Abstract
BACKGROUND: Exposure to anthracyclines (ANT) during childhood represents a high risk for development of late cardiotoxicity. Cardiotoxicity is usually detected only when clinical symptoms or progressive cardiac dysfunction have already occurred. Early detection of cardiotoxicity may lead to better therapeutic outcome. N-terminal pro-brain natriuretic peptide (NTproBNP) has been hypothesized to reflect increased left ventricular wall stress before development of echocardiographic abnormalities. The aim of this study was to detect cardiac abnormalities using plasma NTproBNP and echocardiography in asymptomatic childhood leukemia survivors treated with or without cardiotoxic anthracycline therapy. METHODS: Serum levels of NTproBNP were determined in 69 asymptomatic survivors of childhood leukemia treated with or without anthracyclines and in 44 apparently healthy controls. The survivors were divided into two treatment groups: 36 patients after chemotherapy containing anthracyclines (ANT) and 33 patients after chemotherapy without anthracyclines (nonANT). Levels of NTproBNP were measured by using the Elecsys 2010 immunoassay analyzer (Roche Diagnostics). Echocardiography using M-mode, two-dimensional and Doppler measurements were performed on the same day as blood samples were obtained for NTproBNP analysis in survivors. RESULTS: Serum levels of NTproBNP were significantly higher in the ANT group than in controls (median 51.52 vs 17.37 pg/ml; p=0.0026). Survivors exposed to ANT had significantly increased levels of NTproBNP compared with patients treated without ANT (median 51.52 vs 12.24 pg/ml; p=0.0002). Female exposed and unexposed survivors had significantly higher NTproBNP levels than males. Four of the 36 survivors (11%) treated with ANT and two of the 33 patients (6%) not exposed to ANT had abnormal NTproBNP levels. Although no patient had echocardiographic abnormalities, significant differences were found in values of left ventricular ejection fraction (LVEF) and deceleration time (DT) between survivors treated with or without anthracyclines. CONCLUSIONS: Higher levels of NTproBNP detected in childhood leukemia survivors after low anthracycline cumulative doses might reflect an initial stage of ANT cardiotoxicity before the development of echocardiographic abnormalities. Although the current studies support NTproBNP as one of the best available biochemical markers of late anthracycline cardiotoxicity, a possible strategy toward further improvement and combination with other cardiac biomarkers and novel echocardiographic methods should be explored in additional studies.