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Intractable ventricular tachycardia in a patient with giant cell myocarditis, thymoma and myasthenia gravis
374
Acknowledgement We are thankful to Dr. S.K. Sharma, Professor for his suggestions and guidance.
and Head of Department
of Pharmacology
References 1 Rogers HJ, Spector RG, Trounce JR. The nervous system. In: Rogers HJ, Spector RG. Trounce JR, eds. A textbook of clinical pharmacology. London: Hodder and Stoughton, 1981;194-279. 2 Laurence DR, Bennett PN. General pharmacology. In: Laurence DR. Bennett PN, eds. Clinical pharmacology. Edinburgh: Churchill Livingstone. 1980;104-169.
IJC 0474E
Intractable ventricular tachycardia in a patient with giant cell myocarditis, thymoma and myasthenia gravis M.J.L. de Jongste Departments
of
‘, H.J.G.H.
Oosterhuis
2, K.I. Lie ’
’ Cardiology und ’ Neurology. St&e University of Groningen, Gronrngen. The Netherlands (Received
27 May 1986; revision accepted
23 June 1986)
A 48-year-old man presented with a malignant thymoma in combination with myositis, myasthenia gravis, a giant cell myocarditis and recurrent intractable ventricular tachycardias. Despite various therapies (chemical, electrical and surgical), arrhythmias supervened in the presence of a normal coronary arteriogram. Active myocarditis was believed to be the mechanism of the ventricular tachycardias. (Key words:
Ventricular
tachycardia;
Myocarditis;
Myasthenia
gravis; Thymoma)
Introduction Giant cell myocarditis is a rare, possibly auto-immune mediated, complication of malignant thymoma. Recently we have studied a patient showing recurrent ventricular tachycardias in the presence of giant cell myocarditis, thymoma and myasthenia gravis. We discuss the possible pathophysiological mechanisms of this combination.
Correspondence to: M.J.L. de Jongste, Groningen, The Netherlands.
M.D., State University
International Journal of Cardiology, 13 (1986) 374-378 0 Elsevier Science Publishers B.V. (Biomedical Division)
of Groningen,
59 Oostersingel,
9713 EZ
375 Case Report A 4%year-old man with a 10 year history of lung disease, was admitted because of atelectasis of the right lower lobe and obstructive pneumonia. Since 1976 he was known to have a very slowly enlarging right sided shadow in the anterior mediastinum diagnosed as a pericardial cyst by repeated computer tomography scanning in 1979 and 1982. Four months before admission, he experienced drooping of the eyelids, double vision and weakness of the arms and legs following exertion. Several weeks before admission he experienced crescendo dyspnea, chest pain, greenish sputum and fever. Physical examination on admission revealed a moderate tachypnea of 24 respirations per minute, a blood pressure of 140 mm Hg and an irregular pulse (90 beats/minute). Examination of the heart revealed no abnormalities, apart from extrasystoles. There was a muffled percussion with diminished respiratory sounds on the right and posterior lower side of the chest. Investigation revealed persistent leucocytosis up to 29.3 x 109/1, with a normal differential count and a normochromic anemia of 105 g/l Hb.
Fig. 1. Chest radiograph on admission showing atelectasis of the right lower lobe with a shadow at the right side of the heart.
316
Serum aspartate aminotransferase was constantly elevated to a maximum of 353 U/l (normal < 40 U/l), as was lactic dehydrogenase 770 U/l (normal < 235 U/l) and creatine kinase 380 U/l (normal < 50 U/l), with a MB fraction of 40 U/l at maximum (normal < 15 U/l). Other tests were normal. Electrocardiographical findings on admission showed a sinus rhythm with a heart rate of 80 beats/minute and a mean frontal electrical axis of -10 degrees. The anterior leads showed loss of R wave, with QS in leads V3-V6 and T wave inversion in leads I, AVL, V5 and V6. There were frequent premature ventricular contractions which were multiformed and sometimes coupled. The chest radiograph revealed atelectasis of the right lower lobe with a shadow at the right side of the heart. The heart was not enlarged (Fig. 1). The vital capacity was only 2.35 1 (normal 4.56 1) and the forced expiratory volume was diminished to 2.15 l/minute (normal 3.20 l/mm). An echocardiogram failed to visualize a “cyst” but showed a badly moving anterior ventricular wall. There were no valve abnormalities and the intracardiac diameters
Fig. 2. Electrocardiogram ventricular tachycardia.
in the postoperative
period
showing
limb leads I, II, III with recurrence
of
311
were normal. The inferior caval vein collapsed minimally at inspiration. The pattern of serum enzymes having excluded infarction, we treated his premature beats with disopyramide and performed diagnostic bronchoscopy. This was complicated by a ventricular tachycardia. Because his clinical condition then worsened, mechanical ventilation was started and we considered myasthenic crisis. He reacted to edrophonium with a decrease of ptosis and improvement of ventilation. Myasthenia was then confirmed by identifying antibodies against acetylcholine receptor and striated muscle. The “pericardial cyst” was now suspected to be a thymoma. Peridostigmine was given in combination with prednisolone and the clinical situation improved. Coronary catheterisation and cineangiography showed normal arteries, but the left ventricle revealed a hypokinetic and diffuse contraction pattern. Myocardial biopsies showed a giant cell myocarditis. The recurrence of ventricular tachycardia was associated with collapse and so we undertook an electrophysiological examination. This showed beats originating in the atrioventricular node. No ventricular tachycardia could be induced. Because of development of bradycardias, a Vitatron D.P.G. ventricular inhibited pacemaker with antiarrhythmic features was implanted with initial success. This stabilized the patient. Since no clinical signs of myasthenia gravis were present, thymectomy was performed. A cystic thymoma was removed which had not invaded the surrounding tissues. Ventricular tachycardias recurred in the postoperative period (Fig. 2) despite initially successful treatment with lignocaine, mexilitin, disopyramide, tocainide, amiodarone, beta-blockers and digoxine (separately or in combination) and various modes of temporary pacing. Two weeks after thymectomy he died suddenly because of an intractable ventricular tachycardia. Postmortem examination showed a giant cell myocarditis with some reactive lymph nodes and marked plasma cell reaction. Discussion Giant cell myocarditis has been reported in patients with thymomas with or without myasthenia gravis [l]. Since myasthenia gravis is known to be an auto-immune disease and to be associated with thymoma in about 15% of the cases, and since thymomas themselves are associated with other auto-immune diseases [2], it is tempting to consider giant cell myocarditis in these patients as another sign of disturbed immunoregulation. In our patient, the mediastinal tumor was initially diagnosed as a pericardial cyst. It was thought to be a thymoma when the presence of myasthenia gravis was suspected following diazepam-provoked respiratory failure. The myasthenia was confirmed by finding high titers of striated muscle antibodies [2]. The decision to remove the tumor after control of the myasthenic crisis was influenced by the assumption that the tumor might be the direct cause of the ventricular tachycardias. The findings at operation and the complete removal made this unlikely. A second possibility for the arrhythmias, therefore, is the involvement of the myocardium in the myasthenic pathophysiology. Such a specific pathology has not previously been proven [3]. Some investigators have reported mild subclinical cardiac abnormalities which are reversible by neostigmine [4]. Based on our clinical experience, a direct relationship between the myasthenic process and cardiac arrhythmias is unlikely. A third possibility for the arrhythmias in our patient is widespread focal myocardial necrosis caused by an auto-immune reaction. The association of the thymoma and myasthenia gravis is in support of this possibility. Cross reactivity with the myoid cells in the thymus is conceivable. Comparable myocardial lesions have been evoked in guinea pigs by immunization with
378
fractions of calf thymus [5]. A direct influence of thymectomy on giant cell myocarditis is unrecorded in literature and cannot be assumed, since this operation usually has no effect on other concomitant diseases such as myasthenia gravis or pure red cell anaemia [2]. In retrospect a more prolonged and intensive immunosuppressive treatment of the giant cell myocarditis might have been the therapy of choice.
Acknowledgement The authors
wish to thank Frits Beaumont
for his invaluable
advice.
References 1 2 3 4
Peison B, Lowenstein E. Giant cell myocarditis. NY State J Med 1973;73:2259-2263, Oosterhuis HJGH. In: Myasthenia gravis. Edinburgh: Churchill Livingstone, 1984;61,106. Gibson ZC. The heart in myasthenia gravis. Am Heart J 1975;90:389-396. Ashok PP. Ahuja GK, Manchanda SC, Jalal S. Cardiac involvement in myasthenia gravis. Acta Nemo1 Stand 1983;68:113-120. 5 Kalden JR, Williamsen WA, Vilve WJ. Experimental myasthenia gravis, myositis and myocarditis in guinea pigs immunized with subcellular fractions of calf thymus or calf skeletal muscle in freund’s complete adjuvant. Clin Exp Immunol 1973;13:79-88.
Acknowledgement We are thankful to Dr. S.K. Sharma, Professor for his suggestions and guidance.
and Head of Department
of Pharmacology
References 1 Rogers HJ, Spector RG, Trounce JR. The nervous system. In: Rogers HJ, Spector RG. Trounce JR, eds. A textbook of clinical pharmacology. London: Hodder and Stoughton, 1981;194-279. 2 Laurence DR, Bennett PN. General pharmacology. In: Laurence DR. Bennett PN, eds. Clinical pharmacology. Edinburgh: Churchill Livingstone. 1980;104-169.
IJC 0474E
Intractable ventricular tachycardia in a patient with giant cell myocarditis, thymoma and myasthenia gravis M.J.L. de Jongste Departments
of
‘, H.J.G.H.
Oosterhuis
2, K.I. Lie ’
’ Cardiology und ’ Neurology. St&e University of Groningen, Gronrngen. The Netherlands (Received
27 May 1986; revision accepted
23 June 1986)
A 48-year-old man presented with a malignant thymoma in combination with myositis, myasthenia gravis, a giant cell myocarditis and recurrent intractable ventricular tachycardias. Despite various therapies (chemical, electrical and surgical), arrhythmias supervened in the presence of a normal coronary arteriogram. Active myocarditis was believed to be the mechanism of the ventricular tachycardias. (Key words:
Ventricular
tachycardia;
Myocarditis;
Myasthenia
gravis; Thymoma)
Introduction Giant cell myocarditis is a rare, possibly auto-immune mediated, complication of malignant thymoma. Recently we have studied a patient showing recurrent ventricular tachycardias in the presence of giant cell myocarditis, thymoma and myasthenia gravis. We discuss the possible pathophysiological mechanisms of this combination.
Correspondence to: M.J.L. de Jongste, Groningen, The Netherlands.
M.D., State University
International Journal of Cardiology, 13 (1986) 374-378 0 Elsevier Science Publishers B.V. (Biomedical Division)
of Groningen,
59 Oostersingel,
9713 EZ
375 Case Report A 4%year-old man with a 10 year history of lung disease, was admitted because of atelectasis of the right lower lobe and obstructive pneumonia. Since 1976 he was known to have a very slowly enlarging right sided shadow in the anterior mediastinum diagnosed as a pericardial cyst by repeated computer tomography scanning in 1979 and 1982. Four months before admission, he experienced drooping of the eyelids, double vision and weakness of the arms and legs following exertion. Several weeks before admission he experienced crescendo dyspnea, chest pain, greenish sputum and fever. Physical examination on admission revealed a moderate tachypnea of 24 respirations per minute, a blood pressure of 140 mm Hg and an irregular pulse (90 beats/minute). Examination of the heart revealed no abnormalities, apart from extrasystoles. There was a muffled percussion with diminished respiratory sounds on the right and posterior lower side of the chest. Investigation revealed persistent leucocytosis up to 29.3 x 109/1, with a normal differential count and a normochromic anemia of 105 g/l Hb.
Fig. 1. Chest radiograph on admission showing atelectasis of the right lower lobe with a shadow at the right side of the heart.
316
Serum aspartate aminotransferase was constantly elevated to a maximum of 353 U/l (normal < 40 U/l), as was lactic dehydrogenase 770 U/l (normal < 235 U/l) and creatine kinase 380 U/l (normal < 50 U/l), with a MB fraction of 40 U/l at maximum (normal < 15 U/l). Other tests were normal. Electrocardiographical findings on admission showed a sinus rhythm with a heart rate of 80 beats/minute and a mean frontal electrical axis of -10 degrees. The anterior leads showed loss of R wave, with QS in leads V3-V6 and T wave inversion in leads I, AVL, V5 and V6. There were frequent premature ventricular contractions which were multiformed and sometimes coupled. The chest radiograph revealed atelectasis of the right lower lobe with a shadow at the right side of the heart. The heart was not enlarged (Fig. 1). The vital capacity was only 2.35 1 (normal 4.56 1) and the forced expiratory volume was diminished to 2.15 l/minute (normal 3.20 l/mm). An echocardiogram failed to visualize a “cyst” but showed a badly moving anterior ventricular wall. There were no valve abnormalities and the intracardiac diameters
Fig. 2. Electrocardiogram ventricular tachycardia.
in the postoperative
period
showing
limb leads I, II, III with recurrence
of
311
were normal. The inferior caval vein collapsed minimally at inspiration. The pattern of serum enzymes having excluded infarction, we treated his premature beats with disopyramide and performed diagnostic bronchoscopy. This was complicated by a ventricular tachycardia. Because his clinical condition then worsened, mechanical ventilation was started and we considered myasthenic crisis. He reacted to edrophonium with a decrease of ptosis and improvement of ventilation. Myasthenia was then confirmed by identifying antibodies against acetylcholine receptor and striated muscle. The “pericardial cyst” was now suspected to be a thymoma. Peridostigmine was given in combination with prednisolone and the clinical situation improved. Coronary catheterisation and cineangiography showed normal arteries, but the left ventricle revealed a hypokinetic and diffuse contraction pattern. Myocardial biopsies showed a giant cell myocarditis. The recurrence of ventricular tachycardia was associated with collapse and so we undertook an electrophysiological examination. This showed beats originating in the atrioventricular node. No ventricular tachycardia could be induced. Because of development of bradycardias, a Vitatron D.P.G. ventricular inhibited pacemaker with antiarrhythmic features was implanted with initial success. This stabilized the patient. Since no clinical signs of myasthenia gravis were present, thymectomy was performed. A cystic thymoma was removed which had not invaded the surrounding tissues. Ventricular tachycardias recurred in the postoperative period (Fig. 2) despite initially successful treatment with lignocaine, mexilitin, disopyramide, tocainide, amiodarone, beta-blockers and digoxine (separately or in combination) and various modes of temporary pacing. Two weeks after thymectomy he died suddenly because of an intractable ventricular tachycardia. Postmortem examination showed a giant cell myocarditis with some reactive lymph nodes and marked plasma cell reaction. Discussion Giant cell myocarditis has been reported in patients with thymomas with or without myasthenia gravis [l]. Since myasthenia gravis is known to be an auto-immune disease and to be associated with thymoma in about 15% of the cases, and since thymomas themselves are associated with other auto-immune diseases [2], it is tempting to consider giant cell myocarditis in these patients as another sign of disturbed immunoregulation. In our patient, the mediastinal tumor was initially diagnosed as a pericardial cyst. It was thought to be a thymoma when the presence of myasthenia gravis was suspected following diazepam-provoked respiratory failure. The myasthenia was confirmed by finding high titers of striated muscle antibodies [2]. The decision to remove the tumor after control of the myasthenic crisis was influenced by the assumption that the tumor might be the direct cause of the ventricular tachycardias. The findings at operation and the complete removal made this unlikely. A second possibility for the arrhythmias, therefore, is the involvement of the myocardium in the myasthenic pathophysiology. Such a specific pathology has not previously been proven [3]. Some investigators have reported mild subclinical cardiac abnormalities which are reversible by neostigmine [4]. Based on our clinical experience, a direct relationship between the myasthenic process and cardiac arrhythmias is unlikely. A third possibility for the arrhythmias in our patient is widespread focal myocardial necrosis caused by an auto-immune reaction. The association of the thymoma and myasthenia gravis is in support of this possibility. Cross reactivity with the myoid cells in the thymus is conceivable. Comparable myocardial lesions have been evoked in guinea pigs by immunization with
378
fractions of calf thymus [5]. A direct influence of thymectomy on giant cell myocarditis is unrecorded in literature and cannot be assumed, since this operation usually has no effect on other concomitant diseases such as myasthenia gravis or pure red cell anaemia [2]. In retrospect a more prolonged and intensive immunosuppressive treatment of the giant cell myocarditis might have been the therapy of choice.
Acknowledgement The authors
wish to thank Frits Beaumont
for his invaluable
advice.
References 1 2 3 4
Peison B, Lowenstein E. Giant cell myocarditis. NY State J Med 1973;73:2259-2263, Oosterhuis HJGH. In: Myasthenia gravis. Edinburgh: Churchill Livingstone, 1984;61,106. Gibson ZC. The heart in myasthenia gravis. Am Heart J 1975;90:389-396. Ashok PP. Ahuja GK, Manchanda SC, Jalal S. Cardiac involvement in myasthenia gravis. Acta Nemo1 Stand 1983;68:113-120. 5 Kalden JR, Williamsen WA, Vilve WJ. Experimental myasthenia gravis, myositis and myocarditis in guinea pigs immunized with subcellular fractions of calf thymus or calf skeletal muscle in freund’s complete adjuvant. Clin Exp Immunol 1973;13:79-88.