{'fraction_non_alphanumeric': 0.07351077313054499, 'fraction_numerical': 0.05618926911702577, 'mean_word_length': 4.55868544600939, 'pattern_counts': {'":': 0, '<': 4, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Utility of 2D-speckle tracking echocardiography in diagnosis of left ventricular dysfunction in anti-ErbB2 therapy.

169 Background: ErbB2 is overexpressed in about 25% of breast cancers; in the heart, it modulates myocardial development and function. Trastuzumab (T), an anti-ErbB2 inhibitor, has improved the prognosis of patients with breast cancer, but is related to an increased risk of asymptomatic left ventricular (LV) dysfunction (3-34%) and heart failure (2-4%). Conventional measures of ventricular function, such as fractional shortening (FS) and ejection fraction (FE) are insensitive in detecting early cardiomyopathy induced by antineoplastic therapy. Here, we aim at assessing whether myocardial strain by 2D-speckle tracking (ST) is able to identify early LV dysfunction in mice treated with doxorubicin (D) and T, alone or in combination (D+T) and to relate data of cardiac function with tissue alterations.


METHODS
Cardiac function was measured with FS, by M-mode echocardiography, and with radial myocardial strain with ST in sedated C57BL/6 mice (8-10 wk old) at time 0, 2 and 6 days of daily administration of D (2.17 mg/kg/day), T (2.25 mg/kg/day), D+T (2.17 mg/kg/day + 2.25 mg/kg/day) and in a control group. In excised hearts, we evaluated TNFα and CD68 by immunohistochemistry; interstizial fibrosis was analyzed with picrosirius red staining.


RESULTS
FS was reduced in group D and D+T at 2 days (52+0.2% and 49+2%), both p<0.001 vs 60+0.4% (sham), while in group T it decreased only at 6 days (49+1.5% vs 60+0.5%, p=.002). In contrast, after 2 days, myocardial strain was already reduced not only in D and D+T, but also in T alone: 43+3%, 49+1%, and 44+7%, respectively, all p<0.05 vs sham (66+0.6%). Cardiotoxicity was associated with significant alterations in extracellular matrix remodeling as confirmed by an increase of interstizial collagen with D (4.56%), T (2.17%) and D+T (3.77%)at 6 days p<0.05 vs sham (1.17%) and by increased cardiac inflammation in fact the myocytes were positive for TNFα and CD68 cells/mm2at 6 days in group D (16.46% and 155), in group T+D (12.35% and 74.16) and in group T (5.65% and 72.32) p<0.01 vs sham (0.56% and 2.3).


CONCLUSIONS
Myocardial strain identifies LV systolic dysfunction earlier than conventional echocardiography and can be a useful tool to predict cardiotoxicity in this setting.