Efeitos da inibição do sistema renina-angiotensina-aldosterona e do betabloqueio com Carvedilol na cardiopatia chagásica crônica

• Ano de defesa: 2006
• Autor(a) principal: Fernando Antonio Botoni
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Fracao de ejecao; Muscarinico M2; Enalapril; Anticorpos anti-receptores À1; BNP; RANTES; Carvedilol; Cardiopatia chagasica cronica; Espironolactona; Diametro diastolico do ventriculo esquerdo; Volume sistólico; Espirololactona; Quimiocina CCL5; Medicina; Doença de Chagas; Estudos prospectivos; Cardiopatias
• Link de acesso: http://hdl.handle.net/1843/ECJS-7K6PVZ

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. Chagasmyocardiopathy 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 tothose 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 madeconsecutively 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 selectionwas 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 MIP1) 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 selectedgroup. 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 andrestrictions. 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 afterthe optimized treatment. BNP and RANTES levels decreased and anti1 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 anti1receptor antibodies showed a trend to additional rise (p=0.050) with significant difference between groups (p=0.029). We concluded that, for patients with CCC, optimization of treatment with enalapril and spironolactone followed by the addition of carvedilol was safe and with benefits for their cardiac function and clinical status. Larger trials are needed to show effects on mortality and hospitalization.