- Email: [email protected]
Synchronous carotid artery stenting and open heart surgery
Synchronous carotid artery stenting and open heart surgery Ioannis Velissaris, MD, Dimitrios Kiskinis, MD, and Kyriakos Anastasiadis, MD, Thessaloniki, Greece Background: The optimal management of the patients requiring cardiac surgery with concomitant severe carotid disease remains a controversy. The traditional approach involves staged or combined carotid endarterectomy and cardiac surgery. This study evaluated the feasibility and safety of angioplasty and stenting for the treatment of carotid stenoses concomitantly to cardiac operations to reduce the risk of perioperative stroke. Methods: All patients scheduled for cardiac surgery were screened preoperatively by color duplex ultrasonography for carotid disease. Carotid stenoses >60% in symptomatic patients and >70% in asymptomatic patients were treated using carotid artery stenting (CAS) under local anesthesia immediately before the open heart surgery. Cerebral protection devices were used in all cases. Patients did not receive aspirin or clopidogrel before the procedure. In a prospective, nonrandomized study, we analyzed 90 consecutive patients requiring cardiac surgery with concomitant severe carotid artery disease who underwent one stage CAS and cardiac surgery. Results: Despite the high baseline risk profile, our results were encouraging. Carotid stenting was successful in all patients. No neurologic complications occurred during the carotid stenting procedures. The 30-day death/stroke rate was 2.2% (one death, one contralateral stroke). No myocardial infarction occurred. The carotid restenosis rate was zero during the intermediate-term follow-up. Conclusions: In our experience, CAS followed immediately by cardiac surgery is safe and represents a reasonable option for selected patients presenting with severe carotid and coronary disease. ( J Vasc Surg 2011;53:1237-41.)
Carotid artery stenosis is a well-known risk factor for perioperative stroke in cardiac surgery.1-6 The optimal management of the patients requiring cardiac surgery with simultaneous severe carotid disease remains controversial and debated. Various potential therapeutic options exist. Evidence suggests that carotid endarterectomy (CEA) should be performed before cardiac surgery as a staged or simultaneous operation to reduce the risk of perioperative stroke.6-12 There is also literature claiming that such patients need no carotid intervention at all in conjunction with their coronary bypass procedures.13-15 In our institute, before this study, our strategy with these patients was combined carotid/cardiac surgery. Even though our results have been acceptable (9% rate of death, stroke or myocardial infraction at 30 days), we thought that we could use carotid artery angioplasty with stenting (CAS) instead of CEA to achieve similar goals. Carotid angioplasty with cerebral protection followed immediately by cardiac surgery might represent a less invasive and safer option that could be associated with fewer complications. We chose the one stage approach to avoid the problems and potential complications of the staged approach, due to delay of coronary bypass and early cessation of antiplatelet therapy after CAS and before surgery. From the Department of Cardiovascular Surgery, Kyanous Stavros Hospital. Competition of interest: none. Reprint requests: Ioannis Velissaris, MD, Kyanous Stavros Hospital, Viziis 1, 54636 Thessaloniki, Greece (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2011 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2010.11.049
METHODS Patient population In a prospective, nonrandomized study, we analyzed 90 consecutive patients that underwent one stage CAS and cardiac surgery from September 2003 to March 2010 at our center. The study protocol was approved by the Ethics Committee of our hospital and all patients gave written informed consent. The baseline characteristics of all patients are shown in Table I. The indications for cardiac surgery were established before the carotid angioplasty. At our center, all patients scheduled for cardiac surgery are screened preoperatively by color duplex ultrasonography for carotid disease. The estimation of the degree of carotid stenosis is based on Nicolaides criteria.16 Our policy is to treat symptomatic patients with ⱖ60% carotid stenosis and asymptomatic patients with ⱖ70% stenosis. If both carotid arteries are involved, we treat the symptomatic side or the side with the more severe stenosis in asymptomatic patients. During the study period, 2239 consecutive cardiac surgery patients were screened and 103 of them fulfilled the selection criteria for carotid treatment. Since September 2003, our standard strategy was to treat significant carotid stenosis by percutaneous angioplasty and stenting in patients requiring cardiac surgery. Carotid endarterectomy was used in patients excluded from the protocol or for those who did not provide informed consent. All patients were informed that in the case of unsuccessful carotid angioplasty, they would be treated by synchronous carotid endarterectomy/cardiac surgery without delay. The endovascular procedure was performed by the authors (vascular surgeons) immediately before open heart 1237
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Table 1. Baseline characteristics of the patients Mean age Men Current smoking Hypertension Diabetes mellitus Lipidemia Family history
69.6 (54-85) 68 (75.5%) 33 (37%) 68 (76%) 49 (54.5%) 43 (48%) 30 (33%)
Table II. Severity of carotid and cardiac disease Degree of treated carotid stenosis 60%-79% 80%-89% 90%-99% Degree of contralateral carotid stenosis occluded ⱖ50% ⬍50% Symptomatica Asymptomatic CAD 3 vessel disease Left main stem disease Unstable angina pectoris Previous CABG Valvular disease alone Valvular disease ⫹ CAD Poor LV function (EF⬍25%)
31 (34.5%) 26 (29%) 33 (36.5%) 15 (17%) 24 (26.5%) 51 (56.5%) 12 (13.3%) 78 (86.6%) 68 (75.5%) 23 (25.5%) 13 (14.5%) 6 (6.6%) 0 15 (16.6%) 15 (16.6%)
CABG, Coronary artery bypass grafting; CAD, coronary artery disease; EF, ejection fraction; LV, left ventricular a Stroke or transient ischemic attack or amaurosis fugax in the 12 months prior to CAS.
surgery. The patients with unstable angina, active chest pain, or left main stem stenosis underwent CAS in the cardiac operating room using a C-arm. Stable patients underwent CAS in the catheterization laboratory and were transferred to the operating room after the procedure. The endovascular procedure was performed under local anesthesia with femoral access and was followed by induction of general anesthesia and cardiac surgery. The severity of carotid and cardiac disease is shown in Table II. During the study period, we performed 13 carotid endarterectomies simultaneously with cardiac surgery. Nine of them were patients excluded from CAS; serum creatinine ⬎3 mg/dL (one patient), history of allergic reaction to contrast medium (one patient), extreme tortuosity of brachiocephalic trunk (one patient), type III calcified aortic arch (three patients), complex anatomy of carotid bifurcation (two patients), and kinking of internal carotid artery (one patient). Four patients chose the combined CEA/cardiac surgery treatment. The endpoint of the study was the combined incidence of death and stroke from the day of procedure to 30 days later. The secondary endpoint was myocardial infarction (MI) during the same period. A stroke was defined as a new focal neurologic deficit that persisted ⬎24 hours. Transient ischemic attack was diagnosed if the duration of symptoms lasted ⬍24 hours. The diag-
nosis of MI was based on the presence of new Q waves on the electrocardiogram (ECG) and new regional wall motion abnormalities on the postoperative cardiac ultrasonography. The elevated level of creatine phosphokinase myocardial isoenzyme (CPK-MB) and troponin were also used for the diagnosis of MI. CAS procedure Patients did not receive aspirin or clopidogrel before the procedure and were not sedated during the procedure. Arterial access was obtained through the femoral artery in all cases, using local anesthesia. A 7 or 8F introducer sheath was inserted followed by intravenous heparin administration (5000 IU). The first step was to obtain an angiogram of the aortic arch, the carotid arteries, and the intracranial circulation to confirm the degree of carotid stenosis and identify possible anatomical contraindications for CAS. The degree of stenosis was calculated according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology.17 A 7 or 8F preshaped angioplasty guiding catheter was used to ensure access to the common carotid artery. All procedures were done under embolic protection. Four different cerebral protection devices were used: Accunet system (Abbott Vascular, Abbott Park, Ill), Emboshield system (Abbott Vascular), FilterWire system (Boston Scientific, Natick, Mass), and MO.MA device (Invatec, Roncadelle, Italy). When necessary, an undersized angioplasty balloon was used (3.0-3.5 mm) to predilate the lesion. This was followed by placement of an appropriately sized stent. In our series, three different types of carotid tapered nitinol stents were used: Acculink (Abbott Vascular; an open cell stent), Xact (Abbott Vascular; a closed cell stent), and Cristallo (Invatec; a closed cell in the middle and open cell at the edges stent). The choice of the type of filter/stent depended on the anatomy of the vessels and the carotid plaque characteristics.18,19 After stent placement, atropine (0.5 mg) was administered and postdilation was performed with a 5 or 5.5 mm balloon. Upon completion of the procedure, carotid and intracranial angiography was performed to check the success of the carotid stenting and to exclude distal embolization. Immediately after the procedure, patients were evaluated clinically by a neurologist. If there was no evidence of any neurologic complications, the patients received general anesthesia for the subsequent cardiac surgery. Cardiac surgical procedure Details of the cardiac operations are given in Table III. Postoperative care After CAS and cardiac surgery all patients were admitted to the intensive care unit (ICU). In the absence of a contraindication (ie, bleeding), aspirin (1g intravenously) was administered. When the activated clotting time was ⬍180 the femoral introducer sheath was removed. All patients received 75 mg clopidogrel and 100 mg aspirin
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Table III. Cardiac operations (total 90) Coronary artery bypasses 1 2 3 4 5 Aortic valve replacement ⫹ CABG Mitral valve surgery ⫹ CABG Off pump
Table IV. Thirty-day incidence of death, stroke, TIA, and MI 7 14 28 34 7 10 5 10
Death Stroke TIA MI Death or stroke Death or stroke or MI
1 (1.1%) 1 (1.1%) 1 (1.1%) 0 2 (2.2%) 2 (2.2%)
MI, Myocardial infraction; TIA, transient ischemic attack.
CABG, Coronary artery bypass grafting.
daily from the first postoperative day on, for at least 1 year. In addition, all patients were permanently placed on a statin drug. On the first postoperative day, patients were examined again by a neurologist for evidence of new neurologic deficits. Measurement of serum CPK-MB and troponin levels and a 12-lead ECG was performed daily. Each patient had a pre- and postoperative echocardiography evaluation. Follow-up. Patients were followed from the day of operation to 30 days after discharge. In patients not available for clinical examination at 30 days, follow-up was made by telephone interview. Thereafter, carotid arteries were examined by color duplex ultrasonography at 6-month intervals. The mean follow-up per patient was 29 months (range 6-78 months).
artery and resolved within 24 hours (transient ischemic attack). In both patients, there was no evidence of a neurologic event after CAS before the open heart procedure. The neurologic deficits presented after waking from general anesthesia in the ICU. No MIs happened during or after the combined treatment. One patient died 15 days after the procedures and 6 days after discharge due to massive pulmonary embolism, according to the necrotomy report. In hospital stay was 8.9 ⫾ 3.1 days and was no longer than the mean stay of the patients who had only cardiac surgery. All patients followed with serial duplex ultrasound scanning for a mean of 29 months. The restenosis rate was zero. In four cases, in-stent hyperplasia found without hemodynamic sequel or stenosis.
RESULTS
DISCUSSION AND CONCLUSIONS
Carotid stenting was technically successful in all patients (good final angiographic result, residual stenosis less than 15%). After the diagnostic angiogram (the first step of the CAS procedure), seven patients were excluded from CAS for anatomical reasons. Instead, they promptly received synchronous CEA/cardiac surgery under general anesthesia. These seven patients were not included in the study (see patient population in Methods section). In all cases, duplex criteria for grading carotid stenosis correlated with angiographic measurements, in terms of the selection for carotid treatment degree of stenosis. In the treatment group, there were some differences between duplex and angiography regarding the exact assessment of stenosis. We noticed a trend for underestimation of high grade stenoses by duplex sonography. The degree of treated carotid stenoses given in Table II, are those measured on angiogram using the NASCET methodology. As mentioned before, embolic protection devices were used in all patients. Entrapped visible debris was found in nine (10%) procedures. The 30-day incidence of death, stroke, and MI is listed in Table IV. The single stroke was a minor event presented as a mild left-sided hemiparesis in a male patient who underwent stenting of the left carotid artery (95% stenosis, asymptomatic). The degree of stenosis of his right nontreated carotid artery was 60%. He recovered completely within 30 days. A separate patient had a different neurologic event; suffering mild strength reduction of the left hand. This occurred in a male patient who underwent stenting of the right carotid
Major changes in the revascularization strategies of symptomatic obstructive coronary artery disease have been seen in the past decade with a substantial shift toward percutaneous coronary intervention, mainly in patients with a single- or double-vessel disease on coronary angiography.20 Nevertheless, coronary artery bypass grafting (CABG) remains the standard of care for patients with three-vessel or left main coronary disease and is preferred in diabetics.21 Despite the bad risk profile of the patients referred for CABG, our results with CAS and CABG instead of CEA and CABG are encouraging. In our series, the death/stroke/MI rate was lower than the rate reported by several previously published series of combined or staged endarterectomy and cardiac surgery.8,11,22,23 Our findings concur with those of previous published studies that CAS may provide a safer option for a challenging patient population, ie, patients with comorbid or anatomic features that place them at increased risk for carotid surgery. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial demonstrated a significantly higher incidence of MI with CEA than with CAS in a high risk CEA population.24 A substantial proportion of SAPPHIRE population had cardiac/coronary comorbidities. Additionally, previously published studies showed that CAS followed by open heart surgery is a safer approach than combined CEA and cardiac surgery.25-27 The explanation for the fewer adverse events in patients who underwent CAS instead of CEA is not clear. The longer operating time and greater duration of general
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anesthesia in CEA, combined with the reduction of surgical trauma in CAS were probably the most important factors. To our knowledge, this is the third study on the use of CAS immediately before cardiac surgery (one stage) in the management of simultaneous severe carotid and cardiac disease. Mendiz et al and Versaci et al published the results of CAS/immediate cardiac surgery under aspirin in 30 and 37 patients, respectively, and showed the feasibility and safety of this method.28,29 In these two studies, patients received oral aspirin pre-CAS and there were concerns about bleeding during or following CABG. Cardiac tamponade and chest reopenings for post-CABG bleeding have been reported in patients receiving antiplatelet agents.28-30 In the absence of randomized clinical trials for the optimal use of medications in patients undergoing CAS,31 we decided, in our series, to perform CAS with no antiplatelet pretreatment, to avoid the above-mentioned bleeding complications. In Ziada et al series, CAS was performed 39 ⫾ 22 days before surgery and clopidigrel was stopped 1 week before surgery.25 In Van der Heyden et al study, CAS was performed 14 to 30 days before surgery and aspirin/clopidogrel was discontinued 5 days before cardiac surgery.26 Our opinion is that, in these patients, the antiplatelet agents should not be stopped during the early poststenting period because it may cause complications from carotid or coronary arteries. On the other hand, the delay of CABG in patients with unstable angina, left main, or multivessel coronary artery disease, is not a safe policy. Cardiac causes of death have been reported while patients wait their cardiac bypass procedure.32 The disadvantages of staged treatment can be avoided using the one stage treatment strategy. In a series of 37 patients, Kramer et al studied an intermediate approach where patients had CABG within 48 hours after CAS. These patients were on a continuous infusion of eptifibatide for antiplatelet therapy during the interval between procedures.33 In a systematic review and metaanalysis of staged CAS and CABG, Naylor et al presented the 30-day outcomes of the particular strategy; the overall mortality rate was 5.5% and the risk of suffering any stroke was 4.2%, while the risk of MI was only 1.8%. The 30-day rate of death/any stroke was 9.1%, while the combined risk of death/stroke/MI was 9.4%.34 In our series, the vast majority of the treated patients are asymptomatic (87%) regarding the carotid disease. The benefit from invasive treatment in asymptomatic patients with ⬎70% carotid stenosis is well documented, provided the rate of periprocedural stroke and death is 3% or less and life expectancy is at least 5 years.35-37 Thus, carotid treatment is beneficial to these patients, and this is independent of the need for cardiac surgery. Furthermore, a policy of screening all patients prior to open heart surgery can reveal an unknown severe carotid disease and may contribute to stroke prevention, not only in conjunction with the CABG. To maintain a low rate of CAS-associated complications, two parameters are very important; the practitioners’ experience and the patient selection. Our team, which consists of vascular surgeons, has performed more than 500
carotid interventions. One also must consider that CAS is not the best option for all patients with severe carotid stenosis. Those with complex vessel anatomy, renal failure, and difficult arterial access, should be excluded from endovascular treatment. Furthermore, a “tailored technique” is mandatory: by the choice of the right cerebral protection device and the appropriate stent a safer procedure may be performed. Although there are no randomized studies comparing CAS with and without embolic protection devices, consensus among experts suggests their use in reducing the risk of stroke during CAS.37,38 In International Carotid Stenting Study (ICSS) protection devices were associated with a higher risk for new ischemic lesions on diffusion-weighted brain scans after CAS.39 Nevertheless, the results of the study should be critically considered, because the ICSS trial had unacceptably low requirements in terms of endovascular expertise (minimum ten CAS procedures in a lifetime versus minimum 50 carotid operations) and allowed for CAS procedures under tutoring conditions. The present study provides further guidance for the decision-making process in the management of patients with simultaneous severe carotid artery disease and cardiac disease requiring surgery. The low complication rate suggests that one stage CAS and cardiac surgery may offer a safer therapeutic option compared with the entirely surgical approach. It may also be safer than with the staged CAS and CABG approach as well. The limitations of our nonrandomized study are recognized, but these data add to the limited world literature on carotid stenting immediately before cardiac surgery. We accept that further studies are needed as only correctly powered randomized trials can give definitive answers about the most appropriate strategy. AUTHOR CONTRIBUTIONS Conception and design: VI, KD Analysis and interpretation: VI, KD Data collection: VI, KD, AK Writing the article: VI Critical revision of the article: VI, KD, AK Final approval of the article: VI, KD, AK Statistical analysis: VI Obtained funding: Not applicable Overall responsibility: VI REFERENCES 1. Naylor AR, Mehta Z, Rothwell PM, Bell PRF. Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature. Eur J Vasc Endovasc Surg 2002;23:283-94. 2. Faggioli GL, Curl GR, Ricotta J. The role of carotid screening before coronary artery bypass. J Vasc Surg 1990;12:724-31. 3. Berens ES, Kouchoukos NT, Murphy SF, Wareing TH. Preoperative carotid artery screening in elderly patients undergoing cardiac surgery. J Vasc Surg 1992;15:313-23. 4. Ricotta J, Faggioli G, Castilone A, Hassett J. Risk factors for stroke after cardiac surgery: Buffalo Cardiac-Cerebral Study Group. J Vasc Surg 1995;21:359-64. 5. Brener BJ, Brief DK, Alpert J, Goldenkranz RJ, Parsonnet V. The risk of stroke in patients with asymptomatic carotid stenosis undergoing cardiac surgery: A follow up study. J Vasc Surg 1987;5:269-79.
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6. Hertzer RR, Loop FD, Beven EG, O’Hara PJ, Krajewski LP. Surgical staging for simultaneous coronary and carotid disease: a study including postoperative randomisation. J Vasc Surg 1989;9:455-63. 7. Darling R, Dylewski M, Chang BB, Paty PS, Kreinberg PB, Lloyd WE, et al. Combined carotid endarterectomy and coronary artery bypass grafting does not increase the risk of postoperative stroke. Cardiovasc Surg 1998;6:448-52. 8. Moore W, Barnett H, Beebe H, Bernstein EF, Brener BJ, Brott T. Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the hoc committee, American Heart Association. Circulation 1995;91:566-79. 9. Borger MA, Fremes SE, Weisel RD, Cohen G, Rao V, Lindsay TF, et al. Coronary bypass and carotid endarterectomy: does a combined approach increase risk? A meta-analysis. Ann Thorac Surg 1999;68:14-21. 10. Das S, Brow T, Pepper J. Continuing controversy in the management of concomitant coronary and carotid disease: an overview. Int J Cardiol 2000;74:47-65. 11. Naylor AR, Cuffe RL, Rothwell PM, Bell PR. A systemic review of outcomes following staged and synchronous carotid endarterectomy and coronary artery bypass. Eur J Vasc Endovasc Surg 2003;25:380-9. 12. Ricotta JJ, Wall LP, Blackstone E. The influence of concurrent carotid endarterectomy on coronary bypass: a case-controlled study. J Vasc Surg 2005;41:397-402. 13. Ghosh J, Murray D, Khwaja N, Murphy MO, Walker MG. The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery. Eur J Vasc Endovasc Surg 2005;29:88-90. 14. Nakamura M, Okamoto F, Nakanishi K, Marruyama R, Yamada A, Ushikoshi S, et al. Does intensive management of cerebral haemodynamics and atheromatous aorta reduce stroke after coronary artery surgery? Ann Thorac Surg 2008;85:513-9. 15. Manabe S, Shimokawa T, Fukui T, Fumimoto K-U, Ozawa N, Seki H, et al. Influence of carotid artery stenosis on stroke in patients undergoing off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 2008;34:1005-8. 16. Nicolaides AN, Shifrin E, Bradbury A, Dhanjil S, Griffin M, Belcaro G, et al. Angiographic and duplex grading of internal carotid stenosis: can we overcome the confusion? J Endovasc Surg 1996;3:158-65. 17. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade stenosis. N Engl J Med 1991;325:445-53. 18. Cremonesi A, Setacci C, Manetti R, de Donato G, Setacci F, Balestra G. Carotid angioplasty and stenting: lesion related treatment strategies. Eurointervention 2005;1:289-95. 19. Bosiers M, Peeters P, Deloose K, Verbist J. Carotid artery stenting: which stent for which lesion. Vascular 2005;13:1-17. 20. Singh AK. Percutaneous coronary intervention vs coronary artery bypass grafting in the management of chronic stable angina: a critical appraisal. J Cardiovasc Dis Res 2010;1:54-8. 21. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961-72. 22. Mackey WC, Khabbaz K, Bojar R, O’Donnell TF. Simultaneous carotid endarterectomy and coronary bypass perioperative risk and long-term survival. J Vasc Surg 1996;24:58-64. 23. Donatelli F, Pelenghi S, Pocar M, Moneta A, Grossi A. Combined carotid and cardiac procedures: improved results and surgical approach. Cadiovsc Sur 1998;6:506-10.
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24. Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ. Stenting and angioplasty with protection in patients at high risk for endarterectomy Investigators. Protected carotid-artery stenting versus endarterectomy in high risk patients. N Engl J Med 2004;351:1493501. 25. Ziada KM, Yadav JS, Mukherjee D, Lauer MS, Bhatt DL, Kapadia S, et al. Comparison of results of carotid stenting followed by open heart surgery versus combined endarterectomy and open heart surgery. Am J Cardiol 2005;96:519-23. 26. Van der Heyden J, Suttorp MJ, Bal ET, Ernst JM, Ackerstaff RG, Schaap J, et al. Staged carotid angioplasty and stenting followed by cardiac surgery in patients with severe asymptomatic carotid artery stenosis. Circulation 2007;116:2036-42. 27. Timaran CH, Rosero EB, Smith ST, Valentine RJ, Modrall JG, Clagett GP. Trends and outcomes of concurrent carotid revascularization and coronary bypass. J Vasc Surg 2008;48:355-60. 28. Mendiz M, Carlos F, Leon V, Eduardo D, Hector R, Gustavo L. Synchronous carotid stenting and cardiac surgery: an initial single centre experience. Catheter Cardiovasc Interv 2006;68:424-8. 29. Versaci F, Del Giudice C, Scafuri A, Zeitani J, Gandini R, Nardi P. Sequential hybrid carotid and coronary artery revascularization: immediate and mid-term results. Ann Thorac Surg 2007;84:1508-14. 30. Karthik S, Grayson AD, McCarron EE, Pulan DM, Desmond MJ. Re-exploration for bleeding after coronary artery bypass surgery: risk factors, outcomes, and the effect of the time delay. Ann Thorac Surg 2004;78:527-34. 31. Gortler D, Schlosser FJ, Muhs BE, Nelson MA, Dardik A. Periprocedural drug therapy in carotid artery stenting: the need for more evidence. Vascular 2008;16:303-9. 32. Randall MS, McKevitt FM, Cleveland TJ, Gaines PA, Venables GS. Is there any benefit from staged carotid and coronary revascularization using carotid stents? Stroke 2006;37:435-9. 33. Kramer J, Abraham J, Jones PA. Carotid artery stenting before CABG: a better alternative to treat concomitant coronary and carotid artery disease. Stroke 2006;37:1359. 34. Naylor AR, Mehta Z, Rothwell PM. A systematic review and metaanalysis of 30-day outcomes following staged carotid artery stenting and coronary bypass. Eur J Vasc Endovasc Surg 2009;37:379-87. 35. Moore WS, Barnett HJ, Beebe HG, Bernstein EF, Brener BJ, Brott T, et al. Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc committee. Stroke 1995;26:188-201. 36. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, et al, MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: a randomised controlled trial. Lancet 2004;363:1491-502. 37. Liapis CD, Bell PF, Mikhailidis DP, Sivenius J, Nicolaides A, Fernandes e Fernades J, et al. ESVS Guidelines Collaborators. Invasive treatment for carotid stenosis: indications, techniques. Eur J Vasc Endovasc Surg 2009;37 (Suppl):1-19. Review. 38. Bates ER, Babb JD, Casey DE, Jr, Cates CU, Duckwiler GR, Feldman TE, et al. ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on carotid stenting. J Am Coll Cardiol 2007;49: 126-70. 39. Bonati LH, Jongen LM, Haller S, Flach HZ, Dobson J, Nederkoorn PJ, et al. New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the international Carotid Stenting Study (ICSS). Lancet Neurol 2010;9:353-62. Submitted Jul 15, 2010; accepted Nov 6, 2010.
Carotid artery stenosis is a well-known risk factor for perioperative stroke in cardiac surgery.1-6 The optimal management of the patients requiring cardiac surgery with simultaneous severe carotid disease remains controversial and debated. Various potential therapeutic options exist. Evidence suggests that carotid endarterectomy (CEA) should be performed before cardiac surgery as a staged or simultaneous operation to reduce the risk of perioperative stroke.6-12 There is also literature claiming that such patients need no carotid intervention at all in conjunction with their coronary bypass procedures.13-15 In our institute, before this study, our strategy with these patients was combined carotid/cardiac surgery. Even though our results have been acceptable (9% rate of death, stroke or myocardial infraction at 30 days), we thought that we could use carotid artery angioplasty with stenting (CAS) instead of CEA to achieve similar goals. Carotid angioplasty with cerebral protection followed immediately by cardiac surgery might represent a less invasive and safer option that could be associated with fewer complications. We chose the one stage approach to avoid the problems and potential complications of the staged approach, due to delay of coronary bypass and early cessation of antiplatelet therapy after CAS and before surgery. From the Department of Cardiovascular Surgery, Kyanous Stavros Hospital. Competition of interest: none. Reprint requests: Ioannis Velissaris, MD, Kyanous Stavros Hospital, Viziis 1, 54636 Thessaloniki, Greece (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2011 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2010.11.049
METHODS Patient population In a prospective, nonrandomized study, we analyzed 90 consecutive patients that underwent one stage CAS and cardiac surgery from September 2003 to March 2010 at our center. The study protocol was approved by the Ethics Committee of our hospital and all patients gave written informed consent. The baseline characteristics of all patients are shown in Table I. The indications for cardiac surgery were established before the carotid angioplasty. At our center, all patients scheduled for cardiac surgery are screened preoperatively by color duplex ultrasonography for carotid disease. The estimation of the degree of carotid stenosis is based on Nicolaides criteria.16 Our policy is to treat symptomatic patients with ⱖ60% carotid stenosis and asymptomatic patients with ⱖ70% stenosis. If both carotid arteries are involved, we treat the symptomatic side or the side with the more severe stenosis in asymptomatic patients. During the study period, 2239 consecutive cardiac surgery patients were screened and 103 of them fulfilled the selection criteria for carotid treatment. Since September 2003, our standard strategy was to treat significant carotid stenosis by percutaneous angioplasty and stenting in patients requiring cardiac surgery. Carotid endarterectomy was used in patients excluded from the protocol or for those who did not provide informed consent. All patients were informed that in the case of unsuccessful carotid angioplasty, they would be treated by synchronous carotid endarterectomy/cardiac surgery without delay. The endovascular procedure was performed by the authors (vascular surgeons) immediately before open heart 1237
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Table 1. Baseline characteristics of the patients Mean age Men Current smoking Hypertension Diabetes mellitus Lipidemia Family history
69.6 (54-85) 68 (75.5%) 33 (37%) 68 (76%) 49 (54.5%) 43 (48%) 30 (33%)
Table II. Severity of carotid and cardiac disease Degree of treated carotid stenosis 60%-79% 80%-89% 90%-99% Degree of contralateral carotid stenosis occluded ⱖ50% ⬍50% Symptomatica Asymptomatic CAD 3 vessel disease Left main stem disease Unstable angina pectoris Previous CABG Valvular disease alone Valvular disease ⫹ CAD Poor LV function (EF⬍25%)
31 (34.5%) 26 (29%) 33 (36.5%) 15 (17%) 24 (26.5%) 51 (56.5%) 12 (13.3%) 78 (86.6%) 68 (75.5%) 23 (25.5%) 13 (14.5%) 6 (6.6%) 0 15 (16.6%) 15 (16.6%)
CABG, Coronary artery bypass grafting; CAD, coronary artery disease; EF, ejection fraction; LV, left ventricular a Stroke or transient ischemic attack or amaurosis fugax in the 12 months prior to CAS.
surgery. The patients with unstable angina, active chest pain, or left main stem stenosis underwent CAS in the cardiac operating room using a C-arm. Stable patients underwent CAS in the catheterization laboratory and were transferred to the operating room after the procedure. The endovascular procedure was performed under local anesthesia with femoral access and was followed by induction of general anesthesia and cardiac surgery. The severity of carotid and cardiac disease is shown in Table II. During the study period, we performed 13 carotid endarterectomies simultaneously with cardiac surgery. Nine of them were patients excluded from CAS; serum creatinine ⬎3 mg/dL (one patient), history of allergic reaction to contrast medium (one patient), extreme tortuosity of brachiocephalic trunk (one patient), type III calcified aortic arch (three patients), complex anatomy of carotid bifurcation (two patients), and kinking of internal carotid artery (one patient). Four patients chose the combined CEA/cardiac surgery treatment. The endpoint of the study was the combined incidence of death and stroke from the day of procedure to 30 days later. The secondary endpoint was myocardial infarction (MI) during the same period. A stroke was defined as a new focal neurologic deficit that persisted ⬎24 hours. Transient ischemic attack was diagnosed if the duration of symptoms lasted ⬍24 hours. The diag-
nosis of MI was based on the presence of new Q waves on the electrocardiogram (ECG) and new regional wall motion abnormalities on the postoperative cardiac ultrasonography. The elevated level of creatine phosphokinase myocardial isoenzyme (CPK-MB) and troponin were also used for the diagnosis of MI. CAS procedure Patients did not receive aspirin or clopidogrel before the procedure and were not sedated during the procedure. Arterial access was obtained through the femoral artery in all cases, using local anesthesia. A 7 or 8F introducer sheath was inserted followed by intravenous heparin administration (5000 IU). The first step was to obtain an angiogram of the aortic arch, the carotid arteries, and the intracranial circulation to confirm the degree of carotid stenosis and identify possible anatomical contraindications for CAS. The degree of stenosis was calculated according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology.17 A 7 or 8F preshaped angioplasty guiding catheter was used to ensure access to the common carotid artery. All procedures were done under embolic protection. Four different cerebral protection devices were used: Accunet system (Abbott Vascular, Abbott Park, Ill), Emboshield system (Abbott Vascular), FilterWire system (Boston Scientific, Natick, Mass), and MO.MA device (Invatec, Roncadelle, Italy). When necessary, an undersized angioplasty balloon was used (3.0-3.5 mm) to predilate the lesion. This was followed by placement of an appropriately sized stent. In our series, three different types of carotid tapered nitinol stents were used: Acculink (Abbott Vascular; an open cell stent), Xact (Abbott Vascular; a closed cell stent), and Cristallo (Invatec; a closed cell in the middle and open cell at the edges stent). The choice of the type of filter/stent depended on the anatomy of the vessels and the carotid plaque characteristics.18,19 After stent placement, atropine (0.5 mg) was administered and postdilation was performed with a 5 or 5.5 mm balloon. Upon completion of the procedure, carotid and intracranial angiography was performed to check the success of the carotid stenting and to exclude distal embolization. Immediately after the procedure, patients were evaluated clinically by a neurologist. If there was no evidence of any neurologic complications, the patients received general anesthesia for the subsequent cardiac surgery. Cardiac surgical procedure Details of the cardiac operations are given in Table III. Postoperative care After CAS and cardiac surgery all patients were admitted to the intensive care unit (ICU). In the absence of a contraindication (ie, bleeding), aspirin (1g intravenously) was administered. When the activated clotting time was ⬍180 the femoral introducer sheath was removed. All patients received 75 mg clopidogrel and 100 mg aspirin
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Table III. Cardiac operations (total 90) Coronary artery bypasses 1 2 3 4 5 Aortic valve replacement ⫹ CABG Mitral valve surgery ⫹ CABG Off pump
Table IV. Thirty-day incidence of death, stroke, TIA, and MI 7 14 28 34 7 10 5 10
Death Stroke TIA MI Death or stroke Death or stroke or MI
1 (1.1%) 1 (1.1%) 1 (1.1%) 0 2 (2.2%) 2 (2.2%)
MI, Myocardial infraction; TIA, transient ischemic attack.
CABG, Coronary artery bypass grafting.
daily from the first postoperative day on, for at least 1 year. In addition, all patients were permanently placed on a statin drug. On the first postoperative day, patients were examined again by a neurologist for evidence of new neurologic deficits. Measurement of serum CPK-MB and troponin levels and a 12-lead ECG was performed daily. Each patient had a pre- and postoperative echocardiography evaluation. Follow-up. Patients were followed from the day of operation to 30 days after discharge. In patients not available for clinical examination at 30 days, follow-up was made by telephone interview. Thereafter, carotid arteries were examined by color duplex ultrasonography at 6-month intervals. The mean follow-up per patient was 29 months (range 6-78 months).
artery and resolved within 24 hours (transient ischemic attack). In both patients, there was no evidence of a neurologic event after CAS before the open heart procedure. The neurologic deficits presented after waking from general anesthesia in the ICU. No MIs happened during or after the combined treatment. One patient died 15 days after the procedures and 6 days after discharge due to massive pulmonary embolism, according to the necrotomy report. In hospital stay was 8.9 ⫾ 3.1 days and was no longer than the mean stay of the patients who had only cardiac surgery. All patients followed with serial duplex ultrasound scanning for a mean of 29 months. The restenosis rate was zero. In four cases, in-stent hyperplasia found without hemodynamic sequel or stenosis.
RESULTS
DISCUSSION AND CONCLUSIONS
Carotid stenting was technically successful in all patients (good final angiographic result, residual stenosis less than 15%). After the diagnostic angiogram (the first step of the CAS procedure), seven patients were excluded from CAS for anatomical reasons. Instead, they promptly received synchronous CEA/cardiac surgery under general anesthesia. These seven patients were not included in the study (see patient population in Methods section). In all cases, duplex criteria for grading carotid stenosis correlated with angiographic measurements, in terms of the selection for carotid treatment degree of stenosis. In the treatment group, there were some differences between duplex and angiography regarding the exact assessment of stenosis. We noticed a trend for underestimation of high grade stenoses by duplex sonography. The degree of treated carotid stenoses given in Table II, are those measured on angiogram using the NASCET methodology. As mentioned before, embolic protection devices were used in all patients. Entrapped visible debris was found in nine (10%) procedures. The 30-day incidence of death, stroke, and MI is listed in Table IV. The single stroke was a minor event presented as a mild left-sided hemiparesis in a male patient who underwent stenting of the left carotid artery (95% stenosis, asymptomatic). The degree of stenosis of his right nontreated carotid artery was 60%. He recovered completely within 30 days. A separate patient had a different neurologic event; suffering mild strength reduction of the left hand. This occurred in a male patient who underwent stenting of the right carotid
Major changes in the revascularization strategies of symptomatic obstructive coronary artery disease have been seen in the past decade with a substantial shift toward percutaneous coronary intervention, mainly in patients with a single- or double-vessel disease on coronary angiography.20 Nevertheless, coronary artery bypass grafting (CABG) remains the standard of care for patients with three-vessel or left main coronary disease and is preferred in diabetics.21 Despite the bad risk profile of the patients referred for CABG, our results with CAS and CABG instead of CEA and CABG are encouraging. In our series, the death/stroke/MI rate was lower than the rate reported by several previously published series of combined or staged endarterectomy and cardiac surgery.8,11,22,23 Our findings concur with those of previous published studies that CAS may provide a safer option for a challenging patient population, ie, patients with comorbid or anatomic features that place them at increased risk for carotid surgery. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial demonstrated a significantly higher incidence of MI with CEA than with CAS in a high risk CEA population.24 A substantial proportion of SAPPHIRE population had cardiac/coronary comorbidities. Additionally, previously published studies showed that CAS followed by open heart surgery is a safer approach than combined CEA and cardiac surgery.25-27 The explanation for the fewer adverse events in patients who underwent CAS instead of CEA is not clear. The longer operating time and greater duration of general
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anesthesia in CEA, combined with the reduction of surgical trauma in CAS were probably the most important factors. To our knowledge, this is the third study on the use of CAS immediately before cardiac surgery (one stage) in the management of simultaneous severe carotid and cardiac disease. Mendiz et al and Versaci et al published the results of CAS/immediate cardiac surgery under aspirin in 30 and 37 patients, respectively, and showed the feasibility and safety of this method.28,29 In these two studies, patients received oral aspirin pre-CAS and there were concerns about bleeding during or following CABG. Cardiac tamponade and chest reopenings for post-CABG bleeding have been reported in patients receiving antiplatelet agents.28-30 In the absence of randomized clinical trials for the optimal use of medications in patients undergoing CAS,31 we decided, in our series, to perform CAS with no antiplatelet pretreatment, to avoid the above-mentioned bleeding complications. In Ziada et al series, CAS was performed 39 ⫾ 22 days before surgery and clopidigrel was stopped 1 week before surgery.25 In Van der Heyden et al study, CAS was performed 14 to 30 days before surgery and aspirin/clopidogrel was discontinued 5 days before cardiac surgery.26 Our opinion is that, in these patients, the antiplatelet agents should not be stopped during the early poststenting period because it may cause complications from carotid or coronary arteries. On the other hand, the delay of CABG in patients with unstable angina, left main, or multivessel coronary artery disease, is not a safe policy. Cardiac causes of death have been reported while patients wait their cardiac bypass procedure.32 The disadvantages of staged treatment can be avoided using the one stage treatment strategy. In a series of 37 patients, Kramer et al studied an intermediate approach where patients had CABG within 48 hours after CAS. These patients were on a continuous infusion of eptifibatide for antiplatelet therapy during the interval between procedures.33 In a systematic review and metaanalysis of staged CAS and CABG, Naylor et al presented the 30-day outcomes of the particular strategy; the overall mortality rate was 5.5% and the risk of suffering any stroke was 4.2%, while the risk of MI was only 1.8%. The 30-day rate of death/any stroke was 9.1%, while the combined risk of death/stroke/MI was 9.4%.34 In our series, the vast majority of the treated patients are asymptomatic (87%) regarding the carotid disease. The benefit from invasive treatment in asymptomatic patients with ⬎70% carotid stenosis is well documented, provided the rate of periprocedural stroke and death is 3% or less and life expectancy is at least 5 years.35-37 Thus, carotid treatment is beneficial to these patients, and this is independent of the need for cardiac surgery. Furthermore, a policy of screening all patients prior to open heart surgery can reveal an unknown severe carotid disease and may contribute to stroke prevention, not only in conjunction with the CABG. To maintain a low rate of CAS-associated complications, two parameters are very important; the practitioners’ experience and the patient selection. Our team, which consists of vascular surgeons, has performed more than 500
carotid interventions. One also must consider that CAS is not the best option for all patients with severe carotid stenosis. Those with complex vessel anatomy, renal failure, and difficult arterial access, should be excluded from endovascular treatment. Furthermore, a “tailored technique” is mandatory: by the choice of the right cerebral protection device and the appropriate stent a safer procedure may be performed. Although there are no randomized studies comparing CAS with and without embolic protection devices, consensus among experts suggests their use in reducing the risk of stroke during CAS.37,38 In International Carotid Stenting Study (ICSS) protection devices were associated with a higher risk for new ischemic lesions on diffusion-weighted brain scans after CAS.39 Nevertheless, the results of the study should be critically considered, because the ICSS trial had unacceptably low requirements in terms of endovascular expertise (minimum ten CAS procedures in a lifetime versus minimum 50 carotid operations) and allowed for CAS procedures under tutoring conditions. The present study provides further guidance for the decision-making process in the management of patients with simultaneous severe carotid artery disease and cardiac disease requiring surgery. The low complication rate suggests that one stage CAS and cardiac surgery may offer a safer therapeutic option compared with the entirely surgical approach. It may also be safer than with the staged CAS and CABG approach as well. The limitations of our nonrandomized study are recognized, but these data add to the limited world literature on carotid stenting immediately before cardiac surgery. We accept that further studies are needed as only correctly powered randomized trials can give definitive answers about the most appropriate strategy. AUTHOR CONTRIBUTIONS Conception and design: VI, KD Analysis and interpretation: VI, KD Data collection: VI, KD, AK Writing the article: VI Critical revision of the article: VI, KD, AK Final approval of the article: VI, KD, AK Statistical analysis: VI Obtained funding: Not applicable Overall responsibility: VI REFERENCES 1. Naylor AR, Mehta Z, Rothwell PM, Bell PRF. Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature. Eur J Vasc Endovasc Surg 2002;23:283-94. 2. Faggioli GL, Curl GR, Ricotta J. The role of carotid screening before coronary artery bypass. J Vasc Surg 1990;12:724-31. 3. Berens ES, Kouchoukos NT, Murphy SF, Wareing TH. Preoperative carotid artery screening in elderly patients undergoing cardiac surgery. J Vasc Surg 1992;15:313-23. 4. Ricotta J, Faggioli G, Castilone A, Hassett J. Risk factors for stroke after cardiac surgery: Buffalo Cardiac-Cerebral Study Group. J Vasc Surg 1995;21:359-64. 5. Brener BJ, Brief DK, Alpert J, Goldenkranz RJ, Parsonnet V. The risk of stroke in patients with asymptomatic carotid stenosis undergoing cardiac surgery: A follow up study. J Vasc Surg 1987;5:269-79.
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