Abstract

Abstract Background Trastuzumab (TZ) is a key therapy for HER2+ breast cancer (BC) patients, with well known possible negative effect on left ventricular (LV) function. A decrease in LV global longitudinal strain (GLS) has been demonstrated to be a good predictor of subsequent TZ-related cardiotoxicity (CT). Early left atrial (LA) enlargement preceding LV dysfunction has also been documented. Limited data are available about LA function in this setting. Aim To investigate LA function by deformation indexes (strain rate) in BC patients treated with TZ. Methods HER-2 positive BC metastasis-free patients referring to our echo-lab were prospectively recruited. Patients underwent consecutive transthoracic echocardiography before starting TZ and then every 3 months, up to 12. LV volumes, LV ejection fraction (LVEF) with Simpson biplane methods, LA volume and diastolic parameters were measured; 2D-Speckle Tracking analysis was performed and GLS and peak atrial longitudinal strain (PALS) were analyzed using Philips' QLAB software. Different lab tests and clinical data were also collected. Results 64 patients formed the study population. 40 (62.5%) had a complete 12 months follow up (FU). 53 patients (82.8%) were previously treated with anthracyclines. Mean age was 55.05±12.1 years. CT, as defined by current ESC guidelines, occurred in 6 patients (9.3%). Mean GLS was −21.4±2% and mean baseline PALS was 51.1±12%. GLS analysis was feasible in 91% of patients and PALS analysis in 84%, with excellent reproducibility for GLS (intra-observer ICC 0.93, p=0.8; inter-observer ICC 0.83, p=0.7). Even if during FU cardiotoxicity showed a low prevalence, a drop in LVEF over time was anyway documented, with major worsening at 6 months. Our study confirms previous data reporting a trend of decrease in GLS (p for time = 0.06), with an early drop during the first six months of TZ therapy and a subsequent “plateau” phase; we also reported a significant decrease of PALS over time (p for time = 0.008), with a continuous gradual decrease for the whole FU. A significant positive correlation between baseline PALS and LVEF at 6 months follow up was shown (R2 0.2; p=0.006). Similar result was obtained analyzing the correlation between LAVI and LVEF at 6 months (R2 0,19; p=0,02). Conclusion 2D speckle tracking analysis is feasible and adds useful information about LV and LA functional remodeling. Actual recommendations for CT identification are based upon a joint evaluation of LVEF and GLS, but our study demonstrates that significant variations in GLS and PALS can occur independently of development of CT. Moreover baseline PALS and LAVI predict the trend of LVEF at 6 months of FU, time of the major mean LVEF drop documented. The assessment of LA function by deformation indexes (strain rate) could add further information for daily clinical practice, possibly improving the detection of early CT. More studies are needed to further investigate these exploratory data.

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