Restoration of vision by endovascular revascularization in Takayasu arteritis: A case series

Abstract

Takayasu arteritis (TA) is a rare, inflammatory vasculitis affecting aorta and its branches. Stenotic occlusive lesions of multiple arch arteries can cause severe cerebral ischemia leading to impaired vision. We present three consecutive young patients of TA with severe diminution of vision on upright posture, where we attempted restoration of sight by improving cerebral blood flow by percutaneous endovascular revascularization. All three patients could be successfully revascularized with substantial improvement in vision. There was no complication. On follow up, one patient developed recurrence of visual symptoms due to restenosis, which was successfully treated by cutting balloon angioplasty. The objective of this case series is to highlight the role of endovascular techniques in reversing visual loss in such situations.

<Learning objective: Takayasu arteritis (TA) is an inflammatory vasculitis that can affect arch arteries leading to near complete obliteration and often disabling symptoms such as loss of vision. This case series (3 cases) shows that stent-supported angioplasty is a minimally invasive technique which is safe and effective in restoring impaired vision caused by severe cerebral hypoperfusion in TA.>

Introduction

Takayasu arteritis (TA) is a rare, chronic inflammatory arteriopathy affecting the aorta and its major branches. Arch arteries are commonly involved in this disease. Severe stenosis and occlusion of arch arteries can lead to cerebral hypoperfusion which may present as syncope, stroke/transient ischemic attack, seizures, or visual loss [1], [2]. Occlusion of carotid arteries, vertebral arteries, or the ophthalmic arteries can result in ocular ischemia [3], [4]. In acute phase of TA, immunosuppressive treatment is used to reduce progression of disease [2]. This phase may progress into chronic obliterative phase with occlusion of multiple arch arteries giving rise to devastating neurological symptoms. At this stage revascularization becomes essential to improve perfusion of the severely ischemic cerebrovascular system. Bypass graft surgery has been used in such situations, but has several challenges due to requirement of thoracotomy, multifocal arterial involvement, inflamed fragile, or calcified tissues making surgery difficult [5]. Endovascular revascularization by angioplasty is a less invasive option [5], [6], [7]. However, its use in improving diminution of vision caused by TA has been rarely reported. We report three consecutive cases where we attempted to improve vision by improving perfusion by stent-supported angioplasty.

Case report

Three patients with TA who presented with severe visual impairment were studied. Detailed history, physical examination, diagnostic, and laboratory tests were obtained. The diagnosis of TA was made according to criteria of the American College of Rheumatology [8]. Patients with raised inflammatory markers were given oral glucocorticoids. Antiplatelet drugs were given to all these patients. After written and informed consent, femoral artery access was obtained, under local anesthesia, using standard catheterization techniques. All the cases were discussed at length with a neurologist and ophthalmologist to explore the feasibility of relief after endovascular intervention. Only when all consented were the cases taken up for intervention. All patients underwent thoracic and abdominal aortography to determine the extent of vascular disease. Selective angiography of the stenosed artery was performed to localize the site and extent of vessel involvement and distal circulation.

For the intervention, a 7-F, 90-cm-long, Shuttle Flexor sheath TM (Cook Inc, Bloomington, IN, USA) was advanced over a 5 F cerebral diagnostic catheter into the proximal portion of the stenosed artery. Intravenous heparin (5000 IU) was administered to maintain an activated clotting time of 200–250 s during the procedure. The stenotic lesion was crossed with a floppy-tipped 0.014″ coronary guidewire, taking care not to enter the intracranial segment of the artery. The lesions were dilated with a monorail balloon, inflated with diluted contrast until the waist on the balloon disappeared or rated burst pressure (RBP) of balloon was reached.

Case 1

A 23-year-old man presented with history of dizziness for the previous 2 months, which increased on standing. He had four episodes of syncope during this period. Along with this he gave history of sudden loss of vision in the right eye 4 months previously, which was diagnosed as retinal artery occlusion. Fundus examination at that time showed right eye disc edema, infranasal scarring, cherry red spot at macula, while left fundus showed no abnormal findings. There was no vision in the right eye while it was normal in the left eye. He gradually developed marked diminution of vision in the left eye for the past month with inability to see on standing. His upper limb pulsation and both carotids were not palpable. There was faint bruit in right suprasternal area. There was no renal bruit. There was no murmur.

His hemogram and blood biochemistry were normal. Erythrocyte sedimentation rate (ESR) was 29 mm in first hour, C-reactive protein (CRP) was 5.3 mg/L. Magnetic Resonance angiography of arch of aorta showed marked luminal narrowing of right common carotid artery and right subclavian artery. Left common carotid and left subclavian artery were not visualized. He had normal echocardiography. These findings suggested diagnosis of TA.

The patient was started on oral steroids, aspirin 150 mg, and clopidogrel 75 mg per day. He was taken up for aortography using standard technique as explained above. Aortogram showed total occlusion of left subclavian, left common carotid artery, severe, diffuse narrowing of right common carotid artery (Fig. 1A) and severe short segment stenosis of pre-vertebral right subclavian artery (Fig. 1B). Abdominal aorta and its branches were normal.

Fig 1.

(A) Digital subtraction angiogram (DSA) of arch of aorta in left anterior oblique view shows total occlusion of left subclavian, left common carotid, and right common carotid artery, severe stenosis of pre vertebral segment of right vertebral artery. (B) Selective DSA of innominate artery shows severe stenosis of pre vertebral right subclavian artery. (C) Selective DSA after angioplasty and stent implantation in the pre-vertebral segment of right subclavian artery shows that there is marked improvement in lumen increasing perfusion through vertebral artery.

Angioplasty of pre-vertebral right subclavian artery stenosis was planned. Through right femoral artery approach, innominate artery was engaged as detailed above and dilatation of subclavian artery stenosis was carried out with 5 × 20 mm balloon. Post dilatation angiogram showed flow limiting dissection. A 6-mm diameter, 14-mm long balloon expandable stent (Express vascular SD monorail, Boston Scientific, Natick, MA, USA) was implanted. After stent implantation the pre-vertebral subclavian artery lumen diameter markedly improved with no residual stenosis. Flow through the right vertebral artery markedly improved (Fig. 1C).

The day after angioplasty, the patient reported good improvement in vision in right eye and his symptoms of dizziness on standing also disappeared. On follow up, the patient continued to have sustained improvement in symptoms. Restudy digital subtraction angiogram (DSA) done after 9 months showed continued relief of subclavian stenosis with mild intimal growth (Fig. 2). On follow up of two years, he continued to be asymptomatic with good vision with his left eye.

Fig. 2.

Digital subtraction angiogram on follow-up restudy shows continued patency of pre-vertebral segment of right subclavian artery perfusing the vertebral artery.

Case 2

A 27-year-old female presented to this hospital with complaint of blurred vision for the past 2 months, which used to further deteriorate on sitting up from a lying down position. She also had postural seizures (5–6/day for 1 month) usually precipitated by sitting up. Her symptoms were so severe that she was afraid to sit up. There was no history of headache, fever, vomiting, joint pain, or any focal neurological deficit.

On physical examination, bilateral carotid artery pulses and upper limb pulses were not palpable. On fundus examination Cup to disc ratio was normal i.e. 3:1, disc pallor was present. No evidence of hemorrhage or exudate was seen. Her ESR and CRP were found to be raised. Computed tomography angiography showed severe stenosis of left subclavian and vertebral artery in proximal segment. Bilateral common carotid artery and right vertebral artery were occluded (Fig. 3). The patient was put on oral steroids and antiplatelet therapy. DSA of arch of aorta showed occluded innominate, right subclavian, and right carotid artery. Left carotid artery showed severe diffuse stenosis. Left subclavian artery and left vertebral artery ostium had severe stenosis (Fig. 3A,B). Left subclavian artery was engaged with a 7 F, Shuttle sheath (Cook Inc). Two guide wires were passed across the stenosis into vertebral artery and into left subclavian artery. Serial dilatation of left vertebral artery and post vertebral subclavian artery was done. Post dilatation there was flow-limiting dissection in subclavian artery. The vertebral artery was stented with sirolimus drug-eluting Biomime stent (4.5 mm × 37 mm, Meril Life Sciences Pvt. Ltd, Vapi, India) extending from proximal vertebral artery into subclavian artery. The stent was further expanded with 5 mm noncompliant, monorail balloon. The flow through the vertebral artery markedly improved (Fig. 3C). On the next day, the patient reported good improvement in vision even on standing up. Her other cerebral symptoms also improved.

Fig. 3.

(A) Computed tomography angiogram of arch of aorta shows total occlusion of innominate, left common carotid artery, severe stenosis of left subclavian artery and ostium of left vertebral artery. (B) Selective digital subtraction angiogram (DSA) shows severe stenosis of left subclavian and ostium of left vertebral artery. (C) Selective DSA of left subclavian artery and vertebral artery after angioplasty and stent implantation shows marked improvement in lumen.

Subsequently on 3rd day, balloon angioplasty of severe diffusely narrowed left common carotid artery (7 mm × 100 mm self-expandable nitinol stent) was done to further improve cerebral perfusion. Ostium of common carotid artery was then stented with balloon expandable sirolimus-eluting Biomime (Meril Life sciences, India) (4.5 mm × 37 mm) stent.

She had marked improvement in her visual and neurological symptoms. She had sustained relief of her neurologic symptoms and good vision for 6 months when her vision again started deteriorating. Check angiogram revealed severe in-stent restenosis (ISR) (Fig. 4A) for which cutting balloon angioplasty was done and stenosis was resolved (Fig. 4B). This improved her vision again. In view of her disease activity and restenosis, oral methotrexate was added to her treatment. She continued to do well on follow up of one year.

Fig. 4.

(A) Follow-up digital subtraction angiogram (DSA) of left subclavian artery shows in-stent restenosis and occlusion of distal subclavian artery. The patient developed diminution of vision. (B) DSA of left subclavian artery after cutting balloon angioplasty shows marked relief of stenosis relieving the symptoms.

Case 3

A 37-year-old female was diagnosed with TA type 3 with involvement of arch and abdominal aorta 17 years previously. She at that time had presented with dizziness and pre-syncope. Her angiogram showed total occlusion of left subclavian, left common carotid artery, and 90% stenosis of proximal right common carotid artery and 50% stenosis of proximal right subclavian artery. She underwent successful angioplasty and stenting of this carotid artery with relief of her symptoms. She had recurrence of her previous symptoms after 1 year. Angiogram showed restenosis in the carotid stent. She underwent repeat balloon angioplasty of ISR with relief of her symptoms. She was on regular follow-up, and continued to do well for 16 years. She this time presented with complaints of dizziness, jaw claudication, and loss of vision on standing. Upper limb pulse and carotid pulse was not palpable. Her ESR was 40 mm in first hour, suggestive of activity. Arch angiogram revealed severe stenosis (90%) of pre-vertebral right subclavian artery and significant ISR to the right carotid stent (Fig. 5A). Percutaneous angioplasty was performed by interventional technique given above. A 0.014″ dm, 190 cm long, soft tip, extra support percutaneous transluminal coronary angioplasty guide wire was passed through right subclavian stenosis and another similar guide wire across right carotid stenosis. Initial dilatation of subclavian stenosis was performed by 2 mm coronary balloon. Subsequently, cutting balloon angioplasty (4 mm) of subclavian artery and right carotid artery was done. There was good improvement in lumen of right subclavian and carotid artery (Fig. 5B).

Fig. 5.

(A) Digital subtraction angiogram (DSA) shows severe stenosis of pre-vertebral segment of right subclavian artery and in-stent restenosis of ostial right carotid artery. (B) DSA after cutting balloon angioplasty of subclavian and in-stent carotid stenosis shows marked improvement in lumen.

She had marked improvement in her visual and neurological symptoms. She was continued on oral aspirin and steroids. On follow up of 7 months, she continued to have normal vision and sustained relief of her neurological symptoms.

The cases are summarized in Table 1.

Table 1.

Summary of cases.

Case no.	Age/Sex	Presenting symptom	Artery angioplasty	Procedure	% stenosis		Follow up
					Pre	Post
1	23/M	Dizziness recurrent syncope, decreased vision	Rt. subclavian	PTA & 6 mm dm BE stent	90	0	Good vision No restenosis
2	27/F	Seizures, decreased vision	Lt. subclavian Lt.vertebral Lt Carotid	PTA & 4.5 mm dm BE sirolimus DES	90	10	In stent restenosis, re-balloon Good vision
3	37/F	Dizziness, decreased vision	Rt. subclavian, ISR Rt carotid	PTA cutting balloon	85	25	Good vision No restenosis

Rt, Right; Lt, Left; ISR, In-stent restenosis; PTA, Percutaneous transluminal angioplasty; BE, Balloon expandable; DES, Drug-eluting stent.

Discussion

TA is a rare, inflammatory vascular disease and classically involves the aorta and its major branches. Stenosis, occlusion of supra-aortic arteries is common. Subclavian artery is most frequently involved, followed by proximal segments of brachiocephalic, carotid, and vertebral arteries and may manifest as brain and retinal ischemia. Due to the slow progressive nature of the disease, collateral formation is common. Therefore the symptom of cerebral ischemia is most often associated with obstructive lesion of multiple arch vessels. It may manifest as fainting spell on standing, vertigo (especially when looking upwards), and visual disturbance [1], [2], [3]. Visual symptoms may occur due to ocular or cerebral ischemia caused by extensive obliteration of the branches of the arch of aorta with or without thrombosis. Medical treatment in the form of disease-modifying drugs such as steroids and immunosuppressants may alter the course of the disease during the early active phase [5], [6]. However, in the late, chronic phase once stenosis has developed it is difficult to reverse by medical treatment.

All the patients in this case series had critical cerebral ischemia. Although this insufficient blood flow kept the patients alive, they were severely incapacitated. They kept themselves mostly in the supine position, as they had significant deterioration in vision on getting upright due to a further reduction in cerebral and retinal blood flow in the presence of critical stenosis proximal to vertebral artery. Viability of fundus and optic nerve was probably maintained by blood flow through collateral circulation. This was corroborated by subsequent improvement in visual symptoms after relief of obstruction proximal to vertebral artery in these three consecutive patients. Improvement in vision by improvement in flow through vertebral artery can also be due to improvement in blood flow to the visual cortex in occipital lobe. The vertebral arteries join to form basilar artery, which divides into posterior cerebral artery, which in turn supply the visual cortex. Reduced cerebral perfusion causing bilateral visual loss has been observed in patients with chronic renal failure on dialysis, in perioperative hypotension, and in conditions with orthostatic hypotension [9].

These cases highlight the fact that patients with TA can present with hypoperfusive ocular and cerebral manifestations which can lead to significant visual loss [10]. The majority of the patients with TA are young and any impairment in vision because of disease can be devastating. Whilst some of these ocular manifestations may be irreversible such as chronic retinal artery occlusion causing optic atrophy, others due to hypoperfusion can be reversible as depicted by the cases above. In our patients, the ocular symptoms were of insidious onset, gradually progressive nature, worsened by upright posture, paralleling the gradual ischemia that develops due to progressive vascular occlusion of the arch arteries. Also acute sight loss, as in anterior ischemic optic neuropathy, may not be amenable to therapy that could restore blood flow [7], [8].

Prompt, appropriate, and judicious interventional revascularization is of essence in such cases even before complete control of disease activity in TA. It is important to ascertain whether the main cause for the symptoms is ocular pathology or an extraocular involvement. Diseases such as sarcoidosis, multiple sclerosis, and infectious aortitis may cause ocular involvement and should be excluded. Hence, peri-interventional work up must include a neurologist and an ophthalmologist. Involvement of two main arterial systems (vertebral and carotids) is responsible for vision involvement in TA. The vision loss is attributed to hypoperfusion of optic nerves and retina. Angioplasty of severe steno-occlusive arch arteries can quickly restore circulation to ischemic areas of brain. However, patients have to be carefully observed for symptoms of hyperperfusion phenomenon after endovascular therapy. This is because of sudden restoration of blood supply to the ischemic area. Although bypass graft surgery is effective and has a lower restenosis rate for treating patients of TA with cerebrovascular ischemia, it requires thoracotomy and often requires manipulation of fragile, inflammatory or fibrosed calcified tissue. This is associated with major complications of intracranial hemorrhage (26.3%) and intracranial infarction (21.1%) [4], [9]. This case series suggests that percutaneous angioplasty and stenting is a much less invasive and safer option to open surgical bypass with good clinical results in patients with critical cerebral ischemia.

Restenosis is a problem after angioplasty and is often due to disease activity. New lesions may develop or progress on follow up after angioplasty. Even drug-eluting stent at the current dosage and eluting kinetics may not be able to reduce restenosis in this inflammatory arteriopathy. Case 1 had sustained improvement on follow up. Case 2 had development of restenosis within drug-eluting stent, which was treated by cutting balloon angioplasty. Case 3 had progression of subclavian artery stenosis and carotid ISR 16 years after the previous angioplasty procedure. Inflammatory markers, ESR and CRP, became elevated during recurrence. This suggests that disease activity can reoccur even very late, after being quiet for several years as relapses and remissions are observed in TA. Hence surveillance of disease activity and pharmacological suppression of inflammation by corticosteroids, immunosuppressives, or biologics may be necessary. Late presentation in these cases permitted palliative endovascular revascularization. Detection at earlier stage of disease, that is before total occlusion occurs, could have enabled more complete revascularization by angioplasty of other stenotic arteries before they developed total occlusion.

Conclusion

The present series suggests that reperfusion by endovascular intervention in TA patients is safe and effective in significantly reducing cerebral and retinal ischemia. Even palliative revascularization in a situation when all other arteries are occluded can cause restoration of vision if irreversible ischemic changes have not already occurred. Repeat intervention for new lesions or restenosis on follow up can be performed safely.