Advanced heart failure therapies for patients with chemotherapy-induced cardiomyopathy.

C ontinual advances in antineoplastic therapies have produced better cancer outcomes with 13.7 million cancer survivors in the United States in 2013 1. However, a significant number of survivors may develop cardiac disease as a result of cancer treatment, whether chemotherapy, radiation, or a combination of both. 2 Although radiation can cause significant heart disease 3 both alone and with chemotherapy, this review will only address cardiomyopathy induced by chemotherapy agents, especially anthracyclines, commonly used to treat pediatric and adult cancers. Whereas anthracyclines remain the most common cause of chemotherapy-induced cardiomy-opathy (CCMP), recently developed targeted therapies can also cause cardiac dysfunction. 4–6 Newer drugs that target survival pathways in cancer cells, such as the HER-2 (human epidermal growth factor 2) and vascular endothelial growth factor inhibi-tors, have been directly implicated in left ventricular (LV) sys-tolic dysfunction 7,8 through off-target effects. Because cancer and heart cells share many of the same survival pathways, it is likely that newer targeted therapies will continue to cause off-target impairment of cardiomyocyte survival and heart failure (HF). 9 However, whereas LV dysfunction associated with targeted therapies seems reversible, 10 anthracyclines remain the only agents that seem capable to cause end-stage HF. 11 In this review, we critically appraise the data available to support the use of advanced HF therapies in this patients with CCMP and end-stage HF. Specifically, we review treatments indicated for American College of Cardiology/American Heart Association stages C-D HF, including implantable cardiac defibrillators, cardiac resynchronization therapy (CRT), mechanical circulatory support devices, and orthotopic heart transplantation (OHT). Epidemiology Herein defined as cardiomyopathy caused by anthracy-cline damage with or without exposure to other cardiotoxic agents, 12 CCMP has been described in 1% to 5% of cancer survivors 13,14 and arguably portends the worst survival among cardiomyopathies. 15 Unlike any other cause of HF, CCMP is completely iatrogenic and predictably caused by escalating doses of anthracyclines. At cumulative doses of <400 mg/m 2 , the incidence of HF is 0.14% but increases to 5%, 26%, and 48% at 400, 550, and 700 mg/m 2 , respectively 16,17. Factors that potentiate CCMP are age extremes (<4 years or >65 years), radiation, female sex, pre-existing cardiac diseases, hyperten-sion, liver disease, exposure to cyclophosphamide, and whole-body hyperthermia. Consequently, the 2 groups of survivors most susceptible to CCMP are those with cancers commonly treated with anthracyclines: children and adults with hematologic malig-nancies and women with breast cancer. For example, …