Beta-adrenergic blockers in chronic systolic heart failure secondary to Chagas' disease

Dávila, Diego F.; Donis, José H.; Torres, Argenis; Gottberg, Carlos F.; Ramoni‐Perazzi, Paolo; Bellabarba, Gabriela Arata de

doi:10.1016/j.ijcard.2008.01.001

Cited by 6 publications

(6 citation statements)

References 49 publications

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“…One study concluded that beta-blockers were effective, not detrimental, and may improve survival in Chagas' patients with chronic heart failure and suggested that a randomized trial should be performed to confirm these findings (21). Another study suggested that the absence of beta-blocker use in the treatment of Chagas' cardiomyopathy was associated with poor prognosis (22), and this study was the basis for other studies (23). However, another study with small samples presented controversial results (24).…”

Section: Discussionmentioning

confidence: 57%

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

Pimentel¹,

Ramires²,

lanni³

et al. 2012

Clinics

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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.

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Section: Discussionmentioning

confidence: 57%

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

Pimentel¹,

Ramires²,

lanni³

et al. 2012

Clinics

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“…This finding suggests that neuronal cell loss correlates with the impairment of neurohormonal circuits (251,298,325,388). Therefore, the neurogenic theory suggests that autoimmune-dependent abnormalities in the autonomous nervous system can perpetuate the cycle of catecholamine cardiotoxicity, myocytolysis, and heart failure (93)(94)(95)(96)(97). This theory reminds the physician about the extraordinary variability of clinical and pathological manifestations of Chagas' disease affecting many tissues and organs in the human body (304).…”

Section: Unified Neurogenic Theorymentioning

confidence: 99%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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“…The clinical consequence of parasympathetic denervation is the absence of mechanisms, mediated by the vagus nerve, that trigger bradycardia or tachycardia in response to transient changes in blood pressure or venous return (Miziara et al, 2006;Ribeiro et al, 2009a;Rocha et al, 2009;Rocha et al, 2006b). However, the relative importance of the parasympathetic autonomic dysfunction has been recently questioned, raising the possibility that neurohormonal activation is the main underlying mechanism of disease progression (Davila et al, 2008). In this setting, neurohumoral activation presents with sinus tachycardia, low systolic blood pressure and echocardiographic evidence of severely depressed left ventricular systolic function (Davila et al, 2002).…”

Section: Cardiac Disautonomiamentioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Beta-adrenergic blockers in chronic systolic heart failure secondary to Chagas' disease

Cited by 6 publications

References 49 publications

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

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

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

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