Skip to main content
Log in

Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: Diastolic versus systolic parameters

  • Hematology/Oncology
  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Doxorubicin and daunorubicin are effective anticancer agents in children, however, their therapeutic value is limited by myocardial cardiotoxicity. In 14 children (median age 5,0 years, range 3–12) prospective studies were performed using pulsed Doppler echocardiography to assess the changes in left ventricular systolic and diastolic filling dynamics. None of these children developed cardiomyopathy. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analysed at baseline, after a cumulative anthracycline dose of 138±26 mg/m2 (second examination) and after 240±15 mg/m2 (third examination). At the second examination the acceleration time/ejection time ratio was significantly reduced (P<0.01), but this was no longer evident at the third examination. There was no significant change of peak velocity over aortic valve, preejection period and change of velocity over time. In contrast, three diastolic parameters changed significantly; the late over early inflow velocity (P<0.05), mitral valve late time velocity integral (P<0.01 at the second andP<0.05 at the third examination) and the ratio A-TVI/TVI (P<0.025 andP<0.01). At the third examination the velocity of the A wave was also significantly increased.

Conclusion

In anthracyline treated children left ventricular diastolic function deteriorates before systolic function. Diastolic function parameters should be used rather than systolic parameters to monitor these patients.

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.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

A :

peak late diastolic inflow velocity

A/E ratio :

late over early inflow velocity

AT :

acceleration time

dv/dt :

change of velocity over time

E :

peak early inflow velocity

ET :

ejection time

IVR :

isovolumic relaxation time

PEP :

pre-ejection period

TVI :

time velocity integral

V Ao :

peak velocity over aortic valve

References

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

    PubMed  Google Scholar 

  2. Appleton CP, Hatle LK, Popp RL (1988) Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights form a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 12:426–440

    PubMed  Google Scholar 

  3. Billingham ME, Mason IW, Bristow MR, Daniels JR (1978) Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 62: 865–872

    PubMed  Google Scholar 

  4. Bristow MR, Mason JW, Billingham ME, Daniels JR (1981) Dose effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J 102:709–712

    Article  PubMed  Google Scholar 

  5. Buzdar AU, Marcus C, Smith TL, Blumenschein GR (1985) Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 55:2761–2765

    PubMed  Google Scholar 

  6. Cortes EP, Lutmanb G, Wanka J, Wang JJ, Pickren J, Wallace J, Holland JF (1975) Adriamycin (NSC-123127) Cardiotoxicity: a clinicopathologic correlation. Cancer Chemother Rep 6: 215–225

    Google Scholar 

  7. Courtois M, Kovacs SJ, Ludbrook PA (1988) Transmitral pressure-flow velocity relation: Importance of regional pressure gradients in the left ventricle during diastole. Circulation 78:661–671

    PubMed  Google Scholar 

  8. Fujii J, Yazaki Y, Sawada H, Aizawa T, Watanabe H, Kato K (1985) Non-invasive assessment of left and right ventricular filling in myocardial infarction with a two-dimensional Doppler echocardiographic method. J Am Coll Cardiol 5:1155–1160

    PubMed  Google Scholar 

  9. Galli MA, Conter V, Zanetto F, Jankovic M, Ferrari L, Baio G, Masera G (1987) Cardiotoxicity in children treated with anthracyclines: the role of M-mode echocardiography. Haematologica 72:347–350

    PubMed  Google Scholar 

  10. Gardin JM, Dabestani A, Takenaka K, et al (1986) Effects of imaging view and sample volume location on evaluation of metral flow velocity by pulsed Doppler echocardiography. Am J Cardiol 57:1335–1339

    Article  PubMed  Google Scholar 

  11. Goorin AM, Chauvenet AR, Perez-Atayade AR, Cruz J, McKone R, Lipshultz SE (1990) Initial congestive heart failure, six to ten years after doxorubicin chemotherapy for childhood cancer. J Pediatr 116:144–147

    PubMed  Google Scholar 

  12. Hausdorf G, Morf G, Beron G, Erttmann K, Winkler K, Landbeck G, Keck EW (1988) Long term doxorubicin cardiotoxicity in childhood: noninvasive evaluation of the contractile state and diastolic filling. Br Heart J 60:309–315

    PubMed  Google Scholar 

  13. Koch H, Schmitz E, Brockmeier K, Hartmann R, Bein G, Henze G (1991) Langzeituntersuchung zur Anthracyclininduzierten Kardiomyopathie bei Kindern und Jugendlichen. Klin Pädiatr 203:262–272

    Google Scholar 

  14. Kücherer HF, Ruffmann K, Schaefer E, Kübler W (1988) Doppler echocardiographic assessment of left ventricular filling dynamics in patients with coronary heart disease and normal systolic function. Eur Heart J 9:649–656

    PubMed  Google Scholar 

  15. Marchandise B, Schröder E, Bosly A, Doyen C, Weynants P, Kremer R, Pouleur H (1989) Early detection of doxorubicin cardiotoxicity: interest of Doppler echocardiographic analysis of left ventricular filling dynamics. Am Heart J 118:92–98

    Article  PubMed  Google Scholar 

  16. Pratt CB, Ransom JL, Evans WE (1977) Age related carditoxicity in children. Cancer Treat Rep 62: 1381–1385

    Google Scholar 

  17. Richter v. Arnauld HP, Kleeberg UR, Hassel C, Erdmann H (1983) Kardiologische Überwachung bei der Therapie mit kardiotoxischen Zytostatika. Herz/Kreislauf 4:170–180

    Google Scholar 

  18. Rockey R, Kuo LC, Zoghbi WA, Limbacher MC, Quinones MA (1985) Determination of parameters of left ventricular diastolic filling with pulsed Doppler echocardiography: comparison with cineangiography Circulation 71: 543–550

    PubMed  Google Scholar 

  19. Serwer GA (1990) Echocardiography in pediatric heart disease. In: Snider AR (ed) Year Book Medical Publisher Inc, p 122

  20. Snider AR, Gidding SS, Rocchini AP, Rosenthal A, MacDonald D II, Crowley DC, Peters J (1985) Doppler evaluation of left ventricular diastolic filling in children with systemic hypertension. Am J Cardiol 56:921–926

    Article  PubMed  Google Scholar 

  21. Spirito P, Maron BJ, Bonow RO (1986) Noninvasive assessment of left ventricular diastolic function: comparative analysis of Doppler echocardiographic and radionuclide angiographic techniques. Am J Coll Cardiol 7: 518–526

    Google Scholar 

  22. Stein JI, Langevin A, Benson N, Sonza MD, Wilson G, Chan H (1989) Serielle Bestimmung der Anthracyclintoxizität bei Kindern. Wien Klin Wochenschr 101:45–48

    PubMed  Google Scholar 

  23. Stein PD, Sabah HN (1976) Ventricular performance measured during ejection. Studies in patients of the rate of change of ventricular power. Am Heart J 91:599–606

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmitt, K., Tulzer, G., Merl, M. et al. Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: Diastolic versus systolic parameters. Eur J Pediatr 154, 201–204 (1995). https://doi.org/10.1007/BF01954271

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01954271

Key words

Navigation