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Late Effects to the Heart: Bibliography

These references are separated into anthracycline-induced damage (just below) and radiation-induced damage.

Anthracycline-induced cardiotoxicity

If you search MedLine for anthracycline-induced heart damage, you find many articles. I have not included the articles from the late 1970s-1980s; these articles documented the discovery of this type of damage and set the max dose to 500 mg/m2.

Another interesting search is the use of dexrazoxane to protect the heart during anthracycline treatment.

Anthracyclines are used in many adult cancers. Pediatric reactions to anthracyclines cannot be generally accepted as the same as adult reactions.


Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines. Jeffrey H. Silber, Avital Cnaan, Bernard J. Clark, Stephen M. Paridon, Alvin J. Chin, Jack Rychik, Alexa N. Hogarty, Mitchell I. Cohen, Gerald Barber, Monika Rutkowski, Thomas R. Kimball, Cynthia Delaat, Laurel J. Steinherz, Huaqing Zhao. Journal of Clinical Oncology, Vol 22, No 5 (March 1), 2004: pp. 820-828. Abstract.


Comparison of left ventricular function by echocardiogram in patients with Wilms' tumor treated with anthracyclines versus those not so treated. Iarussi D, Indolfi P, Pisacane C, Casale F, Martino V, Fusco A, De Rosa E, Di Tullio MT, Calabro R. Am J Cardiol. 2003 Aug 1;92(3):359-61. PubMed abstract.


Cardiorespiratory exercise capacity and its relation to a new doppler index in children previously treated with anthracycline. Sato T, Harada K, Tamura M, Watanabe A, Ishii M, Takada G. J Am Soc Echocardiogr 2001 Apr;14(4):256-63. PubMed abstract.

Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. Kremer LC, van Dalen EC, Offringa M, Ottenkamp J, Voute PA. J Clin Oncol 2001 Jan 1;19(1):191-6. PubMed abstract. On Medscape.

Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake. Nousiainen T, Vanninen E, Jantunen E, Remes J, Kuikka J, Hartikainen J. Clin Physiol 2001 Jan;21(1):123-8. PubMed abstract.


Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy. Ishii M, Tsutsumi T, Himeno W, Eto G, Furui J, Hashino K, Sugahara Y, Muta H, Akagi T, Ando A, Eguchi H, Kato H. Am J Cardiol 2000 Dec 1;86(11):1279-81, A9. PubMed abstract. (A more-sensitive way to pick up heart damage.)

Angiotensin-converting enzyme inhibitor therapy for ventricular dysfunction in infants, children and adolescents: a review. Grenier MA, Fioravanti J, Truesdell SC, Mendelsohn AM, Vermilion RP, Lipshultz SE. Prog Pediatr Cardiol. 2000 Nov 4;12(1):91-111. PubMed abstract.

Advances in the Diagnosis and Treatment of Pediatric Tumors. American Society of Clinical Oncology 36th Annual Meeting, May 2000. Talks about A-CHF a couple scrolls down.

Cardiac toxicity after anthracycline chemotherapy in childhood. Iarussi D, Indolfi P, Galderisi M, Bossone E. Herz 2000 Nov; 25(7):676-88. PubMed abstract. "Anthracycline-induced congestive heart failure is usually due to permanent changes in the myocardium, changes most consistent with the contractile failure of cardiomyopathy."

Congestive heart failure (CHF) after treatment for Wilm's tumor. A report from the National Wilms Tumor Study Group. Green, DM, Nan B, Grigoriev Y, Takashima J, Norkool P, D'Angio G, Breslow, N. J. Pediatric Hematol. Oncol. 22(4) 200. 2000. PubMed Abstract.


Left ventricular diastolic filling patterns associated with progressive anthracycline-induced myocardial damage: A prospective study. Bu'Lock FA, Mott MG, Oakhill A, Martin RP. Pediatr Cardiol 1999 Jul-Aug;20(4):252-63. PubMed abstract.

Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography. Suzuki J, Yanagisawa A, Shigeyama T, Tsubota J, Yasumura T, Shimoyama K, Ishikawa K. Angiology 1999 Jan;50(1):37-45. PubMed abstract.

Doxorubicin-induced cardiomyopathy. Singal PK, Iliskovic N. N Engl J Med 1998 Sep 24;339(13):900-5. No abstract on PubMed, but go to NEJM site for more. Several interesting comments - arguments and rebuttals - about this article in N Engl J Med. 1999 Feb 25;340(8):653-4.


Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. Nysom K, Holm K, Lipsitz SR, Mone SM, Colan SD, Orav EJ, Sallan SE, Olsen JH, Hertz H, Jacobsen JR, Lipshultz SE. J Clin Oncol 1998 Feb;16(2):545-50. PubMed abstract.

Epidemiology of anthracycline cardiotoxicity in children and adults. Grenier MA, Lipshultz SE. Semin Oncol 1998 Aug;25(4 Suppl 10):72-85. PubMed abstract.

Anthracycline-induced cardiotoxicity in children and young adults. Giantris A, Abdurrahman L, Hinkle A, Asselin B, Lipshultz SE. Crit Rev Oncol Hematol 1998 Jan;27(1):53-68. A review article; no abstract online available.

Physical performance in long-term survivors of acute leukaemia in childhood. P. Black, P. Gutjahr, H. Stopfkuchen. European Journal of Pediatrics, Volume 157 Issue 6 (1998) pp 464-467. Abstract. Abstract The aim of this study was to assess the physical performance in long-term survivors of of anthracycline therapy. Electrocardiography, echocardiography and spiroergometry were carried out on 56 patients aged 9-28 years, of whom 44 patients had been treated with 15-483 mg/m2 doxorubicin (or equivalent). Acute leukaemia had been diagnosed 1.5-16 years earlier. Of the patients 75% reached normal maximal oxygen uptake, 69% normal oxygen uptake at the anaerobic threshold and 95% normal maximal work rate. Of the patients 75% achieved adequate values for maximal heart rate and 78% normal blood lactate concentration. No difference was seen between patients treated with and without anthracyclines.

Conclusion: The results of this study provide little evidence for cardiopulmonary impairment in long-term survivors of ALL. Both the cardiac function, as evaluated by ECG and echocardiography, and the physical performance in spiroergometry are normal in a large number of these patients. Anthracycline treatment does not appear to have a negative effect on these parameters.

Doxorubicin-Induced Cardiomyopathy. Singal, Pawan K., Iliskovic, Natasha. NEJM, Vol 339, No. 13, 1998. (I have a copy of this article.)


Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity. Sorensen K, Levitt G, Bull C, Chessells J, Sullivan I. J Clin Oncol 1997 Jan;15(1):61-8. PubMed abstract. Good, talks about medium doses, 23% incidence.

Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. J Clin Oncol 1997 Apr;15(4):1544-52. PubMed abstract.


Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation. Pihkala J, Saarinen UM, Lundstrom U, Virtanen K, Virkola K, Siimes MA, Pesonen E. Eur J Cancer 1996 Jan;32A(1):97-103. PubMed abstract.

Cardiorespiratory status after treatment for acute lymphoblastic leukemia. Turner-Gomes SO, Lands LC, Halton J, Hanning RM, Heigenhauser GJ, Pai M, Barr R. Med Pediatr Oncol 1996 Mar; 26(3):160-5. PubMed abstract. "Despite lack of overt morbidity in our pt population, subtle abnormalities persist in cardiac function while pulmonary function is normal. Longitudinal studies will identify if further abnormalities or overt morbidity develop. In later years, continuing obesity and a sedentary state may contribute to clinically relevant heart disease."

Review of tests for monitoring doxorubicin-induced cardiomyopathy. Ganz WI, Sridhar KS, Ganz SS, Gonzalez R, Chakko S, Serafini A. Oncology 1996 Nov-Dec;53(6):461-70. PubMed abstract. (Good discussion in abstract.)

Johnson, G.L., et al. "Late echocardiographic findings following childhood chemotherapy with normal serial cardiac monitoring." Journal of Pediatrics Hematology/Oncology 18, no. 1 (Feb 1996): 72-5.


Cardiac function in Wilms' tumor survivors. Sorensen K, Levitt G, Sebag-Montefiore D, Bull C, Sullivan I. J Clin Oncol 1995 Jul;13(7):1546-56. PubMed abstract.

Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, Orav EJ, Gelber RD, Colan SD. New England Journal of Medicine 332, no. 26 (29 June 1995): 1738-43. PubMed abstract.

Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series of 15 patients. Steinherz LJ, Steinherz PG, Tan C. Med Pediatr Oncol 1995 Jun;24(6):352-61. PubMed abstract.


Monitoring for anthracycline cardiotoxicity. Lipshultz SE, Sanders SP, Goorin AM, Krischer JP, Sallan SE, Colan SD. Pediatrics 93 (1994): 433-7. PubMed abstract.

Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection. Ali MK, Ewer MS, Gibbs HR, Swafford J, Graff KL. Cancer 1994 Jul 1;74(1):182-8. PubMed abstract. Very interesting.

Cardiac diastolic function in pediatric patients receiving doxorubicin. Ewer MS, Ali MK, Gibbs HR, Swafford J, Graff KL, Cangir A, Jaffe N, Thapar MK. Acta Oncol 1994;33(6):645-9. PubMed abstract.


Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, Sandor G, Benson L, Williams R. Pediatrics 1992 May;89(5 Pt 1):942-9. PubMed abstract.

Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Larsen RL, Jakacki RI, Vetter VL, Meadows AT, Silber JH, Barber G. Am J Cardiol 1992 Jul 1;70(1):73-7. PubMed abstract. Good: 244 mg/m2 dose, compares with/without radiation, monitors arrrhymias.


Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. N Engl J Med. 1991 Mar 21;324(12):843-5. PubMed abstract.

Cardiac toxicity 4 to 20 years after completing anthracycline therapy. Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. JAMA 1991 Sep 25;266(12):1672-7. PubMed abstract.

Functional myocardial impairment in children treated with anthracyclines for cancer. Yeung ST, Yoong C, Spink J, et al. Lancet, 1991; 337; 816-8. PubMed abstract not available; article too old to be online at The Lancet.

Radiation-induced Cardiotoxicity


Cardiac damage following therapeutic chest irradiation. Importance, evaluation and treatment. Vallebona A. Minerva Cardioangiol. 2000 Mar;48(3):79-87. Review. PubMed Abstract.


Fatal coronary heart disease in a young woman 20 years after radiotherapy for Hodgkin disease. [Article in Norwegian] Skulstad H, Backstrom J. Tidsskr Nor Laegeforen 1999 Apr 20;119(10):1431-2. PubMed Abstract.

Ischemic heart disease after mantle field irradiation for Hodgkin's disease in long-term follow-up. Reinders, J.G., et al. Radiotherapy and Oncology 51, no. 1 (Apr 1999): 35-42.


Cardiac risk after mediastinal irradiation for Hodgkin's disease. Glanzmann C, Kaufmann P, Jenni R, Hess OM, Huguenin P. Radiother Oncol 1998 Jan;46(1):51-62. PubMed Abstract.


Cardiac function, perfusion, and morbidity in irradiated long-term survivors of Hodgkin's disease. Constine, L.S., et al. International Journal of Radiation Oncology and Biological Physics 39, no. 4 (1 Nov 1997): 897-906.

Cardiovascular function in children following bone marrow transplant: a cross-sectional study. Eames, G.M., et al. Bone Marrow Transplantation 19, no. 1 (Jan 1997): 61-6.

Coronary artery and aortic valve disease as a long-term sequel of mediastinal and thoracic irradiation. Kleikamp, G., U. Schnepper, and R. Korfer. Thoracic and Cardiovascular Surgeon 45, no. 1 (Feb 1997): 27-31.


Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin's disease: an echocardiographic study. Lund, M.B., et al. Heart 75 (1996): 591-5.

Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation. Pinkala, J., et al. European Journal of Cancer 32A (1996): 97-103.


Cardiac disease after chest irradiation for Hodgkin's disease: incidence in 108 patients with long follow-up. Piovaccari G, Ferretti RM, Prati F, Traini AM, Gobbi M, Caravita L, Branzi A, Magnani B. Int J Cardiol 1995 Mar 24;49(1):39-43. PubMed Abstract.

Cardiac function in Wilms' tumor survivors. Sorensen, K., et al. Journal of Clinical Oncology 13, no. 7 (Jul 1995): 1546-56.


Cardiac Disease following treatment of Hodgkin's disease in children and adolescents. Hancock, S.L., et al. Journal of Clinical Oncology 11 (1993): 1208-15.

Factors affecting the late mortality from heart disease after treatment of Hodgkin's disease. Hancock, S.L., et al. Journal of the American Medical Association 270 (1993): 1949-55.

Cardiac dysfunction following spinal irradiation during childhood. Jakacki, R.I., et al. Journal of Clinical Oncology 11, no. 6 (1993): 1033-8.


Late cardiac effects after mantle radiotherapy in patients with Hodgkin's disease. Gustavsson, A., et al. Annals of Oncology 1, no. 5 (Sept 1990): 355-63.

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