Pharmacotoxic myocardial disease: an endomyocardial study.

Drug-induced toxic changes in the myocardium have become an increasing problem. The effect of drugs on heart morphology may be acute or cumulative. In general, adverse drug reactions manifest themselves as myocarditis (toxic or hypersensitivity), cardiomyopathy with chamber dilatation, or restrictive disease. Drugs affecting embryologic development of the heart will not be discussed. Drugs causing myocarditis can be divided into: toxic myocarditis, e.g., cyclophosphamide. The morphologic changes are dose-related and have lesions of different ages, which include myocyte necrosis with hemorrhage and vasculitis. Fibrous endocarditis, e.g., methysergide. These reactions include thickening of the endocardium and sometimes the cardiac valves with fibrosis. Drugs causing hypersensitivity myocarditis, e.g., thiazide diuretics. In this case, the lesions are not dose-related, are the same age, and there is an eosinophilic infiltrate. Drugs causing cardiomyopathic-like changes of ventricular dilatation and failure, e.g., anthracyclines, particularly adriamycin. This group of drugs cause a gradual myofibrillar loss within cardiac myocytes and a sarcotubular dilatation which is characteristic. The damaged cells are replaced by fibrosis and ventricular failure ensues. With the rapid synthesis of new drugs, the problem of drug cardiotoxicity may be an ever-increasing problem. With the more widespread use of the endomyocardial biopsy, drug-induced heart disease can be documented and the effects of different methods of drug delivery and pharmacologic antagonists studied.