Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10-mu-g/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10-mu-g/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p < 0.01). End-systolic left ventricular posterior wall dimension at the 5-mu-g/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p < 0.01). Percent left ventricular posterior wall thickening at baseline for the doxorubicin-treated group was 78 +/- 18% versus 97 +/- 13% for the control group (p < 0.01). Percent left ventricular posterior wall thickening at the 5-mu-g/kg per min dobutamine infusion for the doxorubicin-treated group was 121 +/- 37% versus 185 +/- 20% for the control group (p < 0.01). Decreased left ventricular shortening fraction and increased left ventricular end-systolic meridional wall stress were demonstrated in doxorubicin-treated patients only during dobutamine infusion. No differences were found between results in control subjects and doxorubicin-treated patients for measured diastolic variables. Thus, asymptomatic long-term survivors of childhood cancer treated with doxorubicin may have latent decreased cardiac performance that is undetected by commonly used echocardiographic methods, including rest left ventricular shortening fraction and left ventricular end-systolic meriodional wall stress. Our data establish that evaluation of left ventricular systolic function by end-systolic posterior wall dimension, posterior wall thickening, end-systolic meridional wall stress and shortening fraction measured during inotropic stimulation with dobutamine provides a sensitive technique for examining the cardiac status of asyptomatic doxorubicin-treated patients.
