Acute Doxorubicin Cardiotoxicity
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《新英格兰医药杂志》
To the Editor: A previously healthy 78-year-old woman presented with facial flushing, palpitations, diarrhea, and generalized weakness. The serum serotonin level was markedly elevated (2233 ng per milliliter; normal, <180), as was urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (118.7 mg per 24 hours; normal, <6.0), and a computed tomographic (CT) scan revealed a small-bowel mass, 3 cm by 2.5 cm, with multiple hepatic lesions. Fine-needle liver biopsy demonstrated cytokeratin- and chromogranin-staining cells, which are characteristic of carcinoid tumor. Despite monthly injections of octreotide, the patient's flushing persisted, and a CT scan showed enlargement of both small-bowel and liver masses. She subsequently underwent hepatic-artery chemoembolization with use of cisplatin (100 mg), doxorubicin (50 mg), and mitomycin (10 mg).
Acute pulmonary edema necessitating mechanical ventilation developed 30 hours after chemoembolization. This decompensation was associated with lactic acidosis, anuric renal failure (peak serum creatinine level, 4.6 mg per deciliter), elevated cardiac-enzyme levels (creatine kinase, 668 U per liter; creatine kinase MB isoenzyme, 48.8 ng per milliliter; troponin I, 20.64 ng per milliliter [normal, <1.50]), and a markedly increased brain-type natriuretic peptide level (3330 pg per milliliter; normal, <100). Transthoracic echocardiography showed severe global left ventricular dysfunction with an ejection fraction of 10 percent. Cardiac catheterization revealed normal coronary arteries and severely depressed cardiac output (cardiac index, 1.0 liter per minute per square meter; normal, >2.8). An intraaortic balloon pump was placed, and the patient had marked clinical improvement and was able to be extubated 48 hours later. She was discharged one week later receiving carvedilol and enalapril. Another echocardiogram obtained four weeks later showed that the left ventricular ejection fraction had increased to 45 percent.
Hepatic-artery chemoembolization has become an accepted treatment for patients with metastatic carcinoid tumor, providing long-term palliation of symptoms and control of tumor growth.1 Cardiotoxicity associated with the administration of doxorubicin is most commonly manifested by dose-dependent chronic cardiomyopathy, and acute effects, including left ventricular failure, are rare.2,3 To our knowledge, there have been no previous reports of acute cardiotoxicity after hepatic-artery chemoembolization with an anthracycline antineoplastic agent.
Evidence of both myocardial necrosis and acute myocardial dysfunction developed in our patient after the administration of doxorubicin in a single dose well below that typically associated with cardiotoxic effects. The rapid improvement in left ventricular function observed in this patient within four weeks suggests that substantial myocardial stunning was present. Although it is very rare, acute reversible left ventricular failure should be considered in patients in whom respiratory failure or shock develops after the administration of even a single dose of doxorubicin.
Emil R. Hayek, M.D.
Eric Speakman, M.D.
Esther Rehmus, M.D.
Akron General Medical Center
Akron, OH 44307
ehayek@heartgroupohio.com
References
Roche A, Girish BV, de Baere T, et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 2003;13:136-140.
Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998;339:900-905.
Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996;125:47-58.
Acute pulmonary edema necessitating mechanical ventilation developed 30 hours after chemoembolization. This decompensation was associated with lactic acidosis, anuric renal failure (peak serum creatinine level, 4.6 mg per deciliter), elevated cardiac-enzyme levels (creatine kinase, 668 U per liter; creatine kinase MB isoenzyme, 48.8 ng per milliliter; troponin I, 20.64 ng per milliliter [normal, <1.50]), and a markedly increased brain-type natriuretic peptide level (3330 pg per milliliter; normal, <100). Transthoracic echocardiography showed severe global left ventricular dysfunction with an ejection fraction of 10 percent. Cardiac catheterization revealed normal coronary arteries and severely depressed cardiac output (cardiac index, 1.0 liter per minute per square meter; normal, >2.8). An intraaortic balloon pump was placed, and the patient had marked clinical improvement and was able to be extubated 48 hours later. She was discharged one week later receiving carvedilol and enalapril. Another echocardiogram obtained four weeks later showed that the left ventricular ejection fraction had increased to 45 percent.
Hepatic-artery chemoembolization has become an accepted treatment for patients with metastatic carcinoid tumor, providing long-term palliation of symptoms and control of tumor growth.1 Cardiotoxicity associated with the administration of doxorubicin is most commonly manifested by dose-dependent chronic cardiomyopathy, and acute effects, including left ventricular failure, are rare.2,3 To our knowledge, there have been no previous reports of acute cardiotoxicity after hepatic-artery chemoembolization with an anthracycline antineoplastic agent.
Evidence of both myocardial necrosis and acute myocardial dysfunction developed in our patient after the administration of doxorubicin in a single dose well below that typically associated with cardiotoxic effects. The rapid improvement in left ventricular function observed in this patient within four weeks suggests that substantial myocardial stunning was present. Although it is very rare, acute reversible left ventricular failure should be considered in patients in whom respiratory failure or shock develops after the administration of even a single dose of doxorubicin.
Emil R. Hayek, M.D.
Eric Speakman, M.D.
Esther Rehmus, M.D.
Akron General Medical Center
Akron, OH 44307
ehayek@heartgroupohio.com
References
Roche A, Girish BV, de Baere T, et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 2003;13:136-140.
Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998;339:900-905.
Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996;125:47-58.