Basics of

Endovascular
Therapy
David Kydd, M.D.
Basic Goal
 To close or devascularize
– AVMs, Aneurysms, tumor
embolization

 To open or revascularize
– Stenting, angioplasty, thrombolysis
General
Considerations
 Pre-therapeutic investigations
– CT
– CTA
– MRI/MRA
– Doppler
– DSA
General - Angiography
 Femoral artery
– Brachial sometimes
 Kidney function, PT/PTT, INR,
platelets
 ABILITY TO CONSENT
 Recovery
Angiography - Risks
 Stroke
– Should be less than 0.5%
 Allergic reaction
 Contrast nephropathy
 Puncture related complications
Tumor Embolization
 Usually pre-operatively (few days
before) to reduce blood loss and
facilitate resection
– Meningiomas, glomus tumors, juvenile
nasal angiofibromas, hemangioblastoma,
sarcoma, mets (esp. renal cell ca.)
 Rarely palliative
 Also used for refractory epistaxis
 PVA particles most common material
Tumor Embolization
Risks
 Stroke
– Direct via accidental particle delivery to
ICA/vertebral
– Indirect via potential anastomoses
 These may be open before embo, or may open
during embolization due to changes in vascular
impedence
– Facial palsy (glomus tumor embo), other CN
palsies
– Theoretic risk of endocrine release during
glomus embolizations
Chemoinfusion with
BBB disruption
 Not routinely done
 Transient opening of BBB via IA
infusion of hyperosmotic agents
(e.g. mannitol)
Ischemic Stroke
 Carotid Stenosis
– 0.5% 60-70 year olds
– 10% >80 y.o.

 CEA vs. Carotid Stenting

CAROTID
ANGIOPLASTY and
STENTING
CAROTID STENOSIS
and STROKE
 Stroke 3rd leading cause of death,
and significant cause of disability
 700,000 strokes/year in the USA
 Most related to large and small
vessel atherosclerotic disease
– 25% of all strokes related to carotid
atherosclerosis and stenosis
Case #1
 76 year old female
 Previous left carotid
endarterectomy for symptomatic
stenosis
 Developed two tight strictures in
CCA and proximal ICA
 Premedicated with ASA 325mg and
Plavix 75mg po x 3 days prior to
procedure
Case #2
 67 year old female with prior left
carotid endarterectomy
 Presents with restenosis at
endarterectomy site
Case 3
 57 yo female
 Previous left carotid
endarterectomy
 Now with restenosis
 Right carotid is occluded
Treating Carotid
Stenosis
 Medical Therapy
 Surgical (CEA)
 Endovascular (CAS)
Carotid
Endarterectomy (CEA)
 CEA most common vascular
operation in US (150,000
cases/year)
Rationale for Carotid
Endarterectomy
 50 year experience
 Large volumes (99 CEAs per
100,000/year)
 Two large randomized trials have
established that certain surgical
patients benefit from surgical
treatment of carotid stenosis
– NASCET
– ACAS
NASCET
 1991:North American
Symptomatic Carotid
Endarterectomy Trial
 NEJM 1991 325:445-453
 50 sites USA and Canada

 two cohorts: 30-69%, 70-99% stenoses

NASCET
 no high risk patients,
symptomatic within 180 days of
surgery
 exclusion criteria:
– age>80, presence of significant intracranial
stenoses, life expectancy <5 years, history
of ipsilateral endarterectomy, cardiac
disease likely to cause embolism, non-
atherosclerotic stenosis, surgeons excluded
if perioperative complication rate >6%
NASCET (continued)
 CEA highly beneficial 70-99%. Trial
stopped
 For symptomatic stenosis >70%: 17%
absolute risk reduction for ipsilateral
hemispheric stroke following
endarterectomy (p<0.001) vs medical
treatment
– 9%CEA vs 26% medical Rx at 2 years
 For symptomatic stenosis 50-69%: 6.5%
absolute risk reduction
NASCET (continued)
 Overall rate of any perioperative
stroke/death: 5.8%
 Major stroke/death: 2%
 Perioperative death: 0.6%
 Post-op wound complications
(hematoma,infection): 9.3%
 Cranial nerve palsy: 7%
 General medical complications: 8.1%
 NASCET not applicable to many carotid
stenting cases as they are usually the high
risk cases that fall outside NASCET
ECST
 European Carotid Surgery Trial
 Donnan et al, 1998, Lancet 351:1379-1387
 Confirmed results of NASCET
 576 patients with 80-100% symptomatic
stenosis. All lower risk patients.
 Randomized to CEA or medical Rx
 3 years
– 14.9% stroke CEA
– 26.5% stroke Medical Rx (P<0.001)
 Risk of Major stroke/death from CEA
– 7%
ACAS
 (asymptomatic carotid atherosclerosis
trial)
– JAMA 1995
– 39 sites canada and USA
– >60% stenosis, 1659 patients
– no high risk patients, asymptomatic
– MI not measured as primary endpoint
 Estimated stroke risk over 5 years
– medical group risk 11% (2%/year)
– surgical group risk 5.1% (1%/year)
 CEA beneficial if combined morbidity/mortality
rate <3%
ACAS (continued)
 The benefit of endarterectomy
versus medical therapy was shown
only for minor, not major stroke
 Other trials involving asymptomatic
stenosis have not shown benefit
from CEA
– Hobbson et al, The Veterans Affairs
Cooperative Study Group, NEJM 1993;328:221-
227
– Mayo asymptomatic carotid endarterectomy
study group, Mayo Clin Proc 1992;67:513-518
CEA Follow-up
 Reported restenosis rates vary
from 5-20%
 Long-term stroke rates <5% in 5
years

– Moore et al, Stroke 1998;29:2018-2025

– Sundt et al, Mayo Clin Proc 1990;65:625-635
AHA Guidelines for
CEA*
 Asymptomatic (>60%) Stenoses
<3%
 Symptomatic Stenoses <6%
 Repeat CEA <10%
 * Peri-operative stroke/death

 Carotid angioplasty with stenting must

meet or surpass AHA Guidelines to be
acceptable. Anecdotal reports are of no
use.
Canadian Stroke
Consortium Guidelines
 Insufficient evidence to endorse
CEA for any level of
asymptomatic stenosis
– Biller et al., Canadian Stroke Consortium,
Arch Neurol 1996;54:25-28
Patients considered at
higher risk with CEA
 Prior carotid endarterectomy
– 7-10% perioperative mortality
 Contralateral carotid occlusion
 Prior radiation and/or dissection
for head and neck cancer
 High carotid bifurcation
– Requires jaw subluxation
 CABG
Another Way? CAS
Rationale for CAS
 Suspected that many CEAs done today are
on patients that would have been
excluded from NASCET or ACAS
 ASITN,ASNR,SIR Standards of Practice Committees,
2003:14:S321-335
 Study on Medicare patients undergoing
CEA showed higher perioperative death
rates than in NASCET (1.4% vs 0.6%)
 Wennberg et al, JAMA 1998;279:1278-1281
– Why? Patients in NASCET and ACAS thought to
be younger and healthier than average
Medicare patients
Rationale for CAS
 Hypothesis: older patients are at
increased risk from perioperative
stroke and death from CEA
– Is carotid stenting any safer?
– Is carotid stenting less safe?
 Industry driven
Potential
Complications with
CAS
 Stroke due to microemboli
 Cardiac Arrythmias
 Cerebral Hyperperfusion Syndrome
 Related to angiography
– Minor hematoma 5%
– Major hematoma <0.5%
– AVF/Pseudoaneurysm 0.05%
– Severe contrast reaction 0.01%
 Fatalities approx 1:250,000
The MAJOR Safety
Concern with CAS is
with Microemboli
MICROEMBOLIC
EVENTS DURING CEA
AND
Study of CAS
MRI diffusion abnormalities following
CEA.
– 76 patients.
 34% new DWI lesions following CEA
 only 6.5% had clinically detectable deficits.
 96% had TCD microemboli, and the number of microemboli
correlated with the frequency of diffusion abnormalities
(Muller 2000 AJNR 21:47-54)
 Note that if using MRI or TCD, CAS will be
judged under more stringent conditions than
CEA.
– likely the clinical parameters in NASCET missed more
subtle lesions that today can be seen on MRI/TCD, or
with neuropsych.
How can we make
stenting safer?
CAROTID PROTECTION
during Angioplasty
FilterWire: Boston Scientific Angioguard: Cordis

Accunet: Guidant
Potential
Complications with
CAS
 Stroke due to microemboli
 Cardiac arrythmias/hypotension
 Cerebral Hyperperfusion Syndrome
 Related to angiography
– Minor hematoma 5%
– Major hematoma <0.5%
– AVF/Pseudoaneurysm 0.05%
– Severe contrast reaction 0.01%
 Fatalities approx 1:250,000
Cardiac Arrythmias
 Due to pressure on the carotid sinus during
angioplasty and stenting
 Pressures greater than 10 atm have been
associated with serious and fatal cardiac
arrythmias and asystole
 Morris P, 2002, Interventional and Endovascular Therapy of
the Nervous System, p.105
 Bradycardia = 30%
 Hypotension = 24%
 Can last 1-4 days, less frequent with self-expanding stents
– Neither bradycardia nor hypotension are seen in
post-endarterectomy patients being treated for
restenosis
CEREBRAL
HYPERPERFUSION
SYNDROME
uncommon complication of CEA

 Incidence in CAS unknown
– Seems to occur if bilateral stenoses treated in same
session
 Due to transient hyperemia of the ipsilateral
circulation after surgical reopening in the
setting of impaired autoregulation
 HA, N/V, altered mental state, seizures, focal
neurological deficits, increased ICP,
hemorrhage
 Rx: Manage B/P, anti-seizure meds, control of
cerebral edema
CEREBRAL
HYPERPERFUSION
SYNDROME
 This also occurs in carotid PTA, seems
to be uncommon, though one series
had 5% incidence

 The risk of hyperperfusion syndrome

may be related to extremely stenotic
vessels, leukoaraiosis, and lacunar
infarcts (?signs of impaired
autoregulation)
(Very) Brief Review
of the current
literature
SAPPHIRE
 Randomized multi-center trial (29 sites)
comparing CAS to CEA in HIGH RISK
patients
– The trial was stopped prematurely in June 2002
because of slowing enrollment, with increasing
resistance to randomization
 Preliminary data presented in AHA plenary
session Nov 19 2002 (Dr. Jay Yadav)
 Used Cordis Precise stent and Angioguard
XP embolic protection device (Yadev
inventor of Angioguard)
 Precise Stent
SAPPHIRE

Angioguard Protection device

 SAPPHIRE (continued)
 Inclusion criteria
– symptomatic 50% stenosis in native CC or ICA
– asymptomatic 80% stenosis
– One or more of the following
 CHF (III/IV) and/or LVEF <30%
 Open heart surgery within 6 weeks
 Recent MI (>24h <4 weeks), Unstable angina
 Severe pulmonary disease
 Contralateral carotid occlusion
 Contralateral laryngeal nerve palsy
 Radiation therapy to neck
 Previous CEA with recurrant stenosis
 High cervical ICA lesion of CCA lesion below clavicle
 Severe tandem lesions
 Age >80y
SAPPHIRE (continued)
 Exclusion criteria
 acute stroke <48h
 total occlusion of target artery
 percutaneous or surgical procedure planned
within 30d
 ostial lesions of CCA
 Total 723 patients
 409 patients refused surgery: put into stent
registry
 7 patients refused CAS: put into surgical registry
 307 patients randomized (156 CAS, 151 CEA)
SAPPHIRE (continued)
 CAS Meds
– Pre: ASA 72h, Plavix or Ticlid 24h
– Intra-procedure: Heparin for ACT 300
– Post: ASA forever, Plavix/Ticlid 2 weeks
 CEA
– Pre: ASA 72h
– Post: ASA forever
 F/U: 30days. 6 months. 1 year, 2 years,
3 years
SAPPHIRE (continued)
 Primary endpoints:
– death, stroke, and MI at 30d post, death and
ipsilateral stroke 31 days-12 months post
 Secondary endpoints:
– <50% restenosis (U/S), disabling stroke at
30d and 6 months, MACE at 6 months, 1 y, 2y,
3y, safety assessment of protection device
 Tertiary endpoints:
– quality of life, economic analysis
SAPPHIRE (continued)
 Registry refusal arm stopped Feb 2002
 Randomized trial stopped June 2002
– Acute Procedural Success
 Stent success 91%
 Neuroprotection success (delivery and retrieval) 98%
 RESULTS
 RANDOMIZED 30 DAYS
 combined symptomatic and asymptomatic patients,
significant difference in Death/stroke/MI:
– 5.8% CAS vs 12.6% CEA (p=0.047)
 No significant difference if symptomatic or asymptomatic
patient groups examined separately
 Higher rate of cranial nerve palsy in CEA (5.3% vs 0%)
SAPPHIRE
Adverse Effects CAS CEA

MACE including 5.8 12.6

Death/stroke/MI
Perioperative 4.4 7.3
Death/stroke
MI 2.6 7.3
SAPPHIRE (continued)
 CONCLUSIONS
– Only high risk randomized trial
– Major Adverse events includes MI
– High technical CAS success rate
– Significant difference in Death/stroke/MI:
 5.8% CAS vs 12.6% CEA (p=0.047)
– Restenosis data not presented
– Long-term data pending
Stenting for
Asymptomatic
Stenoses?
Stenting in
Asymptomatic
stenoses
 No large carotid stenting trial has
achieved results for
asymptomatic stenoses as low as
the natural history for medically
treated patients
Asymptomatic Stenting
Stroke Rate Mortality Rate
% %
Roubin 5.9 0.7
1996
Diethrich 10.9 1.7
1996
Wholey 4.4 1.4
1998
Wholey 4.2 0.9
2000
Jordan 12.7 1.1
1998
Asymptomatic
Stenting
 No long-term data on restenosis
or durability of stents
 “Angioplasty and stent placement
for asymptomatic carotid stenosis
should only be considered in
special circumstances”
– ASITN,ASNR,SIR Standards of Practice
Committees, 2003:14:S321-335
CREST
CREST
 Carotid revascularization endarterectomy vs stent trial
 Sponsored by NIH and Guidant
(manufacturer)
 Randomized CAS vs CEA
– Lower risk population similar to NASCET
 primary outcome stroke, MI, death
 30d periprocedural period
 = 50% stenosis by angio, 70% by US, with Hx
TIA/stroke
 Now in phase 3
 841 patients randomized as of Dec 2005.
CREST (continued)
 Neuroprotection optional (Guidant
system)
REGISTRIES
 ARCHeR (2003) –
– presented at Am Coll Cardiol meeting 2003
– High risk underwent CAS
– 437 patients analyzed
– 30 day stroke/death = 6.6%
– 30 day stroke/death/MI = 7.7%
 SAPPHIRE was 5.8%
– Stroke risk on dialysis = 28%
 Ongoing high risk registries
– BEACH,CABERNET,CARESS,MAVErIC,SECURITY,
CREATE,PASCAL,SPACE,SAPPHIRE
ADVANTAGES of CAS
 Local anaesthesia (note that
some CEA is also done without
GA)
 Lower morbidity/mortality in high
risk (preliminary data)
 Minimally invasive, brief occlusion
 ?less expensive
DISADVANTAGES of
CAS
 No long term data
 Few randomized trials
 Thromboembolic risk
 Excellent CEA results
 ?ideal stent
 ?neuroprotection
REASONS for SLOW
ACCEPTANCE of CAS
 proven excellent results with CEA
 CAS stroke and death high in
earlier studies.
 Potential embolic complications
 Multiple specialists required
(referring specialist,
neurointerventionalist)
 No self-referral by radiologists
SUGGESTED CURRENT
INDICATIONS for CAS
– High surgical risk
– High cervical bifucation
– Radical neck dissection/radiation
– Contralateral occlusion
– Restenosis
– Tandem lesions
– Ostial lesion of CCA
– Stenosis secondary to dissection, FMD, arteritis
– Pseudoaneurysm
– Underlying stenosis after thrombolysis
– Refusing surgery
CONTRAINDICATIONS
for CAS
 Relative
 asymptomatic stenosis
 unfavorable anatomy
 acute brain infarct
 ?dialysis
 Do not treat bilateral stenoses in same session
(?risk hyperperfusion syndrome)
 Absolute
 intraluminal thrombus
 Intracranial aneurysm
PreStenting PostStenting
ASITN, ASNR, SCVIR
2001 Consensus
Guidelines
 patients who qualify for NASCET (i.e.
low risk) can only have CAS in
randomized clinical trial or IRB
approval
 Operator must have experience in
cerebral angio, stroke rescue,
cerebrovascular anatomy/pathology
 CAS is appropriate in high-risk patients
 Use cerebral protection if available
SUGGESTED
MEDICATION
PROTOCOL for CAS
1. Clopidogrel (Plavix) 75mg po daily,
or ticlopidine (Ticlid) 250 mg po bid,
for 5 days before procedure
2. ASA 325mg po OD x 5 days prior to
procedure
3. Heparinization during procedure to
ACT 300, or 200-250 if using Reopro
4. Continue ASA and Plavix or Ticlid for
3-6 weeks
5. Use of Reopro and IA nitro optional
Carotid Stents as of
March 2004
 Newfoundland : 0
 Prince Edward Island : 0

 Nova Scotia : 3
 New Brunswick: 50
Intracranial Stenting
 Can be used to treat dissection
 Can be used for bridging wide-
neck aneurysms during coiling
 Coming soon (?) intracranial
stenting with angioplasty from
intracranial stenoses (Wingspan
stent: Boston Sceintific)
Intracranial Stenting
 5-30% strokes secondary to
intracranial atherosclerotic
stenosis
 50% considered significant
 Present with stroke without typical
warnings of TIAs.
 Stenoses distribution:
– ICA: 49%, MCA: 20%, PCA: 11%,
ACA:9%
Intracranial Stenosis
 Stroke rates:
– Carotid Siphon: 8%
– MCA: 10%
– Basilar: 11%
– Vertebral: 8%
– PICA: 6%
 EC/IC bypass: does not reduce
risk of stroke c/w ASA
Intracranial Stenosis
 PTA 1st attempted in early 1980s
– Stopped due to high complication
rates
 Low-profile more flexible stents
coming to market.
Intracranial
PTA/stenting
 Inclusion criteria (Wakhloo et al.):
– >50% stenosis (minimal diameter 2.5mm)
– Previous stroke, TIA, referable to target lesion,
within 6 months
– Acute occlusion or dissection after PTA
 Exclusion criteria
– Severe neurologic deficit
– Chronic total occlusion
– Hemorrhage or recent stroke (major or with
mass effect) within 6 weeks of procedure
 Complication rate: 10-15% (1999)
Intracranial Stenting
 Obliteration of perforators
(“jailed” side branches) can occur
Thrombolysis
 PROACT I:
– Double blinded placebo controlled randomized
trial of IA thrombolysis within 6 hours of
symptoms (rpro-UK) of MCA occlusion

 PROACT II
– R-pro-UK with heparin vs. heparin alone
 Thrombolytics showed significantly
improved clinical outcomes at 90 days,
though hemorrhage rate was higher (10
vs 2%)
IA thrombolysis
 Microcatheter superselectively placed in
thrombosed vessel for tPA administration.
– 60-80% recanalization rate IA
– 20-60% for IV
– TIMI grading:
 0= no recanalization
 1= minimal
 2= partial
 3 = complete
 Mechanical thrombolysis may be quicker
and more efficacious.
IA thrombolysis
 Contraindications
– Mild or resolving symptoms
– Sustained hypertension
>180/100mmHg
– Intracranial hemorrhage
– Known vascular malformation or
tumor
– <6 week history of stroke, trauma,
surgery
Aneurysms
 5% prevalence rate
 10 out 100,000 rupture/year
Unruptured Aneurysms
 Discovered incidentally via CT/MRI
 ISUIA
– <10mm, rupture rate 0.05%/year
 0.5% with a history of SAH
– >=10 rupture rate 1%/year
 1% with a history of SAH
– Posterior circulation more likely to rupture
 Basilar Tip 5.5 relative risk ratio
– Giant aneurysms (>25mm) 6% rupture rate
 Critical size has been further refined to
7mm
 ISUIA - 2003
 Unruptured 5 year rates:
<7mm 7-12 13-24 >25

caverno 0 0 3% 6.4%
us
ACA/ 0 2.6% 14.5% 40%
MCA/ICA
p.comm 2.5% 14.5% 18.4% 50%
ISAT - 2002
 1 year follow-up,anterior circulation,
ruptured
 Dead or Dependent:
– Surgery 30.6%, GDC 23.7%
 Needing 2nd procedure
– Surgery 3.4%, GDC 13%
 Post-Rx Rebleed
– Surgery 1%, GDC 2.4%
 Mortality
– 9% for both
Wide-necked aneurysms can also
be treated using a stent either
primarily or as neck bridging
devices

Until recently only coronary stents

were available for this purpose
( Medtronic AVE and Guidant ACS
Multi-Link Tristar and Duet)
Stents:

Cardiac stents (balloon expandable)

• Aneurysm treatment with primary
stenting alone
• Treatment for dissections,
spontaneous and iatrogenic
• Stents to bridge the aneurysm neck
and assist in coiling

Neuroform Stent (BSc)

Nitinol stent visualized 2 French catheter passes
by platinum end markers easily through struts
Self-expanding.
Variable width.
One stent may be deployed through
struts of another stent and will still
open fully
Vasospasm
 4-14 days post SAH (peak 7 days)
 Vasospasm in 60-80%
 Symptomatic in 30%
 Responsible for 20% or
morbidity/mortality of SAH
 Dx: TCD -> DSA
 Prevention
– Normovolemia, normothermia, normal O2
– Nimodipine for 3 weeks
Vasospasm
 Treatment
– If symptomatic and vasospasm: Triple-
H
 Hypertension, hypervolemia, hemodilution
– If conventional therapies fail, or
medical risk factors preventing triple-H
 DSA - > possible endovascular treatment
Vasospasm
 Endovascular therapy
– Balloon angioplasty (vessels >1.5mm)
 Requires GA, ICP monitoring
 60-70% show improved neuro status
 Long-lasting
 Complications, while very uncommon, can be
catastrophic
 Distal spasm may require pharmacologic
Rx:
– Papaverine, verapamil
– Temporary effect
AVMs
 3% prevalence
 90% supratentorial
 2-3% spontaneous thrombosis
 Sx usually before 40 y.o.
– 65% present with hemorrhage
– 15-35% seizure
– 15% headaches
AVMs
 Hemorrhage
– Annual risk 2-3%
– Mortality 1st hemorrhage 29%
– Disability 23%
 After first bleed, 6% rebleed 1st year
 2-3% following years
– Factors predictive of hemorrhage
 Size, location, deep venous drainage, impaired
venous drainage, intranidal aneurysms (4-17%)
 Rx:
– Surgery with/without pre-surgical embolization
(n-butyl-2-cyanoacrylate), radiosurgery
Other
 CCF
– Direct ICA-venous (Barrow A)
– Indirect
 ICA meningeal branches – cav sinus (B)
 ECA meningeal branches – cav sinus (C)
 Meningeal branches both ECA/ICA (D)
– Rx: detachable ballons (silicone), coils
 Venous Thrombosis
– Medically intractable cases may need
endovascular thrombolysis attempted.