Comparison of plasmatic levels of B-natriuretic peptide with echocardiographic indicators of left ventricle function after doxorubicin therapy

Česká verzia

Authors: L. Elbl ¹; I. Vášová ²; M. Navrátil ²; J. Vorlíček ²; L. Malášková ³
Authors place of work: Interní kardiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC ¹; Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc. ²; Oddělení klinické biochemie FN Brno, pracoviště Bohunice, přednosta doc. MUDr. Milan Dastych, CSc. ³
Published in the journal: Vnitř Lék 2006; 52(6): 563-570
Category: Original Contributions

Summary

The study objective:
The aim of the study was to find out the relationship between plasmatic levels of brain natriuretic peptide (BNP) and echocardiographic indicators of left ventricle (LV) function in patients who were in a long-term remission after the therapy of hematological malignity and examined in order to diagnose the late cardiotoxicity of doxorubicin.

Methods and patient sample:
We enrolled 55 patients (31 men/24 women) aged 43 ± 16 (median 41; 21–79) who were treated for historically diagnosed malignant lymphoma. At the time of examination, all patients were in a long-term remission and, at the same time, they completed their initial therapy 6.2 ± 1.5 (median 5; 5–10) years ago. Patients were examined via resting echocardiography before and after the therapy and during the follow-up examination. We determined the left ventricle ejection fraction (LV EF), parameters of diastolic function and the Doppler parameters of systolic and diastolic function (MPI-Tei index). During the follow-up examination, we measured plasmatic levels of BNP (standard levels were between 0 and 29 pmol/l).

Results:
Followup examination showed that EF of five patients (9 %) decreased below 50% and three patients had symptoms of heart failure. Although EF of another eleven patients (20%) was in the physiological range, it decreased by more than 10 % as compared with their pre-treatment EF values. Seventeen patients (30 %) showed higher MPI > 0.55 and twenty patients (36 %) demonstrated diastolic dysfunction (impaired relaxation). BNP > 29 pmol/l was observed only in patients with EF < 50 % and heart failure symptoms. BNP values significantly correlated only with endsystolic (r = 0.82; p < 0.0001) and enddiastolic (r = 0.72; p < 0.0001) volume of LV. On the other hand, BNP of 11.4 pmol/l showed negative predictive value for the following parameters: 80% for decrease of EF by more than 10%; 72% for detection of MPI > 0.55; and 70% for detection of relaxation disorder, i.e. the diagnostics of subclinical cardiotoxicity.

Conclusions:
The present study highlights the practical importance of measuring BNP levels when diagnosing the late changes of LV functions after doxorubicin chemotherapy. Standard cut-off BNP (29 pmol/l) used in diagnostics of heart failures identifies patients with pathological EF and heart failure symptoms. Cut-off BNP of 11.4 pmol/l has sufficient negative predictive value to exclude subclinical damage to the myocardium.

Key words:
B-natriuretic peptide – late cardiotoxicity – doxorubicin

Zdroje

1. Jain D. Cardiotoxicity of doxorubicin and other anthracycline derivates. J Nucl Cardiol 2000; 7: 53-62.

2. Shan K, Lincoff M, Young J. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996; 125: 47-58.

3. Von Hoff DD, Layard MW, Basa P et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979; 91: 710-717.

4. Giantris A, Abdurrahman L, Hinkle A et al. Anthracycline-induced cardiotoxicity in children and adults. Critical Rev Oncol Hematol 1998; 27: 53-68.

5. Singal P, Iliskovic N. Current concepts: doxorubicin-induced cardiomyopathy. N Engl J Med 1998; 339: 900-905.

6. Ganz WI, Sridhar KS, Ganz SS et al. Review of tests for monitoring doxorubicin-induced cardiomyopathy. Oncology 1996; 53: 461-470.

7. Apple FS, Murakami MA. The diagnostic utility of cardiac biomarkers in detecting myocardial infarction. Clinical Cornerstone 2005; 7: S25-S30.

8. Spinarova L, Toman J, Pospisilova J et al. Humoral response in patients with chronic heart failure. Int J Cardiol 1998; 65: 227-232.

9. Spinarova L, Spinar J, Vasku A et al. Big endothelin in chronic heart failure: marker of disease severity or genetic determination? Int J Cardiol 2004; 93: 63-68.

10. Špinar J, Špinarová L, Vítovec J et al. Big endothelin a chronické srdeční selhání. Vnitř Lék 2002; 48: 3-7.

11. Stejskal D, Oral I, Lačňák B et al. Personal experience with determination of NT-proBNP in clinical practice. Vnitř Lék 2003; 49: 94-96.

12. Maisel A, Mehra MR. Understanding B-type natriuretic peptide and its role in diagnosing and monitoring congestive heart failure. Clinical Cornerstone 2005; 7: S7-S17.

13. Silver MA, Maisel A, Yancy CW et al. BNP consensus panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. CHF 2004; 10: 1-30.

14. Kubanek M, Malek I, Kautzner J et al. The value of B-type natriuretic peptide and big endothelin-1 for detection of severe pulmonary hypertension in heart transplant candidates. Eur J Heart Fail 2005; 7: 1149-1155.

15. Vítovec J, Špinarová L. Natriuretické peptidy - diagnostika a léčba. Remedia 2004; 2: 177-181.

16. Sparano JA, Brown DL, Wolf AC. Predicting cancer therapy-induced cardiotoxicity. Drug Safety 2002; 25: 301-311.

17. Nousiainen T, Jantunen E, Vanninen E et al. Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin’s lymphoma. Eur J Hematol 1999; 62: 135-141.

18. Tikanoja T, Riikonen P, Perkkio M et al. Serum N-terminal atrial natriuretic peptide (NT-ANP) in the cardiac follow-up in children with cancer. Med Pediatr Oncol 1998; 31: 73-78.

19. Pichon MF, Cvitkovic F, Hacene K et al. Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography. In Vivo 2005; 19: 567-576.

20. Otto CM. Echocardiographic evaluation of left and right ventricular systolic function. In: Otto CM Textbook of clinical echocardiography. 2nd ed. Philadelphia: WB Saunders 2000: 100-131.

21. Tei Ch, Ling LH, Hodge DO et al. New index of combined systolic and diastolic myocardial performance: A simple and reproducible measure of cardiac function - a study in normals and dilated cardiomyopathy. J Cardiol 1995; 26: 357-366.

22. Spevack D, Schwartzbard A. B-type natriuretic peptide measurement in heart failure. Clin Cardiol 2004; 27: 489-494.

23. Špinar J, Vítovec J. Normy BNP a NT-proBNP stanoveny. Cor Vasa 2005; 47: 395-398.

24. Maisel AS, McCord J, Nowak RM et al. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. J Am Coll Cardiol 2003; 41: 2010-2017.

25. Mottram PM, Leano R, Marwick T. Usefulness of B-type natriuretic peptide in hypertensive patients with exertional dyspnea and normal left ventricular ejection fraction and correlation with new echocardiographic indexes of systolic and diastolic function. Am J Cardiol 2003; 92: 1434-1438.

26. Catuzzo B, Ciancamerla F, Bobbio M et al. In patients with severe systolic dysfunction only brain natriuretic peptide is related to diastolic restrictive pattern. J Cardiac Fail 2003; 9: 303-310.

27. Diwakar J. Cardiotoxicity of doxorubicin and other anthracycline derivates. J Nucl Cardiol 2000; 7: 53-62.

28. Špinar J, Hradec J, Málek I et al. Doporučení pro diagnostiku a léčbu chronického srdečního selhání. Guidelines - inovovaná verze 2001. Cor Vasa 2001; 43: K123-K137.

29. Nousiainen T, Jantunen E, Vanninen E et al. Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients. Eur J Hematol 1998; 61: 347-353.

30. Suzuki T, Hayashi D, Yamazaki T et al. Evevated B-type natriuretic peptide levels after anthracycline administration. Am Heart J 1998; 136: 362-363.

31. Sandri MT, Salvatici M, Cardinale D et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clinical Chemistry 2005; 51: 1405-1410.

32. Kawai K, Hata K, Tanaka K et al. Attenuation of biologic compensatory action of cardiac natriuretic peptide system with aging. Am J Cardiol 2004; 93: 719-723.

33. Snowden JA, Hill GR, Hunt P et al. Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide. Bone Marrow Transplantation 2000; 26: 309-313.

34. Smith MD, Drinkovic N, Harrison MR et al. Doppler evaluation of left ventricular compliance and ventricular filling abnormalities. Echocardiography 1992; 9: 407-420.

35. Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of left ventricular diastolic function. Circulation 1991; 84: 977-990.

36. Mandinov L, Eberli FR, Seiler Ch et al. Diastolic heart failure. Cardiovascular Research 2000; 45: 813-825.

37. Kusuoka H, Futaki S, Koretsune Y et al. Alterations of intracellular calcium homeostasis and myocardial energetics in acute adriamycin-induced heart failure. J Cardiovasc Pharmacol 1991; 18: 437-444.

38. Bottone AE, Voest EF, deBeer EL. Impairment of the actin-myosin interaction in permeabilized cardiac trabeculae after chronic doxorubicin treatment. Clin Cancer Res 1998; 4: 1031-1037.

39. Nehyba S, Elbl L, Chaloupka V. Index myokardiální funkce. Kardiol Revue 2000; 3: 35-41.

40. Ono M, Tanabe K, Asanuma T et al. Doppler echocardiography-derived index of myocardial performance (TEI index). Comparison with brain natriuretic peptide levels in various heart diseases. Jpn Circ J 2001; 65: 637-642.

41. Perik PJ, De Vries EGE, Boomsma F et al. Use of natriuretic peptides for detecting cardiac dysfunction in long-term disease-free breast cancer survivors. Anticancer Research 2005; 25: 3651-3658.