Why the study?
Does 2D-speckle tracking echocardiography detect early trastuzumab-related cardiotoxicity compared to structural damage in a murine model?
Does 2D-speckle tracking echocardiography detect early trastuzumab-related cardiotoxicity compared to structural damage in a murine model?
Left ventricular systolic strain reduction detects early trastuzumab-induced cardiotoxicity before LVEF decline, correlating with histological myocardial damage in a murine model.
Strain imaging detected early trastuzumab effects in mice before structural damage; leaves open translation to human monitoring protocols.
OBJECTIVE: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. METHODS: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. RESULTS: <0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. CONCLUSION: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue.
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Coppola et al. (2016) studied this question.
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