The Treatment of Carotid Artery Bifurcation Stenoses with Systematic Stenting: Experience of First 100 Consecutive Cardiological

For many years the treatment of the stenosis of the carotid artery bifurcation has been the dominion of the vascular or neurosurgeon. Carotid endarterectomy has been shown to be beneficial with respect to the medical treatment for both symptomatic and asymptomatic patients and clinical benefits are clearly extended to long-term follow-up.1–4 Transluminal angioplasty was also attempted many years ago,5 but was quickly abandoned because of suboptimal angiographic results and high peri-procedural clinical adverse effects. In the last few years, due to the significant development of interventional devices, the increasing skill of the operators and the wide availability of ad hoc metallic endoprosthesis, carotid artery stenting (CAS) has rapidly grown as an alternative method of treatment of the stenosis of the carotid bifurcation.6,7 Although angiographic and clinical results of this type of treatment are now very satisfactory, particularly after the introduction of distal protection devices, not only in the short term but also in the mid and long term,8,9 CAS is still recommended for treatment of carotid stenosis only in patients at high surgical risk, such as those with significant co-morbidities and/or contralateral carotid artery occlusion and/or old age, or in subjects with anatomically difficult lesions, e.g. post endarterectomy restenosis, following neck irradiation and/or high cervical or intrathoracic lesion location.10,11 However, the success of percutaneous stenting of atherosclerotic lesions in other arterial systems, particularly the coronary one, could herald the extensive and systematic use of CAS, especially if ongoing randomized comparisons with surgical endarterectomy confirm and strengthen positive results. This paper reports the results of the first 100 consecutive procedures of CAS performed as routine treatment in a consecutive and unselected series of patients in a single center cardiological setting. Methods Patients. Over a period of 30 months, CAS was performed in consecutive patients admitted to the cardiology unit of our hospital. Inclusion criteria were the presence of a carotid bifurcation lesion with an angiographic diameter stenosis > 70% as visual estimate with the NASCET method,1 both in asymptomatic and symptomatic patients. Exclusion criteria were: the presence of ipsilateral intracranial atherosclerosis worse than cervical lesion, the evidence of a clear potential embolic source for reasons other than carotid bifurcation disease, the preference of the patient for traditional surgical treatment and a known intolerance to the therapeutic association acetylsalicylic acid (ASA)-ticlopidine. All patients were informed of the nature of the interventional procedure and gave written consent. Clinical protocol. Every patient underwent a full cardiological evaluation with standard 12-lead electrocardiogram, chest x-ray, routine laboratory examination and 2-D Doppler color transthoracic echocardiography; transesophageal echocardiography was carried out only in patients with mitral valvular heart disease and/or heart rhythm disorders potentially correlated with embolic brain disease such as atrial fibrillation. Particular attention in this setting was paid to left atrial flow and appendage imaging and to the presence of ascending and aortic arch plaques. Doppler ultrasound (DU) scan of carotid arteries was performed in every patient in order to assess not only the degree of stenosis but also the morpholology of the plaque which was graded as echolucent, predominantly echolucent, predominantly echogenic and echogenic.12 A complete neurologic evaluation was performed by an independent specialist and repeated 24 hours and 30 days after the interventional procedure. A CT scan or a NMR of the brain was carried out on every patient before the procedure and repeated in case of any change in neurologic status after CAS. In all cases ASA (160 mg) and ticlopidine (250 mg b.i.d.) were given for at least two days before the procedure and maintained after discharge for 1 month when ticlopidine was withdrawn and ASA given indefinitely. Procedure. After an overnight fast the patient was taken to the cath lab where, under local anesthesia, a venous catheter for drugs and volume infusions and an 8 Fr arterial sheath were placed percutaneously in the right femoral vessels. Intravenous ASA (500 mg) and 70 U/kg body weight of unfractioned heparin were then given to raise the activated clotting time above 200 sec. With a 5 Fr SIM 2 and/or a Judkins right coronary catheter, a 4-vessel angiogram with selective injection in both carotid and vertebral arteries was obtained with digital subtraction only for the intracranial views. Through the lumen of the SIM catheter, a 0.035 in. extra support wire was introduced and advanced into the external carotid artery of the side to be treated; the diagnostic catheter was exchanged with an 8 Fr large lumen multipurpose guiding catheter (Zuma2, Medtronic Inc, Minneapolis, Minn.) over a 5 Fr multipurpose “shuttle” catheter. In cases of particular anatomical features of the carotid bifurcation, such as a sharp angle origin of the internal branch, an 8 Fr large lumen Judkins right catheter was chosen in order to better direct the intravascular devices at and beyond the stenosis. After administration of atropine 1 mg intravenously to prevent hypotension and bradycardia, a self-expanding stent (Easy Wallstent and Carotid Wallstent, Boston Scientific Ireland Ltd, Galway, Ireland; Acculink stent, Guidant Europe NV, Diegem, Belgium) was advanced over a 0.014-in guide wire into the lesion and, after checking its correct position with contrast dye injection, was directly deployed. Infrequently, high-grade or particularly complex stenoses were pre-dilated with an undersized coronary balloon catheter inflated at low pressure. All stents were post-dilated with a 5.5–6.0 mm balloon, depending on the vessel size, at a pressure allowing complete and tubular expansion of the balloon. A final angiogram was taken after intra-arterial administration of 1 or 2 mg of isosorbide dinitrate in 2 orthogonal incidences for the extracranial tract of the vessel and in a postero-anterior view, with digital subtraction, for the ipsilateral intracranial circulation. Intravenous fluids and vasopressor drugs were given depending on the clinical and circulatory situations at the operator’s discretion. Endpoints. The first endpoint was the investigation of the feasibility and the efficacy of CAS in a cardiological setting in a consecutive series of “real-world” unselected population. Clinical endpoints were peri-procedural and 30-day neurological death; any neurologic event including a transient ischemic attack (TIA), defined as a neurologic deficit that resolved without residuals within 24 hours; a minor stroke, defined as a new neurologic deficit that resulted in slight impairment of neurologic function (speech, motor or sensory skills) and completely resolved within 7 days; and a major stroke, defined as a new neurologic deficit that persisted after 7 days. Statistics. Patients’ age and time of endovascular placement of the cerebral protection filter are expressed as mean ± SD. Results Patient characteristics. In the time span examined, 100 CAS procedures were performed on 94 consecutive subjects. Baseline patient characteristics are shown in Table 1. Almost every patient had a cardiac comorbidity, particularly coronary artery disease (79%); 35% had previously received open heart surgery and 21% had significant left ventricular dysfunction, i.e. ejection fraction 79 years. Neurological asymptomatic patients were clearly prevalent but 39% of them had a pre-procedural CT brain scan consistent with a previous ischemic lesion ipsilateral to the carotid treated. 22% of treated patients had a concomitant significant stenosis of the contralateral carotid artery. Table 2 shows the Doppler ultrasound (DU) characterization of the plaque morphology of the treated lesions. Procedural results and complications. In 3 cases, CAS was performed on a post-carotid endarterectomy restenotic lesion and in 97 on a de novo lesion; right and left stenotic treated arteries were respectively 45 and 55; the diameter stenosis was 71–89% in 71 and 90–99% in 29 cases, respectively. A distal protection device (EPI Filterwire EX, Boston Scientific EPI, Santa Clara, Calif.) was used in 63 procedures with a mean time of endovascular placement of 8.4 ± 4.0 min. Immediate technical success, i.e. residual stenosis of the treated vessel Primary endpoint. This single center study shows that CAS can be used as systematic, elective treatment of the carotid artery bifurcation stenosis in a real-world population with complete procedural success (100%) in a cardiological setting. As in every interventional procedure, operator expertise is pivotal in determining the success of CAS. For the interventional cardiologist in a high-volume center, CAS could represent the natural evolution of an endovascular procedure performed on a small, often tortuous and markedly altered vessel of a beating vital organ (coronary arteries) to a relatively large, straight and immobile arterial conduit perfusing an organ of which tissutal damage can result in devastating clinical consequences; therapeutic complications or failures, therefore, are particularly dreaded by the operators. The wide expansion of coronary angioplasty for treatment of atherosclerotic lesion with high thrombotic burden, such as in acute myocardial infarction, or with much degenerative material, such as in old venous grafts, has led cardiologists to become even more familiar with distal protection devices to reduce peripheral embolization. It is to be remembered that the main way in which a carotid plaque causes symptoms, spontaneously or during therapeutic procedures, is distal embolization. The skill of the interventional cardiologist in the use of distal protection devices can be an advantage for the patient. In our series, the mean time of endovascular placement of the cerebral protection device was only 8 min. and significant reduction of cerebral blood flow due to the filter positioning was rarely observed (4%) and quickly abolished when needed. This, associated with the use of technical equipment of markedly reduced size such as the coronary ones, could explain the complete procedural success of the procedure without any significant influence of the learning curve. The high incidence of cardiological comorbidities, such as 79% of coronary involvement, 24% of concomitant valvular heart disease and 21% of left ventricular dysfunction in the population treated reflects, in part, the known systemic atherosclerotic involvement of patients presenting with carotid stenosis,13 which could lead to potentially severe peri-operative complications with traditional surgical treatment. In our population no intra- or peri-operative cardiovascular event was observed. A complete clinical evaluation in a cardiological setting and a precise therapeutic management could have favored this result, at least in part, making the multidisciplinary approach, i.e. interventional cardiologist, neurologist and interventional neuroradiologist with the availability of vascular and neurosurgeon, as suggested by other authors,6 not so strictly necessary. Clinical endpoint. The study population presents two main findings which deserve some comments: the high incidence of cardiovascular comorbidities and the ratio of asymptomatic/ symptomatic patients. The first was due to the fact that the patients treated were referred to the cardiological unit mainly because of cardiovascular disease. Carotid artery stenosis was frequently a collateral finding of the clinical evaluation. Nevertheless, this incidence of cardiovascular comorbidities made most of the subjects treated NASCET- or ACAS-ineligible.1,2 The rate of intra- and peri-procedural complication related to conventional surgical treatment in these patients seems to be higher14 than that observed in the highly selected population of the randomized trials, particularly if performed in unselected centers.15 So, the 5% total incidence of 30-day clinical complications and, in particular, 2% of irreversible events such as major strokes and death, can compare well with known results of interventional procedures16,17 and of surgical treatment observed in a real world population. It can be stressed that two minor intraprocedural strokes and one TIA were observed in the first 30 procedures of our series. They were performed without distal protection devices and are in the range of what is suggested as the procedural learning curve (50 cases). It is now clearly evident from the literature that systematic use of cerebral protection devices reduces thromboembolic complications during CAS;18,19 this is confirmed, in our population, by the absence of any cerebral complication in the last 63 consecutive procedures of this study which were performed with distal protection. The above mentioned direct referral of patients to a cardiology unit for a cardiovascular problem can also explain, at least partially, the ratio of asymptomatic to symptomatic subjects (66/34%). The prevalence of asymptomatic patients must have favored the overall low incidence of complications. In fact, at least as regards the surgical aspect, the treatment of asymptomatic patients is characterized by a lower incidence of complications,2 so that the AHA guidelines for endoarterectomy in these patients state that the rate of morbility and mortality must be kept below 3%.11 In our series, except for one TIA, all observed in-hospital cerebral complications occurred in symptomatic patients. A separate analysis of the rate of complications in the two groups of patients still compares well with the recommended rate of AHA for endoarterectomy. Study limitations. Some limitations must be considered. This is an observational, not a randomized study. All interventional procedures were performed by a single, highly experienced interventional cardiologist. No comparative studies, in terms of procedural results, between a cardiological and non-cardiological environment are available. Conclusion We have shown that systematic CAS is a feasible treatment of the carotid artery bifurcation stenosis with high procedural success and low peri-operative and short-term complications. Its performance in a cardiological setting may have contributed to the satisfying procedural results and allowed a potential successful handling of cardiovascular complications, particularly frequent in a population with diffuse atherosclerotic involvement and many cardiological co-morbidities.

1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445–453. 2. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. J Am Med Assoc 1995;273:1421–1428. 3. Barnett HJM, Taylor DW, Eliasziw M, et al. for the North American Symptomatic Carotid Endarterectomy Trial Collaborators. Benefit of carotid endarterectomy in patients with symptomatic moderate to severe stenosis. N Engl J Med 1998;339:1415–1425. 4. European Carotid Surgery Trialists’ Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–1387. 5. Mathias K. Perkutane transluminale Katheterbehandlung supraaortaler arterienobstruktionen. Angio 1981;3:47–50. 6. Yadav JS, Roubin GS, Iyer S, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:376–381. 7. Wholey MH, Wholey M, Mathias K, et al. Global experience in cervical carotid artery stent placement. Cathet Cardiovasc Intervent 2000;50:160–167. 8. Roubin GS, New G, Iyer S, et al. Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis. A 5-year prospective analysis. Circulation 2001;103:532–537. 9. Fox DJ, Moran CJ, Cross TD, et al. Long-term outcome after angioplasty for symptomatic extracranial carotid stenosis in poor surgical candidates. Stroke 2002;33:2877–2880. 10. Moore WS, Barnett HJM, Beebe HG, et al. Guidelines for carotid endarterectomy: A multidisciplinary consensus statement from the ad hoc committee, American Heart Association. Circulation 1995;91:566–579. 11. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: A statement for healthcare professionals from a special writing group of the stroke council. Circulation 1998;97:501–509. 12. Joakimsen O, Bonaa KH, Stensland-Bugge E. Reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology. The Tromso Study. Stroke 1997;28:2201–2207. 13. Hertzer NR, Young JR, Beven EG, et al. Coronary angiography in 506 patients with extracranial cerebrovascular disease. Arch Int Med 1985;145:849–852. 14. Rothwell P, Slattery J, Warlow CP. A systematic review of the risks of stroke and death due to endarterectomy for symptomatic carotid stenosis. Stroke 1996;27:260–265. 15. Weenberg DE, Lucas FL, Birkmeyer JD, et al. Variation in carotid endarterectomy mortality in the medicare population. Trial hospitals, volume, and patient characteristics. J Amer Med Assoc 1998;279:1278–1281. 16. Al-Mubarak N, Colombo A, Gaines PA, et al. Multicenter evaluation of carrotid artery stenting with a filter protection system. J Am Coll Cardiol 2002;39:841–846. 17. Whitlow PL, Lylyk P, Londero H, et al. Carotid artery stenting protected with an emboli containment system. Stroke 2002;33:1308–1314. 18. Kastrup A, Groeschel K, Krapf H, et al. Early outcome of carotid angioplasty and stenting with and without cerebral protection devices. A systematic review of the literature. Stroke 2003;34:813–819. 19. Cremonesi A, Manetti R, Setacci F, et al Protected carotid stenting. Clinical advantages and complications of embolic protection devices in 442 consecutive patients. Stroke 2003;34:1936–1941.