DOXORUBICIN CARDIOMYOPATHY - EVALUATION BY PHONOCARDIOGRAPHY, ENDOMYOCARDIAL BIOPSY, AND CARDIAC-CATHETERIZATION

Right ventricular endomyocardial biopsy, right heart catheterization, and systolic time intervals were done in 33 adult patients receiving doxorubicin (Adriamycin(TM)) Doxorubicin administration was associated with a dose-related increase in the degree of myocyte damage, and 27 of 29 patients biopsied at doses ≥ 240 mg/m2 had doxorubicin-associated degenerative changes identified on biopsy. The pre-ejection period to left ventricular ejection time ratio (PEP/LVET) showed a threshold phenomenon and did not begin to increase until a total dose of 400 mg/m2 had been reached. Seven patients with catheterization-proven heart failure had a significantly greater amount of myocyte damage on biopsy than dose-matched control subjects (p < 0.01). Previous mediastinal radiation appeared to potentiate the doxorubicin-associated degenerative process. Mediastinal radiation and age ≥ 70 years appeared to be risk factors for doxorubicin-associated heart failure. Dose limitation by combined clinical, noninvasive, invasive, and morphologic criteria offered an advantage over empirical dose limitation or dose limitation by PEP/LVET alone.