Journal of the American College of Cardiology
ReplyA Vision of Future Treatment in Chagas Heart Disease
Author + information
- Maria Carmo Pereira Nunes, MD, PhD,
- Wistremundo Dones, MD,
- Carlos A. Morillo, MD,
- Juan Justiniano Encina, MD,
- Antonio Luiz Ribeiro, MD, PhD∗ (tom{at}hc.ufmg.br),
- Council on Chagas Disease of the Interamerican Society of Cardiology
- ↵∗Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena, 190, Santa Efigênia, 30130 100–Belo Horizonte, MG, Brazil
We would like to thank Dr. Wallukat and colleagues for their letter regarding our review on Chagas heart disease (CHD) (1), which suggested the potential value of new treatment strategies that focus on removal or neutralization of beta1-autoantibodies (AABs). We agree that this is an appealing possibility, but we consider the role of beta1-AABs in the pathogenesis of Chagas cardiomyopathy (ChCM) to still be controversial. There are a number of studies showing a potential role of beta1-AABs in the genesis of major clinical manifestations of ChCM, such as ventricular dysfunction, ventricular arrhythmias, and conduction disturbances (reviewed in Medei et al. [2]), most of them in vitro or in experimental models. However, as observed for antimuscarinic AABs (3), some of the properties of beta1-AABs observed in vitro or in experimental models may not produce effects in clinical patients, due to the concomitant action of other factors. A major finding favoring a pathogenetic role of beta1-AABs in ChCM was published by Wallukat et al. (4), who showed a higher prevalence of chronotropically active beta1-AABs in CHD with cardiomyopathy than in those in the indeterminate form or with megacolon, as well as a higher activity of those AABs in ChCM patients.
However, much more data is necessary before a specific therapy aimed to neutralize or remove beta1-AABs in CHD could be used in clinical practice. Available clinical data does not show a dose-response effect (i.e., that patients with more severe ChCM have higher levels or activity of antiB1-AABs [4,5]). Longitudinal data that consistently shows that higher AAB activity may provoke or aggravate heart involvement in CHD would be desirable to further confirm the importance of the proposed mechanism. It is conceivable that the pathogenesis of ChCM is multifactorial, as discussed in our review (1). Finally, a formal proof-of-concept clinical trial is needed to determine if this novel approach is safe and effective in CHD. Because CHD is a neglected disease that kills thousands of persons each year, novel and innovative therapies should urgently be tested and are welcomed.
- American College of Cardiology Foundation
