Relação entre Norepinefrina Urinária, Fibrose e Arritmias na Cardiopatia Chagásica Crônica com Fração de Ejeção Preservada ou Minimamente Reduzida / Relationship between Urinary Norepinephrine, Fibrosis, and Arrhythmias in Chronic Chagas Heart Disease with Preserved or Mildly Reduced Ejection Fraction

Resumo Fundamento: Na cardiomiopatia chagásica crônica (CCC), impõem-se estudos com a proposta de identificar fatores de risco arritmogênicos em pacientes nos quais a disfunção ventricular de moderada a grave não está presente. Objetivos: Verificar a dependência entre arritmias ventriculares frequentes (ARV), fração de ejeção de ventrículo esquerdo (FEVE), extensão da fibrose pela ressonância magnética cardíaca (RMC) e dosagem de norepinefrina urinária (NOREPI) na CCC com FEVE preservada ou minimamente comprometida. Métodos: Foi analisada no Holter a presença de extrassístoles ventriculares >30/hora. Na RMC, avaliou-se a FEVE e a quantificação de massa fibrosada. Foi realizada a dosagem de NOREPI pelo método de Muskiet. A matriz de correlação foi calculada para aferir a capacidade de as variáveis preverem outra sendo considerado significante p<0,05. Resultados: Foram incluídos no estudo 59 pacientes, com idade média de 57,9±10,94 anos. Arritmia ventricular frequente (ARV) foi detectada em 28 pacientes. A variável fibrose mostrou-se inversamente proporcional à fração de ejeção de ventrículo esquerdo (FEVE) (R de −0,61) e à norepinefrina urinária (NOREPI) (R de −0,68), assim como a variável ARV mostrou-se inversamente proporcional à FEVE (R de −0,33) e à NOREPI (R de −0,27). Já a FEVE mostrou-se diretamente proporcional à NOREPI (R de 0,83). Conclusão: Nesta amostra, em pacientes com CCC com FEVE preservada ou discretamente reduzida, observa-se a integridade do sistema nervoso autonômico em corações com pouca fibrose e FEVE mais elevada, apesar da presença de tradicionais fatores de risco para morte súbita cardíaca. Há dependência entre os níveis de NOREPI, FEVE e fibrose miocárdica, mas não com ARV.

Abstract Background: In Chronic Chagas Cardiomyopathy (CCC), studies are needed to identify arrhythmogenic risk factors in patients in which moderate to severe ventricular dysfunction is not present. Objective: To verify the correlation between frequent ventricular arrhythmias (PVC), left ventricular ejection fraction (LVEF), extension of fibrosis by cardiac magnetic resonance (CMR), and urinary norepinephrine measurement (NOREPI) in CCC with preserved or mildly compromised LVEF. Methods: The presence of ventricular extrasystoles > 30/h was analyzed on Holter. At CMR, LVEF and quantification of fibrosis mass were evaluated. The dosage of NOREPI was performed using the Muskiet method. The correlation coefficient matrix was calculated to measure the predictive ability of the variables to predict another variable, with p < 0.05 being considered significant. Results: A total of 59 patients were included. The mean age was 57.9 + 10.94 years. PVC was detected in 28 patients. The fibrosis variable was inversely proportional to LVEF (R of −0.61) and NOREPI (R of −0.68). Also, the variable PVC was inversely proportional to LVEF (R of −0.33) and NOREPI (R of −0.27). On the other hand, LVEF was directly proportional to NOREPI (R of 0.83). Conclusion: In this sample, in patients with CCC with preserved or slightly reduced LVEF, integrity of the autonomic nervous system is observed in hearts with little fibrosis and higher LVEF despite the presence of traditional risk factors for sudden cardiac death. There is correlation between the levels of NOREPI, LVEF, and myocardial fibrosis, but not with PVC.

Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach*

Chagas disease (CD), caused by infection by the protozoan parasite Trypanosoma cruzi, presents as main clinical manifestation the chronic chagasic cardiomyopathy (CCC). CCC afflicts millions of people, mostly in Latin America, and vaccine and effective therapy are still lacking. Comprehension of the host/parasite interplay in the chronic phase of T. cruzi infection may unveil targets for rational trait-based therapies to improve CCC prognosis. In the present viewpoint, I critically summarise a collection of data, obtained by our network of collaborators and other groups on CCC and preclinical studies on pathogenesis, targeting identification for intervention and the use of drugs with immunomodulatory properties to improve CCC. In the last two decades, models combining mouse lineages and T. cruzi strains allowed replication of crucial clinical, histopathological, and immunological traits of CCC. This condition includes conduction changes (heart rate changes, arrhythmias, atrioventricular blocks, prolongation of the QRS complex and PR and corrected QT intervals), ventricular dysfunction and heart failure, CD8-enriched myocarditis, tissue remodeling and progressive fibrosis, and systemic inflammatory profile, resembling "cytokine storm". Studies on Chagas' heart disease pathogenesis begins to unveil the molecular mechanisms underpinning the inflammation-related cardiac tissue damage, placing IFNγ, TNF and NFκB signaling as upstream regulators of miRNAs and mRNAs associated with critical biological pathways as cell migration, inflammation, tissue remodeling and fibrosis, and mitochondrial dysfunction. Further, data on preclinical trials using hypothesis-based tools, targeting parasite and inflammation-related alterations, opened paths for multi-therapeutic approaches in CCC. Despite the long path taken using experimental CD models replicating relevant aspects of CCC and testing new therapies and therapeutic schemes, these findings may get lost in translation, as conceptual and economical challenges, underpinning the valley of death across preclinical and clinical trials. It is hoped that such difficulties will be overcome in the near future.

Estilo de vida e nível de atividade física de indivíduos portadores de miocardiopatia chagásica / Lifestyle and level of physical activity in individuals with chagasic myocardiopathy

INTRODUÇÃO: A doença de Chagas (DC) constitui uma infecção parasitária causada pelo protozoário flagelado Tripanosoma cruzi. Estimativas apontam a existência de, aproximadamente, cinco milhões de indivíduos infectados, principalmente na América Latina, com o Brasil datando entre 1,9 a 4,6 milhões de indivíduos sob o mesmo aspecto infeccioso. O desfecho cardíaco configura um dos aspectos mais importantes, com manifestações condizentes à disfunção ventricular sistólica ou diastólica, disfunção autonômica cardíaca e morte súbita. OBJETIVO: correlacionar o estilo de vida e o nível de atividade física de indivíduos portadores de miocardiopatia chagásica (MC). MATERIAL E MÉTODOS: Realizou-se um estudo analítico, de corte transversal, em ambulatório de referência para Miocardiopatias, com abrangência estadual. Utilizou-se formulário próprio construído pelas autoras, o qual contemplava além das variáveis clínicas e demográficas, variáveis relativas à análise do estilo de vida e atividade física dos participantes, sendo esse aplicado em sala de espera, enquanto os sujeitos aguardavam atendimento médico. RESULTADOS: Foram selecionados 74 indivíduos portadores de MC. A média de idade da amostra foi de 61,2 ± 8,5 anos, sendo que 50 (68,0%) indivíduos eram do sexo feminino. Em relação ao nível de atividade física, houve predomínio da categoria "não ativo", correspondendo a 60 indivíduos (71,0%). O estilo de vida foi classificado como "muito bom" para 41 (55,0%) participantes e "bom" para 22 (30,0%) participantes, não havendo indivíduos alocados na categoria "necessita melhorar" do questionário. CONCLUSÃO: Os resultados obtidos permitem concluir que, de modo geral, o estilo de vida e o nível de atividade física de indivíduos portadores de MC caracterizaram-se como "bom" / "muito bom" e não ativos, respectivamente.

INTRODUCTION: Chagas disease (CD) is a parasitic infection caused by the flagellated protozoan Trypanosoma cruzi. Estimates point to the existence of approximately five million infected individuals, mainly in Latin America, with Brazil dating between 1.9 and 4.6 million individuals under the same infectious aspect. The cardiac outcome is one of the most important aspects with manifestations consistent with systolic or diastolic ventricular dysfunction, cardiac autonomic dysfunction, and sudden death. OBJECTIVE: To correlate the lifestyle and physical activity level of individuals with Chagas cardiomyopathy (CM). MATERIAL AND METHODS: A cross-sectional analytical study was carried out in a reference outpatient clinic for cardiomyopathies, with state coverage. A form was created by the authors, which included, in addition to the clinical variables and demographic, variables related to the analysis of the participants' lifestyle and physical activity, this being applied in the waiting room, while the subjects waited for medical care. RESULTS: Seventy-four individuals with CM were selected. The mean age of the sample was 61.2 ± 8.5 years, with 50 (68.0%) individuals being female. Regarding the level of physical activity, the "not active" category was predominant, corresponding to 60 individuals (71.0%). The lifestyle was classified as "very good" for 41 (55.0%) participants and "good" for 22 (30.0%) participants, with no individuals allocated to the "need to improve" category of the questionnaire. CONCLUSION: The results obtained allow us to conclude that, in general, the lifestyle and the level of physical activity of individuals with CM were characterized as "good" / "very good" and not active, respectively.

Correlação entre Cardiomegalia pela Radiografia de Tórax e Diâmetro do Ventrículo Esquerdo pela Ecocardiografia em Pacientes com Doença de Chagas / Correlation between Cardiomegaly on Chest X-Ray and Left Ventricular Diameter on Echocardiography in Patients with Chagas Disease

Resumo Fundamento Cardiomegalia pela radiografia de tórax (RXT) é preditor independente de morte em indivíduos com cardiomiopatia crônica da doença de Chagas (CCDC). Contudo, a correlação entre o aumento do índice cardiotorácico (ICT) na RXT e do diâmetro telediastólico do ventrículo esquerdo (DDVE) pela ecocardiografia (ECO) nessa população não está bem definida. Objetivos Analisar a relação entre cardiomegalia pela RXT e DDVE pela ECO em pacientes com doença de Chagas (DC) e sua aplicabilidade ao escore de Rassi. Métodos Estudo retrospectivo incluiu 63 pacientes ambulatoriais com DC avaliados por RXT e ECO. Cardiomegalia na RXT foi definida como ICT > 0,5. DDVE foi avaliado como variável contínua. Curva ROC foi utilizada para avaliar o potencial do DDVE para identificação de cardiomegalia pela RXT, com ponto de corte definido pela maior somatória de sensibilidade e especificidade. Resultados Idade mediana = 61 anos [intervalo interquartil: 48-68], 56% mulheres. CCDC foi identificada em 58 pacientes; 5 tinham a forma indeterminada da DC. Cardiomegalia foi detectada em 28 indivíduos. A área sob a curva ROC do DDVE para identificação de cardiomegalia foi de 0,806 (IC 95%: 0,692-0,919). O ponto de corte ótimo para DDVE foi de 60 mm (sensibilidade = 64%, especificidade = 89%). O uso do DDVE pela ECO em substituição ao ICT pela RXT alterou o escore de Rassi em 14 pacientes, e em 10 deles houve redução do risco presumido. Conclusão DDVE pela ECO é parâmetro adequado e com alta especificidade para distinguir entre presença e ausência de cardiomegalia na RXT na DC. (Arq Bras Cardiol. 2021; 116(1):68-74)

Abstract Background Cardiomegaly on chest X-ray is an independent predictor of death in individuals with chronic Chagas cardiomyopathy (CCC). However, the correlation between increased cardiothoracic ratio (CTR) on chest X-ray and left ventricular end-diastolic diameter (LVEDD) on echocardiography is not well established in this population. Objectives To assess the relationship between chest X-ray and LVEDD on echocardiography in patients with Chagas disease and its applicability to the Rassi score. Methods Retrospective study on 63 Chagas disease outpatients who underwent chest X-ray and echocardiography. Cardiomegaly on chest X-ray was defined as a CTR>0.5. LVEDD was analyzed as a continuous variable. ROC curve was used to evaluate the ability of LVEDD in detecting cardiomegaly by chest X-ray, with a cut-off point defined by the highest sum of sensitivity and specificity. Results Median age 61 years [interquartile range 48-68], 56% were women. CCC was detected in 58 patients, five patients had the indeterminate form of Chagas disease. Cardiomegaly was detected in 28 patients. The area under the ROC curve for LVEDD was 0.806 (95%CI: 0.692-0.919). The optimal cut-off for LVEDD was 60 mm (sensitivity = 64%, specificity = 89%). The use of LVEDD on echocardiography as a surrogate for CTR on chest X-ray changed the Rassi score values of 14 patients, with a reduction in the presumed risk in 10 of them. Conclusion LVEDD on echocardiography is an appropriate, highly specific parameter to distinguish between the presence and absence of cardiomegaly on chest X-ray in Chagas disease. (Arq Bras Cardiol. 2021; 116(1):68-74)

Resonancia magnética cardíaca en la miocardiopatía chagásica crónica. Una herramienta para optimizar el diagnóstico, la estratificación de riesgo y el pronóstico / Cardiac magnetic resonance imaging in chronic chagasic cardiomyopathy. A tool to optimize diagnosis, risk stratification and prognosis

Resumen La enfermedad de Chagas es un problema de salud pública en Latinoamérica, donde afecta a aproximadamente a 6 millones de personas. En Costa Rica se ha descrito la enfermedad desde 1941, con varios reportes de casos confirmados agudos y crónicos. La miocardiopatía chagásica afecta al 30% de los individuos con infección crónica y es la manifestación más grave de la enfermedad, con una morbimortalidad mayor que otras miocardiopatías. La resonancia magnética cardíaca, debido a su capacidad de caracterización tisular permite identificar con alta correlación histopatológica la presencia de fibrosis, edema e inflamación en la miocardiopatía chagásica. Esto ha permitido una mejor comprensión de la compleja fisiopatología de la enfermedad y además permite el diagnóstico diferencial con otras patologías simuladoras como lo es la cardiopatía isquémica. En la MCh la presencia de fibrosis miocárdica predice de manera independiente eventos adversos mayores tales como taquicardia ventricular sostenida y muerte cardiovascular. Debido a lo anterior la resonancia magnética cardíaca es una robusta herramienta capaz de mejorar el diagnóstico, la estratificación de riesgo y el pronóstico de estos pacientes, con miras a mejores y oportunas intervenciones terapéuticas.

Abstract Chagas disease is a public health problem in Latin America, where it affects approximately 6 million people. In Costa Rica the disease has been described since 1941, with several reports of acute and chronic confirmed cases. Chagas cardiomyopathy affects 30% of individuals with chronic infection and is the most serious manifestation of the disease, with a higher morbidity and mortality than other cardiomyopathies. Cardiac magnetic resonance, due to its capacity for tissue characterization, identifies the presence of fibrosis, aedema and inflammation in Chagas cardiomyopathy with high histopathological correlation. This has allowed a better understanding of the complex pathophysiology of the disease and also allows differential diagnosis with other pathologies that can simulate, such as ischemic heart disease. In Chagas cardiomyopathy, the presence of myocardial fibrosis independently predicts major adverse events such as sustained ventricular tachycardia and cardiovascular death. Due to the above, cardiac magnetic resonance is a robust tool capable of improving the diagnosis, risk stratification and prognosis of these patients, with a view to better and timely therapeutic interventions.

Insuficiencia cardíaca en miocardiopatía chagásica crónica

Acorde al último reporte epidemiológico de la Organización Mundial de la Salud del año 2015, en Argentina existen 1,5 millones de personas infectadas por el Trypanosoma cruzi y alrededor de 370.000 pacientes con distintas manifestaciones de la enfermedad de Chagas. El objetivo de esta revisión es analizar una de las manifestaciones clínicas más graves e invalidantes de esta enfermedad: la miocardiopatía chagásica crónica. Esta patología, que presenta una distribución geográfica dispar en la Argentina, comparte varias características comunes con otras formas etiológicas de insuficiencia cardíaca, aunque su epidemiología, presentación clínica y respuesta al tratamiento médico, eléctrico y quirúrgico le otorgan una distinción particular y en muchos casos, poco conocida. Por tal motivo, existe en la comunidad médica, un creciente interés en alcanzar un mayor conocimiento de esta enfermedad a fin de implementar manejos y decisiones terapéuticas, que si bien demostraron beneficio en otras poblaciones de pacientes con insuficiencia cardíaca, aun no han sido adecuadamente avaladas para su aplicación en insuficiencia cardíaca chagásica. Muchas de las indicaciones e intervenciones se basan en experiencia más que evidencia científica. Es por ello que esta revisión es un desafío oportuno para optimizar el tratamiento y pronóstico de esta población.

According to the last epidemiological report of the World Health Organization in 2015, in Argentina there are 1.5 million people infected with Trypanosoma cruzi and around 370,000 patients with different manifestations of Chagas disease. The objective of this review is to analyze one of the most serious and invalidating clinical manifestations of this disease: chronic chagasic myocardiopathy. This pathology, which has a disparate geographical distribution in Argentina, shares several common characteristics with other etiological forms of heart failure, although its epidemiology, clinical presentation and response to medical, electrical and surgical treatment give it a particular distinction and in many cases, little known. For this reason, there is a growing interest in the medical community to achieve greater knowledge of this disease in order to implement management and therapeutic decisions, which although they have shown benefit in other populations of patients with heart failure, have not yet been adequately endorsed. for its application in chagasic heart failure. Many of the indications and interventions are based on experience rather than scientific evidence. That is why this review is a timely challenge to optimize the treatment and prognosis of this population.

De acordo o último relatório epidemiológico da Organização Mundial da Saúde em 2015, na Argentina existem 1,5 milhão de pessoas infectadas pelo Trypanosoma cruzi e cerca de 370.000 pacientes com manifestações diferentes da doença de Chagas. O objetivo desta revisão é analisar uma das manifestações clínicas mais graves e invalidantes dessa doença: miocardiopatia chagásica crônica. Esta condição, que tem uma distribuição geográfica desigual na Argentina, compartilha várias características comuns com outras formas etiológicos de insuficiência cardíaca, embora sua epidemiologia, apresentação clínica e resposta ao tratamento médico, elétrico e cirúrgico dar uma distinção especial e, em muitos casos, pouco conhecido. Portanto, há na comunidade médica, um crescente interesse na obtenção de uma melhor compreensão da doença, a fim de implementar as decisões de manejo e tratamento, que embora benefício mostrou em outras populações de pacientes com insuficiência cardíaca ainda não foram adequadamente apoiados para sua aplicação na insuficiência cardíaca chagásica. Muitas das indicações e intervenções são baseadas na experiência e não na evidência científica. É por isso que esta revisão é um desafio oportuno para otimizar o tratamento e o prognóstico dessa população.

Miocardiopatía chagásica crónica letal en mujer jóven que se estudiaba por síndrome coronario agudo tras un evento de taquicardia ventricular sostenida / Chronic chagasic lethal cardiomyopathy in young women to be studying for acute coronary syndrome after an event sustained ventricular tachycardia

ResumenLa enfermedad de Chagas, también conocida como Trypanosomiasis Americana, es una infección sistémica protozoaria causada por el flagelado Trypanosoma Cruzi (Trypanosoma cruzi), la cual tiene una alta asociación a situaciones económi cas y sociales limítrofes. Las tasas de mortalidad en los pacientes con insuficiencia cardiaca sintomática por Chagas son tan altas como del 63% y 84% a los 5 y 10 años, respectivamente. Las principales causas de muerte en los pacientes con cardiomiopatía por Chagas se dividen en insuficiencia cardiaca refractaria en primer lugar, seguido por muerte súbita y el evento cerebro-vascular en segundo y tercer lugar, respectivamente. En el siguiente artículo presentaremos el caso de una paciente cuya manifestación de su miocardiopatía chagásica fue un evento taquiarrítmico, seguido de una revisión bibliográfica de una patología cuya incidencia en nuestro país es desconocida y que resurge a nivel mundial aumentando el número de casos fuera de regiones endémicas producto de las migraciones y la globalización.

AbstractChagas disease, also known as American trypanosomiasis, is a systemic infection caused by protozoan Trypanosoma cruzi's, which has a high association with economic and social situations bordering. Mortality rates in patients with symptomatic heart failure due to Chagas are as high as 63% and 84% at 5 and 10 years, respectively. The main causes of death in patients with Chagas cardiomyopathy are divided as refractory heart failure in first, followed by sudden death and cerebrovascular event in second and third place respectively. In the following article we present the case of a patient whose manifestation of Chagas cardiomyopathy was a tachyarrhythmic event, followed by a literature review of a disease whose incidence in our country is unknown and resurgent outside regions endemic product of migration and globalization.

Chagas disease: morbidity profile in an endemic area of Northeastern Brazil

Abstract: INTRODUCTION : This study evaluated the clinical forms and manifestation severities of Chagas disease among serologically reactive individuals from Western Rio Grande do Norte (Northeastern Brazil). METHODS : This cross-sectional study included 186 adults who were evaluated using electrocardiography, echocardiography, chest radiography, and contrast radiography of the esophagus and colon. A clinical-epidemiological questionnaire was also used. RESULTS : The indeterminate, cardiac, digestive, and cardiodigestive clinical forms of Chagas disease were diagnosed in 51.6% (96/186), 32.2% (60/186), 8.1% (15/186) and 8.1% (15/186) of the participants, respectively. Heart failure (functional classes I-IV) was detected in 7.5% (14/186) of the participants, and 36.4% (24/66), 30.3% (20/66), 15.2% (10/66), 13.6% (9/66), and 4.5% (3/66) of the patients were at stage A, B1, B2, C, and D, respectively. Dilated cardiomyopathy and electrocardiographic changes were detected in 10.2% (19/186) and 48.1% (91/186) of the participants, respectively. Apical aneurysm was diagnosed in 10.8% (20/186) of the participants, and other changes in the segmental myocardial contractility of the left ventricle were diagnosed in 33.9% (63/186) of the participants. Megaesophagus (groups I-IV) was observed in 7% (13/186) of the participants, megacolon (grades 1-3) was detected in12.9% (24/186) of the participants, and both organs were affected in 29.2% (7/24) of the megacolon cases. CONCLUSIONS : We detected various clinical forms of Chagas disease (including the digestive form). Our findings indicate that clinical symptoms alone may not be sufficient to exclude or confirm cardiac and/or digestive damage, and the number of patients with symptomatic clinical forms may be underestimated.

SEROPREVALENCE OF T. cruzi INFECTION IN BLOOD DONORS AND CHAGAS CARDIOMYOPATHY IN PATIENTS FROM THE COAL MINING REGION OF COAHUILA, MEXICO / Soroprevalência da infecção pelo T. cruzi em doadores de sangue e cardiomiopatia chagásica em pacientes da região carbonífera de Coahuila, México

Context and Objective: Chagas disease is considered a worldwide emerging disease; it is endemic in Mexico and the state of Coahuila and is considered of little relevance. The objective of this study was to determine the seroprevalence of T. cruzi infection in blood donors and Chagas cardiomyopathy in patients from the coal mining region of Coahuila, Mexico. Design and Setting: Epidemiological, exploratory and prospective study in a general hospital during the period January to June 2011. Methods: We performed laboratory tests ELISA and indirect hemagglutination in three groups of individuals: 1) asymptomatic voluntary blood donors, 2) patients hospitalized in the cardiology department and 3) patients with dilated cardiomyopathy. Results: There were three levels of seroprevalence: 0.31% in asymptomatic individuals, 1.25% in cardiac patients and in patients with dilated cardiomyopathy in 21.14%. Conclusions: In spite of having detected autochthonous cases of Chagas disease, its importance to local public health remains to be established as well as the details of the dynamics of transmission so that the study is still in progress.

Contexto e Objetivo: A doença de Chagas é mundialmente considerada uma doença emergente, é endêmica no México e no estado de Coahuila e considerada de pouca relevância. O objetivo do estudo foi determinar a soroprevalência da infecção pelo T. cruzi em doadores de sangue e cardiomiopatia chagásica em pacientes da região carbonífera de Coahuila, México. Desenho e Local: Estudo epidemiológico, exploratório e prospectivo em um hospital geral no período de janeiro a junho de 2011. Métodos: Foram realizados testes de laboratório ELISA e hemoglutinação indireta em três grupos de indivíduos: 1) doadores de sangue voluntários assintomáticos, 2) pacientes internados na área de cardiologia e 3) pacientes com cardiomiopatia dilatada. Resultados: Foram achados três níveis de soroprevalência: 0,31% em indivíduos doadores de sangue assintomáticos, 1,25% em pacientes cardiopatas e, em pacientes com cardiomiopatia dilatada 21,14%. Conclusão: Detectamos casos autóctones de doença de Chagas em área considerada não endêmica. Deve ser determinada sua importância na saúde pública regional e local, para estabelecer os detalhes do mecanismo de transmissão. O estudo ainda está em desenvolvimento.

Expresión diferencial entre estadios de Trypanosoma cruzi I en el aislamiento de un paciente con cardiomiopatía chagásica crónica de zona endémica de Santander, Colombia / Differential protein expression in developmental stages of Trypanosoma cruzi I isolated from a patient with chronic chagasic cardiomyopathy

Introducción. Trypanosoma cruzi es el agente causal de la enfermedad de Chagas. Durante la infección en los huéspedes mamíferos, se observan dos formas del parásito: tripomastigotes y amastigotes. En el curso de la diferenciación del parásito cada estadio expresa un patrón de proteínas específicas de fase, las cuales son responsables de sus características morfológicas, bioquímicas y biológicas, que podrían estar determinando un papel importante en la capacidad infecciosa, virulencia y supervivencia del parásito. Objetivo. Analizar la expresión diferencial entre los estadios tripomastigote y amastigote de un aislamiento de T. cruzi I, utilizando la electroforesis en dos dimensiones y la identificación de las proteínas diferencialmente expresadas mediante espectrometría de masas. Materiales y métodos. Se utilizó un clon del aislamiento MHOM/07/338 de T. cruzi I y, mediante electroforesis en dos dimensiones, se compararon los perfiles proteicos de los estadios tripomastigote y amastigote del parásito. Las imágenes se analizaron con el software PDQuest y las proteínas diferencialmente expresadas se identificaron por MALDI TOF o LC MS/MS. Resultados. Los geles bidimensionales mostraron un promedio de 325 manchas proteicas en cada estadio. En los análisis comparativos se detectaron 21 manchas "sobre expresadas" en el estadiotripomastigote y 30, en el estadio amastigote. Se seleccionaron 16 proteínas para identificación por espectrometría de masas y se clasificaron en diferentes categorías funcionales. Conclusiones. Las proteínas exclusivas de T. cruzi relacionadas, principalmente, con metabolismo glucolítico y ensamble del citoesqueleto, fueron las que presentaron una mayor expresión diferencial entre los estadios tripomastigote y amastigote del parásito. Estas proteínas podrían ser utilizadas para el diseño de fármacos.

Introduction. Trypanosoma cruzi is the causative agent of Chagas disease. During infection inmammalian hosts, two main forms of the parasite are observed: trypomastigotes and amastigotes. During differentiation, each stage of the parasite expresses a pattern of proteins specific to each phase-proteins which are responsible for the cell’s morphological, biochemical and biological properties. These properties ultimately govern the infectivity, virulence and survival of the parasite. Objective. A differential expression analysis was conducted to compare trypomastigote and amastigote stages of T. cruzi I isolate, and to identify proteins differentially expressed by means of mass spectrometry. Materials and methods. A T. cruzi clone of the strain MHOM/07/338 was used to analyze the differential expression between trypomastigote stages of a T. cruzi isolate, using two-dimensional electrophoresis and identification of diferentially expressed proteins by mass spectrometry. The protein profiles of the stages of the parasite were obtained by two-dimensional gel electrophoresis and visualized in gels dyed with Coomassie blue. The images were analyzed with PDQuest software and the differential expression of the proteins was identified by MALDI TOF or LC MS/MS. Results. The two-dimensional gels revealed an average of 325 protein spots in each stage. The comparative analyses detected 21 spots that were over expressed in the trypomastigote stage and 30 in the amastigote stage. Sixteen of the over expressed proteins were selected for identification by mass spectrometry and classified in several functional categories. Mass spectrophotometry determined that the proteins were associated mainly with glucolytic metabolism and assembly of the cytoskeleton constituents. Conclusions. The differential expression between trypomastigote and amastigote stages consisted of proteins specific to T. cruzi and are potential targets for the design of treatment drugs.

Fibrilación auricular en pacientes con diagnóstico de chagas crónico procedentes de la zona norte del Estado Anzoátegui / Atrial fibrillation in patients with a diagnosis of chronic disease from the northern Anzoategui State

La fibrilación auricular que acompaña a la cardiopatíachagásica crónica constituye un mal pronóstico, dada suasociación con la grave disfunción sistólica ventricularizquierda y la formación de trombos auriculares con tendenciaa la embolización sistémica. Se analizó la fibrilaciónauricular en pacientes chagásicos de la zona norte del estado Anzoátegui. Se estableció la relación de la fibrilación auricularcon eventos cardíacos mayores como la enfermedad vascularcerebral, la muerte cardiovascular y la hospitalizaciónpor causas cardíacas no planificadas. 98 pacientes chagásicos 56 sexo masculino y 42 sexo femenino, con edad promedio de 63,56 años fueron clasificados en losgrupos sero-positivo Ch I (electrocardiograma normal), Ch II(electrocardiograma anormal) y Ch III (electrocardiogramaanormal e insuficiencia cardíaca) y evaluados por tres años consecutivos para determinar la prevalencia de fibrilación auricular y su asociación con los eventos cardíacos mayores. La prevalencia de fibrilación auricular en la totalidad de los pacientes chagásicos fue 22,84 ± 2,76%, con una mayor frecuencia en el grupo Ch III (p = 0,0001). El 69,42 ± 4,65% de los pacientes sufrió uno o más eventos cardíacos mayores (p = 0,06) con un riesgo relativo de 2,42 veces para estos sucesos [RR 2,4 IC 95 % (0,9 – 6,54)]. La asociación independiente entre fibrilación auricular y eventos cardíacos mayores no demostró diferencias estadísticamente significativas entre los grupos. La fibrilación auricular no se encontró asociada a la presencia de eventos cardíacos mayores, pero su incidencia en los pacientes con cardiopatía chagásica crónica es importante en los estadios avanzados de la enfermedad, principalmente en aquellos pacientes que presentan frecuencia ventricular izquierda deprimida.

Atrial fibrillation that accompanies chronic chagasiccardiomyopathy carries a poor prognosis, given its association with severe left ventricular systolic dysfunction and the formation of auricular thrombi with a tendency to systemic embolization. Atrial fibrillation was examined inpatients with Chagas disease in the northern Anzoátegui State.The relationship was examined between atrial fibrillation and major cardiac events such as cerebral vascular disease, death and non-elective hospitalization for cardiac causes. 98 patients chagásicos 56 male and 42 female with average age of 63.56 were classified into a sero-positive Ch I (normal electrocardiogram) group, a Ch II (abnormal electrocardiogram) group and a Ch III (abnormal ECG and heart failure) group and were followed for three consecutive years to determine the prevalence of atrial fibrillation and its association with the major cardiac events. The prevalence of atrial fibrillation in all the patients with Chagas disease was 22.84 ± 2.76%, found more frequently in the Ch III group (p = 0.0001). There were 69.42 ± 4.65% patients who suffered one or more major cardiac events (p = 0.06)with a relative risk of 2.42 for such events [RR 2.4 IC 95% (0.9 – 6.54)]. The independent association between atrial fibrillation and major cardiac events showed no statistically significant differences between groups. The atrial fibrillation not found associated with the presence of major cardiac events, but its impact the incidence of atrial fibrillation in patients with chronic chagasic cardiomyopathy is important in the later stages of the disease, mainly in those patients who have depressed left ventricular function.

Associação do polimorfismo de ifng +874T/A com a cardiopatia chagásica crônica / Association of ifng +874 T/A polymorphism with chronic chagas' disease

A doença de Chagas é uma zoonose causada pelo parasita hemoflagelado Trypanosoma cruzi. Atualmente afeta cerca de 10 milhões de pessoas nas Américas, e aproximadamente 90 milhões de pessoas se encontram em áreas de risco. A cardiopatia chagásica crônica (CCC) se desenvolve em um terço dos indivíduos infectados e corresponde a uma miocardite crônica fibrosante intensa e os possíveis fatores que podem contribuir para o desenvolvimento desta podem estar relacionados com a carga parasitária, a cepa do parasita, a autoimunidade e fatores genéticos do parasita e do hospedeiro. Citocinas e quimiocinas têm um importante papel no desenvolvimento de uma resposta imune protetora contra o parasita, porém esta pode estar envolvida com o aumento da inflamação encontrada no miocárdio de pacientes com CCC. O principal objetivo deste estudo foi identificar a freqüência dos genótipos e alelos para o SNP no IFNG na posição +874T/A através da técnica de ARMS - PCR, em 102 pacientes soropositivos para o T. cruzi apresentando a CCC, 86 pacientes soropositivos sem cardiopatia aparente e 179 controles soronegativos para T. cruzi. Não há diferença estatística quando pacientes com CCC foram comparados com indivíduos saudáveis, indicando que o polimorfismo para IFNG na posição +874T/A não parece ter influencia na infecção. Contudo, observamos que o genótipo AA foi mais freqüentemente encontrado em pacientes portadores da CCC do que naqueles portadores da forma indeterminada, sugerindo que indivíduos com este genótipo estão mais susceptíveis ao aparecimento de lesões cardíacas e ao adoecimento (p=0,024)...

Chagas disease is a zoonosis caused by the parasite hemoflagellate Trypanosoma cruzi. Currently affects approximately 10 millions people in the Americas, where approximately 90 millions people are at risk areas. The Chronic chagasic cardiomyopathy (CCC) develops in one third of infected individuals and represents a severe chronic myocarditi. Possible factors that may contribute to the development of several cariopathy can be related to parasite load and difference on strains, autoimmunity and the genetics of the parasite and host. Cytokines and chemokinesplay an important role in the development of a protective immune response against the parasite, but it may be involved with increased inflammation found in the myocardium of CCC. The main objective of this study was to identify the frequency of genotypes and alleles for the SNP in the IFNG position +874 T/A by ARMS-PCR technique in 102 patients seropositive for T. cruzi presenting the CCC, 86seropositive patients without apparent heart disease and 179 negative controls for T. cruzi. There was no statistical difference when CCC patients were compared withhealthy subjects, indicating that the polymorphism at the position +874 T/A does not seem to influence the infection. However, we observed that the AA genotype was more frequently found among patients with CCC than in patients without apparent heart disease, suggesting that individuals with this genotype are more susceptible to develop cardiac illness (p=0,024)...

Peso cardíaco em chagásicos crônicos com ninhos de Trypanosoma cruzi na veia central da supra-renal / Cardiac Weight in Patients with Chronic Chagas Disease with Trypanosoma Cruzi Nests in the Central Vein of the Adrenal Glands

PURPOSE--Comparative analysis of cardiac weight (CW) in patients with chronic Chagas disease, with or without parasitism by Trypanosoma cruzi in the central vein of the adrenal gland (CVAG). METHODS--The CW has been studied in 96 necropsied individuals with chronic Chagas disease. Among them, 48 of them had Trypanosoma cruzi nests on the wall of the CVAG and the other 48 patients did not have nests in the CVAG. Later, this sample was paired for sex, age and anatomo-clinical form, resulting in 60 patients. Among these patients, 30 of them had Trypanosoma cruzi nests on the walls of the CVAG and the other 30 did not have. RESULTS--The CW of Chagas patients which had nests of T. cruzi in the CVAG, was 484.8 +/- 146.0g, while in the ones that did not have the nests on the walls of the CVAG, the CW weight was 415.8 +/- 125.3g. This difference was statistically significant. In the first group it had a prevail of congestive heart failure. Subsequently to the pairing for sex, age and anatomo-clinical form, the CW was respectively 464.3 +/- 146.2g and 436.0 +/- 108.9g. This difference was not statistically significant. CONCLUSION--These data suggest that the parasitism in the central vein of the adrenal gland, combined with other possible events intrinsic to the chronic Chagas disease patients' hearts, carries a supporting role in the increasing of the cardiac weight and in the congestive cardiac insufficiency.