| Summary: | === 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 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 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 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. === A doenca de Chagas, causada pelo protozoario Trypanosoma cruzi (T. cruzi), foi descoberta e descrita pelo medico brasileiro Carlos Chagas em 1909 (CHAGAS, 1909). Infelizmente, proximo de completar um seculo de sua descricao original, continua representando terrivel impacto sobre a humanidade. A fisiopatologia da cardiopatia chagasica e consequente insuficiencia cardiaca nao parecem diferir das formas de
miocardiopatia idiopatica ou isquemica. Com base nessas premissas, julga-se que os resultados dos grandes ensaios clinicos em insuficiencia cardiaca podem ser extrapolados aqueles portadores de miocardiopatia chagasicoa. Nao obstante, mesmo que se admita
similaridade fisiopatologica entre a miocardiopatia chagasica com as outras varias formas de miocardiopatia, sabe-se que a forma cardiaca da doenca de Chagas apresenta varias peculiaridades patogenicas. Este e um estudo prospectivo em que foi selecionado um grupo
de 42 pacientes com cardiopatia chagasica cronica (CCC). A selecao foi feita de forma consecutiva dentre pacientes atendidos no Ambulatorio de Referencia em Doenca de Chagas do Hospital das Clinicas da UFMG. Utilizou-se como criterio de selecao a presenca de diametro diastolico do ventriculo esquerdo (VED) maior que 55mm ou 2,7cm/m2 e pelo menos um dos seguintes: fracao de ejecao do ventriculo esquerdo (FEVE) menor que 55% (Simpson modificado) ou deficit de funcao do ventriculo esquerdo segmentar ou global. Foram excluidos pacientes com quaisquer co-morbidades que servissem de confusao a analise dos dados. O objetivo primario foi melhora da fracao de ejecao apos inibicao do SRAA e apos adicao do carvedilol. Como objetivos secundarios analisaram-se o comportamento clinico, da qualidade de vida, radiologico, neuro-hormonal (BNP), inflamatorio (RANTES, MCP1, MIP1¿) e o comportamento dos anticorpos antireceptores adrenergico À1 e muscarinico M2. O estudo foi dividido em duas fases. Fase I,
denominada inibicao do sistema renina-angiotencina-aldosterona (iSRAA), e fase II, carvedilol/placebo. No inicio e ao termino de cada fase avaliou-se o comportamento desses pacientes sob os aspectos clinicos, da qualidade de vida, radiologicos, ecocardiograficos,
neuro-hormonais e inflamatorios. Na fase I aplicou-se protocolo de otimizacao das dosagens de maleato de enalapril ate a dosagem de 20mg BID e espironolactona (25mg MID). Posteriormente, o grupo foi randomicamente dividido em dois subgrupos denominados carvedilol e placebo. Ambos receberam carvedilol ou placebo em doses progressivas ate a dose maxima de 25mg BID. A utilizacao de outros medicamentos, como furosemida, hidroclorotiazida, digoxina e amiodarona, foi guiada conforme a necessidade clinica, respeitando-se suas indicacoes e contra-indicacoes. Observou-se, na fase I, que a
otimizacao terapeutica foi segura e eficaz, sendo esta caracterizada por melhora importante no exame clinico (escore de Framingham - p=0,0004), na qualidade de vida, nos parametros radiologicos (reducao no indice cardiotoracico - p = 0,002) e ecocardiograficos (melhora do indice de TEI . p = 0,013). Na analise das diferencas da FEVE (p=0,249) e do VED (p=0,335) pre e pos-iSRAA, nao se observou significancia estatistica. No entanto, quando os pacientes foram estratificados de acordo com o grau de disfuncao sistolica (FE.45%), verificou-se diferenca significativa (p=0,017) entre as duas variaveis antes e
apos iSRAA. O BNP e RANTES declinaram-se significativamente e os anticorpos antiÀ1 aumentaram significativamente(p=0,032; p=0,001; p=0,020, respectivamente). Depois da adicao do carvedilol, houve tendencia a melhora na FEVE no grupo carvedilol (p=0,066) e
nao no placebo (p=0,241). A diferenca entre os grupos tambem demonstrou tendencia significativa (p=0.09). Nao houve melhora adicional nos parametros clinicos, de qualidade de vida, neuro-hormonais e radiologicos apos associacao do carvedilol. Entretanto, nao se registrou piora clinica ou hemodinamica. O RANTES se elevou (p=0,013), mas sem diferencas entre os grupos (p=0,351). Os anticorpos antiÀ1 tenderam a adicional elevacao (p=0,050) no grupo carvediol, com significativa diferenca entre os grupos (p=0.029).
Concluiu-se que o esquema terapeutico com doses otimizadas de maleato de enalapril e espironolactona seguidas da adicao do carvedilol foi seguro e eficaz, demonstrando melhora clnica, ecocardiografica, neuro-hormonal e inflamatoria em pacientes com CCC. Mais estudos sao necessarios para demonstrar-se sobre a mortalidade e hospitalizacao.
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