1. LA CEA E’ ANCORA IL GOLD STANDARD? N. Mangialardi MD San Filippo Neri - Roma NO

2. 3179 CAS30-day results (high volume centers) Death0.2% Disabling stroke0.4% Non disabling stroke0.7% TIA1.5% J Vasc Surg 2008;48:1431-41

3. 3977 PTSSYMPTASYMPT 30 DAYS STROKE3,4%1,0% 30 DAYS MACE4,5%2,2%

4. 30-day composite endpoint (death/stroke/MI) 8.3% 2.3% ≈10 YRS

5. RCT’s: favor CEA rather CAS less TIA, even more MI > CEA remains the gold standard CREST Concluded equivalency in Stroke Death Rate HIGHER STROKE RISK FOR CAS HIGHER MI RISK FOR CEA Higher risk for CAS in symptomatic and elderly RCT trials conclusion (CEA VS CAS) LIMITATIONS: INCLUSION CRITERIA, EXPERIENCE, PREOP EXAMS, PROTECTIONS

6. EJVES 2012

7. OPERATOR EXPERIENCE SELECTION  CERTIFIED GAME CHANGERS

8. Nallamothu B et al JAMA 2011; 306(12): 1338-43

10. CSTC Stroke 2014; 45: 527-32 ≥ 6 CAS/Yr./Operator ≥ 50 CAS/Yr./Operator Stroke 2006; 37: 2004-9 Cerebrovasc Dis 2014; 38: 77-93

11. ACST-2

12. OPERATOR EXPERIENCE  CERTIFIED SELECTION  SUITABILITY CEA & CAS – PATIENT – LESION  angio TC/MRI MANDATORY GAME CHANGERS

13. PRE-RECRUITMENT CT SCAN MANDATORY !!!

14. EVA-3SSPACEICSSCREST Minimum stand. for randomization Carotid duplex ultrasound Carotid duplex ultrasound or angiography Carotid duplex ultrasound Carotid duplex ultrasound or angiography or CT scan/MRI PREVIOUS RCT’S: PRE-OP IMAGING DUPLEX ULTRASOUND CT SCAN OPTIONAL !!!

15. Risk related to catheterism Arch: normal / diseased type I / type III / bovine Com Car: normal / diseased/tortuous Int Car: normal / tortuous Lesion: standard / pinehole

16. Siena CAS scoring system Macdonald S et al. Stroke 2009; 40: 1698-703 Setacci C et al. Stroke 2010; 41: 1259-65 CAS risk

17. UNFAVOURABLE ANATOMY AN EXAMPLE Tortuosity Angulation (Type III)

18. ANATOMICALLY UNSUITABLE PTS MUST NOT BE ENROLLED OR CONSIDERED FOR DIFFERENT STRATEGY

19. 1 choice: Femoral (>90%) No problems with large devices Low complication rate Arterial closure devices ACCESS

20. Dedicated materials Coaxial system Saad catheter (CORDIS)

21. ….for different type of arch

22. SIMULATION FOR COMPLEX CASES Technical skills Training Patient-specific 1. CTA / MRA2. 3D recon3. VR simulation4. CAS procedure Willaert W et al. World J Surg. 2012; 36(7): 1703-12

23. Transfemoral CAS Peri-procedural Stroke Rate 1. N Engl J Med 2010;363:11-23. 2. Stroke. 2011;42(12). 3484-90

24. Alternatives ACCESS

25. Brachial access

26. TRANSCERVICAL ACCESS TO BYPASS AORTIC ARCH TRANSCERVICAL ACCESS WITH FLOW REVERSE SYSTEM

27. TECHNIQUE/MATERIALS OPERATOR CHOICE PRACTICE DRIVEN Is an advantage…

28. D ISTAL P ROTECTION F ILTER Angioguard XP Cordis EmboshieldAbbott Accunet Abbott FilterWire Boston SpiderCovidien Embolic FilterGore FiberNetMedtronic P ROXIMAL P ROTECTION Trancervical Dynamic Flow Reversal (ENROUTE, Silk Road Medical) Flow Blockage (Mo.Ma, Medtronic) …Because Specific Device Training Reduce complication rate

29. New accesses avoid arch navigation & debris dislodgement New brain protection: TCAR (Trans Carotid Artery Revascularisation) (PMA from FDA on May,19,2015) New stents (mesh covered stents) -> smaller stent struts -> smaller debris migration …BUT NEW OPTIONS CAN REDUCE CAS COMPLICATIONS

30. ….and ….. cerebral protection OF COURSE ALWAYS!!!

31. Meta-analisys (24 studies): the relative risk (0.59) of total stroke was significantly lower for protected vs unprotected CAS p < 0.05 IN THE US CAS REIMBURSEMENT IS LIMITED TO PTS AT RISK FOR CEA WITH SYMPTOMATIC LESION>70% EXCLUSIVELY IF PERFORMED USING AN APPROVED EPD

32. EMBOLIC PROTECTION DEVICE TYPE of EPD FILTERSWIRE + FILTER DISTAL PROTECTIONFILTER OVER THE WIRE BALLOONDISTAL OCCLUSION BALLOONFLOW STASIS PROXIMAL PROTECTION PAES CATHETERFLOW REVERSE DIRECT CERVICALFLOW REVERSE

33. THE SELECTION OF EPD IS MAINLY GUIDED BY PATIENT’S ANATOMY AND OPERATOR PREFERENCE AT THE MOMENT THERE IS NO CONSENSUS REGARDING THE IDEAL EPD

34. PROXIMAL EPD 1.9-31.4% Stroke 2008; 39:2325-2330 J Endovasc Ther 2010;17(3):298-307 J Endovasc Ther 2012;19:749-56 Cardiol Pol 2012;70(4):378-86

35. J Vasc Interv Radiol 2013; 24:528-33

36. Stabile E et al. JACC 2014

37. DISADVANTAGES – LARGER SHEAT/SURGICAL ACCESS (C-CAS) – INTOLERANCE RISK (UP TO 13%) – MORE COMPLEX – RIGID PLATFORM – LONGER PROCEDURE – RISK OF SPASM/INJURY OF CCA CEREBRAL PROTECTION DEVICE PROXIMAL PROTECTION

38. PROXIMAL PROTECTION COSTS 30-50% MORE THAN FILTERS PROXIMAL OCCLUSION DEVICE COSTS

39. PROS – PROTECTION BEFORE CROSSING LESION – NO NEED FOR DISTAL LANDING ZONE – AVOID EMBOLIZATION DURING PROCEDURE – USE GUIDEWIRE OF CHOICE CEREBRAL PROTECTION DEVICE PROXIMAL PROTECTION

40. POD clinical study 2010 – ARMOUR 262pts: >15% sympt – 28.9% > 80 yrs Stroke+death+MI2.7% – Symptomatic0 – Age>803.1% 2011 - EMPIRE 245 pts: 32% sympt – 15% > 80 yrs Stroke+death+MI+TIA4.5% Stroke+death 2.9% – Symptomatic2.6% – Age>802.6% 2011 - PROOF study 44 pts: 9% sympt – Stroke+death+MI0 2007 - Criado 103 CAS: 36% sympt Stroke+death2%

41. StudyProcedureEmbolic Protection # subjects% w/ New DWI Lesions ICSS 1 Transfemoral CASDistal filter (various) 5173 ICSS 1 CEAClamp, backbleed 10717 PROFI 2 Transfemoral CAS Distal filter (Emboshield) 3187 Leal 4 TransfemoralDistal Filter (FilterWire) 33 PROFI 2 Transfemoral CAS Proximal occlusion (MoMa) 3145 DESERVE 5 Transfemoral CAS Proximal occlusion (MoMa) 12726 PROOF 3 Transervical CAS High-flow rate flow reversal 4816.7 Leal 4 Transervical CAS Flow Reversal3112.9 1 Lancet Neurol. 2010 Apr;9(4):353-62 2. J Am Coll Cardiol. 2012;59:1383-89 3. JVS 2011;54:1317-23 4. JVS 2012 ;56:1585-90 5. Int J Cardiol 2014;15: 174(2):382-3

42. Direct Carotid Access with High Rate Flow Reversal High Pressure Arterial System Low Pressure Venous System ENROUTE Transcarotid Stent System ENROUTE Transcarotid Neuroprotection System Avoid the arch “CEA-like” neuroprotection Less manipulation Predictable, efficient Silk Road Medical, Inc. CE MarkFDA Approval ENROUTE Transcarotid Neuroprotection System January 2012February 2015 ENROUTE Transcarotid Stent System July 2013May 2015

43. Transcarotid Artery Revascularization and Stroke Reduction Silk Road Clinical Studies PROOFTESLAROADSTER ENROUTE DW-MRI study Study type First In Man EU Multicenter EU Post-Market Registry US Pivotal IDE European registry Number of Patients 755820830 Profile All-comers High Surgical Risk: Symptomatic & Asymptomatic Symptomatic <6 weeks Status Complete Enrolling

44. Protection system First in man study: Controlled blood flow reversal cervical access FAST-CAS (flow alterned slow transcervical CAS) DW- MRI studies 44 patients (9% symptomatic) L.A. No stroke, no TIA 5 (16%) new asymptomatic ischemic brain lesion (comparable to ICSS endarterectomy group 17%) 10% Transient intolerance (11% with controlateral occlusion) Proof Study (Lazlo Pintes JVS 2011)

45. TransCarotid Artery Revascularization Procedure Experience in EU 322 Cases – 30 d Stroke/Death rate 1.5% StudyF/UStatusTotal Enrollment PROOF30-DAYCLOSED75 LOTUS30-DAYCLOSED12 PROOF EC30-DAYCLOSED6 TESLA30-DAYCLOSED75 F-1 (Filter Debris)30-DAYCLOSED24 ROADSTER30-DAYCLOSED29* MINI (KOBI)ACUTEENROLLING39 DW-MRI30-DAYENROLLING9 OtherACUTECOMMERCIAL53 TOTAL322 EndpointsSILK ROAD PROCEDURE Stroke/Death (30-day)5/322 (1.5%)* Intraprocedural0/322 (0.0%) CNI (periprocedural)2/322 (0.6%)

46. ….and ….. STENT CHOICE

47. 30 days. (3179 CAS) TIA e stroke Wallstent 1.2% CC (<2.5 ) 1.3% Exponent5.9% CA (> 7.5 ) 3.4% Eur J Vasc Endovasc Surg 2007 p<0.05 Symptomatic p<0.0001 mm 2

48. POSTOP NEUROLOGIC EVENTS PTSEVENTSDELAYED EVENTS OPEN CELL9374,2%3,4% CLOSE CELL22422,3%1,3% TOTAL31792,8%1,9% Bosiers – Eur J Vasc Endovasc Surg 2007

49. MACE2,1% MAJOR STROKE0,5% MINOR STROKE1,3% MI0,1% DEATH0,2%

50. CURRENT PROBLEMS CLOSE CELLS  MALAPPOSITION OPEN CELLS  PLAQUE PROLAPSE

51. IDEAL CAROTID STENT DESIGN SCAFFOLDING LESION COVERAGE CONFORMABILITY FATIGUE RESISTENCE MINIMAL FISH-SCALING (RECROSSING) VISIBILITY EASY OF USE LOW PROFILE

52. NEW STENT DESIGN

53. CEA IS STILL THE GOLD STANDARD? MAY BE HOWEVER GAME CHANGING

54. CEA IS STILL THE GOLD STANDARD? MAY BE HOWEVER GAME CHANGING

55. TO CHANGE THE GAME…… BE FAMILIAR WITH THE ANATOMY OF CEREBRAL CIRCULATION, SUPRAORTIC ARTERIES AND THEIR VARIATIONS RESPECT ALTERNATIVES (BMT & CEA) HAVE ALL NECESSARY DEVICES ON THE SHELF AND KNOW THEIR FUNCTION DON’T OVERESTIMATE YOUR CAPABILITY