Abstract: |
The highly active chemotherapeutic agents doxorubicin, duanorubicin, idarubicin, epirubicin, and mitoxantrone are also associated with acute, largely reversible cardiotoxic effects and a dose-related cardiomyopathy. This cardiomyopathy is characterized by minimal left ventricular enlargement and global systolic dysfunction, usually with associated mild to moderate mitral insufficiency. Historically, this was characterized by myocardial biopsy and radionuclide angiography. More recently, echocardiography has become the most widely available and cost-efficient tool for diagnosis. The precise mechanism of this toxicity has not been fully defined. However, the maximum tolerated cumulative dose can by increased by reducing peak drug levels and concurrent administration of the iron chelator, dexrazoxane. Because anthracycline-induced cardiomyopathy is largely irreversible and cumulative, prevention is the preferred strategy. Monitoring by assessment of left ventricular function by the most reproducible method available as patients approach potentially toxic doses can substantially reduce toxicity. Stress studies before major procedures such as bone marrow or stem cell transplants may be of benefit. This syndrome responds well to conventional therapy for congestive heart failure with angiotensin-converting enzyme inhibitors, digoxin, and diuretics. The beta-blocker carvedilol is often associated with significant improvement in ejection fraction and symptoms and spironolactone is well tolerated and often of benefit. The long-term outlook of the syndrome is much better than previously reported because of advances in therapy and prevention. Copyright © 2001 by W.B. Saunders Company. |