Avastin and Sutent Induced Cardiotoxicity Study (ASICS): Early Detection of Bevacizumab and Sunitinib Mediated Cardiotoxicity
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BACKGROUND: Bevacizumab (BVZ) and Sunitinib (SNT) are two novel treatments which are used in the setting of colorectal cancer and renal cell carcinoma, respectively. While both agents are known to suppress tumour cell progression, they have been associated with the onset of drug-induced cardiotoxicity. Early, non-invasive methods of detecting cardiac dysfunction would be useful for preventing end stage heart failure. OBJECTIVE: To determine if cardiac biomarkers and/or tissue Doppler echocardiographic techniques may allow for early detection of BVZ and SNT induced LV systolic dysfunction in an acute murine model. METHODS: A total of 75 wild type (WT) C57BI/6 male mice were treated with either 0.9% saline, BVZ, or SNT and followed for a total of 14 days. Serial echocardiography, hemodynamic monitoring, and cardiac biomarkers were performed over the study period after which all mice were euthanized for histological and biochemical analyses. RESULTS: In WT mice receiving BVZ or SNT, left ventricular ejection fraction (LVEF) values decreased from 75±3% at baseline to 52±2% and 49±1% at day 13, respectively. In contrast, there was a significant decrease in tissue Doppler imaging (TDI) parameters by day 8, indicative of early LV systolic dysfunction. Hemodynamic monitoring at day 14 indicated the development of hypertension following BVZ or SNT treatment. Histological and biochemical analyses demonstrated loss of cell integrity and elevated caspase-3, a marker of cell apoptosis, in mice receiving BVZ or SNT. CONCLUSION: In an acute murine model, TDI echocardiographic indices were earlier indicators of BVZ and SNT mediated cardiotoxicity.