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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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Anthracycline-containing regimens have demonstrated significant disease-free and overall survival benefits in the adjuvant setting and also provide palliative benefit in metastatic disease. . Over the past two decades, an increasing proportion of patients have been exposed to adjuvant anthracyclines with concomitant reduction in their use for palliation, as a result of concerns regarding efficacy and cumulative anthracycline-associated cardiotoxicity, as well as the availability of other systemic chemotherapeutic options. This report reflects the consensus view of a meeting of oncologists, pharmacologists and cardiologists held in Florence, Italy, on April 30, 2010. The objectives of the meeting were to review the role and limits of conventional anthracyclines in the treatment of breast cancer, to provide recommendations for the use of novel anthracycline formulations, such as non-pegylated liposomal doxorubicin (NPLD), and to identify potential future indications for NPLD that warrant further research.

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).

Aim: Anthracycline (ANT) chemotherapy for breast cancer, while associated with high response rates, is fraught by risks of irreversible cardiotoxicity. Unfortunately means to detect such cardiotoxicity early on and at a sublinical stage are lacking. We evaluated the role of systolic tissue Doppler imaging (TDI) in appraising postchemotherapy left ventricular (LV) remodelling., Methods: Patients undergoing ANT-chemotherapy for breast cancer were enrolled, and underwent baseline and >6-months echocardiography (standard and TDI). According to the pattern of LV-TDI systolic remodelling from baseline to follow-up, patients were stratified in: group 1 (no LV-TDI worsening), group 2 (minor LV-TDI worsening), and group 3 (major LV-TDI worsening). Fifty-six patients were included (follow-up 9+/-6 months)., Results: At baseline, no patient had abnormal LV ejection fraction (LVEF), LV-TDI systolic dysfunction or New York Heart Association (NYHA) >1. Follow-up overall analysis showed significant deterioration in LVEF, end-diastolic diameter (EDD) end-systolic diameter (ESD), and TDI-systolic parameters (all P<0.05). Specifically, 29 (51.8%) patients showed no adverse LV-TDI systolic remodelling, while 17 (30.4%) were in group 2, and 10 (17.9%) in group 3. All groups shared similar conditions at baseline. Patients with adverse LV-TDI remodelling had significant increases in EDD and ESD, as well as a significantly decreased LVEF (all P<0.05). No patient in group 1 had abnormal LVEF at follow-up, while 1 patient in group 2 and 2 patients in group 3 had abnormal LVEF (P<0.05)., Conclusion: Subclinical systolic dysfunction occurs in almost 50% of patients early after chemotherapy for breast cancer, with a more adverse by LV-TDI remodelling implying a more pronounced deterioration of standard echocardiographic parameters.