Temporal changes in standard and tissue Doppler imaging echocardiographic parameters after anthracycline chemotherapy in women with breast cancer.

Anthracyclines are established cardiotoxic agents; however, the exact extent and time course of such cardiotoxicity has not been appraised in detail. We aimed to exploit serial measurements of standard and tissue Doppler imaging (TDI) echocardiographic parameters collected in a prospective clinical trial to clarify the outlook of cardiac function during and long after anthracycline chemotherapy. Women enrolled in a randomized trial focusing on liposomal doxorubicin-based chemotherapy for breast cancer and providing ≥4 separate echocardiographic assessments were included. Repeat-measure nonparametric analyses were used to appraise changes over time in the standard and tissue Doppler imaging echocardiographic parameters. A total of 39 patients with serial imaging evaluations were enrolled. Significant temporal changes were found for the left ventricular ejection fraction and diastolic parameters, despite different temporal trends. Specifically, the left ventricular ejection fraction exhibited a V-shaped trend, decreasing initially from 63% to 61% but then recovering to 64% (p <0.001), with a similar trend in the TDI E/Em ratio (p = 0.011). In contrast, persistent impairments typical of an L-shaped trend were found for the E wave (p = 0.006), TDI lateral Em wave (p = 0.001), and TDI septal Em wave (p = 0.001). In conclusion, subclinical temporal changes in the standard and TDI echocardiographic parameters after anthracycline chemotherapy showed a distinctive pattern of transient impairment followed by full recovery of the left ventricular ejection fraction versus a persistent impairment of the diastolic parameters, which must be taken into account in the everyday treatment of such patients.

Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: rationale and design of the LITE (Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot study.

BACKGROUND: Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Early detection at subclinical stage is pivotal to minimize the risk of overt cardiotoxicity. Liposomal anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity. OBJECTIVE: We designed a single-center randomized clinical trial, the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation (LITE) pilot study to compare the safety of liposomal doxorubicin vs standard epirubicin in terms of clinical and subclinical cardiotoxicity. METHODS: Whereas diagnostic and prognostic instruments effective at early recognition of cardiomyopathy are lacking, promising data have been reported for tissue Doppler imaging (TDI) echocardiography. The study will enroll 80 patients with breast cancer and indication to anthracycline chemotherapy, randomizing them in a 1:1 ratio to liposomal doxorubicin or standard epirubicin. The primary end-point will be the comparison of changes from baseline to 12-month follow-up of left ventricular TDI systolic function parameters, and the co-primary end-point will be based instead on changes in TDI diastolic function parameters. Among secondary end-points, we will adjudicate changes in standard 2-dimensional echocardiography parameters, including ejection fraction, peak values of biochemical markers of cardiac damage and heart failure, ie cardiac troponin T and BNP, overall survival, functional class, freedom from cancer recurrence, and adverse effects of chemotherapy. CONCLUSIONS: Results of the LITE pilot study should provide important clinical and mechanistic insights on the promising role of liposomal anthracyclines in patients with breast cancer and indication to anthracycline chemotherapy (ClinicalTrials.gov identifier NCT00531973).