Educational Paper: Decreasing the Burden of Cardiovascular Disease in Childhood Cancer Survivors: an Update for the Pediatrician

The cardiovascular impact of cancer therapies on the heart is one of the major concerns in the long-term follow-up of childhood cancer survivors (CCSs). Long-term cardiovascular effects include the development of left ventricular dysfunction resulting in congestive heart failure and ischemic heart disease, as well as valvular and pericardial disease. This is mainly ascribed to the cardiotoxic side effects of chemotherapeutic agents (especially anthracyclines) and radiotherapy, but other factors such as radiation and inflammation play a role in the effect of childhood cancer on the cardiovascular health. The most concerning effect is the high incidence of symptomatic heart failure in CCS patients treated with anthracyclines. More than 50 % of CCSs treated with anthracyclines develop asymptomatic left ventricular dysfunction after cancer therapy, with approximately 5 % developing clinical signs of heart failure during long-term follow-up. Once CCS patients develop congestive heart failure, prognosis is poor and is not influenced by current medical treatment strategies. To reduce the long-term burden of cardiovascular disease in pediatric cancer patients, a diversified approach will be necessary. In the acute phase, prevention of cardiac damage through the use of cardioprotective agents (e.g., dexrazoxane) or by administering less cardiotoxic chemotherapeutic agents is to be considered. A recent randomized trial suggested that the use of dexrazoxane reduced cardiac toxicity without affecting cancer outcomes. Especially patients requiring high doses of chemotherapeutic agents could benefit from this approach. Recent data suggest that genetic testing might identify patients at higher risk for cardiotoxicity. This seems mainly related to genes involved in drug metabolism. This would allow personalized approach adjusting chemotherapy based on cardiovascular risk profiling. This could be combined with newer monitoring strategies in the acute phase using newer echocardiographic techniques and biomarker screening to identify patients with early damage to the myocardium. For the long-term CCS cohort, early detection and treatment of early dysfunction prior to the development of congestive heart failure could potentially improve long-term outcomes. Promoting healthy lifestyles and controlling additional cardiovascular risk factors (e.g., obesity, diabetes, arterial hypertension) is an important task for every physician involved in the care of this growing cohort.