Experimental determination of diagnostic window of cardiac troponins in the development of chronic anthracycline cardiotoxicity and estimation of its predictive value. (15th December 2015)

• Record Type: Journal Article
• Authors: Adamcova, Michaela; Lencova-Popelova, Olga; Jirkovsky, Eduard; Mazurova, Yvona; Palicka, Vladimir; Simko, Fedor; Gersl, Vladimir; Sterba, Martin
• Is Part Of: International journal of cardiology. Volume 201(2015)
• Page Start: 358
• Page End: 367
• Publication Date: 2015-12-15
• Subjects: AMI acute myocardial infarction -- ANT anthracycline -- AUC area under curve -- cTnI cardiac troponin I -- cTnT cardiac troponin T -- cTns cardiac troponins -- DAU daunorubicin -- FS fractional shortening -- H&E hematoxylin and eosin stain -- MT Masson's blue trichrome -- LV left ventricle; Cardiotoxicity -- Chemotherapy -- Anthracyclines -- Cardiomyopathy -- Heart failure -- High sensitive troponin assay; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2015.07.103
• Languages: English
• ISSNs: 0167-5273

Abstract

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 (3 mg/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 4–6 h and a decline until 24 h. 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. Highlights: Diagnostic window of hs cTns in ANT cardiotoxicity was described for the 1st time. Early cTn elevations after the 1 st ANT cycle were found to have no predictive value. cTns after the 5 th & 8 th ANT cycles corresponded with systolic dysfunction (cTnT better). Concentrations in the steady state, but not in cmax were useful for this purpose. AUC of cTns since the 5 th ANT cycle reflected well the severity of the cardiotoxicity.