Author Affiliations: From the Cardiology Division, Section of Vascular Medicine, Massachusetts General Hospital and §Harvard Medical School, Boston, Massachusetts. Disclosures: Dr. Rosenfield has received research grants from Idev, Abbott Vascular, Cordis Corp., Boston Scientific Corp., Bard, Baxter, Invatec, and Lumen; is a consultant to Cordis, Boston Scientific, Baxter, CardioMind, Micelle, Complete Conference Management, Idev, Abbott Vascular, Boston Biomedical Associates; owns stock in Lumen, CardioMind, Xtent, and Cardiomems; and has a financial relationship with VIVA Physicians. Manuscript submitted March 3, 2008, provisional acceptance given April 16, 2008, manuscript accepted April 24, 2008. Address for correspondence: Bryan P. Yan, MBBS, FRACP, Cardiology Division, Massachusetts General Hospital, 55 Fruit Street GRB-800, Boston, MA 02114. E-mail: email@example.com
ABSTRACT: The optimal treatment for renal artery in-stent restenosis (ISR) is not well established. Reintervention with different strategies including balloon angioplasty, cutting-balloon angioplasty, additional stenting with bare-metal, drug-eluting or covered stents and brachytherapy are effective in achieving immediate angiographic success. However, recurrent ISR rates are high irrespective of treatment strategy. We present a case describing the use of a covered stent for the treatment of recurrent bilateral renal artery ISR after bare-metal and drug-eluting stent implantation and cutting-balloon angioplasty.
J INVASIVE CARDIOL 2008;20:E288–E292
Percutaneous transluminal angioplasty with stent implantation has been shown to be effective in the treatment of atherosclerotic renal artery (RA) stenosis.1–3 Analogous to stenting in the coronary artery, long-term efficacy of RA stenting is limited by in-stent restenosis (ISR) in up to 20% of patients.2–6 The optimal treatment of RA-ISR is not well established. Reintervention with different strategies including balloon angioplasty, cutting-balloon angioplasty, additional stenting with bare-metal stents (BMS), drug-eluting stents (DES) or covered stents and brachytherapy are effective in achieving immediate angiographic success, however, recurrent ISR rates are high (30–50%) irrespective of treatment strategy.7–12 Patients with recurrent ISR may experience even higher subsequent restenosis rates. We present a case describing the use of covered stents for the treatment of recurrent bilateral RA-ISR after bilateral BMS and DES implantation.
Case Report. A 78 year-old female presented with her third recurrent bilateral RA-ISR with a background history of diffuse systemic vascular disease involving the coronary, extracranial, peripheral, mesenteric and RA and resistant hypertension on 6 antihypertensive agents (including valartan, amlodipine, hydrochlorothiazide, metoprolol, isosorbide mononitrate and minoxidil). She had a past history of coronary artery bypass grafts, bilateral carotid endarterectomy and subsequent bilateral carotid artery stenting, left vertebral artery stenting, aorto-femoral artery bypass grafting, and stenting to the left common internal iliac artery and superior mesenteric artery. She was on anticoagulation therapy for her mechanical aortic valve (Carbomedics, Austin, Texas) replacement. Her other cardiovascular risk factors included hyperlipidemia, a strong family history of cardiovascular disease and a past history of smoking. Her creatine was normal at 0.8 mg/dL.
Bilateral ostial RA stenoses were diagnosed 2 years prior to this presentation and were treated with balloon angioplasty and implantation of a Genesis 5 x 18 mm stent (Cordis Corp., Miami Lakes, Florida) in the right RA and a Racer 5 x 18 mm stent (Medtronic, Minneapolis, Minnesota) in the left RA (Figure 1). At 6-month follow up, her blood pressure remained poorly controlled and duplex ultrasound of the RA showed high peak systolic velocities (PSV) (305 cm/second on the right and 344 cm/second on the left RA) suggestive of restenosis. Angiography revealed severe bilateral ISR (Figure 2). Additional stenting of the RA-ISR lesions was performed using Cypher 3.5 x 23 mm DES (Cordis) in both RAs and postdilated up to 4.5 mm in the right and 4.0 mm in the left RA, with < 20% residual angiographic stenosis. The patient represented again 6 months later with resistant hypertension and high PSVs in both RAs. Repeat angiography showed recurrent ISR in both RAs, which were dilated using Angiosculpt scoring balloons (Angioscore, Fremont, California) — 6 x 20 mm in the right and 4 x 15 mm in the left RA. The result obtained was satisfactory, with < 25% residual stenosis and a < 20 mmHg peak translesional gradient bilaterally.
Eight months later, the patient re-presented for the third time with resistant hypertension. Duplex renal ultrasound revealed significant increased PSV in the proximal segment of the RA and an increased renal/aortic ratio bilaterally (Table 1). Angiography revealed 95% and 80% recurrent ISR of the right and left RAs, respectively (Figure 3A). Intervention to the right RA lesion was performed first. The artery was engaged with a 7 Fr IMA guide using the “no-touch” technique. A 0.014 inch Prowater guidewire (Abbott Vascular, Abbott Park, Illinois) was used to cross the restenotic lesion. A 4 Fr Glidecath (Boston Scientific Corp., Natick, Massachusetts) advanced beyond the lesion detected minimal pressure in the distal RA. The lesion was pre-dilated with a 3.5 x 20 mm Angiosculpt scoring balloon up to 12 atm. A 5 x 18 mm Graftmaster Jostent covered stent (Abbott) was implanted and postdilated with a 5.5 x 15 mm Viatrec (Abbott) balloon up to 18 atm with no residual stenosis (Figure 3B). Intravascular ultrasound (IVUS) of the stented segment showed good stent apposition.
The left RA was treated 3 days later as a staged procedure. The left RA was engaged using a 5 Fr SOS Omni selective catheter (Angiodynamics, Queensbury, New York) telescoped in a 7 Fr IMA catheter. The recurrent RA-ISR lesion was crossed with a 0.014 inch Prowater guidewire. Similarly, a large translesional gradient was demonstrated with a 4 Fr Glidecath placed distal to the lesion (Figure 4A). Likewise, the lesion was dilated with a scoring balloon and then a 4.5 x 16 mm Graftmaster covered stent was implanted and postdilated with a 4.5 x 16 mm Viatrec balloon at high pressure up to 16 atm with no residual stenosis (Figure 3C) and resolution of the translesional gradient (Figure 4B). Adequate stent apposition was confirmed on IVUS.
The patient remained well 9 months post procedure. Her blood pressure was well controlled with a systolic blood pressure between 130 mmHg and 140 mmHg on two antihypertensive agents. Her creatine was stable at 0.8 mg/dL. Repeat RA duplex ultrasound revealed normal Doppler flow velocities and resistive indices bilaterally (Table 1).
Discussion. ISR due to neointimal hyperplasia remains a major limitation of RA stenting. Most stent restenoses occur during the first year with an incidence between 10–21%.2–6 Irrespective of treatment strategy of RA-ISR, studies have reported recurrent restenosis rates of more than 30%.7–12 There is a paucity of data regarding treatment of recurrent RA-ISR. In a recent study of 33 patients with at least 2 episodes of RA-ISR, the restenosis rates at 36 ± 25 months’ follow up ranged from 0–100% depending on the mode of therapy despite immediate angiographic success in all cases.13
A number of patient and lesion characteristics have been associated with an increased risk of RA-ISR, including age ≤ 67 years, history of peripheral vascular disease or stroke, solitary functioning kidney, aorto-ostial lesion and small RA ≤ 6 mm.4,14,15 In particular, a larger reference vessel diameter and larger acute gain (post-stent minimal lumen diameter [MLD]) are strongly associated with a lower incidence of restenosis.4,14,15 A study of 300 consecutive patients and 361 RA treated with stent implantation demonstrated that vessels with a diameter smaller than 4.5 mm had a restenosis rate of 36% compared with 6.5% in vessels > 6 mm in diameter.4 Our patient received stents ≤ 6 mm in diameter in both RA and her history of diffuse systemic atherosclerosis put her at the highest risk for restenosis. With each additional layer of stent implanted, the minimal lumen diameter became progressively smaller. The original BMS implanted in our patient were 0.5 mm larger in diameter than that of the third and final layer of covered stent implanted. Unfortunately, our patient was not a good candidate for surgical revascularization given her comorbidities and extensive vascular disease.
The principal cause of RA-ISR is neointimal hyperplasia resulting from the excessive proliferation of smooth muscle cells in response to injury after angioplasty and stent implantation.16 Effective treatment of RA-ISR requires suppression of this intimal proliferation. Our patient with recurring RA-ISR represents a subgroup of individuals who has aggressive and progressive neointimal hyperplasia that is likely to cause ongoing restenosis unless this proliferative process is halted. Treatment with balloon angioplasty alone is therefore unlikely to be effective. In a study of patients with recurrent RA-ISR, balloon angioplasty alone was associated with an unacceptable high rate of restenosis of 71%.13 This is much higher than restenosis rates after balloon angioplasty of first-time RA-ISR which is approximately 30%.7 Similarly, cutting-balloon angioplasty appears to be ineffective for the treatment of RA-ISR.8,13
Brachytherapy has been shown to be effective in reducing recurrent restenosis by approximately 50% in some series.9–11 However, long-term efficacy is lacking and this modality is no longer widely available.
Success of DES in inhibiting neointimal hyperplasia and restenosis in the coronary arteries has led to enthusiasm in their use in RA. However, the larger diameter of the RA poses a limitation in the use of currently available DES, which are designed for the coronary artery. The use of DES has been described in small RAs with good short-term outcomes.12 However, the largest DES currently available in the U.S. is 3.5 mm in diameter and can be postdilated to a maximum of 4.0–4.5 mm, which may be inadequate for most renal arteries which are 5–7 mm in diameter. Overdilatation is not advised and may disrupt the integrity of the drug-eluting polymer. There is also concern that thin-strut coronary stents may lack the radial strength required to overcome elastic recoil of aorto-ostial RA stenosis.
Covered stents are available in sizes up to 10 mm and may be the preferred strategy in large RA-ISR. The Jostent covered stent (3–5 mm) is a balloon-expandable stent with a polytetrafluoroethylene (PTFE) layer sandwiched between two coaxially aligned stainless-steel stents. The iCast (Atrium, Hudson, New Hampshire) covered stent (5–10 mm) is another balloon-expandable stent that is encapsulated within layers of PTFE. When implanted, the stent forms a mechanical barrier between the vessel lumen and wall. The potential to barricade the advancement of neointimal proliferation between stent struts has been proposed as a mechanism that might reduce (or prevent) ISR. Decreasing exposure of the vessel wall to components of circulating blood, such as macrophages, might also reduce the incidence of ISR. However, there is currently limited evidence for covered stent use in RA-ISR.7
A recent study by Zeller et al compared the efficacy of five different treatment strategies in 31 patients presenting with at least their second RA-ISR.7 At a mean follow up of 36 ± 25 months, implantation of covered stent or DES was associated with significantly less restenosis (17% and 0%, respectively) compared to angioplasty alone (71%), BMS (43%) or cutting-balloon (100%, p < 0.01).7 The result of this study suggested that either covered stents or DES are the preferred treatment strategy for recurrent RA stenosis. Additional larger studies on covered stents and dedicated DES for RA are warranted to help define optimal treatment for RA-ISR.