Angiographic Profile and Endovascular Interventions in Takayasu`s Arteritis

Abstract: Background. Takayasu’s arteritis (TA) is a rare inflammatory, granulomatous vasculitis primarily involving the aorta and its major branches. Clinical and angiographic manifestations of the disease differ in various parts of the world. Objectives. To analyze the clinical features, angiographic profile, and endovascular interventions in TA patients (pts). Methods. From January 2009 to March 2013, a total of 62 consecutive pts who were diagnosed with Takayasu’s arteritis at our institute based on American College of Rheumatology Criteria were included in the study. Thirty-four pts underwent conventional angiography, while 28 were evaluated using computed tomographic angiography. Endovascular interventions were attempted for 24 lesions in 23 pts who were symptomatic and had significant stenotic lesions. Results. The mean age of presentation was 28.4 ± 9.7 years, with 69.4% female. Limb claudication (52%) was the most common presenting symptom, followed by vertigo (35%) and constitutional symptoms. The most common angiography class was type V (37.1%), followed by type I (32.2%), type IV (17.7%), type IIa (8.1%), type III (3.2%), and type IIb (1.6%). The most common artery involved was the subclavian (64.5%), with the left subclavian more commonly involved than the right, followed by the abdominal aorta (51.6%) and renal artery (32.2%). Stenotic lesions were present in 59 pts (95%), while aneurysmal involvement was seen in 17 (27.4%), with isolated aneurysmal involvement in 3 of these. Conclusions. Our cohort of TA pts had more severe and widespread involvement. Despite a more advanced presentation, percutaneous balloon angioplasty with stent implantation is feasible, with good immediate results but slightly higher complication rates.

J INVASIVE CARDIOL 2015;27(1):8-13
Key words: computerized tomographic angiography, percutaneous transluminal balloon angioplasty, stenting, Takayasu’s arteritis

_____________________________________________________________________________________

Takayasu’s arteritis (TA) is a chronic inflammatory disease of the medium and large arteries of unknown etiology, especially involving the aorta and its major branches (and may involve pulmonary and coronary arteries as well). Clinical and angiographic features of the disease differ in various parts of the world. Surgical revascularization in TA cases involves complex intrathoracic approach due to more proximal involvement of branch vessels compared to the atherosclerotic etiology. Endovascular intervention (EI) with percutaneous transluminal balloon angioplasty (PTA) and stent implantation is a safe and less-invasive therapeutic option compared to surgery. There is a paucity of interventional data from India on the subject. We present a retrospective analysis of 62 TA patients, describing the clinical features and angiographic appearance and endovascular treatment carried out in 23 patients.

Methods

We retrospectively analyzed 62 patients diagnosed with Takayasu’s arteritis who presented to our institute with varying symptoms between January 2009 and March 2013 and underwent diagnostic evaluation or therapeutic endovascular treatment.

TA was diagnosed according to the American College of Rheumatology Criteria for the Classification of TA. The presence of at least three of the following criteria was considered consistent with diagnosis of TA: (1) age of onset <40 years; (2) claudication of an extremity; (3) decreased brachial artery pulse; (4) >10 mm Hg difference in systolic blood pressure between arms; (5) a bruit over the subclavian arteries or the aorta; (6) and arteriographic evidence of narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper and lower extremities. The presence of any three or more criteria has been shown to have a sensitivity of 90.5% and a specificity of 97.8%.¹

Based on the new angiographic classification of Takayasu’s arteritis, which depends on angiographic finding and vessel involvement, the disease is classified as: type I, the branches from the aortic arch; type IIa, the ascending aorta, aortic arch, and its branches; type IIb, the ascending aorta, aortic arch and its branches, and the thoracic descending aorta; type III, the thoracic descending aorta, abdominal aorta; and/or renal arteries; type IV, abdominal aorta and/or renal arteries; and type V, combined features of types IIb and IV.² All patients underwent conventional angiography and/or computerized tomographic (CT) angiography and were grouped as described above.

Twenty-four arterial lesions in 23 patients underwent balloon angioplasty, with stent implantation in most cases. All patients were given aspirin 150 mg twice daily started 1 day prior to procedure, clopidogrel 300 mg on the night prior to the procedure, and 300 mg on the day of the procedure. Patients were advised to continue aspirin 150 mg/day indefinitely and clopidogrel at least 75 mg/day for at least 3 months. All procedures were performed under local anesthesia using femoral approach. After introduction of a 6 to 9 Fr sheath into the femoral artery, a bolus injection of 50 to 80 IU/kg of heparin was given, followed by repeated boluses to achieve an activated clotting time around 200 seconds. Using a 6-8 Fr guiding catheter introduced into the proximal portion of the stenotic artery, the stenosis was initially crossed with a 0.014˝ microguidewire. If stenting was planned, a self-expandable stent delivery catheter was advanced over the immobilized microguidewire. In cases of renal artery interventions and a few other situations, standard coronary-balloon mounted stent systems were used. After stent deployment, postdilatation was performed using a 3-8 mm diameter angioplasty balloon if residual stenosis was >30%.

All patients undergoing EI were prescribed prednisone 1 mg/kg, or methotrexate (7.5-15 mg/week), or both prior to the procedure. Endovascular treatment was performed once systemic symptoms and ESR were under control. After resolution of acute phase symptoms and normalization of ESR, prednisone was tapered by 5 mg/week and stopped unless there was recurrence of symptoms. Patients were continued on methotrexate 7.5-15 mg/week with 3- or 6-month evaluation of complete blood counts.

Statistical analysis. Mean and standard deviations were calculated for the continuous variables, while frequency data were computed for the discrete variables.

Results

Demographic profile. Sixty-two patients were included in the study based on their symptoms and fulfillment of inclusion criteria. The mean age at presentation was 28.4 ± 9.7 years (range, 10-47 years). Females were more frequently affected (n = 43; 69.4%) than males (n = 19; 30.6%). The most common symptoms were intermittent claudication of upper or lower limbs (n = 32; 52%), vertigo (n = 22; 35.5%), fatigue (n = 20; 32%), blurring of vision (n = 3), and/or blindness and chest pain (n = 2). A few of the patients were incidentally detected during evaluation for hypertension (n = 15; 24.2%) with presence of abdominal or subclavian artery bruit.

Angiographic profile and endovascular interventions. 34 patients underwent conventional angiography, 28 patients were evaluated using CT angiography (CT) according to discretion of the treating physician. The most common angiographic classes were types V (n = 23) and I (n = 20) (Tables 1 and 2). The most common artery involved was the subclavian (n = 40; 64.5%) followed by the abdominal aorta (n = 32; 51.6%). Endovascular interventions were performed for 24 lesions in 23 patients and are discussed below (Table 3).

Renal artery. Renal artery involvement was present in 20 patients and ostial in all cases. Five patients had bilateral renal artery disease, while isolated left renal artery was involved in 9 patients and right renal artery was involved in 6 cases. Four patients underwent successful renal angioplasty and drug-eluting stent implantation during the study period. The need for antihypertensive medication reduced from three drugs to one drug at 1-month follow-up for all patients, and all patients continued the same medication at 1-year follow-up. One patient underwent successful bilateral stenting of the left renal artery followed by the totally occluded right renal artery (Figure 1).

Two patients with a history of renal artery stenting were evaluated. One patient who had undergone renal artery stenting with a bare-metal stent 9 years prior showed a patent stent with 50% ISR at follow-up angiogram. However, this patient required four antihypertensive drugs for blood pressure control and has been maintained on methotrexate since the procedure. Another patient had patent stents on CT follow-up 1 year after the procedure.

Descending thoracic and abdominal aorta. Aortic interventions were performed for indications of hypertension or lower-limb claudication in 7 patients, with use of nitinol self-expanding stents in 8 patients. The mean peak systolic gradient reduced from 89.3 ± 22.6 to 5.1 ± 3.2 mm Hg. One patient underwent balloon angioplasty alone due to the discrete nature of the lesion. Vessel dissection was the most common complication during balloon angioplasty (seen in 3 patients), and was subsequently resolved with stent coverage. In 1 case, the dissection was covered sequentially with 3 overlapping self-expanding stents of 100 mm, 80 mm, and 40 mm. However, the end result was satisfactory (Figure 2).

Case #7 underwent abdominal aortoplasty with stenting 13 years prior, and had presented with recurrence of symptoms in the form of claudication in both lower limbs. Aortogram revealed in-stent restenosis (ISR) of 70% in the distal segment of the stent. The patient underwent successful nitinol self-expanding stent implantation followed by good result.

Case #10 underwent balloon angioplasty with stenting to the superior mesenteric artery 5 years prior for symptoms suggestive of intestinal angina. She presented this time with symptoms of claudication in both lower limbs. Angiogram revealed ISR of 80% and significant 70% stenosis of the distal abdominal aorta. Successful stent implantation across the stenosed aortic segment was done using a self-expanding 14 x 80 mm Zilver stent (Cook Medical) with no residual transstenotic gradient.

A 38-year-old man who had undergone stenting to the right renal artery 4 years prior presented with claudication and was found to have total occlusion of the abdominal aorta above the level of the renal arteries. The patient was referred for surgical reconstruction.

Aortic arch vessels. Aortic arch vessel involvement was a common angiographic presentation. Cerebral vessel intervention was attempted in 6 patients. Repeated attempts at crossing the lesion in the left vertebral artery in case #13 with a 0.014˝ coronary guidewire or 0.032˝ hydrophilic guidewire (Terumo Corporation) were unsuccessful, and the procedure was abandoned (Figure 3). Three patients developed cerebral infarction post procedure, with residual hemiparesis; 1 patient died on postoperative day 4 (Figure 4). Follow-up evaluation of the other 2 patients revealed good functional recovery. Two patients underwent successful stent implantations to the right and left common carotid arteries, respectively.

Subclavian artery. The subclavian artery was the most commonly affected, with involvement seen in 40 patients (64.5%). The left subclavian artery (n = 34; 54%) was more commonly involved than the right (n = 21; 34%). Five patients underwent successful angioplasty of the left subclavian artery, with stent implantation in 4 patients. There were no complications, with symptom relief seen in all patients postoperatively. All patients had well-palpable pulse on follow-up.
Aortic root dilatation/aneurysm involving the ascending aorta, aortic arch, and/or proximal descending thoracic aorta was another common presentation (seen in 17 patients, with isolated aneurysmal involvement in 3 of these patients). An interesting observation in 1 patient was occlusion of all aortic arch vessels at the origin and vertebral arteries filling retrogradely from the intercostal arteries (Figure 5).

Coronary and pulmonary artery. Coronary artery evaluation was done in only 10 of our patients. One 19-year-old female presenting with chest pain showed critical ostial left main coronary artery stenosis. Coronaries in all other patients were normal. Pulmonary artery involvement in the form of mural thickening was observed in only 2 patients.

Discussion

Takayasu’s arteritis is a chronic inflammatory granulomatous vasculitis that primarily affects the aorta and its main branches, and often involves the pulmonary arteries or rarely the coronary bed. The clinical presentation consists of constitutional symptoms in the active phase and occlusive symptoms in the chronic or the healing phase, which are related to fibrosis or occlusion of vessels. Hence the clinical diagnosis is often missed until the disease reaches chronicity and manifests due to its occlusive presentation or is incidentally diagnosed during evaluation for hypertension and/or absent pulse.³ There may be an associated mortality of 35% or more in 5 years if left untreated.⁴

Management options for TA include immunosuppressive therapy, with glucocorticoids and/or methotrexate, azathioprine, or cyclophosphamide in the active stage and revascularization with percutaneous or surgical techniques for chronic stage occlusion of vessels.^5-9 The evolution of percutaneous transluminal angioplasty (PTA) with stents offers a less invasive, relatively safe and effective option in the management of occlusive lesions compared to surgery.

Takayasu’s arteritis is a disease of primarily young females in the second or third decade. The mean age of presentation in our study was 28.4 ± 9.7 years, which is very similar to data from around the world.^10-20 Our study showed a predominant female predisposition (69.4% of the current study population). This is in accordance with previous data from India, with female:male ratios of 1.58:1 to 6.4:1.^11,21 This distribution is different from reports in other parts of the world, where females constitute >80% of the total patients.^15,17,20

Our study found the most common angiographic type of disease to be type V, which is similar to a previous study from India.¹¹ However, this was closely followed by type I, unlike only 6% involvement in the previous study. This is in accordance with trends from other parts of the world, where type I is the most common presentation.^12-17,20 In an interesting observation published by Numano et al, vasculitis in Japanese patients generally occurs in the ascending aorta, the aortic arch, and/or its branches and extends into the thoracic and abdominal aorta; however, in Indian patients, vasculitis generally occurs in the abdominal aorta involving renal arteries, subsequently extending into the thoracic aorta within one or two decades.⁷ However, our study population revealed a more generalized involvement (type V) to be the most common pattern, followed by arch vessel involvement.

Another interesting observation by Numano et al was that more Indian patients were found to be hypertensive, while more Japanese patients were found to be pulseless.⁷ However, only 15 of our patients (24.2%) had hypertension, while 32 patients (52%) had pulselessness of either the upper and/or lower limbs.

TA is the most common cause of renovascular hypertension in southeast Asian countries.¹¹ The involvement of renal arteries is mostly bilateral and involves the ostia of the renal arteries. In our series, 20 patients (32.2%) were found to have significant renal artery stenosis, all of the ostial type, with bilateral involvement in 5 patients. Our results with renal stenting were excellent and encouraging, even in cases of bilateral involvement, which is similar to previous reports.²² Even follow-up angiograms done in 2 cases revealed only 50% ISR in 1 patient at 9-year follow-up and no restenosis in the other patient at 1-year follow-up.

Our results reveal the technical challenge involved in interventions of the cerebral arch vessels. In TA, in contrast to atherosclerosis, the vessels are more firm, scarred, and fibrotic. Even technical success may not translate into clinical success and may be associated with grave complications, as in 3 of our cases who developed perioperative infarction and residual hemiparesis, including death in 1 case. Procedural complications and/or hyperperfusion may be the complicating factors leading to the above results. Kim et al reported immediate technical and clinical success in all cases of cerebral vessel interventions in TA.²³ Tyagi et al reported successful balloon angioplasty/stenting in 12 stenotic lesions in the aortic arch vessels of 10 TA patients. No immediate procedure-related complications or neurologic deficits were reported. Two of the patients had diffuse ISR over a mean follow-up of 25 months treated with cutting balloon angioplasty.²⁴

In a previous study from India by Sharma et al comprising 20 patients, carotid, aortic, and renal angioplasty with or without stenting was performed. The safety and efficacy of PTA and stenting in case of renal angioplasty was ~90%. They reported success in 5 of 6 patients who underwent carotid angioplasty. Aortic angioplasty was carried out in 9 patients, with Wallstents used in 4 patients. Aortogram in 3 patients at 6 months of follow-up showed beneficial remodeling, while a saccular aneurysm was seen in 1 case. The results of subclavian angioplasty were also shown to be satisfactory, ie, at up to 10 months of follow-up, all patients had a good palpable pulse.²²

Tyagi et al reported successful subclavian angioplasty in TA in 88.8% cases with short- and long-segment disease. Restenosis occurred in 20.8% over a follow-up of 43 months. Only 1 patient (extensive dissection following the procedure) required stent implantation.²⁵ Subclavian angioplasty was successful in all of our cases, but stent implantation was done in all except an 11-year-old male, anticipating further requirement of repeat procedure as the vessel grows with age.  
Aortic interventions were successfully performed in most of our cases. Two of the patients had developed dissection during balloon dilatation that had to be covered with stents. There was no incidence of stent displacement or dislodgment. Sharma et al performed PTA without stenting in 15 arterial stenoses involving renal arteries, abdominal aorta, and left common iliac artery in 11 TA patients. Good patency was maintained in all abdominal patients and 4 out of 5 renal angioplasty patients over a period of up to 16 months.²⁶    

Our results highlight the challenging nature of interventions in TA, as has been described by others. McKinnon et al faced immediate failure in 2 of the 10 patients (20%) in whom stenting was carried out due to non-deployment or dislodgment of stents. Restenosis occurred in 14 of 18 initially successful angioplasty procedures (78%), with 13 patients requiring repeat interventions and vascular bypass in 6 of those patients over a median follow-up of 3 years.²⁷ Min et al performed successful angioplasty in 52 of 58 lesions (90%) targeted for intervention. Restenosis occurred in 9 treated segments (17%) and 4 were treated with repeat angioplasty over a mean follow-up of 23.7 ± 18.4 months. The overall cumulative primary clinical success rate was 82%.²⁸

Conclusion

Endovascular treatment with stent implantation is feasible and effective for patients with Takayasu’s arteritis with good clinical improvement in most cases. Cerebral vascular and abdominal interventions are technically more challenging and prone to complications. Hence, these require special precautions, especially in cases with long and diffuse stenotic lesions.

Study limitations. Our data are based on a retrospective analysis of hospital records. Coronary and pulmonary angiograms were not performed in all patients due to absence of symptoms pertaining to these systems.

The strength of our study lies in the detailed angiographic description and technical detailing of endovascular interventions carried out in TA patients and the various difficulties met at each step. More comprehensive data are needed to clearly define the role of endovascular treatment in TA.

References

1. Arend WP, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129-1134.
2. Moriwaki R, Noda M, Yajima M, Sharma BK, Numano F. Clinical manifestations of Takayasu arteritis in India and Japan — new classification of angiographic findings. Angiology. 1997;48(5):369-379.
3. Lupi-Herrera E, Sanchez-Torres G , Marcushamer J, et al. Takayasu’s arteritis. Clinical study of 107 cases. Am Heart J. 1977;93(1):94-103.
4. Vijayalakshmi. Recent advances in the management of non-specific aorto-arteritis. Indian J Pediatr. 2002;69(6):523-526.
5. Ogino H, Matsuda H, Minatoya K, et al. Overview of late outcome of medical and surgical treatment for Takayasu arteritis. Circulation. 2008;118(25):2738-2747.
6. Kerr G. Takayasu’s arteritis. Curr Opin Rheumatol. 1994;6(1):32-38.
7. Hoffman GS. Treatment of resistant Takayasu’s arteritis. Rheum Dis Clin North Am. 1995;21(1):73-80.
8. Ishikawa K. Effects of prednisolone therapy on arterial angiographic features in Takayasu’s disease. Am J Cardiol. 1991;68(4):410-413.
9. Martin EC, Diamond NG, Casarella WJ. Percutaneous transluminal angioplasty in non-atherosclerotic disease. Radiology. 1980;135(1):27-33.
10. Lee BB, Laredo J, Neville R, Villavicencio JL. Endovascular management of Takayasu arteritis: is it a durable option? Vascular. 2009;17(3):138-146.
11. Jain S, Kumari S, Ganguly NK, Sharma BK. Current status of Takayasu arteritis in India. Int J Cardiol. 1996;54(Suppl):S95-S100.
12. Cong XL, Dai SM, Feng X, et al. Takayasu’s arteritis: clinical features and outcomes of 125 patients in China. Clin Rheumatol. 2010;29(9):973-981.
13. Kechaou M, Frigui M, Ben Hmida M, Bahloul Z. [Takayasu arteritis in southern Tunisia: a study of 29 patients]. Presse Med. 2009;38(10):1410-1414.
14. Petrovic-Rackov L, Pejnovic N, Jevtic M, Damjanov N. Longitudinal study of 16 patients with Takayasu’s arteritis: clinical features and therapeutic management. Clin Rheumatol. 2009;28(2):179-185.
15. Park MC, Lee SW, Park YB, Chung NS, Lee SK. Clinical characteristics and outcomes of Takayasu’s arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol. 2005;34(4)284-292.
16. Mwipatayi BP, Jeffery PC, Beningfield SJ, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg. 2005;75(3):110-117.
17. Ureten K, Oztürk MA, Onat AM, et al. Takayasu’s arteritis: results of a university hospital of 45 patients in Turkey. Int J Cardiol. 2004;96(2):259-264.
18. McCulloch M, Andronikou S, Goddard E, et al. Angiographic features of 26 children with Takayasu’s arteritis. Pediatr Radiol. 2003;33(4):230-235.
19. Sharma S, Rajani M, Kamalakar T, Talwar KK, Sunderam KR. Clinical and angiographic features of nonspecific aorto-arteritis in children and adults. Acta Radiol. 1991;32(6):485-487.
20. Vanoli M, Daina E, Salvarani C, et al. Takayasu’s arteritis: a study of 104 Italian patients. Arthritis Rheum. 2005;53(1):100-107.
21. Panja M, Kumar S, Sarkar C, et al. Long-term follow-up of Takayasu’s disease. J Am Coll Cardiol. 1997;29(2):P-218A.
22. Sharma BK, Jain S, Bali HK, Jain A, Kumari S. A follow-up study of balloon angioplasty and de-novo stenting in Takayasu arteritis. Int J Cardiol. 2000;75(Suppl 1):S147-S152.
23. Kim HJ, Lee CS, Kim JS, et al. Outcomes after endovascular treatment of symptomatic patients with Takayasu’s arteritis.  Int Neuroradiol. 2011;17(2):252-260. Epub 2011 Jun 20.
24. Tyagi S, Gupta MD, Singh P, et al. Percutaneous revascularization of sole arch artery for severe cerebral ischemia resulting from Takayasu arteritis. J Vasc Interv Radiol. 2008;19(12):1699-1703.
25. Tyagi S, Gambhir DS, Kaul UA, Verma P, Arora R. A decade of subclavian angioplasty: aortoarteritis versus atherosclerosis. Indian Heart J. 1996;48(6):667-671.
26. Sharma S, Rajani M, Kaul U, Talwar KK, Dev V, Shrivastava S. Initial experience with percutaneous transluminal angioplasty in the management of Takayasu’s arteritis Br J Radiol. 1990;63(751):517-522.
27. McKinnon KM, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007;56(3):1000-1009.
28. Min PK, Park S, Jung JH, et al. Endovascular therapy combined with immunosuppressive treatment for occlusive arterial disease in patients with Takayasu’s arteritis. J Endovasc Ther. 2005;12(1):28-34.

________________________________________________________________________

From the Departments of 1Cardiology, 2Radiodiagnosis, and 3Pediatric Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore, India.

Disclosure: The authors have completed and returned the ICMJE Form for Disclo-sure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 4, 2014, provisional acceptance given April 21, 2014, final version accepted April 30, 2014.

Address for correspondence: Dr Ajit Pal Singh, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bannerghatta Road, Bangalore – 560069, India. Email: ajitpal11@yahoo.com