Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection.

Abstract

The most frequently encountered doxorubicin related cardiac toxicity is a dose-related myocardial dysfunction occurring 1-6 months after chemotherapy. Recently, late cardiotoxicity has been the focus of interest. This paper explores the possibility that acute intercurrent viral illness may trigger late cardiotoxicity. Thirty selected pediatric patients were followed for changes in their echocardiographically measured fractional shortening (FS) for 2-10 years after completion of their doxorubicin chemotherapy. They were divided according to the dose of doxorubicin they received (< 300 mg/m2 or > or = 300 mg/m2) and to whether the manifestations of an acute intercurrent viral illness during the observation period were documented. Eleven patients experienced such infections. Changes in FS demonstrated two different responses. The usual response to doxorubicin was a gradual, dose-related fall in FS, followed by recovery; while the second response included an unexpected, late, sudden decrease in FS. Four patients in the low dose subgroup experienced an acute intercurrent viral illness, but none of these demonstrated the unexpected decrease. Of the seven patients who acquired such illness in the high dose subgroup, five demonstrated the sudden, late decrease in FS, with two of them developing severe, reversible congestive heart failure. The most likely explanation for the late, sudden decrease in FS is an additional stress in patients who already have sustained subclinical cardiac damage as a result of their doxorubicin chemotherapy. An acute intercurrent viral illness may have triggered late cardiac dysfunction in some of these patients.