Skip to main content

Advertisement

SpringerLink
Log in

Chemotherapy-induced cardiomyopathy

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Cardiomyopathy is an adverse outcome of antineoplastic drug therapy that has become increasingly relevant in the management of cancer survivors. As the efficacy of anticancer treatments has improved, long-term outcomes are altered by the development of cardiotoxicity, which may be associated with an even worse prognosis than that of the underlying malignancy. From the research into mechanisms, prevention, and treatment, the specialized field of cardio-oncology has evolved, but the recognition and appropriate management of these patients is important for the general internist and general cardiologist as well. Although antineoplastic chemotherapy can cause multiple forms of cardiotoxicity, including arrhythmia, pericardial disease, valvular dysfunction, and myocardial ischemia, in this review we will focus on chemotherapeutic agents associated with cardiomyopathies, from the anthracyclines to newer, the so-called targeted agents such as tyrosine kinase inhibitors. We also review the diagnostic modalities for chemotherapy-induced cardiomyopathy as well as the prevention and treatment strategies which may prolong the lives of those suffering from cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91(5):710–717

    Article  Google Scholar 

  2. Haq MM, Legha SS, Choksi J, Hortobagyi GN, Benjamin RS, Ewer M, Ali M (1985) Doxorubicin-induced congestive heart failure in adults. Cancer 56(6):1361–1365

    Article  CAS  PubMed  Google Scholar 

  3. Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97(11):2869–2879. doi:10.1002/cncr.11407

    Article  CAS  PubMed  Google Scholar 

  4. Menna P, Salvatorelli E, Minotti G (2010) Anthracycline degradation in cardiomyocytes: a journey to oxidative survival. Chem Res Toxicol 23(1):6–10. doi:10.1021/tx9003424

    Article  CAS  PubMed  Google Scholar 

  5. Todaro MC, Oreto L, Qamar R, Paterick TE, Carerj S, Khandheria BK (2013) Cardioncology: state of the heart. Int J Cardiol 168(2):680–687. doi:10.1016/j.ijcard.2013.03.133

    Article  PubMed  Google Scholar 

  6. Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, Jones A (2010) Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 10:337. doi:10.1186/1471-2407-10-337

    Article  PubMed Central  PubMed  Google Scholar 

  7. Anderlini P, Benjamin RS, Wong FC, Kantarjian HM, Andreeff M, Kornblau SM, O’Brien S, Mackay B, Ewer MS, Pierce SA et al (1995) Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia. J Clin Oncol 13(11):2827–2834

    CAS  PubMed  Google Scholar 

  8. van Dalen EC, Michiels EM, Caron HN, Kremer LC (2010) Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev 5:CD005006. doi:10.1002/14651858.CD005006.pub4

    PubMed  Google Scholar 

  9. O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C, Group CBCS (2004) Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 15(3):440–449

    Article  PubMed  Google Scholar 

  10. Hudis CA (2007) Trastuzumab—mechanism of action and use in clinical practice. N Engl J Med 357(1):39–51. doi:10.1056/NEJMra043186

    Article  CAS  PubMed  Google Scholar 

  11. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    Article  CAS  PubMed  Google Scholar 

  12. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17(9):2639–2648

    CAS  PubMed  Google Scholar 

  13. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20(5):1215–1221

    Article  CAS  PubMed  Google Scholar 

  14. Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D’Amico R (2012) Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 4:CD006243. doi:10.1002/14651858.CD006243.pub2

    PubMed  Google Scholar 

  15. Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, Martino S, Gralow JR, Dakhil SR, Ingle JN, Winer EP, Gelmon KA, Gersh BJ, Jaffe AS, Rodeheffer RJ (2008) Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol 26(8):1231–1238. doi:10.1200/JCO.2007.13.5467

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ (2007) Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol 25(25):3859–3865. doi:10.1200/JCO.2006.09.1611

    Article  CAS  PubMed  Google Scholar 

  17. Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, Lenihan DJ (2005) Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23(31):7820–7826. doi:10.1200/JCO.2005.13.300

    Article  CAS  PubMed  Google Scholar 

  18. Ewer MS, Lippman SM (2005) Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol 23(13):2900–2902. doi:10.1200/JCO.2005.05.827

    Article  CAS  PubMed  Google Scholar 

  19. Khouri MG, Douglas PS, Mackey JR, Martin M, Scott JM, Scherrer-Crosbie M, Jones LW (2012) Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues. Circulation 126(23):2749–2763. doi:10.1161/CIRCULATIONAHA.112.100560

    Article  PubMed Central  PubMed  Google Scholar 

  20. Guarneri V, Lenihan DJ, Valero V, Durand JB, Broglio K, Hess KR, Michaud LB, Gonzalez-Angulo AM, Hortobagyi GN, Esteva FJ (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24(25):4107–4115. doi:10.1200/JCO.2005.04.9551

    Article  CAS  PubMed  Google Scholar 

  21. Romond EH, Jeong JH, Rastogi P, Swain SM, Geyer CE Jr, Ewer MS, Rathi V, Fehrenbacher L, Brufsky A, Azar CA, Flynn PJ, Zapas JL, Polikoff J, Gross HM, Biggs DD, Atkins JN, Tan-Chiu E, Zheng P, Yothers G, Mamounas EP, Wolmark N (2012) Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 30(31):3792–3799. doi:10.1200/JCO.2011.40.0010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. doi:10.1056/NEJMoa052122

    Article  CAS  PubMed  Google Scholar 

  23. Choueiri TK, Mayer EL, Je Y, Rosenberg JE, Nguyen PL, Azzi GR, Bellmunt J, Burstein HJ, Schutz FA (2011) Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol 29(6):632–638. doi:10.1200/JCO.2010.31.9129

    Article  CAS  PubMed  Google Scholar 

  24. Morandi P, Ruffini PA, Benvenuto GM, La Vecchia L, Mezzena G, Raimondi R (2001) Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide. Bone Marrow Transplant 28(3):277–282. doi:10.1038/sj.bmt.1703132

    Article  CAS  PubMed  Google Scholar 

  25. Goldberg MA, Antin JH, Guinan EC, Rappeport JM (1986) Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood 68(5):1114–1118

    CAS  PubMed  Google Scholar 

  26. Gottdiener JS, Appelbaum FR, Ferrans VJ, Deisseroth A, Ziegler J (1981) Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med 141(6):758–763

    Article  CAS  PubMed  Google Scholar 

  27. Tiersten A, Wo J, Jacobson C, Weitzman A, Horwich T, Hesdorffer C, Savage D, Troxel A (2004) Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer. Breast 13(4):341–346. doi:10.1016/j.breast.2004.02.007

    Article  PubMed  Google Scholar 

  28. Nagi MN, Al-Shabanah OA, Hafez MM, Sayed-Ahmed MM (2011) Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats. J Biochem Mol Toxicol 25(3):135–142. doi:10.1002/jbt.20369

    Article  CAS  PubMed  Google Scholar 

  29. Mythili Y, Sudharsan PT, Sudhahar V, Varalakshmi P (2006) Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced hyperlipidemic cardiomyopathy. Eur J Pharmacol 543(1–3):92–96. doi:10.1016/j.ejphar.2006.06.007

    Article  CAS  PubMed  Google Scholar 

  30. Quezado ZM, Wilson WH, Cunnion RE, Parker MM, Reda D, Bryant G, Ognibene FP (1993) High-dose ifosfamide is associated with severe, reversible cardiac dysfunction. Ann Intern Med 118(1):31–36

    Article  CAS  PubMed  Google Scholar 

  31. Kandylis K, Vassilomanolakis M, Tsoussis S, Efremidis AP (1989) Ifosfamide cardiotoxicity in humans. Cancer Chemother Pharmacol 24(6):395–396

    Article  CAS  PubMed  Google Scholar 

  32. Duran JM, Makarewich CA, Trappanese D, Gross P, Husain S, Dunn J, Lal H, Sharp TE, Starosta T, Vagnozzi RJ, Berretta RM, Barbe M, Yu D, Gao E, Kubo H, Force T, Houser SR (2014) Sorafenib cardiotoxicity increases mortality after myocardial infarction. Circ Res 114(11):1700–1712. doi:10.1161/CIRCRESAHA.114.303200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Telli ML, Witteles RM, Fisher GA, Srinivas S (2008) Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol 19(9):1613–1618. doi:10.1093/annonc/mdn168

    Article  CAS  PubMed  Google Scholar 

  34. Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J, George S, Morgan JA, Harris DM, Ismail NS, Chen JH, Schoen FJ, Van den Abbeele AD, Demetri GD, Force T, Chen MH (2007) Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370(9604):2011–2019. doi:10.1016/S0140-6736(07)61865-0

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Khakoo AY, Kassiotis CM, Tannir N, Plana JC, Halushka M, Bickford C, Trent J 2nd, Champion JC, Durand JB, Lenihan DJ (2008) Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer 112(11):2500–2508. doi:10.1002/cncr.23460

    Article  CAS  PubMed  Google Scholar 

  36. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356(2):115–124. doi:10.1056/NEJMoa065044

    Article  CAS  PubMed  Google Scholar 

  37. Richards CJ, Je Y, Schutz FA, Heng DY, Dallabrida SM, Moslehi JJ, Choueiri TK (2011) Incidence and risk of congestive heart failure in patients with renal and nonrenal cell carcinoma treated with sunitinib. J Clin Oncol 29(25):3450–3456. doi:10.1200/JCO.2010.34.4309

    Article  CAS  PubMed  Google Scholar 

  38. Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26(32):5204–5212. doi:10.1200/JCO.2007.15.6331

    Article  PubMed  Google Scholar 

  39. Perez EA, Koehler M, Byrne J, Preston AJ, Rappold E, Ewer MS (2008) Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc 83(6):679–686. doi:10.4065/83.6.679

    Article  PubMed  Google Scholar 

  40. Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12(8):908–916. doi:10.1038/nm1446

    Article  PubMed  Google Scholar 

  41. Atallah E, Durand JB, Kantarjian H, Cortes J (2007) Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 110(4):1233–1237. doi:10.1182/blood-2007-01-070144

    Article  CAS  PubMed  Google Scholar 

  42. Ran HH, Zhang R, Lu XC, Yang B, Fan H, Zhu HL (2012) Imatinib-induced decompensated heart failure in an elderly patient with chronic myeloid leukemia: case report and literature review. J Geriatr Cardiol JGC 9(4):411–414. doi:10.3724/SP.J.1263.2012.05251

    PubMed  Google Scholar 

  43. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP, Banchs J, Cardinale D, Carver J, Cerqueira M, DeCara JM, Edvardsen T, Flamm SD, Force T, Griffin BP, Jerusalem G, Liu JE, Magalhaes A, Marwick T, Sanchez LY, Sicari R, Villarraga HR, Lancellotti P (2014) 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 27(9):911–939. doi:10.1016/j.echo.2014.07.012

    Article  PubMed  Google Scholar 

  44. Mackay B, Ewer MS, Carrasco CH, Benjamin RS (1994) Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct Pathol 18(1–2):203–211

    Article  CAS  PubMed  Google Scholar 

  45. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula J, Starling RC, Towbin J, Virmani R, American Heart A, American College of C, European Society of C (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 116(19):2216–2233. doi:10.1161/CIRCULATIONAHA.107.186093

    Article  PubMed  Google Scholar 

  46. Meinardi MT, van der Graaf WT, van Veldhuisen DJ, Gietema JA, de Vries EG, Sleijfer DT (1999) Detection of anthracycline-induced cardiotoxicity. Cancer Treat Rev 25(4):237–247. doi:10.1053/ctrv.1999.0128

    Article  CAS  PubMed  Google Scholar 

  47. Cardinale D, Sandri MT, Martinoni A, Tricca A, Civelli M, Lamantia G, Cinieri S, Martinelli G, Cipolla CM, Fiorentini C (2000) Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36(2):517–522

    Article  CAS  PubMed  Google Scholar 

  48. Roziakova L, Bojtarova E, Mistrik M, Dubrava J, Gergel J, Lenkova N, Mladosievicova B (2012) Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation. J Exp Clin Cancer Res CR 31:13. doi:10.1186/1756-9966-31-13

    Article  CAS  PubMed  Google Scholar 

  49. Okumura H, Iuchi K, Yoshida T, Nakamura S, Takeshima M, Takamatsu H, Ikeno A, Usuda K, Ishikawa T, Ohtake S, Matsuda T (2000) Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity. Acta Haematol 104(4):158–163. doi:10.1159/000046508

    Article  CAS  PubMed  Google Scholar 

  50. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M (2012) Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 5(5):596–603. doi:10.1161/CIRCIMAGING.112.973321

    Article  PubMed Central  PubMed  Google Scholar 

  51. Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M (2014) Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol 63(8):809–816. doi:10.1016/j.jacc.2013.10.061

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Auner HW, Tinchon C, Linkesch W, Tiran A, Quehenberger F, Link H, Sill H (2003) Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann Hematol 82(4):218–222. doi:10.1007/s00277-003-0615-3

    CAS  PubMed  Google Scholar 

  53. Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM (2004) Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109(22):2749–2754. doi:10.1161/01.CIR.0000130926.51766.CC

    Article  CAS  PubMed  Google Scholar 

  54. Mitani I, Jain D, Joska TM, Burtness B, Zaret BL (2003) Doxorubicin cardiotoxicity: prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era. J Nucl Cardiol 10(2):132–139. doi:10.1067/mnc.2003.7

    Article  PubMed  Google Scholar 

  55. Schwartz RG, McKenzie WB, Alexander J, Sager P, D’Souza A, Manatunga A, Schwartz PE, Berger HJ, Setaro J, Surkin L et al (1987) Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med 82(6):1109–1118

    Article  CAS  PubMed  Google Scholar 

  56. Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, Tian G, Kirkpatrick ID, Singal PK, Krahn M, Grenier D, Jassal DS (2011) The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol 57(22):2263–2270. doi:10.1016/j.jacc.2010.11.063

    Article  CAS  PubMed  Google Scholar 

  57. Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH (2013) Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr 26(5):493–498. doi:10.1016/j.echo.2013.02.008

    Article  PubMed  Google Scholar 

  58. Walker J, Bhullar N, Fallah-Rad N, Lytwyn M, Golian M, Fang T, Summers AR, Singal PK, Barac I, Kirkpatrick ID, Jassal DS (2010) Role of three-dimensional echocardiography in breast cancer: comparison with two-dimensional echocardiography, multiple-gated acquisition scans, and cardiac magnetic resonance imaging. J Clin Oncol 28(21):3429–3436. doi:10.1200/JCO.2009.26.7294

    Article  PubMed  Google Scholar 

  59. Kalam K, Marwick TH (2013) Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer 49(13):2900–2909. doi:10.1016/j.ejca.2013.04.030

    Article  CAS  PubMed  Google Scholar 

  60. Lipshultz SE, Scully RE, Lipsitz SR, Sallan SE, Silverman LB, Miller TL, Barry EV, Asselin BL, Athale U, Clavell LA, Larsen E, Moghrabi A, Samson Y, Michon B, Schorin MA, Cohen HJ, Neuberg DS, Orav EJ, Colan SD (2010) Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol 11(10):950–961. doi:10.1016/S1470-2045(10)70204-7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA (1997) Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol 15(4):1333–1340

    CAS  PubMed  Google Scholar 

  62. Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, Jones SE, Wadler S, Desai A, Vogel C, Speyer J, Mittelman A, Reddy S, Pendergrass K, Velez-Garcia E, Ewer MS, Bianchine JR, Gams RA (1997) Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 15(4):1318–1332

    CAS  PubMed  Google Scholar 

  63. Lopez M, Vici P, Di Lauro K, Conti F, Paoletti G, Ferraironi A, Sciuto R, Giannarelli D, Maini CL (1998) Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas. J Clin Oncol 16(1):86–92

    CAS  PubMed  Google Scholar 

  64. Marty M, Espie M, Llombart A, Monnier A, Rapoport BL, Stahalova V, Dexrazoxane Study G (2006) Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Ann Oncol 17(4):614–622. doi:10.1093/annonc/mdj134

    Article  CAS  PubMed  Google Scholar 

  65. Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, Cohen GI, Emami B, Gradishar WJ, Mitchell RB, Thigpen JT, Trotti A 3rd, von Hoff D, Schuchter LM (2009) American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 27(1):127–145. doi:10.1200/JCO.2008.17.2627

    Article  CAS  PubMed  Google Scholar 

  66. Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, Inanc T, Oguzhan A, Eryol NK, Topsakal R, Ergin A (2006) Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 48(11):2258–2262. doi:10.1016/j.jacc.2006.07.052

    Article  CAS  PubMed  Google Scholar 

  67. Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzo M, Esteve J (2013) 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 61(23):2355–2362. doi:10.1016/j.jacc.2013.02.072

    Article  CAS  PubMed  Google Scholar 

  68. Seicean S, Seicean A, Alan N, Plana JC, Budd GT, Marwick TH (2013) Cardioprotective effect of beta-adrenoceptor blockade in patients with breast cancer undergoing chemotherapy: follow-up study of heart failure. Circu Heart Fail 6(3):420–426. doi:10.1161/CIRCHEARTFAILURE.112.000055

    Article  CAS  Google Scholar 

  69. Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, Kalay N, Dikilitas M, Yarlioglues M, Karaca H, Berk V, Ardic I, Ergin A, Lam YY (2013) Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol 167(5):2306–2310. doi:10.1016/j.ijcard.2012.06.023

    Article  PubMed  Google Scholar 

  70. Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, Martinelli G, Veglia F, Fiorentini C, Cipolla CM (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114(23):2474–2481. doi:10.1161/CIRCULATIONAHA.106.635144

    Article  CAS  PubMed  Google Scholar 

  71. Heck SL, Gulati G, Ree AH, Schulz-Menger J, Gravdehaug B, Rosjo H, Steine K, Bratland A, Hoffmann P, Geisler J, Omland T (2012) Rationale and design of the prevention of cardiac dysfunction during an adjuvant breast cancer therapy (PRADA) trial. Cardiology 123(4):240–247. doi:10.1159/000343622

    Article  CAS  PubMed  Google Scholar 

  72. Pruefer D, Scalia R, Lefer AM (1999) Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol 19(12):2894–2900

    Article  CAS  PubMed  Google Scholar 

  73. Jones SP, Teshima Y, Akao M, Marban E (2003) Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res 93(8):697–699. doi:10.1161/01.RES.0000097262.21507.DF

    Article  CAS  PubMed  Google Scholar 

  74. Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH (2012) 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 60(23):2384–2390. doi:10.1016/j.jacc.2012.07.067

    Article  CAS  PubMed  Google Scholar 

  75. Acar Z, Kale A, Turgut M, Demircan S, Durna K, Demir S, Meric M, Agac MT (2011) Efficiency of atorvastatin in the protection of anthracycline-induced cardiomyopathy. J Am Coll Cardiol 58(9):988–989. doi:10.1016/j.jacc.2011.05.025

    Article  PubMed  Google Scholar 

  76. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, American College of Cardiology F, American Heart A (2009) 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart And Lung Transplantation. J Am Coll Cardiol 53(15):e1–e90. doi:10.1016/j.jacc.2008.11.013

    Article  PubMed  Google Scholar 

  77. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM (2010) Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 55(3):213–220. doi:10.1016/j.jacc.2009.03.095

    Article  CAS  PubMed  Google Scholar 

  78. Yoon GJ, Telli ML, Kao DP, Matsuda KY, Carlson RW, Witteles RM (2010) Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? J Am Coll Cardiol 56(20):1644–1650. doi:10.1016/j.jacc.2010.07.023

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Beth Israel Deaconess Medical Center, Deaconess Building, Suite 306, One Deaconess Road, Boston, MA, 02215, USA

    Angela Y. Higgins

  2. Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Thomas D. O’Halloran & James D. Chang

Authors
  1. Angela Y. Higgins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas D. O’Halloran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James D. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angela Y. Higgins.

Ethics declarations

Conflict of interest

Drs. Angela Y. Higgins, Thomas D. O'Halloran, and James D. Chang declare that they have no conflicts of interest or financial ties to disclose.

Statement of human rights

This article does not contain any studies with human participants performed by any of the authors. The manuscript is a review of literature and does not contain novel clinical studies or patient data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Higgins, A.Y., O’Halloran, T.D. & Chang, J.D. Chemotherapy-induced cardiomyopathy. Heart Fail Rev 20, 721–730 (2015). https://doi.org/10.1007/s10741-015-9502-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-015-9502-y

Keywords

Search

Navigation