Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals.
Doxorubicin, whose dose-limiting toxicity is cardiomyopathy, was given to four cancer patients. Endomyocardial biopsy specimens and test results of cardiac function were obtained  before, during, and after treatment. The biopsy specimens were examined by light and electron microscopy and were graded blindly. Evidence of specific doxorubicin injury was found in 3/4 patients with as little as 180 mg/sq m of the drug and became progressively more severe with higher doses. All test results of cardiac function, including systolic time intervals, remained normal. These data suggest that a specific, progressive subclinical injury to the heart occurs with doxorubicin therapy, which cannot be reliably detected by routine tests. This potential risk must be taken into account with the use of doxorubicin, especially when combined with synergistic agents.
D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods; D009202:Cardiomyopathies / Q000139:chemically induced*; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D011446:Prospective Studies; D013599:Systole / Q000187:drug effects
D004317:Doxorubicin