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.

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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

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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