Intestinal permeability evaluation in patients with chronic Chagas heart failure.

AIMS: We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls. BACKGROUND: Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure. METHODS: Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide. RESULTS: Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome. CONCLUSIONS: The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF <55%, measured by lactulose/mannitol urinary excretion ratio. Further investigations are needed to verify if in patients with LVEF <40% intestinal permeability is increased.

Biomakers in Chronic Chagas Cardiomyopathy.

The primary objective was to observe the relationship between serum levels of BNP, Ca-125, C-reactive protein and uric acid as prognostic and functional markers in patients with chronic Chagas cardiomyopathy (CCC). Circulating levels of cytokines: IL-1ß, TNFα, IL-10, IL6, IL-8 and IL-12 were determined and investigated regarding their association with hemodynamic parameters, clinical signs of heart failure and outcome. Chagas is still a neglected disease that affects numerous individuals, many of them in their most productive years. CCC with left ventricular dysfunction is the most severe presentation of Chagas Disease. BNP is a well-recognized prognostic and clinical biomarker, not only in chronic heart failure patients but also in patients with CCC. Previous studies have shown Ca-125, C-reactive protein, and uric acid to be potentially good prognostic markers in heart failure (HF). Fifty patients with left ventricular fraction less (LVEF) than 55% were selected and followed for a mean period of 18 ± 8.3 months. Patient's mean age was 43.42 ± 10.3 years (32 male), their BNP was 293 (160-530) pg/mL, Ca-125 8.5 (5.5-16.75) U/mL, uric acid 6.2 ± 2 mg/dL, and C- reactive protein 4.5 (4.5-7.3) mg/L. Patients who had LVEF less than 35% had higher BNP (p = 0.0023), Ca-125 (p = 0.027) and uric acid (p = 0.01) serum levels. Patients who died also showed higher BNP (p = 0.01), uric acid (p = 0.05) and a trend towards higher Ca-125 serum levels (p = 0.056). All markers: BNP, Ca-125, uric acid and C-reactive had good predictability of death in Cox-regression univariate analysis, however, not on the final multivariate model. Of the inflammatory cytokines, IL-8 and IL-12 showed a relation to LVEF of less than 35%. IL-12 was related to adverse cardiovascular events and non-survival. IL-1ß was a good predictor of mortality in the final Cox regression model. Determination of Ca-125, uric acid levels and C-reactive protein may add useful clinical and prognostic information and may help clinical decision making for patients with CCC.

Avaliação da permeabilidade intestinal em pacientes com cadiopatia chagásica crônica / Intestinal permeability in patients with chronic Chagas cardiomyopathy

A doença de Chagas ao completar mais de um século de sua descrição original, continua representando terrível impacto sobre a humanidade. Estima-se que cerca de 6 milhões de indivíduos estão acometidos na América Latina e atualmente, devido à globalização se tornou um problema de saúde publica mundial. Entre os indivíduos infectados, 30% têm ou terão alguma forma de comprometimento cardíaco e 15% apresentam ou apresentarão formas mais graves de insuficiência ventricular esquerda, principal marcador de sua morbimortalidade. A fisiopatologia da insuficiência cardíaca consequente à cardiopatia chagásica não parece diferir das outras etiologias de miocardiopatia, no que diz respeito à alterações hemodinâmicas e neurohormonais. Recentemente, o papel do intestino na patogênese da insuficiência cardíaca (IC) tem despertado o interesse da comunidade cientifica. A IC é reconhecida como uma doença multisistemica e um estado de inflamação crônica de baixo grau. Propõe-se que a disfunção intestinal, em condições de baixo débito cardíaco, favoreceria à translocação bacteriana que por sua vez ativaria a cascata de inflamação, o que provocaria piora funcional cardíaca, sintomatologia mais exuberante e pior prognóstico. O estudo buscou alterações da permeabilidade intestinal em 50 pacientes chagásicos com fração de ejeção do ventrículo esquerdo (FEVE) menor que 55%. Convidou-se um grupo de 27 indivíduos saudáveis para participar como controle. Foi um estudo prospectivo observacional. Analisamos parâmetros hemodinâmicos obtidos pelo ecocardiograma, manifestações clínicas da IC, marcadores neuro-hormonais e inflamatórios, assim como o desfecho de forma comparativa com o teste da permeabilidade intestinal. O teste da permeabilidade intestinal baseia-se na ingestão de dois marcadores de açucares, no caso o manitol e a lactulose, que são recuperados na urina conforme sua taxa de permeação pela mucosa intestinal. Pacientes com disfunção sistólica do ventrículo esquerdo com manifestações clínicas mais pronunciadas de congestão sistêmica e os que evoluíram de forma desfavorável apresentaram níveis reduzidos de excreção urinária do manitol quando comparados ao grupo controle. Não houve diferença entre a taxa de excreção urinária da lactulose e a taxa de excreção da lactulose pelo manitol com relação aos parâmetros estudados. Portanto, esse estudo sugeriu associação entre a gravidade da IC e taxa reduzida de recuperação urinária do manitol.

After more than a century of its original discovery, Chagas disease continues to inflict a heavy burden upon humanity. Around 6 million people are still infected in Latin America, and recently due to globalization, Chagas has become a world heath problem. Of the individuals infected around 30% will have involvement of the heart, and 15% will develop the more severe left ventricular dysfunction, which is its most important prognostic marker. Chagas heart disease is not that different from the other forms of heart failure, regarding hemodynamic and neurohormonal abnormalities. Recently, the gut role in the pathogenesis of heart failure has received more attention from the scientific community. Heart failure is now regarded as a multisystemic disease and as a state of chronic low grade inflammation. There is a hypothesis that under conditions of low cardiac output, there would be epithelial intestinal dysfunction, allowing bacteria and its product translocation, which would activate inflammatory cytokines and worsen heart failure. Our aim was to analyze intestinal permeability abnormalities and compare it to hemodynamic parameters, clinical signs and symptoms, neurohormonal and inflammatory markers and the outcome of Chagas heart disease. We enrolled a group of 50 Chagas heart disease patients and a group of 27 healthy individuals as control. The intestinal permeability test is based on the urinary recovery of two sugar probes, mannitol and lacutlose, that are orally ingested. Patients who had worse left ventricular systolic dysfunction, more pronounced clinical signs of systemic congestion and those with a worse outcome, had reduced levels of urinary excretion rate of mannitol, when compared to the control group. The was no differenced of urinary excretion rate of lactulose and urinary excretion rate of lactulose/mannitol regarding the variables analyzed. Therefore, the present study has suggested an association of the severity of heart failure and urinary reduced levels of mannitol recovery.