Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with values in non-infected dogs. These findings strongly suggest that the temporary reduction in the parasite load that was induced by benznidazole treatment was not able to prevent myocardial lesions and diastolic dysfunction for long after treatment.

Cardiomyopathy prognosis after benznidazole treatment in chronic canine Chagas' disease.

OBJECTIVES: To evaluate the effects of benznidazole on Chagas' disease cardiac prognosis using an experimental dog model of infection. METHODS: A total of 28 dogs were divided into three groups: 10 were infected with Trypanosoma cruzi and treated benznidazole during the chronic phase, 10 were infected but untreated, and 8 were non-infected/healthy. The trypanocidal efficacy was measured by parasite kDNA detection in blood and cardiac tissue samples. The effects of benznidazole in ameliorating the cardiac systolic function were evaluated by echodopplercardiogram. RESULTS: The benznidazole initially induced a potent suppression of parasitaemia in treated animals. However, 12 months post-treatment, the parasite kDNA detections were similar between infected groups. In the baseline echocardiographic parameters there was no variation among all animals. Similarly, 1 month post-treatment there was no significant difference among healthy and infected animals with regard to systolic function. At 12 months post-treatment, an increase in cardiac chamber size related to cardiomegaly was detected among treated and untreated animals, but not in the healthy controls. Interestingly, in spite of both groups of infected animals developing a decrease in their systolic cardiac function, this decline was slightly less in the treated animals. We also evaluated levels of tumour necrosis factor-α and interleukin-10 in peripheral blood mononuclear cell culture supernatant. Cytokine profiles were similar between infected animal groups and correlated with alterations in cardiac function. CONCLUSIONS: The temporary suppression of the T. cruzi infection induced by benznidazole treatment was efficient in reducing systolic cardiac function alterations, but not in preventing the development of cardiomyopathy.

Premature acute myocardial infarction in a child with nephrotic syndrome.

We report a case of acute myocardial infarction in a nephrotic child. A 7-year-old boy with a 4-year history of steroid-unresponsive nephrotic syndrome due to mesangial proliferation disease presented with acute vomiting and chest pain. An electrocardiogram showed ST elevation and pathological Q waves in leads consistent with anterior and septal myocardial infarction. Subsequent cardiac catheterization showed no evidence of atherosclerotic coronary artery disease, and thrombotic occlusion of the anterior descending coronary artery was the likely cause of the event. Myocardial scintigraphy showed extensive myocardial damage. The child had no long history of extreme hypercholesterolemia or hypertriglyceridemia. The case suggests that children with long-lasting nephrotic syndrome may be at increased risk for ischemic cardiovascular events, due to hyperlipidemia as well as a hypercoagulability state. The literature is reviewed regarding the relationship between nephrotic syndrome and the incidence of ischemic heart disease.

The Valsalva maneuver in Chagas disease patients without cardiopathy.

BACKGROUND: The Valsalva maneuver is a simple and reliable test of parasympathetic heart control that can also be used as a trigger of cardiac arrhythmia. Few studies are available about the Valsalva maneuver in Chagas disease patients without cardiac involvement and their results are contradictory. In a cross-sectional study, we compared Chagas disease patients without cardiac involvement and normal individuals using the Valsalva maneuver in order to study the vagal cardiac control and the occurrence of cardiac arrhythmia in the early phase of Chagas disease. METHODS: Fifty-nine patients with Chagas disease without cardiac involvement and 37 controls were submitted to a carefully standardized Valsalva maneuver. Cardiac vagal control was assessed by the Valsalva ratio and the occurrence of cardiac arrhythmia was recorded and coded. RESULTS: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. When compared to the control group, patients with Chagas disease had significantly lower Valsalva ratios (1.81+/-0.41 versus 2.01+/-0.41, P=0.017) which were not significantly correlated with age, left ventricular function or the presence of radiological esophageal abnormalities. Atrioventricular block (mainly 2nd degree Mobitz type I) occurred exclusively in Chagas disease patients (15,6%, P=0.021) and may indicate an early involvement of the AV node. Premature ventricular contraction was more frequent in Chagas disease patients (16.9% versus 8.1%, P=0.217), although the difference was not statistically significant. CONCLUSION: The Valsalva maneuver is a useful test to detect early vagal dysfunction in Chagas disease patients without cardiac involvement.