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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 micrograms/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 micrograms/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 less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Serial echocardiographic studies were performed on 48 children who received chemotherapy with doxorubicin hydrochloride (Adriamycin). For the group as a whole, no correlation could be made between the cumulative dose of doxorubicin administered and left ventricular systolic function as measured by the fractional shortening of the left ventricle (delta s). Two asymptomatic patients, however, demonstrated depressed delta s and abnormal results from radionuclide studies at cumulative doxorubicin doses of less than 430 mg/sq m. Differentiation of the echoderived curve of left ventricular minor axis dimension indicated that these two patients had abnormalities in both diastolic and systolic function. Good correlation was demonstrated between echocardiographic and radionuclide studies in eight patients, including the two with depressed function. Inherent variability limits the sensitivity of echocardiographic functional studies, but serial studies are helpful in the evaluation of cardiac function in children who receive doxorubicin.

This investigation was designed to evaluate echoes of patients who received a course of doxorubicin (225-550 mg/m2) by two sensitive indicators of myocardial fibrosis: (1) M-mode scans of thickening-thinning curves of the left ventricular posterior wall (LVPW), and (2) two-dimensional qualitative evaluation of LVPW contraction at three levels of the LV short axis (leaflet, chordal, and papillary). These were compared to standard M-mode shortening fraction (delta S). Eighteen children with cancer were evaluated; 11 had received doxorubicin and 7 were treated with other agents. Echocardiographers were unaware of the treatment category. All controls and 10 of 11 doxorubicin patients had normal delta S. An M-mode echocardiogram of the expanded LVPW was digitized and wall thickness was evaluated by determining if diastolic relaxation had the normal two phases or only one; six of ten doxorubicin patients and no controls had abnormal relaxation. Qualitative evaluation of LVPW and septal contraction toward the center of the ventricle showed that seven of eleven patients who received doxorubicin and one control (a postthoracotomy patient) had contraction deficits. Six of seven with contraction deficit were the same patients with slowed relaxation. The greatest contraction deficit occurred in the LVPW behind the posterior mitral leaflet. Patients with more extensive involvement had an additional contraction deficit extending to the apex. These tests are more sensitive for detection of doxorubicin toxicity than delta S.