Proposed management of cardiotoxicity during pediatric AML therapy. This figure depicts our proposed algorithm to manage cardiotoxicity during AML therapy, with the goal of balancing cardiac safety with effective delivery of AML-directed chemotherapy. LVEF cutoffs are based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) V3.0 for LVSD: grade 2 LVSD is defined as asymptomatic LVEF decline of 40% to 49%. Grade 3 LVSD is defined as LVEF decline of 20% to 39%, or symptomatic heart failure. These LVEF thresholds are consistent with grade 2/3 “ejection fraction decreased” in CTCAE V5.0. *Additional testing may include biomarkers (eg, N-terminal-pro B-type natriuretic peptide), CMRI, or alternate testing as indicated. Biomarkers currently have an established role in secondary/further evaluation but are under investigation as a primary screening modality. ^Cardiac remodeling medications may include angiotensin converting enzyme inhibitors (eg, enalapril) and beta-blockers (eg, carvedilol). #When omission of anthracyclines is necessary due to persistent LVSD, efforts should be made to maintain the intensity of chemotherapy, if appropriate. Thus, we suggest replacing with an intensive non-anthracycline-containing chemotherapy block, such as high-dose cytarabine and asparaginase (Capizzi II).