This study investigates the cardiotoxicity associated with the tyrosine kinase inhibitor sunitinib, a drug used to treat metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). The researchers reviewed cardiovascular events in 75 patients with imatinib-resistant, metastatic GIST treated with sunitinib at the Dana-Farber Cancer Institute. Key findings include: - **Cardiovascular Events**: 11% (8/75) of patients experienced cardiovascular events, with congestive heart failure (CHF) occurring in 8% (6/75). - **Left Ventricular Ejection Fraction (LVEF)**: 28% (10/36) of patients treated at the FDA-approved dose had LVEF declines of ≥10 EF%, and 19% (7/36) experienced LVEF declines of ≥15 EF%. - **Blood Pressure (BP)**: Sunitinib induced significant increases in mean systolic and diastolic BP, with 47% (35/75) of individuals developing hypertension (>150/100 mmHg). - **Mechanisms**: In mice and cultured cardiomyocytes, sunitinib caused mitochondrial injury and cardiomyocyte apoptosis. The study suggests that sunitinib can lead to hypertension, LVEF decline, and CHF, with potential mechanisms involving direct cardiomyocyte toxicity and the exacerbation of hypertension. Patients treated with sunitinib should be closely monitored and managed for these cardiovascular risks.This study investigates the cardiotoxicity associated with the tyrosine kinase inhibitor sunitinib, a drug used to treat metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). The researchers reviewed cardiovascular events in 75 patients with imatinib-resistant, metastatic GIST treated with sunitinib at the Dana-Farber Cancer Institute. Key findings include: - **Cardiovascular Events**: 11% (8/75) of patients experienced cardiovascular events, with congestive heart failure (CHF) occurring in 8% (6/75). - **Left Ventricular Ejection Fraction (LVEF)**: 28% (10/36) of patients treated at the FDA-approved dose had LVEF declines of ≥10 EF%, and 19% (7/36) experienced LVEF declines of ≥15 EF%. - **Blood Pressure (BP)**: Sunitinib induced significant increases in mean systolic and diastolic BP, with 47% (35/75) of individuals developing hypertension (>150/100 mmHg). - **Mechanisms**: In mice and cultured cardiomyocytes, sunitinib caused mitochondrial injury and cardiomyocyte apoptosis. The study suggests that sunitinib can lead to hypertension, LVEF decline, and CHF, with potential mechanisms involving direct cardiomyocyte toxicity and the exacerbation of hypertension. Patients treated with sunitinib should be closely monitored and managed for these cardiovascular risks.