Early detection of doxorubicin cardiotoxicity: Interest of Doppler echocardiographic analysis of left ventricular filling dynamics

Abstract

Doxorubicin (Adriamycin) is an effective anticancer agent but its therapeutic value is limited by its myocardial cardiotoxicity. To improve early detection of doxorubicin cardiotoxicity, studies were performed in patients with long-term doxorubicin treatment using pulsed Doppler echocardiography to assess the changes in left ventricular (LV) diastolic filling dynamics. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analyzed in two groups of patients. In group A (45 patients, mean age 45 ± 13 years), the results were compared with those of a control group of 35 normal subjects matched for age. In group B (19 patients, mean age 44 ± 12 years), the pretreatment results were prospectively compared with those obtained during treatment protocol. The patients received a cumulative dosage of 253 ± 125 mg/m 2 of doxorubicin for group A and 240 ± 135 mg/m 2 for group B. After doxorubicin treatment, in the two groups there were no significant changes in LV dimensions, shortening fraction, and mean velocity of circumferential fiber shortening (VCF). In contrast, Doppler echocardiographic parameters of diastolic function were significantly modified after doxorubicin in the two groups:isovolumic relaxation period was prolonged by 32% in group A ( p < 0.001) and by 22% in group B ( p < 0.005). The early peak flow velocity was reduced by 18% in group A ( p < 0.002) and by 13% in group B ( p < 0.04), and the ratio early peak flow velocity/atrial peak flow velocity also decreased significantly, by 23% in group A ( p < 0.001) and by 20% in group B ( p < 0.01). The deceleration rate of the early peak flow velocity decreased from 458 ± 162 to 352 ± 193 cm/sec 2 in group A ( p < 0.005) and from 426 ± 168 to 339 ± 176 cm/sec 2 in group B ( p < 0.007); this parameter was reduced in 84% of group B patients. These changes were not correlated with doxorubicin dosage. In conclusion, in patients with long-term doxorubicin treatment, LV diastolic function abnormalities precede resting systolic dysfunction.