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.

Early clinics of the cardiac forms of Chagas' disease: Discovery and study of original medical files (1909-1915).

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease / Descobertas de Carlos Chagas como Pano de Fundo para a Construção Científica da Cardiopatia Chagásica Crônica

Abstract The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Resumo A construção científica da doença de Chagas crônica (DCC) começou em 1910, quando Carlos Chagas salientou a presença de arritmia cardíaca em exames físicos de pacientes com doença de Chagas crônica, e descreveu um caso de insuficiência cardíaca associada à inflamação do miocárdio e à presença de ninhos de parasitas durante a autópsia. Ele descreveu morte súbita cardíaca associada a arritmias em 1911, e sua associação ao bloqueio AV total detectado com o polígrafo de Jacquet, conforme reportou em 1912. Chagas mostrou a presença de fibrose do miocárdio como subjacente ao quadro clínico da DCC em 1916, e apresentou uma caracterização completa dos aspectos clínicos da DCC em 1922. Em 1928, Chagas detectou fibrose do sistema condutor, e apontou a presença de cardiomegalia acentuada no raio X do tórax, associada a sintomatologia mínima. O uso da reação sorológica no diagnóstico de DCC foi posta em prática clínica em 1936, após a morte de Chagas, e juntamente com o ECG de 12 derivações, revelou a importância epidemiológica da DCC em 1945. Em 1953, ficou comprovado o longo período de tempo entre a infecção inicial e o aparecimento de DCC, enquanto que a incidência anual de DCC na forma indeterminada da doença foi estabelecida em 1956. Os aspectos clínicos fundamentais de DCC descritos por Carlos Chagas foram complementados pelo uso de cateterismo cardíaco em 1965, teste ergométrico em 1973, Holter em 1973, teste eletrofisiológico em 1975, ecocardiografia em 1975, biópsia endomiocárdica em 1981 e ressonância magnética em 1995.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Alterações anatomopatológicas de corações de pacientes chagásicos portadores de marcapasso definitivo endocárdico / Anatomopathological changes in hearts of Chagas disease patients with permanent endocardial pacemakers

OBJETIVO: Descrever as lesões morfológicas, macro e microscópicas, associadas ao marcapasso definitivo (MP) em corações de pacientes falecidos com cardiopatia chagásica crônica e compará-las com as descritas em outras cardiopatias. MÉTODO: Foram estudados 22 corações de pacientes chagásicos crônicos (16 homens e seis mulheres) de 26 a 86 anos de idade (média de 54 anos) portadores de MP definitivo endocárdico. Foram retirados fragmentos das paredes das quatro câmaras, do septo interventricular e da ponta cardíaca, bem como de tecidos que envolviam os cabos-eletrodos e de áreas de aderências para processamento histológico. As características do exsudato leucocitário nos sítios de implante e no miocárdio ventricular foram analisadas por meio da técnica de imuno-histoquímica. RESULTADOS: Inflamação e trombose nos sítios de implante resultaram em encapsulamento fibroso das pontas dos cabos-eletrodos que permaneceram firmemente aderidos ao endocárdio adjacente. Nos sítios de implante, linfócitos B e T ocorreram em proporções semelhantes, diferentemente dos focos da miocardite chagásica ventricular, na qual foi observado marcante predomínio de linfócitos T. CONCLUSÃO: Os cabos-eletrodos não são estruturas biologicamente inertes; sua permanência produz constante estímulo trombogênico, assim como processo inflamatório e fibrogênico nos sítios dos implantes. A organização de trombos vermelhos e/ou de fibrina que se formam em torno dos cabos-eletrodos parece responsável por seu encapsulamento e por frequentes aderências às estruturas adjacentes. As lesões cardíacas associadas aos MP na cardiopatia chagásica crônica dos casos estudados foram semelhantes às descritas em outras cardiopatias.

Objective: Describe morphologic, macro and microscopic lesions associated with permanentpacemaker (PM) in hearts of patients who died with chronic Chagas disease and compare them with those reportedin other heart diseases. Methods: Twenty-two hearts of chronic chagasic patients (16 mean and six women) from26 to 86 years of age (mean 54 years) with a permanent endocardial PM were studied. Fragments representing thewalls of four the chambers, the ventricular septum and the tip of the heart as well as tissue involving the leads and areas of adhesions were obtained for histological processing. The characteristics of leukocyte exudates leukocyte inimplant sites and the ventricular myocardium were analyzed by immunohistochemistry. Results: Inflammationand thrombosis at the site of implantation resulted in fibrous encapsulation of the tips of the electrode leadsthat remained firmly adhered to the adjacent endocardium. At the site of implantation, B and T lymphocytesoccurred in similar proportions, unlike ventricular chagasic myocarditis areas, where a large predominance ofT lymphocytes was observed. Conclusion: The leads are not biologically inert structures, their permanenceproduces constant thrombogenic stimulation, as well as thrombogenic and fibrogenic inflammatory process in thesites of the implants. The organization of red thrombi and/or fibrin formed around the electrode leads seems to beresponsible for the encapsulation and frequent adhesions to adjacent structures. Cardiac lesions associated PM inchronic Chagas disease in the studied cases were similar to those described in other heart diseases.

Objetivo: Describir las lesiones morfológicas, macro y microscópicas, asociadas con marcapasosdefinitivo (MP) en corazones de pacientes fallecidos con cardiopatía chagásica crónica y compararlas con lasdescritas en otras cardiopatías. Métodos: Fueron estudiados 22 corazones de pacientes chagásicos crónicos (16hombres y seis mujeres) de 26 a 86 años de edad (promedio de 54 años) portadores de MP definitivo endocárdico.Fueron retirados fragmentos de las paredes de las cuatro cámaras, del tabique interventricular y la punta cardiaca,así como de tejidos que envolvían los cables-electrodos y de áreas de adherencias para procesamiento histológico.Las características del exudado leucocitario en los sitios de implante y el miocardio ventricular fueron analizadaspor medio de la técnica de inmunohistoquímica. Resultados: Inflamación y trombosis en los sitios de implanteresultaron en encapsulamiento fibroso de las puntas de los cables-electrodos que permanecieron firmementeadheridos al endocardio adyacente. En los sitios de implante, linfocitos B y T ocurrieron en proporcionessemejantes, diferentemente de los focos de la miocarditis chagásica ventricular en la que se observó distintivopredominio de linfocitos T. Conclusión: Los cables-electrodos no son estructuras biológicamente inertes; supermanencia produce constante estímulo trombogénico, así como proceso inflamatorio y fibrogénico en los sitiosde los implantes. La organización de trombos rojos y/o fibrina que se forman alrededor de los cables-electrodosparece responsable de su encapsulamiento y las frecuentes adherencias a las estructuras adyacentes. Las lesionescardiacas asociadas con los MP en la cardiopatía chagásica crónica de los casos estudiados fueron semejantes a lasdescritas en otras cardiopatías.

[The electrocardiographic survey]. / O inquérito eletrocardiográfico.

In order to investigate the prevalence of chagasic heart disease in Brazil, a national electrocardiographic survey was carried out from 1977 to 1981. A total of 5,347 electrocardiograms (ECG) were performed and paired by age and gender. The results obtained in relation with the autochthonous cases, were distributed by Brazilian states, as follows: Rio Grande do Sul (1,078), Minas Gerais (760), Bahia (612), Paraná (400), Paraiba (340), Piauí (218), Sergipe (216), Goiás (176), Pernambuco (170), Ceará (136) and Alagoas 134. The higher proportions of altered ECGs among seropositive individuals were found in the States of Goiás (63.6%), Minas Gerais (57.6%), Ceará (57.3%), Paraná (54.5%), Piauí (53.2%) and Paraiba (52.3%). Among the control individuals, these proportions were respectively 25%, 25.7%, 25%, 12.5%, 22.9% and 26.5%. A significant statistical difference of altered ECGs between positive and negative individuals was verified in all the States, with a single exception (Alagoas). The estimation of the gradient showed to be higher in Paraná State (42%), followed by Goiás (38.6%), Ceará (32.3%), Minas Gerais (31.9%), Piauí (30.3%), Paraíba (25.8%), Pernambuco (22.3%), Bahia (18.9%), Sergipe (16.7%), Rio Grande do Sul (9.9%) and Alagoas (7.5%). Concerning the distribution of the electrocardiographical alterations found in the eleven states, the main alterations find among the seropositive group were: ventricular extrasystoles, complete right bundle branch block, left anterior fascicular block, the association of complete right bundle branch block with left anterior fascicular block and primary alterations of the ST segment and of the T wave. Furthermore, these ECG alterations were more prevalent in the group of infected individuals.

O inquérito eletrocardiográfico / The electrocardiographic survey

Entre 1977 e 1981, foi realizado um inquérito eletrocardiográfico nacional tendo por objetivo avaliar a prevalência da cardiomiopatia chagásica no Brasil. Foram feitos 5.347 eletrocardiogramas. Após o pareamento dos indivíduos, segundo a idade e gênero, a distribuição dos eletrocardiogramas dos autóctones, em cada estado, ficou assim constituída: Rio Grande do Sul (1.078), Minas Gerais (760), Bahia (612), Paraná (400), Paraíba (340), Piauí (218), Sergipe (216), Goiás (176), Pernambuco (170), Ceará (136) e Alagoas (134). Os maiores percentuais de alterações eletrocardiográficas entre os indivíduos com soros reagentes foram encontrados nos Estados de Goiás (63,6 por cento), Minas Gerais (57,6 por cento), Ceará (57,3 por cento), Paraná (54,5 por cento), Piauí (53,2 por cento) e Paraíba (52,3 por cento). Entre os controles, nestes estados, a prevalência das alterações eletrocardiográficas foi de 25 por cento, 25,7 por cento, 25 por cento, 12,5 por cento, 22,9 por cento e 26,5 por cento respectivamente. Observou-se diferença estatisticamente significativa em relação à prevalência das alterações eletrocardiográficas, entre os indivíduos soro reagentes e os não reagentes, em todos os estados, exceção feita para o de Alagoas. O cálculo do gradiente mostrou-se maior no Estado do Paraná (42 por cento), seguido por Goiás (38,6 por cento), Ceará (32,3 por cento) Minas Gerais (31,9 por cento), Piauí (30,3 por cento), Paraíba (25,8 por cento), Pernambuco (22,3 por cento), Bahia (18,9 por cento), Sergipe (16,7 por cento), Rio Grande do Sul (9,9 por cento) e Alagoas (7,5 por cento). Em relação à distribuição das alterações eletrocardiográficas encontradas, nos onze estados analisados, verificou-se que as extrassístoles ventriculares, o bloqueio de grau avançado do ramo direito, o bloqueio da divisão ântero-superior do ramo esquerdo, a associação do bloqueio de grau avançado do ramo direito com o bloqueio da divisão ântero-superior do ramo esquerdo e alterações primárias do segmento ST e da onda T, mostraram diferença estatisticamente significativa, entre os indivíduos com sororreagentes e os não reagentes Além disto, estas alterações eletrocardiográficas foram as de maior prevalência no grupo dos indivíduos chagásicos.

In order to investigate the prevalence of chagasic heart disease in Brazil, a national electrocardiographic survey was carried out from 1977 to 1981. A total of 5,347 electrocardiograms (ECG) were performed and paired by age and gender. The results obtained in relation with the autochthonous cases, were distributed by Brazilian states, as follows: Rio Grande do Sul (1,078), Minas Gerais (760), Bahia (612), Paraná (400), Paraiba (340), Piauí (218), Sergipe (216), Goiás (176), Pernambuco (170), Ceará (136) and Alagoas 134. The higher proportions of altered ECGs among seropositive individuals were found in the States of Goiás (63.6 percent), Minas Gerais (57.6 percent), Ceará (57.3 percent), Paraná (54.5 percent), Piauí (53.2 percent) and Paraiba (52.3 percent). Among the control individuals, these proportions were respectively 25 percent, 25.7 percent, 25 percent, 12.5 percent, 22.9 percent and 26.5 percent. A significant statistical difference of altered ECGs between positive and negative individuals was verified in all the States, with a single exception (Alagoas). The estimation of the gradient showed to be higher in Paraná State (42 percent), followed by Goiás (38.6 percent), Ceará (32.3 percent), Minas Gerais (31.9 percent), Piauí (30.3 percent), Paraíba (25.8 percent), Pernambuco (22.3 percent), Bahia (18.9 percent), Sergipe (16.7 percent), Rio Grande do Sul (9.9 percent) and Alagoas (7.5 percent). Concerning the distribution of the electrocardiographical alterations found in the eleven states, the main alterations find among the seropositive group were: ventricular extrasystoles, complete right bundle branch block, left anterior fascicular block, the association of complete right bundle branch block with left anterior fascicular block and primary alterations of the ST segment and of the T wave. Furthermore, these ECG alterations were more prevalent in the group of infected individuals.

Coronary microvascular disease in chronic Chagas cardiomyopathy including an overview on history, pathology, and other proposed pathogenic mechanisms.

This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease.

Chagas cardiomyopathy--where do we stand after a hundred years?

A hundred years from its description, Chagas cardiomyopathy remains a challenging disease. Although successful vector-control strategies have decreased the incidence of Chagas disease in several Latin American countries, both migration to urban areas and immigration have spread the disease worldwide; and now, blood transfusion, organ transplantation, and vertical transmission are a concern. The pathogenesis of Chagas cardiomyopathy involves complex host-parasite interactions, where low-grade but incessant systemic infection and triggered autoimmune reaction are the main mechanisms for its development, with the contribution of autonomic damage and microvascular disturbances. Chagas cardiomyopathy is the most important clinical presentation of Chagas disease and comprises a wide range of manifestations, including heart failure, arrhythmias, heart blocks, sudden death, thromboembolism, and stroke. Recently, simple clinical prognostic scores have been developed to identify high-risk patients and help with management. The treatment of Chagas cardiomyopathy focuses mostly on managing heart failure, arrhythmias, and thromboembolism. The role of specific antiparasitic therapy in the chronic form is not yet defined, and a randomized trial is now under way to address this crucial point. In this article, we review the main clinical aspects of Chagas cardiomyopathy and underscore some upcoming challenges for the appropriate control, diagnosis, and management of this complex disease.

Early twentieth century descriptions of the Chagas heart disease.

Chagas heart disease is endemic in 21 countries with approximately 100 million people at risk. It is the most common cause of myocarditis in the Americas and is recognized to have existed for more than 4000 years (isolated from mummies). Chagas disease was discovered during the search to find a cause for the overwhelming deaths occurring in Brazil in the late 18th century. Physician Carlos Chagas discovered Trypanosome minasense in 1908 while researching on malaria. Subsequently, the existence of the barbeiro triatomine (insects bites on the face), the isolation of the Trypanosome cruzi in the triatomine and the first human description of a disease in a 9-month-old child depicted the existence of a new human trypanosomiasis. Chagas named the trypanosome species after his colleague and mentor Oswaldo Cruz. In subsequent papers, Chagas described the morphology and evolutionary cycle of the trypanosome and the clinical features of the disease, including involvement of the heart. Never before or since one physician has fully characterized a disease from its grass roots to the clinical forms more or less all by himself.

Chagas' disease and the involvement of the autonomic nervous system.

Chagas' disease is a major endemic disease in Latin America and a great cause for concern due to its high incidence: it afflicts 16 to 18 million individuals and places over 90 million people at risk of infection. At present, five mechanisms can be proposed to explain the pathogenesis of chronic Chagas cardiopathy: 1. direct lesion of the tissue by Trypanosoma cruzi; 2. dysfunction of the autonomic nervous system (neurogenic concept); 3. microvascular disease; 4. immunologic reaction; 5. alterations in the extracellular matrix. The neurogenic concept is the most attractive explanation for the pathogenesis of chronic Chagas cardiopathy through the involvement of the autonomic nervous system, an issue that has been prominent ever since Chagas first initiated research in the field. Köberle, in his pioneering studies on the role of the autonomic nervous system in Chagas patients in the 1950s, adopted the technique of neuron counts, whereby he registered a reduction in parasympathetic nerve cells, and thus considered Chagas cardiopathy a "parasympathetic reduction" with predominance of the sympathetic. In the 1960s, systematic studies on autonomic function, organized by Professor Dalmo Amorim, were initiated in the School of Medicine in Ribeirão Preto. Several aspects of cardiac autonomic control were later described independently by teams in Brazil (Ribeirão Preto and Brasília), Argentina (Cordoba) and Venezuela (Mérida). In general, the studies performed in Ribeirao Preto by Amorim and Marin Neto and in Brasília by Junqueira Jr. reflected the functional involvement of the parasympathetic system, while the studies performed in Córdoba were linked with the view of cardiovascular sympathetic dysfunction. In Brazil, the involvement of the sympathetic system, with relation to the functional aspect of sympathetic denervation, is well characterized by Marin Neto through the assessment of heart rate using the tilt test in both Chagas and control groups. Further evidence of autonomic nervous system dysfunction in Chagas' disease as a factor modulating complex ventricular arrhythmias was demonstrated by Pedrosa (RJ), who reported on a specific group of chronic Chagas patients with complex ventricular arrhythmias and dilated cardiopathy. In this study, when serum from chronic Chagas patients showing neither complex ventricular arrhythmias nor ventricular dilation was inoculated in isolated rabbit hearts, it produced no harmful effect in the conduction system, in contrast to what was observed in the conduction system of rabbits inoculated with serum from the Chagas patients group with complex ventricular arrhythmias and ventricular dilatation. These facts confirm Carlos Chagas as the pioneer in postulating involvement of the autonomic nervous system in Chagas' disease, and provide an important opportunity to understand ventricular involvement in chronic Chagas cardiopathy.

La hipótesis neurogénica modificada puede explicar la historia natural de la enfermedad cardíaca chagásica crónica / The modificated neurogenie hypothesia can explain the natural history of the chronic chagas cardiac disease

Los mecanismos responsables de la progresión del daño miocárdico en la enfermedad de Chagas crónica son aún desconocidos. Las hipótesis de mayor relevancia clínica son la persistencia del parásito en el miocardio de los pacientes crónicos y las respuestas autoinmunes a la presencia de este último. Ninguna de estas hipótesis explica satisfactoriamente los eventos clínicos que se presentaron durante la historia natural de la enfermedad. La hipótesis neurogénica clásica establece que, la activación temprana del sistema nervioso simpático, es responsable de la progresión del daño miocárdico. Sin embargo, la activación simpática y de otros sistemas neurohormonales se detecta en pacientes con dilatación cardíaca y disfunción ventricular. En consecuencia, la activación neurohormonal es un fenómeno tardío y simultáneo al proceso de remodelación ventricular. Más aún, la administración de medicamentos que contrarrestan la activación neurohormonal tiene efectos favorables sobre el proceso de remodelación ventricular y sobre la supervivencia de los pacientes chagásicos crónicos. Por consiguiente, la hipótesis neurogénica clásica debería ser modificada a la luz de estos hechos. La modificación propuesta permite explicar satisfactoriamente los eventos clínicos que tienen lugar en la historia natural de la enfermedad chagásica crónica

Cardiomiopatia de Chagas / Chagas cardiomyopathy

Objetivo: realizar una revisión actualizada sobre la cardiomiopatía de Chagas. Fuente de datos: se efectuó una búsqueda en las bases de datos Medline, Lilacs y Sibra en los siguientes aspectos: reseña histórica, patogenia, fisiopatología, definición de caso, espectro del compromiso cardíaco, experiencia institucional y de otros investigadores en el país y finalmente las bases y enfoque actual del tratamiento etiológico. Selección del estudio: se estudiaron 79 trabajos que informaban sobre las tópicos relacionados con el tema. Extracción de datos: los artículos se clasificaron según se trataran de revisiones, artículos originales o informes de casos. Recopilamos y analizamos los artículos originales y luego elaboramos la revisión, el resumen y las conclusiones. Síntesis de datos y conclusiones: los estudios demuestran que la cardiomiopatía de Chagas es la causa más frecuente de cardiomiopatía en América Latina con una variable forma de presentación y un importante impacto sobre la morbimortalidad. Se resalta el aparente papel del T. cruzi en la patogenia de la fase crónica de la enfermedad, el cual es detectado por técnicas de PCR hasta en 63 por ciento de los casos. Se presenta la propuesta de tratamiento etiológico de la enfermedad publicada por la OPS y la OMS.

Evolution of the clinical and epidemiological knowledge about Chagas disease 90 years after its discovery.

Three different periods may be considered in the evolution of knowledge about the clinical and epidemiological aspects of Chagas disease since its discovery: (a) early period concerning the studies carried out by Carlos Chagas in Lassance with the collaboration of other investigators of the Manguinhos School. At that time the disease was described and the parasite, transmitters and reservoirs were studied. The coexistence of endemic goiter in the same region generated some confusion about the clinical forms of the disease; (b) second period involving uncertainty and the description of isolated cases, which lasted until the 1940 decade. Many acute cases were described during this period and the disease was recognized in many Latin American countries. Particularly important were the studies of the Argentine Mission of Regional Pathology Studies, which culminated with the description of the Romaña sign in the 1930 decade, facilitating the diagnosis of the early phase of the disease. However, the chronic phase, which was the most important, continued to be difficult to recognize; (c) period of consolidation of knowledge and recognition of the importance of Chagas disease. Studies conducted by Laranja, Dias and Nóbrega in Bambuí updated the description of Chagas heart disease made by Carlos Chagas and Eurico Villela. From then on, the disease was more easily recognized, especially with the emphasis on the use of a serologic diagnosis; (d) period of enlargement of knowledges on the disease. The studies on denervation conducted in Ribeirão Preto by Fritz Köberle starting in the 1950 decade led to a better understanding of the relations between Chagas disease and megaesophagus and other visceral megas detected in endemic areas.

[Chagasic myocardiopathy: historical perspective]. / La miocardiopatía chagásica perspectiva histórica.

Considerable advances in the clinical pathological and pathogenic aspects of Chagas disease have been made since the Brazilian physician Carlos Chagas described the disease in 1909. The disease caused by the flagellate protozoon parasite Trypanosoma cruzi is transmitted to humans by a blood sucking triatomine and much less frequently by blood transfusion. It is estimated that 18 million are infected and that about 100 million people from Latin America are at risk of contracting T. cruzi infection. One of the most important contributions to the knowledge of Chagas' disease has been the recognition of the natural history of the disease, which can be divided into three well defined periods: 1. The acute stage; 2. An undetermined or undifferentiated stage and 3. The chronic stage. The primary infection (first stage) occurs mostly unrecognized and clinically apparent acute chagasic myocarditis may appear in less than 5% of the infected individuals, usually children living in endemic areas. The majority of the cases of acute myocarditis are mild and reversible. Autopsied cases of acute chagasic myocarditis are uncommon and correspond to exceptionally severe or fulminant forms showing diffuse myocardial damage with myocytolisis, degenerative changes of myocardial fibers and marked intersticial cellular infiltration. The acute clinical manifestations of the infected individuals include fever, muscular pain, sweating, swollen lymph nodes, hepatospienomegaly. Following this initial stage, all patients enter the undifferentiated or undetermined stage of the chronic period (second stage), which lasts between 10 to 20 years. Of these, 20 to 30% (depending on marked geographical differences) develop symptoms or signs of visceral damage conforming the cohort that enter the third stage. Although megaesophagous and megacolon are not uncommon (mainly in Brazil), the most frequent and important clinical manifestation is a dilated cardiomyopathy. Thus, 70% or more of the infected individuals will never show any clinical manifestation of the disease. The ajmaline test and the endomyocardial biopsy are, probably, the most sensitive methods to unmask latent forms of chagasic myocarditis during the undifferentiated stage. In the most advanced stages of chronic chagasic myocarditis, pathological findings are those of a dilated cardiomyopathy. At autopsy, the apical aneurysm with thrombus in it is a frequent and distinctive finding. The histopathological picture is that of an active and chronic microfocal and disseminated myocarditis. In some cases fibrosis may be confluent, which accounts for the electrocardiographic patterns of myocardial necrosis. The widespread distribution of cardiac lesions also constitute the substrate for atrioventricular and intraventricular conduction disturbances and for atrial and ventricular arrhythmias. The clinical diagnosis of Chagas' heart disease is based on a triad of: positive epidemiology, positive serology and a combination of clinical findings (suggestive electrocardiograhic abnormalities, apical aneurysm, cardiac enlargement). The electrocardiogram in the most advanced forms, usually shows sinus bradycardia, right bundle branch block with or without left anterior hemiblock, primary T wave abnormalities, pathological Q waves and multiform ventricular premature beats. The pathogenesis of the myocardial lesions of acute and also chronic chagasic myocarditis appears to be related in large part to autoimmune mechanisms. The lack of correlation between the location and number of parasitized fibers and the severity, type, and extension of degenerative and inflammatory lesions supports this assumption. Experimental and clinical studies have demonstrated the presence of antibodies directed against different components of T. cruzi and crossreacting with human antigens in patients with chronic chagasic myocarditis. Microvascular dysfunction, myocardial ischemia and autonomic nervous system impairment have also been implica

La miocardiopatia chagasica: perspectiva histórica / Chagasic myocardiopathy: historical perspective

El conocimiento sobre la enfermedad de Chagas ha tenido considerables avances desde la descripción de Carlos Chagas en el año 1909. Esta enfermedad causada por el Trypanosoma cruzi y transmitida habitualmente al ser humano por insectos hematófagos (triatomideos), afecta a unos 18 millones de personas y se estima que alrededor de 100 millones están expuestos a contraerla. El riesgo de adquirir la enfermedad está directamente relacionado a factores económico-sociales y culturales. En la historia natural de la enfermedad se pueden reconecer tres períodos perfectamente definidos: el período agudo que aparece inmediatamente después de la infección inicial (en general en niños de zonas endémicas), que es clínicamente manifesto en un nuy bajo porcetaje (5 a 10 por ciento) con síntomas inespecíficos (fiebre, dolores articulares, quebrantamiento general, adenopatias, esplenomegalia, dermatopatías) o más específicos como el complejo oftalmoganglionar. Las manifestaciones cardíacas del período agudo son las de una miocarditis no severa y reversible en la mayoría de los casos. Excepcionalmente, se observa miocarditis aguda grave y mortal por insuficiencia cardíaca, tromboembolismo o arritmias. Al estadío agudo le sigue un período de 10 a 20 años denominado período indeterminado en el cual no existe evidencia clínica alguna de la enfermedad (en el 100 por ciento de los casos) salvo la serología positiva. Durante el período indeterminado la prueba de ajmalina y la biopsia endomiocárdica son los métodos de diagnóstico que permitirían "detectar" con mayor precocidad a aquellos pacientes candidatos a padecer una miocardiopatía. Después de este período, un 20 a 30 por ciento de los casos desarrolla signos y síntomas de una miocardiopatía dilatada que evoluciona lentamente (10 a 20 años) a formas de severidad variable caracterizadas, en las etapas más avanzadas, por la presencia de insuficiencia cardíaca global, tromboembolismo y arritmias. La muerte súbita es frecuentes y a veces ocurre en estadíos no demasiado avanzados de la miocarditis. El cuadro anátomopatológico corresponde al de una panmiocarditis microfocal diseminada. Se observa por lo general agrandamiento global del corazón con la particularidad de encontrar aneurismas apicales en un alto porcentaje (40-50 por ciento) con trombos intracavitarios. El compromiso de otras vísceras (megaesófago y megacolon) es más frecuente en el Brasil.