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.

O estudo dos autoanticorpos antirreceptores beta1 e anti-m2 na cardiopatia chagásica crônica / The study of anti-beta1 and anti-m2 receptors autoantibodies in chronic chagas cardiopathy

Fundamentos: A Cardiopatia Chagásica Crônica (CCC) cujo agente etiológico é o Trypanosoma cruzi (T.cruzi) compromete 20 a 30 porcento dos indivíduos infectados. No Brasil, 2 a 3 milhões de pessoas estavam infectadas até 1980 e na América Latina 18 milhões de pessoas. Dados mais recentes da OMS (1991) mostram que esse número diminuiu para 11 milhões até 1990. Um dos mecanismos propostos para explicar o dano miocárdico na CCC é o autoimune. Objetivos: Relacionar a titulação dos anticorpos anti beta1 e anti M2 com função ventricular esquerda, disautonomia e arritmias cardíacas. Metodologia: Estudo transversal com 64 pacientes portadores de CCC confirmada sorologicamente por Elisa e Hemaglutinação. A titulação dos anticorpos anti-beta1 e anti-M2 foi obtida pelo imunoensaio ELISA. A análise da função ventricular esquerda foi feita pelo ecocardiograma através da fração de ejeção (FE) pelo método de Simpson. As arritmias cardíacas foram avaliadas pelo Holter cardíaco de 24 h assim como a disautonomia (variabilidade da freqüência cardíaca). O teste ergométrico avaliou disautonomia (queda da frequência cardíaca no primeiro minuto de recuperação) e desempenho cardíaco durante o esforço. O eletrocardiograma de alta resolução (ECGAR) avaliou o potencial arritmogênico em pacientes sem distúrbios de condução ao eletrocardiograma (ECG)Resultados: Holter de 24h: existe uma correlação inversa significativa entre a titulação de anti-beta1 com o SDNN index de 2 às 6h (rs = - 0,313; p= 0,041; n=43) e uma correlação direta significativa entre a titulação do anti- M2 com SDANN de 2 às 6h (rs = 0,317; 0,039; n=43). Teste ergométrico: observou-se correlação direta significativa entre a titulação anti-beta1 e o duplo produto (rs=0,371; p=0,005, n=56)...

O subgrupo com resposta cronotrópica normal apresentou titulação anti-beta1 significativamente maior que o subgrupo com resposta cronotrópica deprimida (p = 0,023). O subgrupo com resposta inotrópica normal apresentou titulação anti-M2 significativamente maior que o subgrupo com resposta inotrópica deprimida (p=0,044). Ecocardiograma: FE (Simpson) não correlacionou significativamente com anti-B1 e anti-M2 (rs =0,045; p = 0,73 ; n=62), (rs =-0,036; p = 0,78), respectivamente. ECGAR: RMS>20 e LAS <38 não mostrou correlação significativa de RMS com as titulações de anti- beta1 (rs-0,268; p= 0,26; n=18) e anti-M2 (rs= - 0,121; p=0,63; n=18) e de LAS com anti- beta1 (rs =0,006; p = 0,98; n=18) e anti- M2 (rs=0,059; p=0,82; n=18). ECG: titulação de anti-beta1 e anti- M2 foram significativamente maiores no grupo com Fibrilação atrial (FA) que no grupo sem FA (p=0,01) e (p=0,029) respectivamente. O subgrupo com ritmo cardíaco sinusal apresentou anti-M2 significativamente menor que o subgrupo sem ritmo cardíaco sinusal (p= 0,035). Análise multivariada: o Duplo Produto (p=0,016) foi variável independente, ao nível de 5 porcento, para titulação anti- beta1. SDANN de 2 ás 6h (p=0,13) foi variável independente ao nível de 15 porcento para explicar a titulação de anti-M2. Conclusões: Os anticorpos anti-beta1 correlacionam de forma inversa e significativa com o SDNN index e o SDANN ao Holter de 24h no período de 2 às 6h, de forma direta com duplo produto ao teste ergométrico, resposta cronotrópica e com fibrilação atrial ao ECG. Os anticorpos anti-M2 correlacionam diretamente com o SDNN index e SDANN ao Holter, com a resposta inotrópica normal ao teste ergométrico e com a fibrilação atrial ao ECG. Análise multivariada: o duplo produto é variável independente (5 porcento) para anti-beta1 e SDANN(15 porcento) é variável independente para anti- M2...

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.

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

Estudo ecodopplercardiográfico em adolescentes e adultos jovens portadores de anemia falciforme / Doppler echocardiographic study in adolescents and young adults with sickle cell anemia

OBJECTIVE: Anatomical and functional assessment of the heart through Doppler and echocardiography in patients with cell anemia (SCA). METHODS: Twenty-five patients with SCA and ages ranging from 14 to 45 years were prospectively studied in a comparison with 25 healthy volunteers. All of them underwent clinical and laboratory evaluation and Doppler echocardiography as well.The measurements were converted into body surface indices. RESULTS: There were increases in all chamber diameters and left ventricle (LV) mass of the SCA patients. It was characterised an eccentric hypertrophy of the left ventricle. The preload was increased (left ventricle end-diastolic volume) and the afterload was decreased (diastolic blood pressure, peripheral vascular resistance and end-systolic parietal stress ESPS). The cardiac index was increased due to the stroke volume. The ejection fraction and the percentage of the systolic shortening , as well as the systolic time intervals of the LV were equivalent. The isovolumetric contraction period of the LV was increased. The mitral E-septum distance and the end-systolic volume index (ESVi) were increased. The ESPS/ESVi ratio,a loading independent parameter, was decreased in SCA, suggesting systolic dysfunction. No significant differences in the diastolic function or in the pulmonary pressure occurred. CONCLUSION: Chamber dilations, eccentric hypertrophy and systolic dysfunction confirm the evidence of the literature in characterizing a sickle cell anemia cardiomyopathy.

Sorologia positiva em doadores voluntários de sangue em área endêmica de doença de Chagas / Positive serology in voluntary blood donors in endemic area of Chagas' disease

Com a finalidade de detectar a prevalência de portadores da doença de Chagas entre doadores de sangue em zona endêmica (município de Piumhy-MG), foram estudados 30 doadores voluntários de sangue (com 1 a 3 doaçöes nos últimos 5 meses). Eram 25 homens e 5 mulheres com idade entre 26 e 52 anos (média 39), todos da raça branca, naturais e residentes no município, assintomáticos e sem contato com "barbeiro" e/ou ter recebido transfusäo sangüínea. Foram realizadas três reaçöes sorológicas: Guerreiro-Machado, Imunofluorescência e Hemaglutinaçäo. As três reaçöes sorológicas foram positivas em 4 doadores (13,3%) e negativas nos demais. Discute-se a importância deste diagnóstico para a prevençäo da disseminaçäo da doença tanto em áreas endêmicas quanto em grandes centros