Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: Diastolic versus systolic parameters

Abstract

Doxorubicin and daunorubicin are effective anticancer agents in children, however, their therapeutic value is limited by myocardial cardiotoxicity. In 14 children (median age 5.0 years, range 3-12) prospective studies were performed using pulsed Doppler echocardiography to assess the changes in left ventricular systolic and diastolic filling dynamics. None of these children developed cardiomyopathy. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analysed at baseline, after a cumulative anthracycline dose of 138 +/- 26 mg/m2 (second examination) and after 240 +/- 15 mg/m2 (third examination). At the second examination the acceleration time/ejection time ratio was significantly reduced (P < 0.01), but this was no longer evident at the third examination. There was no significant change of peak velocity over aortic valve, pre-ejection period and change of velocity over time. In contrast, three diastolic parameters changed significantly; the late over early inflow velocity (P < 0.05), mitral valve late time velocity integral (P < 0.01 at the second and P < 0.05 at the third examination) and the ratio A-TVI/TVI (P < 0.025 and P < 0.01). At the third examination the velocity of the A wave was also significantly increased. CONCLUSION In anthracycline treated children left ventricular diastolic function deteriorates before systolic function. Diastolic function parameters should be used rather than systolic parameters to monitor these patients.

Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

“…Reduced peak myocardial velocities in early diastole together with increased peak velocities in late diastole and decreased ratio between early and late diastolic velocities, as found in this study, points to diastolic dysfunction with impaired capacity to fill and maintain stroke volume (decreased De) without compensatory increase of atrial filling pressure (increased Da), and have been associated with early stages of impaired relaxation of the myocardium and loss of compliance 22–25. Diastolic dysfunction has also previously been associated with anthracycline treatment in childhood 26 and is suggested to precede systolic dysfunction 27. Reduced peak velocities in systole and early diastole, as found in this study, have been associated with hypertrophy of left ventricle 28–30, and might indicate loss of contractile tissue and reduced compliance of the left ventricle due to fibrosis, as myocardial biopsies have shown fibrosis in anthracycline treated patients 6, 31.…”

Fungsi Sistolik dan Diastolik Jantung pada Pasien Anak dengan Osteosarkoma yang Mendapat Terapi Doksorubisin Di RS Cipto Mangunkusumo

“…Doksorubisin mencegah sintesis ribonucleic acid (RNA) dan deoxyribonucleic acid (DNA) melalui proses interkalasi. [3][4][5][6][7] Toksisitas terhadap jantung dilaporkan paling banyak karena penggunaan doksorubisin. Kardiotoksisitas merupakan salah satu komplikasi jangka panjang yang serius pada terapi kanker atau keganasan.…”

Early Detection and Prediction of Cardiotoxicity - Biomarker and Echocardiographic Evaluation

“…If a transthoracic window yield unacceptable cardiac images because of local surgery or radiation-related changes, an alternative imaging modality like radionuclide scanning should be considered (Sengupta et al, 2008). Moreover, ejection fraction is not a very sensitive parameter in detecting early alterations in myocardial function as they occur in early cardiotoxicity (Schmitt et al, 1995).…”

“…It was established that cardiotoxocity lead to diastolic dysfunction of the left ventricle which can be registered with Doppler echocardiography before systolic function occurs (Schmitt et al, 1995). The impairement was not lineary related to the cumulative dose of antracyclines, but may persist years after treatment with antracyclines (Bu'lock et al, 1995;Hausdorf et al, 1988).…”