ISCHEMIC STROKE / PREVENTION

Carotid angioplasty with stenting (CAS)

Created 27/01/2022, last revision 07/11/2023

approx. 10-20% of ischemic strokes are caused by significant carotid stenosis (TOAST 1)
- the risk of stroke or vascular death with symptomatic ICA stenosis >70% is up to 26%/2 years, depending on symptoms, gender, and severity of the stenosis [Rothwell, 2005]
- risk of stroke in asymptomatic carotid stenosis of >60% is ~11%/5 years
- high-risk plaque characteristics and a higher degree of stenosis are associated with an increased risk
revascularization procedures reduce the risk of stroke; the benefit is only present when the perioperative risk is < 6% (symptomatic) or 3% (asymptomatic stenosis) → indications for revascularization are discussed here
endovascular treatment (carotid angioplasty and stenting – CAS) is an alternative to carotid endarterectomy (CEA)
since 1994, there have been significant improvements in technology (including proximal and distal embolic protection devices – EPD) and experience with stenting
new coated stents promise additional safety → see here
- Roadsaver, CGuard, Gore stent

randomized trials showed similar efficacy/safety of CAS and CEA (e.g., SAPPHIRE and CREST)
trials were designed to demonstrate non-inferiority and focused on patients with high surgical risk due to comorbidities (CAD, heart failure, pulmonary disease, etc.)
- CAS does not pose an increased risk compared to CEA and prevents at least the same number of strokes as CEA
patients with extensive white matter lesions on CT/MRI (ARWMC score ≥ 7) should undergo CEA (ICSS trial)

Carotid artery stenosis (ultrasound, CTA, MRA, DSA)

Trial	N of patients	30 days mortality/morbidity	long-term mortality/morbidity
CARESS (2003)	397	2 vs. 3%	–
CAVATAS (2001)	504	10 vs 10%	14.3 vs. 14.2
SAPPHIRE (2004)	334	4.4 vs. 9.9% (stroke+MI+death)	12.2 vs. 20.1
*CREST (2010)*	2502	5.2 vs. 4.6% (CEA) (stroke+MI+death) 4.1% vs 2.3% (CEA) (perioperative stroke)	primary endpoint: 7.2 vs 6.8% / 4 years stroke+death 6.4 (CAS) vs 4.7% (CEA)

Indications

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Contraindications

significant tortuosity and/or severe atherosclerosis of the aortic arch or proximal CCA/BCT that prevent safe catheter insertion
elongated aortic root, bovine arch
tortuous iliac artery
large calcified plaques preventing the artery remodeling
distal ICA diameter < 3 mm preventing the use of distal protection (relative contraindication, proximal protection can be used)
intracranial aneurysm > 5 mm or AV malformation (relative contraindication)

Procedure

order standard laboratory tests (CBC, coagulation test, basic metabolic panel) and other examinations required by an anesthesiologist
insert IV cannula and short-term urinary catheter and shave the groin (if transfemoral access is chosen)
educate the patient about the risks, benefits, and alternatives of the procedure; the patient must sign an informed consent

Premedication

proper medical prevention of thrombotic complications is critical
- start ≥ 3 days before the elective procedure
premedication is not standardized; different regimens were used in trials
- aspirin 300mg + clopidogrel 75 mg (SAPPHIRE trial) for 3 days
- aspirin 2x300mg + clopidogrel 2×75 mg (CREST trial) for 3 days
- aspirin 100mg + clopidogrel 75 mg for 3 days
if clopidogrel is contraindicated, ticlopidine 2×250 mg or ticagrelor can be used (no hard data for this recommendation)
in the acute setting, administer 600mg of aspirin and 4-6 clopidogrel tablets (300-450mg) at least 4 h before the procedure (antiplatelet therapy in acute stroke patients treated with IVT + CAS see here)
follow guidelines for the prevention of contrast-induced nephropathy

Periprocedural monitoring

the procedure is performed in cooperation with an experienced neuroradiologist, anesthesiologist, and a neurologist
analgosedation is preferred
basic monitoring:
- ECG and blood pressure (every 5 minutes)
  - correct BP correction is critical throughout the procedure (prevention of hyperperfusion syndrome) → parenteral antihypertensives
  - if bradycardia occurs, it may be necessary to administer ATROPIN 0.5 mg IV (which may also be given prophylactically)
- a pulse oximetry
- patient’s neurological status (level of consciousness, speech, visual field, acral motor skills)
TCD/TCCD monitoring (optional)
- hemodynamic information (hyperperfusion syndrome is associated with a significant increase in blood flow velocity in the MCA during the procedure, with a concomitant decrease of PI and RI)
- detection of embolization
  - microembolization (MES)
    - during contrast administration (dissolved air bubbles)
    - detection of particles released during critical phases of the procedure (distal protection filter insertion, pre-dilatation, stent deployment, post-dilatation, and protection withdrawal
    - increased risk of stroke with > 5 series of microembolizations
  - macroembolization leads to transient or permanent flow restriction in the MCA (vessel occlusion)

CAS technique

angioplasty – an inflatable balloon is used to dilate the narrowed area
angioplasty with secondary stenting – angioplasty with an inflatable balloon is performed, followed by the stent placement
primary stenting with a balloon-expandable stent – after insertion, the stent is expanded by balloon dilatation
primary stenting with a self-expanding stent (preferred)
- less traumatic and safer than angioplasty alone due to a reduced risk of distal embolization, plaque rupture, or dissection
- predilate lesion only if stenosis does not allow stent insertion; perform with a balloon smaller than the lumen diameter to achieve a lumen > 2.5 mm
- after stent deployment, post-dilatation is performed if a satisfactory result is not achieved or if the stent does not completely adhere to the arterial wall (contrast is visible between the wall and the stent)
- post-dilatation may lead to higher morbidity/mortality ⇒ perform in severe residual stenosis only [Obeid, 2015]
- self-expanding stents are less susceptible to deformation
it is recommended to use embolic protection devices (EPD)
- distal (both F-EPD and DO-EPD seem to be equally effective)
  - filter EPD (F-EPD)
  - distal occlusive EPD (DO-EPD)
- proximal
  - no need for a suitable landing zone
  - may be safer for highly embolic lesions
medication during procedure
- heparin with ACT > 250s
- aggressive hydration
- vasopressors if significant hypotension occurs
- Atropin IV
  - if bradycardia occurs during dilatation
  - prophylactic administration (problematic in patients with significant CAD)

CAS in patient with radiation-induced vasculopathy

Post-procedural management

retrieve filter (aspirate filter prior to retrieval if slow flow occurs)
remove the sheath and secure the groin (use Angioseal or other devices)
observe the patient in the ICU
continue monitoring of vital signs with careful BP control (check it every 15 minutes in the first hour, then every 30 minutes for at least 24 hours)
- careful correction of BP is the key to the prevention of hyperperfusion syndrome
check for complications and monitor neurological status (GCS, NIHSS)
perform control Doppler ultrasound (neurosonography) within 24 hours
- record PSV in the proximal, mid, and distal portions of the stent and in the segment distal to the stent
- stent artifactually increases flow velocities
after the procedure, continue dual antiplatelet therapy (DAPT; aspirin 100 mg + clopidogrel 75 mg) for at least 4 weeks (1-3 months)
then switch the patient to monotherapy (either ASA or CLP)

Complications

only complications related to stenting are discussed below
common adverse events related to endovascular procedures and diagnostic DSA are discussed elsewhere → overview of complications during endovascular procedures

Central complications
	1.1 Distal complications
	distal micro/macro embolization hyperperfusion syndrome (incl. hemorrhagic transformation) hypoperfusion (slow-flow) due to distal protection filter occlusion with dislodged thrombi and plaque debris hypoperfusion during prolonged inflation of the angioplasty balloon difficulty with retraction or intra-stent entrapment of the distal protection filter
	1.2 In-stent complications
	artery dissection or perforation/rupture vasospasms stent deformation, fracture, or migration stent thrombosis
	1.3 Proximal complications
	aorta / CCA dissection or perforation vasospasms
Peripheral (access-site) complications Femoral arterial access is commonly used for CAS, but radial or brachial approaches may be considered. Complications range from asymptomatic to life-threatening conditions
	femoral artery thrombosis dissecting pseudoaneurysm or groin AV fistula (shunt) groin hematoma (requires treatment in less than 0.5% of cases) retroperitoneal bleeding a rare but life-threatening complication with an incidence of 0.15% hemodynamic instability up to a hemorrhagic shock are the typical signs CT scan is mandatory
Systemic complications
hemodynamic instability with cerebral hypoperfusion hypotension and bradycardia are common in CAS and are of concern in the high-risk patients typically occurs after carotid sinus manipulation, leading to parasympathetic activation contrast-related complications (pseudo)allergic reaction contrast-induced nephropathy (CIN) contrast-induced encephalopathy (CIE)

Distal embolization

microembolization (most common) x microembolization
- responsible for a substantial portion of the 30-day mortality/morbidity
distal and proximal protection devices prevent cerebral embolization
- a meta-analysis of approximately 2400 patients showed that the 30-day mortality and morbidity were 5.5% and 1.8% (without and with protection) [Kastrup, 2003]
use of distal protection is debated; many centers have comparable results without it
- its insertion is associated with additional manipulation in carotid bifurcation, which itself increases the risk of embolization or vasospasm
- other complications, such as filter thrombosis, stent entrapment, and damage, must be considered
mechanical recanalization or intraarterial thrombolysis may be performed in the case of symptomatic distal embolization

Stent thrombosis

the main mechanism of acute stent thrombosis is the platelet activation
- the highest risk in the first 72h
- the incidence of acute and subacute carotid stent thrombosis is 0.5-2%
besides occlusion, mural thrombi occur and can embolize to the brain
any change in the patient’s neurological status after the procedure should raise suspicion of acute stent thrombosis and requires urgent diagnosis (most easily by duplex ultrasound) and therapy with Ilb/IIIa receptor inhibitors
proper premedication (see above) and stent placement are key to the prevention of such complication
- prophylactic add-on therapy with IV abciximab reduces the risk of ischemic complications while increasing the risk of bleeding
therapy → IV or IA abciximab

EPTIFIBATID

(Integrilin) usually 1mL/2mg or 1ml/0.75 mg

IV bolus: 0.2 mg/kg within 5 minutes, followed by infusion (Sedat, 2014)
IV infusion: 5ml(10mg) + 45ml of NS (1ml=0.2 mg) …… 3ml/h (0.6 mg/h) 0.125ug/kg/min (max 10ug/min!)
IA bolus: 5ml /10mg) + 45 ml of NS (1ml=0.2 mg) …… bolus 10 ml (2mg) every 5 minutes till max dose 10 mg

ABCIXIMAB

(Reopro) 1ml/2mg

a monoclonal anti-glycoprotein IIb/IIIa receptor antibody
IV bolus: 0.25 mg/kg within 5 minutes, followed by infusion
IV infusion: 5ml (10mg) + 45ml NS (1ml of solution = 0.2 mg) …… 3ml/h (0.6 mg/h) 0.125ug/kg/min (max rate 10ug/min!)
IA bolus: 5ml (10mg) + 45 ml NS (1ml of solution = 0.2 mg) …… bolus 10 ml (2mg) every 5 minutes, max dose 10mg

Stent thrombosis on the ultrasound examination

Acute thrombosis of the stent in the carotid artery

Vasospasms

most vasospasms are transient and resolve after catheter removal
if hemodynamically severe vasospasm persists, PTA or vasodilators (local/systemic) may be used

Stent deformation, fracture or migration

endovascular microsnare loops have been developed to remove the migrated stent (stentectomy) (Oh, 2012)
deformation is more common with balloon-expandable stents compared to self-expanding stents
- uncorrectable deformation may require surgical revision
stent fracture may result in dissection with possible pseudoaneurysm formation $Stent fracture$

Problems with distal protection extraction and its wedging in the stent

difficulties with distal protection retrieval can usually be resolved percutaneously
careful manipulation is crucial
it may be helpful to move the patient’s head, have the patient swallow, or choose a more torquable retrieval sheath. In case of filter fracture, it is recommended to ‘jail’ the filter against the arterial wall with an additional stent

Restenosis

early restenosis (intimal hyperplasia) < 2-3 years
- low risk of embolization
late restenosis (recurrent atherosclerosis) > 3 years
- lower risk of restenosis with stenting compared to angioplasty alone

Follow-up

neurosonology – method of choice; always examine the velocities within the stent and in the proximal and distal segments
MR angiography may be subject to artifacts
- contrast-enhanced MRA (CE-MRA) is recommended instead of 3D-TOF
- when a stent graft is used (e.g., for aneurysm treatment), contrast-enhanced MRA is inconclusive and CTA should be performed
- modern stents are MR-compatible and should not migrate in the magnetic field
CT angiography