Early detection and prediction of taxanes-induced cardiac dysfunction by assessment of myocardial deformation

Taxanes are extremely potent drugs, used in therapeutic regimes for breast cancer. However, the applicability is limited by the risk of cardiotoxicity. Guidelines define chemotherapy-induced cardiac dysfunction based on conventional parameters, such as left ventricular (LV) ejection fraction (EF) or fractional shortening (FS). Since normal EF or FS can mask LV impairment, our aim was to define other parameters, such as 4D LV deformation or biomarkers, able to diagnose early cardiac dysfunction, and to predict cardiotoxicity. Methods: 20 women with breast cancer (51±9 yrs), without cardiac disease, EF>50%, scheduled to be treated with taxanes, were assessed at baseline, after 1st cycle, and at the completion of treatment (cumulative dose of 417±154 g/m2). Conventional and 4D auto LV quantification echo were used to assess LV geometry, EF, FS, and systolic deformation: radial, longitudinal, circumferential strain (RS, LS, CS), and area strain (AS). STE was used to measure LV rotation: peak apical and basal rotation (RotA and RotB), LV twist (LVT), and twist and un-twist rate (TR and UTR). Cardiac troponin I and C-reactive protein were also measured. Results: After the 1st cycle of taxanes, there were reductions in longitudinal and radial deformation, and area strain, persistent after the completion of treatment, whereas LV dimensions, EF, FS, circumferential deformation, and rotation remained unchanged. On contrary, at the final of chemotherapy there was a significant decrease of EF (57±4% vs 63±3%, p=0.001), with no further changes of circumferential deformation and rotation or biomarkers level. A decrease of AS of 18% after the 1st cycle of taxanes was the best independent (r2=0.81, p=0.001) and accurate (100% sensitivity and 73% specificity, AUC 0.63) predictor of EF reduction at the completion of treatment. View this table: LV deformation and rotation Conclusion: Assessment of myocardial deformation by 4D echo detects early LV dysfunction and can predict further changes in EF, and therefore, can be used to monitor taxanes-induced cardiac dysfunction.