Skip to main content

Advertisement

Log in

Advanced Heart Failure Due to Cancer Therapy

  • Cardio-Oncology (SA Francis, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Certain chemotherapeutic agents and mediastinal irradiation can be cardiotoxic and place cancer survivors at risk for developing advanced heart failure (HF). Anthracyclines are the prototypical agents associated with left ventricular (LV) dysfunction. Newer agents including trastuzumab and certain tyrosine kinase inhibitors such as sunitinib can also cause cardiomyopathy. Cancer survivors with advanced HF refractory to standard medical management should be considered for advanced therapies, including mechanical circulatory support (MCS) and transplantation. While overall outcomes after MCS and transplantation are similar in cancer survivors compared to other etiologies of HF, patients with radiation-induced restrictive cardiomyopathy have a significantly worse prognosis after transplantation. The increased need for right ventricular (RV) support after MCS in cancer survivors necessitates a careful evaluation for pre-operative RV dysfunction. Special consideration must also be given to the risk for recurrent malignancy, neurocognitive dysfunction, and increased psychological needs in this patient population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Mulrooney DA, Yeazel MW, Kawashima T, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009;339:b4606.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572–82.

    Article  CAS  PubMed  Google Scholar 

  3. van der Pal HJ, van Dalen EC, van Delden E, et al. High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol. 2012;30:1429–37.

    Article  PubMed  Google Scholar 

  4. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342:1077–84.

    Article  CAS  PubMed  Google Scholar 

  5. Oliveira GH, Hardaway BW, Kucheryavaya AY, et al. Characteristics and survival of patients with chemotherapy-induced cardiomyopathy undergoing heart transplantation. J Heart Lung Transplant. 2012;31:805–10. This study compares post-transplant outcomes and complications in 232 chemotherapy induced cardiomyopathy patients to 8,890 non-ischemic cardiomyopathy patients who underwent cardiac transplantation in the U.S. between 1/2000 and 12/2008.

    Article  PubMed  Google Scholar 

  6. Oliveira GH, Dupont M, Naftel D, et al. Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63:240–8. This study compares baseline characteristics, outcomes and survival between chemotherapy induced cardiomyopathy patients and non-ischemic and ischemic cardiomyopathy patients who underwent mechanical circulatory support between 6/2006 and 3/2011.

    Article  PubMed  Google Scholar 

  7. Common Terminology Criteria for Adverse Events (CTCAE). In: http://evs.nci.nih.govftpCTCAEbout.html 2010.

  8. Bristow MR, Billingham ME, Mason JW. Adriamycin cardiotoxicity. Am J Cardiol. 1984;53:263–4.

    Article  CAS  PubMed  Google Scholar 

  9. Lyu YL, Kerrigan JE, Lin CP, et al. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007;67:8839–46.

    Article  CAS  PubMed  Google Scholar 

  10. De Angelis A, Piegari E, Cappetta D, et al. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation. 2010;121:276–92.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc. 2014;3:e000665.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996;125:47–58.

    Article  CAS  PubMed  Google Scholar 

  13. van der Pal HJ, van Dalen EC, Hauptmann M, et al. Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch Intern Med. 2010;170:1247–55.

    PubMed  Google Scholar 

  14. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–7.

    Article  Google Scholar 

  15. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.

    Article  CAS  PubMed  Google Scholar 

  16. Bristow MR, Mason JW, Billingham ME, et al. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J. 1981;102:709–18.

    Article  CAS  PubMed  Google Scholar 

  17. Wojnowski L, Kulle B, Schirmer M, et al. NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation. 2005;112:3754–62.

    Article  CAS  PubMed  Google Scholar 

  18. Blanco JG, Sun CL, Landier W, et al. Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes–a report from the Children's Oncology Group. J Clin Oncol. 2012;30:1415–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Plana JC, Galderisi M, Barac A, et al. Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27:911–39.

    Article  PubMed  Google Scholar 

  20. Steinherz LJ, Steinherz PG, Tan CT, et al. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991;266:1672–7.

    Article  CAS  PubMed  Google Scholar 

  21. Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 2002;13:699–709.

    Article  CAS  PubMed  Google Scholar 

  22. Cardinale D, Sandri MT, Colombo A, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109:2749–54.

    Article  CAS  PubMed  Google Scholar 

  23. Daugaard G, Lassen U, Bie P, et al. Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. Eur J Heart Fail. 2005;7:87–93.

    Article  CAS  PubMed  Google Scholar 

  24. Vogelsang TW, Jensen RJ, Hesse B, et al. BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxicity. Int J Cardiol. 2008;124:193–7.

    Article  PubMed  Google Scholar 

  25. Legha SS, Benjamin RS, Mackay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982;96:133–9.

    Article  CAS  PubMed  Google Scholar 

  26. Smith LA, Cornelius VR, Plummer CJ, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Ryberg M, Nielsen D, Cortese G, et al. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100:1058–67.

    Article  CAS  PubMed  Google Scholar 

  28. Posner LE, Dukart G, Goldberg J, et al. Mitoxantrone: an overview of safety and toxicity. Invest New Drugs. 1985;3:123–32.

    CAS  PubMed  Google Scholar 

  29. Swain SM, Whaley FS, Gerber MC, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15:1318–32.

    CAS  PubMed  Google Scholar 

  30. Tebbi CK, London WB, Friedman D, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol. 2007;25:493–500.

    Article  CAS  PubMed  Google Scholar 

  31. Georgakopoulos P, Roussou P, Matsakas E, et al. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010;85:894–6.

    Article  CAS  PubMed  Google Scholar 

  32. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114:2474–81.

    Article  CAS  PubMed  Google Scholar 

  33. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48:2258–62.

    Article  CAS  PubMed  Google Scholar 

  34. Kaya MG, Ozkan M, Gunebakmaz O, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013;167:2306–10.

    Article  PubMed  Google Scholar 

  35. Bosch X, Rovira M, Sitges M, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61:2355–62.

    Article  CAS  PubMed  Google Scholar 

  36. Seicean S, Seicean A, Plana JC, et al. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60:2384–90.

    Article  CAS  PubMed  Google Scholar 

  37. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010;16:e1–194.

    Article  PubMed  Google Scholar 

  38. van Dalen EC, Caron HN, Kremer LC. Prevention of anthracycline-induced cardiotoxicity in children: the evidence. Eur J Cancer. 2007;43:1134–40.

    Article  PubMed  Google Scholar 

  39. Cardinale D, Colombo A, Torrisi R, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol. 2010;28:3910–6.

    Article  CAS  PubMed  Google Scholar 

  40. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  CAS  PubMed  Google Scholar 

  41. Chen MH, Kerkela R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation. 2008;118:84–95.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Sawyer DB, Zuppinger C, Miller TA, et al. Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation. 2002;105:1551–4.

    Article  CAS  PubMed  Google Scholar 

  43. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21.

    Article  CAS  PubMed  Google Scholar 

  44. Bria E, Cuppone F, Fornier M, et al. Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Treat. 2008;109:231–9.

    Article  CAS  PubMed  Google Scholar 

  45. Bowles EJ, Wellman R, Feigelson HS, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104:1293–305.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Chen J, Long JB, Hurria A, et al. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012;60:2504–12.

    Article  CAS  PubMed  Google Scholar 

  47. Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:3584–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Telli ML, Witteles RM, Fisher GA, et al. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol. 2008;19:1613–8.

    Article  CAS  PubMed  Google Scholar 

  49. Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370:2011–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Choueiri TK, Mayer EL, Je Y, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol. 2011;29:632–8.

    Article  CAS  PubMed  Google Scholar 

  51. Hall PS, Harshman LC, Srinivas S, et al. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail. 2013;1:72–8.

    Article  PubMed  Google Scholar 

  52. Uraizee I, Cheng S, Moslehi J. Reversible cardiomyopathy associated with sunitinib and sorafenib. N Engl J Med. 2011;365:1649–50.

    Article  CAS  PubMed  Google Scholar 

  53. Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–98.

    Article  CAS  PubMed  Google Scholar 

  54. Heidenreich PA, Hancock SL, Vagelos RH, et al. Diastolic dysfunction after mediastinal irradiation. Am Heart J. 2005;150:977–82.

    Article  PubMed  Google Scholar 

  55. Aleman BM, van den Belt-Dusebout AW, De Bruin ML, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007;109:1878–86.

    Article  CAS  PubMed  Google Scholar 

  56. Hooning MJ, Botma A, Aleman BM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99:365–75.

    Article  PubMed  Google Scholar 

  57. Mancini D, Lietz K. Selection of cardiac transplantation candidates in 2010. Circulation. 2010;122:173–83.

    Article  PubMed  Google Scholar 

  58. Jim HS, Phillips KM, Chait S, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. J Clin Oncol. 2012;30:3578–87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Weaver KE, Forsythe LP, Reeve BB, et al. Mental and physical health-related quality of life among U.S. cancer survivors: population estimates from the 2010 National Health Interview Survey. Cancer Epidemiol Biomarkers Prev. 2012;21:2108–17.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Barendswaard EC, Prpic H, Van der Wall EE, et al. Right ventricle wall motion abnormalities in patients treated with chemotherapy. Clin Nucl Med. 1991;16:513–6.

    Article  CAS  PubMed  Google Scholar 

  61. Tanindi A, Demirci U, Tacoy G, et al. Assessment of right ventricular functions during cancer chemotherapy. Eur J Echocardiogr. 2011;12:834–40.

    Article  PubMed  Google Scholar 

  62. Grover S, Leong DP, Chakrabarty A, et al. Left and right ventricular effects of anthracycline and trastuzumab chemotherapy: a prospective study using novel cardiac imaging and biochemical markers. Int J Cardiol. 2013;168:5465–7.

    Article  PubMed  Google Scholar 

  63. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? J Thorac Cardiovasc Surg. 2012;144:584–603.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Viana MB, Vilela MI. Height deficit during and many years after treatment for acute lymphoblastic leukemia in children: a review. Pediatr Blood Cancer. 2008;50:509–16.

    Article  PubMed  Google Scholar 

  65. DePasquale EC, Nasir K, Jacoby DL. Outcomes of adults with restrictive cardiomyopathy after heart transplantation. J Heart Lung Transplant. 2012;31:1269–75. This study describes post-transplant outcomes in chemotherapy and radiation induced cardiomyopathy patients who present with a restrictive rather than dilated cardiac phenotype.

    Article  PubMed  Google Scholar 

  66. Uriel N, Vainrib A, Jorde UP, et al. Mediastinal radiation and adverse outcomes after heart transplantation. J Heart Lung Transplant. 2010;29:378–81.

    Article  PubMed  Google Scholar 

  67. Chang AS, Smedira NG, Chang CL, et al. Cardiac surgery after mediastinal radiation: extent of exposure influences outcome. J Thorac Cardiovasc Surg. 2007;133:404–13.

    Article  PubMed  Google Scholar 

  68. Topilsky Y, Pereira NL, Shah DK, et al. Left ventricular assist device therapy in patients with restrictive and hypertrophic cardiomyopathy. Circ Heart Fail. 2011;4:266–75.

    Article  PubMed  Google Scholar 

  69. Hoy SM. Ponatinib: a review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic leukaemia. Drugs. 2014;74:793–806.

    Article  CAS  PubMed  Google Scholar 

  70. Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367:107–14.

    Article  CAS  PubMed  Google Scholar 

  71. Gottdiener JS, Appelbaum FR, Ferrans VJ, et al. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981;141:758–63.

    Article  CAS  PubMed  Google Scholar 

  72. Cazin B, Gorin NC, Laporte JP, et al. Cardiac complications after bone marrow transplantation. A report on a series of 63 consecutive transplantations. Cancer. 1986;57:2061–9.

    Article  CAS  PubMed  Google Scholar 

  73. Ferrajoli A, O'Brien SM, Cortes JE, et al. Phase II study of alemtuzumab in chronic lymphoproliferative disorders. Cancer. 2003;98:773–8.

    Article  CAS  PubMed  Google Scholar 

  74. Harvey RD. Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib. Clin Pharmacol. 2014;6:87–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Atallah E, Durand JB, Kantarjian H, et al. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood. 2007;110:1233–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Sachin Shah and Anju Nohria declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anju Nohria.

Additional information

This article is part of the Topical Collection on Cardio-Oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, S., Nohria, A. Advanced Heart Failure Due to Cancer Therapy. Curr Cardiol Rep 17, 16 (2015). https://doi.org/10.1007/s11886-015-0570-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-015-0570-3

Keywords

Navigation