title: Experimental determination of diagnostic window of cardiac troponins in the development of chronic anthracycline cardiotoxicity and estimation of its predictive value.
abstract: 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.
authors: Department of Physiology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic. Electronic address: adamcova@lfhk.cuni.cz.
authors: Michaela
authors: M
authors: Adamcova
authors: Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
authors: Olga
authors: O
authors: Lencova-Popelova
authors: Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
authors: Eduard
authors: E
authors: Jirkovsky
authors: Department of Histology and Embryology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
authors: Yvona
authors: Y
authors: Mazurova
authors: Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, Hradec Králové 500 05, Czech Republic.
authors: Vladimir
authors: V
authors: Palicka
authors: 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.
authors: Fedor
authors: F
authors: Simko
authors: Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
authors: Vladimir
authors: V
authors: Gersl
authors: Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, Hradec Králové 500 38, Czech Republic.
authors: Martin
authors: M
authors: Sterba
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000633:toxicity*; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced; D066126:Cardiotoxicity / Q000097:blood* / Q000000981:diagnostic imaging; D003630:Daunorubicin / Q000633:toxicity; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008297:Male; D011237:Predictive Value of Tests; D011817:Rabbits; D012044:Regression Analysis; D013599:Systole / Q000187:drug effects / Q000502:physiology; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T; D003630:Daunorubicin
keywords: Anthracyclines; Cardiomyopathy; Cardiotoxicity; Chemotherapy; Heart failure; High sensitive troponin assay