Chagasic myocardiopathy. Historical perspective.

Considerable advances in the clinical pathological and pathogenic aspects o f Chagas disease have been made since the Brazilian physician Carlos Chagas described the disease in 1909. The disease caused by the flagellate protoz oon parasite Trypanosoma cruzi is transmitted to humans by a blood sucking triatomine and much less frequently by blood transfusion. It is estimated t hat 18 million are infected and that about 100 million people from Latin Am erica are at risk of contracting T. cruzi infection. One of the most import ant contributions to the knowledge of Chagas disease has been the recogniti on of the natural history of the disease, which can be divided into three w ell defined periods: 1. The acute stage; 2. An undetermined or undifferenti ated stage and 3. The chronic stage. The primary infection (first stage) oc curs mostly unrecognized and clinically apparent acute chagasic myocarditis may appear in less than 5% of the infected individuals, usually children l iving in endemic areas. The majority of the cases of acute myocarditis are mild and reversible. Autopsied cases of acute chagasic myocarditis are unco mmon and correspond to exceptionally severe or fulminant forms showing diff use myocardial damage with myocytolisis, degenerative changes of myocardial fibers and marked intersticial cellular infiltration. The acute clinical m anifestations of the infected individuals include fever, muscular pain, swe ating, swollen lymph nodes, hepatosplenomegaly. Following this initial stag e, all patients enter the undifferentiated or undetermined stage of the chr onic period (second stage), which lasts between 10 to 20 years. Of these, 2 0 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 cardio myopathy. Thus, 70% or more of the infected individuals will never show any clinical manifestation of the disease. The ajmaline test and the endomyoca rdial biopsy are, probably, the most sensitive methods to unmask latent for ms of chagasic myocarditis during the undifferentiated stage. In the most a dvanced stages of chronic chagasic myocarditis, pathological findings are t hose of a dilated cardiomyopathy. At autopsy, the apical aneurysm with thro mbus in it is a frequent and distinctive finding. The histopathological pic ture is that of an active and chronic microfocal and disseminated myocardit is. In some cases fibrosis may be confluent, which accounts for the electro cardiographic patterns of myocardial necrosis. The widespread distribution of cardiac lesions also constitute the substrate for atrioventricular and i ntraventricular conduction disturbances and for atrial and ventricular arrh ythmias. The clinical diagnosis of Chagas' heart disease is based on a tria d of. positive epidemiology, positive serology and a combination of clinica l findings (suggestive electrocardiograhic abnormalities, apical aneurysm, cardiac enlargement). The electrocardiogram in the most advanced forms, usu ally shows sinus bradycardia, right bundle branch block with or without lef t anterior hemiblock, primary T wave abnormalities, pathological Q waves an d multiform ventricular premature beats. The pathogenesis of the myocardial lesions of acute and also chronic chagasic myocarditis appears to be relat ed in large part to autoimmune mechanisms. The lack of correlation between the location and number of parasitized fibers and the severity, type, and e xtension of degenerative and inflammatory lesions supports this assumption. Experimental and clinical studies have demonstrated the presence of antibod ies directed against different components of T. cruzi and crossreacting wit h human antigens in patients with chronic chagasic myocarditis. Microvascul ar dysfunction, myocardial ischemia and autonomic nervous system impairment have also been implicated in the development and progression of chronic Ch agas' heart disease.