A New Paradigm for an Old Classic
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Anthracyclines are potent antineoplastic agents with proven efficacy in the treatment of many pediatric and adult hematologic and solid organ cancers. Dose-dependent anthracycline-induced cardiomyopathy is the most notorious and well-studied chemotherapy-induced cardiovascular toxicity that was first described in 1971 in 67 patients treated with Adriamycin for a variety of tumors.1 The clinical significance of anthracycline cardiotoxicity is growing with increasing cancer survivorship and increasing use of anthracyclines in cohorts predisposed to adverse cardiac effects such as the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic irradiation. However, our current knowledge of anthracycline cardiotoxicity derives mainly from retrospective analyses of patients with cancer who have symptomatic heart failure during or after chemotherapy. This had led to wide variations in the estimated incidence and prognosis of anthracycline cardiotoxicity and has contributed to the lack of accepted guidelines for the surveillance and management of this potentially important complication of cancer therapy. For these reasons, the prospective study by Cardinale et al2 in this issue of Circulation evaluating the incidence of cardiotoxicity, its timing of occurrence, and its clinical response to medical therapy in a large population of anthracycline-treated adults is an important step toward resolving these uncertainties.
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Cardinale et al2 describe a 9% incidence of cardiotoxicity among 2625 anthracycline-treated patients who underwent periodic, scheduled surveillance of left ventricular (LV) function, before, during, and after chemotherapy, over a median follow-up of 5.2 years. In this cohort, cardiotoxicity, defined as a >10% decline in LV ejection fraction (LVEF) from baseline and a final LVEF of <50%, occurred almost exclusively (98% of cases) within the first year after completing anthracycline treatment. Late reductions in LVEF were observed in only 5 (2%) patients and occurred >5.5 years after chemotherapy. Full or partial recovery of LVEF was …