lnternutional
Journal
IF 1992 Elsevier
CARD10
of Cardiology,
Science
Publishers
2X’)
34 (1992) 289-295
B.V. All rights reserved
0167-5273/97/$0.5.00
013Y7
Cardiac involvement in non-specific aorto-arteritis Manotosh Panja ‘, A.K. Kar ‘, A.L. Dutta ‘, M. Chhetri ‘, S. Kumar ’ and S. Panja ’ ’
Department
of Cardiology, ’ Department
Institute of Post-Graduate of Paediatric
(Received
17 April
Medical Educuriorl and Research, C‘ulcuttu. lndiu;
Medicitle. Sishu Sudan Hospital,
1989: revision
accepted
C‘alcuttcr. Imliu
IO October
1991)
Panja M, Kar AK, Dutta AL, Chhetri M, Kumar S, Panja S. Cardiac involvement aorto-arteritis. Int J Cardiol 1992;34:289-295.
in non-specific
Cardiac involvement in 75 cases (mean age 21.1 + 6 years) with non-specific aorto-arteritis was studied. Detailed clinical examination, echocardiography and cardiac catheterization, including angiography, were done in all the cases, as was coronary angiography. Features of cardiac failure like sinus tachycardia, cardiomegaly, left ventricular third heart sound gallop and pulmonary congestion were detected in 27 cases with reduction of left ventricular ejection fraction (25-48%). Systemic hypertension was seen in 60 cases. Central aortic pressure, left ventricular systolic pressure and left ventricular end-diastolic pressure were increased in 66 cases. Pulmonary hypertension and increased pulmonary vascular resistance were detected in 6 cases. Aortic and mitral regurgitation were seen in 15 and 12 cases, respectively. Three patients had features of dilated cardiomyopathy such as generalized cardiomegaly, systemic and pulmonary congestion hut without any cardiac murmurs and with normal central aortic pressure. The coronary angiogram revealed obstruction of the left anterior descending artery in 3 cases and right coronary artery obstruction in another 3 cases. Histopathological studies revealed non-specific inflammatory changes with fibrosis in cardiac musculature and the great vessels. Key words: Aortic disease; Arterial disease
Introduction Non-specific aorto-arteritis is quite common in India, but the cardiac involvement in this condition has not been reported in detail in that country. Some scanty reports are available from western countries. The purpose of this paper is to
to; Dr. Manotosh Panja, Dept. of Cardiolof Post-Graduate Medical Education & Re244, Acharya J.C. Bose Road, Calcutta-700 020, India.
Correspondence
ogy, Institute search.
report on the features of cardiac involvement in 75 cases with non-specific aorto-arteritis. The involvement of cardiac valves, myocardium, coronary arteries and pulmonary arteries in particular are described. Materials and Methods Two-hundred-and-fifty-five cases with nonspecific aorto-arteritis (Takayasu’s arteritis) were investigated during the period 1977 to 1988, at the Cardiology Department of the S.S.K.M. Hos-
290
pita1 in Calcutta, India. Diagnostic clinical criteria included young individuals, systemic manifestations like low grade fever, arthralgia, loss of weight, asymmetry of peripheral pulses, abdominal bruit with or without high blood pressure. Detailed history taking, clinical examination, Xray of the chest and 1Zlead electrocardiogram were done in all 255 cases. Of the 255 cases, 75 patients who reported for regular follow-up were selected for this study and 66 of these patients presented with features of cardiac involvement either in the form of atypical chest pain, dyspnoea, features of pulmonary hypertension, cardiac murmurs on clinical examination or manifested features of cardiomegaly or heart failure on the X-ray of the chest and the electrocardiogram. All the 75 patients thus selected were subjected to echocardiography, angiocardiography, coronary and pulmonary arteriography, in view of the basic objective of our study. Aortography was also performed in all cases to confirm the clinical diagnosis. Irregularity of the intimal surface, stenosis of the aorta or its tributory arteries, post-stenotic dilatations, saccular aneurysms and even complete occlusion were taken to be typical and diagnostic findings of aortography. The diagnosis of aorto-arteritis was finally accepted if patients with signs and/or symptoms of large-vessel disease also showed typical findings on aortography.
TABLE
I
Age/sex
distribution
Clinical
and clinical
presentation
presentation
in 75 patients
Echocardiography included M-mode, crosssectional and Doppler studies. Cardiac catheterization included angiocardiography, coronary and pulmonary angiography. At first, right-heart cardiac catheterization was done using a Cournand catheter by the usual percutaneous femoral puncture technique. Pressures were recorded from the right atrium, the right ventricle, the pulmonary artery and the pulmonary wedge positions. Then the left-heart catheterization was done by using a pig-tail catheter and pressures were recorded from different parts of the aorta and left ventricle. The total aortography and left ventriculography, coronary angiography (both right and left) were done by Judkin’s technique and tine films were taken in different views including cephalocaudal tiltings. Limited autopsy studies of the heart (macro- and microscopic) were done in 6 patients who succumbed to congestive heart failure.
Results Clinically, 66 cases presented with signs and symptoms related to the cardiovascular system. Fifty-one patients presented with systemic hypertension and amongst these, 22 had congestive heart failure. Nine patients had intermittent claudication either in the upper or in the lower limbs. Central nervous system involvement like hemiple-
of aorto-arteritis
Age groups 5-10 yr total = 9 M: 3. F: 6
10-20 yr total = 21 M: 0, F = 21
20-30 yr total = 42 M: 6, F: 36
30 yr total = 3 M: 0, F: 3
Total 15 M: 9, F: 66
CNS features (headache. vomiting, convulsion, blurring of vision. hemiplegia) CVS features (dyspnoea, oedema, palpitation, angina. claudication,
1
3
IO
1
1s (20%)
hypertension) CNS & CVS features Miscellaneous (fever, cough,
7 1
17 2
40 3
2 0
66 (88%) 12 (16%)
2
3
1
0
6 (8%)
arthralgia, CNS = central
etc.) nervous
system;
CVS = cardiovascular
system.
TABLE
2
TABLE
Types of cardiac
involvement
in 75 cases of aorto-arteritis No. of cases
Cardiomegaly due to hypertension Heart failure
Dilated cardiomyopathy (non-hypertensive. normal coronary arteries) Valvular involvement Coronary artery involvement AR = aortic
regurgitation:
51 27 (hypertensive 22, dilated cardiomyopathy coronary artery involvement 4)
3.
TABLE
MR = mitral
regurgitation.
3 data in 75 cases of aorto-arteritis
Type of lesion
No. of cases
Percentage
Type Type Type Type Type
9 1s 51 18 6
12 20 68 24 8
I: II: III: IV: V:
thorax abdomen combined pulmonary artery coronary artery
findings
Abnormal Left ventricular hypertrophy Left ventricular hypertrophy with strain Left atrial enlargement Cardiac arrhythmias Ventricular ectopic Atrial ectopic Atrial fibrillation
in 75 cases with aorto-arteritis 43 21
Normal
36 77 9 h
7
1
3 23 (AR: 15, MR: 12) 6
gia and blurring of vision with headache, vomiting, convulsion were present in 15 cases. Six patients presented with non-specific symptoms like low-grade fever, dry cough and arthritis (Table 1). Detailed examination of the cardiovascular system revealed cardiomegaly in 54 cases, hypertension in 60 cases, and arrhythmias in 9 cases. Three patients had features of dilated cardiomyopathy with congestive heart failure. Aortic incompetence murmur was detected in 15 cases and mitral incompetence in 12 cases (Table 2). Electrocardiographic examination revealed left ventricular hypertrophy in 21 patients and left ventricular hypertrophy with strain in 36 patients. Left atria1 enlargement was present in 27 patients. Different arrhythmias were detected in 9 cases (Table 3). Echocardiographic abnormalities were detected in 51 patients. Amongst these, 24 were
Angiographic
-l
Electrocardiographic
found to have concentric hypertrophy of the left ventricle, and 27 had increased left ventricular cavity dimension. Left ventricular end-systolic diameter and end-diastolic diameter in these 27 patients ranged from 42 to 48 mm and 54 to 69 mm, respectively. Ejection fraction was significantly reduced in those patients and varied from 28 to 48%. Left ventricular contraction was very poor in 21 cases. Mitral valve opening was very much reduced in 6 patients due to severe heart failure. Three patients were found to have classical echocardiographic features of dilated cardiomyopathy in the form of increased left ventricular internal diameter during both systole and diastole, poor wall motion with thinning of intcrventricular septum and left ventricular posterior wall, increased E-point septal separation and double-diamond appearance of the mitral valve during diastole (Table 4). Incidentally, these patients were later seen to have normal coronary arteries. Haemodynamic data revealed raised systemic vascular resistance in 60 cases and raised pulmonary vascular resistance in 18. In 15 cases, central aortic pressure was normal. Three of these cases were in congestive failure with raised left ventricular end-diastolic pressure (Table 5). Pulmonary hypertension was detected in 6 cases in the presence of normal wedge pressure. Left ventricular angiography showed presence of mitral regurgitation of mild to moderate severity in 12 cases (Seller’s grade I-III) with poor left ventricular function in 3 cases (Fig. 1). Aortic root angiography showed the presence of aortic regurgitation of grade I to II in 15 cases. Aortography
292 TABLE Pattern
5 of coronary
artery
involvement
among
75 cases
No. of cases 6 2 1 3 1
Angiographic involvement Right coronary ostium Right coronary artery (proximal) Left anterior descending Left coronary ostium
typically showed extensive involvement of the aorta in the form of irregular intimal surface with stenosis. The origin of the tributary arteries of the aorta was found to be narrowed in all cases and in some cases even to the extent of complete occlusion. Depending upon the extent of involvement of the aorta and that of the coronary and pulmonary arteries, it was classified into different types (Table 6). The thoracic aorta was found to be involved alone in 9 of 75 cases (12%), abdominal aorta in 15 cases (20%) and combined involvement was found in 51 cases (68%). Pulmonary artery involvement was detected in 18 cases (24%) and coronary artery involvement in 6
TABLE
6
Clinical,
echo, haemodynamic
and angiographic
correlation
Clinical features
Echo findings
51
Hypertension
LV hypertrophy:
27
Heart
Reduced ejection fraction: 27 LV dilatation: 27
54
Cardiomegaly (a) Hypertensive: 51 (b) Non-hypertensive (dilated cardiomyapathy)
LV = left ventricular;
cases (8%) (Fig. 3). Three cases had obstruction in the left anterior descending artery (Fig. 2b) and another 3 had lesions in the right coronary artery. The possibility of right coronary and left coronary ostial narrowing was considered in two and one cases, respectively.
in 75 cases of aortoarteritis
No. of cases
failure
Frg. 1. Left ventricular angiogram showing dilated heart with very poor contraction and trivial mitral regurgitation. Diagnosed as dilated cardiomyopathy due to aorto-arteritis. Central aortic pressure is normal but left ventricular end-diastolic pressure is high.
24
LV dilatation: 3 MV opening: 3 Reduced ejection fraction: 3
MV = mitral valve; LVEDP
= left ventricular
Haemodynamic study
Coronary angiographic data
Raised systemic vascular resistance; central aortic pressure: 51
Abnormal:
2
Abnormal:
4
Raised
LVEDP:
27
Raised pulmonary vascular resistance: 18
Raised
end-diastolic
LVEDP:
pressure.
3
Normal
Pig. 2. a. Aortic arch angiography shows the origin of right subclavian narrowed and irregular and left subclavian is not visualised at all and left carotid is faintly visible. b. Selective coronary arteriography of same patient as in Fig. a showing left coronary artery with definite irregularities and narrowing of proximal and middle part of left anterior descending as well as slight narrowing of circumflex in a case with aorto-arteritis. Partial focal ostial narrowing of left coronary artery is also present.
During the follow-up study, 6 patients died due to congestive heart failure and limited postmortem studies were carried out in these cases. In 3 of these cases, the aorta was cicatrized to the extent of tree bark appearance of luetic aortitis. Microscopically, Iinvolved segments showed features of panarteritis with perivascular round cell infiltration of the vasa vasorum. Adventitia and
Fig. 3. Pulmonary angiogram in a case showing gross narrowing of pulmonary lower lobe vessels are faintly visualised. vessels of left lung show minor and upper lung show minor irregularities and
with aorto-arteritis artery. Only right Right upper lobe lobe vessels of left narrowing.
intima showed marked thickening due to fibrous scarring and media showed degeneration of elastic fibres. Heart chambers were found to be dilated, especially the ventricles. Macroscopic study also showed focal and diffuse endocardial thickening, multiple mural thrombi and dilated valve rings. Endocardial ‘thickening was similar to that of the aorta and its branches. Microscopically, interstitial fibrosis, cellular hypertrophy and myocardial cell degeneration were found to be prominent features. Small areas of necrosis and cellular infiltrate were seen occasionally. but these were not prominent features. Seventy-five patients included in this study were followed-up for an average of 2.2 years. Fifty patients with active inflammatory arteritis were treated with glucocorticoids to which 30 responded. Ten patients had clinical or angiographic progression of their vasculitis even while on corticosteroid therapy. Vascular reconstructive surgery was carried out successfully in 12 cases. Of 27 cases who manifested features of congestive heart failure, 6 succumbed. These 6 included 2 patients with angiographically demonstrable coronary artery involvement and the remaining 4 patients had poorly controlled systemic hypertension.
294
Discussion Non-specific aortoarteritis (Takayasu’s disease) is a disease of unknown origin that predominantly affects women and usually has its onset during the second or third decades of life [1,2]. It is a disease believed to be of autoimmune origin [3]. In its classical form, the disease consists of two phases: an early symptomatic and a late occlusive stage [5]. Usually it involves the aorta and proximal segments of its major branches [4,6,8,11]. Since Frovig and Loken [7] first described narrowing of the coronary arteries due to Takayasu’s arteritis in 1951, coronary artery involvement has been considered an uncommon yet potentially fatal complication of this disease. Pulmonary hypertension is usually a late complication of the disease [16]. Involvement of the aortic and mitral valves, resulting in aortic and mitral regurgitation, has also been described [20]. Nonspecific aorto-arteritis has been the subject of a number of studies in India. Studies by Das et al. [19] (55 patients), Datey et al. [21] (92 patients), and Majumdar et al. 1221 (70 patients) are some of the other large series reported apart from our study. Whereas in our study 88% of the patients were females, in the studies by Das et al. [19] and Majumdar et al. [22], the percentages were 66 and 60, respectively. Datey et al. [21] on the other hand reported 82.5% of their patients to be males. This is, however, in sharp contrast to the global preponderance of the disease in females. Headache, syncope and even cerebrovascular accident featured prominently amongst the manifestations in studies by Das et al. [19] and Majumdar et al. [22]. This was in contrast to our study which reported features of the central nervous system in only 20% of patients. However, hypertension was found more frequently in our series of patients (88%) than in the series by Das et al. 1191 (58.2%) and Majumdar et al. [22] (62.7%). Datey et al. [21] reported peripheral vessel involvement in as many as 60.8% of their patients and Leriche’s syndrome in 21.7%. These were not observed at all in our series of patients. Das et al. [I91 reported the following angiographic data. Type I lesion: 7.2%, Type II lesion: 29% and Type III lesion: 7.2%. In our study,
Type III lesion comprised 68% of the total number of patients. Despite detailed reports on non-specific aorto-arteritis from various parts of India, studies on cardiac involvement are hard to find in this country. Amongst a few authors from abroad [12-171, Rosen et al. and Young et al. demonstrated coronary artery involvement by selective coronary angiography [12,13]. From India, in contrast to our large series of 75 patients, Jalal et al. 1181 reported a clinicopathological study of cardiac involvement in 4 patients with non-specific aortoarteritis. In this report, besides cardiac involvement in the form of valvular regurgitation, cardiomegaly and congestive heart failure secondary to hypertension and coronary arterial narrowing, involvement of myocardium by the diffuse vascular inflammatory process is mentioned. In our study, cardiomegaly was detected in 54 cases, hypertension in 60 cases and arrhythmias in 9 cases. Aortic incompetence was detected in 15 cases and mitral incompetence in 12 cases. At autopsy, valve leaflets have been found to be thickened, their edges rolled and retracted, presumably because of chronic valvulitis. This may be due to progression of inflammation from aortic root to adjacent valve leaflets and also to mitral valve leaflets due to aorticomitral continuity. On angiography, pulmonary artery involvement was detected in 18 cases (24%) and coronary artery involvement in 6 cases (8%). Thus this study further confirms coronary artery involvement as a well-recognized but uncommon complication of non-specific aortoarteritis. Three patients with normal coronary arteries and normal central aortic pressure presented with congestive heart failure due to dilated cardiomyopathy, as reliably demonstrated by echocardiography and angiocardiography. Unfortunately, endomyocardial biopsy by bioptome, which could have been very helpful, could not be done due to non-availability, However, both macro- and microscopic findings on limited post-mortem studies in 6 patients who succumbed to congestive heart failure were very informative in this respect. Macroscopically, all 6 patients had dilated ventricles, focal and diffuse endocardial thickening, multiple mural thrombi and dilated valve rings.
295
Microscopically, interstitial fibrosis and cellular infiltrate were seen in the myocardium. Thus, apart from hypertension or coronary arterial involvement, myocardial involvement also contributed to congestive heart failure in these 6 patients. These findings fully corroborate the view expressed by Jalal et al. [18] in their small series, i.e. diffuse vascular inflammation in aorto-arteritis may extend to involve the cardiac muscle and this alone may result in clinicopathological features of congestive cardiomyopathy as observed in our 3 patients with normal coronary arteries and central aortic pressure. References Schrire V, Asherson RA. Arteritis of the aorta and its major branches. Q J Med lY64:33:439-463. Ueda H, Morooka S. Jto J et al. Clinical observation of 52 causes of aortitis syndrome. Jpn Heart J 1969:10:277-2X8. Nakao K. Ideda M. Kimata S et al. Takayasu’s arteritis: clinical report of X4 cases and immunological study of seven cases. Circulation lYh7:35:1141-1155. Lande A. Gross A. Total aortography in the diagnosis of Takayasu’s arteritis. Am J Roentgen01 Radium Ther Nucl Med 1972:l 16:16&17X. Strachan RW. The natural history of Tdkayasu’s arteriopathy. Q J Mrd 1964;33:57-69. Lemdc A. Rossi P. The value of total aortography in the diagnosis of Takayasu’s artrritis. Radiology 197S;l 14:2X77Y7. Frovig AG. Loken AC. Syndrome of obliteration of the arterial branches of the aortic arch due to arteritis. Acta Psychiatr Neural Stand lYSl;26:313-337. Takeda F, Domeda G. Sute K et al. Pulseless disease report of an autopsy case with special reference to the
morphogenesis of the arterial lesions. Gunma J Med Sci lY61;10:27-45. 9 Reddy CRRM. Rao NR. Reddy MR et al. Pathology of pulseless disease. Path01 Microbial 1969;34:10-21). 10 Judge DR. Currier DR. Gracic AW. Figlry MM. Takayasu’s arteritis and aortic arch syndrome. Am J Med I Y68;32:32 I-330. 11 Cheitlein MD. Carter PB. Takayaau’s disease. Arch Intern Med lY6S;llh:283-‘XX. 12 Young JA. Sengupta A, Khaja F. Coronary arterial stenosis, angina pectoris, and a :ypical coarctation of the aorta due to non-specific arteritis. Am J Cardiol lY73:33:356360. I? Rosen N. Gaten E. Tdkayasu’s arteritis of coronary arteries. Arch Pathol lS72;94:225-229. PH. Silverman JF. Perlroth MG et al. Coronary 14 Ciproano arterial narrowing in Takayasu’s aortitis. Am J Cardiol 1077:30:744-750. 15 Kozuka T. Nosaki T. Sato K, lnare K. Aortitits syndrome with special reference to pulmonary vascular changes. Acta Radio], Diagn 1978;7:23-52. I 6 Lande A. Bard R. Takayasu’s arteritis: an unrecognized cause of pulmonary hypertension. Angiology lY76:27: 113121. 17 Lupi Herreira R. Sanchez-Torras G. Narcushamer J et al. Takayasu’s arteritis: clinical study of 107 cases. Am ffeart J lY77:Y3:94- 108. aortoartrritia 1X Jalal S. Bhatia ML, Chopra P. Non-specrfic with cardiac involvement. Indian Heart J lYX7:34:2Xl. 19 Das JP. Misra H. Dasit MA, Nayak CR. Swain Il. Nonspecific artcritis. Indian Heart J 19X2:34:3Yl. ‘0 Gupta SK. Khanna MN, Lahiri TK. Gorl AK. Involvement of cardiac valves in Takayasu’s urtrritrs. Report of 7 cases. Indian Heart J lY47;32:147. 21 Datey KK. Kulkarni TP. Goyal BK. Kumar N. Non-specific aortoarteritis. Indian Heart J lYX2:34:2XO. 22 Majumdar S. Mukhcrjre R. Paul DK. Batahyal SK. Kundu SC. Aortoarteritis in Eastern India - a 15.year study. Indian Heart J lYX3;34:2Xl.