Shan and colleagues [1] provided a thorough, insightful, and well-balanced review of anthracycline cardiomyopathy. However, the discussion of the clinical significance of late-onset cardiotoxicity presented some confusing information that needs to be clarified. The authors stated that "new-onset symptomatic ventricular dysfunction was not seen until 12 to 14 years after treatment in the study by Lipshultz and coworkers." However, the symptomatic patients reported by Lipshultz and colleagues actually had "recurrent heart failure 3.7 to 10.3 years after completing doxorubicin treatment, and ... [n]o patient had late heart failure as a new event" [2]. In fact, the patients Shan and colleagues cited as having "new-onset symptomatic ventricular dysfunction" were described in a study my colleagues and I conducted; in this study, the four patients with de novo late symptoms had been treated 12 to 18 years earlier [3]. Although most patients we described had been followed for less than 10 years after completion of chemotherapy, our cohort contained 56 patients who were followed for more than 10 years ( 20 years after chemotherapy). The incidence of systolic ventricular dysfunction in this subset was as high as 38%, as can be seen in our figure (Shan and colleagues' Figure 3.

More recently, we described 42 patients who had cardiac evaluations 15 or more years after anthracycline therapy, including a growing subset studied more than 20 years after chemotherapy [4]. This study explored the question posed in Shan and colleagues' closing paragraph. In our study, the incidence of left ventricular systolic dysfunction was 43%. We have now evaluated more than 70 patients 15 to 28 years after completion of chemotherapy. Unfortunately, the incidence of ventricular dysfunction continues to increase with time, and we have already seen several cases of de novo cardiac failure in young adults more than 20 years after they had had chemotherapy during childhood.

These findings underscore the importance of the quest for a method of protecting the heart during anthracycline therapy. In another report (reference 97 of Shan and coworkers' review), we substantiated the effectiveness of monitoring systolic function during chemotherapy for reducing but not eliminating short-term cardiotoxicity in 750 patients. In another study [5], we also documented the efficacy of continuous infusion of anthracycline for reduction of cardiac dysfunction in children; antileukemic efficacy was shown to be enhanced rather than decreased.

As Shan and colleagues mentioned, it has been estimated that by the year 2000, 1 of every 900 young adults will be a survivor of childhood cancer. Thus, it is gratifying that the important subject of anthracycline cardiomyopathy has been reviewed so thoroughly in Annals. It is hoped that further investigation and reports on this subject will be forthcoming.