Objectives To detect the early subclinical myocardial injury during and shortly after epirubicin exposure in asymptomatic patients with large B-cell non-Hodgkin lymphoma by two-dimensional speckle tracking imaging and high sensitive cardiac troponin T (hs-cTnT) and to investigate whether alterations of myocardial strains and high sensitive cardiac troponin T could predict future cardiac dysfunction in patients after epirubicin exposure.
Methods Seventy-five patients aged 53.9 ± 13.8 years with newly-diagnosed large B-cell non-Hodgkin lymphoma treated with anthracycline were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after chemotherapy completion. After 4–6 months of chemotherapy, echocardiography was followed up. Levels of cTnT were detected with a highly sensitive assay. Longitudinal (LS), circumferential (CS) and radial strain (RS) were calculated using two-dimensional speckle tracking echocardiography. Left ventricular ejection fraction (LVEF) was analysed by real-time 3D echocardiography. Cardiotoxicity was defined according to the guidelines (Cardiac Review and Evaluation Committee of Trastuzumab-associated cardiotoxicity, CREC) as a reduction of the left ventricular ejection fraction (LVEF) of ≥5% to <55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of ≥10% to <55%.
Results LVEF remained stable and within normal limits in the whole course of chemotherapy. However it was decreased from 65.0 ± 3.8% at baseline to 60.8 ± 4.9% during follow-up (p = 0.000). Fourteen patients (18.67%) developed cardiotoxicity 4–6 months after treatment. Global LS (-18.5 ± 1.7% vs -16.5 ± 1.9%), CS (-20.9 ± 2.9% vs -19.3 ± 3.5%), RS (39.2 ± 6.4% vs 35.3 ± 5.2%) were markedly reduced and cTnT was elevated from 0.0010 ± 0.0020 ng/ml to 0.0063 ± 0.0089 ng/ml (p all<0.01) at the completion of the third cycle of chemotherapy compared with baseline values. The correlation between the increment of cTnT levels and percentage of global LS deduction was good (rho = 0.60, p < 0.01), and percentage of CS and RS decrease was modest (rho = 0.31, -0.29, respectively, p all <0.01). A >15.9% decrease in longitudinal strain ( sensitivity: 86%, specificity: 75%, AUC = 0.815, P = 0.001) and a >0.004ng/ml elevation in cTnT levels (sensitivity: 79%, specificity: 64%, AUC = 0.757, P = 0.005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease of longitudinal strain between baseline and the third cycle of chemotherapy remained the only independent predictor of cardiotoxicity (p = 0.000).
Conclusions Two-dimensional speckle tracking imaging combined with high sensitive cTnT may provide a reliable and accurate non-invasive method to detect subtle myocardial injury and to predict cardiac dysfunction in patients receiving anthracycline-based chemotherapy. The decrease of longitudinal strain is the only independent predictor of cardiotoxicity.