Acute Myocardial Infarction Due to Chronic Myelogenous Leukemia

1 Barrett RJ, Tuttle WM: A study of essential hemoptysis. J Thorac Cardiovasc Surg 40:468-474, 1960 2 Jackson CL, Diamond S: Hemorrhage from the trachea, bronchi and lungs of nontuberculous origin. Am Rev Tuberc 46:126-138, 1942 3 Bird RM, Hammarsten JF, Marshall RA, et al: A family reunion. A study of hereditary hemorrhagic telangiectasia. N Engl J Med 257:105-109, 1957 4 Harrison DFN: Familial hemorrhagic telangiectasia. Twenty cases treated with systemic estrogen. Q J 33:25-38, 1964 5 Hanes FM: Multiple hereditary telangiectases causing hemorrhage (hereditary hemorrhagic telangiectasia). Bull Johns Hopkins Hosp 20:63, 1909 6 Osler W: On a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes. Bull Johns Hopkins Hosp 12:333-337, 1901 7 Jacobson G, Krause U: Hereditary haemorhragic telangiectasia localized to the gastrointestinal tract. Scand J GastroenteroI5:283-288, 1970

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Acute Myocardial Infarction Due to Chronic Myelogenous Leukemia * Gary A. Bergeron, M.D.,oO and Brian Datnow, M.B., B.Ch.t

Myocardial infiltration by leukemic granulocytes in association with a myeloproliferative malignancy is common. For reasons not clearly understood, clinical manifestations are unusual and myocardial infarction is rare. A patient is described in whom acute myocardial infarction is associated with myocardial granulocytic and myeloblastic infiltration and normal coronary arteries. The diagnosis of infarction in this cUnical setting was supported by appropriate ECG and enzyme changes, as weD as histologic examination of the myocardium and pathologic study of the coronary arteries. The findings in this patient may have been caused by extensive ventricular leukemic btfiltration and small vessel distortion resulting in necrosis. With the advent of new therapeutic regimens, a diagnosis of this condition may be made with increasing frequency. infarction as a consequence of infiltration M yocardial by malignant cells a patient with normal coroin

nary vasculature is rare. A histologically documented case due to chronic myelogenous leukemia is described. CASE REPORT

A 68-year-old woman with a three-and-one-half-year his·From the Cardiovascular Unit, Department of Medicine and Department of Pathology, Peter Bent Brigham Hospital and Harvard Medical School, Boston. Supported by USPHS Grant No.5 TOI HL 05679-08 and Peter Bent Brigham Hospital. .ooResearch Fellow, Cardiovascular Unit, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School. tJunior Assistant Resident, Department of Pathology, Peter Bent Brigham Hospital and Harvard Medical School. Reprint requests: Dr. Bergeron, 47 Claf/moss Road, Brighton, Massachusetts 02135

452 BERGERON, BAYNOW

tory of chronic myelogenous leukemia (CML) was treated with chlorambucil, with good hematologic remission. Four weeks prior to admission her peripheral leukocyte count increased and she received melphalan, with minimal response. She was admitted to the Levine Cardiac Unit (1:00 PM, Sept. 10) of the Peter Bent Brigham Hospital, complaining of chest pain, nausea and vomiting, diaphoresis and dyspnea of sudden onset (6:00 AM, Sept. 10). An admission electrocardiogram showed changes of an evolving acute inferior myocardial infarction with Q waves and ST segment elevation in leads 2, 3 and aVF and atrial flutter (2: 1 A-V block and a ventricular rate of 170 per minute) as shown in Figure 1. Physical findings included blood pressure of 100/70 mm Hg, a respiratory rate of 28, a pulse rate of 170/minute and a temperature of 101°F. The lungs were dull to percussion at the bases, without rales. Cardiac examination revealed a feeble impulse in the mi,d-clavicular line, with a diffuse bulging left ventricular impulse parasternally in the second, third, and fourth intercostal spaces. St and S2 were faint, an S3 gallop was present and there was a soft grade 2/6 systolic murmur along the left sternal border. Chest x-ray films revealed mild cardiomegaly, pulmonary vascular redistribution to the upper lobes and right hilar adenopathy. Hematologic values were as follows: hematocrit, 30.6 percent; platelets, 334,OOO/mm3; leukocyte count, 65,OOO/mm3, with 70 percent neutrophils, 9 percent band cells, 2 percent lymphocytes, 3 percent monocytes, 1 percent atypical lymphocytes, 7 percent myelocytes and 8 percent metamyelocytes. Determinations for serum glucose, electrolytes, blood gases and amylase were normal. Serial enzyme studies documented an immediate elevation of serum creatine phosphokinase (CPK) and lactic dehydrogenase (LDH) (Table 1). Direct current (DC) countershock (50 watt-seconds) resulted in a junctional rhythm (rate 9O/minute), and ouabain and quinidine were given. Atrial flutter recurred (11:00 PM, Sept. 10) and was refractory to further attempts at cardioversion with high electrical energies (300 watt-seconds). Therapy with propranolol, 1 mg intravenously, however, converted the atrial flutter to the previous junctional focus at a rate of SO/minute. Hypotension was first noted 14 hours after the patient's arrival and did not respond to treatment with oxygen, sodium bicarbonate or vasopressors. The patient died 30 hours after admission with ventricular failure characterized by pulmonary edema and shock. Autopsy findings revealed leukemic infiltration in the liver, spleen, lymph nodes, kidneys, adrenal glands, as well as the pericardium and heart. Skeletal muscle infiltration was not demonstrated. Before sectioning the heart, the right and left coronary arteries were cannulated and injected at a pressure of 70 mm Hg with a radiopaque dye consisting of barium sulphate gelatin suspension with potassium iodide.! Postmortem angiography revealed patent left anterior descending, left circumflex and right coronary arteries (Fig 2)". Gross examination of these arteries revealed no atherosclerotic lesions. In addition, both the angiogram and gross examination revealed no vessel abnonnalities in the area of the localized diaphragmatic ventricular lesion described below. On the diaphragmatic surface of the left ventricle there was a large, poorly circumscribed zone of pallor, which measured approximately 2 x 2 x 1.5 CIn. Multiple hematoxylin and eosin stained, 6-1£ sections of the left and right ventricles and atria were examined. All sections showed leukemic infiltration in the interstitium, which varied in intensity in different areas. The infiltrate was composed of viable as well as necrotic myeloblasts and granulocytes of varying maturity. The area of pallor on the diaphragmatic "surface of the left

CHEST, 65: 4, APRIL, 1974

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FIGURE 1. Electrocardiogram on admission, showing marked ST segment elevation and Q waves in leads 2, 3 and aVF indicating acute inferior myocardial infarction. Rhythm is atrial flutter, with ventricular rate of 170 (2: 1 A-V block) . ventricle was composed of necrotic and ischemic myocardium as illustrated in Figure 3.~ The interstitial leukemic infiltrate was denser here than elsewhere and some leukemic cells appeared to be encroaching upon necrotic muscle fibers (Fig 4). Microscopic examination of the coronary arteries revealed neither atherosclerosis of small arteries nor plugging by leukemic cells. The pericardium was diffusely involved. Macroscopic inspection demonstrated a fibrinous exudate; microscopically there was a dense leukemic infiltrate. DISCUSSION

This case report illustrates myocardial infarction due to leukemic cell infiltration, with normal coronary arteries as documented by histologic examination of the myocardium and pathologic study of the coronary arteries. Other examples of CML as an etiologic factor in acute myocardial infarction with normal coronary arteries have not been found in the literature." Although a recent communications has objected to the word "infarction" in this clinical setting, we, as well as others," use "infarction" and "necrosis" interchangeably. Myocardial infiltrates, even when marked, usually do not alter the basic architecture of the myocardium," Changes reported with heavy leukemic infiltration include lysis, as well as hydropic, fatty or eosinophilic degeneration of myocardial fibers, with necrosis an unusual finding.t Leukemic infiltration of the heart and pericardium is common.v" but clinical manifestations are unusual.":" This discrepancy between the clinical manifestations and the findings at postmortem examination may be due to leukemic cell infiltrates, hemorrhages or infection in other body organs or tissues masking the clinical expression of cardiac involvement.'

The enzyme changes in this patient appear to be significant (Table 1) . Hepatic infiltration with granulocytes and myeloblasts may explain the initial abnormal transaminase, lactic dehydrogenase and alkaline phosphatase levels . It does not account for the subsequent acute rise in CPK and LDH. Furthermore, the sections of skeletal muscle examined were normal. Direct current (DC) countershock may elevate the CPK,lO but the initial low energy used (50 watt-seconds) and the unusually short interval observed here for maximal enzyme activity are not consistent with this explanation. The ECG localization in this patient corresponded to the anatomic site of infarction. ECG abnormalities have frequently been reported in leukemia and usually consist of nonspecific ST-T wave changes, arrhythmias, and conduction disturbances. 1 • n- u Progressive injury current with metastatic tumor of the heart is rare .5.6.15-16

Table I-Enzyme Value. in Palienl wilh Myocardiallnlarction

Time. Hrs. After Admission

CPK" LDH"" SGOTt A.P.t Date (Nl. 0-48) (N!. 131-231) (Nl. 11-33) (Nl. 18-70)

Admission

9/10

30

12

9/10

81

24

9/11

41

1730

72 76

1940

60

"Milli international units. ""Wackerunits. tSerum glutamic oxaloacetic trsnsaminase. Henryunits. tAlkaline phosphotase, international units.

CHEST, 65: 4, APRil, 1974

191

FIGURE 2. Postmortem coronary angiogram demonstrating patency of left and right coronary arteries.

ACUTE MYOCARDIAL INFARCTION 453

electrolyte abnormalities, muscular dystrophy, pulmonary embolism, stroke, idiopathic hypertrophic subaortic stenosis or Wolff-Parkinson-White syndrome.U'<" Hypotension was not clinically apparent until the terminal phase. In addition, the ECG and pathologic changes of subendocardial necrosis associated with hypotension and an elevated left ventricular end-diastolic pressure were not present." With the advent of new therapeutic regimens which may decrease mortality from hemorrhage and infection, it is suggested that a diagnosis of myocardial infarction due to myeloproliferative malignancy may be made with increasing frequency in the future. Furthermore, in such patients vigorous chemotherapy and radiation therapy applied to the cardiac area may be of some benefit in decreasing mortality in this acute phase. 2 2 - 2 4 ACKNOWLEDGMENTS : We are grateful to Doctors A. Abbas, G. Busch, M. Cohen, R. Gorlin and M. V. Herman for their suggestions. FIGURE 3. Left ventricular myocardium , showing darkly stained ischemic myocardial fibers associated with leukemic infiltrate (hematoxylin-basic fuchsin-picric acid stain ; X 200). The injury current and Q waves in this patient may have been due to extensive ventricular infiltration and direct small vessel distortion or compression, resulting in myocellular necrosis . Although not detected in microscopic sections, plugging of capillaries cannot be excluded as the cause of infarction. Local biochemical alterations must also be considered. Other conditions which may simulate the ECG changes of myocardial infarction were not present, ie, pancreatitis, amyloidosis, hypoglycemia, marked anemia,

FIGURE 4. Interstitial leukemic infiltrate with necrotic myocardial fibers and encroaching leukemic cells (hematoxylin and eosin; X 320) .

454 BERGERON, DATNOW

REFERENCES

1 Evans H: Postmortem angiography. Arch Pathol 83 :479484, 1967 2 Lie J, Holley K, Kampa W, et al : New histochemical method for morphologic diagnosis of early stages of myocardial ischemia. Mayo Clin Proc 46 :319-326, 1971 3 Lisker S, Finkelstein D, Brody J. et al: Myocardial infarction in acute leukemia . Arch Intern Med 119:532535,1967 4 Rabson S: Cardiac involvement in childhood lymphoma. N Engl J Med 287:989, 1972 5 Bagby G, Goldman R, Newman H, et al : Acute myocardial infarction due to childhood lymphoma . N Engl J Med 287 :338-340, 1972 6 Sumners JE, Johnson WW, Ainger LE : Childhood leukemic heart disease. a study of 116 hearts of children dying of leukemia. Circulation 40:575-581, 1969 7 Roberts WC, Bexley GP, Wertlake PT : The heart in acute leukemia-a study of 420 autopsy cases. Am J Cardiel 21 :388-412, 1968 8 Bisel H, Wroblewski F: Incidence and clinical manifestations of cardiac metastases. JAMA 153:712-715, 1953 9 Dameshek W, Gunz F : Leukemia. (ed 2). New York, Grune & Stratton, 1964, pp 187-188 10 Konttinen A, Hupli V, Louhija A, et al : Origin of elevated serum enzyme activities after direct-current countershock. N Engl J Med 281 :231-234, 1969 11 Mehrotra T, McMillan J : Electrocardiographic changes in chronic myeloid leukemia. Br J Clin Pract 21 :366-367, 1967 12 Aronson S, Leroy E: EKG findings in leukemia . Blood 2 :356-362, 1947 13 Dresdale E, Spain D, Perez-Pina F : Heart block and leukemic cell infiltration of interventricular system of heart. Am J Med 6:530-533, 1949 14 James T, Carrera G: Pathogenesis of arrhythmia associated with metastatic tumors of the heart . N Engl J Med 260 :869-871, 1959 15 Harris TR, Copeland GD, Brody DA: Progressive injury current with metastatic tumor of the heart. Case report and review of the literature. Am Heart J 69:392-400. 1965 16 Rosenbaum FF, Johnston FD, Alzamora VV: Persistent displacement of the RS-T segment in a case of metastatic tumor of the heart . Am Heart J 27 :667-675, 1944 17 Goldman AG, Gross H, Rubin IL: Transitory Q waves

CHEST, 65: 4, APRIL, 1974

18 19 20 21 22 23 24

simulating the Q waves of myocardial infarction. Am Heart J 60:61-72, 1960 Hugenholtz P: Electrocardiographic abnormalities in cerebral disorders: Report of 6 cases and review of the literature. Am Heart J 63 :451-461, 1962 De Pasquale NP, Burch GE, Phillips JH : ECG alteration associated with electrically "silent" areas of myocardium. Am Heart J 68 :697-709,1964 Cohen M, Rotsztain A, Bowen P, et al : Electrocardiographic changes in acute pancreatitis resembling acute myocardial infarction. Am Heart J 82:672-677, 1971 Salisbury P, Cross C, Rieben P : Acute ischemia of inner layers of ventricular wall. Am Heart J 66:650-656, 1963 Blattner H, Sosrnan H : Leukemia, heart block and hypertension treated with x-ray therapy. N Engl J Med 230 :793796,1944 Terry LN, Kligerman MM : Pericardial and myocardial involvement by lymphomas and leukemias : The role of radiotherapy. Cancer 25 : 1003-1008, 1970 Liedtke J, Adams D, Weber E, et al : Remission of cardiac lymphoma with supervoltage radiation. Am J Med 50 :816822 , 1971

Baygon-Induced Pulmonary Edema* Brian G. Salisbury, M.D.,"" Charles F. Tate, [r., M.D., F.C.C.P.t and John E. Davies, M.D.t

A 39-year-old black woman was in coma with propoxur (Baygon)-induced pulmonary edema. Vigorous supportive therapy resulted in prompt clinical resolution. A cuffed endotracheal tube and mechanical ventilation are especially important in propoxur-induced pulmonary edema because of the marked bronchorrhea requiring frequent suctioning and the danger of respiratory failure. Propoxur presence and toxicity are best revealed by determination of its metabolite 2-isopropoxyphenol in the gastric aspirate and/ or the urine.

absorption curve on ultraviolet spectrophotometry. Degradation of propoxur in vivo by hydrolysis produces 2-isopropoxyphenol which is then excreted in the urine in the glucuronide form. The 2-isopropoxyphenol was assayed in the gastric aspirate and the urine by the colorimetric method.v red blood cell and plasma cholinesterase levels were determined by the Michel or electrometric method .s CASE REPORT

A 39-year-old-black woman was brought to the emergency room in a coma on Nov. 3, 1971. Vital signs revealed spontaneous labored respirations of 24 per minute, a pulse rate of 120 per minute, blood pressure of 180/100 mm Hg and rectal temperature of 36·C. No history was available. On physical examination, white frothy secretions were bubbling from the mouth. The skin had normal texture, with no petechiae, needle tracks or diaphoresis. The neck was supple, and there was no evidence of head trauma. Both pupils were pinpoint (2-3 mm ) and un respon sive to light. The sclerae were nonicteric and the optic fundi were normal. The trachea was midline, with no evidence of thyrorn egaly or jugular venous distention at 45° . The lungs demonstrated bilateral coarse inspiratory rales anteriorly and posteriorly, with inspiratory and expiratory wheezes and rhonchi. Cardiac examination showed no cardiomegaly, murmurs or gallops. The neurologic examination revealed negative cold calories , corneal and gag reflexes. There was no sensation to pinprick and all extremities were hypotonic and flaccid, with bilaterally depressed deep tendon reflexes. No pathologic reflexes were found . The rest of the physical examination was noncontributory . Complete blood count revealed a hemoglobin level of 14 gm /loo ml, a hematocrit level of 42 percent and a white blood cell count of 9,OOO/mm 3 , with a normal differential. Measurement of serum electrolyte values revealed the following : sodium, 143 mEq/liter; potassium, 4.0 mEq/liter; chloride, 100 mEq/liter; and carbon dioxide combining power, 21 mEq/liter. Results of laboratory studies of blood urea

P

ro poxur (Baygon) (o-isopropoxyphenol methylcarbamate) is a common household insecticide and member of the carbamyl ester family . Pharmacologically it is an anticholinesterase characterized by more reversible binding to acetyl cholinesterase than is found with organophosphate insecticides.' This study describes the only reported case of propoxur-induced pulmonary edema and serves as a model for anticholinesterase-induced pulmonary edema. METHODS

Initial identification of propoxur resulted from the N-haptane extraction of the gastric aspirate and the characteristic "From the Department of Medicine, Pulmonary Disease Division, University of Miami School of Medicine, Jackson Memorial Hospital, Miami, Fla. ""Resident, Department of Medicine ; at present, Pulmonary Fellow, Hospital of the University of Pennsylvania, Philadelphia, Pa. t Associate Professor of Medicine, University of Miami School of Medicine; Chief, Pulmonary Disease Section, Jackson Memorial Hospital, Miami. :l:Associate Professor of Medicine, University of Miami School of Medicine; Director of Community Studies on Pesticides of Dade County, Miami, Fla. Reprint requests: Dr . Tate, PO Box 875, Biscayne Annex, Miami 33152

CHEST, 65: 4, APRIL, 1974

FIGURE

1. Admission chest x-ray film.

BAYGON.JNDUCED PULMONARY EDEMA 455