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Background High-dose chemotherapy (HDC) is utilized in high-risk cancer patients. This type of treatment may induce cardiac toxicity which becomes clinically evident weeks or months after HDC. Hence, the possibility of early identification of patients who will develop cardiac impairment is strategic for its clinical implications. The aim of this study was to identify possible early changes of left ventricular contractile reserve (LVCR) in cancer patients undergoing HDC, as well as to evaluate the relevance of such changes as predictors of chemotherapy-induced cardiotoxicity. Methods In forty-nine female patients scheduled for HDC, due to poor-prognosis breast cancer, dobutamine stress echocardiography (DSE) was performed, before each of the three HDC cycles (C1, C2, C3), and 1, 4, and 7 months after the end of chemotherapy. According to rest left ventricular ejection fraction (LVEF) evaluated within 18 months after HDC (f-LVEF), patients were allocated to Group A (LVEF 10 absolute units reduction) and to Group B (LVEF≥50%). Results Rest LVEF didn't show any significant difference between the two groups except at f-LVEF. Peak LVEF and LVCR significantly decreased in Group A only, starting from C3. At C3, a ≥5 units fall in LVCR was found to be predictive for f-LVEF drop below 50%. Conclusions In patients undergoing HDC, low-dose DSE allows the early identification of patients at a high risk of developing cardiac dysfunction.