Avaliação funcional pelo teste de caminhada de seis minutos, resposta aguda do BDNF ao esforço e seu valor prognóstico na cardiopatia chagásica

Abstract

Cardiac functional impairment may occur in various degrees in Chagas heart disease (CHD). To evaluate the functional capacity (FC) of these patients, simple and inexpensive methods as the Six-Minute Walk Test (6MWT) are recommended since the Cardiopulmonary Exercise Testing (CPET), the gold standard in this evaluation, is expensive and difficult to perform in areas with limited financial and technological resources. Previous studies have reported that the concentration of brain-derived neurotrophic factor (BDNF) is increased in CHD. This increase seems to be positively associated with FC and concentration of serum BDNF may change in response to exercise in this group. Thus, the objectives of this thesis were, in four separate studies, to verify in patients with CHD: 1) the possible correlation between the distance walked in the 6MWT with VO2peak and minute ventilation/carbon dioxide production (VE/VCO2 slope) and demonstrate the accuracy of the distance walked in identifying patients with functional impairment; 2) the regression model that better predict the VO2peak by 6MWT and easily measured clinical variables; 3) the acute response of serum BDNF levels after exercise and 4) the functional and echocardiographic predictors and prognostic value of serum BDNF. In three cross-sectional studies (n=30, n=41, n=81), patients with CHD underwent echocardiography, maximal exercise testing, 6MWT and measurement of serum BDNF before and after one aerobic exercise session. In a longitudinal study (n=75), patients were followed during 48 months. A significant correlation between the 6MWT distance and VO2peak (r = 0.586; p<0.001) was found, but not with the VE/VCO2 slope (r = -0.046; p = 0.776). The distance of 522m showed 72.4% of sensitivity and 81.8% of specificity in identifying patients with functional impairment. The model represented by the equation VO2peak = 53.43 + (1.35 x sex) - (5.59 x NYHA) + (0.01 x 6MWD) - (0.29 x age) - (0.035 x BMI) showed a strong correlation between the observed and predicted values of VO2peak (r = 0.81; p <0.001). The acute aerobic exercise significantly reduced the serum concentration of BDNF (p = 0.006) and the concentration of this neurotrophin was intensity-dependent. The independent predictors of serum BDNF were left ventricular ejection fraction (LVEF) (p=0.004) and E/e' ratio (p=0.016). Despite the lower serum BDNF levels in the group with adverse cardiovascular events after 48 months (p=0.030), the prognostic value of serum BDNF is limited and LVEF was the only independent predictor of morbidity and mortality found in patients with CHD (HR 0.935, 95% CI from 0.875 to 0.999, p=0.048). We concluded that the 6MWT was useful in the evaluation of FC in patients with CHD, the exercise intensity seems to be closely related to BDNF response in these patients and, when analyzed in isolation, there is no evidence for its use as a prognostic marker.