Share This Article:

Risk Factors Associated with Anthracycline Induced Cardiac Dysfunction in Pediatric Patients

Abstract Full-Text HTML XML Download Download as PDF (Size:910KB) PP. 377-383
DOI: 10.4236/wjcd.2014.47047    2,369 Downloads   3,275 Views   Citations

ABSTRACT

Anthracyclines (i.e., doxorubicin, daunorubicin) have significant impact on outcome in many pediatric chemotherapy protocols and therefore remain the mainstay of treatment. The objective of this study was to identify the risk factors for anthracycline induced cardiac dysfunction in pediatric patients. Multiple logistic regression model was applied to assess the risk factors for development of cardiac dysfunction. 110 pediatric oncology patients were available for final analysis. 75 (66%) children were males and mean age was 74 ± 44 months. ALL (n = 70, 64%) was the most common primary diagnosis followed by lymphoma (n = 19; 17%) and AML (n = 12, 11%). Daunorubicin alone or in combination with doxorubicin was used in (n = 94, 85%) patients and cumulative dose < 300 mg was used in (n = 95; 86%) children. 24 (22%) children received radiation therapy as per protocol and sepsis were observed in 47 (43%) cases. Post anthracycline, 15 (14%) children had cardiac dysfunction within a month; out of them 10/15 (67%) had isolated diastolic dysfunction, while 28 (25%) developed dysfunction within a year. 19 (17%) had pericardial effusion. 11 expired and out of them, 7 had significant cardiac dysfunction. Cumulative dose > 300 mg/m2 (p < 0.001; AOR 2.3), radiation therapy (p = 0.009; AOR 3.5) and sepsis (p = 0.002; AOR 2.6) were found to be independent risk factors associated anthracycline induced cardiac dysfunction. At univariant level use of daunorubicin alone or in combination therapy (p < 0.001, OR 7) and mode of delivery (p 0.048, OR 9.7) were also found statistically significant. In conclusion anthracycline induced cardiac dysfunction is mostly related to cumulative dose > 300 mg/m2, use of Daunorubicin alone or in combination with doxorubicin, mode of delivery, radiation therapy and sepsis. Regular long term follow-up with cardiologist is the key point for early diagnosis and therapy for a long term survival.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Shaikh, A. , Alam, M. , Mohsin, S. , Abbas, Q. , Fadoo, Z. and Atiq, M. (2014) Risk Factors Associated with Anthracycline Induced Cardiac Dysfunction in Pediatric Patients. World Journal of Cardiovascular Diseases, 4, 377-383. doi: 10.4236/wjcd.2014.47047.

References

[1] Singal, P.K. and Iliskovic, N. (1998) Doxorubicin-Induced Cardiomyopathy. The New England Journal of Medicine, 13, 900-905.
http://dx.doi.org/10.1056/NEJM199809243391307
[2] Lipshultz, S.E., Alvarez, J.A. and Scully, R.E. (2008) Anthracycline Associated Cardiotoxicity in Survivors of Childhood Cancer. Heart, 4, 525-533.
[3] Roodpeyma, S., Moussavi, F. and Kamali, Z. (2008) Late Cardiotoxic Effects of Anthracycline Chemotherapy in Childhood Malignancies. Journal of Pakistan Medical Association, 12, 683-687.
[4] Monsuez, J.J., Charniot, J.C., Vignat, N. and Artigou, J.Y. (2010) Cardiac Side-Effects of Cancer Chemotherapy. International Journal of Cardiology, 144, 3-15.
http://dx.doi.org/10.1016/j.ijcard.2010.03.003
[5] Cardinale, D., Sandri, M.T., Martinoni, A., Tricca, A., Civelli, M., Lamantia, G., Cinieri, S., Martinelli, G., Cipolla, C.M. and Fiorentini, C. (2000) Left Ventricular Dysfunction Predicted by Early Troponin I Release after High-Dose Chemotherapy. Journal of the American College of Cardiology, 36, 517-522.
http://dx.doi.org/10.1016/S0735-1097(00)00748-8
[6] Puma, N., Ruggiero, A., Ridola, V., Maurizi, P., Lazzareschi, I., Attina, G., Mastrangelo, S., De Rosa, G. and Riccardi, R. (2008) Anthracycline-Related Cardiotoxicity: Risk Factors and Therapeutic Options in Childhood Cancers. Signa Vitae, 3, 30-34.
[7] Kremer, L.C., van Dalen, E.C., Offringa, M. and Voute, P.A. (2002) Frequency and Risk Factors of Anthracycline-Induced Clinical Heart Failure in Children: A Systematic Review. Annals of Surgical Oncology, 13, 503-512.
http://dx.doi.org/10.1093/annonc/mdf118
[8] Krischer, J.P., Epstein, S., Cuthbertson, D.D., Goorin, A.M., Epstein, M.L. and Lipshultz, S.E. (1997) Clinical Cardiotoxicity Following Anthracycline Treatment for Childhood Cancer: The Pediatric Oncology Group Experience. Journal of Clinical Oncology, 4, 1544-1552.
[9] Tukenova, M., Diallo, I., Hawkins, M., Guibout, C., Quiniou, E., Pacquement, H., Dhermain, F., Shamsaldin, A., Oberlin, O. and de Vathaire, F. (2010) Long-Term Mortality from Second Malignant Neoplasms in 5-Year Survivors of Solid Childhood Tumors: Temporal Pattern of Risk According to Type of Treatment. Cancer Epidemiology, Biomarkers & Prevention, 19, 707-715.
http://dx.doi.org/10.1158/1055-9965.EPI-09-1156
[10] Von Hoff, D.D., Layard, M.W., Basa, P., Davis Jr., H.L., Von Hoff, A.L., Rozencweig, M. and Muggia, F.M. (1979) Risk Factors for Doxorubicin-Induced Congestive Heart Failure. Annals of Internal Medicine, 91, 710-717.
http://dx.doi.org/10.7326/0003-4819-91-5-710
[11] Yeh, E.T. and Bickford, C.L. (2009) Cardiovascular Complications of Cancer Therapy: Incidence, Pathogenesis, Diagnosis, and Management. Journal of the American College of Cardiology, 53, 2231-2247.
http://dx.doi.org/10.1016/j.jacc.2009.02.050
[12] Erdogan, D.Y.H., Youcel, H., Alanoglu, E.G., Uysal, B.A., Kocer, M., Ozaydin, M. and Dogan, A. (2011) Can Comprehensive Echocardiographic Evaluation Provide an Advantage to Predict Anthracycline-Induced Cardiomyopathy? Turk Kardiyoloji Dernegi Arsivi’s, 39, 646-653.
http://dx.doi.org/10.5543/tkda.2011.01700
[13] Gatta, G., Capocaccia, R., Coleman, M.P., Ries, L.A. and Berrino, F. (2002) Childhood Cancer Survival in Europe and the United States. Cancer, 95, 1767-1772.
http://dx.doi.org/10.1002/cncr.10833
[14] Sohn, D.W., Chai, I.H., Lee, D.J, Kim, H.C., Kim, H.S., Oh, B.H., Lee, M.M., Park, Y.B., Choi, Y.S., Seo, J.D. and Lee, Y.W. (1997) Assessment of Mitral Annulus Velocity by Doppler Tissue Imaging in the Evaluation of Left Ventricular Diastolic Function. Journal of the American College of Cardiology, 30, 474-480.
http://dx.doi.org/10.1016/S0735-1097(97)88335-0
[15] Tei, C., Ling, L.H., Hodge, D.O., Bailey, K.R., Oh, J.K., Rodeheffer, R.J., Tajik, A.J. and Seward, J.B. (1995) New Index of Combined Systolic and Diastolic Myocardial Performance: A Simple and Reproducible Measure of Cardiac Function—A Study in Normals and Dilated Cardiomyopathy. International Journal of Cardiology, 26, 357-366.
[16] Nagueh, S.F., Middleton, K.J., Kopelen, H.A., Zoghbi, W.A. and Quinones, M.A. (1997) Doppler Tissue Imaging: A Noninvasive Technique for Evaluation of Left Ventricular Relaxation and Estimation of Filling Pressures. Journal of the American College of Cardiology, 30, 1527-1533.
http://dx.doi.org/10.1016/S0735-1097(97)00344-6
[17] Ommen, S.R., Nishimura, R.A., Appleton, C.P., Miller, F.A., Oh, J.K., Redfieldm M.M. and Tajik, A.J. (2000) Clinical Utility of Doppler Echocardiography and Tissue Doppler Imaging in the Estimation of Left Ventricular Filling Pressures: A Comparative Simultaneous Doppler-Catheterization Study. Circulation, 102, 1788-1794.
http://dx.doi.org/10.1161/01.CIR.102.15.1788
[18] Velensek, V., Mazic, U., Krzisnik, C., Demsar, D., Jazbec, J. and Jereb, B. (2008) Cardiac Damage after Treatment of Childhood Cancer: A Long-Term Follow-Up. BMC Cancer, 8, 141.
http://dx.doi.org/10.1186/1471-2407-8-141
[19] Barry, E., Alvarez, J.A., Scully, R.E., Miller, T.L. and Lipshultz, S.E. (2007) Anthracycline-Induced Cardiotoxicity: Course, Pathophysiology, Prevention and Management. Expert Opinion on Pharmacotherapy, 8, 1039-1058.
http://dx.doi.org/10.1517/14656566.8.8.1039
[20] Van Dalen, E.C., van der Pal, H.J., Kok, W.E., Caron, H.N. and Kremer, L.C. (2006) Clinical Heart Failure in a Cohort of Children Treated with Anthracyclines: A Long-Term Follow-Up Study. European Journal of Cancer, 42, 3191-3198.
http://dx.doi.org/10.1016/j.ejca.2006.08.005
[21] Nysom, K., Holm, K., Lipsitz, S.R., Mone, S.M., Colan, S.D., Orav, E.J., Sallan, S.E., Olsen, J.H., Hertz, H., Jacobsen, J.R. and Lipshultz, S.E. (1998) Relationship between Cumulative Anthracycline Dose and Late Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology, 16, 545-550.
[22] Gharib, M.I. and Burnett, A.K. (2000) Chemotherapy-Induced Cardiotoxicity: Current Practice and Prospects of Prophylaxis. European Journal of Heart Failure, 4, 235-242.
[23] Godoy, L.Y., Fukushige, J., Igarashi, H., Matsuzaki, A. and Ueda, K. (1997) Anthracycline-Induced Cardiotoxicity in Children with Malignancies. Acta Paediatrica Japonica, 39, 188-193.
http://dx.doi.org/10.1111/j.1442-200X.1997.tb03579.x
[24] Lipshultz, S.E. and Adams, M.J. (2010) Cardiotoxicity after Childhood Cancer: Beginning with the End in Mind. Journal of Clinical Oncology, 28, 1276-1281.
http://dx.doi.org/10.1200/JCO.2009.26.5751
[25] Court, O., Kumar, A. and Parrillo, J.E. (2002) Clinical Review: Myocardial Depression in Sepsis and Septic Shock. Critical Care, 6, 500-508.
http://dx.doi.org/10.1186/cc1822
[26] Kowald, A. and Klipp, E. (2004) Alternative Pathways Might Mediate Toxicity of High Concentrations of Superoxide Dismutase. Annals of the New York Academy of Sciences, 1019, 370-374.
http://dx.doi.org/10.1196/annals.1297.065
[27] Shankar, S.M., Marina, N., Hudson, M.M., Hodgson, D.C., Adams, M.J., Landier, W., Bhatia, S., Meeske, K., Chen, M.H., Kinahan, K.E., Steinberger, J. and Rosenthal, D. (2008) Monitoring for Cardiovascular Disease in Survivors of Childhood Cancer: Report from the Cardiovascular Disease Task Force of the Children’s Oncology Group. Pediatric, 121, e387-396.
http://dx.doi.org/10.1542/peds.2007-0575
[28] Lipshultz, S.E., Giantris, A.L., Lipsitz, S.R., Kimball Dalton, V., Asselin, B.L., Barr, R.D., Clavell, L.A., Hurwitz, C.A., Moghrabi, A., Samson, Y., Schorin, M.A., Gelber, R.D., Sallan, S.E. and Colan, S.D. (2002) Doxorubicin Administration by Continuous Infusion Is Not Cardioprotective: The Dana-Farber 91-01 Acute Lymphoblastic Leukemia Protocol. Journal of Clinical Oncology, 20, 1677-1682.
http://dx.doi.org/10.1200/JCO.20.6.1677
[29] Lipshultz, S.E., Lipsitz, S.R., Sallan, S.E., Dalton, V.M., Mone, S.M., Gelber, R.D. and Colan, S.D. (2005) Chronic Progressive Cardiac Dysfunction Years after Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology, 23, 2629-2636.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.