Myocardial
Infarction
Due to Coronary
Three Young Adults with Systemic
JOSE MELLER. MD CESAR A. CONDE, MD LUDWIG M. DEPPISCH, MD EPHRAIM DONOSO, MD, FACC SIMON DACK, MD, FACC New York, New York
Atherosclerosis
in
Lupus Erythematosus
Three patients, 24, 24 and 25 years of age, with systemic lupus erythematosus had signs of myocardial infarction. Two had serial electrocardiographic changes indicative of infarction without any cardiac symptoms. The third patient had clinical evidence of an acute massive myocardial infarction, which was proved at autopsy to be due to coronary atherosclerosis. This case is presented tn detail and the association between systemic lupus erythematosus and myocardial infarction is reviewed. It is postulated that the relation between lupus erythematosus and coronary atherosclerosis is more than coincidental.
Myocardial infarction is seen infrequently in patients with systemic lupus erythematosus and there has been some controversy concerning the relation between lupus erythematosus and coronary atherosclerosis-1-3 In 1 year we observed three young adults with systemic lupus erythematosus and signs of coronary artery disease. The first patient, a 25 year old woman, was admitted with an acute myocardial infarction complicated by cardiogenic shock; she died and on autopsy had evidence of coronary atherosclerosis as the cause of the infarction. The other two patients, both 24 years of age, had only classic electrocardiographic changes indicative of myocardial infarction and no symptoms referable to the heart. Case Reports
From the Division of Cardiology, Department of Medicine and the Department of Pathology, Mount Sinai School of Medicine of the City University of New York, New York, N. Y. Manuscript accepted July 17, 1974. Address for reprints: Simon Dack, MD, The Mount Sinai Hospital, Division of Cardiology, Department of Medicine, 100th St. and Fifth Ave., New York, N. Y. 10029.
Case 1. A 25 year old woman was admitted to Mount Sinai Hospital because of chest pain of six days’ duration. Twelve years earlier she had choreiform movements that lasted several weeks but responded to treatment with corticosteroids. Four years later she again had episodes of chorea, this time accompanied by pain in the hips and elbows. On admission to another hospital where lupus erythematosus preparations were reportedly positive, she was treated with prednisone, 75 mg daily; this dose was gradually decreased. The choreiform movements, especially of the hands and tongue, recurred frequently, always responding to reinstitution of large doses of corticosteroids. While receiving steroid therapy she was noted to have hypertension but was not treated for it. Six months before admission she was hospitalized because of arthralgia and pleuritic chest pain. A chest roentgenogram and an electrocardiogram were reported to be normal. The amount of prednisone administered was increased and the pains disappeared; 3 months later she was asymptomatic and prednisone was administered in gradually reduced doses and then discontinued. Two weeks before admission she had an episode of severe chest pain precipitated by exertion and relieved by resting. This pain was substernal without radiation and made worse by deep inspiration. Six days before admission the same pain recurred and persisted until her hospitalization. She also complained of rapidly progressive dyspnea on exertion, diaphoresis and fainting sensation. She denied fever, hemoptysis, the use of birth-control pills and smoking. Her serum cholesterol had been normal. The family history was noncontributory.
February 1975
The American Journal of CARDIOLOGY
Volume 35
309
MYOCARDJAL INFARCTION IN LUPUS ER~H~MATOSUS-MELLER
ET AL.
FIGURE 1. Case 1. Chest roentgenogram on hospital admission revealing a markedly enlarged cardiac silhouette.
On ph~si&a~ e~a~~~a~~on she appeared acutely ill, tachypneic, diaphoretic and cold. The pulse was 140/min, regular and weak, the blood pressure was obtainable by palpation only at 60 mm Hg, the respiratory rate was 36/ min and the temperature was 98’F. The skin was pale and clammy with livedo reticularis pattern. Jugular veins were not seen and no hepatojugular reflux could be demonstrated. The lungs were clear. Examination of the heart revealed normal heart sounds and a loud diastolic gallop; no
I
II
III
8VR
8VL
FIGURE 3. Case 1. Transverse sections of the heart manifesting a recent extensive myocardial infarct in the anterior and septal walls.
pericardial rub or murmurs were heard. The abdomen was obese with striae. laboratory studies disclosed the following: hemoglobin 10.6 g/100 ml, hematocrit 31 percent, white blood cell count 5,400/mm3, 2+ proteinuria, blood urea nitrogen 23 mg/lOO
rVF
VI
v2
V3
v4
vs
‘6
FIGURE 2. Case 1. Serial electrocardiograms demonstrating an anteroseptaf wall myocardial infarction, intermittent right bundle branch block and probable left posterior hemiblock.
310
February 1975
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Volume 35
MYOCARDIAL
ml and serum creatinine 1.4 mg/lOO ml. The serum electrolytes, uric acid, protein and cholesterol findings were normal. The initial serum enzyme values were: glutamic oxaloacetic transaminase (SGOT) 75 U (normal up to 45 U) and creatine phosphokinase (CPK) 410 U (normal up to 125 U). The chest roentgenogram revealed a markedly enlarged cardiac silhouette (Fig. 1). The electrocardiogram disclosed sinus tachycardia, right axis deviation, QS pattern in leads Vr to Vs, S-T elevation in leads III and aVF and S-T depression in leads I, aVL and Vs to Vs (Fig. 2). An emergency pericardiocentesis was performed, hut no fluid was obtained. After administration of isoproterenol and hydrocortisone the blood pressure increased to 80/60 mm Hg. A repeat chest X-ray film revealed fluid in the left costophrenic angle, and small doses of furosemide were given. Serial electrocardiograms disclosed changes consistent with an acute anteroseptal myocardial infarction; complete right bundle branch block appeared intermittently. T$he serum CPK increased to 2,100 U, SGOT to 360 U and lactic dehydrogenase (LDH) to 330 U. On the 2nd day the pain was mild during deep inspiration and when the patient was supine. She required isoproterenol to maintain blood pressure. On the 5th day ventricular fibrillation developed and all resuscitative efforts were unsuccessful. Autopsjr findings: The heart was enlarged, weighing 400 g. An extensive fibrinous pericarditis was present. A large recent transmural myocardial infarct involved the entire anterior wall and interventricular septum of the left ventricle from the cardiac apex to 1 cm below the base of the aortic valve (Fig. 3). A healed infarct, 3 cm in diameter, involved the posterior wall and posterior septum. FIGURE 5. Case 1. Sections of coronary arteries. A, cross section of the left anterior descending coronary artery showing an occlusive thrombus superimposed upon an atheromatous plaque. B, longitudinal section of the right coronary artery showing an early organizing occlusive thrombus attached to an atheromatous plaque. C, cross section of a coronary artery manifesting severe eccentric intimal fibrosis. (Hematoxylin-eosin X 10.)
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
FIGURE 4. Case 1. Opened left anterior descending coronary artery showing complete occlusion by an organizing thrombus.
The coronary arteries displayed focal, but severe atherosclerosis. The left anterior descending coronary artery was completely occluded by an organizing thrombus 3 cm distal to its origin (Fig. 4). This thrombus was superimposed upon a hemprrhagic intimal atheroma (Fig. 5A). An atheromatous plaque with superimposed thrombus significantly narrowed the right coronary artery 4.5 cm from its ostium (Fig. 5B). Microscopic sections of coronary arteries revealed eccentric intimal fibrosis and dystrophic calcification (Fig. 5C). There was no inflammation or fibrinoid ne-
A
\
February 1975
The American Journal of CARDIOLOGY
Volume 35
311
MYOCARDIAL
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
Case 3: A 24 year old woman with systemic lupus erythematosus was admitted several times to Mount Sinai Hospital because of neurologic, dermatologic and renal symptoms. A pattern of inferior wall myocardial infarction developed in serial electrocardiograms, but she had no cardiac symptoms (Fig. 7).
crosis in the coronary vessels. Immunofluorescent staining of a coronary artery revealed no gamma globulin or complement deposition. Multiple 1 to 3 mm pink verrucae were attached to the atria1 surface of both mitral valve cusps. Multiple similar verrucae covered the atria1 and ventricular surfaces of all cusps of the tricuspid valve and, by extension, the adjacent right atria1 and right ventricular endocardium. Microscopically these verrucae consisted of thrombi in various stages of early organization. Valvular destruction or microorganisms were not observed. Several extracardiac anatomic findings characteristic of systemic lupus erythematosus were seen: mild focal glomerulonephritis with immune complex deposition within glomerular capillary walls, “onion-skin” periadventitial fibrosis of medium-sized splenic arteries and a focal interstitial pulmonary infiltration.
Discussion Cardiac symptoms are seen in 50 to 89 percent of patients with systemic lupus erythematosus,3-10 but are rarely the first manifestation of the disease.‘cJl The most frequent cardiac diagnoses in these patients are pericarditis and myocarditis; both are found more frequently in autopsy than in clinical studies.3,5J2 Electrocardiographic abnormalities are also common,2,4F7J2 usually consisting of S-T segment and T wave changes secondary to pericarditis, myocarditis or metabolic abnormalities caused by the basic disease. Abnormal Q waves indicating myocardial infarction are very rare, even in patients found to have myocardial infarction at autopsy.8 Libman-Sacks valvulitis can be diagnosed with
Case 2: A 24 year old man with systemic lupus erythematosus was admitted several times to Mount Sinai Hospital because of neurologic symptoms. His electrocardiogram revealed an anteroseptal wall myocardial infarction pattern in serial tracings, but he had no symptoms referable to the heart (Fig. 6).
II
I
III
aVR
aVL
aVF
A
X2/6/72
FIGURE 6. Case 2. Electrocardiograms revealing a developing pattern of anteroseptal myocardial infarction. . I
II
III
aVR
aVL
aVF
VI
V2
v3
FIGURE 7. Case 3. Electrocardiograms revealing a developing pattern of inferior wall myocardial infarction.
312
February 1975
The American Journal of CARDIOLOGY
Volume 35
V4
V5
‘6
MYOCARDIAL
certainty only at autopsy,g and its reported incidence has been reduced in the last 2 decades.13p14 Some2vg,11 have attributed this decreased incidence to corticosteroid treatment, but otherslO believe that steroid therapy has not been a factor. In several large clinical series, totaling 1,186 patients with systemic lupus erythematosus, with 147 autopsies,2p4-7pg*12 myocardial infarction was not reported. Among their patients with lupus erythematosus Taubenhaus et al-l5 found two with angina pectoris, one a 53 year old woman with electrocardiographic criteria for myocardial infarction. Since autopsy was not performed the coronary artery disease in these patients cannot be characterized. Coronary atherosclerosis and myocardial infarction in lupus: Coronary arteritis was the cause of myocardial infarction in a 35 year old woman with systemic lupus erythematosus described by Dubois16 and in a 16 year old youth observed by Bonfiglio et a1.17 The latter suspected coronary arteritis in three other patients found to have coronary artery disease on arteriographic studies performed because of angina pectoris; later one had a myocardial infarction. Brigden et a1.8 found myocardial infarction in 2 of 27 autopsies of patients with lupus erythematosus, in both cases associated with widespread arterial occlusions and acute necrotizing lesions in the small vessels. Hejtmancik et al. lo described coronary arteritis in 6 of 16 autopsies of patients with systemic lupus erythematosus, but no patient had myocardial infarction due to such involvement. Six of their 142 patients had angina pectoris; 4 of the 6 had an electrocardiographic pattern of myocardial infarction without a history of it, but one died and was found to have coronary atherosclerosis and myocardial infarction at autopsy. Kong et al.ll described two patients, 42 and 46 years old, respectively, with myocardial infarction due to coronary atherosclerosis in 30 autopsies of patients with systemic lupus erythematosus. Tsakraklides et a1.i8 cited a 29 year old woman with lupus erythematosus who died of acute myocardial infarction and who had marked atherosclerosis in the major coronary trunks without signs of active or healed arteri-
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
tis. This case and our Case 1, both describing young women without underlying risk for coronary atherosclerosis, suggest an association between systemic lupus erythematosus and coronary atherosclerosis that is probably not coincidental, considering the very low incidence of myocardial infarction in persons under age 30. In this age group the incidence of myocardial infarction in women is much lower than in menig-21; of 398 patients of three series with myocardial infarction at age 40 or less only 1 woman was less than 30 years old and she had severe diabetes of juvenile onset and hyperlipidemia.20 Pathogenesis of coronary atherosclerosis in lupus: The mechanism by which systemic lupus erythematosus may influence the development of coronary atherosclerosis is not known. Rich and Gregory22 described sclerotic lesions of the coronary arteries in lupus erythematosus, indistinguishable from ordinary atherosclerosis in its more advanced and fibrous form. They proposed an antigen-antibody reaction as the pathogenesis of these lesions. The influence of corticosteroids in coronary atherosclerosis is not clear. Necrotizing arteritis has been reported in patients with rheumatoid arthritis treated with steroids.23,24 Kemper et a1.25 found lesions of periarteritis nodosa in 4 of 14 patients with rheumatoid arthritis treated with steroids, whereas none of the 38 patients who did not receive steroids had such lesions; there was no correlation between dosage or duration of treatment and the appearance of vascular lesions. However, they did not mention atherosclerotic lesions in their cases. The latter were not found at autopsy in Finck’s patient26 with rheumatoid arthritis and necrotizing arteritis supposedly due to overdosage of cortisone. Autopsy in our Case 1 revealed atherosclerosis, but the other two patients with electrocardiographic pattern of myocardial infarction could have either coronary atherosclerosis or arteritis, and there is no way to differentiate, clinically, between them. This distinction may become important if coronary arterial surgery is ever contemplated in these young patients. Further clinical, arteriographic and pathologic correlations will be necessary to clarify this problem.
References Humpreys EM: The cardiac lesions of acute disseminated lupus erythematosus. Ann Intern Med 28:12-14, 1948 Shearn MA: The heart in systemic lupus erythematosus. Am Heart J 581452-466, 1959 Marks AD: The cardiovascular manifestations of systemic lupus erythematosus. Am J Med Sci 264:254-265, 1972 Jessar RA, Lamoni-Havers RW, and Ragan C: Natural history of lupus erythematosus disseminatus. Ann Intern Med 38:717731,1953 5. Turn&y PA: The clinical course of systemic lupus erythematosus. JAMA 156:947-953, 1954 6. Armas-Cruz R, Harnecker J, Ducach, G, et al: Clinical diagnosis of systemic lupus erythematosus. Am J Med 25:409-419, 1958 7. Copeland GD, Von Capeller D, Stern TN: Systemic lupus er-
8. 9. 10.
11.
12.
February 1975
ythematosus: a clinical report of 47 cases with pathologic findinas in 18. Am J Med Sci 236:318-328, 1958 Bigden W, Bynaiers EGL, Lessof MH, et al: The heart In systemic lupus erythematosus. Br Heart J 22:1-16, 1960 Dubols EL, Tuffanelll DL: Clinical manifestations of systemic lupus erythematosus. JAMA 190:104-l 11, 1964 Hejimanclk MR, Wright JC, Quint R, et al: The cardiovascular manifestations of systemic lupus erythematosus. Am Heart J 68:119-130, 1964 Kong TO, Kellum RE, Haserlck JR: Clinical diagnosis of cardiac involvement in systemic lupus erythematosus: a correlation of clinical and autopsy findings in thirty patients. Circulation 26:711, 1982 Grlfflth GC, Vural IL: Acute and subacute disseminated lupus erythematosus: a correlation of clinical and postmortem findings
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INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
in eighteen cases. Circulation 3:492-500, 195 1 13. Gross L: The cardiac lesions in Libman-Sacks disease. With a consideration of its relationship to acute diffuse lupus erythematosus. Am J Pathol 16:375-407. 1940 14. Yuehreke RC: Lupus nephritis: clinical and pathological study based on renal biopsies. Medicine 36:1-145, 1957 15. Taubenhaus M, Eisenstein B, Pick A: Cardiovascular manifestations of collagen diseases. Circulation 12:903-920, 1955 16. Dubois EL: Lupus erythematosus, New York, McGraw-Hill, 1966, p 166 17. Bonflgiio TA, Bottl RE, Hagstrom JWC: Coronary arterkrs, occlusion, and myocardial infarction due to lupus erythematosus. Am Heart J 83:153-158, 1972 18. Tsakrakiides VG, Blleden LC, Edwards JE: Coronary atherosclerosis and myocardial infarction associated with systemic lupus erythematosus. Am Heart J 87:637-641, 1974 19. Kagan A, Dawber TR, Kannel WB, et al: The Framingham study: a prospective study of coronary heart disease. Fed Proc 21:suppl ll:52-57, 1962 20. Roth 0, Berkl A, Wolff GD: Long range observations in fifty-
314
February 1975
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ET AL.
21.
22.
23.
24. 25.
26.
three young patients with myocardiai infarction. Am J Cardiol 19:331-338, 1967 Gertler MM, White PD: Coronary heart disease in young adults. A multidisciplinary study. Cambridge, Mass, Harvard University Press, 1954 Rich AR, Gregory JE: Experimental anaphyiactic lesions of the coronary arteries of the “sclerotic” type, commonly associated with rheumatic fever and disseminated lupus erythematosus. Bull Johns Hopkins Hosp 81:312-324, 1947 Good TA, Benton JW, Kelly VC: Symptomatology resulting from withdrawal of steroid hormone therapy. Arthritis Rheum 2: 299-320, 1959 Rosenberg AL, Smyth CL, Gospe SR: Steroid vasculitis in rheumatoid arthritis (abstr). Arthritis Rheum 12:327, 1969 Kemper JW, Baggenstoss AH, Siocumb CH: The relationship of therapy with cortisone to the incidence of vascular lesions in rheumatoid arthritis. Ann Intern Med 46:831-851, 1957 Finck PA: Cortisone overdosage in rheumatoid arthritis. Arch Pathol 601374-377. 1955
Volume 35
Infarction
Due to Coronary
Three Young Adults with Systemic
JOSE MELLER. MD CESAR A. CONDE, MD LUDWIG M. DEPPISCH, MD EPHRAIM DONOSO, MD, FACC SIMON DACK, MD, FACC New York, New York
Atherosclerosis
in
Lupus Erythematosus
Three patients, 24, 24 and 25 years of age, with systemic lupus erythematosus had signs of myocardial infarction. Two had serial electrocardiographic changes indicative of infarction without any cardiac symptoms. The third patient had clinical evidence of an acute massive myocardial infarction, which was proved at autopsy to be due to coronary atherosclerosis. This case is presented tn detail and the association between systemic lupus erythematosus and myocardial infarction is reviewed. It is postulated that the relation between lupus erythematosus and coronary atherosclerosis is more than coincidental.
Myocardial infarction is seen infrequently in patients with systemic lupus erythematosus and there has been some controversy concerning the relation between lupus erythematosus and coronary atherosclerosis-1-3 In 1 year we observed three young adults with systemic lupus erythematosus and signs of coronary artery disease. The first patient, a 25 year old woman, was admitted with an acute myocardial infarction complicated by cardiogenic shock; she died and on autopsy had evidence of coronary atherosclerosis as the cause of the infarction. The other two patients, both 24 years of age, had only classic electrocardiographic changes indicative of myocardial infarction and no symptoms referable to the heart. Case Reports
From the Division of Cardiology, Department of Medicine and the Department of Pathology, Mount Sinai School of Medicine of the City University of New York, New York, N. Y. Manuscript accepted July 17, 1974. Address for reprints: Simon Dack, MD, The Mount Sinai Hospital, Division of Cardiology, Department of Medicine, 100th St. and Fifth Ave., New York, N. Y. 10029.
Case 1. A 25 year old woman was admitted to Mount Sinai Hospital because of chest pain of six days’ duration. Twelve years earlier she had choreiform movements that lasted several weeks but responded to treatment with corticosteroids. Four years later she again had episodes of chorea, this time accompanied by pain in the hips and elbows. On admission to another hospital where lupus erythematosus preparations were reportedly positive, she was treated with prednisone, 75 mg daily; this dose was gradually decreased. The choreiform movements, especially of the hands and tongue, recurred frequently, always responding to reinstitution of large doses of corticosteroids. While receiving steroid therapy she was noted to have hypertension but was not treated for it. Six months before admission she was hospitalized because of arthralgia and pleuritic chest pain. A chest roentgenogram and an electrocardiogram were reported to be normal. The amount of prednisone administered was increased and the pains disappeared; 3 months later she was asymptomatic and prednisone was administered in gradually reduced doses and then discontinued. Two weeks before admission she had an episode of severe chest pain precipitated by exertion and relieved by resting. This pain was substernal without radiation and made worse by deep inspiration. Six days before admission the same pain recurred and persisted until her hospitalization. She also complained of rapidly progressive dyspnea on exertion, diaphoresis and fainting sensation. She denied fever, hemoptysis, the use of birth-control pills and smoking. Her serum cholesterol had been normal. The family history was noncontributory.
February 1975
The American Journal of CARDIOLOGY
Volume 35
309
MYOCARDJAL INFARCTION IN LUPUS ER~H~MATOSUS-MELLER
ET AL.
FIGURE 1. Case 1. Chest roentgenogram on hospital admission revealing a markedly enlarged cardiac silhouette.
On ph~si&a~ e~a~~~a~~on she appeared acutely ill, tachypneic, diaphoretic and cold. The pulse was 140/min, regular and weak, the blood pressure was obtainable by palpation only at 60 mm Hg, the respiratory rate was 36/ min and the temperature was 98’F. The skin was pale and clammy with livedo reticularis pattern. Jugular veins were not seen and no hepatojugular reflux could be demonstrated. The lungs were clear. Examination of the heart revealed normal heart sounds and a loud diastolic gallop; no
I
II
III
8VR
8VL
FIGURE 3. Case 1. Transverse sections of the heart manifesting a recent extensive myocardial infarct in the anterior and septal walls.
pericardial rub or murmurs were heard. The abdomen was obese with striae. laboratory studies disclosed the following: hemoglobin 10.6 g/100 ml, hematocrit 31 percent, white blood cell count 5,400/mm3, 2+ proteinuria, blood urea nitrogen 23 mg/lOO
rVF
VI
v2
V3
v4
vs
‘6
FIGURE 2. Case 1. Serial electrocardiograms demonstrating an anteroseptaf wall myocardial infarction, intermittent right bundle branch block and probable left posterior hemiblock.
310
February 1975
The American Journal of CARDIOLOGY
Volume 35
MYOCARDIAL
ml and serum creatinine 1.4 mg/lOO ml. The serum electrolytes, uric acid, protein and cholesterol findings were normal. The initial serum enzyme values were: glutamic oxaloacetic transaminase (SGOT) 75 U (normal up to 45 U) and creatine phosphokinase (CPK) 410 U (normal up to 125 U). The chest roentgenogram revealed a markedly enlarged cardiac silhouette (Fig. 1). The electrocardiogram disclosed sinus tachycardia, right axis deviation, QS pattern in leads Vr to Vs, S-T elevation in leads III and aVF and S-T depression in leads I, aVL and Vs to Vs (Fig. 2). An emergency pericardiocentesis was performed, hut no fluid was obtained. After administration of isoproterenol and hydrocortisone the blood pressure increased to 80/60 mm Hg. A repeat chest X-ray film revealed fluid in the left costophrenic angle, and small doses of furosemide were given. Serial electrocardiograms disclosed changes consistent with an acute anteroseptal myocardial infarction; complete right bundle branch block appeared intermittently. T$he serum CPK increased to 2,100 U, SGOT to 360 U and lactic dehydrogenase (LDH) to 330 U. On the 2nd day the pain was mild during deep inspiration and when the patient was supine. She required isoproterenol to maintain blood pressure. On the 5th day ventricular fibrillation developed and all resuscitative efforts were unsuccessful. Autopsjr findings: The heart was enlarged, weighing 400 g. An extensive fibrinous pericarditis was present. A large recent transmural myocardial infarct involved the entire anterior wall and interventricular septum of the left ventricle from the cardiac apex to 1 cm below the base of the aortic valve (Fig. 3). A healed infarct, 3 cm in diameter, involved the posterior wall and posterior septum. FIGURE 5. Case 1. Sections of coronary arteries. A, cross section of the left anterior descending coronary artery showing an occlusive thrombus superimposed upon an atheromatous plaque. B, longitudinal section of the right coronary artery showing an early organizing occlusive thrombus attached to an atheromatous plaque. C, cross section of a coronary artery manifesting severe eccentric intimal fibrosis. (Hematoxylin-eosin X 10.)
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
FIGURE 4. Case 1. Opened left anterior descending coronary artery showing complete occlusion by an organizing thrombus.
The coronary arteries displayed focal, but severe atherosclerosis. The left anterior descending coronary artery was completely occluded by an organizing thrombus 3 cm distal to its origin (Fig. 4). This thrombus was superimposed upon a hemprrhagic intimal atheroma (Fig. 5A). An atheromatous plaque with superimposed thrombus significantly narrowed the right coronary artery 4.5 cm from its ostium (Fig. 5B). Microscopic sections of coronary arteries revealed eccentric intimal fibrosis and dystrophic calcification (Fig. 5C). There was no inflammation or fibrinoid ne-
A
\
February 1975
The American Journal of CARDIOLOGY
Volume 35
311
MYOCARDIAL
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
Case 3: A 24 year old woman with systemic lupus erythematosus was admitted several times to Mount Sinai Hospital because of neurologic, dermatologic and renal symptoms. A pattern of inferior wall myocardial infarction developed in serial electrocardiograms, but she had no cardiac symptoms (Fig. 7).
crosis in the coronary vessels. Immunofluorescent staining of a coronary artery revealed no gamma globulin or complement deposition. Multiple 1 to 3 mm pink verrucae were attached to the atria1 surface of both mitral valve cusps. Multiple similar verrucae covered the atria1 and ventricular surfaces of all cusps of the tricuspid valve and, by extension, the adjacent right atria1 and right ventricular endocardium. Microscopically these verrucae consisted of thrombi in various stages of early organization. Valvular destruction or microorganisms were not observed. Several extracardiac anatomic findings characteristic of systemic lupus erythematosus were seen: mild focal glomerulonephritis with immune complex deposition within glomerular capillary walls, “onion-skin” periadventitial fibrosis of medium-sized splenic arteries and a focal interstitial pulmonary infiltration.
Discussion Cardiac symptoms are seen in 50 to 89 percent of patients with systemic lupus erythematosus,3-10 but are rarely the first manifestation of the disease.‘cJl The most frequent cardiac diagnoses in these patients are pericarditis and myocarditis; both are found more frequently in autopsy than in clinical studies.3,5J2 Electrocardiographic abnormalities are also common,2,4F7J2 usually consisting of S-T segment and T wave changes secondary to pericarditis, myocarditis or metabolic abnormalities caused by the basic disease. Abnormal Q waves indicating myocardial infarction are very rare, even in patients found to have myocardial infarction at autopsy.8 Libman-Sacks valvulitis can be diagnosed with
Case 2: A 24 year old man with systemic lupus erythematosus was admitted several times to Mount Sinai Hospital because of neurologic symptoms. His electrocardiogram revealed an anteroseptal wall myocardial infarction pattern in serial tracings, but he had no symptoms referable to the heart (Fig. 6).
II
I
III
aVR
aVL
aVF
A
X2/6/72
FIGURE 6. Case 2. Electrocardiograms revealing a developing pattern of anteroseptal myocardial infarction. . I
II
III
aVR
aVL
aVF
VI
V2
v3
FIGURE 7. Case 3. Electrocardiograms revealing a developing pattern of inferior wall myocardial infarction.
312
February 1975
The American Journal of CARDIOLOGY
Volume 35
V4
V5
‘6
MYOCARDIAL
certainty only at autopsy,g and its reported incidence has been reduced in the last 2 decades.13p14 Some2vg,11 have attributed this decreased incidence to corticosteroid treatment, but otherslO believe that steroid therapy has not been a factor. In several large clinical series, totaling 1,186 patients with systemic lupus erythematosus, with 147 autopsies,2p4-7pg*12 myocardial infarction was not reported. Among their patients with lupus erythematosus Taubenhaus et al-l5 found two with angina pectoris, one a 53 year old woman with electrocardiographic criteria for myocardial infarction. Since autopsy was not performed the coronary artery disease in these patients cannot be characterized. Coronary atherosclerosis and myocardial infarction in lupus: Coronary arteritis was the cause of myocardial infarction in a 35 year old woman with systemic lupus erythematosus described by Dubois16 and in a 16 year old youth observed by Bonfiglio et a1.17 The latter suspected coronary arteritis in three other patients found to have coronary artery disease on arteriographic studies performed because of angina pectoris; later one had a myocardial infarction. Brigden et a1.8 found myocardial infarction in 2 of 27 autopsies of patients with lupus erythematosus, in both cases associated with widespread arterial occlusions and acute necrotizing lesions in the small vessels. Hejtmancik et al. lo described coronary arteritis in 6 of 16 autopsies of patients with systemic lupus erythematosus, but no patient had myocardial infarction due to such involvement. Six of their 142 patients had angina pectoris; 4 of the 6 had an electrocardiographic pattern of myocardial infarction without a history of it, but one died and was found to have coronary atherosclerosis and myocardial infarction at autopsy. Kong et al.ll described two patients, 42 and 46 years old, respectively, with myocardial infarction due to coronary atherosclerosis in 30 autopsies of patients with systemic lupus erythematosus. Tsakraklides et a1.i8 cited a 29 year old woman with lupus erythematosus who died of acute myocardial infarction and who had marked atherosclerosis in the major coronary trunks without signs of active or healed arteri-
INFARCTION IN LUPUS ERYTHEMATOSUS-MELLER
ET AL.
tis. This case and our Case 1, both describing young women without underlying risk for coronary atherosclerosis, suggest an association between systemic lupus erythematosus and coronary atherosclerosis that is probably not coincidental, considering the very low incidence of myocardial infarction in persons under age 30. In this age group the incidence of myocardial infarction in women is much lower than in menig-21; of 398 patients of three series with myocardial infarction at age 40 or less only 1 woman was less than 30 years old and she had severe diabetes of juvenile onset and hyperlipidemia.20 Pathogenesis of coronary atherosclerosis in lupus: The mechanism by which systemic lupus erythematosus may influence the development of coronary atherosclerosis is not known. Rich and Gregory22 described sclerotic lesions of the coronary arteries in lupus erythematosus, indistinguishable from ordinary atherosclerosis in its more advanced and fibrous form. They proposed an antigen-antibody reaction as the pathogenesis of these lesions. The influence of corticosteroids in coronary atherosclerosis is not clear. Necrotizing arteritis has been reported in patients with rheumatoid arthritis treated with steroids.23,24 Kemper et a1.25 found lesions of periarteritis nodosa in 4 of 14 patients with rheumatoid arthritis treated with steroids, whereas none of the 38 patients who did not receive steroids had such lesions; there was no correlation between dosage or duration of treatment and the appearance of vascular lesions. However, they did not mention atherosclerotic lesions in their cases. The latter were not found at autopsy in Finck’s patient26 with rheumatoid arthritis and necrotizing arteritis supposedly due to overdosage of cortisone. Autopsy in our Case 1 revealed atherosclerosis, but the other two patients with electrocardiographic pattern of myocardial infarction could have either coronary atherosclerosis or arteritis, and there is no way to differentiate, clinically, between them. This distinction may become important if coronary arterial surgery is ever contemplated in these young patients. Further clinical, arteriographic and pathologic correlations will be necessary to clarify this problem.
References Humpreys EM: The cardiac lesions of acute disseminated lupus erythematosus. Ann Intern Med 28:12-14, 1948 Shearn MA: The heart in systemic lupus erythematosus. Am Heart J 581452-466, 1959 Marks AD: The cardiovascular manifestations of systemic lupus erythematosus. Am J Med Sci 264:254-265, 1972 Jessar RA, Lamoni-Havers RW, and Ragan C: Natural history of lupus erythematosus disseminatus. Ann Intern Med 38:717731,1953 5. Turn&y PA: The clinical course of systemic lupus erythematosus. JAMA 156:947-953, 1954 6. Armas-Cruz R, Harnecker J, Ducach, G, et al: Clinical diagnosis of systemic lupus erythematosus. Am J Med 25:409-419, 1958 7. Copeland GD, Von Capeller D, Stern TN: Systemic lupus er-
8. 9. 10.
11.
12.
February 1975
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