System Chief Of Cardiovascular President, Lankenau Heart .

William A. Gray MDSystem Chief of CardiovascularServices, Main Line HealthPresident, Lankenau Heart InstituteWynnewood, PAUSA

2Disclosures Consultant to Silk Road Medical, Contego,Abbott Vascular, WL Gore, Medtronic, BSC

What are the possiblecauses of stroke in CAS? Operator error Technique (balloon sizing, wire misadventure, EPD error, etc.,) Patient factors Vulnerable plaque (lesion, carotid, aorta) Vascular anatomy or characteristics (calcium, thrombus, etc.,) Genetics related to thienopyridine metabolism Inadequate technology EPD, stent, procedural pharmacologyLankenau Heart InstituteMain Line Health

Open and closed cell design elementsOpen cellClosed cellLankenau Heart InstituteMain Line Health

Stent design: open vs. closed cellLankenau Heart InstituteMain Line Health

Closed cell stent leading to kinkingLankenau Heart InstituteMain Line Health

Open cell stent conforming to vesselLankenau Heart InstituteMain Line Health

Differences in cell size by stentLankenau Heart InstituteMain Line Health

Also need to consider MCUSALankenau Heart InstituteMain Line Health

Pore (MCUSA) sizesNo significant difference between OC and CC stentsN.B. filter pore size 1/10th the stent pore iseAcculinkXact, PROTÉGÉ RX and Acculink 8-6mm tapered stents (distal portion)Lankenau Heart InstituteMain Line HealthPrecise and Wallstent 8mm straight stent

Clinical event rates vary by free cell area?Bosiers M, de Donato G, Deloose K, Verbist J, Peeters P, Castriota F, Cremonesi A, Setacci C. Does free cell areainfluence the outcome in carotid artery stenting? Eur J Vasc Endovasc Surg. 2007 Feb;33(2):135-41;Lankenau Heart InstituteMain Line Health

European Registry:no effect of stent type on outcomesSymptomatic Patients (n 674)p 0.43p 0.847.5% 5.8%TIA, stroke&death3.8% 3.4%stroke&deathp 0.16p 0.32p 0.48p 0.2410%8%6%4%2%0%day 0 to 30day 0 to 306.5% 3.9% 3.1% 1.8%TIA, stroke& stroke&deathdeathday 0day 00.7% 1.6% 0.3% 1.3%TIA, stroke& stroke&deathdeathday 1 to 30 day 1 to 30

EXACT (CC) and CAPTURE 2 (OC)No differences in prospective, adjudicated study10EXACT% Death and stroke9CAPTURE XACT (N 2145)*CAPTURE 2 (N 4175)Combined (N 6320)Lankenau Heart InstituteMain Line HealthSymptomaticAsymptomaticEXACT (N 213)CAPTURE 2 (N 548)Combined (N 761)EXACT (N 1931)CAPTURE 2 (N 3627)Combined (N 5558)

Stroke timing paradox:Not all strokes appear on the day of 8%44%% of patients50%40%23%30%16%20%10%14%0%4%0%Ipsi (n 139)Non- Ipsi (n 31)Fairman R, Gray W, Scicli A et al. Ann Surg 246 (4) Oct 2007Lankenau Heart InstituteMain Line Health

MRI DWI white matter changes post CAS aregreater than CEA: numerically but not by volumeLankenau Heart InstituteMain Line Health

Fly-through of a conventional stent

Plaque prolapse on OCT common

New mesh stent designs WL Gore InspireMD TerumoLankenau Heart InstituteMain Line Health

Ideal Pore SizeCGUARD*165µ3755001050Closed cell stent1900Open cell stentTERUMOGORE Heart InstituteLankenauMain Line Health* Average in lesion at expanded state

WL Gore SCAFFOLD stent*CAUTION: Investigational Device. Limited by United States Law to Investigational Use only.Lankenau Heart InstituteMain Line Health

CE Approved Not available for sale in the USAMAL-017-14-01Lankenau Heart InstituteMain Line Health

CARENET ILankenau Heart InstituteMain Line Health

TERUMO: A Novel CAS Design– Closed cell structure with flexible Nitinolweave– Dual layer micromesh design for sustainedembolic prevention– Retrievable and repositionableLankenau Heart InstituteMain Line Health

CASPER/Roadsaver vs. Other Closed Cell CASOCTLankenau Heart InstituteMain Line HealthFurnished by Dr. M Amor, Polyclinique Louis Pasteur, Nancy, France

Regulatory status of CASPER FDA IDE is in preparation for US investigation Initiation planned 2016 Lankenau HeartInstituteMain Line Health

Summary Mesh-covered carotid stents likely to addbenefit in terms of reducing not only clinicalevents but also surrogate DWI lesions As the stent becomes the “protector” and notthe “provocateur”, CAS outcomes—alreadygood—should improve furtherLankenau Heart InstituteMain Line Health

GORE Carotid StentAttributes– Stent: Open Cell NiTi Frame Closed Cell 500 µ latticeon outside of NiTi Frame Permanently BoundCBAS Heparin on alldevice surfaces*CAUTION: Investigational Device. Limited by United States Law to Investigational Use only.Lankenau Heart InstituteMain Line Health

GORE Carotid Stent Clinical Study forthe treatment of carotid Artery stenosisin patients at increased risk For adverseevents From carOtid enDarterectomyThe Gore SCAFFOLD Clinical Study*CAUTION: Investigational Device. Limited by United States Law to Investigational Use only.Lankenau Heart InstituteMain Line Health

Inspire MD CGuard MicroNet TechnologyInspireMD’s Core TechnologyThe MicroNetTM is a bio-stable mesh woven from a singlestrand of 20μm Polyethylene Terephthalate (PET).The MicroNetTM is designed to trap and sealthrombus and plaque against the vesselwall, preventing embolization. TheMicroNet is sutured to both thedistal and proximal crowns ofthe stent platform.Advantages of technology: Flexible structure Does not promote thrombosis Minimal foreign body reaction Does not alter procedure Optimal pore sizeLankenau Heart InstituteMain Line Health

CGuard stent cut new DWI lesions inhalf c/w historical outcomesLankenau Heart InstituteMain Line Health

PALADIN Carotid Post-Dilation Balloon withIntegrated Embolic ProtectionFilterChassisFilter Membrane with40-Micron Pore SizeAngioplastyBalloonLankenau Heart InstituteMain Line Health

Pallidin: key features Sheathless design 40-Micron Pore Size 95% capture efficiency with 100 micron particles Filter open time of 15-30 seconds ensures minimal risk ofthrombin/fibrin deposition Ability to adjust size to suit patient anatomy Continguous treatment portion and embolic protectionportion, with minimal landing zone requirementsLankenau Heart InstituteMain Line Health

Direct Carotid Access withHigh Rate Flow Reversal: TCARLow PressureVenous SystemENROUTE TranscarotidStent SystemHigh PressureArterial System “CEA-like”neuroprotection Less manipulationENROUTE TranscarotidNeuroprotection SystemSilk Road Medical, Inc.CAUTION: Investigational device. Limited by federal (USA) law to investigational use.The ENROUTE Transcarotid Stent and Neuroprotection Systems bear the CE markof conformity.Lankenau Heart InstituteMain Line Health Avoid the arch Predictable, efficient

ROADSTER OutcomesIntention to Treat, Per ProtocolHigh Surgical RiskS/D/MI*Pivotal Group, ITT(n 141)Pivotal Group, PP(n 136)53.5%42.9%Major Stroke00%00%Minor Stroke21.4%10.7%Death21.4%21.5%MI10.7%10.7%Stroke & Death42.8%32.2%Cranial Nerve Injury (CNI)10.7%10.7%CNI Unresolved at 6 Mos00%00%*HierarchicalPer Protocol excludes major protocol deviationsAll FDA-approved carotid stent systems were used per site preference(Acculink, Xact, Precise, Protégé, Wallstent)Lankenau Heart InstituteMain Line Health

Unique Benefit of CGuardAbility to dilate MicroNet with balloon tooptimize blood flow into carotid sidebranches without any net ruptureLankenau Heart InstituteMain Line Health

Xact, PROTÉGÉ RX and Acculink 8-6mm tapered stents (distal portion) Precise and Wallstent 8mm straight stent Pore (MCUSA) sizes Wallstent Xact Protégé Precise Acculink 0.92 0.96 1.08 1.12 1.06 N.B. filter pore size 1/10th the stent pore size