BACKGROUND: Cardiac troponins (cTns) seem to be more sensitive for the detection of anthracycline cardiotoxicity than the currently recommended method of monitoring LV systolic function. However, the optimal timing of blood sampling remains unknown. Hence, the aims of the present study were to determine the precise diagnostic window for cTns during the development of chronic anthracycline cardiotoxicity and to evaluate their predictive value. METHODS: Cardiotoxicity was induced in rabbits with daunorubicin (3mg/kg, weekly, for 8 weeks). Blood samples were collected 2-168 h after the 1st, 5th and 8th drug administrations, and concentrations of cTns were determined using highly sensitive assays: hs cTnT (Roche) and hs cTnI (Abbott). RESULTS: The plasma levels of cTns progressively increased with the rising number of chemotherapy cycles. While only a mild non-significant increase in both cTn levels occurred after the first daunorubicin dose, a significant rise was observed after the 5th and 8th administrations. Two hours after these administrations, a significant increase occurred with a peak between 4-6h and a decline until 24h. Discrete cTn release continued even after cessation of the therapy. While greater variability of cTn levels was observed around the peak concentrations, the values did not correspond well with the severity of LV systolic dysfunction. Unlike AMI in cardiotoxicity, cTn elevations may be better associated with cumulative dose and concentrations at steady state than cmax. CONCLUSIONS: To the best of our knowledge, this is the first study to precisely describe the diagnostic window and predictive value of cTns in anthracycline cardiotoxicity.

Department of Clinical Biochemistry and Diagnostics University Hospital Hradec Králové Sokolská 581 Hradec Králové 500 05 Czech Republic

Department of Histology and Embryology Faculty of Medicine in Hradec Králové Charles University Prague Šimkova 870 Hradec Králové 500 38 Czech Republic

Department of Pathophysiology School of Medicine Comenius University Sasinkova 4 Bratislava 81372 Slovakia; 3rd Clinic of Medicine School of Medicine Comenius University 83305 Bratislava Slovakia; Institute of Experimental Endocrinology Slovak Academy of Sciences 83305 Bratislava Slovakia; Center of Excellence NOREG 81372 Bratislava Slovakia

Department of Pharmacology Faculty of Medicine in Hradec Králové Charles University Prague Šimkova 870 Hradec Králové 500 38 Czech Republic

Department of Physiology Faculty of Medicine in Hradec Králové Charles University Prague Šimkova 870 Hradec Králové 500 38 Czech Republic

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