Experimental Oncology 29, 309–313, 2007 (December) 309 29, 309–313, 2007 (December) 309 December) 309 ) 309 309 Cardiac toxicity is a relatively frequent and potentially serious complication of oncology treatment. From cy- tostatics, anthracyclines (ANT) represent the greatest risk for development of cardiotoxicity. Despite reports conflict, proposed risk factors for ANT cardiotoxic- ity include: 1. cumulative dose of the drug (the most important and independent risk factor), 2. extremes of age (under 3 years, over 65 years), 3. irradiation of the mediastinum, 4. combination with other cardio- toxic chemotherapy, 5. female gender, 6. heart damage caused by another disease (coronary atherosclerosis, arterial hypertension, diabetes mellitus, valvular heart disease), 7. bolus administration of the drug. The most common manifestations of ANT cardiotoxicity are ar- rhythmias, cardiac dysfunction (cardiomyopathy, heart failure), pericardial injury and myocardial ischemia. Cardiotoxicity of ANT may develop during the treatment (acute cardiotoxicity) and during the follow-up (chronic and late cardiotoxicity) [1, 2]. Various methods have been recommended for monitoring of cardiotoxicity in oncology [3–5]. In our conditions, echocardiography (ECHO) and electrocardiography are routinely used. Recently, biochemical markers of cardiac injury, espe- cially natriuretic peptides and cardiac troponins, have been studied in this context [6]. Natriuretic peptides — atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) — are produced by myocardium in response to wall strain and pressure overload [7]. Natriuretic peptides get increased in sub- jects with acute and chronic cardiac dysfunction and heart failure [8]. As such, testing for natriuretic peptides has been recognized and incorporated in guidelines for diagnosis and management of heart failure [9]. Normal plasma BNP/NT-proBNP concentrations practically exclude heart failure due to a high negative predictive value of the test (97%) [10, 11]. Cardiac troponins — cardiac troponin T (cTnT), cardiac troponin I (cTnI) — and myocardial izoenzyme of creatine kinase (CK-MB mass) are cardiospecific markers that are released from cardiomyocytes injured from various causes, including cardiotoxic effect of oncology treatment [12, 13]. Only a few studies have been published address- ing the role of biochemical markers of functional and ASSESSMENT OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY WITH BIOCHEMICAL MARKERS J.M. Horacek 1, 4, *, R. Pudil 2 , L. Jebavy 1, 4 , M. Tichy 3, 4 , P. Zak 1 , J. Maly 1 1 2 nd Department of Medicine — Clinical Hematology, University Hospital and Charles University, Faculty of Medicine in Hradec Kralove, Czech Republic 2 1 st Department of Medicine, University Hospital and Charles University, Faculty of Medicine in Hradec Kralove, Czech Republic 3 Institute of Clinical Biochemistry and Diagnostics, University Hospital and Charles University, Faculty of Medicine in Hradec Kralove, Czech Republic 4 Department of Internal Medicine, University of Defence, Faculty of Military Health Sciences in Hradec Kralove, Czech Republic Aim: Assessment of acute and chronic cardiotoxicity of anthracyclines in patients treated for acute leukemia (AL) with biochemical mark- ers — “N-terminal pro brain natriuretic peptide” (NT-proBNP), cardiac troponin T (cTnT), creatine kinase MB (CK-MB mass), and echocardiography. Methods: Twenty-six adult AL patients (mean age 46.2 ± 12.4 years, 15 males) treated with 2–6 cycles of chemotherapy (CT) containing anthracyclines in the total cumulative dose of 464.3 ± 117.5 mg/m 2 were studied. Cardiac evaluation was performed at baseline, after first and last CT with anthracyclines and 6 months after CT. Results: Mean baseline NT-proBNP concentration was 117.7 ± 46.4 ng/L (slightly elevated in 3 patients). After first and last CT, NT-proBNP elevations to 299.7 ± 176.2 ng/L and 287.1 ± 147.4 ng/L were observed, respectively. Six months after CT, mean NT-proBNP concentration was 362.5 ± 304.9 ng/L (elevated in 16 patients). Changes in NT-proBNP were significant in comparison with the baseline values (p < 0.001). Six months after CT, two patients with marked NT-proBNP elevations during CT developed treatment-related cardiomyopathy with symptoms of heart failure. NT-proBNP correlated with systolic and diastolic LV dysfunction on echocardiography (r = 0.514; p < 0.01) and (r = 0.587; p < 0.01). CTnT concentrations were negative (bellow 0.01 µg/L) during CT in all patients. Six months after CT, delayed cTnT positivity occurred in 3 patients. CK-MB mass remained within the reference range in all patients. Conclusion: Our study shows that anthracycline treatment is associated with acute and chronic neurohumoral activation of cardiac dysfunction that is manifested by a significant increase in NT-proBNP. It seems that NT-proBNP could be useful in the early detection of anthracycline cardiotoxicity. CTnT negativity during anthracycline treatment suggests that anthracyclines, even in higher cumulative doses, do not cause detectable acute injury to cardiomyocyte structure. Further studies using more sensitive markers of cardiac damage will be needed in this context. Key Words: cardiotoxicity, anthracyclines, biochemical markers, NT-proBNP, cTnT. Received: October 7, 2007. *Correspondence: E-mail address: jan.hor@post.cz Abbreviations used: AL – acute leukemia; ANP – atrial natriuretic peptide; ANT – anthracycline(s); BNP – brain natriuretic pep- tide; CK-MB mass – creatine kinase MB; CT – chemotherapy; cTnI – cardiac troponin I; cTnT – cardiac troponin T; ECHO – echo- cardiography; LV – left ventricular; LVEF – ejection fraction of left ventricle; NT-proBNP – N-terminal pro brain natriuretic peptide. Exp Oncol 2007 29, 4, 309–313