Echocardiographic assessment of anthracycline cardiotoxicity during different therapeutic regimens

The use of doxorubicin (Dx) in treating malignancies is limited by a potentially fatal cardiomyopathy. Prevention of this related cardiotoxicity has been attempted either by using doxorubicin analogues such as 4'-epidoxorubicin (4'-EpiDx) or by simultaneous administration of other pharmacological substances. Fifteen patients with breast and lung cancer divided into three groups, treated respectively with Dx alone, Dx and L-carnitine and 4'-EpiDx, were studied to assess the effects of these therapeutic regimens on left ventricular performance. For this purpose the maximum velocities of fibre shortening and lengthening (VcF), obtained by computerized M-Mode echocardiography were used as indices of systolic and diastolic function respectively. Data from patients and from 25 healthy subjects were evaluated by analysis of variance and Tukey test. No significant difference was found in baseline systolic and diastolic VcF values. Significantly lower systolic VcF (p less than 0.05) was shown by patients treated with Dx alone, while diastolic VcF was significantly lower in those treated with 4'-EpiDx after four cycles. Systolic VcF of patients treated with Dx and L-carnitine and with 4'-EpiDx did not significantly differ from controls even after six therapeutic cycles. These data demonstrate that systolic VcF is not affected by 4'-EpiDx or by Dx when administrated with L-carnitine. The reduction of diastolic VcF by 4'-EpiDx and not by Dx could be due to different effects of these drugs on the calcium transport since early isovolumic relaxation depends on an energy-dependent process of calcium removal.