TNF gene polymorphisms are associated with reduced survival in severe Chagas' disease cardiomyopathy patients.

Chronic Chagas' disease cardiomyopathy (CCC) is the most important clinical outcome of infection by the parasite Trypanosoma cruzi, affecting 18 million individuals in Latin America. One-third of CCC patients develop heart failure due to end-stage dilated cardiomyopathy, and their survival is reduced by 50% compared to patients with other cardiomyopathies. Genetic susceptibility may play a role in the differential survival of severe CCC patients. Given the role of TNF-alpha in the progression of heart failure, and the increased TNF-alpha plasma and heart tissue levels observed in these patients, we chose TNF as a candidate gene for increased mortality in severe CCC patients. We typed the TNFa microsatellite and the -308 TNF promoter polymorphism and then analyzed the survival curves of 42 patients with severe ventricular dysfunction (left ventricular ejection fraction

Identification of multiple HLA-A*0201-restricted cruzipain and FL-160 CD8+ epitopes recognized by T cells from chronically Trypanosoma cruzi-infected patients.

Chronic Chagas disease occurs in 16 million individuals chronically infected by the protozoan Trypanosoma cruzi in Latin America, and may lead to a dilated cardiomyopathy in 10-30% of patients. A vigorous cellular immune response holds parasitism in check. However, up to now, few T. cruzi proteins have been shown to be recognized by CD8+ T cells from Chagas disease patients. In this study, we designed 94 peptides derived from T. cruzi proteins cruzipain and FL-160, predicted to bind to HLA-A2 molcules. After in vitro binding assays to HLA-A*0201, 26 peptides were selected, and their recognition by PBMC from Chagas disease patients was tested with the IFN-gamma ELISPOT assay. All 26 peptides were recognized by PBMC from at least one patient. Furthermore, a tetrameric HLA-A*0201 complex built with the cruzipain 60-68 peptide that was frequently recognized in the periphery also bound to CD8+ T cells from a heart-infiltrating T cell line obtained from a single patient with Chagas disease cardiomyopathy. Thus, our results suggest that the recognition of CD8+ T cell epitopes in cruzipain and FL-160 may have a pathogenic or protective role in chronic Chagas disease.

The role of storage of interstitial myocardial collagen on the overlife rate of patients with idiopathic and Chagasic dilated cardiomyopathy.

OBJECTIVE: To find out whether there is a correlation between a myocardial structural marker and the overlife rate of patients with dilated cardiomyopathy. METHODS: Using endomyocardial biopsy and 2D-echocardiogram, we studied nine patients with no changes in myocardial structure (control) and 45 patients with severe dilated cardiomyopathy of idiopathic etiology (IDCM) and of Chagasic etiology (CDCM). We analyzed the correlation between the quantity of interstitial myocardial collagen (ICVF) and the overlife rates of these patients. We also evaluated the difference in ICVF between these groups and whether fibrosis interfered on the geometry and function of the myocardium. RESULTS: We observed that ICVF was 15 times higher in cardiomyopathy patients than in the control group, but there was no difference in ICVF between CDCM and IDCM (*p < 0.001) patients. There was no correlation between ICVF and the overlife rate in cardiomyopathy patients (IDCM p = 0.249, and CDCM p = 0.587). We observed a significant correlation between ICVF and left ventricular ejection fraction (LVEF) only for IDCM. There was no correlation between ICVF and left ventricular diastolic diameter in either etiology. CONCLUSION: There was no difference in myocardial fibrosis between patients with CDCM or IDCM, and there was no correlation between fibrosis and the prognosis either for IDCM or CDCM. There was a correlation between myocardial fibrosis and LVEF only for IDCM.

O papel do acúmulo de colágeno no interstício miocárdico na sobrevida dos pacientes com cardiomiopatia dilatada idiopática e chagásica / The role of storage of interstitial myocardial collagen on the overlife rate of patients with idiopathic and chagasic dilated cardiomyopathy

OBJETIVO: Avaliar a correlação entre um marcador estrutural do miocárdio e a sobrevida dos pacientes com cardiomiopatia dilatada. MÉTODOS: Mediante realização da biópsia endomiocárdica e exame ecocardiográfico foram estudados 9 indivíduos sem doença estrutural miocárdica (controle) e 45 pacientes com cardiomiopatia dilatada grave de etiologia idiopática (MCDI) e chagásica (MCDC). Foi analisada a correlação entre a quantidade de colágeno miocárdico intersticial (FVCI) e a sobrevida desses pacientes, se a FVCI diferia entre as etiologias, e se a fibrose interferia na função e geometria do miocárdio. RESULTADOS: Foi observado que a FVCI foi 15 vezes maior nos cardiomiopatas em relação ao grupo-controle, mas não diferiu em relação às MCDI e MCDC (*p < 0,001). Não houve correlação da FCVI com a sobrevida dos pacientes com cardiomiopatias (MCDI p = 0,249 e na MCDC p = 0,587) e apenas na MCDI a fração de ejeção do ventrículo esquerdo teve correlação com a FVCI. O diâmetro diastólico final do ventrículo esquerdo não se correlacionou com a FCVI nas duas etiologias. CONCLUSÃO: A fibrose miocárdica não diferiu entre as duas etiologias, não se correlacionou com o prognóstico das MCDC e MCDI e apenas na MCDI ela se correlacionou com a FEVE.

OBJECTIVE: To find out whether there is a correlation between a myocardial structural marker and the overlife rate of patients with dilated cardiomyopathy. METHODS: Using endomyocardial biopsy and 2D-echocardiogram, we studied nine patients with no changes in myocardial structure (control) and 45 patients with severe dilated cardiomyopathy of idiopathic etiology (IDCM) and of Chagasic etiology (CDCM). We analyzed the correlation between the quantity of interstitial myocardial collagen (ICVF) and the overlife rates of these patients. We also evaluated the difference in ICVF between these groups and whether fibrosis interfered on the geometry and function of the myocardium. RESULTS: We observed that ICVF was 15 times higher in cardiomyopathy patients than in the control group, but there was no difference in ICVF between CDCM and IDCM (*p < 0.001) patients. There was no correlation between ICVF and the overlife rate in cardiomyopathy patients (IDCM p = 0.249, and CDCM p = 0.587). We observed a significant correlation between ICVF and left ventricular ejection fraction (LVEF) only for IDCM. There was no correlation between ICVF and left ventricular diastolic diameter in either etiology. CONCLUSION: There was no difference in myocardial fibrosis between patients with CDCM or IDCM, and there was no correlation between fibrosis and the prognosis either for IDCM or CDCM. There was a correlation between myocardial fibrosis and LVEF only for IDCM.

Investigação invasiva nas miocardiopatias: quando indicar? / Invasive investigation in the cardiomyopathy: when to indicate?

Os estudos invasivos compreendem a biópsia endomiocárdica e a angiografia coronariana. A biópsia endomiocárdica está indicada na avaliação das miocardiopatias com suspeita de doenças infiltrativas, miocardites, e para monitorizar a rejeição do transplante cardíaco e a cardiotoxicidade. Seu papel na avaliação do prognóstico das miocardiopatias ainda não está estabelecido. A angiografia coronariana é um exame indispensável no caso de miocardiopatias dilatadas em que há forte suspeita de origem isquêmica e em que os exames não-invasivos não esclarecerem a etiologia; como também para auxiliar o diagnóstico das endomiocardiofibroses. Esses exames podem acrescentar informações valiosas na conduta dos pacientes e até mudanças no prognóstico de suas doenças.

O papel do acúmulo do colágeno miocárdico intersticial na sobrevida dos pacientes com miocardiopatia dilatada idiopática e chagásica / The role of myocardial interstitial collagen in the survival rate of patients with idiopathic and chagasic cardiomyopathy

Um marcador prognóstico estrutural se faz necessário nas miocardiopatias dilatadas. Estudamos, por biópsia endomiocárdica e ecocardiograma, indivíduos normais (C) e com miocardiopatia dilatada idiopática (MCDI) e chagásica (MCDC). Avaliamos a relação entre a quantidade de colágeno (FVCI) e a sobrevida, se a FVCI diferia entre as etiologias e se ela interferia na função miocárdica. A FVCI foi maior nos miocardiopatas e não diferiu entre eles (MCDC= 6,83 5,47; MCDI = 5,75 4,45; C= 0,42 0,14* p<0,001). Ela não correlacionou com sobrevida e na MCDI a fração de ejeção do ventrículo esquerdo (FEVE) teve relação com a FVCI/A structural prognostic marker is needed regarding dilated cardiomyopathy. We studied, by endomyocardial byopsies and 2D-echocardiogram, normal patients (C) and with idiopathic and chagasic dilated cardiomyopathy (IDC, CDC). We evaluated the correlation between myocardial collagen (ICVF) and the survival rate, the difference between the two etiologies and it correlation with myocardial function. The ICVF was higher in the cardiomyopathy groups but did not differ between them (CDC= 6,83 5,47; IDC= 5,75 4,45; C= 0,42 0,14* p<0,001). The ICVF did not correlate with survival rate and in IDC it correlated with left ventricular ejection fraction...