DS. The utility of cardiac biomarkers and echocardiography for the early detection of bevacizumab-and sunitinib-mediated cardiotoxicity. Am J Physiol Heart Circ Physiol 309: H692-H701, 2015. First published June 19, 2015; doi:10.1152/ajpheart.00172.2015.-The recent introduction of novel anticancer therapies, including bevacizumab (BVZ) and sunitinib (SNT), is associated with an increased risk of cardiotoxicity. However, early identification of left ventricular (LV) systolic dysfunction may facilitate dose modification and avoid the development of advanced heart failure. Using a murine model of BVZ-and SNTmediated cardiotoxicity, we investigated whether cardiac biomarkers and/or tissue velocity imaging (TVI) using echocardiography can detect early changes in cardiac function, before a decrease in LV ejection fraction is identified. A total of 75 wild-type C57Bl/6 male mice were treated with either 0.9% saline, BVZ, or SNT. Serial monitoring of blood pressure, high-sensitivity troponin I, and echocardiographic indexes were performed over a 14-day study period, after which the mice were euthanized for histological and biochemical analyses. Mice treated with either BVZ or SNT developed systemic hypertension as early as day 7, which increased by day 14. Cardiac biomarkers, specifically high-sensitivity troponin I, were not predictive of early LV systolic dysfunction. Although conventional LV ejection fraction values decreased at day 13 in mice treated with either BVZ or SNT, TVI confirmed early LV systolic dysfunction at day 8. Histological and biochemical analysis demonstrated loss of cellular integrity, increased oxidative stress, and increased cardiac apoptosis in mice treated with BVZ or SNT therapy at day 14. In a murine model of BVZ-or SNT-mediated cardiomyopathy, noninvasive assessment by TVI detected early LV systolic dysfunction before alterations in conventional echocardiographic indexes.cardio-oncology; heart failure; cardiotoxicity; hypertension; bevacizumab; sunitinib; cardiac biomarkers; echocardiography; apoptosis
NEW & NOTEWORTHYThe current basic science study evaluates the utility of cardiac biomarkers and echocardiography using tissue velocity imaging and strain rate imaging for the early detection of bevacizumab-and sunitinib-mediated cardiotoxicity.CARDIO-ONCOLOGY IS A NOVEL discipline that focuses on the prevention, diagnosis, and management of cancer patients who are at risk of developing cardiovascular complications as a result of their anticancer treatment. Despite the beneficial effects of chemotherapy agents in increasing overall survival of cancer patients, cardiotoxicity remains a serious complication of many systemic anticancer therapies (4,5,26,32,36,47,49,58). The treatment strategy for each patient is individualized, involving a combination of surgical intervention, radiation, chemotherapy, and novel targeted biological therapy.Two types of targeted therapies widely used for treating metastatic colorectal (CRC) and renal cell cancer (RCC), respectively, are the monoclonal antibody bev...