1. Embolic Protection Devices Sripal Bangalore, M.D., M.H.A. and Deepak L. Bhatt, M.D., M.P.H., F.A.H.A.

2. Overview Embolic Protection Devices (EPDs) Rationale for use Types of EPDs Indications Vein graft intervention Other indication Equipment Technique

3. Rationale for Use Manipulation of atherosclerotic lesions (with wires, balloons, atherectomy catheters and stents) releases plaque debris Plaque debris leads to no/slow flow as a result of: Obstruction of macro and microvascular channels Promotion of local platelet adhesion/thrombosis (by releasing tissue factors) Promotion of microvascular spasm (by releasing thromboxane) Clinical manifestation of distal embolization depends on the amount of debris, size of particles and sensitivity of perfused organ Coronary circulation (especially vein grafts): Ischemia/infarction Cerebral circulation: TIA/stroke EPDs prevent/reduce plaque debris from reaching the distal bed and have the potential to reduce adverse clinical events

4. Rationale for Use Magnified photographs of the FilterWire device after the procedure (scale bar=1 cm) showing plaque debris collected in the filter basket Reproduced with permission from Choudhury, R. P. et al. Circulation 2004;109:803-804.

5. According to mechanism of operation: Distal occlusion aspiration system: occlusion balloon passed distal to lesion and inflated, before intervention, to occlude flow so as to create a column of stagnant blood which collects plaque debris that is subsequently removed with an aspiration catheter [Ex: PercuSurge GuardWire (Medtronic, Minneapolis, MN) and TriActiv system (Kensey Nash Corp., Exton, PA)] Distal filter: uses a filter basket as opposed to a balloon, traps debris but maintains distal perfusion and ability for contrast imaging during the procedure (Ex: Spider, FilterWire, etc.) Proximal occlusion aspiration system: inflow balloon occlusion proximal to the lesion (Ex: Proxis, Parodi, Gore flow reversal, Mo.Ma Ultra proximal cerebral protection device, etc.) Types of EPDs

6. EPD Types: Strengths and Limitations Distal Occlusion Distal FilterProximal Occlusion Embolization on wiring / pre- dilatation/device crossing ++- Failure to capture debris < 100μm -+- Failure to capture soluble mediators -+- Ischemia during balloon occlusion +-+ Limited contrast opacification +-+ Unlimited debris capture+-+ Shunting of debris into proximal side branches +--

7. Major Trials of EPDs in SVG Intervention TrialDeviceNo. of Patients 30-Day MACE, % P- Value Design Distal occlusion device SAFERGuardWire vs. Conventional guidewire8019.6 vs. 16.50.004Superiority PRIDETriActiv vs. GuardWire63111.2 vs. 10.10.02Non-inferiority Distal filter device FIREFilterWire vs. GuardWire6519.9 vs. 11.60.0008Non-inferiority CAPTIVECardioShield vs. GuardWire65211.4 vs. 9.1NSNon-inferiority TRAPTRAP vs. Conventional guidewire35812.7 vs. 17.30.24Superiority SPIDERSPIDER vs. FilterWire or GuardWire7329.1 vs. 8.40.012Non-inferiority AMEthystInterceptor PLUS vs. FilterWire or GuardWire 7978.0 vs. 7.30.025Non-inferiority Proximal occlusion device PROXIMAL Proxis vs. FilterWire or GuardWire 5949.2 vs. 100.006Non-inferiority

8. Major Trials of EPDs in Native Coronary STEMI TrialDeviceNo. of Patients Primary EndpointResult, %P- Value Distal occlusion device EMERALDGuardWire Plus vs. Conventional guidewire 501ST-segment resolution at 30 mins Infarct size 63.3 vs. 61.9 12.0 vs. 9.5 0.78 0.34 Tahk et al.*GuardWire Plus vs. Conventional guidewire 116TIMI grade-3 flow TMP grade-3 Hyperemic Average Peak Velocity 96 vs. 81 65 vs. 38 39.2 ± 16.7 vs. 30.6 ± 10.8 cm/s 0.016 0.001 0.014 MICADOGuardWire Plus vs. Conventional guidewire 167No-reflow TIMI grade-3 flow TMP grade-3 4 vs. 3 80 vs. 76 58 vs. 44 0.73 0.182 0.054 Ochala et al.GuardWire Plus vs. Abciximab 120TIMI grade-3 flow89 vs. 89NS ASPARAGUSGuardWire Plus vs. Conventional guidewire 329TIMI grade-3 flow77 vs. 780.73

9. Major Trials of EPDs in Native Coronary STEMI TrialDeviceNo. of Patients Primary EndpointResult, %P- Value Distal filter device PROMISEFilterWire EX vs. Conventional guidewire 200Maximum adenosine- induced flow velocity 34±17 vs. 36±20 cm/s 0.46 UpFlow MIFilterWire EZ vs. Conventional guidewire 100TIMI grade-3 flow Blush score-3 ST-segment resolution at 60 mins 88.2 vs. 93.9 68.1 vs. 66 9.4 vs. 10.7 NS DEDICATIONFilterWire vs. Conventional PCI 626ST-segment resolution at 90 mins 72 vs. 760.29 PREMIARSpiderRX vs. Conventional PCI 140ST-segment resolution at 60 mins 60 vs. 600.99 Proximal occlusion devices PREPAREProxis vs. Conventional PCI284Complete ST-segment resolution at 60 mins 80 vs. 720.14

10. Class I Distal embolic protection devices be used with PCI to saphenous vein grafts when technically feasible Indications Smith SC Jr, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. Available at: http://www.acc.org/clinical/guidelines/percutaneous/update/index.pdf.

11. Carotid artery stenting Data to date do not support the routine use of EPDs for native coronary artery PCI (either stable CAD or acute MI setting) Other vascular beds - EPDs have been studied for renal artery stenting and other peripheral stenting. There are no robust data to attest to their efficacy at present Other Indications

12. Avoid distal EPDs in vessels with excessive tortuosity Do not deploy EPDs in the region of stent Do not over- or under-size the EPD Contraindications / Caution

13. Equipment Distal filter device (FilterWire EZ) FilterWire device is composed of a protection wire and a delivery and a retraction catheter Protection wire - composed of a nitinol mesh filter with a distal radiopaque spring tip, mounted on a 190 cm or a convertible 300/190 cm cm PTFE-coated 0.014 inch stainless steel wire Reproduced with permission from Boston Scientific Corporation

14. Equipment Distal filter device (SpiderFX® Embolic Protection Device ) SpiderFX device is composed of a Capture wire and a SpiderFX Catheter Capture wire - composed of a nitinol mesh filter with a distal floppy tip, mounted on a 190 cm or a convertible 320/190 cm PTFE-coated 0.014 in stainless steel wire pre-loaded through the delivery end of the SpiderFX catheter Reproduced with permission from eV3 Inc.

15. Equipment SpiderFX Catheter - dual-ended catheter, with a delivery end (green) and a recovery end (blue) at the opposite end of the catheter Reproduced with permission from eV3 Inc.

16. Technique Antiplatelet: Aspirin and thienopyridine as per institutional practice Anticoagulation: bivalirudin or heparin (with or without GP2b3a) as per routine clinical practice 6F guide catheter to engage the coronary ostium Standard 0.014 inch guidewire to cross the lesion (with the Spider) Identify the location where the filter will be deployed, preferably 2.5 to 3 cm distal to the lesion site Measure the vessel diameter in this location and choose the appropriate filter diameter size Do not undersize (inadequate vessel wall apposition resulting in embolization of debris) or oversize (vessel wall damage and or slow/no-flow)

17. Technique Preparing the device Under sterile conditions, remove the EPD device components with the hoop from the packaging Hold the catheter at the distal tip and submerge only the filter in heparinized saline to wet and remove air. Pull the capture wire proximally until the filter portion stops in the clear segment of the catheter Flush through the distal tip with heparinized saline until all air is removed and saline passes from the primary wire exit port Gently apply pressure to the primary wire exit port and continue flushing until all air is removed and saline passes from the capture wire exit port

18. Technique Deploying the device After crossing the lesion with a standard 0.014 in guidewire, load the distal tip of the EPD catheter (green) on to the proximal part of the guidewire Gently bend the catheter at the primary wire exit port to allow the primary guide wire to exit easily Advance the catheter over the primary guidewire, past the lesion until the radiopaque marker at the distal tip of the delivery end is at least 4-5 cm beyond the distal edge of the lesion Fix the catheter in this position and now withdraw the primary guidewire, leaving the delivery catheter with the capture wire in place With the catheter fixed with one hand, gently advance the capture wire until the distal radiopaque marker band on the filter aligns with the radiopaque marker on the catheter distal tip Under fluoroscopy ensure that the proximal radiopaque marker band is at least 2 cm distal to the lesion treated. If not, advance the unit as a whole until the desired position is reached Fix the capture wire with one hand and gently pull back the catheter to expose and deploy the filter. Remove the catheter from the patient

19. Technique Recovery and removal of the device After completion of PCI using the capture wire as the primary guidewire, use the recovery end of the catheter to remove the filter Flush the distal tip of the recovery end (blue) to remove all air, until saline passes from the capture wire exit port Load the recovery end of the catheter and advance until the distal tip radiopaque marker aligns with the proximal radiopaque marker band on the filter Gently advance the recovery end over the filter until the proximal portion of the filter is inside the catheter (partial enclosure recovery) or until all radiopaque markers on the filter are within the catheter (full enclosure recovery) Carefully remove the catheter and the capture wire together as a unit Open the hemostasis valve on the guide catheter to allow the EPD catheter to exit and also to flush any thrombus which may have escaped into the guide catheter

20. Technique FilterWire The deployment of FilterWire is similar, except the protection wire serves as the guidewire and a conventional guidewire is not used prior to deployment of the FilterWire Submerge the filter and distal tip of the delivery sheath in heparinized saline and capture the filter by pulling it into the sheath Place the peel-away introducer sheath over the spring tip and insert into the hemostasis valve of the guiding catheter and advance Peel the sheath introducer off and advance both the wire and delivery sheath together to the end of the guide catheter Now attach a torquer to the protection wire and steer the wire using the torquer with one hand while advancing the sheath with the second Advance the filter and deploy minimum 3.0 cm distal to the lesion. Advance the torquer to the hemostasis valve and tighten Holding this in place, pull back and remove the delivery sheath by peeling it away. The filter is now ready for use Retrieval is similar to the description above

21. Short flexible catheter attached to a hypertube catheter shaft (7F) Short distal circumferential balloon at the tip Proximal balloon within guide Proximal end of the catheter has a built in standard Y-adaptor with a hemostasis valve for guidewire and device entry, a luer connection for aspiration and an additional luer connection for the sealing balloon inflation device Deployed in proximal vessel (needs at least 10mm landing zone) Balloon inflated at 2/3 atm, causing stasis of flow Proximal EPD - Proxis Device* Proxis(tm) is a trademark of St. Jude Medical. Reprinted with permission from St. Jude Medical, (c) 2010 all rights reserved Distal balloon *currently not in production in the US

22. Proximal vs. Distal Protection Ideal case for proximal protection Distal lesion with <4-5 cm length of vessel beyond the lesion Minimal proximal atherosclerosis Ideal case for distal protection Lesion with at least 4-5 cm length of vessel beyond the lesion as a landing zone Minimal landing zone atherosclerosis

23. Distal protection - GuardWire Reproduced with permission from Baim, D. S. et al. Circulation 2002;105:1285-1290.