Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used to treat metastatic renal cell carcinoma and gastrointestinal stromal tumor. However, it is associated with cardiotoxicity, including left ventricular ejection fraction (LVEF) decline, hypertension, and congestive heart failure (CHF). A study of 75 patients with imatinib-resistant, metastatic GIST treated with sunitinib found that 11% experienced cardiovascular events, including 8% with CHF. Twenty-eight% of patients treated at the FDA-approved dose had LVEF declines of ≥10 EF%, and 19% had declines of ≥15 EF%. Sunitinib also caused significant increases in blood pressure, with 47% of patients developing hypertension. CHF and LV dysfunction generally responded to drug withdrawal and medical management. In mice and cultured cardiomyocytes, sunitinib caused mitochondrial injury and cardiomyocyte apoptosis. The study suggests that sunitinib can lead to HTN, LVEF decline, and/or CHF, possibly due to direct cardiomyocyte toxicity exacerbated by HTN. Patients treated with sunitinib should receive close monitoring and prompt treatment for HTN and/or LVEF decline. The findings highlight the need for further research to define the nature and incidence of sunitinib-associated cardiovascular effects, particularly in patients with cardiac risk factors.Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used to treat metastatic renal cell carcinoma and gastrointestinal stromal tumor. However, it is associated with cardiotoxicity, including left ventricular ejection fraction (LVEF) decline, hypertension, and congestive heart failure (CHF). A study of 75 patients with imatinib-resistant, metastatic GIST treated with sunitinib found that 11% experienced cardiovascular events, including 8% with CHF. Twenty-eight% of patients treated at the FDA-approved dose had LVEF declines of ≥10 EF%, and 19% had declines of ≥15 EF%. Sunitinib also caused significant increases in blood pressure, with 47% of patients developing hypertension. CHF and LV dysfunction generally responded to drug withdrawal and medical management. In mice and cultured cardiomyocytes, sunitinib caused mitochondrial injury and cardiomyocyte apoptosis. The study suggests that sunitinib can lead to HTN, LVEF decline, and/or CHF, possibly due to direct cardiomyocyte toxicity exacerbated by HTN. Patients treated with sunitinib should receive close monitoring and prompt treatment for HTN and/or LVEF decline. The findings highlight the need for further research to define the nature and incidence of sunitinib-associated cardiovascular effects, particularly in patients with cardiac risk factors.