BRAF and heart failure: Treatment with BRAF and MEK inhibitors could lead to a perturbance of the physiological mechanisms of hypertrophy, apoptosis, remodeling of myocytes, and subsequently to a reduction in LVEF though this pathway.19,22 Another hypothesis is that an impairment of angiogenesis relies on the MAPK pathway to activate smooth muscle cell proliferation.20 This may contribute to hypertension, decreased LVEF, occurrence of atrial fibrillation, and, in the long term, the development of heart failure.