Angiogenesis inhibitors exert their effect by either neutralising VEGF (bevacizumab) or blocking signaling within the endothelial cell (sunitinib or sorafinib).12 This results in a unique group of cardiac effects such as:34
- reduced left ventricular ejection fraction (LVEF)
- cardiovascular events including:
- myocardial ischemia
- myocardial infarction
- congestive heart failure
Although the exact mechanism is unknown, theories that have been proposed include:
- blockade of nitric oxide, which is required for the walls of arterioles and other resistance vessels to relax11
- direct toxicity to cardiomyocytes.34
Cardiac toxicity associated with trastuzumab can range from an asymptomatic reduced LVEF to congestive heart failure.9, 34 Although the exact mechanism of cardiotoxicity is unknown, the damage has been described as a type II antineoplastic agent-related cardiac dysfunction (CRCD), which appears mostly reversible with improvement on discontinuation of therapy.34
The risk of cardiotoxicity increases with the concomitant administration of antineoplastic agents such as anthracyclines and paclitaxel. The two most significant risk factors have been identified as age and combination of trastuzumab and anthracycline therapy. The two agents should therefore not be given together.34 A feature of trastuzumab cardiotoxicity is its reversible nature, which may allow therapy to be reintroduced in certain individuals after improvement in LVEF.
The significance of the cardiotoxic related events has led to warnings with regards to the use of these agents in individuals with a history of cardiovascular events and exposure to other cardiotoxic agents.34
Outline the evidence based information and supportive care strategies to prevent and manage cardiac toxicity in the individual receiving targeted therapies.