BackgroundCardio-Oncology is an evolving discipline that focuses on the management of cancer patients who develop cardiovascular complications as a result of their treatment. Although the current combination of surgical resection, radiation, and chemotherapy may lead to a cure in cancer patients, the administration of anti-cancer drugs, in particular Doxorubicin (DOX) and Trastuzumab (TRZ), is associated with an increased risk of cardiotoxicity. Little is known on the potential cardioprotective role of renin angiotensin system (RAS) antagonists in the prevention of DOX+TRZ mediated cardiotoxicity.ObjectiveThe aim of the study was to determine whether RAS antagonists would be useful in attenuating DOX+TRZ induced cardiotoxicity.MethodsA total of 240 C57Bl/6 mice were randomized to prophylactic treatment with placebo, Aliskiren, Perindopril, or Valsartan for a total of 13 weeks. Within each arm, mice received treatment with either DOX, TRZ, or the combination of both drugs. Serial murine echocardiography was performed weekly to characterize the degree of cardiovascular remodeling within each group.ResultsIn wild-type (WT) mice treated with DOX+TRZ, LV end diastolic internal diameter (LVID) increased from 3.1 ± 0.2 mm at baseline to 4.6 ± 0.3 mm at week 13 (p < 0.05) and the LV fractional shortening (FS) decreased from 52 ± 2% at baseline to 26 ± 2% at week 13 (p < 0.05). Prophylactic treatment with Aliskiren, Perindopril, or Valsartan attenuated the degree of LV cavity dilatation with LVID dimensions of 3.9 ± 0.2 mm, 4.1 ± 0.2 mm, and 4.2 ± 0.1 mm at week 13, respectively (p < 0.05). Similarly, prophylactic treatment with Aliskiren, Perindopril, or Valsartan was partially cardioprotective with FS of 40 ± 1%, 32 ± 1%, and 33 ± 2% at week 13, respectively (p < 0.05). As compared to WT mice receiving DOX+TRZ, prophylactic treatment with RAS inhibition was also associated with improved survival, corroborating the echocardiographic findings.ConclusionThe cardiotoxic effects of DOX+TRZ were partially attenuated by the prophylactic administration of RAS antagonists in a chronic murine model of chemotherapy induced cardiac dysfunction.

BackgroundSpontaneous coronary and vertebral artery dissections are rare events occurring most commonly in otherwise healthy women during pregnancy or the post-partum period.Case presentationThis report describes a 35-year-old female who presented with an acute inferior ST elevation myocardial infarction 7 months post-partum secondary to spontaneous dissection of the left obtuse marginal coronary artery. Despite appropriate medical therapy with dual anti-platelet therapy, the patient presented four weeks later with a spontaneous dissection of the right vertebral artery.ConclusionWe review the presentation, diagnosis, and management of spontaneous dissections of the vasculature in the peri-partum period.

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...

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Background: Anthracycline therapy with Doxorubicin (DOX) is very effective in