Heart failure resulting from cancer treatment: still serious but an opportunity for prevention

Success in the diagnosis and treatment of many cancers has resulted in a growing population of people living either cured of cancer or with their cancer controlled as a chronic disease by long-term treatment. This success story in modern medicine has created a new problem with some survivors developing cardiovascular disease as a result of their cancer treatment.1 This is not a surprise given the biology of cancer and the strategies for treating cancer which frequently inhibit molecular pathways or cellular organelles critical for healthy cardiac function. One of the most serious consequences of cardiotoxic cancer therapy is heart failure (HF) which can lead to significant morbidity and premature mortality.1–3 A growing number of cancer therapies may cause cardiac dysfunction, either via direct myocardial injury or by inhibition of essential molecular pathways for normal cardiac function in healthy hearts or pathways which serve to stabilise function in individuals with pre-existing cardiovascular disease. The most common and best understood is anthracycline cardiotoxicity, with drugs such as doxorubicin and epirubicin still being the cornerstone of treatment for breast cancer, lymphoma, sarcoma and various haematological malignancies. Anthracyclines initially cause a functional impairment of ventricular myocardium, which with increasing dose and time can lead to irreversible damage via myocyte necrosis, apoptosis and replacement fibrosis. Radiation to the heart can also cause direct toxicity leading to HF, both via direct myocardial damage and indirectly via myocardial infarction from radiation-induced coronary artery disease, valvular heart disease and pericardial constriction.1 4 The list of newer cancer drugs causing HF is expanding rapidly, including trastuzumab and HER2-targeted treatments, tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors or the BCr-Abl fusion protein, proteasome inhibitors and the new checkpoint inhibitors. When compared with other forms of HF, cancer therapy-induced HF has historically been considered one of the …