The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy

Abstract

OBJECTIVE:Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model.METHODS:We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red.RESULTS:The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality.CONCLUSION:Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.

Autonomic dysfunction and beta blocker therapy in Chagas heart disease

“…Although there are no other studies for comparison, we agree with the assertion of Pimentel et al (1) that intense myocarditis, extensive myocardial fibrosis, and sympathetic denervation may have overshadowed the beneficial effects of the beta blocker therapy in this animal model.…”

“…Pimentel et al (1) did not observe any effects of the chronic use of carvedilol on myocardial function and left ventricular remodeling in their hamster model of chronic Chagas heart disease. Although there are no other studies for comparison, we agree with the assertion of Pimentel et al (1) that intense myocarditis, extensive myocardial fibrosis, and sympathetic denervation may have overshadowed the beneficial effects of the beta blocker therapy in this animal model.…”

“…In a hamster model of Chagas disease, Pimentel et al (1) recently found that 1) carvedilol decreased mortality in the acute, but not in the chronic stage and 2) in the chronic stage, carvedilol neither changed the left ventricular diameter and/or function, nor attenuated changes in the resting electrocardiogram (ECG), nor decreased the myocardial collagen content. …”

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

“…A similar increase in IFN-γ and TNF-α expression is observed in cardiac tissue from animals infected with T. cruzi [9] . CCC patients have a progressive myocardial remodeling process with hypertrophy and fibrosis causing heart fiber damage, heart conduction abnormalities, arrhythmias, apical aneurysm, heart failure and sudden death [10,11] . Several hypotheses have been raised to explain the lesions in the myocardium of CCC, which includes persistence of the parasite or its antigens at the inflammatory site and autoimmune tissue damage [5,12] .…”

Cardiovascular research in CLINICS

“…Pimentel et al (22) evaluated the role of carvedilol in cardiac remodeling and mortality in Chagas' cardiomyopathy in 55 Syrian hamsters, divided into the following groups: control, infected, and infected+carvedilol. The left ventricular diastolic and diastolic diameters, fractional shortening, and collagen accumulation in the interstitial space were measured.…”