Objective. To investigate the ability of two-dimensional longitudinal strain echocardiography (2DST), to detect the early doxorubicin cardiotoxicity. Patients and Methods. The study included 25 children with newly diagnosed acute lymphoblastic leukemia (ALL) aged 5–15 years and 30 healthy control children. They had echocardiographic examination with conventional 2-dimensional (2D), pulsed tissue Doppler (PTD), and 2DST echocardiography before and within 1 week after doxorubicin treatment. Results. There was no significant difference in left ventricle (LV) systolic and diastolic functions measured by conventional 2-D and PTD echocardiography between patients and controls. However, there was significant decrease in LV global and peak systolic strain detected by 2-DST echocardiography in study group than control. After doxorubicin treatment, there was no significant difference in LV systolic and diastolic functions measured by conventional 2-D and PTD echocardiography than before treatment except for prolonged IVCT and IVRT, but LV global and peak systolic strain was significantly lower after treatment. Conclusion. 2-D longitudinal strain echocardiography was more sensitive than conventional 2-D and PTD in detecting the early LV doxorubicin-induced cardiotoxicity in children with ALL. 1. Introduction Doxorubicin is one of the most effective available anthracycline chemotherapeutic agents that have been widely used in the treatment of pediatric malignancies. Its introduction has led to the successful treatment of childhood cancer with improved survival rates. Nearly two-thirds of survivors have one or more related chronic medical problems and may require multidisciplinary care [1]. Because doxorubicin plays a key role in the treatment of many malignancies, its loss from the field of cancer treatments would lead to a dramatic reduction in cure rates. Its efficacy is often limited by its related cardiotoxicity, which leads to cardiomyopathy that may evolve into heart failure [2–4]. Cardiotoxicity can arise acutely, during or shortly after treatment and regardless of dose in the form of cardiac arrhythmias, for example, sinus tachycardia, ventricular, and supraventricular. Pericarditis, potentially fatal congestive heart failure, and acute pulmonary edema can also occur during doxorubicin therapy caused by myocyte necrosis as a result of increased cardiac apoptosis and alteration of cardiac cytochrome P450 expression and arachidonic acid metabolism [5, 6]. Chronic dose-related cardiotoxicity is the most common and dangerous and can manifest as cardiac failure,
References
[1]
H. L. Curry, S. E. Parkes, J. E. Powell, and J. R. Mann, “Caring for survivors of childhood cancers: the size of the problem,” European Journal of Cancer, vol. 42, no. 4, pp. 501–508, 2006.
[2]
R. Danesi and R. Zucchi, “Cardiac toxicity of antineoplastic anthracyclines,” Current Medicinal Chemistry—Anti-Cancer Agents, vol. 3, no. 2, pp. 151–171, 2003.
[3]
G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni, “Anthracyclines: molecular advances and pharmacologie developments in antitumor activity and cardiotoxicity,” Pharmacological Reviews, vol. 56, no. 2, pp. 185–229, 2004.
[4]
K. A. Wouters, L. C. M. Kremer, T. L. Miller, E. H. Herman, and S. E. Lipshultz, “Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies,” British Journal of Haematology, vol. 131, no. 5, pp. 561–578, 2005.
[5]
O. J. Arola, A. Saraste, K. Pulkki, M. Kallajoki, M. Parvinen, and L. M. Voipio-Pulkki, “Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis,” Cancer Research, vol. 60, no. 7, pp. 1789–1792, 2000.
[6]
B. N. M. Zordoky, A. Anwar-Mohamed, M. E. Aboutabl, and A. O. S. El-Kadi, “Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats,” Toxicology and Applied Pharmacology, vol. 242, no. 1, pp. 38–46, 2010.
[7]
A. Kruger and L. Wojnowski, “Cardiotoxicity of Anthracyclines—an Unsolved Problem,” Deutsches Arzteblatt, vol. 103, no. 37, pp. A2393–A2397, 2006.
[8]
J. R. Carver, C. L. Shapiro, A. Ng et al., “American society of clinical oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects,” Journal of Clinical Oncology, vol. 25, no. 25, pp. 3991–4008, 2007.
[9]
L. J. Steinherz, P. G. Steinherz, C. T. C. Tan, G. Heller, and M. L. Murphy, “Cardiac toxicity 4 to 20 years after completing anthracycline therapy,” JAMA, vol. 266, no. 12, pp. 1672–1677, 1991.
[10]
J. D'Hooge, A. Heimdal, F. Jamal et al., “Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations,” European Journal of Echocardiography, vol. 1, no. 3, pp. 154–170, 2000.
[11]
A. Frigiola, A. N. Redington, S. Cullen, and M. Vogel, “Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of fallot,” Circulation, vol. 110, no. 11, pp. II153–II157, 2004.
[12]
L. Li, G. Takemura, Y. Li et al., “Preventive effect of erythropoietin on cardiac dysfunction in doxorubicin-induced cardiomyopathy,” Circulation, vol. 113, no. 4, pp. 535–543, 2006.
[13]
J. S. Gottdiener, J. Bednarz, R. Devereux et al., “American Society of Echocardiography recommendations for use of echocardiography in clinical trials: a report from the american society of echocardiography's guidelines and standards committee and the task force on echocardiography in clinical trials,” Journal of the American Society of Echocardiography, vol. 17, no. 10, pp. 1086–1119, 2004.
[14]
M. Al-Biltagi, M. Issa, H. A. Hagar, M. Abdel-Hafez, and N. A. Aziz, “Circulating cardiac troponins levels and cardiac dysfunction in children with acute and fulminant viral myocarditis,” Acta Paediatrica, International Journal of Paediatrics, vol. 99, no. 10, pp. 1510–1516, 2010.
[15]
R. L. Goldman, “The κ statistic,” JAMA, vol. 11, pp. 2513–2514, 1992.
[16]
K. Chatterjee, J. Zhang, N. Honbo, and J. S. Karliner, “Doxorubicin cardiomyopathy,” Cardiology, vol. 115, no. 2, pp. 155–162, 2010.
[17]
R. Q. Migrino, D. Aggarwal, E. Konorev, T. Brahmbhatt, M. Bright, and B. Kalyanaraman, “Detection of doxorubicin cardiomyopathy using 2-dimensional strain echocardiography,” Ultrasound in Medicine and Biology, vol. 34, no. 2, pp. 208–214, 2008.
[18]
J. Sanderson, “Heart failure with a normal ejection fraction,” Heart, vol. 93, no. 2, pp. 155–158, 2007.
[19]
D. Iarussi, M. Galderisi, G. Ratti et al., “Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood,” Clinical Cardiology, vol. 24, no. 10, pp. 663–669, 2001.
[20]
L. Kapusta, J. M. Thijssen, J. Groot-Loonen, T. Antonius, J. Mulder, and O. Dani？ls, “Tissue Doppler imaging in detection of myocardial dysfunction in survivors of childhood cancer treated with anthracyclines,” Ultrasound in Medicine and Biology, vol. 26, no. 7, pp. 1099–1108, 2000.
[21]
S. E. Lipshultz, S. D. Colan, R. D. Gelber, A. R. Perez-Atayde, S. E. Sallan, and S. P. Sanders, “Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood,” The New England Journal of Medicine, vol. 324, no. 12, pp. 808–815, 1991.
[22]
H.-R. Tsai, O. Gjesdal, T. Wethal et al., “Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of hodgkin's lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy,” American Journal of Cardiology, vol. 107, no. 3, pp. 472–477, 2011.
[23]
E. Piegari, G. Di Salvo, B. Castaldi et al., “Myocardial strain analysis in a doxorubicin-induced cardiomyopathy model,” Ultrasound in Medicine and Biology, vol. 34, no. 3, pp. 370–378, 2008.
[24]
S. Urheim, T. Edvardsen, H. Torp, B. Angelsen, and O. A. Smiseth, “Myocardial strain by Doppler echocardiography: validation of a new method to quantify regional myocardial function,” Circulation, vol. 102, no. 10, pp. 1158–1164, 2000.
[25]
E. Yamada, M. Garcia, J. D. Thomas, and T. H. Marwick, “Myocardial Doppler velocity imaging—a quantitative technique for interpretation of Dobufamine echocardiography,” American Journal of Cardiology, vol. 82, no. 6, pp. 806–809, 1998.
