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Alex Abou-Chebl, MD
Medical Director, Stroke
Baptist Health, Louisvile
Alex Abou-Chebl, MD
No Conflicts or Disclosures
Alex Abou-Chebl, MD
Post SAMMPRIS
Too many unanswered questions
Is stenting too risky?
What aspects of the procedure resulted in such a high-complication rate?
Are there better devices or approaches?
What aspects of medical therapy resulted in lower 30-day event rate?
Are there any patients who could still benefit from revascularization?
Are all patients with ICAD the same?
Alex Abou-Chebl, MD
Possible Explanations for
SAMMPRIS Trial Results 20 Cases Vetting
Only 3 Wingspan, no need for atherosclerosis experience
General Anesthesia
Cross lesion with microcatheter and exchange for balloon
Initially no post-dilation allowed, protocol changed after
SBP<150mmHg post-op SBP<120 reduced risk of ICH with CAS
Abou-Chebl et al. CCI
Alex Abou-Chebl, MD
Possible Explanations for
SAMMPRIS Trial Results
Average 7days to randomization ½ patients w ICH Tx 17days after event- Low WASID
risk
No assessment of cerebrovascular reserve
No angiographic collateral criteria
Perforator strokes included
Stenting vessels <2.5mm
Lesion characteristics not considered Mori Classification
No assessment of ASA/Plavix response
Alex Abou-Chebl, MD
Alex Abou-Chebl, MD
Pathophysiology
Thrombotic occlusion Acute plaque rupture Thrombosis Vessel Occlusion Ischemia
Artery-to-artery embolism Acute plaque rupture/Turbulence/Sheer Stress
Thrombosis Embolism Ischemia
Hypoperfusion Flow-limiting stenosis Autoregulation Failure
Hypoperfusion Ischemia
Branch Origin Occlusion- Perforator Syndromes Atherosclerotic plaque buildup
Encroachment/Occlusion ostia of perforators Ischemia
Combination- Impaired “Washout of Emboli”
Alex Abou-Chebl, MD
Determinants of Risk & Severity
of Clinical Manifestations Stenosis Characteristics
Collateral Blood Flow Cerebrovascular Reserve
Freq & Size of Embolism
Severity of Hypoperfusion
Underlying Brain Substrate Neuronal Reserve
Age
Medical Co-morbidities Hyper/Hypoglycemia
CRP & Fibrinogen predictors of recurrent CAD and stroke
○ Bang OY teal. JNNP 2005
○ Arenillas JF et al. Stroke.
2003;34:2463-2468.
% S
urv
ival fr
ee o
f
ILO
D-r
ela
ted
ev
en
ts
Months after inclusion
Patients with CRP 1.41 mg/dl Patients with CRP > 1.41 mg/dl
P< .0001
Patterns of Ischemia
MCA Stenosis
MRI & TCD study of 30pts
50% Single infarcts % 50% Multiple
○ Single- 67% penetrator strokes
○ Multiple- 73% unilateral, deep, “chainlike”
border zone infarcts
HITS in 9 with Multiple Strokes vs. 1 with
single stroke
○ HITS Predicted # of DWI lesions
Wong KS et al. Ann Neurol 2002;52:74-81
Alex Abou-Chebl, MD
Distal Territory Borderzone Strokes
Penetrator Infarcts
Why Differentiating Hemodynamic
vs. Perforator Ischemia Matters
Volume of Territory at Risk
Eloquence of Tissue at Risk
Maximizing Benefit from
Revascularization
Reducing Risk of Revascularization
In WASID- 9% of recurrent strokes
lacunar
Alex Abou-Chebl, MD
Fate of Perforators During PCI
Plaque shift- lateral dislocation of plaque with PTA Soft Lipid-rich plaque
“Snow-plowing”
Carina Shift
Occlusion of Perforator Ostia by Stent Struts
Dissection
Spasm?
Increased peri-procedural MI
Alex Abou-Chebl, MD
Karanasos A, et al. Card Diag Ther 2012;
Predictors & Incidence of Perforator
and Sidebranch Occlusion with PTCA
Alex Abou-Chebl, MD
Furukawa E, et al. Circ 2005
Importance of Collaterals WASID Angiographic Dataset N=287 (of 569)
“Across all stenoses extent of collaterals was a
predictor for subsequent stroke in the symptomatic arterial territory” None vs. good HR 1.14, CI 0.39-3.30
Poor vs. good HR 4.36; 95% CI, 1.46-13.07; p < 0.0001
70-99% stenoses, more extensive collaterals risk of territorial stroke None vs. good HR 4.60; 95% CI, 1.03-20.56
Poor vs. good HR 5.90; 95% CI, 1.25-27.81, p = 0.0427
Multivariate analyses: extent of collaterals independent predictor for subsequent stroke None vs. good HR 1.62; 95% CI, 0.52-5.11
Poor vs. good, 4.78; 95% CI, 1.55-14.7; p = 0.0019
Alex Abou-Chebl, MD
Liebeskind D et al Ann Neurolo 201;69:963-74
Assessment of Cerebrovascular
Reserve
Acetazolamide SPECT
Useful in combination with an anatomical study
Measures hemodynamic significance of stenosis
Identify pts. who may benefit from
revascularization
Annual Stoke Rates as high 25% ○ Eskey & Sanelli Neuroimag Clin N Am 2005;15
○ Ozgur H, et al. AJNR 2001
Common Pathophysiology of
Intracranial Atherosclerosis & CAD?
Do the vessels behave the same?
Same risk factors
Same markers of disease
Responds to same medical treatment
Risk of instent restenosis same as with
same sized coronary vessels
Looks the same pathologically
Must be the same disease
Decreased Flow Reserve in
Coronary Circulation
Stenting of non-ischemic stenoses has
no benefit compared to Med Rx only
Stenting of ischemia-related stenoses
improves Sx and outcome
In multivessel CAD (MVD), identifying
which stenoses cause ischemia difficult:
Non-invasive tests often unreliable
Coronary angiography often results in under- or
overestimation of functional stenosis severity
FAME Study: Rationale
Fractional Flow Reserve (FFR), is most accurate & selective index to indicate whether a particular stenosis is responsible for inducible ischemia
FFR can be easily determined in the cathlab just prior to stenting
FFR guidance of PCI in patients with multivessel disease may improve outcome
FFR-guided
30 days
2.9% 90 days
3.8%
180 days
4.9%
360 days
5.3%
Angio-guided
Absolute Difference in MACE-free Survival
FAME Study: Event-free Survival
Death/MI/CABG/Repeat PCI
Microemboli
N=114 MCA stenoses
MES detected in 25 (22%) patients.
MES more common with severe stenosis (48% vs. 15%) (p=0.02).
Mean 13.6 months f/u 12 (12%) patients had recurrence: 10 strokes
and 2 TIA
Presence of MES was the only predictor of a further ischemic stroke/TIA by Cox regression (adjusted OR 8.45, CI 1.69 to 42.22; P=0.01)
Gao S et al. Stroke 2004;35:2832-6
Alex Abou-Chebl, MD
CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
Wang Y, et al. N Engl J Med 2013; 369:11-19
.00
.02
.04
.06
.08
.10
.12
.14
Cu
mu
lati
ve
Ha
zard
Ra
te
Clopidogrel
+ Aspirin*
3 6 9
Placebo
+ Aspirin*
Follow-up (Months)
P=.00009†
N=12,562
0 12
CURE and CHANCE
Dual Antiplatelet Therapy Effective in Early
Ischemia Prevention
Alex Abou-Chebl, MD
High Dose Statin Treatment
REVERSAL Trial – 18months of therapy 654 Pts w CAD randomized with IVUS
Pravastatin 40mg vs. Atorvastatin 80mg
LDL ○ Reduced to 110mg/dl vs. 79mg/dl
CRP ○ Reduced 5.2% vs. 36.4%
Plaque Volume ○ Progressed in Pravastatin , Regressed in
Atorvastatin
ASTEROID Trial- 24months Rosuvastatin
Alex Abou-Chebl, MD
Cilostazol for Lesion Progression
Cilostazol (Pletal)- Phosphodiesterase inhibitor
135 Symptomatic MCA stenoses randomized
200mg/day vs. Placebo
Baseline and 6month TCD and MRA
38 Prematurely Terminated
No recurrent strokes in either arm
Lesion Progression 6.7% vs. 28.8%, p=0.008
Lesion Regression 24.4% vs. 15.4%
Kwon et al. Stroke 2005;36:782-6
Natural History of ICAD:
A Dynamic Process
Wong et al. Stroke 2005;33:532-6. Serial TCD study of 143 symptomatic MCA stenoses
○ At 6 month TCD
29% Normalized 4.8% Recurrent Events
62% Stable 12.5% Recurrent Events
9% Progressed 38.5% Recurrent Events
Total 10.5% Recurrent Events
Arenillas et al. Stroke 2001;32:2898-2904 26.5month TCD study of 40 symptomatic MCA
○ 32.5% Progressed
○ 20% recurrent events
Predictor of Stroke ○ Tandem stenosis in cervical ICA
○ Lesion Progression Alex Abou-Chebl, MD
Alex Abou-Chebl, MD
Smout J, Macdonald S, Stansby G International Journal of Stroke. Vol5, Dec 2010; 477-482
Gray et al: JACC Interv 2011
Importance of Experience
Alex Abou-Chebl, MD
Mori Classification
Lesion based
Length
Eccentricity
Predicts complications and reocclusion
Type A: concentric, <5mm, smooth 8%
Type B: eccentric, 5-10mm, angulated, irregular 26%
Type C: >10mm, extreme angulation, total occl. 87%
Mori T, Kazita K, Chokyu K, Mima T, Mori K. Short-term arteriographic and clinical outcome after cerebral angioplasty and stenting for intracranial vertebrobasilar and carotid atherosclerotic occlusive disease. AJNR Am J Neuroradiol 2000 Feb;21:249-254.
Alex Abou-Chebl, MD
Clopidogrel Non-responders
Prospective collection of Platelet Aggregation Peripheral Interventional Laboratory Database
N=60
Periprocedural Thromboembolic Events N=7
Mean %-aggregation 32±14.2% vs. 54.6±16.2% p=0.009
Inadequate platelet inhibition major risk factor for ischemic complications
Matetzky Circulation 2004; 109(25):3171-3175.
Alex Abou-Chebl, MD
U.S.-China Multicenter Balloon Expandable vs. Self-
Expanding Stent Registry
670 lesions were treated in 637 patients
Mean age of 57±13 years
222 (32%) women
Location of stent placement:
MCA 270 (40%)
Posterior circulation 263 (39%)
Intracranial ICA 137 (21%)
Stent type:
BMS: 454 lesions (68%); 23 (5%) DES
SES: 216 lesions (32%)
Technical failure rate: BMS 7.1% and SES 1.4%, (p<0.001)
Jiang W, Cheng-Ching E, Abou-Chebl A , et al. Neurosurgery 2011 Alex Abou-Chebl, MD
Results
30 day peri-procedural stroke or death 6.1%
31 ischemic strokes
8 hemorrhagic strokes
No difference between BES vs. SES
Deaths 6 (0.94%)
4 deaths due to the complications of the peri-procedural stroke
2 other deaths aspiration pneumonia and sepsis
Independent Predictors of Stroke or Death
Variable OR 95% CI p
Treatment < 24 hrs 4.0 1.6 -6.7 < 0.001
Mori Type A 0.31 0.13 – 0.72 0.007
Alex Abou-Chebl, MD
Meta-Analysis of Angioplasty and
Stenting
Angioplasty Alone
Stent P-value
Technical success 79.8% 95% 0.001
30 day stroke/death
8.9% 8.1% 0.48
1 year stroke/death
19.7% 14.2% 0.009
Restenosis 14.2% 11.1% 0.04
Siddiq F, et al. Neurosurgery 2009; 65(6): 1024-1033
Personal Experience
Abou-Chebl A, Krieger D, Bajzer C, Yadav J. Intracranial angioplasty and
stenting in the awake patient. Stroke 2003;34(1):312.
Alex Abou-Chebl, MD
Indications
>70% symptomatic stenosis
Failed medical Rx
Abnormal cerebrovascular reserve Radiographic
Clinical
Local anesthesia Intraprocedural neurological assessments guide
therapeutic approach
Primary stenting for vessels >2.5mm diameter PTA for smaller vessels
Bailout stenting
Alex Abou-Chebl, MD
Intra-procedural Patient Monitoring
67% Developed Headache
Balloon Inflation 79.2%
Wire Positioning 62.5%
Stent Delivery 20.9%
Stent Deployment 16.7% 4.8% Developed Sx of Ischemia
2/3 Brainstem Hypoperfusion during PTA ○ Decrease Inflation Duration
1/3 Hemispheric after Completion of Intervention ○ Repeat Angiogram Stent Thrombosis
○ GPIIb/IIIa Inhibitor
○ Successful Recanalization Recovery
Alex Abou-Chebl, MD
Results
30Day Morbidity and Mortality 7% Morbidity
○ 0% Death
○ 2.8% (2) ICH
One MCA Branch Wire Perforation
- Only patient ever treated under general anesthesia
One hyperperfusion
Both had been pressure dependent or progressive infarction despite maximal medical Rx
○ 4.2% (5) Ischemia
2 Clopidogrel resistant
2 Perforator infarcts in same territory as presenting TIA/stroke
Alex Abou-Chebl, MD
Illustrative Case - Perforators
81y.o. WM with DM, HTN,CAD,PVD
Platelet Count 70k
Recurrent VB TIAs and Strokes with BA stenosis by MRA and TCD
Stereotyped spells of
○ Dysarthria
○ Left Hemiplegia
○ Gait Unsteadiness
Alex Abou-Chebl, MD
Angiographic Findings
Alex Abou-Chebl, MD
Technical Result
Alex Abou-Chebl, MD
Outcome
Normal Post-Op
4 hours later TIA Sx recurred and resolved
Recurred again and progressed slowly
MRI showed Perforator Infarct
To NH, mRS=4
Alex Abou-Chebl, MD
Illustrative Case- Vessel Size
73yo Male with HTN, HLD
Recurrent Aphasia & Right Hemiplegia
Failed ASA and Clopidogrel
Decreased Cerebrovascular Reserve
Alex Abou-Chebl, MD
Angiogram
L MCA: 1.7mm Diameter
Alex Abou-Chebl, MD
Medical vs. Endovascular
Treatment Algorithm
Recurrent Event in Territory distal to Stenosis
Impaired Cerebrovascular Reserve Hemodynamic TIAs
Failure of Medical Therapy
Lesion Progression
Lesion Characteristics Tandem Lesions
Multi-focal Disease
Eccentricity of Plaque
Presence of perforators in plaque
Elevated HSCRP, etc.
Alex Abou-Chebl, MD
Summary
Intracranial Atherosclerosis is best Treated
with Aggressive Medical Rx
Aspirin + clopidogrel + rosuvastatin
PTA/Stenting can be safe and effective in
selected patients if performed correctly
Most effective in patients with decreased
cerebrovascular reserve
Lesion characteristics should be used in
decision making
Well designed randomized trial needed
Alex Abou-Chebl, MD