efeitos da inibição do sistema renina-angiotensina-aldosterona e do ...

ABSTRACT
Chagas’ disease, caused by Trypanosoma cruzi (T. cruzi), was discovered and reported by
Carlos Chagas, a Brazilian physician, in 1909. Unfortunately, near to a century since its
original description, it continues to represent a terrible impact on humanity. Chagas’
myocardiopathy pathogenesis and consequent heart failure do not seem to differ from other
forms of idiopathic and ischemic myocardiopathy. Bearing this in mind, we consider that
the results of great clinical assays in patients with cardiac insufficiency can be extended to
those carriers of Chagas’ cardiomyopathy. Even though it is admitted that pathophysiology
of Chagas’ cardiomyopathy is similar to non-chagasic myocardiopathy, there are many
peculiarities in Chagas’ myocardiopathy. For this prospective study, we selected a group of
42 patients with chronic Chagas’ cardiomyopathy (CCC). The selection was made
consecutively among patients assisted in the Ambulatório de Referência em Doença de
Chagas do HC-UFMG (Reference Ambulatory in Chagas’ Disease of the Teaching County
Hospital of the Federal University of Minas Gerais). The premise used for the selection
was the presence of the left ventricle diastolic diameter (LVD) larger than 55mm or 2.7
cm/m2 and at least one of the following criteria: left ventricular ejection fraction (LVEF)
smaller than 55% (modified Simpson) or evidence of diffuse or segmental systolic
dysfunction. Patients with any co-morbidities, which might have caused confusion to the
data analysis, were excluded. The primary aim of the study was a change in the LVEF after
renin-angiotensin system inhibition (RASi) and after addition of carvedilol. Secondary
objectives were changes in clinical, life quality, radiological, neurohormonal (BNP), and
inflammatory (RANTES, MCP1, and MIP1α) parameters, as well as the behavior of the
anti-adrenergic and anti-muscarinic antibodies. The study was divided in two phases:
Phase I was named RASi and the second one, carvedilol/placebo. These patients were
assessed for clinical, life quality, radiological, ECG, neurohormonal and inflammatory
aspects in the beginning and at the end of each phase. The protocol of dosage optimization
of enalapril (20 mg BID) and spironolactone (25 mg MID) was applied to the selected
group. Subsequently, the group was randomly assigned to a carvedilol group (n=19) and a
placebo group (n=20). Both were uptitrated to use carvedilol or placebo 25mg qd. The
utilization of other drugs, such as furosemide, hidroclorotiazidics, digoxin and amiodarone
were guided in accordance to clinical requirement, respecting their basic indications and
restrictions. In phase I, it was observed that the therapeutic optimization was safe and
efficient, being characterized by a meaningful improvement on the clinical examination
(Framingham score – p = 0.0004), life quality, radiological (reduction in the cardiothoracic
index – p = 0.002) and echocardiographic parameters (improvement of the index TEI – p =
0.013). Regarding the analysis of the differences of the LVEF (p = 0.249) and the LVD (p
= 0.335) before and after RASi, statistical significance was not observed. However, when
patients were rated according to the degree of systolic dysfunction (EF < = 45%), a
significant difference was observed (p = 0.017) between the two variables prior and after
the optimized treatment. BNP and RANTES levels decreased and antiβ1 receptor antibody
levels increased significantly (p = 0.032; p = 0.001; p = 0.020, respectively). After the
association of carvedilol, it was observed a trend towards an increase in LVEF (p=0.066)
in the carvedilol group, but not in the placebo group (p=0.241). The difference between
these groups also showed a trend to significance (p=0.09). After the association of
carvedilol, there was no additional improvement on clinical, life quality, and
neurohormonal parameters, but there was no criterion of worsening as well. However, it
was not observed clinical or hemodynamic worsening. RANTES levels showed significant
increase (p=0.013), but there was no difference between groups (p=0.351). The
antiβ1receptor antibodies showed a trend to additional rise (p=0.050) with significant