Valor incremental do peptídeo natriurético cerebral na predição de morte em indivíduos com cardiomiopatia chagásica em área endêmica

Abstract

INTRODUCTION: Chagas cardiomyopathy is an important cause of heart failure in endemic areas and assessment of cardiac function by echocardiogram is essential to define prognosis. Natriuretic peptides are well established in the diagnostic of heart failure, but its prognostic value additional to echocardiographic parameters is not well defined, especially in community-based Chagas patients. OBJECTIVES: This study aims to assess the incremental value of N-terminal Pro-brain natriuretic peptide (NT-ProBNP) over echocardiographic parameters in predicting mortality in patients with Chagas cardiomyopathy from remote areas. METHODS: Patients with Chagas disease from endemic areas in Brazil who had heart failure defined as left ventricular ejection fraction (LVEF) < 50% and/or NT-ProBNP >300 pg/ml were eligible for the study. Clinical data were obtained using a standardized questionnaire. A resting 12-lead ECG was recorded at baseline and read by trained cardiologists. A range of readily obtained echocardiographic measures were collected using portable equipment at public health primary centers. The end point was all-cause mortality. Two Cox regression models were performed to test the incremental value of NT-Pro-BNP over conventional echocardiographic variables that were independently predictive of mortality. In the first multivariable model, prespecified echocardiographic variables of prognostic impact were included, adjusted for age, sex, NYHA functional class, and ECG parameters, including heart rate, QRS duration, atrial fibrillation, and pacemaker. In the second model, NT-Pro-BNP was added to these echocardiographic variables, and a head-to-head comparison of both models was performed. The Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC) were calculated for each model. Net Reclassification Improvement (NRI) was calculated comparing the model including echocardiographic variables to the model including these and NT-Pro-BNP. The global goodness of fit of the models was evaluated by Likelihood ratio tests. Kaplan-Meier curves were presented to display survival rate using the log-rank test. RESULTS: The mean age was 66  13 years and 210 (57%) were women. Most of the patients were in functional class II and III, with left ventricular (LV) systolic dysfunction (LVEF = 41  12%). During a mean follow-up of 31 months, 133 patients died (36%) with overall mortality incidence rate of 39.6 deaths per 100 patient-years. Four key echocardiographic parameters were predictors of mortality, including LVEF (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.95 - 0.98), right ventricular (RV) end-diastolic area (HR 1.06; 95% CI 1.03 - 1.09), E/e’ ratio (HR 1.03; 95% CI 1.01 - 1.05), and left atrial (LA) volume (HR 1.01; 95% CI 1.00 - 1.01). The inclusion of NT-ProBNP on top of echocardiographic parameters resulted in significant improvement in model performance (HR 1,80; IC% 1,19 – 2,73; p < 0,005). CONCLUSIONS: In a contemporary cohort of patients with Chagas cardiomyopathy, echocardiographic variables that express the severity of left and right ventricular dysfunction were important predictors of mortality. NT-ProBNP was a strong predictor of death, improving risk stratification beyond that provided by echocardiographic measurements. NT-ProBNP assessment may be used in a clinical setting to improve the risk stratification of patients with Chagas cardiomyopathy living in endemic areas.