A Clinical Study on the Cardiac Toxicity of Adriamycin

摘要

To clarify the exact role of endomyocardial biopsy in the diagnosis and monitoring of adriamycin-induced cardiotoxicity and to observe the actual relationship between pathologic changes and cardiac dysfunction, a cross-sectional clinical study was conducted. Echocardiography was used to evaluate cardiac dysfunction in 18 patients who had received chemotherapy including adriamycin(mean dose : 410mg/m2 of B.S.A.) without clinical evidence of congestive heart failure, and in 19 normal controls. Six patients receiving adriamycin underwent 7 transfemoral endomyocardial biopsy procedures, and the specimens were evaluated by light and electron microscopy for evidence of drug-related cardiotoxicity. Indexes of cardiac systolic function obtained by M-mode echocardiography(left ventricular dimension, excursion of interventricular septum and left ventricular posterior wall, shortening fraction and ejection fracton) did not show any statistically significant difference between patients who received adriamycin and normal controls. In transmitral flow-velocity curves recorded by Doppler echocardiography with a 2.25MHz probe, the patients showed less E peak velocity and decreased E/A ratio compared with normal controls, which suggests left ventricular diastolic dysfunction in the patients who received adriamycin. All the specimens of the endomyocardial biopsy showed significant pathologic changes of adriamycin indnced cardiotoxicity which was characterized by myofibrillar loss and vacuolization of the cytoplasm. In 2 specimens, pathologic grade was II, while 5 specimens showed pathologic changes of grade III and further chemotherapy with adriamycine was not done in thse 5 cases. From these results it is suggested that pathologic changes precede the clinical onset of congestive cardiomyopathy in the patients receiving adriamycin and left ventricular diastolic dysfunction occurrs before ejection fraction falls to subnormal levels. We conclude that sequential endomyocardial biopsy is absolutely indicated for exact diagnosis and monitoring of adrinamycin-induced cardiotoxicity to prevent the development of irreversible and often fatal cardiomyopathy.