observer. Patients diagnosed with nonvalvular AF, on warfarin or dabigatran, cared for at a cardiology referral center, and requiring single or multiple dental extractions, were evaluated up to seven days post-extraction. The following outcomes were assessed: bleeding time between the beginning and the end of suture and complete hemostasis; bleeding before the procedure, after 24 hours, 48 hours, 7 days, during and after suture removal (late); p<0.05 was defined as of statistical relevance. RESULTS: We evaluated 37 individuals, 25 in the warfarin group and 12 in the dabigatran group. Age, sex, weight, height, blood pressure, color, schooling, family income and comorbidities were similar between the two groups. Regarding bleeding after 24 hours of the procedure, no one in the dabigatran group had bleeding, whereas 32% in the warfarin group had documented bleeding (p = 0.028). The other variables analyzed did not differ between the groups. CONCLUSIONS: This study suggests that, regarding dental extraction, there is no statistically significant difference in the intensity of bleeding of patients taking dabigatran as compared to those taking warfarin. Bleeding 24 hours after the procedure was less frequent among patients on dabigatran.

Impact of the Use of Different Diagnostic Criteria in the Prevalence of Dyslipidemia in Pregnant Women.

Background: There is a physiologic elevation of total cholesterol (TC) and triglycerides (TG) during pregnancy. Some authors define dyslipidemia (DLP) in pregnant women when TC, LDL and TG concentrations are above the 95th percentile (p95%) and HDL concentration is below the 5th percentile (P5%) for gestational age (GA). Objective: To compare the prevalence of DLP in pregnant women using percentiles criteria with the V Brazilian Guidelines on Dyslipidemia and the association with maternal and fetal outcomes. Results: Pregnant women with high-risk conditions, aged 18-50 years, and at least one lipid profile during pregnancy was classified as the presence of DLP by two diagnostic criteria. Clinical and laboratorial data of mothers and newborns were evaluated. Conclusion: 433 pregnant women aged 32.9 ± 6.5 years were studied. Most (54.6%) had lipid profile collected during third trimester. The prevalence of any lipid abnormalities according to the criteria of the National Guidelines was 83.8%: TC ≥ 200 mg/dL was found in 49.9%; LDL ≥ 160 mg/dL, in 14.3%, HDL ≤ 50 mg/dL in 44.4% and TG ≥ 150 mg/dL in 65.3%. Any changes of lipid according to percentiles criteria was found in 19.6%: elevation above the P95% for TC was found in 0.7%; for LDL, 1.7%; for TG 6.4% and HDL lower than the P5% in 13%. The frequency of comorbidity: hypertension, diabetes, smoking, obesity and preeclampsia was similar among pregnant women when DLP was compared by both criteria. Conclusion: The prevalence of DLP during pregnancy varies significantly depending on the criteria used, however none demonstrated superiority in association with comorbidities.

Fundamento: Durante a gestação ocorrem, fisiologicamente, elevações do colesterol total (CT) e triglicerídios (TG). Alguns autores definem dislipidemia (DLP) gestacional quando as concentrações de CT, LDL e TG são superiores ao percentil 95 (P95%) e de HDL, inferiores ao percentil 5 (P5%) para a idade gestacional. Objetivo: Comparar a prevalência da DLP em gestantes conforme critério por percentis com o da V Diretriz Brasileira de Dislipidemia e avaliar a associação com desfechos materno-fetais. Métodos: Gestantes com patologias de alto risco, idade entre 18 a 50 anos, e, pelo menos um perfil lipídico durante a gestação foram classificadas quanto à presença de DLP por dois critérios. Dados clínicos e laboratoriais das mães e neonatos foram avaliados. Resultados: Estudou-se 433 gestantes com idade de 32,9 ± 6,5 anos. A maioria (54,6%) teve o perfil lipídico coletado no terceiro trimestre. A prevalência de quaisquer das alterações lipídicas, conforme os critérios da Diretriz Nacional, foi de 83,8%: CT ≥ 200 mg/dL foi encontrado em 49,9%; LDL ≥ 160 mg/dL, em 14,3%, HDL ≤ 50 mg/dL em 44,4% e TG ≥ 150 mg/dL, em 65,3%. Quaisquer das alterações lipídicas pelo critério dos percentis foi encontrada em 19,6%: sendo que elevação superior ao P95% para CT foi encontrada em 0,7%; para LDL, em 1,7%; para TG, em 6,4% e inferiores ao P5% para o HDL em 13%. A frequência das comorbidades: hipertensão, diabetes, tabagismo, obesidade e pré-eclâmpsia foi semelhante entre as gestantes quando se comparou DLP pelos dois critérios. Conclusão: A prevalência de DLP na gestação variou significativamente conforme o critério utilizado, entretanto nenhum demonstrou superioridade na associação com comorbidades.

Fatores que Impactam a Decisão de Realizar Ventriculografia Esquerda em Doença Arterial Coronariana / Factors That Impact the Decision to Perform Left Ventriculography in Coronary Artery Disease

Resumo Fundamento A ventriculografia esquerda é um método invasivo para avaliar a função sistólica do ventrículo esquerdo. Depois do advento de métodos não invasivos, o seu uso tem sido questionado por resultar em algum risco para o paciente. Objetivos Avaliar quais fatores associam-se independentemente com a decisão de realizar ventriculografia em pacientes com doença arterial coronariana. Métodos Tratou-se de um estudo analítico, retrospectivo, avaliando prontuários eletrônicos e banco de dados e comparando 21 variáveis de interesse pré-definidas entre pacientes submetidos a cineangiocoronariografia. Foi considerado significante p < 0,05. Resultados Avaliamos 600 pacientes consecutivos, e a ventriculografia esquerda foi realizada na maioria dos pacientes submetidos a uma cineangiocoronariografia (54%). Depois da análise multivariada, os pacientes com síndromes coronarianas crônicas ( odds ratio [OR] 1,72; intervalo de confiança de 95% [IC 95%]: 1,20-2,46; p < 0,01) tiveram maior chance de serem submetidos ao procedimento. Os pacientes com função ventricular conhecida (OR = 0,58; IC 95%: 0,40-0,85; p < 0,01), os revascularizados (OR 0,31; IC 95% 0,14-0,69; p < 0,01), os hipertensos (OR 0,58; IC 95%: 0,36-0,94; p = 0,02) e aqueles com maiores valores de creatinina (OR 0,42; IC 95% 0,26-0,69; p < 0,01) tiveram maior chance de não realizar ventriculografia. Conclusões Nos pacientes submetidos a cineangiocoronariografia, o diagnóstico de síndrome coronariana crônica associou-se de modo independente com uma maior realização da técnica, enquanto ter a função ventricular previamente conhecida, ser hipertenso, ter sido submetido a revascularização cirúrgica prévia e ter valores de creatinina mais elevados associaram-se a uma maior chance de não realizar o método.

Abstract Background Left ventriculography is an invasive method for assessment of left ventricular systolic function. Since the advent of noninvasive methods, its use has been questioned, as it carries some risk to the patient. Objective To assess which factors are independently associated with the decision to perform ventriculography in patients with coronary artery disease. Methods Analytical, retrospective, database review study of electronic medical records comparing 21 predefined variables of interest among patients undergoing coronary angiography. P-values <0.05 were considered significant. Results We evaluated 600 consecutive patients undergoing coronary angiography. Left ventriculography was performed in the majority of cases (54%). After multivariate analysis, patients with chronic coronary syndrome (OR 1.72; 95% CI: 1.20-2.46; p < 0.01) were more likely to undergo the procedure. Patients with known ventricular function (OR 0.58; 95% CI: 0.40-0.85; p < 0.01); those with a history of CABG (OR 0.31; 95% CI: 0.14-0.69; p < 0.01) or hypertension (OR 0.58; 95% CI: 0.36-0.94; p = 0.02); and those with higher creatinine levels (OR 0.42; 95% CI: 0.26-0.69; p < 0.01) had greater odds of not undergoing ventriculography. Conclusions In patients undergoing coronary angiography, a diagnosis of chronic coronary syndrome was independently associated with greater likelihood of left ventriculography, while having previously determined ventricular function, a history of hypertension or CABG, and higher creatinine levels were associated with a decreased likelihood of undergoing this procedure.

[The "LOTHAR" study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension]. / Estudo "LOTHAR": avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária.

OBJECTIVE: The LOTHAR study evaluated medium and long term (one year) efficacy, tolerability and metabolic effects of the fixed combination of amlodipine and losartan compared to amlodipine or losartan alone. METHODS: Brazilian multicenter, randomized, double-blind and comparative trial performed with 198 patients in stage 1 and 2 essential hypertension. RESULTS: The fixed combination has a high antihypertensive efficacy that is sustained in the long term with very low percentage of loss of blood pressure control. This percentage is incidentally lower than that of the two monotherapy comparative regimens. In the long term, more than 60% of the patients treated with the fixed combination remained with DBP < or = 85 mmHg, and the antihypertensive effect, when assessed by ABPM persisted for 24 hours with a trough-to-peak ratio of 76.7%. The frequency of adverse events was quite low in this group, and the long-term incidence of leg edema was approximately four-fold lower than that observed with amlodipine alone. The fixed combination did not change glucose and lipid metabolism in the medium or in the long term. CONCLUSION: Based on these results, we can say that the combination of amlodipine and losartan--the first fixed combination of a calcium channel blocker and an angiotensin II receptor blocker available in the pharmaceutical market, is an excellent option for the treatment of a wide range of hypertensive patients.

Bone marrow cell transplantation to the myocardium of a patient with heart failure due to Chagas' disease.

We report the first case of bone marrow cell transplantation to the myocardium of a patient with heart failure due to chagas' disease. The patient is a 52-year-old man with chronic heart failure, NYHA functional class III, despite the optimized clinical therapy. The procedure consisted of aspiration of 50 mL of bone marrow through puncture of the iliac crest, followed by filtration, separation of the mononuclear cells, resuspension, and intracoronary injection. The left ventricular ejection fraction at rest, measured using radionuclide ventriculography with labeled red blood cells prior to transplantation, was 24%, and, after 30 days, it increased to 32% with no change in the medicamentous schedule. The following measurements were assessed before and 30 days after transplantation: left ventricular end diastolic diameter (82 mm and 76 mm, respectively); Minnesota living with heart failure questionaire score (55 and 06, respectively); and distance walked in the 6-minute walking test (513 m and 683 m, respectively). Our findings show that intracoronary injection of bone marrow cells may be performed, suggesting that this is a potentially safe and effective procedure in patients with due to Chagas' disease heart failure.

Evaluation of the Bleeding Intensity of Patients Anticoagulated with Warfarin or Dabigatran Undergoing Dental Procedures / Avaliação da Intensidade de Sangramento de Procedimentos Odontológicos em Pacientes Anticoagulados com Varfarina ou Dabigatrana

Abstract Background: Thrombotic disorders remain one of the leading causes of death in the Western world. Dabigatran appeared as an alternative to warfarin for anticoagulation in the treatment of atrial fibrillation (AF). The risk associated with bleeding due to its use has been documented in several randomized clinical trials, but no large study has examined in detail the risk of bleeding during dental extraction and other dental procedures involving bleeding. Objective: To compare the intensity of bleeding in individuals taking dabigatran or vitamin K antagonist (warfarin) and undergoing dental procedures. Methods: Prospective, single-center, controlled study with one single observer. Patients diagnosed with nonvalvular AF, on warfarin or dabigatran, cared for at a cardiology referral center, and requiring single or multiple dental extractions, were evaluated up to seven days post-extraction. The following outcomes were assessed: bleeding time between the beginning and the end of suture and complete hemostasis; bleeding before the procedure, after 24 hours, 48 hours, 7 days, during and after suture removal (late); p<0.05 was defined as of statistical relevance. Results: We evaluated 37 individuals, 25 in the warfarin group and 12 in the dabigatran group. Age, sex, weight, height, blood pressure, color, schooling, family income and comorbidities were similar between the two groups. Regarding bleeding after 24 hours of the procedure, no one in the dabigatran group had bleeding, whereas 32% in the warfarin group had documented bleeding (p = 0.028). The other variables analyzed did not differ between the groups. Conclusions: This study suggests that, regarding dental extraction, there is no statistically significant difference in the intensity of bleeding of patients taking dabigatran as compared to those taking warfarin. Bleeding 24 hours after the procedure was less frequent among patients on dabigatran.

Resumo Fundamento: Distúrbios trombóticos permanecem como uma das principais causas de morte no mundo ocidental. A dabigatrana surgiu como alternativa à varfarina para a anticoagulação no tratamento da fibrilação atrial (FA). O risco associado a eventos hemorrágicos com a sua utilização foi documentado em vários ensaios clínicos randomizados, mas nenhum grande estudo analisou detalhadamente o risco de hemorragia durante a extração dentária e em outros procedimentos odontológicos que envolvam sangramentos. Objetivo: Em indivíduos submetidos a procedimentos odontológicos, avaliar a intensidade de sangramento com o uso de dabigatrana em comparação ao uso de anticoagulante oral antagonista da vitamina K (varfarina). Métodos: Estudo prospectivo, controlado, unicêntrico, observador único. Pacientes com diagnóstico de FA não valvar atendidos em um centro de referência em cardiologia e com indicação de anticoagulação que necessitavam de tratamento odontológico para exodontia única ou múltipla, estando em uso de varfarina ou dabigatrana e avaliados até sete dias pós-exodontia. Foram avaliados os efeitos sobre: tempo de sangramento entre o início e o fim da sutura e hemostasia completa; sangramento antes do procedimento, após 24 e 48 horas, 7 dias, durante e após a remoção da sutura (tardio), sendo considerado como estatisticamente significativo valor de p < 0,05. Resultados: Foram avaliados 37 indivíduos, sendo 25 no grupo varfarina e 12 no dabigatrana. Idade, sexo, peso, altura, pressão arterial, cor, escolaridade, renda familiar e comorbidades foram semelhantes nos dois grupos. Em relação ao sangramento 24 horas após o procedimento, ninguém do grupo dabigatrana apresentou sangramento, que esteve presente em 32% do grupo varfarina (p = 0,028). Não houve diferenças entre os grupos em relação às outras variáveis analisadas. Conclusões: Os dados deste estudo permitem sugerir que, em indivíduos submetidos a procedimento odontológico de exodontia, não há diferença estatisticamente significante na intensidade de sangramento em uso de dabigatrana em comparação ao uso de varfarina. Há uma menor frequência de sangramento 24 horas após o procedimento nos indivíduos em uso de dabigatrana.

1st Guidelines of the Brazilian Society of Cardiology on processes and skills for education in cardiology in Brazil--executive summary.

This article summarizes the "1st Guidelines of the Brazilian Society of Cardiology on Processes and Skills for Education in Cardiology in Brazil," which can be found in full at: . The guideline establishes the education time required in Internal Medicine and Cardiology with Specialization through theoretical and practical training. These requirements must be available at the center forming Specialists in Cardiology and the Cardiology contents.

Bone marrow cell transplantation in Chagas' disease heart failure: report of the first human experience.

BACKGROUND: Heart failure due to Chagas' disease (HFCD) is a progressive inflammatory cardiomyopathy that affects millions of individuals in Latin America. Studies using mice models of HFCD indicate that bone marrow mononuclear cell transplantation (BMCT) may reduce inflammation, fibrosis, and improve myocardial function. OBJECTIVE: The purpose of this study was to evaluate, for the first time in humans, the safety and efficacy of BMCT to the myocardium of patients with HFCD. METHODS: A total of 28 HFCD patients (mean age 52.2 ± 9.9 years) with NYHA class III and IV were submitted to BMCT through intracoronary injection. Effects on the left ventricle ejection fraction (LVEF), functional capacity, quality-of-life, arrhythmias, biochemical, immunological, and neuro-humoral parameters, were evaluated. RESULTS: There were no complications directly related to the procedure. LVEF was 20.1 ± 6.8% and 28.3 ± 7.9%, p < 0.03 at baseline and 180 days after the procedure, respectively. In the same period, significant improvements were observed in the NYHA class (3.1 ± 0.3 to 1.8 ± 0.5; p < 0.001), quality-of-life (50.9 ± 11.7 to 25.1 ± 15.9; p < 0.001), and in the six-minute walking test (355 ± 136 m to 437 ± 94 m; p < 0,01). There were no changes in markers of immune or neurohormonal activation. No complications were registered. CONCLUSION: Our data suggest that the intracoronary injection of BMCT is safe and potentially effective in patients with HFCD. The extent of the benefit, however, appears to be small and needs to be confirmed in a larger randomized, double blind, placebo controlled clinical trial.