Although the exact mechanism for cardiomyopathy and congestive heart failure upon VEGF signaling blockade has not yet been fully delineated, the current notion is that existing conditions depleting the vascular reserve, such as hypertension and coronary artery disease, may be considered risk factors for cardiotoxicity with VEGF signaling inhibitors, while reduced nitric oxide production, mitochondrial dysfunction and pericyte population depletion have been attributed as potential mechanisms (62, 63). The gene discussed is VEGFA; the disease is cardiomyopathy.