Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy

A nthracyclines are among the most widely used chemo-therapeutic agents and have been shown to be effective in a wide range of tumors, in particular, breast cancer and lymphoma. Their clinical effectiveness, however, may be thwarted by the development of cardiotoxicity that negatively affects patients' outcomes and seriously limits their onco-logical therapeutic opportunities. According to the time of onset, 3 distinct types of cardiotoxicities have been recognized: (1) acute, occurring after a single dose, or a single course, of anthracyclines, with the onset of clinical manifestations within 2 weeks from the end of treatment; (2) early-onset chronic, developing within 1 year. This is the most frequent and clinically relevant form of cardiotoxicity, usually presenting as a dilated and hypokinetic cardiomyopathy leading to heart failure (HF); (3) late-onset chronic, developing years, or even decades, after the end of chemotherapy. This classification dates back to the early 1980s, and it is based on small retrospective studies reporting the occurrence of HF symptoms in childhood cancer survivor populations. 5–8 The clinical relevance of such a classification, however, is unclear, particularly when applied to adult populations. Actually, the timing of anthracycline-induced cardiotoxicity is not well defined, because, at present, no prospective study has regularly monitored cardiac function in adult patients for >3 years. Thus, the questions of whether this classification is based on diagnosis , rather than onset, of cardiotoxicity, and whether it reflects 3 distinct diseases rather than a single process, remain unanswered. As a result, recommendations for monitoring patients with cancer who are treated with anthracycline-containing chemotherapy (ACT) are still unclear, and often limited to symptomatic patients. Although several guidelines Background—Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. Methods and Results—We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6–8.0) years. The overall …