Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Acurácia do Ecocardiograma Transtorácico como Método de Triagem na Prática Clínica da Investigação da Hipertensão Pulmonar / Accuracy of Transthoracic Echocardiogram as a Screening Method in the Clinical Practice of Pulmonary Hypertension Investigation

Resumo Fundamento O ecocardiograma transtorácico (ETT) tem um papel de triagem no algoritmo diagnóstico da hipertensão pulmonar (HP). Estudos demonstraram uma discordância significativa entre as medições do ETT da pressão arterial pulmonar sistólica (PAPs) e da pressão atrial direita (PAD) e as obtidas pelo cateterismo do coração direito (CCD). Objetivo Comparar as medições do ETT da PAPs e da PAD com as obtidas pelo CCD em pacientes com suspeita de HP. Métodos Pacientes encaminhados a um centro de referência com probabilidade alta ou intermediária de PH ao ETT na admissão hospitalar passaram por CCD. A concordância entre a PAPs e a PAD em ambos os procedimentos foi avaliada pelo teste de Bland-Altman. Diferenças de até 10 mmHg na PAPs e de até 5 mmHg na PAD foram consideradas dentro da variabilidade do teste. A curva de característica de operação do receptor (ROC) foi construída para determinar os valores mais precisos de PAPs e VRT associados ao diagnóstico de HP pelo CCD. O nível de significância estatística adotado foi 5%. Resultados Foram incluídos noventa e cinco pacientes. A análise de Bland-Altman análise revelou um viés de 8,03 mmHg (IC 95%: -34,9 a 50,9) na PAPs e -3,30 mmHg (IC 95%: -15,9 a 9,3) na PAD. AUC da PAPs e VRT medidas pelo ETT para a discriminação de provável HP foram de 0,936 (IC 95%: 0,836 a 1,0) e 0,919 (IC 95%: 0,837 a 1,0), respectivamente. Entretanto, apenas 33,4% da estimativa ecocardiográfica da PAPs e 55,1% da PAD foram precisas, em comparação às medições obtidas pelo CCD. Conclusão O ETT tem um alto poder discriminatório como método diagnóstico de triagem para HP, apesar de apresentar discordâncias entre os valores absolutos de PAPs e PAD, em comparação às medições por CCD.

Abstract Background The transthoracic echocardiogram (TTE) plays a screening role in the diagnostic algorithm of pulmonary hypertension (PH). Studies have shown a significant disagreement between TTE measurements of the systolic pulmonary artery pressure (sPAP) and right atrial pressure (RAP) and those obtained by right heart catheterization (RHC). Objective To compare TTE measurements of sPAP and RAP with those obtained by RHC in patients being investigated for PH. Methods Patients referred to a PH reference center with a high or intermediate TTE probability of PH upon admission were submitted to RHC. The agreement between sPAP and RAP from both procedures was assessed through the Bland-Altman test. Differences of up to 10 mmHg for sPAP and 5 mmHg for RAP were considered within the variability of the test. Receiver Operating Characteristic (ROC) curve was constructed to determine the most accurate sPAP and Tricuspid regurgitation maximal velocity (TRV)values associated with the diagnosis of PH by RHC. The adopted level of statistical significance was 5%. Results Ninety-five patients were included. The Bland-Altman analysis showed a bias of 8.03 mmHg (95% CI:-34.9-50.9) for sPAP and -3.30 mmHg (95% CI:-15.9-9.3) for RAP. AUC for sPAP and TRV measured by TTE for discrimination of probable PH were 0.936 (95% CI: 0.836-1.0) and 0.919 (95% CI: 0.837-1.0), respectively. However, only 33.4% of the echocardiographic estimate of sPAP and 55.1% of RAP were accurate, as compared to the measurements obtained by RHC. Conclusion TTE has a high discriminatory power as a screening diagnostic method for PH despite presenting disagreements between sPAP and RAP absolute values when compared to RHC measurements.

Contextual influence on poor self-rated health in patients with Chagas disease: multilevel study / Influência contextual na pior autopercepção em saúde de portadores de Doença de Chagas: estudo multinível

Abstract Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

Resumo A Doença de Chagas (DC) é reconhecida pela Organização Mundial da Saúde como uma das treze doenças tropicais mais negligenciadas do mundo. A autopercepção de saúde é considerada um melhor preditor de mortalidade do que medidas objetivas do estado de saúde, e o contexto em que se vive influencia esse preditor. O objetivo deste estudo foi avaliar a prevalência e os fatores individuais e contextuais associados à pior autopercepção em saúde de pacientes com DC de uma região endêmica do Brasil. É um estudo transversal multinível. Os dados individuais vêm de um corte transversal de um estudo de coorte denominado SaMi-Trop. Os dados contextuais foram coletados a partir de plataformas e sistemas de informações institucionais acessíveis ao público. A variável dependente foi a autopercepção de saúde. A análise foi realizada por meio de regressão logística binária multinível. Participaram do estudo 1.513 pacientes com DC, sendo 335 (22,1%) com pior autopercepção de saúde. Este estudo revelou a influência da organização/oferta do serviço público de saúde brasileiro e de características individuais na autopercepção de saúde de pacientes com DC.

Prognosis of chronic Chagas heart disease and other pending clinical challenges

In this chapter, the main prognostic markers of Chagas heart disease are addressed, with an emphasis on the most recent findings and questions, establishing the basis for a broad discussion of recommendations and new approaches to managing Chagas cardiopathy. The main biological and genetic markers and the contribution of the electrocardiogram, echocardiogram and cardiac magnetic resonance are presented. We also discuss the most recent therapeutic proposals for heart failure, thromboembolism and arrhythmias, as well as current experience in heart transplantation in patients suffering from severe Chagas cardiomyopathy. The clinical and epidemiological challenges introduced by acute Chagas disease due to oral contamination are discussed. In addition, we highlight the importance of ageing and comorbidities in influencing the outcome of chronic Chagas heart disease. Finally, we discuss the importance of public policies, the vital role of funding agencies, universities, the scientific community and health professionals, and the application of new technologies in finding solutions for better management of Chagas heart disease.

Artificial Inteligence-Based Decision for the Prediction of Cardioembolism in Patients with Chagas Disease and Ischemic Stroke.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. AIMS: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. MATERIALS AND METHODS: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. RESULTS: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. CONCLUSIONS: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.

Analysis of Iron Metabolism in Chronic Chagasic Cardiomyopathy.

Changes in iron metabolism in heart failure (HF) have been described as an important prognostic marker. To check if the markers of iron kinetics are related to the morbidity and etiology of chagasic cardiomyopathy. Patients with Chronic Chagasic Cardiomyopathy (CCC, n = 40), with indeterminate form (IND, n = 40), besides non-chagasic cardiomyopathy (NCh, n = 40). The mean age was 50.98 ± 5.88 in CCC, 50% were male, 49.68 ± 5.28 in IND, 52.2% were male, and 49.20 ± 10.09 in NCh, 12.5% were male. Lower levels of iron (FeSe) were observed in the CCC groups (93.15 ± 36.53), when compared to IND (125.30 ± 22.79) and NCh (114.77 ± 18.90) (p = 0.0004), lower IST transferrin saturation index in CCC (29.48 ± 6.59), when compared to IND (30.95 ± 7.06) and in the NCh group (39.70 ± 7.54) p = 0.0001), total binding capacity of the lower CTLF iron in the CCC group (297.30 ± 36.46), when compared to the IND group (196.52 ± 56.95) and the NCh group (275.18 ± 33, 48) (p = 0.0001), lower ferritin in the CCC group (134.55, 1.56-42.36), when compared to the IND group (156,25, 1,72-42,20) and the NCh group (112.95, 2.88-42.66) (p = 0.0004). It was also observed that FeSe (95% CI 1.00-1.04, p = 0.0014), IST (95% CI 1.02-1.22) (p = 0.0012) and gender (95% CI 1.07-14.43 p = 0.0038) were independently associated with the degree of ventricular dysfunction in chagasic cardiomyopathy. CCC patients showed greater change in iron metabolism regarding the indeterminate form and other forms of cariomyopathies.

Analysis of Iron Metabolism in Chronic Chagasic Cardiomyopathy / Análise do Metabolismo do Ferro na Cardiomiopatia Chagásica Crônica

Abstract Changes in iron metabolism in heart failure (HF) have been described as an important prognostic marker. To check if the markers of iron kinetics are related to the morbidity and etiology of chagasic cardiomyopathy. Patients with Chronic Chagasic Cardiomyopathy (CCC, n = 40), with indeterminate form (IND, n = 40), besides non-chagasic cardiomyopathy (NCh, n = 40). The mean age was 50.98 ± 5.88 in CCC, 50% were male, 49.68 ± 5.28 in IND, 52.2% were male, and 49.20 ± 10.09 in NCh, 12.5% were male. Lower levels of iron (FeSe) were observed in the CCC groups (93.15 ± 36.53), when compared to IND (125.30 ± 22.79) and NCh (114.77 ± 18.90) (p = 0.0004), lower IST transferrin saturation index in CCC (29.48 ± 6.59), when compared to IND (30.95 ± 7.06) and in the NCh group (39.70 ± 7.54) p = 0.0001), total binding capacity of the lower CTLF iron in the CCC group (297.30 ± 36.46), when compared to the IND group (196.52 ± 56.95) and the NCh group (275.18 ± 33, 48) (p = 0.0001), lower ferritin in the CCC group (134.55, 1.56-42.36), when compared to the IND group (156,25, 1,72-42,20) and the NCh group (112.95, 2.88-42.66) (p = 0.0004). It was also observed that FeSe (95% CI 1.00-1.04, p = 0.0014), IST (95% CI 1.02-1.22) (p = 0.0012) and gender (95% CI 1.07-14.43 p = 0.0038) were independently associated with the degree of ventricular dysfunction in chagasic cardiomyopathy. CCC patients showed greater change in iron metabolism regarding the indeterminate form and other forms of cariomyopathies.

Resumo A alteração do metabolismo do ferro na insuficiência cardíaca (IC) tem sido descrita como um importante marcador prognóstico. Verificar se os marcadores da cinética do ferro guardam relação com a morbidade e a etiologia da cardiomiopatia chagásica. Pacientes com cardiomiopatia chagásica crônica (CCC, n = 40), com a forma indeterminada (IND, n = 40), além de cardiomiopatia não chagásica (NCh, n = 40). A idade média foi de 50,98 ± 5,88 no CCC, 50% eram do sexo masculino, 49,68 ± 5,28 no IND, 52,2% eram do sexo masculino e 49,20 ±10,09 no NCh, 12,5% eram do sexo masculino. Observaram-se níveis de ferro (FeSe) menores no grupos CCC (93,15 ± 36,53), quando comparados ao IND (125,30 ± 22,79) e NCh (114,77 ± 18,90) (p = 0,0004), índice de saturação de transferrina (IST) menor no CCC (29,48 ± 6,59), quando comparado ao IND (30,95 ± 7,06) e no grupo NCh (39,70 ± 7,54) (p= 0,0001), capacidade total de ligação do ferro CTLF menor no grupo CCC (297,30 ± 36,46), quando comparado ao grupo IND (196,52 ± 56,95) e ao grupo NCh (275,18 ± 33,48) (p = 0,0001), ferritina menor no grupo CCC (134,55, 1,56-42,36), quando comparada ao grupo IND (156,25, 1,72 - 42,20) e ao grupo NCh (112,95, 2,88-42,66) (p = 0.0004). Verificou-se também que o FeSe (IC% 95% 1,00-1,04; p = 0,0014), o IST (IC 95% 1,02-1,22) (p = 0,0012) e o sexo (IC 95% 1,07-14,43 p = 0,0038) associaram-se independentemente ao grau de disfunção ventricular na cardiomiopatia chagásica. Os pacientes com CCC demonstraram maior alteração no metabolismo do ferro em relação a forma indeterminada e outras formas de miocardiopatias.

Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease / Predição de Risco de Complicações Cardiovasculares em Gestantes Portadoras de Cardiopatia

Abstract Background: Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy. Objective: To determine the risk factors associated with cardiovascular and neonatal complications. Methods: We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class > II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories. Results: Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG > 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity. Conclusion: The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and > 1, and underestimated it in low-risk patients (CARPREG 0).

Resumo Fundamento: Cardiopatia na gravidez é a primeira causa de morte materna não obstétrica. Poucos estudos brasileiros avaliaram o impacto da cardiopatia na gestação. Objetivo: Determinar os fatores de risco associados às complicações cardiovasculares e neonatais. Métodos: Foram avaliadas 132 gestantes cardiopatas, acompanhadas em um Setor de Gestação de Alto Risco, de janeiro de 2005 a julho de 2010. Foram selecionadas variáveis que poderiam influenciar no desfecho materno/fetal: idade, paridade, tabagismo, etiologia, gravidade da cardiopatia, complicações cardíacas prévias, cianose, classe funcional New York Heart Association (NYHA) > II, disfunção/obstrução do ventrículo esquerdo, arritmia, mudança de tratamento, início e número de consultas de pré-natal. Foi calculado, retrospectivamente, o índice de risco materno-fetal de acordo com o Cardiac Disease in Pregnancy (CARPREG) no início do pré-natal. As pacientes foram estratificadas nas três categorias de risco do CARPREG. Resultados: A cardiopatia reumática foi a cardiopatia mais prevalente (62,12%). As complicações mais frequentes foram descompensação cardíaca (11,36%) e arritmias (6,82%). Fatores associados às complicações cardiovasculares na análise multivariada foram mudança do tratamento (p = 0,009), complicações cardíacas prévias (p = 0,013) e classe funcional III NYHA na primeira consulta pré-natal (p = 0,041). O porcentual de complicação cardiovascular foi 15,22% no grupo CARPREG 0; 16,42% no CARPREG 1; e 42,11% no CARPREG >1 − diferentemente do estimado pelo índice original: 5%, 27% e 75%, respectivamente. Na amostra, tivermos 26,36% de prematuridade. Conclusão: Os fatores de risco para complicação cardiovascular nessa população foram a mudança de tratamento, as complicações cardíacas prévias e a classe funcional III NYHA no início do acompanhamento pré-natal. O índice CARPREG, nesta amostra, composta principalmente por pacientes com cardiopatia reumática, superestimou o número de eventos em gestantes classificadas como CARPREG 1 e > 1, e subestimou o risco em pacientes de baixo risco (CARPREG 0).

Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease.

BACKGROUND: Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy. OBJECTIVE: To determine the risk factors associated with cardiovascular and neonatal complications. METHODS: We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class > II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories. RESULTS: Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG > 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity. CONCLUSION: The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and > 1, and underestimated it in low-risk patients (CARPREG 0).

Prognóstico da coronariopatia aterosclerótica não significativa detectada pela tomografia de coronárias / Prognosis of non-significant coronary atherosclerotic disease detected by coronary artery tomography

Introdução: Embora os estudos tenham demonstrado elevada acurácia diagnóstica da tomografia de coronárias (TC)na detecção de doença arterial coronariana (DAC), os dados sobre o valor prognóstico desse método em pacientes com obstrução coronariana não significativa são limitados.Objetivo: Avaliar o valor da TC na predição de eventos adversos em pacientes com suspeita de DAC e obstrução coronária não significativa. Métodos: Foram avaliados prospectivamente 440 pacientes entre janeiro de 2008 e julho de 2013 pela TCMD, diagnosticados com obstrução não significativa ou sem obstrução aterosclerótica coronariana e com seguimento médio de 33 meses. Os desfechos avaliados foram: morte de origem cardíaca, infarto do miocárdio, angina instável associado à hospitalização ou revascularização do miocárdio. Resultados: Dos 440 pacientes estudados, 295 (67%) eram homens, com idade média de 55,9 ± 12,0 anos. Foi encontrada obstrução não significativa em 152 (35%) dos pacientes e ocorreram 49 (11%) desfechos. Na análise multivariada, utilizando-se modelo de regressão de Cox, os preditores de desfechos clínicos foram obstrução não significativa à TC(hazard ratio 3,51; IC 95% 1,73 – 7,8; p < 0,01), idade e hipertensão arterial sistêmica. A obstrução não significativa à TC apresentou associação com desfechos clíncos adversos, e a análise de sobrevida mostrou diferença significativa (log-rank 24,6; p < 0,01) na predição desses desfechos. Conclusão: A detecção de obstrução aterosclerótica não significativa pela TC mostrou associação com a presença de eventos adversos em pacientes com suspeita de DAC, podendo se mostrar útil na estratificação de risco desses pacientes.

Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD),data on the prognostic value of this method in patients with no significant coronary obstruction are limited.Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting.Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes werenon-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 — 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT wasassociated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes.Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients withsuspected CAD, which may prove useful in the risk stratification of these patients.

Relação entre a fração de ejeção do ventrículo esquerdo e razão e/e' com a capacidade funcional na cardiopatia chagásica / Relationship between left ventricular ejection fraction and e /e' ratiowith functional capacity in chagas heart disease

Introdução: disfunção ventricular e capacidade funcional são importantes marcadores de morbimortalidade na cardiopatia chagásica (CCh). Objetivos: verificar a associação entre a capacidade funcional e funções sistólica e diastólica do ventrículo esquerdo na CCh. Metodologia: foram submetidos 35 pacientes com CCh (47,11±8,15 anos) a avaliação clínica, ecocardiograma e teste de esforço cardiopulmonar (TECP), sendo classificados em dois grupos: dilatado (com cardiomiopatia dilatada) e não dilatado (função sistólica preservada). Foram consideradas as variáveis fração de ejeção do ventrículo esquerdo (FEVE), razão E/e' e o pico do consumo de oxigênio (VO2pico). Na análise estatística foram realizados os testes de Pearson ou Spearman e a análise de regressão linear múltipla avaliou o efeito da FEVE e E/e' no VO2pico. Resultados: na amostra total houve correlação significativa entre o VO2pico e a FEVE (r=0,536, p=0,001) e correlação negativa e significativa entre o VO2pico e razão E/e' (r=-0,399; p=0,022). No grupo dilatado (n=16), correlação significativa foi observada entre o VO2pico com a FEVE (r=0,611, p=0,016) e a razão E/e' (r=-0,601, p=0,018). A análise multivariada das variáveis identificou a FEVE e a razão E/e' como fortes preditores do VO2pico (r=0,850; r2 =0,723).Não houve correlação significativa entre o VO2pico e a FEVE (r=0,393, p=0,107) e a razão E/e' (r=0,102, p=0,687) no grupo não dilatado (n=19). Conclusão: a capacidade funcional avaliada pelo VO2pico relaciona-se à função sistólica e diastólica em pacientes com cardiomiopatia dilatada chagásica.

Background: Left ventricular dysfunction and functional capacity (FC) are important markers of morbidity and mortality in Chagas heart disease (CHD), however, the relationship between these clinical parameters remains controversial. Objective: To verify the association between FC and systolic and diastolic functions of the left ventricle in CHD patients. Methods: Thirty-five CHD patients (47.11±8.15 years) underwent clinical evaluation, echocardiography and Cardiopulmonary Exercise Testing (CPET) and were classified into two groups: dilated group (dilated cardiomyopathy) and non-dilated group (preserved systolic function). The left ventricular ejection fraction (LVEF), E/e' ratio and peak oxygenuptake (VO2peak)were considered. Statistical analysis was carried outwith Pearson or Spearman correlation tests and backward multivariate linear regression analysis was performed to assess the effect of LVEF and E/e' ratio on VO2peak. Results: In the overall study population, there was a significant correlation between VO2peak and LVEF (r=0.536; p=0.001) and a significant negative correlation between VO2peak and E/e' ratio (r=-0.399;p=0.022). In the dilated group (n=16), a significant correlation was also observed between VO2peak and both LVEF(r=0.611; p=0.016) and E/e' ratio (r=-0.601; p=0.018). The multivariate analysis of these variables identified the LVEF and E/e' ratio as strong predictors of VO2peak (r=0.850; r2=0.723). In contrast, in the non-dilated group (n=19), there was no significant correlation between VO- 2peak and LVEF (r=0.393; p=0.107) and E/e' ratio (r=0.102; p=0.687). Conclusion: Functional capacity assessed by VO2peak was related to systolic and diastolic function in CHD patients with dilated cardiomyopathy.

Aplicações do Balão Farmacológico na Doença Arterial Coronária / Applications of the Drug-Eluting Balloon in Coronary Artery Disease

As estratégias de revascularização percutânea evoluíram significativamente nas últimas décadas. No entanto, toda nova tecnologia apresenta um benefício sobre a anterior, mas traz consigo também novos riscos. A hiperplasia neointimal, associada aos stents não farmacológicos, e a endotelização tardia das hastes e reação inflamatória vascular ao polímero, associada aos stents farmacológicos, são exemplos dessa premissa. Os balões farmacológicos foram desenvolvidos com o racional de modular a hiperplasia neointimal após a intervenção e de não suscitar os problemas tardios relacionados aos stents com eluição de fármacos antiproliferativos. No entanto, as evidências e as recomendações para sua utilização ainda não foram adequadamente definidas. Esta revisão objetiva apresentar e caracterizar os tipos de balão farmacológico disponíveis no mercado mundial, fazendo uma revisão dos estudos mais relevantes presentes na literatura sobre seu uso nos diversos cenários clínicos e descrever as principais indicações e atuais recomendações para seu uso.

Percutaneous revascularization strategies have evolved significantly in the past decades. However, every new technology has advantages over the previous ones, but also carries new risks. Neointimal hyperplasia, associated with bare metal stents, and delayed strut endothelialization and vascular inflammatory reaction to the polymer, associated with drug-eluting stents, are examples of this premise. Drug-eluting balloons were developed with the aim to modulate neointimal hyperplasia after intervention, avoiding the late risks associated with drug-eluting stents. However, the evidence and recommendations for their use have not been adequately defined. This review aims to present and characterize the different types of drug-eluting balloons commercially available worldwide, reviewing the most relevant studies in the literature in different clinical scenarios and describe the main indications and recommendations for their use.

Effects of Exercise Training on Heart Rate Variability in Chagas Heart Disease / Efeitos do Treinamento Físico sobre a Variabilidade da Frequência Cardíaca na Cardiopatia Chagásica

Background: Heart rate variability (HRV) is a marker of autonomic dysfunction severity. The effects of physical training on HRV indexes in Chagas heart disease (CHD) are not well established. Objective: To evaluate the changes in HRV indexes in response to physical training in CHD. Methods: Patients with CHD and left ventricular (LV) dysfunction, physically inactive, were randomized either to the intervention (IG, N = 18) or control group (CG, N = 19). The IG participated in a 12-week exercise program consisting of 3 sessions/week. Results: Mean age was 49.5 ± 8 years, 59% males, mean LVEF was 36.3 ± 7.8%. Baseline HRV indexes were similar between groups. From baseline to follow-up, total power (TP): 1653 (IQ 625 - 3418) to 2794 (1617 - 4452) ms, p = 0.02) and very low frequency power: 586 (290 - 1565) to 815 (610 - 1425) ms, p = 0.047) increased in the IG, but not in the CG. The delta (post - pre) HRV indexes were similar: SDNN 11.5 ± 30.0 vs. 3.7 ± 25.1 ms. p = 0.10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms. p = 0.43; TP 943 (731 - 3130) vs. 1780 (921 - 2743) Hz. p = 0.46; low frequency power (LFP) 1.0 (150 - 197) vs. 60 (111 - 146) Hz. p = 0.85; except for high frequency power, which tended to increase in the IG: 42 (133 - 92) vs. 79 (61 - 328) Hz. p = 0.08). Conclusion: In the studied population, the variation of HRV indexes was similar between the active and inactive groups. Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD. .

Fundamento: A variabilidade da frequência cardíaca (VFC) é marcador de gravidade da disfunção autonômica. Os efeitos do treinamento físico sobre índices de VFC na miocardiopatia chagásica (MPC) não são bem estabelecidos. Objetivo: Avaliar as mudanças nestes índices em resposta ao treinamento físico na MPC. Métodos: Pacientes com MPC e disfunção do ventrículo esquerdo (VE), fisicamente inativos, foram aleatorizados para os grupos intervenção (GI, N = 18) e controle (GC, N = 19). O GI participou de um programa de exercícios de 12 semanas, três sessões/semana. Resultados: A idade média foi de 49,5 ± 8 anos, 59% homens, FEVE de 36,3 ± 7,8%. Índices basais de VFC foram similares. Do basal ao seguimento, observamos no GI aumento da potência total (TP): 1.653 (IQ 625 - 3.418) para 2.794 (1.617 - 4.452) ms, p = 0,02) e potência de frequência muito baixa: 586 (290 - 1.565) para 815 (610 - 1.425) ms, p = 0,047), mas não no GC. A variação (pós/pré) dos índices de VFC foi similar: SDNN 11,5 ± 30,0 vs. 3,7 ± 25, 1 ms, p = 0,10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms, p = 0,43; TP 943 (731 - 3.130) vs. 1.780 (921 - 2.743) Hz, p = 0,46 e potência de frequência baixa (LFP) 1,0 (150 - 197) vs. 60 (111 - 146) Hz, p = 0,85, exceto pela potência de alta frequência, que teve tendência a aumento no GI: 42 (133 - 92) vs. 79 (61 - 328) Hz, p = 0,08). Conclusão: Na população estudada, a variação dos índices de VFC foi similar entre os grupos ativo e inativo. A melhora clínica com o treinamento físico parece ser independente de marcadores de disfunção autonômica na MPC. .

Escore de cálcio na predição de eventos adversos em pacientes com suspeita de doença coronariana / Calcium score in the Prediction of Adverse Events in Patients with Suspected Coronary Artery Disease / Score de calcio en la predicción de eventos adversos en pacientes con sospecha de enfermedad coronaria

Fundamento: A Doença Arterial Coronariana (DAC) representa importante causa de morbimortalidade no mundo, e os modelos de predição de eventos baseados em fatores de risco possuem capacidade limitada. Dentre os novos marcadores disponíveis na prática clínica, o Escore de Cálcio (EC) caracteriza-se como ferramenta potencial para predição de eventos adversos, podendo agregar valor aos modelos preexistentes. Objetivo: Determinar o valor do EC na predição de desfechos clínicos adversos em pacientes com suspeita de DAC. Métodos: Foram avaliados prospectivamente 380 pacientes consecutivos com idade média de 57,5 anos, sendo 114 do sexo masculino, com suspeita de DAC, entre janeiro de 2008 e junho de 2012. Evento adverso foi definido como a presença de morte cardiovascular, revascularização e internação por Infarto Agudo do Miocárdio (IAM). Resultados: Durante um acompanhamento médio de 15 meses, houve 57 eventos cardíacos. Na análise multivariada utilizando-se o modelo de regressão de Cox, classe funcional da NYHA – classe II, III e IV (HR 2,18 IC 95% 1,28 - 3,72), tabagismo (HR 2,72 IC 95% 1,54 - 4,83) e EC (HR 8,62 IC 95% 3,16- 23,51) foram preditores de desfecho clínico adverso. Conclusão: O EC em pacientes com suspeita de DAC apresentou valor independente dos fatores de risco convencionais na predição de eventos clínicos adversos, podendo se mostrar útil na estratificação de risco de pacientes.

Background: Coronary Artery Disease (CAD) is an important cause of morbidity and mortality worldwide, and models to predict events based on risk factors have limited capacity. Among the new markers available in clinical practice, the Calcium Score (CS) is characterized as a potential tool for predicting adverse events and can add value to existing models. Objective: Determine the value of CS in predicting adverse clinical outcomes in patients with suspected CAD. Methods: The study prospectively evaluated 380 consecutive patients with a mean age of 57.5 years, including 114 men with suspected CAD from January 2008 to June 2012. Adverse event was defined as the presence of cardiovascular death, coronary artery bypass grafting and hospitalization for Acute Myocardial Infarction (AMI). Results: During a mean follow-up of 15 months, there were 57 cardiac events. In the multivariate analysis, using the Cox regression model, NYHA functional class — class II, III and IV (HR 2.18 95% CI 1.28 — 3.72), smoking (HR 2.72 95% 1 , 54 to 4.83) and CS (HR 8.62 95% CI 3.16 — 23.51) were predictors of adverse clinical outcome. Conclusion: CS in patients with suspected CAD presented a value independent from conventional risk factors in the prediction of adverse clinical events and may prove useful in risk stratification of patients.

Fundamento: La Enfermedad Arterial Coronaria (EAC) representa importante causa de morbimortalidad en el mundo, y los modelos de predicción de eventos basados en factores de riesgo tienen capacidad limitada. Entre los nuevos marcadores disponibles en la práctica clínica, el Score de Calcio (SC) se caracteriza como herramienta potencial para predicción de eventos adversos, pudiendo agregar valor a los modelos preexistentes. Objetivo: Determinar el valor do SC en la predicción de desenlaces clínicos adversos en pacientes con sospecha de EAC. Métodos: Fueron evaluados prospectivamente 380 pacientes consecutivos con edad media de 57,5 años, siendo 114 del sexo masculino, con sospecha de EAC, entre enero de 2008 y junio de 2012. Evento adverso fue definido como la presencia de muerte cardiovascular, revascularización e internación por Infarto Agudo de Miocardio (IAM). Resultados: Durante un control medio de 15 meses, hubo 57 eventos cardíacos. En el análisis multivariado utilizando el modelo de regresión de Cox, clase funcional de la NYHA ­ clase II, III y IV (HR 2,18 IC 95% 1,28 - 3,72), tabaquismo (HR 2,72 IC95% 1,54 - 4,83) y SC (HR 8,62 IC 95% 3,16- 23,51) fueron predictores de desenlace clínico adverso. Conclusión: El SC en pacientes con sospecha de EAC presentó valor independiente de los factores de riesgo convencionales en la predicción de eventos clínicos adversos, pudiendo mostrarse útil en la estratificación de riesgo de pacientes. (Arq Bras Cardiol: Imagem cardiovasc. 2014;27(3):191-196)