Advertisement

Cardiotoxicity: Left Ventricular Dysfunction

  • Stefano Oliva
  • Ines Monte
  • Daniela Cardinale
Chapter

Abstract

The left ventricular dysfunction (LVD), from asymptomatic reduction of left ventricular ejection fraction (LVEF) up to heart failure (HF), is probably the most studied and feared late effect of anticancer therapy because it is often unpredictable and because it has a poor prognosis. It may result from many anticancer drugs through different mechanisms and often for a different combination of cardiotoxic effects in a polychemotherapy schedule.

References

  1. 1.
    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. Eur Heart J Cardiovasc Imaging. 2014;15(10):1063–93.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Smith LA, Cornelius VR, Plummer CJ, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 2010;10:337–50.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol. 1998;25(10):72–85.PubMedGoogle Scholar
  4. 4.
    Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710–7.CrossRefGoogle Scholar
  5. 5.
    Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–47.CrossRefPubMedGoogle Scholar
  7. 7.
    Vejpongsa P, Yeh ET. Topoisomerase 2β: a promising molecular target for primary prevention of anthracycline-induced cardiotoxicity. Clin Pharmacol Ther. 2014;95(1):45–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18(11):1639–42.CrossRefPubMedGoogle Scholar
  9. 9.
    Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart. 2008;94(4):525–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.CrossRefPubMedGoogle Scholar
  11. 11.
    Bowles EJA, 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(17):1293–305.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hershman DL, McBride RB, Eisemberger A, et al. Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26(19):3159–65.CrossRefPubMedGoogle Scholar
  13. 13.
    Batist G, Ramakrishnan G, Rao CS, et al. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol. 2001;19(5):1444–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Bird BR, Swain SM. Cardiac toxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res. 2008;14(1):14–24.CrossRefPubMedGoogle Scholar
  15. 15.
    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(11):783–92.CrossRefPubMedGoogle Scholar
  16. 16.
    Dahabreh IJ, Linardou H, Siannis F, et al. Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist. 2008;13(6):620–30.CrossRefPubMedGoogle Scholar
  17. 17.
    de Korte MA, et al. 111Indium trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: A clue to uncover the mechanism of trastuzumab-related cardiotoxicity. Eur J Cancer. 2007;43:2046–51.CrossRefPubMedGoogle Scholar
  18. 18.
    Ewer MS, et al. Changes in left ventricular ejection fraction (LVEF) from baseline to re-treatment with trastuzumab in a selected population. JCO. 2005;23:7820–6.CrossRefGoogle Scholar
  19. 19.
    Ewer MS, Lippman SM. Type 2 chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23(13):2900–2.CrossRefPubMedGoogle Scholar
  20. 20.
    Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370:2011–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Richards CJ, Je Y, Schutz FA, et al. Incidence and risk of congestive heart failure in patients with renal and nonrenal cell carcinoma treated with sunitinib. J Clin Oncol. 2011;29:3450–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, et al. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol. 2008;52:1574–80.CrossRefPubMedGoogle Scholar
  23. 23.
    Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH, et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012;33:1268–78.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Tham E, Chow K, Spavor M, Pagano JJ, Haykowsky M, Thompson RJ. Degree of diffuse fibrosis measured by MRI correlates with LV remodelling in childhood cancer survivors after anthracycline chemotherapy. J Cardiovasc Magn Reson. 2011;13:P276.CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Neilan TG, Coelho-Filho OR, Shah RV, Feng JH, Pena-Herrera D, Mandry D, et al. Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy. Am J Cardiol. 2013;111:717–22.CrossRefPubMedGoogle Scholar
  26. 26.
    Schwartz RG, McKenzie WB, Alexander J, Sager P, D’Souza A, Manatunga A, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med. 1987;82:1109–18.CrossRefPubMedGoogle Scholar
  27. 27.
    Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25:3808–15.CrossRefPubMedGoogle Scholar
  28. 28.
    Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.CrossRefPubMedGoogle Scholar
  29. 29.
    Zamorano JL, Lancellotti P, Munoz DR, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under auspices f the ESC Committee for Practice Guidelines. Eur Heart J 2016; Aug: 2-34. doi:10.109/eurheartj/ehw.211.Google Scholar
  30. 30.
    Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am Soc Echocardiogr 2016;29:277–314.Google Scholar
  31. 31.
    Mele D, Rizzo P, Pollina AV, et al. Cancer therapy-induced cardiotoxicity: role of ultrasound deformation imaging as an aid to early diagnosis. Ultrasound Med Biol. 2015;41(3):627–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N, et al. Normal range of left ventricular 2-dimensional strain: Japanese ultrasound speckle tracking of the left ventricle (JUSTICE) study. Circ J. 2012;76:2623–32.CrossRefPubMedGoogle Scholar
  33. 33.
    Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109:2749–54.CrossRefPubMedGoogle Scholar
  34. 34.
    Cardinale D, Sandri MT. Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis. 2010;53:121–9.CrossRefPubMedGoogle Scholar
  35. 35.
    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(15):1077–84.CrossRefPubMedGoogle Scholar
  36. 36.
    Lefrak EA, Pitha J, Rosenheim S, Gotilieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973;32:302–14.CrossRefPubMedGoogle Scholar
  37. 37.
    Cohen M, Kronzon I, Lebowitz A. Reversible doxorubicin-induced congestive heart failure. Arch Intern Med. 1982;142:1570–1.CrossRefPubMedGoogle Scholar
  38. 38.
    Haq MM, Legha SS, Choksi J, et al. Doxorubicin-induced congestive heart failure in adults. Cancer. 1985;56:1361–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Saini J, Rich MW, Lyss AP. Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases. Ann Intern Med. 1987;106:814–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Jensen BV, Nielsen SL, Skovsgaard T. Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy. Lancet. 1996;347:297–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Fazio S, Calmieri EA, Ferravate B, Bonè F, Biondi B, Saccà L. Doxorubicin-induced cardiomyopathy treated with carvedilol. Clin Cardiol. 1998;21:777–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Noori A, Lindenfeld J, Wolfel E, Ferguson D, Bristow MR, Lowes BD. Beta-blockade in adriamycin-induced cardiomyopathy. J Card Fail. 2000;6:115–9.PubMedGoogle Scholar
  43. 43.
    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.CrossRefPubMedGoogle Scholar
  44. 44.
    Mukai Y, Yoshida T, Nakaike R, et al. Five cases of anthracycline-induced cardiomyopathy effectively treated with carvedilol. Intern Med. 2004;43:1087–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Tallaj JA, Franco V, Rayburn BK, et al. Response of doxorubicin-induced cardiomyopathy to the current management strategy of heart failure. J Heart Lung Transplant. 2005;24:2196–201.CrossRefPubMedGoogle Scholar
  46. 46.
    Tabet JY, Meurin P, Ben Driss A, et al. Beta-blockade intolerance in anthracycline-induced cardiomyopathy. Int J Cardiol. 2006;106:132–4.CrossRefPubMedGoogle Scholar
  47. 47.
    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.CrossRefPubMedGoogle Scholar
  48. 48.
    Cardinale D, Colombo A, Lamantia G, et al. Anthracycline-induced cardiomyopathy. Clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55:213–20.CrossRefPubMedGoogle Scholar
  49. 49.
    Ewer SM, Ewer MS. Cardiotoxicity profile of trastuzumab. Drug Saf. 2008;31:459–67.CrossRefPubMedGoogle Scholar
  50. 50.
    Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007;25:3525–33.CrossRefPubMedGoogle Scholar
  51. 51.
    Tocchetti CG, Ragone G, Coppola C, Rea D, Piscopo G, Scala S. Detection, monitoring, and management of trastuzumab-induced left ventricular dysfunction: an actual challenge. Eur J Heart Fail. 2012;14:130–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Morris PG, Iyengar NM, Patil S, Chen C, Abbruzzi A, Lehman R, Steingart R, Oeffinger KC, Lin N, Moy B, Come SE, Winer EP, Norton L, Hudis CA, Dang CT. Long-term cardiac safety and outcomes of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab with and without lapatinib in patients with early breast cancer. Cancer. 2013;119:3943–51.CrossRefPubMedGoogle Scholar
  53. 53.
    de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J, Jackisch C, Cameron DA, Bell R, Leyland-Jones B, Dowsett M, Gelber RD, Piccart-Gebhart MJ, Suter TM. Trastuzumab-associated cardiac events at 8 years of median follow-up in the herceptin adjuvant trial (BIG 1-01). J Clin Oncol. 2014;32:2159–65.CrossRefPubMedGoogle Scholar
  54. 54.
    Mackey JR, Clemons M, Coté MA, Delgado D, Dent S, Paterson A. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group. Curr Oncol. 2008;15:24–35.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Sengupta PP, Northfelt DW, Gentile F, Zamorano JL, Khandheria BK. Trastuzumab-induced cardiotoxicity: heart failure at the crossroads. Mayo Clin Proc. 2008;83:197–203.CrossRefPubMedGoogle Scholar
  56. 56.
    Jones AL, Barlow M, Barrett-Lee PJ, Canney PA, Gilmour IM, Robb SD. Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring. Br J Cancer. 2009;100:684–92.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Martin M, Esteva FJ, Alba E, Khandheria B, Pérez-Isla L, Garcìa-Sàenz JA. Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist. 2009;14:1–11.CrossRefPubMedGoogle Scholar
  58. 58.
    Thakur A, Witteles R. Cancer therapy-induced left ventricular dysfunction: interventions and prognosis. J Card Fail. 2014;20:155–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity. New insight based on clinical course and response to medical treatment. J Clin Oncol. 2005;23:7820–6.CrossRefPubMedGoogle Scholar
  60. 60.
    Cardinale D, Salvatici M, Sandri MT. Role of biomarkers in cardioncology. Clin Chem Lab Med. 2011;49:1937–48.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Cardiology UnitNational Cancer Institute “Giovanni Paolo II”BariItaly
  2. 2.Cardio-Thorax-Vascular and Transplant DepartmentUniversity of CataniaCataniaItaly
  3. 3.Cardioncology UnitEuropean Institute of OncologyMilanItaly

Personalised recommendations