Case Report

A case of Acute Myelogenous Leukemia with Advanced Atrioventricular Block and Caused by Leukemic Cell Infiltration Kiyohiko Hatake, MD, Kazuya Saito, MD, Takashi Saga, MD, Nobuhiro Akashi, MDand Kenji Doishita, MD*

A 40 year-old womanwith acute myelogenous leukemia developed an advanced atrioven- tricular block and pericardial effusion. On autopsy, pericardial effusion without and mononuclear cell infiltration in His bundle were found. Focal infiltration of His bundle by leukemic cells was suggested as the cause of the atrioventricular block. Key Words: Advanced atrioventricular block, Pericardial effusion, Leukemic heart dis- ease, Leukemia.

Various kinds of peri-myocardial damage she was relatively small (150cm height, 35 are manifested during the course of acute kg weight), and moderately anemic. Lungs leukemia as the results of leukemic cell in- were normal. Systolic functional murmur filtration to the heart, viral or other agents- was heard on apex. There was no hepato- induced , anthracycline car- splenomegaly, generalized lymphadenopathy, diotoxicity, coronary heart disease and so on. and edema. In this report, we describe a case of Laboratory data on admission revealed advanced atrioventricular block and pericar- CRP 1+, erythrocyte sedimentation rate dial effusion which occurred during the 120mm/h, and alkaline phosphatase 12.5 course of her acute myelogenous leukemia. (K.A.). On chest X-ray films, both lungs Autopsy showeda presence of mononuclear were clear, and no was present cell infiltration in His bundle. (cardiothoracic ratio 47%). EGGwas normal. CASE REPORT A 40 year-old womanwas admitted to out department because of persistent slight fever on October 20, 1979. Three months before admission, sho often had an attack of cough at night. Her complaint progres- sively increased. On September 26, she was admitted to another hospital with the diag- nosis of bacterial pneumonia. Her slight fever persisted, and she was transferred to our department. Fig. 1. Photomicrograph of myeloblasts On physical examination at admission, in the bone marrow. From the Department of Internal Medicine, and the Department of Pathology*, Fukui Prefectural Hospital, Fukui. Received for publication January ll, 1982. Reprint request to: Kiyohiko Hatake, MD, The Department of Internal Medicine, Fukui Prefectural Hospital, 8-1, 2-chome Yotsui, Fukui, 910, Japan.

JapJ Med Vol 21, No 2 (April 1982) 115 Hatake et al

Hemoglobin was 8.3g/dl, red blood cell captopurine, and prednisolone for four days. count 278xlO4/mm3, white blood cell count Peripheral white blood cell count, myelo- 1100/mm3 with 35% myeloblast, platelet blasts percentage, and platelet count pro- count 19.3X104/mm3. Bone marrow aspira- gressively decreased. 14 days after the start tion revealed hypercellularity with 71.6% of the treatment, she complained dyspnea, myeloblast. Myeloblasts were peroxidase chest oppression, and palpitation. Facial positive, and PAS negative (Fig. 1.). cyanosis and leg edema were present. The Wediagnosed her as acute myelogenous blood pressure dropped to 40mmHg, pulse leukemia and started a treatment with daunorubicin, cytosine arabinoside, 6-mer-

Fig. 2. EGG showing sinus and Fig. 3. Chest X-ray film disclosing cardio- pulmonary P wave in II, III, aVF during the megaly (cardiothoracic ratio 53%) and suspected episode of shock. of presence of pleural effusion of the left side.

Fig. 4. EGG showing second degree atrioventricular block (Mobit2 type II) on two days after the episode of shock.

116 JapJ Med Vol 21, No 2 (April 1982) AV block and pericardial effusion in leukemia rate was 130/min. Heart rate was regular. effusion was detected, but calculated ejection ECG showed associated fraction was normal (Fig. 5.). Cardiac out- with pulmonary P in II, III, aVF (Fig. 2.). put was 4.91/min. Carotid pulse recording Chest X-ray film disclosed cardiomegaly was normal. White blood cell count was (cardiothoracic ratio 53%) (Fig. 3.). On the 1200/mm3, with 30% myeloblast. Serum FDP next day of this episode, she complained of was negative, fibrinogen 480[ig/dl, and slight dyspnea, chest oppression, and palpita- platelet count 33000/mm3. Serum antibody tion again. Blood pressure was 100/60mmHg, test for viruses (Coxsackie B group, ECHO, but was found. ECGshowed a cytomegalovirus, adenovirus, influenza, para- second (Mobitz type I) atrioventricular block. influenza, hepatitis B, and so on), toxoplasma, A few hours later, Mobitz type II atrioven- and Mycoplasmawere all negative. Lung tricular block developed (Fig. 4.). On echo- per fusion scan using 131I-MAA (Macroag- cardiogram, moderate amountsof pericardial gregates ofalbumin) was normal. Westarted drip infusion of isoproterenol, then blood pressure recovered gradually and the sinus rhythm was returned. We added cyclophosphamide to the drug regimen. Bone marrow aspira- tion revealed hypocellularity with 80% myeloblast. On December 8, she had high fever and complained right chest pain, and died. Autopsy findings revealed gener- alized subcutaneous hemorrhages, pulmonary thromboembolism of the right upper lobe, and slight pericar- dial effusion. The effusion was turbid, cytology and culture were both neg- ative. Neither pericarditis nor hem- orrhage were observed. Infiltration by peroxidase positive, PASnegative Fig. 5. Echocardiogram showing presence of mononuclear cells was observed only moderate amounts of pericardial effusion. in the His bundle. No myocardial

Fig. 6. Photomicrograph of the section of Fig. 7. Photomicrograph of the section of His bundle, showing mononuclear cell infiltra- His bundle, showing mononuclear cell infiltra- tion; hematoxylin and eosin, x 100. tion; hematoxylin and eosin, x400. Compare these mononuclear cells those of bone marrow smear (Fig. 1). .; å -å *

JapJ Med Vol 21, No 2 (April 1982) 117 Hatake et al was found (Fig. 6, 7.). the disease. ECG findings were left ven- tricular hypertrophy and ST changes due DISCUSSION to chronic anemia. Roberts, W.C. et al.8> In the extensive review on 42 cases of described the cardiac findings in 420 patients Coxsackie B group viral myopericarditis by with acute leukemia. In their report, only Smith, W. G. et al.1}, abnormal findings were one case of atrioventricular block was ob- found on ECG in all cases, and all of the served. From the review of cardiac pathol- cases showed elevated viral antibody titer. ogy, leukemic infiltration of the heart or They described three cases of transient com- hemorrhage in the myocardiumwere found plete atrioventricular block. in 69%, and only infiltration to the heart Daniel, D. Van Ho ff. et al.2) reviewed 110 was found in 37%. Foci of the leukemic cases treated with large doses of daunoru- cell infiltration are usually in the endocar- bicin. Congestive was present dium, interstitium, and perivascular region in 65 cases, and remaining 45 cases showed of the myocardium and . In 39 only an ECG changes. ECG changes ob- patients pericardial effusion was found, and served in highest incidence, were nonspecific over 300ml of fluid was recorded in four ST or ST-T changes occurring in 33 cases, patients. The etiology of the pericardial and low voltage in QRScomplexes in 22 effusion was variable, most were due to cases. Two cases of atrioventricular block leukemic infiltration. Several authors re- were reported, but details were not known. ported pericardial effusion caused by leu- Bristow, M. R. et al.3) reported early anthra- kemic infiltration9~18). In these reports, ECG cycline cardiotoxicity. Singers, J.W.4) de- changes were observed, for example, non- scribed acute lowering of ejection fraction specific ST-T changes, low voltage in QR$ from the studies of and complexes, inverted T, multiple premature radionucleide angiography. Ferrans, V. J.5) ventricular beats, sinus tachycardia, and so described pathologic changes of acute and on. chronic cardiotoxicity after anthracycline 8 cases of atrioventricular block observed treatment. These changes consisted of during courses of leukemia were report- cardiac dilatation, degeneration and atrophy ed19"2^. Dresdale, D.T. et al.21) reported a of the muscle cells, and interstitial edema case of atrioventricular dissociation in acute and fibrosis. Appelbaum, F.A. et al.6) re- myelogenous leukemia, and observed a leu- ported 4 cases of acute lethal caused kemic cell infiltration into interventricular by high-dose combination chemotherapy septum. Other authors reported cases of utilising primarily cyclophosphamide. All atrioventricular block in leukemia, but of the cases showed no specific ECG changes. pathologic findings were not investigated in Pericardial effusion was detected in some detail. From the review of the literature, of them on echocardiogram. These changes as pathological study was not performed began on 5th to 9th day after the start of sufficiently except in Dresdale's case, we treatment, and fibrin microthrombi in capil- can't know an accurate incidence of focal laries, fibrin strands in the interstitium, leukemic cell infiltration to His bundle in fibrin strands within the heart muscle cells acute leukemia or in leukemic heart disease. were observed on autopsy. In our case, it was very difficult to differ- Summers, J. E.7) reported from the review rentiate leukemic infiltration to the heart on 110 autopsy cases of childhood leukemia from myopericarditis or anthracycline car- that 44% of the patients had at least one diotoxicity before autopsy. From the review focus of leukemic infiltration, and showed of the literature, lowered cardiac output was higher percentage of incidence of infiltration observed in anthracycline cardiotoxicity, and of the heart, with higher peripheral white elevated antibody titer of agents was detedted blood cell counts, and longer duration of in myopericarditis. In our case, since all of 118 Jap J Med Vol 21, No 2 (April 1982) AVblock and pericardial effusion in leukemia the viral antibody tests were negative, and HeartJ 22: 417, 1941. Bierman HR, Perkins EK, Ortega, P: Peri- cardiac output was normal (on dye-dilution carditis in patients with leukemia. Amer methodmeasurement and echocardiographic calculation), we speculated that the atrio- HeartJ 43: 413, 1952. Thusber DL, Edwards JE, Achor RWP: ventricular block might be due to leukemic Secondary malignant tumors of the pericar- cell infiltration to His bundle. On autopsy, dium. Circulation 16: 228, 1962. leukemic cell infiltration limited to the area Banerjea JC, Mukherjee SK: Haemoperi- of His bundle was observed. No infiltration cardium in chronic myeloid leukaemia. Indian to pericardium wasobserved. HeartJ 16: 155, 1964. Rab SM, Yee A: Initial ACKNOWLEDGEMENTS:We wish to thank in acute leukaemia. BritMedJ 1 : 612, 1967. Prof. Fumimaro Takaku, the Department of Hema- Haets HW,Selsky LM: X-raytherapyinthe tology, and Prof. Saichi Hosoda, the Department treatment of cardiac tamponade in chronic of , Jichi Medical School, Tochigi, myelocytic leukemia. Conn Med J 32: 523, for their help during the preparation of this 1968. manuscript. Battle CU, Bonfiglio TA, Miller DR: Peri- carditis as the initial manifestation of acute REFERENCES leukemia. Report of a case. J Pediat 75: 1) Smith WG: Coxsackie B myopericarditis in 692, 1969. adults. Amer HeartJ 80: 34, 1970. 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