Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy

Abstract

Anthracyclines (doxorubicin, daunorubicin, and derivatives) are among the most effective antineoplastic drugs for pediatric cancer with dose-limiting acute and long-term cardiotoxicity. The exact mechanism of the development of cardiomyopathy is still not clear. Anthracyclines may induce subclinical acute myocardial injury leading to lysis of a limited number of myocytes. Alternatively, myocytes may experience a transient loss of cytoplasmic membrane integrity. Both conditions may lead to a transient efflux of small amounts of cytoplasmic enzymes and other proteins specific to the heart muscle fibers. To test these hypotheses we assayed plasma creatine kinase (CK) MB mass and cardiac specific troponin T (TnT). CKMB may be released even in case of reversible cell membrane injury, while prolonged elevation of TnT is the most sensitive and specific marker of limited myocardial necrosis. Thirty-five anthracycline-containing chemotherapy courses in 22 children with cancer were analyzed. CKMB mass and TnT concentrations were within the normal range in all children before anthracycline therapy. Within 72 hours from anthracycline therapy no increment of one of these two marker proteins was detected (ANOVA for repeated measures, P = 0.94 [TnT] and 0.25 [CKMB]). We conclude that only minimal if any acute necroses of cardiac myocytes occur after anthracycline therapy. Even membrane integrity appears to be maintained within the first 3 days after anthracycline therapy, in the absence of electrocardiographic or echocardiographic signs of acute cardiotoxicity.

Glutathione S-transferase overexpression protects against anthracycline-induced H9C2 cell death

“…With the use of a targeting dosage similar to that used in humans, the peak plasma concentration of DOX after bolus infusion in experimental animals (i.e., 1 to 2 g/ml) was observed to be closer to the level producing apoptosis than oncosis (11). Typical indexes of cardiomyocyte necrosis (i.e., creatine kinase or troponin release) are not detected in patients after treatment with AC, further suggesting that apoptosis may be the more relevant cell death mechanism associated with clinical ACT (14). In leukemic cells, the concentration of DOX also determines the mechanism of cell death, with apoptosis occurring over a concentration range of 1-3 M, and necrosis at higher doses, possibly because the apoptotic program requires ongoing RNA synthesis, which is inhibited at high concentrations of DOX.…”

ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations

“…Observational studies limited to children were less likely to document troponin elevations during anthracycline chemotherapy (166) or, when troponin was elevated, found no relation to systolic function (167). Other studies did correlate LV dilation to troponin elevation, at least in the short term (168).…”

It’s Time for a Change to a Troponin Standard

“…Biomarker increases can occur secondary to direct trauma to the heart, 2,3 as a result of myocardial toxins such as adriamycin or 5-fluorouracil, 41 or in response to endogenous substances released in critically ill patients (eg, patients with septic shock). 42,43 Mechanical injury (such as ablation), 44 implantable cardioverter defibrillator discharges, 45 and cardioversion 46 all induce cardiac injury.…”