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Proximal endovascular occlusion for CAS

Carotid artery stenting (CAS) is a validated treatment to reduce the incidence of stroke in patients with moderate-to-severe symptomatic carotid stenosis as well as among those with severe asymptomatic carotid stenosis. CAS showed no inferiority to carotid endarterectomy (CEA) in the prevention of stroke; consequently CAS is considered to be an adequate alternative to CEA, particularly in patients at increased risk for CEA.
Because of the occurrence of peri-procedural neurological ischaemic events, the use of embolic protection devices (EPDs) during CAS is currently recommended by guidelines and is thought to be partially responsible for the improved outcomes.1 No randomised trials have demonstrated the safety and efficacy of EPDs and early meta-analysis demonstrated a reduction of stroke or death risk with these devices.2,3
Embolic protection devices (EPDs)
Two types of EPDs are commercially available:
  • Distal filters. They act by placing a basket distal to the lesion aiming at capturing embolic debris and are currently the most frequently used in clinical practice. They do not occlude cerebral blood flow and allow visualisation of target lesions during stent deployment but are encumbered by some embolic risk (possible passage of small particles to the brain) and possible difficulties in retrieving 
  • Proximal occlusion devices (PODs).These stop or reverse flow by clamping the external and common carotid artery. Theoretically they are more effective in preventing embolisation because they establish neuroprotection before crossing the lesion.
Proximal EPDs
The only commercially available proximla EPD is the Mo.Ma system (Medtronic), which is a 8 or 9 Fr introducer sheath (working length 95cm) placed into the common carotid artery (CCA) via placing a stiff wire into the external carotid artery (ECA). The sheath has a distal ECA balloon and a CCA balloon located 60mm proximal to the tip. The balloons are sized to fit a reference vessel diameter of the CCA from 5 to 13mm and an ECA from 3 to 6mm. By inflating the compliant balloons in both the CCA and ECA, flow in the internal carotid artery (ICA) is halted. There is a working channel with an exit port located between the balloons. Blood is manually aspirated from the sheath, effectively creating intermittent active flow reversal. After flow arrest is instituted, the lesion can be crossed with any variety of wire. With the aspiration of the stagnant column of blood, both micro- and macro-emboli are captured prior to resuming antegrade flow. The presence of critical stenosis of the ECA does not preclude the safe placement of the device.4
Clinical experience with proximal EPDs
In a prospective single-centre Italian registry of 1300 consecutive patients underging CAS using the Mo.Ma system, a 30-day stroke and death rate of 1.4% was reported.5 The authors found a higher risk for symptomatic patients and for those at high surgical risk. Independent predictors of adverse outcome were lack of CAS experience, the presence of a symptomatic lesion, and the absence of clinical hypertension. Of note, in this registry, the CAS risk for patients age >80 years was the same as for younger patients.
The ARMOUR trial,6 is a prospective, multicentre trial that evaluated the 30-day safety and effectiveness of CAS in high-risk surgical patients using the Mo.Ma device. A total of 34 (15%) symptomatic and 188 (75%) asymptomatic patients were enrolled (mean age: 74.7; male: 66.7%; >80 years: 29%). Contralateral carotid stenosis  >70% was an exclusion criterion. The 30-day stroke, death, and MI rate was 2.7%, with a 30-day stroke rate of 0.9%. The authors concluded that the Mo.Ma device is safe and effective for high-risk surgical patients undergoing CAS.
Intolerance to proximal EPDs
Proximal EPDs act through occlusion of the CCA and expose the ipsilateral cerebral hemisphere to hypoperfusion with consequent transient neurological symptoms. This phenomenon is termed occlusion intolerance (OI) (defined as any transient neurological deficit observed during occlusion time, but showing a complete recovery within 20 min after restoring antegrade flow).5
In the ARMOUR trial, OI occurred in 13.8% of patients after the proximal EPD deployment, with recovery of symptoms within 20 min in the majority (29 of 31 patients).6 In the Italian single centre registry, 20% developed OI, still allowing the completion of procedure. Only four patients (0.3%) were unable to tolerate proximal occlusion with conversion to a distal EPD or intermittent clamping technique.5 The low rate of OI is explained by the brief duration of arterial clamping (3–15 min) and the frequent presence of collateralisation avenues. 
The ability to predict in advance the risk of OI, which is relatively frequent, might help the operators to be ready to face this event.
In order to identify the predictors of developing carotid occlusion intolerance during proximal protected CAS, Giugliano et al analysed more than 600 consecutive patients undergoing CAS using the Mo.Ma device.7 In this study, OI occurred in 30.4% of patients. The most powerful independent predictor of OI was an occlusion pressure (OP; the pressure that can be measured in the internal carotid artery when both ECA and CCA balloons are inflated) ≤40mmHg, and the most powerful clinical predictor of such OP was the presence of contralateral ICA occlusion. In patients with OP >40mmHg, a periprocedural arterial pressure drop (≥50mmHg) and/or a prolonged occlusion time (time from the inflation to the deflation of the proximal balloon in the CCA) (≥300s) increase the chances of having OI.7
Proximal versus distal EPDs
It is generally accepted that EPDs reduce the risk of stroke from CAS. Proximal EPDs may afford better neuroprotection because their efficacy throughout all phases of the procedure, high efficiency in capturing particulate debris and better capture efficiency of large particles.
Embolic signals (ES) measured by transcranial doppler (TCD) during the procedure can be used as surrogate markers of atheroembolism. A randomised study of Mo.Ma versus the Filterwire EZ distal EPD demonstrated fewer microembolic signals (MES) with the Mo.Ma device throughout every phase of the CAS procedure.8
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a sensitive tool in identifying cerebral embolism after acute ischaemic neurological events and for the detection of silent ischaemic brain lesions after CEA, stenting and diagnostic cerebral angiography. A randomised clinical trial demonstrated that CAS with proximal EPD provides better cerebral protection than distal EPD, based on the occurrence of new ischaemic lesions detected by DW-MRI.9 These results are consistent with data reported by Montorsi10 but other studies have shown different results.11,12 
A meta-analysis of available studies13 compared the efficacy of the two neuroprotection systems in preventing embolisation during CAS detected by DW-MRI, evaluating the incidence of new ischaemic lesions per patient during procedure with filters or proximal balloon occlusion. In 357 patients included in the study, the number of new ischaemic lesions per patient detected by DW-MRI was significantly lower in the proximal balloon occlusion. Following CAS, the incidence of new ischaemic lesions detected at the contralateral site by DW-MRI was significantly lower in the proximal protection group. This meta-analysis suggests that the use of proximal balloon occlusion during CAS is associated with a significant reduction of the number of distal embolisations, when compared with the use of distal EPDs. It is important to note that some of the studies included in this meta-analysis lacked information about the operator experience, which is known to influence the outcome.14,15 This, together with plaque echogenicity, stent design, and patient responsiveness to drug therapy, could justify the differences in post-CAS distal embolisation and might justify discrepancies between the analysed studies.
An individual patient-based meta-analysis demonstrated that the use of proximal EPDs for neuroprotection in patients undergoing CAS was associated with a very low incidence of total stroke (1.71%) and composite major adverse cardiac and cerebrovascular event (MACCE; 2.25%) at 30 days.16 The excellent outcomes achieved are independent of patient gender, symptomatic status, and other baseline clinical characteristics, including the presence of a contralateral carotid occlusion.
Only patient age and diabetic status of the patient were identified among the baseline clinical patient characteristics as independent risk predictors of MACCE. Multiple previous studies employing the use of distal EPDs have identified patient age and symptomatic status as risk predictors of MACCE in CAS. The fact that the symptomatic status was not found to be a predictor of MACCE with use of proximal EPDs suggests that differences in the method of neuroprotection afforded by each type of device may alter or neutralise some of the potential risks, especially in symptomatic patients.
A more recent meta-analysis, including 12,281 patients, found no significant difference between proximal and distal EPDs in term of stroke incidence, 30-day mortality, or the incidence of new cerebral lesions or contralateral cerebral lesions detected by DW-MRI.17 In conclusion, the potential superiority of proximal EPDs is still not definitively proved.
EPDs in transradial and transbrachial CAS
In challenging anatomies, a transradial (TR) or transbrachial (TB) approach may be necessary. 
TR CAS with proximal protection has not been accepted widely because of the large size and stiffness of the device, making access and navigation of the supra-aortic vessels difficult. TB CAS is a valid alternative in selected cases but associated with a higher rate of vascular complications. The crossover rate to a TF approach could be a good indicator of feasibility.
Montorsi18 analysed 214 CAS patients treated via either a TR (n=154) or TB (n=60) approach. Mo.Ma system was used in 61 patients (28%) and distal filter protection in 153 (72%) patients.
Crossover to a femoral approach was required in 1/61 (1.6%) Mo.Ma patient vs 11/153 (7.1%) filter patients. A TR patient was shifted to filter because the Mo.Ma system was too short. The MACCE rate was 0% in the Mo.Ma patients and 2.8% in the filter group. Major vascular complications with a similar rate between the groups were confined to the TB approach. Chronic radial artery occlusion occurred in 6.6% of the Mo.Ma patients and in 3.2% of the filter patients.
These results confirm that CAS with a proximal protection device via a TR or TB approach is feasible, safe and effective, with low rate of vascular complications.
The use of EPDs during CAS procedure is recommended by guidelines to reduce the risk of periprocedural stroke. PODs are safe and effective in improving the outcome even in surgical patients at high risk, with a very high rate of technical success and a low rate of MACCE. 
OI is a possible complication, which can be predicted, but rarely requires switching to an alternative protection system and does not predict MACCE. 
Different clinical and imaging-based studies support the idea that a proximal protected CAS provides a more efficient and reliable cerebral protection; unfortunately this concept still has to be definitively proven in the clinical practice. 
1 Brott TG et al. ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/ CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease. J Am Coll Cardiol 2011;57:1002–44.
2 Touze E et al. Systematic review of the perioperative risks of stroke or death after carotid angioplasty and stenting. Stroke 2009;40:e683–e693. 
3 Garg N et al. Cerebral protection devices reduce periprocedural strokes during carotid angioplasty and stenting: A systematic review of the current literature. J Endovasc Ther 2009;16:412–27. 
4 Stabile E et al. Use of endovascular clamping as neuroprotection during carotid stenting in the presence of a critical ipsilateral stenosis of the external carotid artery. Euro Intervention 2008;3(5):588–92.
5 Stabile E et al. Proximal endovascular occlusion for carotid artery stenting: Results from a prospective registry of 1,300 patients. J Am Coll Cardiol 2010;55:1661–7.
6 Ansel GM et al; Investigators for the ARMOUR Pivotal Trial. Safety and effectiveness of the INVATEC MO.MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial. Catheter Cardiovasc Interv 2010;76:1–8.
7 Giugliano G et al. Predictors of carotid occlusion intolerance during proximal protected carotid artery stenting. JACC Cardiovasc Interv 2014:1237–44. 
8 Schmidt A et al. Effect of two different neuroprotection systems on microembolization during carotid artery stenting. J Am Coll Cardiol 2004;44(10):1966–9.
9 Bijuklic K et al. The PROFI study (Prevention of Cerebral Embolization by Proximal Balloon Occlusion Compared to Filter Protection During Carotid Artery Stenting): a prospective randomized trial. J Am Coll Cardiol 2012;59:1383–9. 
10 Montorsi P et al. Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque. A randomized trial of proximal versus distal cerebral protection. J Am Coll Cardiol 2011;58:1656–63. 
11 Cano MN et al. Randomized comparison of distal and proximal cerebral protection during carotid artery stenting. JACC Cardiovasc Interv 2013;6:1203–9. 
12 Castro-Afonso LH et al. Flow reversal versus filter protection: a pilot carotid artery stenting randomized trial. Circ Cardiovasc Interv 2013;6:552–9.  
13 Stabile E et al. Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting. A meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion. JACC Cardiovasc Interv 2014;7:1177–83. 
14 Stabile E et al. European registry of carotid artery stenting: Results from a prospective registry of eight high volume European institutions. Catheter Cardiovasc Interv 2012;80(2):329–34.  
15 Stabile E, Esposito G. Operator’s experience is the most efficient embolic protection device for carotid artery stenting. Circ Cardiovasc Interv 2013;6:496–7. 
16 Bersin RM et al. A meta-analysis of proximal occlusion device outcomes in carotid artery stenting. Catheter Cardiovasc Interv 2012;80(7):1072–8. 
17 Omran J et al. Proximal balloon occlusion versus distal filter protection in carotid artery stenting: A meta-analysis and review of the literature. Catheter Cardiovasc Interv 2017;89(5):923–31. 
18 Montorsi P et al. Carotid artery stenting with proximal embolic protection via a transradial or transbrachial approach: Pushing the boundaries of the technique while maintaining safety and efficacy. J Endovasc Ther 2016;23(4):549–60.