Microembolization: The Achilles’ Heel of CAS?

The incidence of procedural microembolization may depend on the type of EPD employed.

By Sumaira Macdonald, MBCHB, FRCP, FRCR, PhD; Barry T. Katzen, MD, FACC, FACR, FSIR; AND Claudio Schönholz, MD
 

Stroke is a major public health concern, with more than 750,000 incidents of stroke occurring each year in the United States.1-4 It is the third leading cause of death after heart disease and cancer, and it is the leading neurologic cause of long-term disability.5

Approximately 30% of strokes are caused by carotid artery occlusive disease.6 When patients with significant carotid artery occlusive disease develop symptoms, it is usually the result of embolization from the embolic site. The therapeutic goal of carotid endarterectomy (CEA) and carotid artery stenting (CAS) is to reduce the risk of ipsilateral stroke. However, both the surgical and endovascular treatment approaches carry a procedural risk of ischemic stroke, which results primarily from manipulation of the plaque that can lead to macro- and microembolization.

Since the introduction of CEA in 1954, the technique has improved to the point that two well-known randomized trials have proven CEA’s superiority over medical treatment,7,8 and it is currently considered to be the standard of care for patients with significant carotid artery disease. Thromboembolism is recognized as the most important factor in the pathogenesis of perioperative stroke associated with CEA.9,10

First performed 20 years ago, CAS has until lately had a limited effect on the management of carotid artery disease, mainly because it was performed only at a few institutions for a few selected indications, and its cost was not reimbursed by insurance carriers and government regulation. However, with the perfecting and standardization of endovascular techniques and improvements in stents and distal embolic protection devices (EPDs), CAS has become a viable alternative treatment for carotid artery occlusive disease.11

Periprocedural embolization is cited as a factor that prevents CAS from achieving optimal procedural safety. The greatest perceived risk associated with CAS is periprocedural stroke or asymptomatic brain infarction resulting from the release, migration, and embolization of debris during predilatation, stenting, and postdilatation of the carotid artery stenosis. Therefore, it is intuitive to attempt to prevent these presumptive emboli, whether they are composed of air or formed elements, from reaching the brain. This is the justification for the employment of cerebral protection, which may follow three philosophies: balloon occlusion (either proximal or distal), distal filtration, and flow reversal.12

Embolization has been shown to occur during every stage of CAS,13 but embolic protection starts once the cerebral protection device is deployed and finishes when the device is retrieved. This means that embolization can still occur during the initial placement of the guide catheter in the artery and can also be seen after the procedure has been completed. Careful technique and limitation of instrumentation is crucial to reduce or suppress embolization during the initial phase of the procedure, and administration of dual-antiplatelet medication, statins, and appropriate use of stents of adequate size and cell configuration will sufficiently address most of the postprocedure emboli.14

Preprocedural identification of lesions with a high embolic potential has been studied as a means of optimizing the treatment algorithm of carotid revascularization. In a published study of carotid plaques after endarterectomy, Milei et al found that 24% of plaques have thrombus lining. 15 In another study performed at Stanford, the incidence was 49%.16

Reliable identification of vulnerable carotid plaque remains elusive.17 Echogenicity, heterogenicity, and degree of stenosis (a surrogate marker of embolic load) have all been postulated to correlate with increasing procedural risk, although some of the findings are conflicting. An objective ultrasonic parameter, the grayscale median, has been used to specifically determine embolic risk during CAS.18 A grayscale median < 25 is believed to be associated with increased risk of stroke during CAS. This technique is not widely available, perhaps because the evaluation of this parameter requires software modifications of the ultrasound machine and specific sonographer training. Lacking a definitive test that can identify embolic risk in specific patients, and with some evidence of benefit for the use of EPDs (albeit not level I evidence), their use has become mandatory in the United States as part of the reimbursement approval process. Payment is not allowed unless embolic protection is employed.

CEREBRAL PROTECTION DEVICES AND MACROEMBOLI
There is no doubt that macroemboli can be retrieved from each of the three types of cerebral protection (Figure 1). This includes devices affecting flow arrest, such as distal balloon occlusion (PercuSurge GuardWire, Medtronic, Inc., Minneapolis, MN) or proximal flow arrest (Mo.Ma, Invatec S.p.A., Roncadelle, Italy), flow reversal (GORE Flow Reversal System, W. L. Gore & Associates), or distal filtration. There is level IV and level V evidence to support this contention from reported series. In 2001, the first cerebral protection device to become available was the PercuSurge distal balloon occlusion system, and filters generally started becoming available thereafter. Early reports indicated that debris, including fibrin, cholesterol clefts, red and white cell aggregates, and organized thrombus, could be retrieved from filters (Figure 2).19 It was thought that this material was likely to have been liberated by the endovascular manipulation of the carotid bifurcation plaque with subsequent entrapment rather than forming on the filter device in situ, although this remains unproven.

Although ex vivo work on the prototype of the Neuroshield (originally MedNova, now Emboshield, Abbott Vascular, Santa Clara, CA) suggested that 88% of the liberated embolic burden during carotid angioplasty was trapped, the in vivo capture rate is not known.20 Distal filters are not designed to capture particles smaller than the pore size of the available devices (currently 60–140 µm) that may pass unhindered to the brain. Filters may also exhibit failure to capture debris when suboptimal wall apposition is achieved. In vitro testing showed that filters can allow particles much larger than the pore size to pass by the filter.21 Supporting evidence for the passage of smaller particles (ie, particles < 60 μm) comes from ex vivo work analyzing carotid angioplasty.1 Guidewire passage alone generated 40,000 microemboli, although emboli were generated at each procedural stage, and a substantial number of emboli < 60 µm were produced. These are likely to evade capture by currently available filters but may be controlled by alternative protection strategies. The reported mean size of trapped particles ranged from 4 to 5,043 µm, and the numbers released range from 12 to 34,000 µm for all earlier devices. Regarding contemporary CAS practice, visible debris was present in 169 of 279 filters (60%) evaluated.22 This would imply that despite a number of technical advances since the inception of percutaneous carotid intervention as a rudimentary angioplasty technique, there might still be a substantial macroembolic penalty.12

DISTAL PROTECTION DEVICES AND MICROEMBOLI
The majority of CAS procedures are performed under some form of mechanical protection. During procedures in which embolic protection is used, 90% of treatments involve distal protection/filtration devices. Even so, current protected CAS procedures yield microemboli that are detected on transcranial Doppler (TCD) and diffusion- weighted magnetic resonance imaging (DW-MRI) of the brain. TCD is the only examination that can monitor intracranial blood flow in real time, thus detecting both symptomatic and asymptomatic cerebrovascular embolic events as they occur.23

Microemboli Detected on TCD
Differentiating gaseous from solid emboli with a high level of sensitivity has been reported using insonation at two ultrasound transducer frequencies of 2.5 and 2 MHz (Embo-Dop system, Compumedics, Singen, Germany) and would help determine the embolic source. Differentiation between solid and gaseous microemboli is based on the principle that solid microemboli reflect more ultrasound at a higher rather than lower frequency, whereas the opposite is the case for gaseous microemboli. This technique is still under investigation.24-26

TCD was used to compare the frequency of microembolic signals (MES) during CAS without protection versus CAS using a distal occlusion balloon (PercuSurge GuardWire). In the group of patients protected by distal balloon, a significant reduction of MES (MES counts = 164 ± 108 in the control vs 68 ± 83 in the protected group; P = .002) was observed during predilation, stent deployment, and postdilation.27

A Dutch single-center prospective analysis of microembolic signals on procedural TCD for unprotected CAS and filter-protected CAS reported that the use of filters may be associated with an increase in the numbers of distal microemboli.28 Patients were divided into three groups: 161 patients treated before filters had become available (group 1), 151 patients treated with filters (group 2), and 197 patients treated without filters after these devices had become available (group 3). The authors concluded that carotid angioplasty and stent placement yielded more microemboli in patients treated with filters than in unprotected procedures; however, the infrequent occurrence of cerebral sequelae did not allow comprehensive statistical comparison among groups. Within a clinical randomized trial performed at the Sheffield Vascular Institute (SVI), there were significantly more MES in patients in whom a filter-type cerebral protection device had been employed (Neuroshield). Furthermore, off-site analysis determined that a substantial proportion of these MES corresponded to particulate matter and could not be simply dismissed as air due to agitated contrast injection.29 It is well established that TCD can detect small emboli, but predicting which of these emboli will result in focal brain ischemia is not yet possible with the current technology.

DWI Findings
DWI is the most powerful tool for the detection of focal brain ischemia in the acute stage. It has been used for the detection of cerebral embolism (Figure 3) after acute ischemic neurologic events and for the detection of silent ischemic brain lesions after diagnostic cerebral angiography, coronary bypass surgery, CEA, and CAS. The hyperintense DWI lesions vanish over 2 weeks and may reappear as hypointense lesions thereafter. Therefore, optimal timing of the DWI is critical.30 However, it should be noted that many DWI lesions reverse within months, and the extent of permanent injury may be overestimated.31

DWI is the most powerful tool for the detection of focal brain ischemia in the acute stage. It has been used for the detection of cerebral embolism (Figure 3) after acute ischemic neurologic events and for the detection of silent ischemic brain lesions after diagnostic cerebral angiography, coronary bypass surgery, CEA, and CAS. The hyperintense DWI lesions vanish over 2 weeks and may reappear as hypointense lesions thereafter. Therefore, optimal timing of the DWI is critical.30 However, it should be noted that many DWI lesions reverse within months, and the extent of permanent injury may be overestimated.31

A prospective study that included 53 patients was conducted to determine the incidence of new areas of cerebral ischemia by DWI in high-surgical-risk patients undergoing filter-protected CAS. Postprocedural DWI detected new focal ischemic lesions in 21 patients (40%). The average number of lesions was 5.9 per patient, and the mean lesion volume was 1 mL or less in 19 patients (90%). Small differences were found in the lesion distribution: homolateral anterior circulation in eight cases (15.1%), other vascular territories in seven cases (13.2%), and homolateral anterior circulation plus other vascular territories in six cases (11.3%). The microembolization risk seemed nonpredictable on the basis of clinical parameters and internal carotid artery lesion characteristics. An increased risk in the rate of ipsilateral hemispheric embolization has been observed in difficult carotid arch configurations (P = .04).32

In a prospective nonrandomized study including 48 patients, a DWI study was performed 1 hour before and 48 hours after filter-protected CAS. In the 23 patients imaged 1 hour postprocedure, new lesions were found in two (9%), and 18 (78%) had new lesions at 48 hours (P < .001). For the entire study group, the incidence of new lesions at 48 hours was 67% (36 of 54). The investigators believe that significant embolization continues for at least 48 hours postprocedure causing lesions on DWI when there is no mechanism for cerebral protection.33

A recent randomized trial compared unprotected CAS with filter protection using the Accunet filter (formerly Guidant Corporation, now Abbott Vascular).34 This work postdates and references the SVI’s randomized trial and had the same findings. There was a nonsignificant increase in lesions on DWI in the filter-protected group. The findings did not reach significance, probably because there were insufficient numbers (30 in the SVI trial and 35 in the Pittsburgh trial). Kastrup et al later stated that approximately 120 to 140 patients would be needed for a randomized trial based on DWI lesions to be adequately powered; however, Kastrup’s article postdates the SVI trial.35 Furthermore, it is important to note that Kastrup’s estimated numbers are based on a “etrospective analysis of nonrandomized data with all its inherent limitations.”36 Although distal filters have been shown to capture emboli released during CAS, there is also evidence to indicate that emboli are missed either through the pores of the filters or around them due to suboptimal wall apposition. The evidence showing that filter-protected CAS produces more microemboli as detected with TCD or DWI when compared with CEA (and more microemboli than unprotected CAS) indicates that there is still room for improvement in filter design.

PROXIMAL PROTECTION OR FLOW REVERSAL AND MICROEMBOLI
The Mo.Ma system provides cerebral protection by endovascular occlusion of the common and external carotid arteries leading to a flow cessation in the target vessel. A TCD study comparing this device with the FilterWire (Boston Scientific Corporation, Natick, MA) showed that the Mo.Ma system significantly reduced MES counts during the procedural phases of wire passage of the stenosis, stent deployment, balloon dilation, and in total (MES counts for the filter device were 25 ± 22, 73 ± 49, 70 ± 31, and 196 ± 84 during the three phases and in total, respectively, and MES counts for the Mo.Ma system were 1.8 ± 3.2, 11 ± 19, 12 ± 21, and 57 ± 41, respectively; P < .0001).37

The GORE Flow Reversal System is a closed system that allows the arrest of common carotid artery flow, continuous passive internal carotid artery (ICA) flow reversal, or augmented active ICA flow reversal so that any particles released during CAS will pass retrograde through the catheter and be retrieved in the arteriovenous conduit filter outside the body. The three components of the device were designed specifically to allow retrograde flow in the ICA and minimize migration of particles or collection of material that could subsequently embolize. The establishment of a shunt (and subsequent flow reversal) allows for additional protection from uncovered collaterals that can contribute to continued antegrade ICA flow if the shunt is not in place. The functional principle behind this device is based on an observation made on TCD during CEA, that is, clamping the common carotid artery and the external carotid artery and inserting a shunt in the distal end of an arteriotomy-induced flow reversal in the middle cerebral artery (MCA) if the other end of the shunt was left open to the air.38

A preliminary evaluation of flow reversal in 28 of 30 patients in whom satisfactory reversal of flow could be established revealed a complete absence of MES on procedural TCD.39 In a larger series including 200 patients, TCD monitoring was used in 132 patients, and no embolic signals were registered during reversal of flow. In some patients, TCD showed intracranial ICA or MCA flow reversal, in others, there was sufficient collateralization from the anterior cerebral artery.40 The GORE Flow Reversal System is unique in this finding.

In an ongoing study at the Medical University of South Carolina, bilateral temporal monitoring TCD was performed in patients undergoing CAS. Seven patients were protected using various distal filters that had been approved by the US Food and Drug Administration and another seven using the reversal of flow technique with the GORE Flow Reversal System. Doppler spectral and Mmode signals from ultrasound probes mounted to a headframe were continuously recorded. The use of software detecting high-intensity transient signals allowed for realtime intraoperative feedback about the efficacy of the embolic protection method used, as well as the cerebral blood flow dynamics. The recorded data were digitally stored for postprocedural comparison between the findings obtained with the different protection techniques and phases of the procedures. Quantification of MES for statistical analysis was performed by manual review to allow for differentiation from injection and other artifacts. TCD signal recordings were evaluated for three stages of the procedure: (1) protection device deployment (PD); (2) stent delivery including pre- and postdilatation (SD); and (3) protection device removal (PR). MES were counted when detected in the MCA of the side of the treated carotid artery and are presented as filter versus flow reversal treatment group means. Patients undergoing CAS using the GORE Flow Reversal System demonstrated significantly less average total MES counts compared to procedures using filter devices (431.3 ± 65.4 vs 116.3 ± 20.8, N = 14; P < .001). Although the PD and PR phases were not significantly different (PD = 102.3 ± 28.4 vs 73.7.0 ± 19.6; P = not significant; and PR = 34.3 ± 24.4 vs 36.7 ± 8.9; P = not significant), in the SD phase, with the respective protection device in place, the average MES counts were significantly higher in patients treated with filter protection (294.7 ± 5 6.2 vs 6 ± 1.03; P < .001). In conclusion, preliminary analysis of the study data suggests that patients undergoing CAS under reversal of flow with the GORE device have significantly fewer MES than patients protected with filter devices (Figures 4 and 5).41

A single-center, prospective, nonrandomized study compared DWI lesions in patients undergoing CAS with flow reversal and patients undergoing cerebral angiography alone. There was no statistical difference between the control group (12%) and the flow reversal group (18%). CAS with flow reversal can be performed with the same embolic risk as diagnostic angiography.42

Early TCD and DWI data from flow-reversal-protected CAS shows promise in reducing embolic activity during the most highly embologenic phases of CAS. Data from the EMPIRE trial show a low stroke and death rate of 2.6% for both symptomatic patients and octogenarians. Both are patient populations that are considered to be at high risk for ischemic events during CAS. These data hint at real clinical benefit for these high-risk subgroups in CAS. Whether these benefits remain through more extensive evaluation and are shown to be a result of reduced emboli injury during CAS needs further study.

The clinical effect of these “silent” ischemic lesions within brain areas without primary motor, sensory, or linguistic function (“noneloquent” brain areas) is debated. Subtle changes in cognitive function are currently being assessed after CAS. There is increasing evidence, however, that the cumulative burden of ischemic brain injury causes neuropsychological deficits or a steeper decline in cognitive function and increases the incidence of dementia in the clinical setting of coronary artery bypass surgery and in screened healthy populations with DWI lesions.43-45

CONCLUSION
Macro- and microembolization are associated with the treatment of carotid artery stenoses by carotid stenting. Various types of filter devices seem to be effective in preventing macroembolization but are not designed to provide complete protection from particles smaller than the pore sizes of the device and may in fact increase the number of MES. Microembolization remains the Achilles’ heel of CAS, and the incidence of procedural microembolization may depend on the type of EPD employed.

A systematic review of MRI studies showed that cerebral protection devices appeared to significantly reduce the number of new ipsilateral DWI lesions after CAS. However, none of the evaluated studies were randomized trials, and many studies employed historical nonconcurrent controls in which important confounding variables such as type of stent, learning curve, and the demographics of the patient population were not corrected for. Furthermore, 33% of patients had new DWI lesions within the vascular territory of the treated carotid artery even after mostly filter-protected CAS, which documents that dislodgement of a large number of embolic particles to the brain is not prevented by the use of filter-type protection devices.46 The flow reversal technique showed no MES during phases of the procedure when most particles are released.

There is not yet proof that MES are related to new lesions using DW-MRI studies. The correlation between these factors and cognitive function is still debatable and remains troublesome when observed. It is recognized, however, that MES are better tolerated in young patients with good cerebral functional reserve than in older individuals with low functional reserve.47 It seems reasonable to say that MES cannot do any good to the brain, and their occurrence should be at least a reason for concern. Until we have conclusive evidence about MES and their potential damage to the brain, it would seem preferable to try to suppress or minimize its occurrence. All embolic protection devices have advantages and disadvantages and likely vary in their efficacy. Although filtration devices clearly protect the brain from larger particles, which would otherwise likely cause major stroke, embolic events have been documented during their use. Proximal occlusion may offer some improvement in events in this regard; however, flow reversal appears to be closer to the ideal device in terms of providing complete protection from embolic debris through establishment of the reverse flow circuit.

Sumaira Macdonald, MBChB, FRCP, FRCR, PhD, is a Consultant Vascular Radiologist and Honorary Clinical Senior Lecturer at Freeman Hospital, Newcastle upon Tyne, England. She has disclosed that she receives research fees and is a consultant to Abbott Vascular, Cordis Corporation, W. L. Gore & Associates, Invatec, and Medtronic, Inc. Dr. Macdonald may be reached at sumaira.macdonald@nuth.nhs.uk.
Barry T. Katzen, MD, FACC, FACR, FSIR, is the Founder and Medical Director of Baptist Cardiac and Vascular Institute and Clinical Professor of Radiology at the University of South Florida College of Medicine in Florida. He has disclosed that he is a member of the scientific advisory board for W. L. Gore & Associates. Dr. Katzen may be reached at btkatzen@aol.com.
Claudio Schönholz, MD, is with MUSC Heart and Vascular Center in Charleston, South Carolina. He has disclosed that he is a member of the scientific advisory board for W. L. Gore & Associates. Dr. Schönholz may be reached at (843) 693-2077; schonhol@musc.edu.

  1. Carandang R, Seshadri S, Beiser A, et al. Trends in incidence, lifetime risk, severity, and 30- day mortality of stroke over the past 50 years. JAMA. 2006;296:2939-2946.
  2. Wolf PA. Epidemiology of stroke. In: Mohr JP, Choi DW, Grotta JC, et al, eds. Stroke: Pathophysiology, Diagnosis, and Management. 4th ed. Philadelphia, PA: Churchill Livingstone; 2004:13-34.
  3. American Heart Association. Heart Disease and Stroke Statistics—2006 Update. Dallas, TX: American Heart Association; 2006.
  4. Broderick J, Brott T, Kothari R, et al. The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first ever and total incidence rates of stroke among blacks. Stroke. 1998;29:415-421.
  5. Kwan J. Clinical epidemiology of stroke. CME J Geriatr Med. 2001;3:94-98.
  6. American Heart Association. Heart and stroke facts: 1994 statistical supplement. Dallas, TX: American Heart Association; 1993.
  7. 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.
  8. Randomized trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351:1379-387.
  9. Krul JM, van Gijn J, Ackerstaff RG, et al. Site and pathogenesis of infarcts associated with carotid endarterectomy. Stroke. 1989;20:324-328.
  10. Spencer MP. Transcranial Doppler monitoring and causes of stroke from carotid endarterectomy. Stroke. 1997;28:685-691.
  11. Schonholz C, Uflacker R, Parodi JC, et al. Is there evidence that cerebral protection is beneficial? Clinical data. J Cardiovasc Surg. 2006;47:137-141.
  12. Macdonald S. The evidence for cerebral protection: an analysis and summary of the literature. Eur J Radiol. 2006;60:20-25.
  13. Coggia M, Goeau-Brissonniere O, Duval JL, et al. Embolic risk of the different stages of carotid bifurcation balloon angioplasty: an experimental study. J Vasc Surg. 2000;31:550-557.
  14. Uflacker R. How to optimize carotid artery stenting. J Cardiovasc Surg (Torino). 2007;48:131-149.
  15. Milei J, Parodi JC , Ferreira M, et al. Atherosclerotic plaque rupture and intraplaque hemorrhage do not correlate with symptoms in carotid artery stenosis. J Vasc Surg. 2003;38:1241- 1247.
  16. Bassiouny H, Davis H, Massawa N, et al. Critical carotid stenoses: morphologic and chemical similarity between symptomatic and asymptomatic plaques. J Vasc Surg. 1989;9:202-212.
  17. Macdonald S. Brain injury secondary to carotid intervention. JEVT. 2007;14:219-231.
  18. Biasi GM, Froio A, Diethrich EB, et al. Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) study. Circulation. 2004;110:756-762.
  19. Macdonald S, Venables GS, Cleveland TJ, et al. Protected carotid stenting: safety and efficacy of the mednova neuroshield filter. J Vasc Surg. 2002;35:966-972.
  20. Ohki T, Roubin G, Veith FJ, et al. Efficacy of a filter device in the prevention of embolic events during carotid angioplasty and stenting: an ex vivo analysis. J Vasc Surg. 1999;30:1034- 1044.
  21. Finol EA, Siewiorek GM, Scotti CM, et al. Wall opposition and performance of distal protection filters. JEVT. 2008;15:177-185.
  22. Sprouse II LR, Peeters P, Bosiers MJ. The capture of visible debris by distal cerebral protection filters during carotid artery stenting: is it predictable? J Vasc Surg. 2005;41:950-955.
  23. Garami Z, Charlton-Ouw K, Broadbent K, et al. A practical guide to transcranial Doppler monitoring during carotid interventions. Vascular Ultrasound Today. 2008;1:13.
  24. Chen CI, Iguchi Y, Garami Z, et al. Analysis of emboli during carotid stenting with distal protection device. Cerebrovasc Dis. 2006;21:223-228.
  25. Markus H, Punter M. Can transcranial Doppler discriminate between solid and gaseous microemboli? Assessment of a dual-frequency transducer system. Stroke. 2005;36:1731-1734.
  26. Russell D, Brucher R. Online automatic discrimination between solid and gaseous cerebral microemboli with the first multifrequency transcranial Doppler. Stroke. 2002;33:1975-1980.
  27. Al-Mubarak N, Roubin GS, Vitek J, et al. Effect of the distal balloon protection system on microembolization during carotid stenting. Circulation. 2001;104:1999-2002.
  28. Vos JA, van den Berg JC, Ernst SM, et al. Carotid angioplasty and stent placement: comparison of transcranial Doppler US data and clinical outcome with and without filtering cerebral protection devices in 509 patients. Radiology. 2005;237:374-375.
  29. Macdonald S. Thesis for the Degree of Doctor of Philosophy: Neuroprotection and flow dynamics in carotid stenting, October 2004.University of Sheffield Main Library Volumes I & II; 2004 [MO115661SH] Main Lib Thesis 12638.
  30. Lacroix V, Hammer F, Astarci P, et al. Ischemic cerebral lesions after carotid surgery and carotid stenting. Eur J Vasc Endovasc Surg. 2007;33:430-435.
  31. Palombo G, Faraglia V, Stella N, et al. Late evaluation of silent cerebral ischemia detected by diffusion-weighted MR imaging after filter-protected carotid artery stenting. AJNR Am J Neuroradiol. 2008;29:1340-1343.
  32. Hammer F, Lacroix V, Duprez T, et al.Cerebral microembolization after protected carotid artery stenting in surgical high-risk patients: results of a 2-year prospective study. J Vasc Surg. 2005;42:847-853
  33. Rapp JH, Wakil L, Sawhney R, et al. Subclinical embolization after carotid artery stenting: new lesions on diffusion-weighted magnetic resonance imaging occur postprocedure. J Vasc Surg. 2007;45:867-874
  34. Barbato JE, Dillavou E, Horowitz MB, et al. A randomized trial of carotid artery stenting with and without cerebral protection. J Vasc Surg. 2008;47:760-765.
  35. Kastrup A, Nägele T, Gröschel K, et al. Incidence of new brain lesions after carotid stenting with and without cerebral protection. Stroke. 2006;37:2312-2316.
  36. Kastrup A, Schnaudigel S, Gröshel K. Regarding “A randomized trial of carotid artery stenting with and without cerebral protection.” J Vasc Surg. 2008;48:505; author reply 505.
  37. Schmidt A, Diederich KW, Scheinert S, et al. Effect of two different neuroprotection systems on microembolization during carotid artery stenting. J Am Coll Cardiol. 2004;44:1966-1969.
  38. Parodi JC, La Mura R, Ferreira LM, et al. Initial evaluation of carotid angioplasty and stenting with three different cerebral protection devices. J Vasc Surg. 2000;32:1127-1136.
  39. Adami C, Scuro A, Spinamano L, et al. Use of the Parodi anti-embolism system in carotid stenting: Italian trial results. JEVT. 2002;9:147-154.
  40. Parodi JC, Schönholz C, Parodi FE, et al. Initial 200 cases of carotid artery stenting using a reversal-of-flow cerebral protection device. J Cardiovasc Surg. 2007;48:117-124.
  41. Schönholz C, Kasirajan K, Welzig C, et al. Transcranial Doppler monitoring during carotid artery stenting: comparison between flow reversal and filter for cerebral protection. Presented at the TCT 2009 Symposium; September 2009; San Francisco, CA.
  42. Asakura F, Kawaguchi K, Sakaida H, et al. Diffusion-weighted MR imaging in carotid angioplasty and stenting with protection by the reversed carotid arterial flow. AJNR. 2006;27:753-758.
  43. Bendszus M, Stoll G. Silent cerebral ischemia: hidden fingerprints of invasive medical procedures. Lancet Neurol. 2006;5:364-372.
  44. Pugsley W, Klinger L, Paschalis C, et al. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke. 1994;25:1393-1399.
  45. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215-1222.
  46. Schnaudigel S, Groschel K, Pilgram S, et al. New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature. Stroke. 2008;39:1911-1919.
  47. Parodi JC, Parodi FE, Schönholz C. Proximal occlusion and flow reversal: the ideal cerebral protection method during carotid artery stenting. Endovascular Today. 2006;5:67-72.
 

Contact Info

For advertising rates and opportunities, contact:
Craig McChesney
484-581-1816
cmcchesney@bmctoday.com

Stephen Hoerst
484-581-1817
shoerst@bmctoday.com

Charles Philip
484-581-1873
cphillip@bmctoday.com

About Endovascular Today

Endovascular Today is a publication dedicated to bringing you comprehensive coverage of all the latest technology, techniques, and developments in the endovascular field. Our Editorial Advisory Board is composed of the top endovascular specialists, including interventional cardiologists, interventional radiologists, vascular surgeons, neurologists, and vascular medicine practitioners, and our publication is read by an audience of more than 22,000 members of the endovascular community.