Association of Anti-β 1 and Anti-M2 Antibodies with Autonomic Nervous System Modulation in Patients with Chronic Chagas Cardiomyopathy

Abstract Background: Different immune mechanisms of myocardial damage involved in the pathophysiology of Chagas disease coexist with high titers of autoantibodies induced by T. cruzi . There are few studies in the literature about the adaptive role of anti-β1 and anti-M2 antibodies in chronic Chagas cardiomyopathy (CCC). Objectives: To evaluate the association between anti-β1 and anti-M2 antibodies with heart rate variability (HRV) parameters on 24h Holter monitoring and the rate-pressure product (RPP) on cardiopulmonary exercise testing (CPET). Methods: Anti-β1 and anti-M2 antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) in 64 patients affected by CCC. Analysis of HRV was performed through the time-domain indices NNs, mean NN, SDNN, SDANN, SDNN index, NNNs, RMSSD, and pNN50. Spearman's correlation coefficient was used to assess the association between antibody titers and numerical variables. The Mann-Whitney test was used for comparison between two groups. Multiple linear regression was used to identify independent variables capable of explaining anti-β1 and anti-M2 antibody titers at the 5% significance level. Results: On 24h Holter, during the period of greatest parasympathetic activation (2:00-6:00 a.m.), an inverse association was found between anti-β1 titers and SDNN (rs=-0.13, p =0.041, n=43), as well as a direct association between anti-M2 titers and SDANN ( r s=0.317, p =0.039, n=43). Regarding CPET variables, anti-β1 titers were directly associated with RPP (rs=0.371, p =0.005, n=56). The subgroup of patients with a normal chronotropic response showed higher anti-β1 titers than the subgroup with an impaired response (p=0.023). RPP was an independent explanatory variable for anti-β1 titers, although with a low coefficient of determination (R2=0.147). Conclusion: The findings of this study suggest that, in patients with CCC, anti-β1 and anti-M2 antibodies may affect HRV parameters. RPP was directly associated with higher anti-β1 titers.

Revisiting the History of Chagas Disease: "Live to tell"

Abstract In 1907, Carlos Chagas was designated to fight paludism in the Rio das Velhas region along the Central do Brasil railroad. During his field research, Chagas discovered a hematophagous insect ( Panstrongylus megitus ) carrying a new trypanosomatide, which he named Trypanosoma cruzi . On April 14th, 1909, he found the same parasite in the blood of a febrile child, submitting the announcement of his discoveries to the Brasil Médico scientific journal. Here, we discuss the early stages in the establishment of a new human morbid entity during the first decades after its discovery with a definite influence from its discoverer, Carlos Chagas, as well the first collaborators. Moreover, we cover the importance of the Center for the Study and Prophylaxis of Chagas Disease in Bambuí (MG), unraveling the most advanced developments in research within the disease's habitat and the widening perspectives for modern research that have emerged after the 1960s and continue to improve to this day. In this revisitation to the history of Chagas disease, we begin at Manguinhos (RJ ), making our way to Lassance (MG), where the discovery took place. Then, we travel back to Rio de Janeiro in the beginning of the twentieth century and Brazilian republic until the current day, revealing milestone publications that settled Chagas disease both as a source of pride for Brazilian medicine and as a challenge with important aspects that remain to be clarified. Any similarities to our country's politics and economy in the twentieth century are not mere coincidences.

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Abstract Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized. Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease. Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded. Results A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia. Conclusions The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas' disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Effects of an exercise program on the functional capacity of patients with chronic Chagas' heart disease, evaluated by cardiopulmonary testing / Efeitos de um programa de exercícios sobre a capacidade funcional de pacientes com cardiopatia chagásica crônica, avaliados por teste cardiopulmonar

INTRODUCTION: Despite all efforts to restrict its transmission, Chagas' disease remains a severe public health problem in Latin America, affecting 8-12 million individuals. Chronic Chagas' heart disease, the chief factor in the high mortality rate associated with the illness, affects more than half a million Brazilians. Its evolution may result in severe heart failure associated with loss of functional capacity and quality of life, with important social and medical/labor consequences. Many studies have shown the beneficial effect of regular exercise on cardiac patients, but few of them have focused on chronic Chagas' heart disease. METHODS: This study evaluated the effects of an exercise program on the functional capacity of patients with chronic Chagas' disease who were treated in outpatient clinics at the Evandro Chagas Institute of Clinical Research and the National Institute of Cardiology, Rio de Janeiro, Brazil. The exercises were performed 3 times a week for 1 h (30 min of aerobic activity and 30 min of resistance exercises and extension) over 6 months in 2010. Functional capacity was evaluated by comparing the direct measurement of the O2 uptake volume (VO2) obtained by a cardiopulmonary exercise test before and after the program (p < 0.05). RESULTS: Eighteen patients (13 females) were followed, with minimum and maximum ages of 30 and 72 years, respectively. We observed an average increase of VO2peak > 10% (p = 0.01949). CONCLUSIONS: The results suggest a statistically significant improvement in functional capacity with regular exercise of the right intensity.

INTRODUÇÃO: Mesmo com todos os esforços para interrupção de sua transmissão, a doença de Chagas permanece como grave problema de saúde pública na América Latina, onde atinge entre 8 e 12 milhões de indivíduos. A cardiopatia chagásica crônica, principal responsável pela elevada morbimortalidade da doença, chega a acometer mais de meio milhão de brasileiros. Sua evolução atinge estágios graves de insuficiência cardíaca com perda de capacidade funcional e qualidade de vida, com grande impacto social e médico-trabalhista. Muitos estudos demonstram o resultado benéfico da prática regular de exercícios em cardiopatas, porém, há escassez de investigações em cardiopatia chagásica. MÉTODOS: O presente estudo avaliou efeitos de um programa de exercícios sobre a capacidade funcional de dezoito pacientes (13 mulheres) com cardiopatia chagásica crônica, com idade entre 30 e 72 anos, atendidos nos ambulatórios do Instituto de Pesquisa Clínica Evandro Chagas e do Instituto Nacional de Cardiologia, na cidade do Rio de Janeiro. Os exercícios foram executados 3 vezes por semana, durante 1 hora (30 minutos de atividade aeróbica e 30 minutos de exercícios contra-resistência e alongamentos), ao longo de 6 meses, no ano de 2010. A avaliação da capacidade funcional foi realizada pela comparação da medida direta do VO2 obtido pelo Teste de Exercício Cardiopulmonar, antes e depois do programa. Para análise estatística foram utilizados testes T de Student pareado e de Wilcoxon. RESULTADOS: Os resultados mostram aumento médio do VO2pico acima de 10%(p=0,01949). CONCLUSÕES: Os resultados sugerem melhora significativa da capacidade funcional com prática regular de exercícios na população amostral.

Intervenção nos hábitos de vida em instituição pública / Life-habit intervention in a public institution

FUNDAMENTO: A doença coronariana é a maior causa mortis mundial, segundo a Organização Mundial de Saúde (OMS), e a segunda no Brasil. Morte súbita ocorre de 4 a 6 vezes mais nos que já sofreram um infarto agudo do miocárdio (IAM); em 6 anos, 18 por cento dos homens e 35 por cento das mulheres terão novo IAM. A prevenção secundária, cuja eficácia já foi demonstrada, é de fundamental importância. OBJETIVO: Testar a efetividade de um programa multiprofissional que visa a modificar fatores de risco para aterosclerose no sistema público. MÉTODOS: Dos 2.337 coronariopatas em tratamento ambulatorial, 513 com estudo coronariográfico concordaram em participar deste estudo, que utilizou como arma terapêutica palestras de como e por que controlar os fatores de risco. Análise estatística: variação significativa pré e pós-intervenção; teste t de Student emparelhado ou o teste de Wilcoxon; existência de diferença significativa entre dois grupos; teste t de Student para amostras independentes ou o teste de Mann-Whitney. Comparação entre três grupos: análise de variância (ANOVA) ou Kruskal-Wallis. RESULTADOS: Colesterol, LDL, triglicérides, índice de massa corpórea, índices de Castelli I e II e medida da cintura apresentaram diminuição significativa, mesmo nos pacientes sem hipolipemiante. Na avaliação do impacto em relação à dieta, verificou-se que 72 por cento dos que não faziam dieta passaram a fazê-la. Atividade física: dos 55 por cento sedentários, 71 por cento passaram a exercitar-se três ou mais vezes/semana. Tabagismo: dos fumantes, 60 por cento (9 por cento do total) interromperam este hábito e 32 por cento o diminuíram. CONCLUSÃO: Esses resultados demonstram a eficácia de programas para melhorar hábitos de vida, aplicados em unidades do sistema público de saúde.

BACKGROUND: Coronary disease is the major worldwide cause of death, according to the World Health Organization (WHO) and the second in Brazil. Sudden death occurs 4 to 6 times more frequently in those who have suffered an acute myocardial infarction (AMI); within 6 years, 18 percent of the men and 35 percent of the women will have a new AMI. The secondary prevention, of which effectiveness has been previously demonstrated, is of utmost importance. OBJECTIVE: To test the effectiveness of a multiprofessional program that aims at modifying risk factors for atherosclerosis in the public health system. METHODS: Of the 2,337 patients with coronary artery disease undergoing outpatient treatment, 513 with a coronary angiography study agreed to participate in the present study, which used lectures on how and why to control risk factors as therapeutic tool. Statistical analysis: significant variation pre and post-intervention; paired Student's t test or Wilcoxon's test ; existence of a significant difference between the two groups; Student's t test for independent samples or Mann-Whitney test. Comparison among three groups: analysis of variance (ANOVA) or Kruskal-Wallis. RESULTS: Cholesterol, LDL, triglycerides, body mass index, Castelli indexes I and II and waist circumference showed a significant decrease, even in patients without hypolipemiant treatment. The assessment of the diet impact showed that 72 percent of the patients that did not follow a diet, started to do so. Physical activity: of the 55 percent sedentary patients, 71 percent started to exercise three or more times a week. Smoking: of the smokers, 60 percent (9 percent of the total) stopped smoking and 32 percent decreased the number of cigarettes. CONCLUSION: These results demonstrated the effectiveness of the programs to improve life habits when applied to the units of the public health system.

Avaliação dos efeitos da reabilitação cardíaca em pacientes pós-infarto do miocárdio / Assessment of the effects of cardiac rehabilitation in patients post myocardial infarction

Fundamentos: O princípio dos programas de reabilitação cardíaca é permitir aos pacientes com diagnóstico de cardiopatias retornar à vida produtiva e ativa apesar das limitações impostas por seu processo patológico. Objetivo: Avaliar os efeitos metabólicos, hemodinâmicos e bioquímicos obtidos através do programa de reabilitação cardíaca após infarto do miocárdio. Métodos: Estudo prospectivo, observacional, incluindo 27 homens e 10 mulheres, com idade variando entre 20 anos e 80 anos (idade média 56 anos), com estabilidade clínica e hemodinâmica, fração de ejeção >40 por cento (método de Simpson), em uso regular de fármacos e assiduidade >75 por cento às sessões de reabilitação cardíaca. A prescrição do exercício foi individual, três vezes por semana, 90 min por sessão, e intensidadde de esforço determinada pelo limiar ventilatório obtido através do teste de exercício cardiorrespiratório. Resultados: Dos 37 pacientes avaliados, observou-se aumento de 14 por cento no V'O2pico (p=0,0001) e 9,2 por cento no pulso de oxigênio (p=0,005). Aumento na frequência cardíaca máxima de 6,2 por cento (0,0001), na frequência de recuperação...

Monitorização ambulatorial da pressão arterial e pressão casual em hiper-reatores ao esforço / Ambulatory blood pressure monitoring and casual blood pressure in hyper-reactive individuals

FUNDAMENTO: O desenvolvimento de hipertensão arterial sustentada é, pelo menos, duas vezes maior em indivíduos hiper-reatores ao esforço. Poucos trabalhos têm avaliado os parâmetros da monitorização ambulatorial da pressão arterial de 24 horas (MAPA) nesses indivíduos. OBJETIVO: Avaliar a relação da pressão arterial (PA) casual com a resposta hiper-reativa ao esforço (RHR) e comparar os padrões da monitorização ambulatorial de pressão arterial (MAPA) de indivíduos hiper-reatores ao esforço a um grupo controle, visando detectar alterações precoces que permitam uma atuação preventiva com implicação prognóstica. MÉTODOS: A PA casual e os dados da MAPA de 26 indivíduos adultos, com idade média de 41,50±11,78 anos, normotensos em repouso, hiper-reatores ao teste ergométrico (TE), foram comparados aos de 16 adultos, com média de idade de 41,38±11,55 anos, também normotensos em repouso, com resposta normal de PA ao esforço. Como normotensão foram considerados valores de PA <140x90mmHg. Para o diagnóstico de hiper-reatividade foram aceitos valores de pressão arterial sistólica (PAS) >220mmHg e/ou incremento >15mmHg de pressão arterial diastólica (PAD) no TE, partindo-se de níveis de PA normais. RESULTADOS: A PAS (p=0,03) e PAD (p=0,002) casuais, a média da PAS (p=0,050) e as cargas pressóricas sistólicas na vigília (p=0,011) e nas 24 horas (p=0,017) à MAPA foram significativamente superiores nos hiper-reatores. CONCLUSÃO: A PA casual se correlacionou positivamente com a RHR. Os hiper-reatores apresentaram características peculiares na PA casual e MAPA, que, embora dentro da normalidade, se diferenciaram das observadas nos normorreatores.

BACKGROUND: Developing hypertension is likely to be at least two times greater in individual with exaggerated blood pressure response on exercise testing (ET). Few reports have evaluated the parameters of 24-hour Ambulatory Blood Pressure Monitoring (ABPM) in normotensive individuals with exaggerated blood pressure response to exercise. OBJECTIVE: To evaluate the relationship among the casual blood pressure with hyper-reactive response on ET and to compare Ambulatory Blood Pressure Monitoring (ABPM) data of hyper-reactive individuals with a control group in order to detect early disorders, that allows a preventive action with prognostic implication. METHODS: Casual BP measurement and parameters of ABPM of 26 adult individuals, with mean age of 41.50±11.78 years, normotensive at rest and hyper-reactive on ET was compared to those of 16 adult individuals, with mean age of 41.38±11.55 years, normotensive at rest with normal BP response on exercise. The values <140 x 90 mmHg were considered normal for casual BP. The values <220 mmHg for systolic BP and/or an increase >15mmHg diastolic BP on ET for hyper-reactive response diagnosis. RESULTS: Hyper-reactive individuals presented the systolic (p=0.03) and diastolic (p=0.002) casual BP and mean systolic BP (p=0.050), systolic pressure load during the day (p=0.011), and systolic (p=0.017) pressure load higher when compared to the control group. CONCLUSION: Casual high normal BP had a positive correlation with exaggerated BP response. The hyper-reactive individuals showed particular characteristics in casual BP as well as in ABPM parameters, which, although within the range of reference values, differed from those of individuals with normal response to exercise.

Mixoma em átrio esquerdo associado a doença arterial coronariana obstrutiva / Left atrial myxoma associated with obstructive coronary artery disease

Descrevemos o caso de um paciente de 67 anos, portador de doença arterial coronariana obstrutiva, o qual, em avaliação pré-operatória para cirurgia de herniorrafia inguinal, realizou ecocardiograma demonstrando um volumoso tumor em átrio esquerdo, móvel, não-obstrutivo, com pedículo proveniente da veia pulmonar superior direita. O paciente realizou cineangiocoronariografia com ventriculografia esquerda, evidenciando lesão obstrutiva grave em terço médio da artéria descendente anterior, moderada em terço proximal da artéria circunflexa, no local de saída do primeiro ramo marginal, e coronária direita com lesão não-obstrutiva em terço distal. Havia, ainda, disfunção ventricular esquerda moderada. O paciente foi então submetido a cirurgia para retirada do tumor e revascularização do miocárdio. O exame histopatológico mostrou tratar-se de um mixoma.

We describe a case of a 67 year-old patient with obstructive coronary artery disease that, in the preoperative survey for inguinal herniorraphy surgery, discovered, by a two-dimensional echocardiogram, a tumor in left atrium, mobile, non-obstructive. The patient underwent a cineangiocoronariography showing severe stenosis in the left anterior descending artery, moderate stenosis in the left circumflex artery, near the origin of the first marginal branch, and a non-obstructive plaque in the right coronary artery. There was also moderate left ventricular dysfunction. After that, the patient has gone coronary artery bypass surgery and resection of the left atrial tumor. The histological exam revealed that the tumor was, in fact, a myxoma.

Avaliação funcional dos enxertos coronarianos através do ecocardiograma sob estresse farmacológico com dobutamina / Functional assessment of coronary grafts on dobutamine pharmacological stress echocardiogram / Functional assessment of coronary grafts on dobutamine pharmacological stress echocardiogram

OBJETIVO: Verificar a sensibilidade, a especificidade e a acúracia diagnósticas do ecocardiograma de estresse com dobutamina (EED) ao avaliar o estado funcional dos enxertos coronarianos: suficientes (SUF) ou insuficientes (INS). MÉTODOS: Estudo observacional, prospectivo, que incluiu 25 pacientes submetidos a cirurgia de revascularização miocárdica (CRVM). Foram realizados o EED e a coronariografia, antes e três meses após a CRVM. O ventrículo esquerdo foi dividido em três territórios por paciente, de acordo com as três principais artérias do coração: descendente anterior (DA), circunflexa (CX) e coronária direita (CD). Dos 75 territórios possíveis, 54 foram revascularizados: 25 específicos da artéria DA e 29 das artérias CX/CD. INS significa oclusão ou obstrução luminal maior ou igual a 50 por cento. RESULTADOS: Dos 54 territórios revascularizados, em quatorze (26 por cento) os enxertos estavam INS. O EED detectou isquemia em dezesseis (28 por cento) territórios; em dez desses os enxertos estavam INS.O EED detectou isquemia em seis (15 por cento) dos quarenta territórios cujos enxertos estavam SUF. Portanto, o EED teve sensibilidade de 71,4 por cento, especificidade de 85 por cento, e acurácia diagnóstica de 81,4 por cento. CONCLUSÃO: O EED é um método diagnóstico com alta especificidade e acurácia diagnóstica e boa sensibilidade, na avaliação funcional dos enxertos coronarianos.

OBJECTIVE: To verify the sensitivity, specificity and diagnostic accuracy of dobutamine stress echocardiogram (DSE) when assessing the functional status of coronary grafts: sufficient (SUF) or insufficient (INS). METHODS: We carried out a prospective, observational study which included 25 patients submitted to coronary artery bypass grafting (CABG). The DSE and the coronary angiography were performed before the CABG and three months after the CABG. The left ventricle was divided into three territories per patient according to the three major coronary arterie: the anterior descending (AD), the circumflex (CX) and the right coronary (RC). Of the 75 possible territories, 54 were revascularized: 25 were specific to the AD artery and 29 of the CX/RC arteries. INS means luminal obstruction or occlusion greater than or equal to 50 percent. RESULTS: In 14 (26 percent) of the 54 revascularized territories the grafts were INS. The DSE detected ischemia in 16 (28 percent) territories; 10 of which had INS grafts. The DSE detected ischemia in 6 (15 percent) of the 40 territories whose grafts were SUF. Therefore, the DSE had a sensitivity of 71.4 percent, specificity of 85 percent and diagnostic accuracy of 81.4 percent. CONCLUSION: The DSE is a diagnostic method with high specificity and diagnostic accuracy, and good sensitivity for the functional assessment of coronary grafts.

Avaliação ecocardiográfica dos diferentes padrões geométricos do ventrículo esquerdo em pacientes hipertensos / Echocardiographic assessment of the different left ventricular geometric patterns in hypertensive patients

OBJECTIVE: To identiy left ventricular geometric patterns in hypertensive patients on echocardiography, and to correlate those patterns with casual blood pressure measurements and with the parameters obtained on a 24-hour ambulatory blood pressure monitoring. METHODS: We studied sixty hypertensive patients, grouped according to the Joint National Committee stages of hypertension.. Using the single- and two-dimensional Doppler Echocardiography, we analyzed the left ventricular mass and the geometric patterns through the correlation of left ventricular mass index and relative wall thickness. On ambulatory blood pressure monitoring we assessed the means and pressure loads in the different geometric patterns detected on echocardiography RESULTS: We identified three left ventricular geometric patterns: 1) concentric hypertrophy, in 25 percent of the patients; 2) concentric remodeling, in 25 percent; and 3) normal geometry, in 50 percent. Casual systolic blood pressure was higher in the group with concentric hypertrophy than in the other groups (p=0.001). Mean systolic pressure in the 24h, daytime and nighttime periods was also higher in patients with concentric hypertrophy, as compared to the other groups (p=0.003, p=0.004 and p=0.007). Daytime systolic load and nighttime diastolic load were higher in patients with concentric hypertrophy ( p=0.004 and p=0.01, respectively). CONCLUSIONS: Left ventricular geometric patterns show significant correlation with casual systolic blood pressure, and with means and pressure loads on ambulatory blood pressure monitoring