Cutting Balloon to Treat Carotid In-Stent Stenosis: Technical Note

Key words: angioplasty, carotid stent, cutting balloon, in-stent stenosis Carotid angioplasty with stenting for atherosclerotic stenosis is currently under examination in numerous trials as an alternative to carotid endarterectomy (CEA) and as an option for high-risk patients.¹ In-stent stenosis is one of the possible long-term complications of vascular angioplasty and stenting. This condition is defined as >= 50% increase in the narrowing of the lumen within a stent, as compared with the diameter of the lumen immediately after treatment. The incidence of carotid in-stent stenosis has been found to be approximately 5%.² In the peripheral and coronary circulations, in-stent stenosis that occurs within the first 2 years after stenting is attributed to myointimal hyperplasia with smooth muscle cell proliferation as the predominant mechanism involved.³ The net result is a fibrous tissue collection within the stent. The natural history of in-stent stenosis is not clear. At most institutions, patients without symptoms who have >= 80% in-stent stenosis or those who have symptoms related to >= 50% in-stent stenosis are considered for angioplasty. The currently accepted treatment for in-stent stenosis is balloon angioplasty with a non-compliant balloon.⁴ The long-term outcome from this treatment has not yet been documented. Experience from the coronary literature suggests that angioplasty of in-stent stenosis with traditional balloons is associated with significant recurrence. Given the low incidence of carotid in-stent stenosis, technology will likely advance more rapidly than long-term outcome data will be accumulated. A growing experience in the interventional cardiology literature suggests that the Cutting Balloon (CB) angioplasty catheter (Boston Scientific Interventional Technologies, San Diego, California) may be superior to conventional angioplasty balloon catheters for the treatment of coronary in-stent stenosis. The concept of a CB was first introduced in 1980.⁵ The CB consists of a non-compliant balloon with three or four atherotomes (Figure 1), which are microsurgical blades, each 0.005´´ thick, mounted longitudinally on its outer surface. As the balloon is inflated, the microblades protrude to fit inside the vessel. The blades then score the plaque, causing it to crack evenly. The balloon is folded to shield the blades and protect the vessel wall as the catheter is passed to and from the lesion. This process, which is referred to as atherotomy, allows for dilation of the target coronary lesion with less pressure and precise incision into the plaque and causes less injury than is exerted by a traditional angioplasty balloon. Experience from the coronary literature suggests that the CB is superior to conventional balloon angioplasty for the treatment of certain coronary artery atherosclerotic lesions and for in-stent stenosis.^6–8 Several reports have shown a superior initial result and less recurrence both for de novo and recurrent lesions with use of the CB.^9.10 It is presumed that the incisions made by the CB cause less trauma to the vessel wall during dilation as well as decreased recoil of fibrotic plaque. On the basis of these observations, we postulated that the CB might be a superior option compared with conventional balloon angioplasty for carotid in-stent stenosis. In this report, we present our initial experience with this balloon in three patients. To our knowledge, this is the first use of the CB for this indication. Case Report Patient #1. A 64-year-old man with a medical history significant for renal calculi and viral cardiomyopathy and a surgical history significant for a right CEA presented in October 2000 with amaurosis fugax of the left eye. Angiography revealed severe left ICA stenosis. He was enrolled in the Carotid Endarterectomy versus Stenting Trial (CREST)^11,12 and was randomized to undergo angioplasty and stenting in December 2000. A 3.5 cm x 40 mm Savvy balloon (Cordis Corporation, Miami Lakes, Florida) was used for predilation of the stenotic lesion. A 6 mm x 30 mm Acculink stent (Guidant Corporation, Temecula, California) was successfully deployed. Post-stenting angioplasty was performed with a 4 mm x 20 mm Savvy balloon. An excellent result was achieved. He did well until January of 2002, when he experienced a recurrent episode of left-sided amaurosis fugax. Carotid Doppler testing was suggestive of restenosis of the left ICA. Angiography confirmed severe 80–85% left carotid in-stent stenosis (Figures 2A and 2B). He was placed on clopidogrel 75 mg daily and angioplasty was recommended because of the severity of the stenosis. After positioning a 7 French (Fr) armored sheath (Arrow International, Reading, Pennsylvania) in the left common carotid artery, we navigated a 4 mm Accunet distal protection system (Guidant Corporation) into the distal left cervical ICA. We then advanced a 3.5 mm x 10 mm CB over the Accunet wire into the left common carotid artery. After deploying the balloon over the distal portion of the stent, we inflated the balloon for 90 seconds to 8 atmospheres (atm) of pressure. The balloon was held at this pressure for 5 minutes. The angioplasty resulted in resolution of the distal portion of the stenosis within the stent (Figure 2C). We then positioned the balloon over the more proximal portion of the stenosis within the stent and inflated the balloon to 8 atm for 5 minutes. The balloon was then deflated and withdrawn. Post-angioplasty angiography showed an excellent immediate result (Figures 2D and 2E). There were no complications or neurological deficits associated with the procedure. The patient was discharged home the following day in excellent condition. Patient #2. A 39-year-old man with a history of right-sided neck radiation in 1970 presented in June 1997 with an episode of right-sided amaurosis fugax. He was found to have a radiation-induced stenosis in his right ICA and had Wallstent (Boston Scientific/Scimed, Inc., Maple Grove, Minnesota) placement. He had no further symptoms, but had progressive narrowing of the stent over the next 2 years on the basis of ultrasound examination. Repeat balloon angioplasties were performed in November 1999 and June 2000 for significant in-stent stenosis at the proximal margin of the previously placed Wallstent with good angiographic results. A routine carotid Doppler ultrasound study in January 2002, however, suggested a high-grade recurrent stenosis of the right ICA. Angiography confirmed the presence of a severe, right carotid in-stent stenosis (90% stenosis) at the proximal stent margin (Figure 3A). He was placed on clopidogrel 75 mg daily and aspirin 325 mg daily, and angioplasty was recommended because of the severity of the stenosis. After positioning a 6 Fr Shuttle-SL sheath (Cook Incorporated, Bloomington, Indiana) in the right common carotid artery, we advanced a 0.014´´ PercuSurge Guardwire (Medtronic AVE, Santa Rosa, California) into the distal right common carotid artery. Following inflation of the occlusion balloon, an angiogram was obtained to verify that the right ICA was occluded. We then advanced a 4.0 mm x 15 mm CB over the Guardwire into the ICA. After positioning the balloon over the proximal margin of the in-stent stenotic lesion, we inflated the balloon for 10 seconds to 12 atm of pressure (Figure 3B). The CB was then deflated and withdrawn. The angioplasty resulted in resolution of the stenosis, but there was evidence of recoil at the proximal end of the Wallstent. A 6 Fr, 10 x 20 mm Precise stent (Cordis Corporation) was then advanced and successfully deployed into position across the proximal margin of the previous stent. The Precise stent was post-dilated using a 5.5 mm x 20 mm Gazelle angioplasty balloon catheter (Boston Scientific Medi-Tech, Natick, Massachusetts) at 18 atm for 10 seconds. After removal of the balloon catheter, an aspiration catheter (Export, PercuSurge, Medtronic AVE) was introduced over the Guardwire for aspiration of the embolic material. After complete aspiration, the PercuSurge balloon was deflated and withdrawn. Post-angioplasty angiography showed an excellent immediate result (Figure 3C). The patient had an uncomplicated procedure and was discharged the same day. Patient #3. A 50-year-old woman presented with a 1-month history of right facial and upper extremity numbness associated with vague symptoms in the left lip area. The patient also complained of “swishing” sounds behind both ears. She experienced an ipsilateral cerebrovascular accident 2 years earlier, which resulted in mild residual speech difficulty and a minimal decrease in memory. Her past medical history was significant for hypertension and left parotid gland carcinoma for which she underwent a left parotidectomy with chemotherapy and local radiation. The patient continued to smoke one pack of cigarettes per day. Carotid duplex ultrasound imaging obtained at the time of her initial evaluation demonstrated total occlusion of the left ICA and 40–60% narrowing of the right ICA. Carotid angiography demonstrated 75% stenosis (Figure 4A) several centimeters from the origin of the right ICA. After informed consent had been obtained, the patient was enrolled in the Stenting and Angioplasty with Protection in Patients at High-risk for Endarterectomy (SAPPHIRE) trial and underwent successful placement of a 6 x 20 mm Precise stent (Cordis Corporation). The stent was dilated post-implantation using a 5 mm angioplasty balloon, and an excellent angiographic result was achieved (Figure 4B). The patient’s post-procedural course was uneventful, and she was maintained on clopidogrel 75 mg daily and aspirin 81 mg daily for 30 days, with subsequent aspirin therapy alone. She had total resolution of her intermittent recurrent symptoms until 12 months following therapy, at which time she developed recurrence of similar symptoms. Duplex evaluation demonstrated a progressive increase in velocities, suggesting in-stent stenosis in the 60–80% range. On the basis of her reliable history and the carotid duplex findings, the patient underwent diagnostic angiography, where in-stent stenosis with 68% luminal reduction was identified (Figure 4C). She was again placed on clopidogrel, and we elected to proceed with an endovascular solution because of the clinical and angiographic findings. Because of the short length of the lesion and the potential for balloon movement during inflation (“watermelon seeding”), we decided to use a CB. A 7 Fr Shuttle Sheath (Cook Corporation) was placed in the right ICA without difficulty. An Angioguard distal protection device (Cordis Corporation) was used to cross the lesion and placed high in the ICA. A 4.0 x 15 mm CB was placed over the Angioguard wire into the area of in-stent stenosis without difficulty, with balloon inflation (Figure 4D) for 60 seconds at 8 atm of pressure. The balloon was then deflated, rotated minimally, and re-inflated at similar pressures and duration. The inflations totally covered the length of the lesion as well as that of the stent, without the need for subsequent dilation or extension of the balloon outside the stented area. The CB was then deflated and withdrawn. Completion angiography (Figure 4E) demonstrated an excellent immediate result, with no evidence of a residual stenotic lesion. A neurological evaluation performed after the procedure demonstrated no significant change in the patient’s neurological status. Findings on carotid duplex imaging were within normal limits. Discussion Incidence of in-stent stenosis. In an analysis of survey data involving 2,048 patients from multiple centers,² the incidence of in-stent stenosis 6 months after carotid angioplasty and stenting was found to be 4.8%. In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS),¹³ a randomized trial in which surgical and endovascular treatment of carotid stenosis were compared, severe (70–99%) restenosis was seen in 14% of patients who were treated by endovascular methods. Of note, only 26% of the patients who underwent endovascular treatment received a stent (74% received balloon angioplasty alone). Some evidence suggests that the rate of in-stent stenosis after angioplasty and stent placement might be as low as 2%.¹⁴ Most authors define restenosis as >= 50% narrowing of the artery lumen that is found on follow-up angiography and is not observed after the initial treatment.¹⁵ Indications for treatment, however, are not clearly defined. Chakhtoura et al.⁴ used 80% restenosis as a cut-off for treatment. In the coronary circulation, the use of multiple stents, diabetes mellitus and a smaller final luminal diameter have been strongly associated with the risk of in-stent stenosis.¹⁶ In the peripheral circulation, restenosis has been associated with tobacco use, small vessel size and the use of multiple stents.¹⁷ Pathophysiology. The pathophysiology of carotid in-stent stenosis can be inferred from what has been learned about carotid restenosis after CEA, as well as what has been learned about coronary and peripheral vascular in-stent restenosis. Because of the longer track record of CEA, restenosis has been better characterized after this operation than after angioplasty and stenting. Restenosis occurring within the first 2 years after CEA has been attributed to intimal hyperplasia. Recurrent atherosclerosis is believed to be the culprit for restenosis that occurs in later years.¹⁸ By analogy, we assume that in-stent stenosis developing within the first 2 years is caused by intimal hyperplasia. In a review by Dangas and Fuster,¹⁹ the pathophysiology of coronary in-stent stenosis in vessels was divided into 3 phases: early elastic recoil (first day); formation and organization of mural thrombus (first 2 weeks); and neointimal proliferation (first 3 months). Elastic recoil is believed to be a mechanical phenomenon. Mural thrombus formation is thought to be related to tissue injury, such as endothelial denudation. Several studies have associated coronary angioplasty with neutrophil activation.^20–22 Activated neutrophils then release a number of inflammatory mediators, which can aggravate endothelial damage and stimulate platelet aggregation.⁸ Organization of the mural thrombus involves smooth muscle proliferation and extracellular matrix deposition.²³ This process leads to neointimal hyperplasia.^8,19 The net result is a firm fibrous tissue build-up within the stent. This process is believed to result from the traumatic effects of angioplasty. The tissue reaction is probably proportional to the amount of injury. Natural history. Given the paucity of long-term follow-up data regarding carotid in-stent stenosis, data must be inferred once again from the endarterectomy, coronary and peripheral vascular literature for the time being. Severe recurrent stenosis after CEA has been associated with carotid occlusion and stroke.²⁴ After a thorough review and rigorous statistical analysis of the literature, Frericks et al.¹⁸ concluded that restenosis after CEA is associated with risk for ipsilateral stroke (odds ratio, 2). Smoking has been associated with risk for restenosis after CEA.²⁵ Although the natural history of in-stent stenosis in the carotid artery is not well defined, the CEA experience indicates that treatment should be considered for high-grade and symptomatic restenotic lesions. Similarly, myocardial ischemic complications have been associated with coronary restenosis.^26,27 Balloon angioplasty of intimal hyperplasia after CEA has been associated with recurrence that is felt to be caused by recoil of the fibrotic lesion.²⁸ In-stent stenosis is probably vulnerable to the same recurrence risk. The Cutting balloon. Several well-documented observations in the coronary literature led us to believe that the CB would be a better option than traditional balloon angioplasty for carotid in-stent stenosis. In the Cutting Balloon Global Randomized Trial and the Cutting Balloon vs. Conventional Angioplasty (CUBA) study, angioplasty with conventional and Cutting Balloons was compared for treatment of de novo native coronary artery stenosis.^29,30 Use of the CB was associated with statistically lower restenosis rates in both studies. Lower restenosis rates using the CB have also been established for vessels less than 3 mm, when compared with conventional balloon angioplasty.⁷ Relatively greater enlargement of the lumen has been found after CB angioplasty than after conventional balloon angioplasty.¹⁰ In an intravascular ultrasound study comparing both methods of angioplasty, restenosis was significantly less with the CB than conventional balloons.³¹ Less clinically significant dissections have been observed with use of CB angioplasty.³⁰ The CB has recently been studied in the treatment of coronary in-stent stenosis and was found to be superior to rotational atherectomy and additional stenting during the same procedure.⁶ Several recent reports have confirmed the superiority of CB angioplasty in treating coronary in-stent stenosis.^9,32 The authors of these studies theorize that the decreased trauma associated with the CB is associated with less recurrence. It is believed that microsurgical incisions made by this balloon in the plaque reduce the extent of injury in the vessel wall induced by balloon dilation. The precise incisions are also believed to reduce the elastic recoil that can be seen with fibrotic lesions.⁵ A recent study by Inoue et al.⁸ suggests that the CB induces less neutrophil activation than traditional balloon angioplasty. Use of this balloon has also been reported for the treatment of renal artery in-stent restenosis.³³ In patients #1 and #3, an excellent result was achieved by use of the CB alone. In patient #2, some recoil did occur in the proximal stent, which prompted the placement of a second stent. It is unclear whether the use of a traditional angioplasty balloon or a second, longer inflation of the CB would have obviated the need for an additional stent in this patient. We speculate that the same or worse recoil would have been seen with use of a traditional balloon. It is possible that a second inflation of the CB may have obviated the need for a stent. The duration of balloon inflation varied among the 3 patients according to local practice patterns and patient tolerance of the inflation period. It is unclear whether a short (several seconds) or long (several minute) inflation should be used. Conclusion Successful results achieved with the use of CB angioplasty to treat coronary in-stent stenosis led us to consider changing our strategy for treating carotid in-stent stenosis. In patients #1 and #3, an excellent angioplasty result was achieved with the CB alone. Even though an additional stent was needed in patient #2, excellent angiographic and clinical results were achieved. This report demonstrates the safety and feasibility of the CB for the treatment of carotid in-stent stenosis. Larger studies are needed to further examine the role of this balloon for this indication. Acknowledgments. We thank Ricardo A. Hanel, MD, for assistance with the review of the literature and Paul H. Dressel for preparation of the illustrations. The authors have the following financial relationships to disclose: Dr. Bendok and Dr. Boulos receive funding from the AANS/CNS Joint Section on Cerebrovascular Surgery Mullan Neuroendovascular Surgery Award. Dr. Guterman is a Consultant for Guidant Corporation. Dr. Hopkins receives research support from and is a consultant for Boston Scientific, Cordis, Guidant, and Medtronic; in addition, he has a financial interest in Boston Scientific. Dr. Katzen has received educational grants from Cordis and Boston Scientific.

1. Bettmann MA, Katzen BT, Whisnant J, et al. Carotid stenting and angioplasty: A statement for healthcare professionals from the Councils on Cardiovascular Radiology, Stroke, Cardiothoracic, and Vascular Surgery, Epidemiology and Prevention, and Clinical Cardiology. American Heart Association. Stroke 1998;29:336–338. 2. Wholey MH, Wholey M, Bergeron P, et al. Current global status of carotid artery stent placement. Cathet Cardiovasc Diagn 1998;44:1–6. 3. Mintz GS, Popma JJ, Hong MK, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78:18–22. 4. Chakhtoura EY, Hobson RW II, Goldstein J, et al. In-stent restenosis after carotid angioplasty stenting: Incidence and management. J Vasc Surg 2001;33:220–226. 5. Lary BG. Coronary artery incision and dilation. Arch Surg 1980;115:1478–1480. 6. Adamian M, Colombo A, Briguori C, et al. Cutting balloon angioplasty for the treatment of in-stent restenosis: A matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty. J Am Coll Cardiol 2001;38:672–679. 7. Ergene O, Seyithanoglu BY, Tastan A, et al. Comparison of angiographic and clinical outcome after cutting balloon and conventional balloon angioplasty in vessels smaller than 3 mm in diameter: A randomized trial. J Invas Cardiol 1998;10:70–75. 8. Inoue T, Sakai Y, Hoshi K, et al. Lower expression of neutrophil adhesion molecule indicates less vessel wall injury and might explain lower restenosis rate after cutting balloon angioplasty. Circulation 1998;97:2511–2518. 9. Abizaid AS, Abizaid A, Assad A, et al. Cutting balloon versus balloon alone for treatment of in-stent restenosis: An intravascular ultrasound study (Abstr 1070-12). J Am Coll Cardiol 2001;37(Suppl A):10A. 10. Muramatsu T, Reiko T, Mami H, et al. Efficacy of cutting balloon angioplasty for lesions at the ostium of the coronary arteries. J Invas Cardiol 1999;11:201–206. 11. Hobson RW II. Randomized clinical trials: What can we expect? J Vasc Surg 1991;13:539–543. 12. Hobson RW II. CREST (Carotid Revascularization Endarterectomy versus Stent Trial): Background, design and current status. Semin Vasc Surg 2000;13:139–143. 13. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): A randomized trial. Lancet 2001;357:1729–1737. 14. Shawl F, Kadro W, Domanski MJ, et al. Safety and efficacy of elective carotid artery stenting in high-risk patients. J Am Coll Cardiol 2000;35:1721–1728. 15. Yadav JS, Roubin GS, Iyer S, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:376–381. 16. Kastrati A, Schomig A, Elezi S, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30:1428–1436. 17. Sapoval MR, Chatellier G, Long AL, et al. Self-expandable stents for the treatment of iliac artery obstructive lesions: Long-term success and prognostic factors. Am J Roentgenol 1996;166:1173–1179. 18. Frericks H, Kievit J, van Baalen JM, van Bockel JH. Carotid recurrent stenosis and risk of ipsilateral stroke: A systematic review of the literature. Stroke 1998;29:244–250. 19. Dangas G, Fuster V. Management of restenosis after coronary intervention. Am Heart J 1996;132:428–436. 20. De Servi S, Mazzone A, Ricevuti G, et al. Granulocyte activation after coronary angioplasty in humans. Circulation 1990;82:140–146. 21. Ikeda H, Nakayama H, Oda T, et al. Neutrophil activation after percutaneous transluminal coronary angioplasty. Am Heart J 1994;128:1091–1098. 22. Ricevuti G, Mazzone A, Pasotti D, et al. Role of granulocytes in endothelial injury in coronary heart disease in humans. Atherosclerosis 1991;91:1–14. 23. Kearney M, Pieczek A, Haley L, et al. Histopathology of in-stent restenosis in patients with peripheral artery disease. Circulation 1997;95:1998–2002. 24. Carballo RE, Towne JB, Seabrook GR, et al. An outcome analysis of carotid endarterectomy: The incidence and natural history of recurrent stenosis. J Vasc Surg 1996;23:749–754. 25. Ricotta JJ, O’Brien-Irr MS. Conservative management of residual and recurrent lesions after carotid endarterectomy: Long-term results. J Vasc Surg 1997;26:963–972. 26. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994;331:496–501. 27. Rodes-Cabau J, Candell-Riera J, Domingo E, et al. Frequency and clinical significance of myocardial ischemia detected early after coronary stent implantation. J Nucl Med 2001;42:1768–1772. 28. Lanzino G, Mericle RA, Lopes DK, et al. Percutaneous transluminal angioplasty and stent placement for recurrent carotid artery stenosis. J Neurosurg 1999;90:688–694. 29. Bassand J-PL, Weiner BH, McFadden EP, et al. Efficacy and safety of cutting balloon in small coronary arteries