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A variety of medications, illicit drugs, and toxic substances can produce acute or chronic myocardial injury; the clinical presentation varies widely. The phenothiazines, lithium, chloroquine, disopyramide, antimony-containing compounds, and arsenicals can also cause ECG changes, arrhythmias, or heart failure. Hypersensitivity reactions to sulfonamides, penicillins, and aminosalicylic acid as well as other medications can result in cardiac dysfunction. Radiation can cause an acute inflammatory reaction as well as a chronic fibrosis of heart muscle, usually in conjunction with pericarditis.
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Cardiotoxicity from cocaine may occur from coronary artery spasm, MI, arrhythmias, and myocarditis. A cocaine cardiomyopathy has also been described. Because many of these processes are believed to be mediated by cocaine’s inhibitory effect on norepinephrine reuptake by sympathetic nerves, beta-blockers have been used in patients with fixed stenosis. In documented coronary spasm, calcium channel blockers and nitrates may be effective. Usual therapy for heart failure or conduction system disease is warranted when symptoms occur. Other recreational drug use has been associated with myocarditis in various case reports.
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Systemic disorders are also associated with myocarditis. These include giant cell myocarditis, eosinophilic myocarditis, celiac disease, granulomatosis with polyangiitis, and sarcoidosis. A benefit from immunosuppressive therapy, especially in giant cell myocarditis has been suggested in a number of observational studies, including those directed primarily at T cells (ie, using muromonab-CD3). Treatment of eosinophilic myocarditis includes the use of high-dose corticosteroids and removal of the offending medication or underlying trigger, if known. Most studies suggest that HIV is only indirectly responsible for HIV cardiomyopathy, and other factors, gp 120 protein, adverse reaction to antiretroviral therapy, and opportunistic infections have been implicated more often. Epstein-Barr and herpes simplex viruses have been identified in some patients’ myocardium.
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The problem of cardiovascular side effects from cancer chemotherapy agents is an ever growing one and has spawned a new clinical area in cardiology called cardio-oncology. Anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin, and mitoxantrone) remain the cornerstone of treatment of many malignancies but may result in cardiomyopathy. Heart failure can be expected in 5% of patients treated with a cumulative dose of 400–450 mg/m2, and this rate is doubled if the patient is over age 65. While symptoms and evidence for myocardial dysfunction usually appear within 1 year of starting therapy, late onset manifestation of heart failure may appear up to a decade later. The major mechanism of cardiotoxicity is thought to be due to oxidative stress inducing both apoptosis and necrosis of myocytes. There is also disruption of the sarcomere. This pathologic understanding is the rationale behind the superoxide dismutase mimetic and iron-chelating agent, dexrazoxane, to protect from the injury. The use of trastuzumab in combination with anthracyclines increases the risk of cardiac dysfunction up to 28%; this has been an issue since combined use of these agents is particularly effective in HER2-positive breast cancer. Other risk factors for patients receiving anthracyclines include the use of paxlitaxel, concurrent radiation, and preexisting cardiovascular disease (including hypertension, ...