Abstract 1875: Early Strain Rate Impairment During Epirubicin Treatment Correlates With Markers Of Inflammation And Oxidative Stress
INTRODUCTION Epirubicin (EPI) cardiotoxicity (CTX) is associated with progressive impairment of cardiac function, which proceeds slowly and continues irreversible for years after treatment cessation.
HYPOTHESIS Doppler-derived myocardial systolic Strain Rate (SR), not affected by preload and afterload, could be an ideal index to evaluate in these patients left ventricular (LV) contractility.
METHODS We enrolled 16 patients (mean [±SD] age 53±16 years) suffering from various solid cancers assigned to EPI adjuvant therapy. The cumulative dose of EPI was 400±20 g/m2. Patients were studied by tissue Doppler (TD), Strain (S) and SR imaging. Plasma concentrations of reactive oxygen species (ROS), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and biochemical markers of inflammation (IL-6, sIL-6R, TNFα, sR-TNFα) were assessed. Patients underwent a complete investigation before chemotherapy, 24 hours and 7 days after every new 100 mg/m2 dose of EPI. We evaluated longitudinal function using pulsed TD, S and SR at the basal segments of the LV septum, at the mitral annulus. Moreover, ΔSR as the difference between SR values at baseline and at each dose of EPI, was calculated.
RESULTS A significant reduction of the peak of SR (2.01±0.8 s−1 vs 1.34±0.2 s−1; p<0.05) and of the IVRT (92.2±8.3 msec vs 66.3±6.4 msec; p<0.001), first signs of systolic and diastolic dysfunction, respectively, were observed at the 200±20 g/m2 dose of EPI. At this time, the highest levels of ROS (530±99 FORT-U vs 320±64 FORT-U; p<0.0001), sIL-6R (128,7±10,3 ng/ml vs 78,1±20,8 ng/ml; p<0.026), as well as the peak of reduction of GPX (5431±2317 UI/ml vs 8492±3739 UI/ml; p<0.0001) were found in comparison with the respective basal values. IL-6, TNFα and sR-TNFα increased not significantly. Furthermore, a significant correlation was found between the ΔSR and the peak of ROS, GPX, SOD and TNFα (all p<0.05).
CONCLUSION Our data show that
the reduction of the peak SR is a reliable and early marker of the EPI-induced subclinical CTX;
the first sign of EPI-induced CTX already occurs at level of EPI 200mg/m2 dose;
the relationship between TD parameters and markers of inflammation and oxidative stress seems to give an explanation of the EPI-induced CTX.