Cardiomyopathy Induced by Antineoplastic Drugs

Summary

Two types of CM are induced by drugs used in the treatment of cancer. The first, produced by anthracycline drugs (adriamycin and daunorubicin), is characterized by congestive heart failure, cardiac dilatation, and structural evidence of myocardial cellular degeneration. The second results from high doses of cyclophosphamide used in combination with other chemotherapeutic agents to ablate bone marrow in preparation for bone marrow transplantation. It is manifested by acute, fulminating cardiac failure, pericarditis, and myocardial microthrombosis. The pathogenesis of these CMs is discussed here.

Drug-induced eM may be defined as any type of heart muscle disease resulting either directly or indirectly from the administration of drugs or from exposure to chemical agents. Among the many drugs known to have cardiotoxic properties are sympathomimetic amines (isoproterenol, epinephrine and norepinephrine), cardiac glycosides, antihypertensives (hydralazine and minoxidil), vasoconstrictors, anticoagulants, hormones (thyroid hormone, insulin and corticosteroids), phenothiazines and other psychotherapeutic agents, antibiotics, antineoplastic agents (anthracyclines and cyclophosphamide), antimalarials (Plasmocid), emetine, histamine, anesthetics, vitamin D, ethanol, and a number of compounds of heavy metals [1]. Some of these agents, particularly when used in very large doses, have direct toxic or necrotizing effects on the myocardium; many others affect mainly the coronary circulation, with or without direct concomitant effects on the myocardium, and others act by precipitating unusual side effects or hypersensitivity reactions that involve the heart [1]. Regardless of the mechanism of action, most of these drugs exert acute rather than chronic effects manifested by the clinical picture of congestive or dilated type of cardiomyopathy. Anthracycline compounds constitute the main exception to this generalization. Until the introduction of daunorubicin and adriamycin, two anthracycline-type agents, the clinical use of a large number of powerful antimetabolites and antibiotics with antineoplastic properties had been associated with a remarkable paucity of clinically evident cardiac complications, perhaps because the main effects of most drugs used in the treatment of cancer are directed against rapidly growing and dividing cells, and because the effects on such cells overshadow any mild cardiac toxic effects of such drugs. In contrast to other clinically useful antineoplastic agents, both daunorubicin and adriamycin produce acute cardiac effects as well as a significant incidence of a unique syndrome of drug-induced chronic cardiomyopathy. This cardiomyopathy is characterized by congestive heart failure, cardiac dilatation, and structural evidence of severe myocardial cellular degeneration. More recently, a second syndrome of cardiomyopathy induced by antineoplastic drugs has been observed when high doses of cyclophosphamide are used in combination with other chemotherapeutic agents in patients undergoing ablation of bone marrow in preparation for bone marrow transplantation. This cardiomyopathy is manifested by acute, fulminating cardiac failure, pericarditis, and myocardial microthrombosis. The present communication reviews the clinical and pathologic features of these two types of cardiomyopathy produced by antineoplastic agents.