Skip to main content

Advertisement

Log in

Systolic versus diastolic cardiac function variables during epirubicin treatment for breast cancer

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Anthracyclines are important in the treatment of numerous malignant diseases but the use is limited by a risk of heart failure (CHF). LVEF (left ventricular ejection fraction) measurements by radio-nuclide ventriculography with multiple gated acquisition (MUGA) is often used for cardiac monitoring. However, diastolic variables have been proposed as sensitive supplements. It was hypothesized that a change in diastolic filling variables measured by MUGA could identify individuals after epirubicin treatment (ET) in risk of developing heart failure. A retrospective analysis of registered raw data. Individuals completing high-dose ET for breast cancer were selected from a 2-year period. All had MUGA-scans performed prior to and after ET and were observed clinically for late development of CHF. Eleven of 34 individuals developed CHF. A significant LVEF-reduction was recorded after ET with only minor changes in diastolic parameters. Development of CHF was related to dose, entry-blood pressure and inversely to post-epirubicin LVEF. Risk of CHF was high if LVEF <50% (Hazard ratio 3.31). Epirubicin induces considerable decrease in LVEF and a high risk of CHF. The risk of CHF is significantly higher if LVEF is reduced after ET. Diastolic MUGA-variables seem to add little information to conventional measurements of LVEF.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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

    Article  CAS  PubMed  Google Scholar 

  2. Appel JM, Nielsen D, Zerahn B, Jensen BV, Skagen K (2007) Anthracycline-induced chronic cardiotoxicity and heart failure. Acta Oncol 46(5):576–580

    Article  CAS  PubMed  Google Scholar 

  3. 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

    Google Scholar 

  4. Xu MF, Tang PL, Qian ZM, Ashraf M (2001) Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. Life Sci 68(8):889–901

    Article  CAS  PubMed  Google Scholar 

  5. Escriba PV, Sastre M, Garcia-Sevilla JA (1995) Disruption of cellular signalling pathways by daunomycin through destabilization of non lamellar membrane structures. Proc Natl Acad Sci USA 92(16):7595–7599

    Article  CAS  PubMed  Google Scholar 

  6. Zhou S, Starkov A, Froberg MK, Leino RL, Wallace KB (2001) Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Cancer Res 61(2):771–777

    CAS  PubMed  Google Scholar 

  7. Tokarska-Schlattner M, Zaugg M, Zuppinger C, Wallimann T, Schlattner U (2006) New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. J Mol Cell Cardiol 41(3):389–405

    Article  CAS  PubMed  Google Scholar 

  8. Kapelko VI, Williams CP, Gutstein DE, Morgan JP (1996) Abnormal myocardial calcium handling in the early stage of adriamycin cardiomyopathy. Arch Physiol Biochem 104(2):185–191

    Article  CAS  PubMed  Google Scholar 

  9. Early Breast Cancer Trialists’ Collaborative Group (1998) Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352(9132):930–942

    Article  Google Scholar 

  10. Henderson IC, Canellos GP (1980) Cancer of the breast: the past decade (second of two parts). N Engl J Med 302(2):78–90

    CAS  PubMed  Google Scholar 

  11. Ryberg M, Nielsen D, Skovsgaard T, Hansen J, Jensen BV, Dombernowsky P (1998) Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol 16(11):3502–3508

    CAS  PubMed  Google Scholar 

  12. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA (1973) A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32(2):302–314

    Article  CAS  PubMed  Google Scholar 

  13. Ritchie JL, Bateman TM, Bonow RO, Crawford MH, Gibbons RJ, Hall RJ, O’Rourke RA, Parisi AF, Verani MS (1995) Guidelines for clinical use of cardiac radionuclide imaging. Report of the American College of Cardiology/American Heart Association task force on assessment of diagnostic and therapeutic cardiovascular procedures (Committee on Radionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology. J Am Coll Cardiol 25(2):521–547

    Article  CAS  PubMed  Google Scholar 

  14. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, Sandor G, Benson L, Williams R (1992) Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the cardiology committee of the children’s cancer study group. Pediatrics 89(5 Pt 1):942–949

    CAS  PubMed  Google Scholar 

  15. Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, Duffy T, Schwartz P, Gottschalk A, Zaret BL (1979) Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med 300(6):278–283

    Article  CAS  PubMed  Google Scholar 

  16. Belham M, Kruger A, Mepham S, Faganello G, Pritchard C (2007) Monitoring left ventricular function in adults receiving anthracycline-containing chemotherapy. Eur J Heart Fail 9(4):409–414

    Article  CAS  PubMed  Google Scholar 

  17. 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

    Article  PubMed  Google Scholar 

  18. Jensen BV, Skovsgaard T, Nielsen SL (2002) Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 13(5):699–709

    Article  CAS  PubMed  Google Scholar 

  19. Ganame J, Claus P, Eyskens B, Uyttebroeck A, Renard M, D’hooge J, Gewillig M, Bijnens B, Sutherland GR, Mertens L (2007) Acute cardiac functional and morphological changes after anthracycline infusions in children. Am J Cardiol 99(7):974–977

    Article  CAS  PubMed  Google Scholar 

  20. Suzuki J, Yanagisawa A, Shigeyama T, Tsubota J, Yasumura T, Shimoyama K, Ishikawa K (1999) Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography. Angiology 50(1):37–45

    Article  CAS  PubMed  Google Scholar 

  21. Schmitt K, Tulzer G, Merl M, Aichhorn G, Grillenberger A, Wiesinger G, Hofstadler G (1995) Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: diastolic versus systolic parameters. Eur J Pediatr 154(3):201–204

    Article  CAS  PubMed  Google Scholar 

  22. Nagy AC, Tolnay E, Nagykalnai T, Forster T (2006) Cardiotoxicity of anthracycline in young breast cancer female patients: the possibility of detection of early cardiotoxicity by TDI. Neoplasma 53(6):511–517

    CAS  PubMed  Google Scholar 

  23. Lu P (2005) Monitoring cardiac function in patients receiving doxorubicin. Semin Nucl Med 35(3):197–201

    Article  PubMed  Google Scholar 

  24. Clements IP, Sinak LJ, Gibbons RJ, Brown ML, O’Connor MK (1990) Determination of diastolic function by radionuclide ventriculography. Mayo Clin Proc 65(7):1007–1019

    CAS  PubMed  Google Scholar 

  25. Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML (1991) Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 266(12):1672–1677

    Article  CAS  PubMed  Google Scholar 

  26. Meinardi MT, van Veldhuisen DJ, Gietema JA, Dolsma WV, Boomsma F, van den Berg MP, Volkers C, Haaksma J, de Vries EG, Sleijfer DT, van der Graaf WT (2001) Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and loco regional radiotherapy in breast cancer patients. J Clin Oncol 19(10):2746–2753

    CAS  PubMed  Google Scholar 

  27. Muntinga HJ, van den Berg F, Knol HR, Niemeyer MG, Blanksma PK, Louwes H, van der Wall EE (1997) Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography. Int J Card Imaging 13(2):165–171 (discussion 173)

    Article  CAS  PubMed  Google Scholar 

  28. Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC, Gerstenblith G (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Physiol 263(6 Pt 2):H1932–H1938

    CAS  PubMed  Google Scholar 

  29. Kremer LC, van Dalen EC, Offringa M, Ottenkamp J, Voute PA (2001) Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 19(1):191–196

    CAS  PubMed  Google Scholar 

  30. Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK (2008) New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst 100(15):1058–1067

    Article  CAS  PubMed  Google Scholar 

  31. Bonow RO (1991) Radionuclide angiographic evaluation of left ventricular diastolic function. Circulation 84(3 Suppl):I208–I215

    CAS  PubMed  Google Scholar 

  32. Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL (2005) Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol 23(34):8597–8605

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jon M. Appel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Appel, J.M., Jensen, B.V., Nielsen, D.L. et al. Systolic versus diastolic cardiac function variables during epirubicin treatment for breast cancer. Int J Cardiovasc Imaging 26, 217–223 (2010). https://doi.org/10.1007/s10554-009-9518-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-009-9518-2

Keywords

Navigation