Alex Abou-Chebl, MD Medical Director, Stroke Baptist Health, Louisvile. Alex Abou-Chebl, MD

Transcription

1 Medical Director, Stroke Baptist Health, Louisvile

2 No Conflicts or Disclosures

3 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?

4 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

5 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

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7 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

8 % Survival free of ILOD-related events 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: Patients with CRP 1.41 mg/dl Patients with CRP > 1.41 mg/dl P<.0001 Months after inclusion

9 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

10 Distal Territory Borderzone Strokes

11 Penetrator Infarcts

12 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

13 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 periprocedural MI Karanasos A, et al. Card Diag Ther 2012;

14 Predictors & Incidence of Perforator and Sidebranch Occlusion with PTCA Furukawa E, et al. Circ 2005

15 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 Poor vs. good HR 4.36; 95% CI, ; p < % stenoses, more extensive collaterals risk of territorial stroke None vs. good HR 4.60; 95% CI, Poor vs. good HR 5.90; 95% CI, , p = Multivariate analyses: extent of collaterals independent predictor for subsequent stroke None vs. good HR 1.62; 95% CI, Poor vs. good, 4.78; 95% CI, ; p = Liebeskind D et al Ann Neurolo 201;69:963-74

16 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

17 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

18 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

19 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

20 FAME Study: Event-free Survival Death/MI/CABG/Repeat PCI Absolute Difference in MACE-free Survival FFR-guided Angio-guided 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.3%

21 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

22 Cumulative Hazard Rate CURE and CHANCE Dual Antiplatelet Therapy Effective in Early Ischemia Prevention Placebo + Aspirin* Clopidogrel + Aspirin* Follow-up (Months) P= N=12,562 CURE Trial Investigators. N Engl J Med. 2001;345: Wang Y, et al. N Engl J Med 2013; 369:11-19

23 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

24 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

25 Natural History of ICAD: A Dynamic Process Wong et al. Stroke 2005;33: Serial TCD study of 143 symptomatic MCA stenoses At 6 month TCD 29% Normalized 62% Stable 9% Progressed Total 4.8% Recurrent Events 12.5% Recurrent Events 38.5% Recurrent Events 10.5% Recurrent Events Arenillas et al. Stroke 2001;32: month TCD study of 40 symptomatic MCA 32.5% Progressed 20% recurrent events Predictor of Stroke Tandem stenosis in cervical ICA Lesion Progression

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27 Importance of Experience Gray et al: JACC Interv 2011 Smout J, Macdonald S, Stansby G International Journal of Stroke. Vol5, Dec 2010;

28 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:

29 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):

30 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

31 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 < Mori Type A

32 Meta-Analysis of Angioplasty and Stenting Angioplasty Alone Stent P-value Technical success 79.8% 95% day stroke/death 1 year stroke/death 8.9% 8.1% % 14.2% Restenosis 14.2% 11.1% 0.04 Siddiq F, et al. Neurosurgery 2009; 65(6):

33 Personal Experience Abou-Chebl A, Krieger D, Bajzer C, Yadav J. Intracranial angioplasty and stenting in the awake patient. Stroke 2003;34(1):312.

34 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

35 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

36 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

37 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

38 Angiographic Findings

39 Technical Result

40 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

41 Illustrative Case- Vessel Size 73yo Male with HTN, HLD Recurrent Aphasia & Right Hemiplegia Failed ASA and Clopidogrel Decreased Cerebrovascular Reserve

42 Angiogram L MCA: 1.7mm Diameter

43 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.

44 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