Skip to main content

Advertisement

SpringerLink
Log in

Early Detection of Chemotherapy-Related Left Ventricular Dysfunction

  • Echocardiography (RM Lang, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Modern advances in cancer treatment have resulted in improved survival. As a result, effects of cancer therapy on other organ systems such as the heart are more likely to become clinically relevant. One such possibility is chemotherapy-related left ventricular dysfunction. Although in clinical practice cardiotoxicity is evaluated by symptoms and left ventricular ejection fraction, these occur relatively late in the disease process after the heart’s compensatory mechanisms have been expended. Ideally, left ventricular dysfunction would be identified early so that cancer patients and their physicians can make informed decisions about their therapeutic options and institute careful surveillance and early initiation of cardioprotective medication where appropriate. This review discusses the role of echocardiography to detect subclinical left ventricular dysfunction in cancer patients exposed to chemotherapy with potential cardiotoxicity, particularly anthracyclines and trastuzumab.

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

Fig. 1

Similar content being viewed by others

References

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

  1. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973;32(2):302–14.

    Article  PubMed  CAS  Google Scholar 

  2. 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.

    Google Scholar 

  3. • Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–47. This is a comprehensive review of various chemotherapeutic agents and their cardiac toxicities.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart. 2008;94(4):525–33.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  7. Altena R, Perik PJ, van Veldhuisen DJ, de Vries EG, Gietema JA. Cardiovascular toxicity caused by cancer treatment: strategies for early detection. Lancet Oncol. 2009;10(4):391–9.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. • Sawyer DB, Peng X, Chen B, Pentassuglia L, Lim CC. Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection? Prog Cardiovasc Dis. 2010;53(2):105–13. The basic science mechanisms underlying anthracycline injury are well described.

    Article  PubMed  CAS  Google Scholar 

  10. Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep. 1978;62(6):865–72.

    PubMed  CAS  Google Scholar 

  11. Mackay B, Ewer MS, Carrasco CH, Benjamin RS. Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct Pathol. 1994;18(1–2):203–11.

    Article  PubMed  CAS  Google Scholar 

  12. 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(6):814–6.

    PubMed  CAS  Google Scholar 

  13. Haq MM, Legha SS, Choksi J, et al. Doxorubicin-induced congestive heart failure in adults. Cancer. 1985;56(6):1361–5.

    Article  PubMed  CAS  Google Scholar 

  14. Hudziak RM, Schlessinger J, Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987;84(20):7159–63.

    Article  PubMed  CAS  Google Scholar 

  15. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.

    Article  PubMed  CAS  Google Scholar 

  16. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.

    Article  PubMed  CAS  Google Scholar 

  17. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.

    Article  PubMed  CAS  Google Scholar 

  18. Chien KR. Myocyte survival pathways and cardiomyopathy: implications for trastuzumab cardiotoxicity. Semin Oncol. 2000;27(6 Suppl 11):9–14. discussion 92–100.

    PubMed  CAS  Google Scholar 

  19. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–21.

    Article  PubMed  CAS  Google Scholar 

  20. Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6.

    Article  PubMed  CAS  Google Scholar 

  21. • Hunt SA, Abraham WT, Chin MH, et al. 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. 2009;53(15):e1–e90. These heart failure guidelines indicate that ACE inhibitors may be appropriate for patients receiving cardiac toxins.

    Article  PubMed  Google Scholar 

  22. • Yoon GJ, Telli ML, Kao DP, Matsuda KY, Carlson RW, Witteles RM. Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally? J Am Coll Cardiol. 2010;56(20):1644–50. In this provocative paper, the authors present single-center data suggesting that chemotherapy-related LVD is not always treated optimally with conventional heart failure therapy or cardiologist consultation.

    Article  PubMed  Google Scholar 

  23. • Cardinale D, Colombo A, Lamantia G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213–20. These investigators demonstrate that contrary to prior belief, anthracycline-induced cardiomyopathy may respond to modern conventional heart failure therapy.

    Article  PubMed  CAS  Google Scholar 

  24. Noori A, Lindenfeld J, Wolfel E, Ferguson D, Bristow MR, Lowes BD. Beta-blockade in adriamycin-induced cardiomyopathy. J Card Fail. 2000;6(2):115–9.

    PubMed  CAS  Google Scholar 

  25. 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(12):2196–201.

    Article  PubMed  Google Scholar 

  26. Chu TF, Rupnick MA, Kerkela R, et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet. 2007;370(9604):2011–9.

    Article  PubMed  CAS  Google Scholar 

  27. Khakoo AY, Kassiotis CM, Tannir N, et al. Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer. 2008;112(11):2500–8.

    Article  PubMed  CAS  Google Scholar 

  28. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440–63.

    Article  PubMed  Google Scholar 

  29. Spencer KT, Bednarz J, Mor-Avi V, et al. The role of echocardiographic harmonic imaging and contrast enhancement for improvement of endocardial border delineation. J Am Soc Echocardiogr. 2000;13(2):131–8.

    PubMed  CAS  Google Scholar 

  30. Malm S, Frigstad S, Sagberg E, Larsson H, Skjaerpe T. Accurate and reproducible measurement of left ventricular volume and ejection fraction by contrast echocardiography: a comparison with magnetic resonance imaging. J Am Coll Cardiol. 2004;44(5):1030–5.

    Article  PubMed  Google Scholar 

  31. Jacobs LD, Salgo IS, Goonewardena S, et al. Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data. Eur Heart J. 2006;27(4):460–8.

    Article  PubMed  Google Scholar 

  32. • Walker J, Bhullar N, Fallah-Rad N, et al. 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. 2010;28(21):3429–36. The authors compare 2D and 3D echocardiography to cardiac MRI for the assessment of LVEF. They suggest that 3D echocardiography is superior to 2D echocardiography for precise and reproducible LVEF determination.

    Article  PubMed  Google Scholar 

  33. Cardinale D, Sandri MT, Martinoni A, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36(2):517–22.

    Article  PubMed  CAS  Google Scholar 

  34. Cardinale D, Sandri MT, Martinoni A, et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol. 2002;13(5):710–5.

    Article  PubMed  CAS  Google Scholar 

  35. 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(22):2749–54.

    Article  PubMed  CAS  Google Scholar 

  36. • Mor-Avi V, Lang RM, Badano LP, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24(3):277–313. This consensus statement describes the various echocardiographic techniques that are utilized to assess myocardial mechanics, along with their respective strengths and limitations.

    Article  PubMed  Google Scholar 

  37. Neilan TG, Jassal DS, Perez-Sanz TM, et al. Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury. Eur Heart J. 2006;27(15):1868–75.

    Article  PubMed  Google Scholar 

  38. • Jassal DS, Han SY, Hans C, et al. Utility of tissue Doppler and strain rate imaging in the early detection of trastuzumab and anthracycline mediated cardiomyopathy. J Am Soc Echocardiogr. 2009;22(4):418–24. These investigators demonstrate the value of echocardiographic indices of myocardial deformation in the early detection of chemotherapy-related LVD in an animal model.

    Article  PubMed  Google Scholar 

  39. Tassan-Mangina S, Codorean D, Metivier M, et al. Tissue Doppler imaging and conventional echocardiography after anthracycline treatment in adults: early and late alterations of left ventricular function during a prospective study. Eur J Echocardiogr. 2006;7(2):141–6.

    Article  PubMed  Google Scholar 

  40. • Ho E, Brown A, Barrett P, et al. Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart. 2010;96(9):701–7. This group of investigators used tissue Doppler and speckle tracking to compare strain patterns in patients exposed to anthracyclines or anthracyclines followed by trastuzumab to controls. They also examined serial diastolic parameters in each group.

    Article  PubMed  CAS  Google Scholar 

  41. • Hare JL, Brown JK, Leano R, Jenkins C, Woodward N, Marwick TH. Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab. Am Heart J. 2009;158(2):294–301. These investigators demonstrate the value of tissue Doppler and speckle tracking echocardiography for the early detection of chemotherapy-related LVD in humans receiving trastuzumab.

    Article  PubMed  CAS  Google Scholar 

  42. • Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107(9):1375–80. This study was the first to employ both biomarkers and echocardiographic parameters of myocardial deformation to detect LVD in patients receiving anthracyclines and trastuzumab. Sensitivity, specificity, positive and negative predictive values for TNI and global longitudinal strain are estimated.

    Article  PubMed  CAS  Google Scholar 

  43. • Fallah-Rad N, Walker JR, Wassef A, et al. 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. 2011;57(22):2263–70. These investigators were the first to combine multiple biomarkers, echocardiographic indices, and cardiac MRI with gadolinium enhancement for early detection of LVD in patients receiving trastuzumab. A pattern of delayed enhancement was found in the lateral wall of all 10 subjects who developed LVD.

    Article  PubMed  CAS  Google Scholar 

  44. • 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(23):2474–81. This study demonstrates the role of TNI to identify patients who will benefit from cardioprotective medication while receiving trastuzumab.

    Article  PubMed  CAS  Google Scholar 

  45. • Bosch X, Esteve J, Sitges M, et al. Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial. J Card Fail. 2011;17(8):643–8. These investigators outline their intention to study the role of conventional heart failure therapy to prevent chemotherapy-induced cardiotoxicity in patients with hematological malignancies undergoing autologous stem cell transplant. They will incorporate cardiac MRI, echocardiographic parameters of myocardial deformation, and biomarkers into their serial patient assessment.

    Article  PubMed  Google Scholar 

  46. • Pituskin E, Haykowsky M, Mackey JR, et al. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101—Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI. BMC Cancer. 2011;11:318. This study will utilize cardiac MRI and biomarkers to study the effect of cardioprotective medications to prevent LVD in patients treated with trastuzumab.

    Article  PubMed  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Section of Cardiology, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 5084, Chicago, IL, 60637, USA

    Jeanne M. DeCara

Authors
  1. Jeanne M. DeCara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeanne M. DeCara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeCara, J.M. Early Detection of Chemotherapy-Related Left Ventricular Dysfunction. Curr Cardiol Rep 14, 334–341 (2012). https://doi.org/10.1007/s11886-012-0256-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-012-0256-z

Keywords

Search

Navigation