Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide...

To study the longitudinal variations of plasma B-type natriuretic peptide (BNP) with reference to left ventricular ejection fraction (LVEF) during and after chemotherapy with cardiotoxic drugs.

We prospectively measured plasma BNP using an immunoradiometric assay in 12 anthracycline-treated breast cancer patients monitored for a mean time of 880+/-293 days (pilot group). Prior to each cycle and throughout the following year, LVEF and cardiac output were measured by radionuclide ventriculography. Anthracycline pharmacokinetics was studied during the first cycle. Relationships between serial observations were analysed with the general linear mixed effects model. Identical methods were subsequently applied to a test group of 67 anthracycline or trastuzumab-treated patients.

Five out of 70 (6.33%) patients developed anthracycline-induced heart failure. BNP concentrations were found to be positively correlated to anthracycline cumulative dose and negatively to LVEF values. Variables entering the mixed models were cumulative anthracycline dose, time and cardiac output.

An infra-clinical cardiotoxicity of anthracyclines as defined by BNP elevation is frequent but reversible. Patients who developed heart failure showed a continuous BNP increase and concentrations over 100 ng/ml.