Anthracycline-Induced Cardiotoxicity

PURPOSE: To review the current understanding of the clinical significance, detection, pathogenesis, and prevention of anthracycline-induced cardiotoxicity. DATA SOURCES: A MEDLINE search of the English-language medical literature and a manual search of the bibliographies of relevant articles, including abstracts from national cardiology meetings. STUDY SELECTION: Pertinent clinical and experimental studies addressing the clinical relevance, pathogenesis, detection, and prevention of anthracycline cardiotoxicity were selected from peer-reviewed journals without judgments about study design. A total of 137 original studies and 9 other articles were chosen. DATA EXTRACTION: Data quality and validity were assessed by each author independently. Statistical analysis of combined data was inappropriate given the differences in patient selection, testing, and follow-up in the available studies. DATA SYNTHESIS: Anthracycline-induced cardiotoxicity limits effective cancer chemotherapy by causing early cardiomyopathy, and it can produce late-onset ventricular dysfunction years after treatment has ceased. Detection of subclinical anthracycline-induced cardiomyopathy through resting left ventricular ejection fraction or echocardiographic fractional shortening is suboptimal. Conventional doses of anthracycline often lead to permanent myocardial damage and reduced functional reserve. Underlying pathogenetic mechanisms may include free-radical-mediated myocyte damage, adrenergic dysfunction, intracellular calcium overload, and the release of cardiotoxic cytokines. Dexrazoxane is the only cardioprotectant clinically approved for use against anthracyclines, and it was only recently introduced for selected patients with breast cancer who are receiving anthracycline therapy. CONCLUSIONS: A rapidly growing number of persons, including an alarming fraction of the 150 000 or more adults in the United States who have survived childhood cancer, will have substantial morbidity and mortality because of anthracycline-related cardiac disease. The development of effective protection against anthracycline-induced cardiotoxicity will probably have a significant effect on the overall survival of these patients.