The use of biochemical markers in
assessment of acute and chronic cardiotoxicity of anthracyclines in hematooncology patients
Horáček J.M.1, 2, Pudil R.3, Tichý M.1, 4, Jebavý L.1, 2, Pástorová J.5, Slováček L.1, 2
1Katedra válečného vnitřního lékařství, Univerzita obrany v Brně, Fakulta vojenského zdravotnictví v Hradci Králové 2Oddělení klinické hematologie II. interní kliniky, UK v Praze, LF v Hradci Králové a FN Hradec Králové 3I. interní klinika, UK v Praze, LF v Hradci Králové a FN Hradec Králové 4Ústav klinické biochemie a diagnostiky, UK v Praze, LF v Hradci Králové a FN Hradec Králové 5Klinika gerontologická a metabolická, UK v Praze, LF v Hradci Králové a FN Hradec Králové |
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Summary:
Objective: Monitoring of acute and chronic cardiotoxicity of anthracyclines with biochemical markers – N-terminal pro brain
natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and myocardial izoenzyme of creatine kinase (CK-MB mass).
Setting: University of Defence in Brno, Faculty of Military Health Sciences in Hradec Králové, Department of Field
Internal Medicine, Charles University in Prague, Medical Faculty in Hradec Králové and Faculty Hospital Hradec
Králové, Department of Internal Medicine II – Clinical Hematology, Department of Internal Medicine I, Institute of
Clinical Biochemistry and Diagnostics, Department of Gerontology and Metabolic Care.
Patients and Methods: Twenty six consecutive patients treated for newly diagnosed acute leukemia were studied. The
patients consisted of 15 males and 11 females with the mean age of 46.2 ± 12.4 years. The patients were given 2–6
cycles of chemotherapy (CT) containing anthracyclines in the total cumulative dose of 464.3 ± 117.5 mg/m2. Evaluation
of biochemical markers and echocardiography were performed at the baseline, after first CT with anthracyclines, after
last CT with anthracyclines and circa 6 months after completion of the treatment.
Results: Mean baseline NT-proBNP concentration was 117.7 ± 46.4 ng/l, values were slightly elevated in 3 patients
(above 100 ng/l for male, above 150 ng/l for female). After the administration of the first CT with anthracyclines, NTproBNP
elevation to 299.7 ± 176.2 ng/l was observed. After last CT with anthracyclines, NT-proBNP concentration was
287.1 ± 147.4 ng/l. Six months after completion of the treatment, NT-proBNP concentration was 362.5 ± 304.9 ng/l,
values were elevated in 16 patients. Changes in NT-proBNP were statistically significant in comparison with the
baseline value (p < 0.001). We found correlation between NT-proBNP and systolic and diastolic left ventricular (LV)
dysfunction on echocardiography. CTnT concentrations were negative (bellow 0.01 µg/l) during the treatment in all
patients. Six months after the treatment, cTnT became positive in 3 patients. CK-MB mass concentrations remained
negative (bellow 4.94 µg/l) in all patients during the treatment and the follow-up.
Conclusion: Our results show that oncology treatment containing anthracyclines has a toxic effect on the heart, which
becomes manifest both during the treatment (acute cardiotoxicity) and during the follow-up (chronic cardiotoxicity). We
found changes in biochemical markers of functional myocardial damage (NT-proBNP elevations showing acute and
chronic neurohumoral activation) and deterioration of diastolic and systolic LV function on echocardiography. In
asymptomatic patients, these changes are regarded as subclinical cardiotoxicity. These findings represent the risk for
manifestation of cardiotoxicity in terms of heart failure in the future and require further follow-up. According to our
results, anthracycline treatment – even in higher cumulative doses – does not lead to acute damage of cardiomyocyte
structure.
Key words:
biochemical markers, NT-proBNP, cardiotoxicity, anthracyclines.
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