Percutaneous Treatment of Severe Carotid Stenosis Due to Takayasu’s Arteritis Early after Carotid Endarterectomy

Takayasu’s arteritis (TA) is a chronic inflammatory large-vessel disease of unknown etiology involving the aorta, its major branches and the pulmonary arteries.^1,2 Resultant mixed areas of stenosis, occlusion, thrombosis and/or dilatation may cause a variety of symptoms including hypertension, congestive heart failure, mesenteric ischemia and claudication. Involvement of the supra-aortic branches may lead to visual changes including blindness, transient ischemic attacks (TIAs) and cerebral vascular accidents (CVAs). Predominantly a disease of women in the second and third decades of life, with a female-to-male ratio of 1.3–9:1, TA is also seen in the pediatric population.^2–5 It is most common in Southeast Asia, but is recognized worldwide and has been described in patients of all races.^4,6,7 The goal of medical treatment is to control active inflammation, as measured by clinical and laboratory indices, in order to prevent progression of vascular damage. Those patients who have developed symptomatic fibrotic lesions or aneurysms may undergo surgical or percutaneous intervention. The diffuse, progressive nature of TA can make revascularization difficult. It has been thought that surgical intervention is best reserved for undilatable stenotic lesions or large aneurysms.^8,9 Angioplasty has proven successful in dilating the stiff fibrotic lesions, and the advent of stents has significantly diminished restenosis rates. We present a case of successful revascularization of a patient who developed symptoms from restenosis of a left internal carotid artery 6 months after carotid endarterectomy (CEA).

Case Report. A 39-year-old, non-smoking, Asian female with a history of hypertension and hyperlipidemia presented with complaints of angina and claudication. A workup revealed total occlusion of the infrarenal aorta, although the superior mesenteric, celiac and bilateral renal arteries were spared. There was 100% left anterior descending artery (LAD), 90% mid-right coronary artery (RCA) and 90% left internal carotid artery (LICA) stenosis, with 100% occlusion of the left subclavian artery. She was therefore diagnosed with TA and was treated with an aorto-bifemoral bypass graft followed by stenting of the LAD and RCA. One month later, she underwent left CEA for TIA symptoms.

Six months later, the patient presented with recurrent headaches and TIAs. Angiography revealed a long (40–50 mm), 95% stenosis of the LICA extending into the intracranial portion of the vessel. This lesion was inaccessible to surgical revision.

Following diagnostic carotid angiography, an embolic protection device, the 4.5 mm AccuNetRX (Guidant Corp., Indianapolis, Indiana), was placed distal to the restenosis in the LICA. This was followed by angioplasty using an Aviator 4.0 x 40 mm balloon (Cordis Endovascular, Miami Lakes, Florida). An Acculink RX 6.0 x 30 mm stent was deployed in the distal segment of the LICA, followed by deployment of a second Acculink RX 6.0 x 20 mm stent more proximally. A third stent, the tapered Acculink RX 6.0 mm x 8.0 mm x 30 mm, was deployed at the ostium of the LICA. Following stent deployment, dilatation was performed with the Aviator 4.0 x 40 mm balloon at multiple sites. Final angiography revealed no residual stenosis. The patient tolerated the procedure well without neurological sequelae. Prednisone 60 mg p.o. daily was reinitiated on the following day for aggressive immunosuppression followed by methotrexate therapy. The patient was free of neurologic symptoms with < 15% residual stenosis 6 months later.

Discussion. Since initially described by Japanese ophthalmologist M. Takayasu in 1908, much has been learned about TA, although the etiology remains unclear.¹⁰ Recognized worldwide with no race being exempt, it is a common affliction in third-world countries, occurring more frequently in Southeast Asia, Africa and South America. Predominantly a disease of women in the second and third decades of life with a female-to-male ratio of 1.3–9:1, TA is also seen in the pediatric population. Also termed the pulseless disease, asymmetric pulses are the predominant finding; absence of peripheral pulses occurs late in the course of the disease in some patients.^{2–7,11–13}

TA consists of an early, active, inflammatory phase and a late, chronic, fibrotic phase. The early phase is characterized by nonspecific constitutional symptoms (fever, night sweats, anorexia, weight loss, lethargy, arthralgia and rash), frequently delaying diagnosis for months to years.^2,14 Tenderness along arteries, bruits and aneurysms may aid in recognition of the disease. Inflammatory markers (CRP, ESR) are frequently elevated, but do not consistently correlate with the level of disease activity.^2,3 The acute phase may last for weeks to months and may have a fluctuating course. The chronic phase is characterized by symptoms resulting from stenosis or occlusion of the involved vessels.^15,16

Initial pathology involves exudative, granulomatous inflammation around the vasa vasorum in the media and adventitia. Fragmentation of elastic fibers and necrosis of smooth muscle cells in the media lead to vessel wall weakening and dilatation. Reactive fibrosis of the intima at the site of medial inflammation appears early, with nodular fibrosis in all layers of the artery occurring later. The intima may obliterate the lumen as it becomes several times thicker than the media. These stenotic lesions account for most of the characteristic later clinical findings. Poststenotic dilatations and aneurysms are also seen. Lesions are typically patchy and heterogeneous in nature, making surgical repair much more difficult.

Attempts have been made to establish diagnostic criteria, but none are entirely adequate.^17,18 Angiography or magnetic resonance imaging is considered the gold standard in diagnosing TA. Angiography characteristically shows luminal irregularity, stenosis, dilatation or aneurysms in the aorta and its major branches. TA is divided into four types based on vessel involvement. Type I involves the aortic arch and its branches. Type II involves the thoraco-abdominal aorta and its branches. Type III applies when vessels of both Types I and II are involved. Patients with involvement of the pulmonary arteries have Type IV TA.^3,6 Pulmonary artery involvement is seen in up to 70% of patients, but usually to a mild degree.¹⁹ Coronary arteries are involved in approximately 10% of patients.²⁰ The infrarenal aorta and iliac vessels are not usually involved.⁵ Active disease is suggested by constitutional symptoms, signs and symptoms of vascular ischemia, elevated inflammatory markers and angiographic changes. Histologic changes and angiographic progression have both been seen in the absence of clinically active disease.^3,21

Treatment in the acute phase of TA with corticosteroids (1 mg/kg/day) will lead to remission in 60% of patients. Immunosuppressive agents (cyclophosphamide 1–2 mg/kg/day, azathioprin 1–2 mg/kg/day or methotrexate 0.15–0.35 mg/kg/week), including monoclonal antibody therapies (anti-TNF antibody adalimumab and infliximab), are utilized in more resistant cases.^3,13,22–24 Even with the progression of disease, overall mortality remains low, with reports of 15-year survival rates of 85–95% of patients. However, patients may suffer significant morbidity related to stenosis of the involved vessels. Angioplasty of the aorta and renal arteries, with and without stenting, has proven to be highly successful. Improvements in hypertension, congestive heart failure and exercise tolerance are seen quickly after dilatation and persist for years. Surgical intervention, including excision and graft placement, has had a role in the treatment of TA. Lesions in TA tend to be diffuse, patchy, frequently ostial and potentially progressive in nature. Recently, the success of angioplasty and stenting has made surgery a less preferable approach, except in cases of undilatable fibrotic stenoses and large aneurysms.^8,9,25–28

Up to 69% of patients with TA will have carotid artery involvement. As in our patient, neurologic sequelae, including TIAs, visual loss, seizures and hemiplegia^1,15,17,29 may develop. CVAs contribute to 20% of mortality in TA. Carotid stenting has recently been more widely accepted as a validtreatment option for atherosclerotic carotid stenosis, particularly in patients with comorbid conditions.^12,30–32 The lesions found in TA tend to be more diffuse, multifocal, more fibrotic, and less likely to ulcerate and thrombose than those due to atherosclerotic disease. Little experience has been reported in stenting of carotid stenoses in TA. The literature reports a broad range of safety and success rates, mostly in case reports and small series.^12,33–38 Little is known on intermediate- and long-term follow up of carotid stenting in TA.^29,36,39

Conclusion. Our patient demonstrates many of the above characteristics of TA, with a remarkably aggressive carotid restenosis distal to the endarterectomy site. She had involvement of multiple vascular beds including the coronary arteries and the iliac vessels, which are seen in the minority of TA cases. Using embolic protection, we successfully deployed carotid stents covering the long, severely stenotic area with no residual stenosis and continued patency at 6 months.

Further studies evaluating the overall safety and long-term follow up of carotid stenting in TA are needed. Such trials may be difficult due to the low incidence and prevalence of this disease. We believe that carotid angioplasty and stenting, combined with aggressive immunotherapy, will prove to be a safe and effective mode of treatment of carotid stenosis in patients with TA.

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