The Effects of Immunosuppressive and Cytotoxic Drugs on the Heart

Antiinflammatory therapy is the principal therapy for most rheumatic diseases with the primary therapeutic goal being to reduce the destructive effects of the inflammatory process without causing systemic side effects due to overimmunosuppression. The heart is one of the primary organs affected by the side effects of these agents through both direct (myocardial injury) and indirect (hypertension, hyperlipidemia, etc.) actions that can result in myocardial injury in a number of different ways. Cyclophosphamide has direct cardiotoxic effects and can result in heart failure. Prednisone has secondary side effects including hypertension and hyperlipidemia, which can cause and/or accelerate coronary artery disease, and if a myocardial infarction happens can result in heart failure due to ischemic injury. Conversely, prednisone and other agents are often used for the therapy of inflammatory processes of the heart and in that setting can actually preserve left ventricular function and result in an improvement in ejection fraction. Finally, cyclosporine, which was the principal immunosuppressive agent responsible for the vast increase in organ transplantation, has resulted in many patients undergoing heart transplantation safely that otherwise would never have received a heart. This chapter will review the positive and negative cardiac properties of the traditional antiinflammatory agents prednisone, azathioprine, methotrexate, cyclosporine, and cyclophosphamide.