Secondary recurrent carotid stenosis David Rosenthal, M D , Joseph P. Archie, Jr., M D , Mario H . Avila, M D , Dennis F. Bandyk, M D , J. D o n a l d Carmichael, M D , G. Patrick Clagett, M D , Jack L. H a m m a n , M D , H y u n g M. Lee, ME), Patti R. Liebman, M D , Joseph L. Mills, M D , Stanley L. Minken, M D , Georgia W. Plonk, M D , Marc P. Posner, M D , R o b e r t B. Smith III, M D , and S. T i m o t h y String, M D ,
Atlanta, Ga.; Raleigh and Winston-Salem, N.C.; Tamarac, Tampa, and West Palm Beach, Fla.; Birmingham and Mobile, Ala.; Dallas, Tex.; Madisonville, Ky.; Richmond, Va.; and Baltimore, Md. Purpose: Recurrent carotid stenosis after carotid endarterectomy has been extensively reported. The occurrence, however, of another ipsilateral restenosis that requires a third carotid operation is rare. The purpose of this study was to evaluate possible risk factors and the most efficacious management of the patient with "secondary" recurrent carotid stenosis. Methods:A survey of the Southern Association for Vascular Surgery was performed, and 31 patients who had had surgery for secondary recurrent carotid stenosis were identified. Results: The mean interval between the recurrent stenosis operation and secondary recurrent carotid stenosis was 39.8 months (range, 9 to 83 months). At the third operation, 21 patients underwent carotid patch angioplasty and 10 underwent carotid resection with an interposition saphenous vein graft. No postoperative strokes or deaths occurred; three patients (10%) had a peripheral nerve injury. Nine early (<24 mo) secondary recurrent carotid stenoses occurred, and these patients underwent patch angioplasty. Twenty-three female, cigarette-smoking patients and 20 patients with elevated lipid levels had early restenosis and were identified as being at high risk for the development of another stenosis. A fourth significant stenosis developed in five of these high-risk patients who had saphenous vein patch angioplasty at their third carotid operation; eight other high-risk patients had carotid resection with an interposition saphenous vein graft, and no other stenosis developed. Conclusion: Patients who have secondary recurrent carotid stenoses can safely undergo a third carotid operation. Female habitual smokers with elevated lipid levels and an early restenosis appear to be at high risk of secondary recurrent carotid stenoses. When surgery is necessary, carotid resection with an interposition saphenous vein graft appears more durable than patch angioplasty. (J Vasc Surg 1996;24:424-9.)
The true incidence o f recurrent carotid stenosis after carotid endarterectomy (CEA) is unlmown, but symptomatic recurrent carotid stenosis has been reported to range from 0.6% to 3.6% 1'2 and asymptomatic recurrent stenosis, based on noninvasive studies, from 8.8% to 19%. 3-5 The occurrence o f another ipsilateral recurrent stenosis that requires a third carotid operation is rare, From the DepartmentofVascularSurgery,GeorgiaBaptistMedical Center, Medical College of Georgia. Presented at the Twentieth Annual Meeting of The Southern Associationfor VascularSurgery,Naples,Fla., Jan. 24-27, 1996. Reprint requests: David Rosenthal, MD, 315 Boulevard N.E., Suite 412, Atlanta, GA 30312. Copyright © 1996 by The Society for Vascular Surgery and International Societyfor CardiovascularSurgery,North American Chapter. 0741-5214/96/85.00 +0 24/6/74806 424
but the incidence o f "secondary" recurrent carotid stenosis (SRCS) will likely increase with the widespread use o f serial ultrasound surveillance examinations after carotid operations. The purpose o f this study, which has not been previously reported, was to evaluate the possible risk factors and most appropriate operative management of the patient who has an SRCS. MATERIALS AND METHODS A survey o f the Southern Association for Vascular Surgery membership was performed, and 15 surgeons (Joseph P. Archie, Jr., Raleigh, N.C.; Mario H. Avila, Tamarac, Fla.; Dennis E. Bandyk, Tampa, Fla.; J. Donald Carmichael, Birmingham, Ala.; G. Patrick Clagett, Dallas, Tex.; Jack L. Hamman, Madisonville,
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Table II. Operative procedures
Table I. Risk factors
Interval between operations (mo) Age (yr) Abnormal lipid profiles Female Coronary disease Hypertension Diabetes rnellitus Smoking
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Recurrent carotid stenosis
Secondary recurrent carotid stenosis
73,1 59.9 20 (64%) 23 (74%) 14 (45%) 10 (32%) 6 (19%) 19 (61%)
39.8 64.5 20 (64%) 23 (74%) 17 (55%) 13 (42%) 8 (26%) 23 (74%)
Ky.; Hyung M. Lee, Richmond,Va.; Paul R. Liebman, West Palm Beach, Fla.; Joseph L. Mills, Tampa, Fla.; Stanley L. Minken, Baltimore, Md.; Georgia W. Plonk, Winston-Salem, N.C.; Marc P. Posner, Richmond, Va.; David Rosenthal, Atlanta, Ga.; Robert B. Smith, III, Atlanta, Ga.; and S. Timothy String, Mobile, Ala.) identified 31 patients who had undergone operations for SRCS. After the initial CEA, the mean interval until a recurrent carotid stenosis developed was 73.1 months (range, 11 to 168 months); five recurred within 24 months. The patients' mean age at the second carotid operation was 59.9 years (range, 44 to 73 years). The risk-facto.r characteristics with regard to lipid profile, gender, coronary artery heart disease, hypertension, diabetes mellitus, and smoldng are listed in Table I. Indications for second operation included hemispheric transient ischemic attacks (TIAs) in 14 patients, asymptomatic arteriographic high-grade stenosis (,>75% reduction in diameter of the carotid artery at the point of maximal stenosis compared with the diameter of normal artery) in five patients, amaurosis fugax in four patients, vertebrobasilar insufficiency symptoms in three patients, reversible ischemic neurologic deficit in three patients, and cerebrovascular accident in two patients. At the second operation, 11 patients underwent repeat CEA and patch angioplasty (five with saphenous vein, four with Dacron, two with polytetrafluoroethylene [PTFE]), whereas 19 patients underwent carotid patch angioplasty alone (12 with saphenous vein, four with Dacron, three with PTFE) and one patient underwent carotid resection with an interposition saphenous vein graft (Table II). No strokes or deaths occurred after operation; however, one patient had a TIA that resolved uneventfully and two patients sustained cranial nerve injuries (Table III). All patients were given aspirin after surgery. The mean interval between the recurrent stenosis
Operation (n = 31)
Recurrent carotid stenosis (second operation)
Secondary recurrent carotid stenosis (third operation)
"Repeat" CEA with patch angioplasty Patch angioplasty alone Carotid resection/interposition graft
11 19 1
operation and SRCS was 39.8 months (range, 9 to 83 months). In nine patients SRCS occurred within 24 months of the second operation. The mean age at the third operation was 64.5 years (range, 45 to 76 years). The risk-factor characteristics are listed in Table I. Indications for a third operation included amaurosis fugax in 13 patients, asymptomatic arteriographic high-grade stenosis (>75%) in 11 patients, hemispheric TIAs in six patients, and a stroke in one patient. All patients underwent an arteriographic examination to confirm the diagnosis of SRCS and to determine the degree ofstenosis. After operation for SRCS, all patients continued a regimen of aspirin, and all patients had follow-up duplex examinations. These patients were considered at high risk for the development of another recurrent stenosis and underwent carotid duplex ultrasonography surveillance on average 6.8 times per patient between their recurrent stenosis operation and SRCS. Statistical analysis was performed by the life-table method where appropriate. Because patient selection was not randomized, any statistical conclusions must be guarded. RESULTS Thirty-one patients underwent operations for SRCS. At the third operation, 21 patients underwent carotid patch angioplasty (16 with saphenous vein, three with Dacron, two with PTFE) and 10 underwent carotid resection with interposition saphenous vein grafts (Table II). No postoperative strokes or deaths occurred; however, three patients (10%) had traction cranial nerve injuries (two vagal, one hypoglossal) that resolved uneventfully (Table III). Of these 31 patients, 23 were female habitual cigarette smokers, and 20 had elevated serum lipid levels. With this risk-factor profile such patients were considered to be at high risk for the development of another recurrent stenosis (Table IV). These 23 patients underwent carotid patch angioplasty (15) or carotid resection with an interposition saphenous vein graft (8) at the third operation. None of these
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Table IV. High-risk patient/operation
Table I l L Operative results Recurrent carotid stenosis
Secondary recurrent carotid stenosis
Cerebrovascular accident Death
Postoperative complication (n = 31)
Cranial nerve injury
Third operation (n = 23)
Fourth carotid stenosis
Fourth operation (n = 4)
Carotid/resection SV graft
Carotid patch Angioplasty None
PTFE (2) Carotid resection/SV graft (8)
SV, Saphenous vein.
high-risk patients who had carotid resection with an interposition saphenous vein graft at the third operation had another recurrent stenosis. However, five of the patients who had carotid patch angioplasty at the third operation (four with saphenous vein, one with Dacron) had another recurrent stenosis (>75% diameter) documented by carotid ultrasonography. Four patients in this subgroup ultimately underwent carotid resection with a saphenous vein interposition graft (three for a symptomatic high-grade stenosis, one for TIAs), and the fifth patient refused operation despite TIA symptoms. The four carotid resection patients have had serial ultrasonography surveillance; no recurrent stenosis developed in follow-up extending to 30 months. Eight male patients with SRCS had either elevated lipid levels or were smokers, but not both risk factors together. None of these male patients had another recurrent stenosis. It was of interest to note that the mean interval between the recurrent carotid stenosis and the SRCS (39.8 months) was approximately half the interval between the initial CEA and development of a recurrent carotid stenosis (mean, 73.1 months). Nine of the SRCSs occurred within 24 months of the second carotid operation and were believed to be caused by myointimal hyperplasia. In seven of these patients, the SRCS was noted to have occurred at the previous repeat CEA or patch graft angioplasty site. The indications for operation among these nine early restenotic patients were asymptomatic stenosis >75% in 7 patients, amaurosis fugax in one, and stroke in one. These nine patients underwent carotid patch angioplasty at the third operation (six with saphenous vein, two with Dacron, one with PTFE). Four of these patients who had patch angioplasty for early restenosis had a fourth stenosis; all four patients were in the high-risk category (female, habitual cigarette smoking, elevated lipid levels). Twenty-two other patients had surgery for SRCS 24 months or later. In 17 of these patients the SRCS was noted to occur primarily at the proximal and distal repeat CEA or patch graft angioplasty sites. The indications for operation in
these patients were morc consistent with recurrent atherosclerotic embolic-type symptoms, which included amaurosis fugax in I2 patients, hemispheric TIAs in six, and asymptomatic high-grade stenosis in four. After these 22 operations (10 carotid resections with saphenous vein interposition grafts; 10 saphenous vein, one Dacron, and one PTFE patch angioplasties), only one patient who underwent a saphenous vein patch angioplasty had a fourth stenosis. During follow-up (mean, 40.4 months; range, 1 to 96 months) after surgery for SRCS, one patient had an ipsilateral stroke. This patient had undergone carotid resection with a saphenous vein interposition graft 31 months earlier. Arteriography demonstrated a patent bypass graft; however, proximal common carotid ulcerated occlusive disease was identified. The patient refused another operation. Five deaths occurred during follow-up, none related to stroke (Fig. 1). DISCUSSION
Many previous publications have dealt with the symptoms, pathologic condition, and operative results associated with recurrent carotid stenosis after CEA. To our knowledge, however, no publication has solely addressed the rare occurrence of another ipsilateral recurrent stenosis that required a third operation. The cause of SRCS is unknown, but like recurrent carotid stenosis, it may be related to local factors, systemic factors, or both. At the time of the operation for recurrent carotid stenosis, local factors include repeat CEA, which may create foci for SRCS as a result of damp trauma, residual plaque, or intimal flaps at the repeat CEA site. When repeat CEAis not possible, carotid patch angioplasty has been advocated by several authors, 6-s especially for myointimal hyperplasia where an endarterectomy plane cannot be established. After carotid patch angioplasty, however; local geometry changes in the configuration of the artery
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Rosenthal et al.
Months Fig. 1. Survival and stroke-free interval after operation for SRCS. can occur, which may lead to altered hemodynamics with laminated thrombus formation and, ultimately, an SRCS. In this study 21 patients underwent carotid patch angioplasty alone at the third operation, and a fourth carotid stenosis developed in five of these patients. 'This finding would suggest that carotid patch angioplasty may be an inadequate operation for patients who have SRCS. Carotid resection with the placement of an interposition graft is another surgical option. This option historically has been reserved for those patients in whom repeat CEA or patch angioplasty is not possible either because the luminal surface is too diseased or the arterM wall is too scarred or thin. Treiman et al. 9 demonstrated that carotid resection with saphenous vein interposition graft placement is as safe and effective as repeat CEA with patch angioplasty and should be used when repeat CEA cannot be performed. Sise et al.10 advocated the use of PTFE interposition grafts for carotid reconstruction; however, one third of patients who underwent carotid resection and interposition PTFE grafting procedures for recurrent carotid stenosis had an SRCS. Ten patients in this study underwent carotid resection with an interposition saphenous vein graft at the third operation, and none had another stenosis. Raithel, 1~ however, reported a series of 43 patients who underwent PTFE interposition grafting procedures for recurrent carotid stenosis; an SRCS did not develop in any of these patients. Contradictory data have been presented that define systemic risk factors, but female gender, continued cigarette smoking after CEA, young age at the
time of initial presentation, hyperlipidemia, hypertension, and diabetes have all been implicated321s It was of interest to note that all patients in this series who had SRCS also had at least three of these risk factors, with female gender (74%), continued cigarette smoking (74%), and abnormal lipid profiles (64%) being the most common (Table I). It has been generally accepted that myointimal hyperplasia is responsible for early (<24 mo) recurrent carotid stenosis, whereas late recurrent carotid stenosis is generally atherosclerotic in nature. SRCS caused by myointimal hyperplasia usually involves the entire arterial wall in exuberant scar. It was noted that when early SRCS occurred it was located at the endarterectomy site, whereas late SRCS was more pronounced at the proximal and distal endarterectomy endpoints. Symptomatically, patients who had early SRCS "behaved" differently than patients with late SRCS. For example, only two patients who had early SRCS also had embolic type symptoms (one with amaurosis fugax, one with stroke), compared with 18 late SRCS patients (12 with amaurosis fugax, 6 with TIAs), which may be explained on the basis of arterial morphologic characteristics. Bernstein et al. 16 theorized that the myointimal coveting of an early recurrent stenotic artery may inhibit the subsequent development of progressive atherosclerosis, with degenerative change and, ultimately, embolization. Although it is difficult to draw definitive conclusions about the necessity for operation in these patients, asymptomatic patients who have an early SRCS may not warrant another operation as they may be protected against future embolic events. Operation in such patients may
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Rosenthal et al.
only be necessary if symptoms occur, but this remains to be proved. I n this study, 21 patients u n d e r w e n t carotid patch angioplasty and 10 u n d e r w e n t carotid resection with interposition saphenous vein graft at the third operation. M t h o u g h these operations were safe (no postoperative strokes or deaths) and durable (one late stroke caused by progression o f proximal carotid artery disease), a fourth stenosis developed in five female cigarette-smoking patients with elevated lipid levels in w h o m an early SRCS had developed and w h o had carotid patch angioplasty at their third operation (Table IV). W o m e n , in general, appear to be at higher risk for the development o f myointimal hyperplasia after carotid operations. Ten H o l t e r et al.17 reported a 14% recurrent stenosis rate in w o m e n c o m p a r e d with a 9% rate in m e n during the first year after CEA; after the first year, however, the recurrent stenosis rates were equivalent. Thus the female patient w h o has an early SRCS with the additional risk factors o f continued cigarette smoking and abnormal lipid profile appears to be at very high risk to have another recurrent stenosis. I n this difficult subset o f patients, caution is warranted in r e c o m m e n d i n g prophylactic operation for an asymptomatic stenosis. W h e n operation is necessary, however, carotid resection with an interposition saphenous vein graft appears m o r e durable than patch angioplasty. Risk-factor modification may ultimately be the m o s t effective means o f preventing SRCS, but this possible solution requires further investigation.
5. 6. 7.
10. 1 i.
12. 13. 14. 15. 16.
1. CallowAD. Recurrent stenosis after carotid endarterectomy. Arch Surg 1982;117:1082-5. 2. Cossman DV, Callow AD, Stein A, et al. Early restenosis after carotid endarterectomy. Arch Surg 1978;113:275-8. 3. Turnipseed WD, Berkoff HA, Crummy A. Postoperative occlusion after carotid endarterectomy. Arch Surg 1980;115: 573-4. 4. Zierler RE, Bandy KDF, Thiele BL, Strandness DE Jr. Carotid
artery stenosis following endarterectomy. Arch Surg 1982; 117:408-15. Roederer CO, LangloisYE, Jagar KA, et al. The natural history of carotid artery disease in asymptomatic patients with cervical bruits. Stroke 1984;15:605-I3. Bartlett FF, Rapp JH, Goldstone J, Ehrenfeld WK, Stoney RJ. Recurrent carotid stenosis: operative strategy and late results. J Vasc Surg 1987;5:452-6. Rosenthal D, Archie IP Jr, Garcia-Rinaldi R, Seagraves MA, Baird DR, McKinsey JF, et al. Carotid patch angioplasty: immediate and long-term results. J Vasc Surg 1990;12:32633. Das MB, Hertzer NR, RatliffNB. Recurrent carotid stenosis: five-year series of 65 reoperations. Ann Surg 1985;28:202-7. Treiman GS, Jenkins JM, Edwards WH St, BatlowW, Edwards WH Jr, Martin KS III, Mulherin JL Jr. The evolving surgical management of recurrent carotid stenosis. J Vasc Surg 1992; 16:354-63. Sise MJ, Ivy ME, Malanche R, Ranbarger KR. Polytetrafluoroethylene interposition grafts for carotid reconstruction. J Vasc Surg 1992;16:101-8. Raithel D. Choice of graft material in carotid surgery: Vein vs PTFE. In: Veith FJ, editor. Current critical problems in vascular surgery. New York: Quality Medical Publishing, Inc., 1994:259-63. Salvian A, Baker JD, Mechleder HI, et al. Cause and noninvasivedetection ofrestenosis after carotid endarterectomy. Am J Surg 1988;146:29-34. Ouriel K, Green RM. Clinical and technical factors influencing recurrent carotid stenosis and occlusion after endarterectomy. J Vasc Surg 1987;5:702-6. Rapp JH, Ovarfordt P, Krupski WC, et al. Hypercholesterolemia and early restenosis after carotid endarterectomy. Surgery i987;101:277-88. Clagett GP, Rich NM, McDonald DT, et al. Etiologic factors for recurrent carotid artery stenosis. Surgery 1983;93:313-8. Bernstein EF, Torem S, Dilley IL Does carotid restenosis predict an increased risk of late symptoms, stroke, or death? Ann Surg 1990;212:629-36. Ten Holter JBM, Ackerstaff RGA, Thoe-Schwartcenberg GWS, et al. The impact of vein patch angioplastyon long-term surgical outcome after carotid endarterectomy. J Cardiovasc Surg i990;31:58-65.
Submitted Jan. 31, 1996; accepted May 10, 1996.
Dr. Williams H. Edwards, St. (Nashville, Tenn.). I appreciate the opportunity to discuss this paper on "secondary" recurrent carotid stenosis. I congratulate Dr. Rosenthal on putting together this group of patients. It is difficult to direct questions to the shepherd who has assembled such a heterogenous group of sheep. Dr. Rosenthal has covered the salient features and has pointed out the dangers of drawing statistical conclusions from this heterogeneous group of patients. The first report that described symptomatic recurrent carotid stenosis after CEA was written by Sterling Edwards
in 1968. He reported in 1987 a study that was carried out to evaluate techniques to widen the carotid bifurcation with autologous material to determine whether the incidence of recurrent stenosis could be reduced. The total number of patients he studied was small, and follow-up with ultrasonography was fairly short. He found, however, that there was no difference in recurrent significant stenosis, the range being 12% to 16%. Many reports of recurrent symptomatic carotid stenosis have tried to incriminate the usual risk factors--hyperlipidemia, hypertension, smoking, small internal carotid ar-
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tery, female gender--as being the primary causes for recurrence. In Dr. Rosenthal's collection of patients, the primary risk factors were hyperlipidemia, female gender, and heavy smoking. Because there does not appear to be one systemic factor that stands out, I think the algorithm presented by Dr. Clagett in his article presented at the ISCVS meeting in 1985 is a reasonable approach. He divided the factors into local and systemic; the local factors being ongoing thrombogenesis and the neointimal fibromuscular hyperplasia progressing to degeneration and a complex atherosclerotic lesion. This begins immediately after the CEA. Add to these the factors of clamp trauma or an intimal flap and the incidence ofrestenosis is probably increased. The systemic factors of gender, smoking, hyperlipidemia, and--probably the most significant--the atherosclerotic predisposition of the genes that we bring into life cause recurrent atherosderotic disease',. In this same article, Dr. Clagett pointed out that there were morphologic differences between the early recurrences and late recurrences, such as the pale white rubbery hyperplastic lesion densely adherent to the arterial wall that with time will probably undergo subintimal thrombosis and degenerate into atherosclerotic plaque. CEA is the most frequently performed peripheral vascular procedure. With randomized, controlled studies that prove the efficacy of CEA, both symptomatic and asymptomatic, we can say that we are going to continue to see symptomatic recurrent carotid stenosis. Fortunately, SRCS is unusual. In our series of CEAs dating back to 1973, our rate of recurrent first-time symptomatic carotid artery stenosis was in the range of 3% to 4%; however, of those patients with one recurrence, about 23% are candidates for a secondary recurrence. During this time period, we performed a resection of the
Rosenthal et al.
carotid bifurcation and vcin interposition on 36 occasions in 29 patients for SRCS. We first rcported this in 1987. In 1989 we recommended that resection of the carotid bifurcation with vein interposition was a safe and durable alternative to multiple recurrent CEAs, patch or no patch. I mentioned in that article that orthograde placement of the vein would give a bettcr anastomotic match than reversing thc saphenous vein. I still believe that this is appropriate if the valves can be adequately lysed. In 1992 we again reported on the management of recurrent carotid artery stenosis, at which time we had performed 57 vein interpositions. Of those 57, 20 were for secondary symptomatic stenosis. Follow-up of those 20 patients has revealed one operation for thrombus formation at a valve. One vein had to be removed because of aneurysmal dilatation, and stenosis <50% has occurred in four additional veins. The first patient we operated on with vein interposition was in 1983 for secondary stenosis. She did well and died in 1993 of coronary artery disease. The second patient who also underwent surgery in 1983 is still alive with no recurrent stenosis. A comment on the surgical technique: this can be a difficult and tedious operation, but sometimes it is amazingly simple. Sometimes these carotid bifurcations in the internal carotid artery can be dissected very easily. Care must be taken, however, not to dissect subadventitially because then you have a problem. This will require higher dissection until you have good distal artery to which you can hopefully interpose a vein. These can be challenging patients to manage. I would, however, not necessarily caution against the operation for SRCS. I r a patient is asymptomatic but has a high degree of stenosis, I think that the risks of operation still are less than the risk of patients having stroke.