Cardiomyopathy in childhood cancer survivors: Etiology, pathophysiology, diagnosis, treatment, and screening

Background: There is an increase in childhood cancer survivors because of advancements in cancer treatment. Current overall survival of childhood cancer in developed nations is >80 %. Increased survival is associated with an increase in long-term therapy-related adverse events. Cardiotoxicity from exposure to chemo- and radiation therapy may cause major short- and long-term sequelae. Aim of review: The purpose of this article is to review current concepts about cardiotoxicity associated with pediatric cancer therapy including etiology, pathophysiology, diagnosis, treatment, and screening. Key scientific concepts of review: Anthracycline drugs produce reactive oxygen species that cause damage to myocytes. Radiation therapy causes collagen replacement and fibrosis in the pericardium and myocardium. Acute complications include arrhythmias, decreased left ventricle (LV) function, and heart failure. Chronic complications occurring >1 year after treatment initiation include coronary artery disease, valvular disease, and cardiomyopathy. These adverse events are observed mostly with high cumulative doses of anthracyclines (>250 mg/m2) or radiation therapy (>30 Gy). Additional risk factors such as preexisting cardiac illness, hypertension, dyslipidemia, and diabetes may contribute to adverse outcomes. Echocardiography is the most commonly used method of screening and diagnosis of cardiac dysfunction. In contrast, cardiac magnetic resonance imaging is more precise but also costly and requires sedation. Prevention of cardiotoxicity includes the use of dexrazoxane, enalapril, and methods to modify the dosage and delivery of chemo- and radiation therapy. Treatment of established cardiomyopathy may include interventions for LV preload and afterload reduction, implantable devices, and heart transplant. With emphasis on prevention, current guidelines recommend frequent screening echocardiography and individualized multimodal care for each patient. Further studies are justified to develop safe and effective alternatives to cardiotoxic cancer therapy regimens and improved treatments for established cardiomyopathy.