Chemotherapy-induced myocardial necrosis in a patient with ... · Barraine R. Two new cases of...
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RESPIRATORY MEDICINE (1997) 91, 565-567 Chemotherapy-induced myocardial necrosis in a patient with chronic lymphocytic leukemia D. G. FEDERMAN AND G. HENRY Yale University School of Medicine, General Infernal Medicine Section 111, West Haven V.A. Medical Center, Wesf Haven, CT 06516, U.S.A. Cardiac toxicity following the administration of chemotherapeutic agents is well documented. Vinca alkaloids, as well as high-dose cyclophosphamide, have been associated with myocardial ischemia. The present report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both vincristine and conventional chemotherapeutic doses of cyclophos- phamide for the treatment of chronic lymphocytic leukemia. Physicians should possess a heightened awareness of this potentially serious complication. RESPLR. MED. (1997) 91, 565-567 Introduction Cardiac toxicity following the administration of anti- neoplastic agents is well documented (1). Cardiomy- opathy, angina pectoris, myocardial infarction, arrhythmias, heart block, myocarditis and pericardi- tis have all been reported following chemotherapy. Although the best-described cardiac toxicity ascribed to antineoplastic agents is with anthracyclines, adverse cardiac events have been reported with other agents. The present case report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both cyclo- phosphamide and vincristine intravenously for the treatment of chronic lymphocytic leukemia. Case Report A 67-year-old man without a previous history of heart disease was admitted to the hospital after a complete blood count was suggestive of chronic lym- phocytic leukemia (CLL). He claimed to have been in excellent health until 1 month prior to admission when he developed fatigue, mild anorexia and a 10 Received 22 February 1996 and accepted in revised form 19 September 1996. Correspondence should be addressed to: D. G. Federman, Yale University School of Medicine, General Internal Medicine Section 111, West Haven V.A. Medical Center, 950 Campbell Avenue, West Haven, CT 06516, U.S.A. 0954.6111/97/090565 +03 $12.00/O pound weight loss. He denied fevers, chills, night sweats, chest pains, shortness of breath or a history of diabetes or hypertension. Prior to admission, he had been using acetami- nophen as needed for foot pain. He was unaware of his serum cholesterol level. He had an 80 pack-year smoking history, but had not smoked cigarettes for 15 yr. He was employed as a carpenter, and was extremely active at work. Family history was not significant for either leukemia or premature heart disease. On physical examination, he was noted to be slightly pale. He was 66 inches tall and weighed 147 pounds. Vital signs were unremarkable except for a pulse of 102 beats min ‘. No adenopathy was appre- ciated. The cardiac examination revealed a regular tachycardia without murmurs, rubs or gallops. The patient’s lungs were clear to auscultation, and no hepatomegaly or splenomegaly were palpated. Results of a complete blood count revealed a hemoglobin of 8 g dl - ‘, and a white blood count of 300 000 mm- 3 with 88% lymphocytes, 9% blasts and 3% prolymphocytes. The platelet count was 180 000 mmm3. Routine chemistries including elec- trolytes, blood urea nitrogen and creatinine were unremarkable. Serum aspartate aminotransferase was 26 U 1- ‘, alanine aminotransferase 18 1- r, alkaline phosphatase 82 U 1- ‘, total bilirubin 0.3 mg dl- ’ and direct bilirubin 0.1 mg dl - ‘. On the second hospital day, he was treated with a chemotherapy regimen including 1300 mg of cyclo- phosphamide (738 mg m - 2 based on his body surface 0 1997 W. B. SAUNDERS COMPANY LTD
Transcript of Chemotherapy-induced myocardial necrosis in a patient with ... · Barraine R. Two new cases of...
RESPIRATORY MEDICINE (1997) 91, 565-567
Chemotherapy-induced myocardial necrosis in a patient with chronic lymphocytic leukemia
D. G. FEDERMAN AND G. HENRY
Yale University School of Medicine, General Infernal Medicine Section 111, West Haven V.A. Medical Center, Wesf Haven, CT 06516, U.S.A.
Cardiac toxicity following the administration of chemotherapeutic agents is well documented. Vinca alkaloids, as well as high-dose cyclophosphamide, have been associated with myocardial ischemia. The present report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both vincristine and conventional chemotherapeutic doses of cyclophos- phamide for the treatment of chronic lymphocytic leukemia. Physicians should possess a heightened awareness of this potentially serious complication.
RESPLR. MED. (1997) 91, 565-567
Introduction
Cardiac toxicity following the administration of anti- neoplastic agents is well documented (1). Cardiomy- opathy, angina pectoris, myocardial infarction, arrhythmias, heart block, myocarditis and pericardi- tis have all been reported following chemotherapy. Although the best-described cardiac toxicity ascribed to antineoplastic agents is with anthracyclines, adverse cardiac events have been reported with other agents.
The present case report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both cyclo- phosphamide and vincristine intravenously for the treatment of chronic lymphocytic leukemia.
Case Report
A 67-year-old man without a previous history of heart disease was admitted to the hospital after a complete blood count was suggestive of chronic lym- phocytic leukemia (CLL). He claimed to have been in excellent health until 1 month prior to admission when he developed fatigue, mild anorexia and a 10
Received 22 February 1996 and accepted in revised form 19 September 1996. Correspondence should be addressed to: D. G. Federman, Yale University School of Medicine, General Internal Medicine Section 111, West Haven V.A. Medical Center, 950 Campbell Avenue, West Haven, CT 06516, U.S.A.
0954.6111/97/090565 +03 $12.00/O
pound weight loss. He denied fevers, chills, night sweats, chest pains, shortness of breath or a history of diabetes or hypertension.
Prior to admission, he had been using acetami- nophen as needed for foot pain. He was unaware of his serum cholesterol level. He had an 80 pack-year smoking history, but had not smoked cigarettes for 15 yr. He was employed as a carpenter, and was extremely active at work. Family history was not significant for either leukemia or premature heart disease.
On physical examination, he was noted to be slightly pale. He was 66 inches tall and weighed 147 pounds. Vital signs were unremarkable except for a pulse of 102 beats min ‘. No adenopathy was appre- ciated. The cardiac examination revealed a regular tachycardia without murmurs, rubs or gallops. The patient’s lungs were clear to auscultation, and no hepatomegaly or splenomegaly were palpated.
Results of a complete blood count revealed a hemoglobin of 8 g dl - ‘, and a white blood count of 300 000 mm- 3 with 88% lymphocytes, 9% blasts and 3% prolymphocytes. The platelet count was 180 000 mmm3. Routine chemistries including elec- trolytes, blood urea nitrogen and creatinine were unremarkable. Serum aspartate aminotransferase was 26 U 1 - ‘, alanine aminotransferase 18 1 - r, alkaline phosphatase 82 U 1 - ‘, total bilirubin 0.3 mg dl- ’ and direct bilirubin 0.1 mg dl - ‘.
On the second hospital day, he was treated with a chemotherapy regimen including 1300 mg of cyclo- phosphamide (738 mg m - 2 based on his body surface
0 1997 W. B. SAUNDERS COMPANY LTD
566 D. G. FEDERMAN AND G. HENRY
FIG. 1. Electrocardiogram of the patient (a) prior to receiving chemotherapy and (b) with chest pain after receiving chemotherapy.
area of 1.76 m - 2, over 15 min and 2 mg of vincristine given intravenously. Approximately 8 h after the initiation of the chemotherapy, the patient developed prolonged retrosternal chest pressure radiating down both arms, only minimally relieved by nitroglycerin and morphine sulfate. ST segment elevation was noted by ECG in leads II, III and a VF, and in leads V3-V6. In addition, the electrical voltage was deceased when compared to the admission ECG (Fig. 1). Creatine phosphokinase (CPK) rose from 82 U 1 - ’ with an MB fraction of 2 ng ml - ’ at the inception of chest pain to 2049 U 1 - ’ with an MB of 274 ng ml - ’ 16 h later (normal values: CPK O-180 U 1 - ‘, MB less than 5 ng ml - ‘). An echo- cardiogram performed 2 days after the chest pain episode demonstrated apical dyskinesis with a mural
thrombus. The left ventricular ejection fraction was estimated to be between 35 and 40%, and a small non-hemodynamically significant posterior pericar- dial effusion was observed. A dipyridamole cardiac positron emission scan revealed severe fixed infralat- era1 and apical perfusion defects. There was no evi- dence of inducible myocardial ischemia. The patient was eventually discharged home and has remained without chest pain.
Discussion
Cyclophosphamide and vincristine are widely utilized chemotherapeutic agents, and each has been associ- ated with cardiotoxicity (2,lO). Several reports have
emerged in the literature implicating vinca alkaloids and myocardial ischemia. Chest pain, T-wave inver- sions on ECG, congestive heart failure without a rise of cardiac enzymes [suggesting reversible cardiac ischemia (2)] as well as complicated myocardial infarction have been attributed to vinca alkaloids. In at least two of the cases of completed infarction, coronary angiography revealed normal epicardial vessels (3,4).
High-dose cyclophosphamide, frequently employed in combination with autologous bone marrow trans- plantation, has been noted to cause myocarditis, pericardial effusion, reduction in electrocardiographic voltage, congestive heart failure, arrhythmias, non- specific ST-T wave changes, heart block and myocar- dial necrosis (S-7). Autopsy reports from fatal cases have revealed diffuse myocardial edema, ischemic degeneration, focal cardiac necrosis with hemorrhage, fibrin deposition and vascular endothelial damage (6-8).
Conventional chemotherapeutic doses of cyclo- phosphamide have been reported to cause toxicity that resembles myocardial ischemia with chest pain and abnormal ECG, but without cardiac enzyme elevation (9,lO). One patient who experienced chest pain with ECG abnormalities subsequently under- went dipyriadmole-thallium imaging which revealed no reversible perfusion abnormalities (10).
The authors are unaware of any prior report of a myocardial infarction in a patient receiving a conven- tional dose of cyclophosphamide. It is unclear whether or not the ST segment elevation, loss of electrocardiographic voltage and myocardial enzyme elevation was caused by coincident coronary artery disease, vincristine or cyclophosphamide alone, or the potentiation of one chemotherapeutic agent’s cardio- toxicity by the other. This patient’s complete absence of chest pain while performing heavy manual labor prior to admission, and the striking temporal rela- tionship between receiving the antineoplastic agents and manifesting chest pain, mitigate against him exhibiting coincidental coronary artery disease and myocardial infarction.
Although there have been reports of vinca alkaloid as well as high-dose cyclophosphamide induced
CHEMOTHERAPY-INDUCED MYOCARDIAL NECROSIS 567
cardiac toxicity, it is possible that the combination of these two agents, even with conventional chemothera- peutic doses of cyclophosphamide, pose a significant threat to patients. Although the rarity of this syn- drome should not dictate that physicians administer these agents in a monitored setting, the authors feel it would be prudent to possess a heightened aware- ness of this serious and potentially life-threatening complication.
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