Heart Vessels (1992) Suppl. 7:26-31
Heart
andVesse]S
© Springer-Verlag1992
Coronary artery lesions in Takayasu arteritis: Pathological considerations Osamu Matsubara, 1 Takeshi Kuwata, 1 Tetsuo N e m o t o , 1 T s u t o m u Kasuga, 1 and Fujio N u m a n o 2 1Departments of Pathology and 2Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113 Japan
Summary. This communication reviews the clinical and p'athological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments o f the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed. Key words: Takayasu arteritis (disease) - Coronary ostial stenosis - Coronary arteritis - Coronary artery aneurysm
Address correspondence to: O. Matsubara
Introduction Takayasu arteritis is a disease of unknown etiology, predominantly in young women, that affects the aorta and its main branches segmentally [1]. Histological examinations of arterial lesions in Takayasu arteritis show that this disease produces a kind of panarteritis characterized by marked thickening of the wall with granulomatous, diffuse productive or fibrosing inflammations [2]. The main lesions are usually in the ascending aorta and the proximal segments of arteries arising from the aortic arch. These inflamed lesions usually have a patchy or scattered distribution. Despite advances in diagnosis and treatment of this disease, its pathogenesis is still unknown. Recently, lesions of the coronary artery in this disease have received attention clinically and pathologically. Most of the coronary artery lesions are thought to be due to extension of intimal proliferation and fibrous contraction due to the inflammatory process that involves the ascending aorta [3-5]. However, there are reports that the incidence of aortic regurgitation in Takayasu's arteritis is 13%-44% [6, 7], and that the incidence of coronary artery lesions is about 9% to 10% [1, 8, 9]. Nagata [10] reviewed 82 autopsied cases of Takayasu arteritis reported in the Annuals of Pathological Autopsy Cases in Japan from 1975 to 1984. Among these cases, cardiac failure occurred in 49 cases (59.8%), aortic regurgitation in 21 (25.6%), and myocardial infarction in 10 (12.2%). He also reported that the incidence of coronary artery lesions was higher than that noted previously. This communication reviews the clinical and patho!ogical features of coronary artery lesions in Takayasu arteritis.
O. Matsubara et al. : Coronary artery lesions in Takayasu arteritis
27
Fig. 1. Scheine of the three types of
A
'E 1 AV
2
F"
»E 3
LV
Clinical observation Generalized systemic symptoms are frequently present early in the disease [11, 12], whereas the late occlusive phase of the disease is characterized by claudication, cerebral ischemia, systemic hypertension or cardiac symptoms [11, 13, 14]. Frovig and Loken [15] first described narrowing of the coronary arteries in Takayasu arteritis in 1951, but coronary artery lesions have been considered to be an uncommon [9, 11], although potentially fatal complication in this disease. Myocardial infarction, systemic hypertension and aortic regurgitation are common causes of heart failure and death in Takayasu arteritis [11, 12, 1O, 17]. The incidence of coronary artery involvement has been reported to be 9% to 10% [1, 8, 9]. It has been noted mainly in autopsy cases, because it is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. In 1977, Cipriano et al. [4] reported the clinical features of 16 cases with coronary artery lesions in Takayasu arteritis, which were detected either angiographically or at autopsy. They found that angina pectoris was a symptom of only 3 of 8 cases with evidence of myocardial infarction. They also reported cardiac related death in 9 of 16 cases. These findings suggest the difficulty of detecting coronary artery lesions due to Takayasu arteritis and also the absence of a natural history of patients with combined coronary artery lesions.
coronary artery lesions in Takayasu arteritis. Cut sections of the ascending aorta show marked fibrous thickening of the adventitia, disruption of the elastic fibers in the media and fibrous thickening of the intima on both sides. Cut section of the left coronary ostium and Valsalva sinus shows normal structure with elastic fibers in the media, and no thickening of the adventitia or intima. Type 1 lesion: stenosis or occlusion of the coronary ostium and the proximal segment of the coronary artery. Type 2 lesion: diffuse or focal coronary arteritis (the latter is shown here). ~ Type 3 lesion: coronary aneurysm. Chronic inflammation of the aneurysmal wall and thrombosis is shown here. ASA, Ascending aorta; FT, subepicardial fatty tissue; AV, aortic valve; VS, Valsalva sinus; MC, myocardium; T, thrombus; LV, left ventricle
Makino et al. [18] reviewed reported cases of Takayasu arteritis in which coronary involvement was detected by coronary angiography. All cases revealed subtotat, from 50% to 100%, ostial narrowing of either the right (4 cases) or the left (8 cases) coronary artery or both (2 cases), and all had a history of angina pectoris. An aortocoronary bypass graft operation was undertaken in 8 of these cases.
Pathological report From the many reports and reviews on the pathology of Takayasu arteritis, the following observations are generally accepted [2, 19, 20]. The early histological changes of Takayasu arteritis are granulomatous inflammation, with various degrees of cellular infiltration in the adventitia and the outer part of the media, and marked inflammation of the vasa vasorum. Subsequently, marked intimal thickening occurs in the areas that overlie granulomatous and fibrotic lesions in the media and adventitia. This marked fibrosis and thickening of the arterial wall eventually becomes stenotic or occluded, and less commonly, a saccular aneurysm may develop. Aortic regurgitation is thought to develop primarily by annular dilatation resulting from extensive dilatational changes of the ascending aorta and secondarily, by primary valvular lesions such as fibrous thickening, enrolling, retraction, and calcification, and by aneurysms arising from the aortic annulus [6, 7, 21, 22], although aneurysms are less common.
28
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis
Table 1. Reported cases of coronary arteritis in Takayasu arteritis with pathohistologic descriptions Case
Age
Sex
Involvement of coronary orifice
Involvement of coronary artery
Microscopic findings
MGHCase record [24]
45
M
Both orifices narrowed
Rosen and Gaton [25]
44
M
Patent
Rose and SinclairSmith [5]
29
M
nd
Throughout thelength reduced to less than i mm in externai diameter A short segment of LCA, a 3.5 cm-long segment of LAD, a 2.5 cm-long segment of RCA Distal circulflex branch of LCA
Adventitial fibrosis, inflammatory cellular infiltration to the media, and severe intimal fibrosis Wall replaced by dense collagenous tissue, and lumen obliterated by granulation tissue Thrombotic occlusion with recanalization (healed arteritis)
M
nd
Chronic, nonnecrotizing, desmoplastic, granulomatous inflammation
60
M
nd
Chronic fibrosing inflammation
71
M
nd
Main LCA, proximal third of LAD, and RCA, most severely 4 cm from its origin LCA and RCA from their origin to their primary branches Epicardial coronary arteries
No MI
Aufderheide / 49
Myocardial fibrosis and MI AMI
62
M
Patent
Proximal segment of LAD
5
F
nd
RCA and LCA
{ 62
M
Patent
All main epicardial branches
64
M
Patent
All main epicardial branches
et al. [26]
Payan and Gilbert [27] Sciagra et al. [281 Wolf et al. [291
Tanaka et al.
[30]
Granulomatous inflammatory panarteritis Granulomatous inflammation, thickening of the wall, unrecognizable lumen, and collaterals Dense transmural fibrosis with luminal stenosis, thrombosis with organization, and aneurysm Marked fibrous thickening of the adventitia, intimal fibrosis, and cellualr infiltration to the media Marked fibrous thickening of the adventitia, intimal fibrosis, and cellular infiltration to the media
Disease of the heart OMI and AMI OMI
No MI
Unstable angina pectoris AMI and OMI AMI AMI
OMI, old myocardial infarction; AMI, acute myocardial infarction; L CA, left coronary artery; LAD, left anterior descending branch; nd, not described; RCA, right coronary artery The following 3 types of coronary artery lesions are distinguished on the basis of their pathological features: type 1, stenosis or occlusion of the coronary ostia and the proximal segment of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysms (Fig. 1). Type 1 is the commonest, and types 2 and 3 are very rare.
Coronary ostial stenosis Narrowing of the coronary arteries is mainly due to extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the ascending aorta. Cipriano et al. [4] presented a case of Takayasu arteritis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia, and r e v i e w e d 16 cases in which this disease involved
coronary arteries. Angina pectoris was a symptom in 7 of the 16 cases. Eight cases had evidence of myocardial infarction, and 3 had angina pectoris and myocardial infarction. In 10 of these cases, coronary narrowing was purely ostial due to healing of the inttamed aortic ro0t. Cipriano et al. concluded that stenosis is characteristically limited to the aorta and proximal segments of the coronary arteries. Amano et al. [23] reviewed 54 cases including 34 autopsy cases with coronary artery lesions, also reporting that about 80% of the coronary lesions were limited to the ostia and proximal segments of the coronary arteries.
Coronary arteritis In some cases, the coronary stenosis may be caused by coronary arteritis as one of the skip lesions of Takayasu arteritis, but even in these cases the lesions mainly affect the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery are very
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis rare. Table 1 lists the reports of cases of Takayasu arteritis with coronary arteritis, that give pathohistologic descriptions. The ages ranged ffom 5 to 71 years. Although Takayasu arteritis predominantly affects females, 9 cases were males and 1 was a young female. In 9 of 10 cases, coronary artery lesions were continuous from the ostia and proximal segments. Diffuse involvement of'coronary branches was observed in only 3 cases. Regarding the character of coronary arteritis, fibrosing inflammation was seen in 4 cases, granulomatous inflammation in 3 cases, and diffuse productive inflammation in 3 cases. Thrombosis and recanalization were seen in 2 cases.
Coronary an«urysm Coronary artery aneurysm seems to be rare in Takayasu arteritis, as it is in general. Falsetti and Carroll [31] reviewed 34 reported cases of coronary artery aneurysms and Markis et al. [32] reported a further 30 cases. Atherosclerosis is the most common cause, accounting for about 50% of the cases. Other causes of coronary artery aneurysms include congenital arteriovenous fistulae, trauma, polyarteritis nodosa, septic emboli, localized congenital myoelastic defects, and Kawasaki disease (acute febrile infantile mucocutaneous lymph node syndrome). We found reports of 7 cases of coronary aneurysm in Takayasu arteritis [1, 5, 33-37]. The cases with this association ranged in age from 11 to 53 years, and all were females. Three cases had aneurysms in the distal branch of the right coronary artery and left anterior descending branch, and 2 cases had them in the coronary ostia. Pathological descriptions were insufficient except in the cases reported by Rose and Sinclair-Smith [5]. Direct extension of the inflammatory process of the ascending aorta into the coronary ostia and the coronary artery roots and severe disruption of the media are important factors in the formation of coronary artery aneurysms in this disease.
Other causes of coronary ostial stenosis Coronary ostial stenosis is a rare lesion. From examinations by coronary angiography its incidence was estimated as 0.093% to 0.13% [38, 39]. The most frequent cause was atherosclerosis of the coronary artery and sinus of Vatsalva. Severe reduction of the coronary ostium may result from an aortic atherosclerotic plaque protruding or extending into the lumen. Such paraostial obstructive atherosclerosis was present in 73.3% of the cases with myocardial infarction and in 51.6% of those without it [40]. Coronary ostial stenosis is ffequently associated with syphilitic aortitis, being found in one-fourth to
29 one-third of such cases [41, 42]. Ostial stenosis is also seen in other types of aortitis including Takayasu arteritis, aortic dissection, embolic occlusion, papillary elastofibroma or hamartoma of the aortic valve, congenital coronary anomaly, fibromuscular dysplasia, and miscellaneous other conditions such as those due to radiation, trauma and iatrogenic causes.
Other types of coronary arteritis Subepicardial coronary arteritis is a relatively rare event that may occur in many conditions. Any septicemic state may cause a coronary response, and this is the most common cause. Tuberculous coronary arteritis is seen chiefly in cases with pericardial and myocardial tuberculosis. Coronary lesion in the course of systemic polyarteritis nodosa is relatively frequent. In most cases, acute myocardial infarction was described and a case of hemopericardium due to rupture of an aneurysm was reported [43]. Kawasaki disease is regarded as a form of polyarteritis occurring in children. Typical lesions can also be seen in rare cases of coronary giant cell arteritis [44]. Less specific histologic changes are present in rheumatic coronary arteritis, the involvement of the subepicardial vessels being less common than that of intramural ones [45]. Severe inflammatory subepicardial involvement has been described in systemic lupus erythematosus (SLE) [46]. Of 30 cases of Buerger disea'se, only one had a lesion in the coronary artery [47].
Discussion It is generally accepted that cardiac lesions a r e a major cause of death in cases of Takayasu arteritis. Next to aortic regurgitation, heart failure followed by acute and old myocardial infarction is the most common cause of death in this disease [1, 10-12, 16, 17]. Thus a better understanding of the nature of coronary artery lesions in Takayasu arteritis is becoming increasingly important. This communication reviews reported cases of Takayasu arteritis and those that we have experienced, and proposes that three types of coronary artery lesions can be distinguished on the basis of their pathologic features. In addition to their differences in clinical features, the treatments of these three types will be somewhat different. Cases of type 1 fange widely in age and are predominantly, though not exclusively, female. On the other hand, most cases of type 2 are middle-aged or elderly males [5, 24-30], whereas all those of type 3 are young or middle-aged females [1, 5, 33-37]. The cause of death in almost all cases of types 2 and 3 is acute myocardial infarction, whereas in cases
30 of type 1, the causes vary including sudden death, myocardial infarction and heart failure. Cases of type 1 are suitable candidates for coronary artery bypass grafting (CABG) because lesions are limited to the coronary orifice [48], but cases of types 2 and 3 have higher risk for this operation, because they orten have more diffuse coronary artery lesions. C A B G seems to be an effective treatment for preventing myocardial infarction, but careful examination of the coronary artery lesions is recommended. Why is the coronary artery involved in this disease? As the etiology of Takayasu arteritis is still unknown, we do not know why. But it seems reasonable that the coronary arteries should be involved, because the brachiocephalic branches are commonly involved and the coronary arteries are the first branches from the ascending aorta. Small arteries such as muscular arteries or arterioles have seldom been reported to be involved in Takayasu arteritis. Except for the pulmonary artery [49, 50], the coronary artery is the only site of lesions reported. If lesions of large blood vessels cannot be observed or are not examined, and only coronary arteritis is seen, a misdiagnosis may be made. Small artery disease is very rare in Takayasu arteritis, but we need to determine whether it is just a complication of Takayasu arteritis or whether it is a distinct disease entity. In conclusion, according to their pathologic features the coronary artery lesions observed in Takayasu arteritis can be classified into the following three types: type 1, stenosis or occlusion of the coronary ostia and/or the proximal segment of the coronary arteries; type\2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; type 3, coronary aneurysm. The coronary artery lesions in most cases of Takayasu arteritis are of type 1. Coronary ostial stenosis is thought to be due to extension of intimal proliferation and fibrous contraction due to the inflammatory process from the ascending aorta and the coronary ostia. In some cases, the coronary stenosis may be caused by coronary arteritis as one of the skip lesions of Takayasu arteritis, but even in these cases the lesions mainly affect the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysms seem to be very rare in Takayasu arteritis. Direct extension of the inflammatory process from the ascending aorta into the coronary ostia and the coronary artery roots and severe disruption of the media also seem to be causes of coronary artery aneurysms in this disease.
Acknowledgments. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, Mitsui Life Social Welfare Foundation, and Araki Medical and Biochemical Research Foundation.
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis
References 1. Lupi-Herrera E, Sanchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE (1977) Takayasu's arteritis. Clinical study of 107 cases. Am Heart J 93:94103 2. Nasu T (1962) Pathology of pulseless disease: Systemic study and critical review of twenty-one autopsy cases reported in Japan. Angiology 14:225-242 3. Saito Y, Hirota K, Ito I, Yamaguchi H, Takeda T, Morooka S, Ueda H (1972) Clinical and pathologic studies of five autopsied cases of aortitis syndrome. Jpn Heart J 13:107-117 4. Cipriano PR, Silverman JF, Perlroth MG, Griepp RB, Wexler L (1977) Coronary narrowing in Takayasu's aortitis. Am J Cardiol 39:744-750 5. Rose AG, Sinclair-Smith CC (1980) Takayasu's arteritis: A study of 16 autopsy cases. Arch Pathol Lab Med 104:231-237 6. Isomura T, Hisatomi K, Yanagi I, Shimada S, Uraguchi K, Aoyagi S, Kosuga K, Ohishi K (1988) The surgical treatment of aortic regurgitation secondary to aortitis. Ann Thorac Surg 45:181-185 7. Uehara K, Kitamura N, Ito T, Koyanagi H, Hashimoto .A, Konno H (1981) Severe aortic regurgitation in Takayasu's arteritis. J Jpn Assoc Thorac Surg 24:188197 8. Juzi U (1967) Arteriitis mit Herzinfarkt. Schweiz Med Wochenschr 13:397-405 9. Ueda H (1968) Clinical and pathological studies of aortitis syndrome: Committee report. Jpn Heart J 9:7687 10. Nagata S (1990) Present state of autopsy cases of Takayasu's arteritis (aortitis syndrome) in Japan (in Japanese). Myakkangaku 30:1303-1308 11. Strachan RW (1964) The natural history of Takayasu's arteriopathy. QJ Med 33:57-69 12. Nakao K, Ikeda M, Kimata S, Niitani H, Miyahara M, Ishimi Z, Hashiba K, Takeda Y, Ozawa T, Matsushita S, Kuramochi M (1967) Takayasu's arteritis: Clinical report of eighty-four cases and immunological study of seven cases. Circulation 35:1141-1155 13. Lande A, Gross A (1972) Total aortography in the diagnosis of Takayasu's arteritis. Am J Roentgenol Radium Ther Nucl Med 116:165-178 14. Lande A, Rossi P (1975) The value of total aortography in the diagnosis of Takayasu's arteritis. Radiology 114:287-297 15. Frovig AG, Loken AC (1951) Syndrome of obliteration of the arterial branches of the aortic arch due to arteritis. Acta Psychiatr Scand 26:313-337 16. Ishikawa K (1978) Natural history and classification of occlusive thromboaortopathy (Takayasu's disease). Circulation 57:27-35 17. Ishikawa K (1981) Survival and morbidity after diagnosis of occlusive thromboaortopathy (Takayasu's disease). Am J Cardiol 47:1026-1032 18. Makino N, Orita Y, Takeshita A, Nakamura M, Matsui K, T0kunaga K (1982) Coronary arterial involvement in Takayasu's disease. Jpn Heart J 23:1007-1013 19. Nasu T (1975) Takayasu's truncoarteritis in Japan. A statistical observation of 76 autopsy cases. Pathol Microbiol 43:140-146 20. Hotchi M, Fujihara M (1982) Aortitis syndrome (in Japanese). Rinsho Meneki 14:350-358 21. Ueda H, Sugiura M, Ito I, Salto Y, Morooka S (1967) Aortic insufficiency associated with aortitis syndrome. Jpn Heart J 8:107-120
O. Matsubara et al. : Coronary artery lesions in Takayasu arteritis 22. Akikusa B, Kondo Y, Muraki M (1981) Aortic insuß ficiency caused by Takayasu's arteritis without usual clinical features. Arch Pathol Lab Med 105:650-651 23. Amano J, Kameda T, Okamura T, Yakemasa A, Suzuki K, Tanaka J, Suzuki A, Wakiya Y, Abe H, Okada R, Kitamura K, Ban T, Nobuyoshi M (1982) Surgical treatment for coronary arterial lesions associated with aortitis syndrome (in Japanese). Nihon Shinzo Kekkan Geka Gakukai Zasshi 10:94-96 24. Case Records of the Massachusetts General Hospital 46-1967 (1967) N Engl J Med 277:1025-1033 25. Rosen N, Gaton E (1972) Takayasu's arteritis of coronary arteries. Arch Pathol 94:225-229 26. Aufderheide AC, Henke BW, Parker EH (1981) Granulomatous coronary arteritis (Takayasu's disease). Arch Pathol Lab Med 105:647-649 27. Payan HM, Gilbert EF (1984) Granulomatous coronary arteritis. Arch Pathol Lab Med 108:136-137 28. Sciagra R, Tebbe U, Rahlf G, Neuhaus KL, Kreuzer H (1986) Fatal outcome of aortocoronary bypass grafting in a 62-year-old man with unsuspected coronary arteritis. Clin Cardiol 9:583-586 29. Wolf RL, Gould NS, Green CA (1987) Unusual arteritis causing myocardial infarction in a child. Arch Pathol Lab Med 1i1:968-971 30. Tanaka A, Fukayama M, Funata N, Koike M, Salto K (1988) Coronary arteritis and aortoarteritis in the elderly males: A report of two autopsy cases with review of the literature. Virchows Archiv lA] 414:9-14 31. Falsetti HL, Carroll RJ (1976) Coronary artery aneurysm: A review of literature with a report of eleven new cases. Chest 69:630-636 32. Markis JE, Joff CD, Cohn PF, Feen D J, Herman MV, Gorlin R (1976) Clinical significance of coronary arterial ectasia. Am J Cardiol 37:217-222 33. Hachiya J (1968) Angiography of pulseless disease. A study of 50 cases (in Japanese). Nippon Acta Radiologica 27:1537-1557 34. Tamaki M (1968) Coronary arteriography (in Japanese). Nippon Acta Radiologica 28:733-738 35. Ellis R, Kurth RJ (1968) Calcified coronary artery aneurysms. JAMA 203:105-107 36. Fukuhara M, Koyama O, Onishi K, Adachi K, Tanemoto K, Matsuura S (1979) An autopsy case of
31
37.
38. 39. 40. 41. 42. 43.
44. 45. 46. 47. 48. 49. 50.
aortitis syndrome with aneurysm of bilateral coronary arteries (in Japanese). Shinzo 11:629-634 Fukuda I, Ijima H, Itoh T, Iriyama T, Maeta H, Okamura K, Mitsui T, Hori M (1983) Coronary artery aneurysm associated with aortitis syndrome diagnosed pre- and intraoperatively. Jpn Heart J 24:10071015 Pritchard CL, Mudd JG, Barner HB (1975) Coronary ostial stenosis. Circulation 52:46-48 Hutter JA, Pasaoglu I, Williams BT (1985) The incidence and management of coronary ostial stenosis. J Cardiovasc Surg 26:581-584 Heggtveit HA (1967) The role of coronary ostial stenosis in the etiology of myocardial infarction. Pathol Microbiol 30:716-717 Heggtveit HA (1964) Syphilitic aortitis. A clinicopathologic autopsy study of 100 cases, 1950 to 1960. Circulation 29:346-354 Burch GE, Winsor T (1942) Syphilitic coronary stenosis, with myocardial infarction. Am Heart J 24:740-751 Synclair W Jr, Nittsch E (1949) Polyarteritis nodosa of the coronary arteries. Report of a case of an aneurysm and intrapericardial hemorrhage. Am Heart J 38:898904 Harrison CV (1948) Giant-cell or temporal arteritis: Review. J Clin Pathol 1:197-211 Karsner HT, Bayless F (1934) Coronary arteries in rheumatic fever. Am Heart J 9:557-585 Bonfiglio TA, Botti RE, Hagstrom JWC (1972) Coronary arteritis, occlusion and myocardial infarction due to lupus erythematosus. Am Heart J 83:153-158 Saphir O (1936) Thromboangiitis obliterans of the coronary arteries and its relation to atherosclerosis. Am Heart J 12:521-535 Suzuki A, Amano J, Tanaka H, Sakamoto T, Sunamori M (1989) Surgical consideration of aortitis involving the aortic root. Circulation 80 (Suppl I):I-222-I-232 Rose AG, Halper J, Factor SM (1984) Primary arteriopathy in Takayasu's disease. Arch Pathol Lab Med 108:644-648 Matsubara O, Yoshimura N, Tamura A, Kasuga T, Yamada I, Numano F, Mark EJ (1992) Pathologic features of pulmonary artery in Takayasu's arteritis. Heart Vessels (Supp 7):18-25
Heart
andVesse]S
© Springer-Verlag1992
Coronary artery lesions in Takayasu arteritis: Pathological considerations Osamu Matsubara, 1 Takeshi Kuwata, 1 Tetsuo N e m o t o , 1 T s u t o m u Kasuga, 1 and Fujio N u m a n o 2 1Departments of Pathology and 2Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113 Japan
Summary. This communication reviews the clinical and p'athological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments o f the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed. Key words: Takayasu arteritis (disease) - Coronary ostial stenosis - Coronary arteritis - Coronary artery aneurysm
Address correspondence to: O. Matsubara
Introduction Takayasu arteritis is a disease of unknown etiology, predominantly in young women, that affects the aorta and its main branches segmentally [1]. Histological examinations of arterial lesions in Takayasu arteritis show that this disease produces a kind of panarteritis characterized by marked thickening of the wall with granulomatous, diffuse productive or fibrosing inflammations [2]. The main lesions are usually in the ascending aorta and the proximal segments of arteries arising from the aortic arch. These inflamed lesions usually have a patchy or scattered distribution. Despite advances in diagnosis and treatment of this disease, its pathogenesis is still unknown. Recently, lesions of the coronary artery in this disease have received attention clinically and pathologically. Most of the coronary artery lesions are thought to be due to extension of intimal proliferation and fibrous contraction due to the inflammatory process that involves the ascending aorta [3-5]. However, there are reports that the incidence of aortic regurgitation in Takayasu's arteritis is 13%-44% [6, 7], and that the incidence of coronary artery lesions is about 9% to 10% [1, 8, 9]. Nagata [10] reviewed 82 autopsied cases of Takayasu arteritis reported in the Annuals of Pathological Autopsy Cases in Japan from 1975 to 1984. Among these cases, cardiac failure occurred in 49 cases (59.8%), aortic regurgitation in 21 (25.6%), and myocardial infarction in 10 (12.2%). He also reported that the incidence of coronary artery lesions was higher than that noted previously. This communication reviews the clinical and patho!ogical features of coronary artery lesions in Takayasu arteritis.
O. Matsubara et al. : Coronary artery lesions in Takayasu arteritis
27
Fig. 1. Scheine of the three types of
A
'E 1 AV
2
F"
»E 3
LV
Clinical observation Generalized systemic symptoms are frequently present early in the disease [11, 12], whereas the late occlusive phase of the disease is characterized by claudication, cerebral ischemia, systemic hypertension or cardiac symptoms [11, 13, 14]. Frovig and Loken [15] first described narrowing of the coronary arteries in Takayasu arteritis in 1951, but coronary artery lesions have been considered to be an uncommon [9, 11], although potentially fatal complication in this disease. Myocardial infarction, systemic hypertension and aortic regurgitation are common causes of heart failure and death in Takayasu arteritis [11, 12, 1O, 17]. The incidence of coronary artery involvement has been reported to be 9% to 10% [1, 8, 9]. It has been noted mainly in autopsy cases, because it is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. In 1977, Cipriano et al. [4] reported the clinical features of 16 cases with coronary artery lesions in Takayasu arteritis, which were detected either angiographically or at autopsy. They found that angina pectoris was a symptom of only 3 of 8 cases with evidence of myocardial infarction. They also reported cardiac related death in 9 of 16 cases. These findings suggest the difficulty of detecting coronary artery lesions due to Takayasu arteritis and also the absence of a natural history of patients with combined coronary artery lesions.
coronary artery lesions in Takayasu arteritis. Cut sections of the ascending aorta show marked fibrous thickening of the adventitia, disruption of the elastic fibers in the media and fibrous thickening of the intima on both sides. Cut section of the left coronary ostium and Valsalva sinus shows normal structure with elastic fibers in the media, and no thickening of the adventitia or intima. Type 1 lesion: stenosis or occlusion of the coronary ostium and the proximal segment of the coronary artery. Type 2 lesion: diffuse or focal coronary arteritis (the latter is shown here). ~ Type 3 lesion: coronary aneurysm. Chronic inflammation of the aneurysmal wall and thrombosis is shown here. ASA, Ascending aorta; FT, subepicardial fatty tissue; AV, aortic valve; VS, Valsalva sinus; MC, myocardium; T, thrombus; LV, left ventricle
Makino et al. [18] reviewed reported cases of Takayasu arteritis in which coronary involvement was detected by coronary angiography. All cases revealed subtotat, from 50% to 100%, ostial narrowing of either the right (4 cases) or the left (8 cases) coronary artery or both (2 cases), and all had a history of angina pectoris. An aortocoronary bypass graft operation was undertaken in 8 of these cases.
Pathological report From the many reports and reviews on the pathology of Takayasu arteritis, the following observations are generally accepted [2, 19, 20]. The early histological changes of Takayasu arteritis are granulomatous inflammation, with various degrees of cellular infiltration in the adventitia and the outer part of the media, and marked inflammation of the vasa vasorum. Subsequently, marked intimal thickening occurs in the areas that overlie granulomatous and fibrotic lesions in the media and adventitia. This marked fibrosis and thickening of the arterial wall eventually becomes stenotic or occluded, and less commonly, a saccular aneurysm may develop. Aortic regurgitation is thought to develop primarily by annular dilatation resulting from extensive dilatational changes of the ascending aorta and secondarily, by primary valvular lesions such as fibrous thickening, enrolling, retraction, and calcification, and by aneurysms arising from the aortic annulus [6, 7, 21, 22], although aneurysms are less common.
28
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis
Table 1. Reported cases of coronary arteritis in Takayasu arteritis with pathohistologic descriptions Case
Age
Sex
Involvement of coronary orifice
Involvement of coronary artery
Microscopic findings
MGHCase record [24]
45
M
Both orifices narrowed
Rosen and Gaton [25]
44
M
Patent
Rose and SinclairSmith [5]
29
M
nd
Throughout thelength reduced to less than i mm in externai diameter A short segment of LCA, a 3.5 cm-long segment of LAD, a 2.5 cm-long segment of RCA Distal circulflex branch of LCA
Adventitial fibrosis, inflammatory cellular infiltration to the media, and severe intimal fibrosis Wall replaced by dense collagenous tissue, and lumen obliterated by granulation tissue Thrombotic occlusion with recanalization (healed arteritis)
M
nd
Chronic, nonnecrotizing, desmoplastic, granulomatous inflammation
60
M
nd
Chronic fibrosing inflammation
71
M
nd
Main LCA, proximal third of LAD, and RCA, most severely 4 cm from its origin LCA and RCA from their origin to their primary branches Epicardial coronary arteries
No MI
Aufderheide / 49
Myocardial fibrosis and MI AMI
62
M
Patent
Proximal segment of LAD
5
F
nd
RCA and LCA
{ 62
M
Patent
All main epicardial branches
64
M
Patent
All main epicardial branches
et al. [26]
Payan and Gilbert [27] Sciagra et al. [281 Wolf et al. [291
Tanaka et al.
[30]
Granulomatous inflammatory panarteritis Granulomatous inflammation, thickening of the wall, unrecognizable lumen, and collaterals Dense transmural fibrosis with luminal stenosis, thrombosis with organization, and aneurysm Marked fibrous thickening of the adventitia, intimal fibrosis, and cellualr infiltration to the media Marked fibrous thickening of the adventitia, intimal fibrosis, and cellular infiltration to the media
Disease of the heart OMI and AMI OMI
No MI
Unstable angina pectoris AMI and OMI AMI AMI
OMI, old myocardial infarction; AMI, acute myocardial infarction; L CA, left coronary artery; LAD, left anterior descending branch; nd, not described; RCA, right coronary artery The following 3 types of coronary artery lesions are distinguished on the basis of their pathological features: type 1, stenosis or occlusion of the coronary ostia and the proximal segment of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysms (Fig. 1). Type 1 is the commonest, and types 2 and 3 are very rare.
Coronary ostial stenosis Narrowing of the coronary arteries is mainly due to extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the ascending aorta. Cipriano et al. [4] presented a case of Takayasu arteritis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia, and r e v i e w e d 16 cases in which this disease involved
coronary arteries. Angina pectoris was a symptom in 7 of the 16 cases. Eight cases had evidence of myocardial infarction, and 3 had angina pectoris and myocardial infarction. In 10 of these cases, coronary narrowing was purely ostial due to healing of the inttamed aortic ro0t. Cipriano et al. concluded that stenosis is characteristically limited to the aorta and proximal segments of the coronary arteries. Amano et al. [23] reviewed 54 cases including 34 autopsy cases with coronary artery lesions, also reporting that about 80% of the coronary lesions were limited to the ostia and proximal segments of the coronary arteries.
Coronary arteritis In some cases, the coronary stenosis may be caused by coronary arteritis as one of the skip lesions of Takayasu arteritis, but even in these cases the lesions mainly affect the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery are very
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis rare. Table 1 lists the reports of cases of Takayasu arteritis with coronary arteritis, that give pathohistologic descriptions. The ages ranged ffom 5 to 71 years. Although Takayasu arteritis predominantly affects females, 9 cases were males and 1 was a young female. In 9 of 10 cases, coronary artery lesions were continuous from the ostia and proximal segments. Diffuse involvement of'coronary branches was observed in only 3 cases. Regarding the character of coronary arteritis, fibrosing inflammation was seen in 4 cases, granulomatous inflammation in 3 cases, and diffuse productive inflammation in 3 cases. Thrombosis and recanalization were seen in 2 cases.
Coronary an«urysm Coronary artery aneurysm seems to be rare in Takayasu arteritis, as it is in general. Falsetti and Carroll [31] reviewed 34 reported cases of coronary artery aneurysms and Markis et al. [32] reported a further 30 cases. Atherosclerosis is the most common cause, accounting for about 50% of the cases. Other causes of coronary artery aneurysms include congenital arteriovenous fistulae, trauma, polyarteritis nodosa, septic emboli, localized congenital myoelastic defects, and Kawasaki disease (acute febrile infantile mucocutaneous lymph node syndrome). We found reports of 7 cases of coronary aneurysm in Takayasu arteritis [1, 5, 33-37]. The cases with this association ranged in age from 11 to 53 years, and all were females. Three cases had aneurysms in the distal branch of the right coronary artery and left anterior descending branch, and 2 cases had them in the coronary ostia. Pathological descriptions were insufficient except in the cases reported by Rose and Sinclair-Smith [5]. Direct extension of the inflammatory process of the ascending aorta into the coronary ostia and the coronary artery roots and severe disruption of the media are important factors in the formation of coronary artery aneurysms in this disease.
Other causes of coronary ostial stenosis Coronary ostial stenosis is a rare lesion. From examinations by coronary angiography its incidence was estimated as 0.093% to 0.13% [38, 39]. The most frequent cause was atherosclerosis of the coronary artery and sinus of Vatsalva. Severe reduction of the coronary ostium may result from an aortic atherosclerotic plaque protruding or extending into the lumen. Such paraostial obstructive atherosclerosis was present in 73.3% of the cases with myocardial infarction and in 51.6% of those without it [40]. Coronary ostial stenosis is ffequently associated with syphilitic aortitis, being found in one-fourth to
29 one-third of such cases [41, 42]. Ostial stenosis is also seen in other types of aortitis including Takayasu arteritis, aortic dissection, embolic occlusion, papillary elastofibroma or hamartoma of the aortic valve, congenital coronary anomaly, fibromuscular dysplasia, and miscellaneous other conditions such as those due to radiation, trauma and iatrogenic causes.
Other types of coronary arteritis Subepicardial coronary arteritis is a relatively rare event that may occur in many conditions. Any septicemic state may cause a coronary response, and this is the most common cause. Tuberculous coronary arteritis is seen chiefly in cases with pericardial and myocardial tuberculosis. Coronary lesion in the course of systemic polyarteritis nodosa is relatively frequent. In most cases, acute myocardial infarction was described and a case of hemopericardium due to rupture of an aneurysm was reported [43]. Kawasaki disease is regarded as a form of polyarteritis occurring in children. Typical lesions can also be seen in rare cases of coronary giant cell arteritis [44]. Less specific histologic changes are present in rheumatic coronary arteritis, the involvement of the subepicardial vessels being less common than that of intramural ones [45]. Severe inflammatory subepicardial involvement has been described in systemic lupus erythematosus (SLE) [46]. Of 30 cases of Buerger disea'se, only one had a lesion in the coronary artery [47].
Discussion It is generally accepted that cardiac lesions a r e a major cause of death in cases of Takayasu arteritis. Next to aortic regurgitation, heart failure followed by acute and old myocardial infarction is the most common cause of death in this disease [1, 10-12, 16, 17]. Thus a better understanding of the nature of coronary artery lesions in Takayasu arteritis is becoming increasingly important. This communication reviews reported cases of Takayasu arteritis and those that we have experienced, and proposes that three types of coronary artery lesions can be distinguished on the basis of their pathologic features. In addition to their differences in clinical features, the treatments of these three types will be somewhat different. Cases of type 1 fange widely in age and are predominantly, though not exclusively, female. On the other hand, most cases of type 2 are middle-aged or elderly males [5, 24-30], whereas all those of type 3 are young or middle-aged females [1, 5, 33-37]. The cause of death in almost all cases of types 2 and 3 is acute myocardial infarction, whereas in cases
30 of type 1, the causes vary including sudden death, myocardial infarction and heart failure. Cases of type 1 are suitable candidates for coronary artery bypass grafting (CABG) because lesions are limited to the coronary orifice [48], but cases of types 2 and 3 have higher risk for this operation, because they orten have more diffuse coronary artery lesions. C A B G seems to be an effective treatment for preventing myocardial infarction, but careful examination of the coronary artery lesions is recommended. Why is the coronary artery involved in this disease? As the etiology of Takayasu arteritis is still unknown, we do not know why. But it seems reasonable that the coronary arteries should be involved, because the brachiocephalic branches are commonly involved and the coronary arteries are the first branches from the ascending aorta. Small arteries such as muscular arteries or arterioles have seldom been reported to be involved in Takayasu arteritis. Except for the pulmonary artery [49, 50], the coronary artery is the only site of lesions reported. If lesions of large blood vessels cannot be observed or are not examined, and only coronary arteritis is seen, a misdiagnosis may be made. Small artery disease is very rare in Takayasu arteritis, but we need to determine whether it is just a complication of Takayasu arteritis or whether it is a distinct disease entity. In conclusion, according to their pathologic features the coronary artery lesions observed in Takayasu arteritis can be classified into the following three types: type 1, stenosis or occlusion of the coronary ostia and/or the proximal segment of the coronary arteries; type\2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; type 3, coronary aneurysm. The coronary artery lesions in most cases of Takayasu arteritis are of type 1. Coronary ostial stenosis is thought to be due to extension of intimal proliferation and fibrous contraction due to the inflammatory process from the ascending aorta and the coronary ostia. In some cases, the coronary stenosis may be caused by coronary arteritis as one of the skip lesions of Takayasu arteritis, but even in these cases the lesions mainly affect the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysms seem to be very rare in Takayasu arteritis. Direct extension of the inflammatory process from the ascending aorta into the coronary ostia and the coronary artery roots and severe disruption of the media also seem to be causes of coronary artery aneurysms in this disease.
Acknowledgments. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, Mitsui Life Social Welfare Foundation, and Araki Medical and Biochemical Research Foundation.
O. Matsubara et al.: Coronary artery lesions in Takayasu arteritis
References 1. Lupi-Herrera E, Sanchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE (1977) Takayasu's arteritis. Clinical study of 107 cases. Am Heart J 93:94103 2. Nasu T (1962) Pathology of pulseless disease: Systemic study and critical review of twenty-one autopsy cases reported in Japan. Angiology 14:225-242 3. Saito Y, Hirota K, Ito I, Yamaguchi H, Takeda T, Morooka S, Ueda H (1972) Clinical and pathologic studies of five autopsied cases of aortitis syndrome. Jpn Heart J 13:107-117 4. Cipriano PR, Silverman JF, Perlroth MG, Griepp RB, Wexler L (1977) Coronary narrowing in Takayasu's aortitis. Am J Cardiol 39:744-750 5. Rose AG, Sinclair-Smith CC (1980) Takayasu's arteritis: A study of 16 autopsy cases. Arch Pathol Lab Med 104:231-237 6. Isomura T, Hisatomi K, Yanagi I, Shimada S, Uraguchi K, Aoyagi S, Kosuga K, Ohishi K (1988) The surgical treatment of aortic regurgitation secondary to aortitis. Ann Thorac Surg 45:181-185 7. Uehara K, Kitamura N, Ito T, Koyanagi H, Hashimoto .A, Konno H (1981) Severe aortic regurgitation in Takayasu's arteritis. J Jpn Assoc Thorac Surg 24:188197 8. Juzi U (1967) Arteriitis mit Herzinfarkt. Schweiz Med Wochenschr 13:397-405 9. Ueda H (1968) Clinical and pathological studies of aortitis syndrome: Committee report. Jpn Heart J 9:7687 10. Nagata S (1990) Present state of autopsy cases of Takayasu's arteritis (aortitis syndrome) in Japan (in Japanese). Myakkangaku 30:1303-1308 11. Strachan RW (1964) The natural history of Takayasu's arteriopathy. QJ Med 33:57-69 12. Nakao K, Ikeda M, Kimata S, Niitani H, Miyahara M, Ishimi Z, Hashiba K, Takeda Y, Ozawa T, Matsushita S, Kuramochi M (1967) Takayasu's arteritis: Clinical report of eighty-four cases and immunological study of seven cases. Circulation 35:1141-1155 13. Lande A, Gross A (1972) Total aortography in the diagnosis of Takayasu's arteritis. Am J Roentgenol Radium Ther Nucl Med 116:165-178 14. Lande A, Rossi P (1975) The value of total aortography in the diagnosis of Takayasu's arteritis. Radiology 114:287-297 15. Frovig AG, Loken AC (1951) Syndrome of obliteration of the arterial branches of the aortic arch due to arteritis. Acta Psychiatr Scand 26:313-337 16. Ishikawa K (1978) Natural history and classification of occlusive thromboaortopathy (Takayasu's disease). Circulation 57:27-35 17. Ishikawa K (1981) Survival and morbidity after diagnosis of occlusive thromboaortopathy (Takayasu's disease). Am J Cardiol 47:1026-1032 18. Makino N, Orita Y, Takeshita A, Nakamura M, Matsui K, T0kunaga K (1982) Coronary arterial involvement in Takayasu's disease. Jpn Heart J 23:1007-1013 19. Nasu T (1975) Takayasu's truncoarteritis in Japan. A statistical observation of 76 autopsy cases. Pathol Microbiol 43:140-146 20. Hotchi M, Fujihara M (1982) Aortitis syndrome (in Japanese). Rinsho Meneki 14:350-358 21. Ueda H, Sugiura M, Ito I, Salto Y, Morooka S (1967) Aortic insufficiency associated with aortitis syndrome. Jpn Heart J 8:107-120
O. Matsubara et al. : Coronary artery lesions in Takayasu arteritis 22. Akikusa B, Kondo Y, Muraki M (1981) Aortic insuß ficiency caused by Takayasu's arteritis without usual clinical features. Arch Pathol Lab Med 105:650-651 23. Amano J, Kameda T, Okamura T, Yakemasa A, Suzuki K, Tanaka J, Suzuki A, Wakiya Y, Abe H, Okada R, Kitamura K, Ban T, Nobuyoshi M (1982) Surgical treatment for coronary arterial lesions associated with aortitis syndrome (in Japanese). Nihon Shinzo Kekkan Geka Gakukai Zasshi 10:94-96 24. Case Records of the Massachusetts General Hospital 46-1967 (1967) N Engl J Med 277:1025-1033 25. Rosen N, Gaton E (1972) Takayasu's arteritis of coronary arteries. Arch Pathol 94:225-229 26. Aufderheide AC, Henke BW, Parker EH (1981) Granulomatous coronary arteritis (Takayasu's disease). Arch Pathol Lab Med 105:647-649 27. Payan HM, Gilbert EF (1984) Granulomatous coronary arteritis. Arch Pathol Lab Med 108:136-137 28. Sciagra R, Tebbe U, Rahlf G, Neuhaus KL, Kreuzer H (1986) Fatal outcome of aortocoronary bypass grafting in a 62-year-old man with unsuspected coronary arteritis. Clin Cardiol 9:583-586 29. Wolf RL, Gould NS, Green CA (1987) Unusual arteritis causing myocardial infarction in a child. Arch Pathol Lab Med 1i1:968-971 30. Tanaka A, Fukayama M, Funata N, Koike M, Salto K (1988) Coronary arteritis and aortoarteritis in the elderly males: A report of two autopsy cases with review of the literature. Virchows Archiv lA] 414:9-14 31. Falsetti HL, Carroll RJ (1976) Coronary artery aneurysm: A review of literature with a report of eleven new cases. Chest 69:630-636 32. Markis JE, Joff CD, Cohn PF, Feen D J, Herman MV, Gorlin R (1976) Clinical significance of coronary arterial ectasia. Am J Cardiol 37:217-222 33. Hachiya J (1968) Angiography of pulseless disease. A study of 50 cases (in Japanese). Nippon Acta Radiologica 27:1537-1557 34. Tamaki M (1968) Coronary arteriography (in Japanese). Nippon Acta Radiologica 28:733-738 35. Ellis R, Kurth RJ (1968) Calcified coronary artery aneurysms. JAMA 203:105-107 36. Fukuhara M, Koyama O, Onishi K, Adachi K, Tanemoto K, Matsuura S (1979) An autopsy case of
31
37.
38. 39. 40. 41. 42. 43.
44. 45. 46. 47. 48. 49. 50.
aortitis syndrome with aneurysm of bilateral coronary arteries (in Japanese). Shinzo 11:629-634 Fukuda I, Ijima H, Itoh T, Iriyama T, Maeta H, Okamura K, Mitsui T, Hori M (1983) Coronary artery aneurysm associated with aortitis syndrome diagnosed pre- and intraoperatively. Jpn Heart J 24:10071015 Pritchard CL, Mudd JG, Barner HB (1975) Coronary ostial stenosis. Circulation 52:46-48 Hutter JA, Pasaoglu I, Williams BT (1985) The incidence and management of coronary ostial stenosis. J Cardiovasc Surg 26:581-584 Heggtveit HA (1967) The role of coronary ostial stenosis in the etiology of myocardial infarction. Pathol Microbiol 30:716-717 Heggtveit HA (1964) Syphilitic aortitis. A clinicopathologic autopsy study of 100 cases, 1950 to 1960. Circulation 29:346-354 Burch GE, Winsor T (1942) Syphilitic coronary stenosis, with myocardial infarction. Am Heart J 24:740-751 Synclair W Jr, Nittsch E (1949) Polyarteritis nodosa of the coronary arteries. Report of a case of an aneurysm and intrapericardial hemorrhage. Am Heart J 38:898904 Harrison CV (1948) Giant-cell or temporal arteritis: Review. J Clin Pathol 1:197-211 Karsner HT, Bayless F (1934) Coronary arteries in rheumatic fever. Am Heart J 9:557-585 Bonfiglio TA, Botti RE, Hagstrom JWC (1972) Coronary arteritis, occlusion and myocardial infarction due to lupus erythematosus. Am Heart J 83:153-158 Saphir O (1936) Thromboangiitis obliterans of the coronary arteries and its relation to atherosclerosis. Am Heart J 12:521-535 Suzuki A, Amano J, Tanaka H, Sakamoto T, Sunamori M (1989) Surgical consideration of aortitis involving the aortic root. Circulation 80 (Suppl I):I-222-I-232 Rose AG, Halper J, Factor SM (1984) Primary arteriopathy in Takayasu's disease. Arch Pathol Lab Med 108:644-648 Matsubara O, Yoshimura N, Tamura A, Kasuga T, Yamada I, Numano F, Mark EJ (1992) Pathologic features of pulmonary artery in Takayasu's arteritis. Heart Vessels (Supp 7):18-25
