Seminars in Radiation Oncology
Volume 13, Issue 3 , Pages 346-356 , July 2003

Radiation-associated cardiovascular disease: manifestations and management

  • M.Jacob Adams

      Affiliations

    • Department of Pediatrics, University of Rochester School of Medicine and Dentistry and Golisano Children’s Hospital at Strong, Rochester, NY USA
    • Department of Community and Preventive Medicine, and Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    • ,
  • Steven E Lipshultz

      Affiliations

    • Department of Pediatrics, University of Rochester School of Medicine and Dentistry and Golisano Children’s Hospital at Strong, Rochester, NY USA
    • Department of Community and Preventive Medicine, and Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    • ,
  • Cindy Schwartz

      Affiliations

    • Department of Pediatrics, Division of Pediatric Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA
    • ,
  • Luis F Fajardo

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA
    • ,
  • Veronique Coen

      Affiliations

    • Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    • ,
  • Louis S Constine

      Affiliations

    • Department of Pediatrics, University of Rochester School of Medicine and Dentistry and Golisano Children’s Hospital at Strong, Rochester, NY USA
    • Corresponding Author InformationAddress reprint requests to Louis S. Constine, MD, Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 647, Rochester, NY 14642, USA

References 

  1. Hancock SL, Hoppe RT. Long-term complications of treatment and causes of mortality after Hodgkin’s disease. Semin Radiat Oncol. 1996;6:225–242
  2. Lee CK, Aeppli D, Nierengarten ME. The need for long-term surveillance for patients treated with curative radiotherapy for Hodgkin’s disease (University of Minnesota experience). Int J Radiat Oncol Biol Phys. 2000;48:169–179
  3. Mauch P, Kalish LA, Marcus KC. Long-term survival in Hodgkin’s disease (Relative impact of mortality, second tumors, infection and cardiovascular disease). Cancer J Sci Am. 1995;1:33–42
  4. Hancock SL, Tucker MA, Hoppe RT. Factors affecting late mortality from heart disease after treatment for Hodgkin’s disease. JAMA. 1993;270:1949–1955
  5. Reinders JG, Heijmen BJ, Olofsen-van Acht MJ. Ischemic heart disease after mantlefield irradiation for Hodgkin’s disease in long-term follow-up. Radiother Oncol. 1999;51:35–42
  6. Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin’s disease in children and adolescents. J Clin Oncol. 1993;11:1208–1215
  7. Totterman KJ, Pesonen E, Siltanen P. Radiation related chronic heart disease. Chest. 1983;83:875–878
  8. Boivin J-F, Hutchison G, Lubin J. Coronary artery disease mortality in patients treated for Hodgkin’s disease. Cancer. 1992;69:1241–1247
  9. Cuzick J, Stewart H, Rutqvist L. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol. 1994;12:447–453
  10. Jones JM, Ribeiro GG. Mortality pattern over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. Clin Radiol. 1989;40:204–208
  11. Paszat LF, Mackillop WJ, Groome PA. Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol. 1998;16:2625–2631
  12. Early Breast Cancer Trialists’ Collaborative Group . Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer (An overview of randomised trials). Lancet. 2000;355:1757–1770
  13. Gyenes G, Rutqvist LE, Liedberg A. Long-term cardiac morbidity and mortality in a randomized trial of pre- and post-operative radiation therapy versus surgery alone in primary breast cancer. Radiother Oncol. 1998;48:185–190
  14. Rutqvist LE, Johansson H. Mortality by laterality of the primary tumor among 55, 000 breast cancer patients from the Swedish center registry. Br J Cancer. 1990;61:866–868
  15. Nixon AJ, Manola J, Gelman R. No long-term increase in cardiac related mortality after breast-conserving surgery and radiation therapy using modern techniques. J Clin Oncol. 1998;16:1374–1379
  16. Paszat LF, Mackillop WJ, Groome PA. Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer (Population-based study in Ontario, Canada). Int J Radiat Oncol Biol Phys. 1999;43:755–762
  17. Cameron EH, Lipshultz SE, Tarbell NJ. Cardiovascular disease in long-term survivors of pediatric Hodgkin’s disease. Prog Pediatr Cardiol. 1998;8:139–144
  18. Tolba KA, Deliargyris EN. Cardiotoxicity of cancer therapy. Cancer Invest. 1999;17:408–422
  19. Burns RJ, Bar Shlomo BZ, Druck MN. Detection of radiation cardiomyopathy by gated radionuclide angiography. Am J Med. 1983;74:297–301
  20. Constine LS, Schwartz RG, Savage D. Cardiac function, perfusion, and morbidity in irradiated long-term survivors of Hodgkin’s disease. Int J Radiat Oncol Biol Phys. 1997;39:897–906
  21. Hardenbergh PH, Munley MT, Bentel GC. Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin (preliminary results). Int J Radiat Oncol Biol Phys. 2001;49:1023–1028
  22. Gyenes G, Fornander T, Carlens P. Myocardial damage in breast cancer patients treated with adjuvant radiotherapy (A prospective study). Int J Radiat Oncol Biol Phys. 1996;36:899–905
  23. Fajardo LF, Stewart JR. Pathogenesis of radiation-induced myocardial fibrosis. Lab Invest. 1973;29:244–257
  24. Billingham ME, Bristow MR, Glatstein E. Adriamycin cardiotoxicity (Endomyocardial biopsy evidence of enhancement by irradiation). Am J Surg Pathol. 1977;1:17–23
  25. Merrill J, Geco FA, Zimber H, et al.  Adriamycin and radiation (Synergistic cardiotoxicity). Ann Intern Med. 1975;82:122–123
  26. Kinsella TJ, Ahmann DL, Giuliani ER. Adriamycin toxicity in stage IV breast cancer (Possible enhancement with prior left chest radiation therapy). Int J Radiat Oncol Biol Phys. 1979;5:1979–2002
  27. Fajardo LF, Eltringham JR, Stewart JR. Combined cardiotoxicity of adriamycin and x-radiation. Lab Invest. 1976;34:86–96
  28. Eltringham JR, Fajardo LF, Stewart JR. Investigation of cardiotoxicity in rabbits from adriamycin and fractionated cardiac irradiation (Preliminary results). Front Radiat Ther Oncol. 1979;13:21–35
  29. Pihkala J, Saarinen U, Lundstrom U. Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation. Eur J Cancer. 1996;32A:97–103
  30. Leonard GT, Green DM, Spangenthal EL, et al.  Cardiac mortality and morbidity after treatment for Hodgkin disease during childhood and adolescence. Pediatr Res. 2000;47:46A; (abstr)
  31. Shapiro CL, Hardenbergh PH, Gelman R. Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol. 1998;16:3493–3501
  32. Stewart JR, Fajardo LF. Radiation-induced heart disease (An update). Prog Cardiovasc Dis. 1984;27:173–194
  33. Carmel RJ, Kaplan HS. Mantle irradiation in Hodgkin’s disease. Cancer. 1976;37:2813–2815
  34. Carlson RG, Mayfield W, Normann S. Radiation-associated valvular disease. Chest. 1991;99:538–545
  35. Glanzmann C, Huguenin P, Lutolf UM. Cardiac lesions after mediastinal radiation for Hodgkin’s disease. Radiother Oncol. 1994;30:43–54
  36. Gustavsson A, Eskilsson J, Landberg T. Late cardiac effects after mantle radiation in patients with Hodgkin’s disease. Ann Oncol. 1990;1:355–363
  37. Lund MB, Ihlen H, Voss BM. Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin’s disease (An echocardiographic study). Heart. 1996;75:591–595
  38. Gustavsson A, Bendahl PO, Cwikiel M. No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer. Int J Radiat Oncol Biol Phys. 1999;43:745–754
  39. Larsen RL, Jakacki RI, Vetter VL. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992;70:73–77
  40. Orzan F, Brusca A, Gaita F. Associated cardiac lesions in patients with radiation-induced complete heart block. Int J Cardiol. 1993;39:151–156
  41. Slama MS, Le Guludec D, Sebag C. Complete atrioventricular block following mediastinal irradiation (A report of six cases). PACE. 1991;14:1112–1118
  42. Pohjola-Sintonen S, Totterman KJ, Kupari M. Sick sinus syndrome as a complication of mediastinal radiation therapy. Cancer. 1990;65:2494–2496
  43. Strender LE, Lindahl J, Larsson LE. Incidence of heart disease and functional significance of changes in electrocardiogram 10 years after radiotherapy for breast cancer. Cancer. 1986;57:929–934
  44. Adams MJ, Lipitz SR, Colan SD, et al.  Late cardiotoxicity of mediastinal irradiation. ASCO 2003 Annual Meeting, Chicago, IL, June 1. 2003;
  45. Hancock SL. Cardiac toxicity after cancer therapy. Presented at Research Issues In Cancer Survivorship. Bethesda, MD, March 3. 1998;
  46. Constine LS. Late effects of cancer treatment. In:  Halperin EC,  Constine LS,  Tarbell NJ editor. Pediatric Radiation Oncology. New York, NY: Lippincott, Williams and Wilkins; 1999;p. 457–537
  47. Warda M, Khan A, Massumi A. Radiation-induced valvular dysfuction. J Am Coll Cardiol. 1983;2:180–185
  48. Van Renterghem D, Hamers J, De Shryver A. Chylothorax after mantle irradiation for Hodgkin’s disease. Respiration. 1985;48:188–189
  49. Polikar R, Burger AG, Scherrer U. The thyroid and the heart. Circulation. 1993;87:1435–1441
  50. Steinherz LJ, Graham T, Hurwitz R. Guidelines for cardiac monitoring of children during and after anthracycline therapy (Report of the cardiology committee of the Children’s Cancer Study Group). 1992;89:942–949
  51. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults . Executive summary of the Third Report of The National Cholesterol Education Program. JAMA. 2001;285:2486–2497
  52. Maunoury C, Pierga JY, Valette H. Myocardial perfusion damage after mediastinal irradiation for Hodgkin’s disease (A Thalium-201 single photon emission tomography study). Eur J Nucl Med. 1992;19:871–873
  53. Mancini DM, Eisen H, Kussmaul W. Value of peak exercise oxygen consumption for the optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991;83:778–786
  54. Pihkala J, Happonen JM, Virtanen K. Cardiopulmonary evaluation of exercise tolerance after chest irradiation and anticancer chemotherapy in children and adolescents. Pediatrics. 1995;95:722–726
  55. Patel AR, Konstam MA. Assessment of the patient with heart failure. In:  Crawford MH,  DiMarco JP editor. Cardiology. London: Mosby International Ltd; 2001;p. 5–10
  56. Orzan F, Brusca A, Conte MR. Severe coronary artery disease after radiation therapy of the chest and mediastinum (Clinical presentation and treatment). Br Heart J. 1993;69:496–500
  57. Levitt GA, Jenney MEM. The reproductive system after childhood cancer. Br J Obstet Gynaecol. 1998;105:946–953
  58. Morton DL, Glancy D, Joseph WL. Management of patients with radiation-induced pericarditis with effusion (A note on the development of regurgitaion in two of them). Chest. 1973;64:291–297
  59. McEniery PT, Dorosti K, Schiavone W. Clinical and angiographic features of coronary artery disease after chest irradiation. Am J Card. 1987;60:1020–1024
  60. Hicks GL. Coronary artery operation in radiation-associated atherosclerosis (Long-term follow-up). Ann Thorac Surg. 1992;53:670–674
  61. Gharagozloo F, Clements I, Mullany C. Use of the internal mammary artery for myocardial revascularization in a patient with radiation-induced coronary artery disease. Mayo Clin Proc. 1992;67:1081–1084
  62. Handa N, McGregor CG, Danielson GK. Coronary artery bypass grafting in patients with previous mediastinal radiation therapy. J Thorac Cardiovasc Surg. 1999;117:1136–1142
  63. van Son JA, Noyez L, van Asten W. Use of internal mammary artery in myocardial revascularization after mediastinal irradiation. J Thorac Cardiovasc Surg. 1992;104:1539–1544
  64. Reber D, Birnbaum DE, Tollenaere P. Heart diseases following mediastinal irradiation (Surgical management). Eur J Cardiothorac Surg. 1995;9:202–205
  65. Mittal S, Berko B, Bavaria J. Radiation-induced cardiovascular dysfunction. Am J Cardiol. 1996;78:114–115
  66. Stewart JR, Fajardo LF, Gillette SM. Radiation injury to the heart. Int J Radiat Oncol Biol Phys. 1995;31:1205–1211
  67. Fajardo LF, Berthrong M, Anderson RE. Radiation Pathology. Oxford, England: Oxford University Press; 2001;
  68. Lipshultz SE, Sallan SE. Cardiovascular abnormalities in long-term survivors of childhood malignancy. J Clin Oncol. 1993;11:1199–1203
  69. Veinot JP, Edwards WD. Pathology of radiation-induced heart disease (A surgical and autopsy study of 27 cases). Hum Pathol. 1996;27:766–773
  70. Brosius FC, Waller BF, Roberts WC. Radiation heart disease. Analysis of 16 young (aged 15-33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med. 1981;70:519–530
  71. Adams MJ, Constine LS, Lipshultz SE. Radiation. In:  Crawford MH,  DiMarco JP editor. Cardiology. London: Mosby International Ltd; 2001;p. 1–8
  72. Glanzmann C, Kaufmann P, Jenni R. Cardiac risk after mediastinal irradiation for Hodgkin’s disease. Radiother Oncol. 1998;46:51–62
  73. Jakacki RI, Goldwein JW, Larsen RL. Cardiac dysfunction following spinal irradiation during childhood. J Clin Oncol. 1993;11:1033–1038
  74. Perrault DJ, Levy M, Herman JD. Echocardiographic abnormalities following cardiac radiation. J Clin Oncol. 1985;3:546–551

☆ Supported by the National Institute of Cancer (CA-79060); National Heart, Lung, and Blood Institute (HL-53392), (5K30HL04161), Preventive Cardiology Training Grant (1T32HL07937) and Wilmot Cancer Research Fellowship of the James P. Wilmot Foundation.

PII: S1053-4296(03)00026-2

doi: 10.1016/S1053-4296(03)00026-2

Seminars in Radiation Oncology
Volume 13, Issue 3 , Pages 346-356 , July 2003

Article Tools