Myocardial dysfunction late after low-dose anthracycline treatment in asymptomatic pediatric patients

Background: The occurrence of chronic anthracycline cardiotoxicity leading to heart failure and even death is a major concern in the treatment of childhood malignancies. Currently, most treatment protocols use reduced anthracycline doses compared with historical exposure. The long-term effect of these reduced doses on myocardial function has not been well studied. Methods: We examined 56 asymptomatic patients. They all had been treated with anthracyclines at a cumulative dose less than 300 mg/m(2) 5.2 (range: 2.0-15.2) years before the current evaluation. In all patients, standard two-dimensional, Doppler echocardiographic measurements, end-systolic wall stress calculation, and color Doppler myocardial imaging data were obtained. From the color Doppler myocardial imaging data, peak systolic myocardial velocities, peak systolic strain rate, and peak systolic strain (epsilon) were computed. The myocardial acceleration during isovolumetric contraction was measured at the basal left ventricular (LV) lateral and right ventricular free wall. Data were compared with 32 age-matched normal controls. Results: In asymptomatic patients previously exposed to low-dose anthracycline treatment, several changes in cardiac function were noted: 1. LV diastolic function was abnormal with a prolonged isovolumetric relaxation time and abnormal pulmonary venous flow patterns. 2. End-systolic wall stress was increased. 3. LV annular motion was reduced. 4. Systolic myocardial deformation was reduced with a significant decrease in both radial and longitudinal peak systolic strain rate and epsilon. Conclusions. Changes in systolic and diastolic function are noted in asymptomatic patients with normal ejection fraction late after low-dose anthracycline treatment. This confirms that subclinical LV dysfunction is present in patients after low-dose anthracycline treatment during childhood. The long-term significance of these findings warrants further follow-up.