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Autonomic dysfunction and beta blocker therapy in

Chagas heart disease

Reinaldo B. Bestetti,IAugusto Cardinalli-NetoII

IUNAERP Medical School, Ribeira˜o Preto/SP, Brazil.IIHospital de Base, Sa˜o Jose´ do Rio Preto/SP, Brazil.

Email: rbestetti@netsite.com.br Tel.: 55 16 3603-7013

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 myo-cardial collagen content.

In contrast, we did not observe a decrease in the mortality rate of rats that were infected with Trypanosoma cruzi and then received metoprolol to treat the ensuing acute Chagas disease (2). Conceivably, both the animal model and theT. cruzistrain might account for this disparity. Furthermore, we found that chronic metoprolol administration reversed the ECG abnormalities in the T. cruzi-infected rats at the chronic stage of the disease. Left axis deviations and intraventricular conduction delays have been observed in almost half of rats chronically infected withT. cruzi, which we believe supports the theory that the different animal models used in the two studies were responsible for the different results.

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.

Our message is that the absence of a beneficial effect of carvedilol use in a hamster model should not preclude the use of beta blockers in Chagas disease patients, particularly in the following two clinical settings. First, beta blockers may be appropriate for patients with chronic systolic heart failure because the activation of the autonomic nervous system in these patients is similar to that observed in heart

failure patients without Chagas disease (3) and because beta blocker therapy has produced good preliminary results in this group of patients (4-7). Second, beta blocker therapy may be suitable for patients receiving implantable cardio-verter-defibrillator therapy for the secondary prevention of sudden cardiac death due to the high recurrence rate of malignant arrhythmias in this patient group in the absence of beta blocker therapy (8).

& REFERENCES

1. Pimentel WS, Ramires FJA, Ianni BM, Salemi VMC, Bilate AMB, Cunha-Neto E, et al. The effect of beta-blockade on myocardial remodeling in Chagas cardiomyopathy. Clinics. 2012;67(9):1063-9, http://dx.doi.org/ 10.6061/clinics/2012(09)14.

2. Bestetti RB, Sales-Neto VN. Pinto LZ, Soares EG, Muccillo G, Oliveira JSM. Effects of long-term metoprolol administration on the electro-cardiogram of rats infected with T. cruzi. Cardiovasc Res. 1990;24(7):521-7, http://dx.doi.org/10.1093/cvr/24.7.521.

3. Bestetti RB, Coutinho-Neto J, Staibano L, Pinto LZ, Muccillo G, Oliveira JSM. Peripheral and coronary sinus catecholamine levels in patients with severe congestive heart failure due to Chagas disease. Cardiology. 1995;86(3):202-6, http://dx.doi.org/10.1159/000176874.

4. Botoni FA, Poole-Wilson PA, Ribeiro ALP, Okonko DO, Oliveira BMR, Pinto AS, et al. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J. 2007;153(4):544.e1-8, http://dx.doi.org/10.1016/j.ahj.2006.12.017. 5. Da´vila DF, Angel F, Bellabarba GA, Donis JH. Effects of metoprolol in

chagasic patients with severe congestive heart failure. Int J Cardiol. 2002;85(2-3):255-60.

6. Bestetti RB, Otaviano AP, Cardinalli-Neto A, da Rocha BF, Theodoropoulos TA, Cordeiro JA. Effects of B-Blockers on outcome of patients with Chagas’cardiomyopathy with chronic heart failure. Int J Cardiol. 2011;151(2):205-8.

7. Issa VS, Amaral AF, Cruz FD, Ferreira SM, Guimara˜es GV, Chizzola PR, et al. Beta-blocker therapy and mortality of patients with Chagas cardiomyopathy: a subanalysis of the REMADHE prospective trial. Circ Heart Fail. 2010;3:82-8, http://dx.doi.org/10.1161/CIRCHEARTFAILURE. 109.882035.

8. Cardinalli-Neto A, Bestetti RB, Cordeiro JA, Rodrigues VC. Predictors of all-cause mortality for patients with chronic Chagas heart disease receiving implantable cardioverter-defibrillator therapy. J Cardiovasc Electrophysiol. 2007;18(12):1236-40, http://dx.doi.org/10.1111/j.1540-8167. 2007.00954.x.

Copyrightß2013CLINICS– This is an Open Access article distributed under

the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

No potential conflict of interest was reported.

DOI:10.6061/clinics/2013(02)LE01

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