An Overview of Filter-Protected Carotid Artery Stenting

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These slides give an overview of cerebral protection devices used today in carotid artery stenting, with special emphasis on distal protection filters. Previous work in the field, results from our laboratory, and future directions of device development are covered.

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An Overview of Filter-Protected Carotid Artery Stenting

  1. 1. An Overview of Filter-Protected Filter-Protected Carotid Artery Stenting Gail M. Siewiorek1, Ender A. Finol1,2 1Biomedical Engineering Department, Carnegie Mellon University, Pittsburgh, PA; gail@cmu.edu 2Institute for Complex Engineered Systems, Carnegie Mellon University, Pittsburgh, PA; finole@cmu.edu Vascular Biomechanics and Biofluids Laboratory (VBBL) http://www.ices.cmu.edu/vascular-biomechanics/
  2. 2. Introduction Severe carotid artery occlusive disease is a • vascular condition in which there is: Build up of plaque – Hardening of the arteries (atherosclerosis) – Causes narrowing (stenosis) of internal carotid artery – (ICA) Incidence • Stroke is 3rd leading cause of death in the US [1] – Approximately 1 million stroke-related events each – year [1] Most common and disabling neurological disorder in – elderly population [2] Approximately 50% of strokes due to atherosclerotic – plaque in carotid bifurcation [1] Estimated US$57.9 billion spent on stroke in 2006 • [3] Carotid artery anatomy and atherosclerotic plaque at the carotid bifurcation. 1
  3. 3. Introduction Treatment • Carotid endarterectomy (CEA) Carotid artery stenting (CAS) • Small incision in neck Catheter through femoral – – Clamp carotid Expand stent – – Remove plaque Balloon angioplasty – – 2 Source: http://www.vascularweb.org
  4. 4. Introduction Distal plaque embolization poses Device • greatest risk of CAS Emboshield (Abbott) Use of embolic protection filters (EPFs) • RX Accunet may reduce risk of stoke due to occlusive (Boston Sci.) carotid disease while maintaining flow Angioguard XP throughout procedure (Cordis) Protected CAS: 2.23% vs unprotected CAS: – FilterWire EZ 5.29% [2] (Boston Sci.) Rubicon Patient may be eligible for CAS if: • (Boston Sci.) Symptomatic >50% stenosis – Spider RX Asymptomatic >80% stenosis – (ev3) Interceptor PLUS (Medtronic) FiberNet (Lumen Biomedical) Embolic protection filters that have FDA approval 3 or are currently in clinical trials.
  5. 5. Introduction Criteria from Stenting and Angioplasty • with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial [4] – Under debate whether asymptomatic patients can be considered “high risk” [5,6] SAPPHIRE: first randomized trial for • protected CAS and CEA procedures are not inferior – Protected CAS = 4.4% (30 day) – CEA = 9.9% (30 day) Carotid artery before and after CAS. 4
  6. 6. Introduction Alternative Devices • Distal balloon occlusion – Consists of 0.014 inch hollow nitinol wire with floppy distal tip – Compliant elastomeric polyurethane occlusion balloon inflated distal to plaque lesion – Advantages • Low crossing profile • Ability to capture particles of all size – Disadvantages • Possible external carotid artery (ECA) embolization during lesion crossing • Inability to perform angiograms • Possible injury to ICA • Potential for patient intolerance to complete occlusion [7] Schematic of distal balloon occlusion device. Distal filter • Source: M. Bosiers, P. Peeters Proximal balloon occlusion • 5
  7. 7. Introduction Alternative Devices • Distal balloon occlusion • Distal filter – Consist of 0.014 inch guidewire with floppy distal tip – Filter manufactured of porous polyurethane membrane with nitinol struts, nitinol wire mesh, or polymer fibers – Deployed distal to plaque lesion – Advantages Maintain distal perfusion • Ability to perform angiograms • – Disadvantages Large crossing profile • Embolization of emboli smaller than pore size of • device Possible embolization during lesion crossing and • device retrieval Difficulty navigating severely stenosed or tortuous • vessels Potential for ICA spasm or dissection Schematic of distal filter device. • Incomplete wall apposition [7,8] • Source: M. Bosiers, P. Peeters Proximal balloon occlusion • 6
  8. 8. Introduction Alternative Devices • Distal balloon occlusion • Distal filter • Proximal balloon occlusion – Exclude antegrade ICA flow by either stopping or reversing flow – Consists of two occlusion balloons located in common carotid artery (CCA) and ECA – Advantages • Protects against any size of debris • Protected lesion crossing – Disadvantages • Inability to perform angiograms • Potential for patient intolerance to Schematic of proximal balloon occlusion device. complete occlusion Source: M. Bosiers, P. Peeters • Large delivery sheath size 7
  9. 9. Performance assessment: in vitro testing Müller-Hülsbeck et al. • Bench-top flow loop – Carotid bifurcation modeled with 5 mm inner diameter (ID) silicone tubes with 35° angle between ICA and ECA – Particles injected to simulate embolization during CAS • Polyvinyl alcohol particles (PVA): average mass 5 mg; small (150-250 μm), medium (250-355 μm), large (710-1000 μm) [9,10] • Human plaque: average mass 6 mg: 8-12 particles 500-1500 μm [11,12] Schematic of bench-top flow loop used by – 0.9% saline solution working fluid Müller-Hülsbeck. – Constant flow rate Q = 700 mL/min – Mean CCA pressure P = 78-80 mmHg 8
  10. 10. Performance assessment: in vitro testing Müller-Hülsbeck et al. [9] • Capture efficiency of GuardWire (Medtronic), a distal balloon occlusion device, and Angioguard (Cordis Endovascular), a distal filter • Results: – Overall Angioguard missed 0.80 mg (5.0%) of PVA particles of all sizes while GuardWire missed 1.1 mg (7.0%) – Angioguard missed the smallest of medium particles (0.24 mg vs GuardWire’s 0.28 mg), Schematic of bench-top flow loop used by followed by small (0.25 vs 0.37 mg) and large Müller-Hülsbeck. (0.31 vs 0.45 mg) – Significant effect among devices tested (p<0.001) but not significant between mass of captured particles and device for three sizes (p=0.259) 9
  11. 11. Performance assessment: in vitro testing Müller-Hülsbeck et al. [10] • Capture efficiency of GuardWire Plus, Angioguard, and three additional EPFs: FilterWire EX (predecessor to FilterWire EZ, Boston Scientific), Neuroshield (first generation Emboshield, Abbott Vascular), Trap (formerly Microvena) • Results: – Angioguard was second to Trap for the most missed PVA particles for all three sizes (Angioguard: 1.21 mg, 8.03%; Trap: 1.24 mg, Schematic of bench-top flow loop used by 8.2%) Müller-Hülsbeck. – Angioguard missed the smallest mass of large particles (0.26 mg, 5.1%), followed by medium (0.41 mg, 8.1%) and small (0.56 mg, 11.3%) 10
  12. 12. Performance assessment: in vitro testing Müller-Hülsbeck et al. [11,12] • Capture efficiency of Angioguard, FilterWire EX, Neuroshield, Trap • Results: – Angioguard missed the most human plaque particles (0.27 mg, 4.4%) – Angioguard missed significantly more human plaque particles compared to the other devices (p<0.001) Discrepancies between PVA and human plaque particles studies • – Slightly different subset of devices tested – Common devices between two studies all performed better with human plaque than PVA particles – Comparing Angioguard’s performance using large PVA (710-1000 μm) and human plaque (500-1500 μm) particles: • Angioguard’s relative performance was different (performing the best with PVA particles and performing the worst with human plaque particles) • Angioguard’s absolute performance was similar (missing 0.26 mg vs 0.27 mg, respectively) 11
  13. 13. Performance assessment: in vitro testing Order et al. [13] • Investigate the effect tortuousity has on capture efficiency of Angioguard, FilterWire EX, Neuroshield, Trap • Use similar experimental set-up as Müller-Hülsbeck using PVA particles – Normal: straight silicone tube – Mildly tortuous: 6 cm curved silicone tube – Severely tortuous: 7 cm curved silicone tube Results: • – Angioguard missed the most particles for all sizes in both mildly tortuous (small: 1.19 mg, 23.71%; medium: 0.78 mg, 15.51%; large: 0.57 mg, 11.30%) and severely tortuous (small: 1.47 mg, 29.71%; medium: 0.99 mg, 19.92%; large: 0.68 mg, 13.57%) geometries – Angioguard missed significantly more particles for all particle sizes and all geometries (p<0.001, except large particles comparing mild to severe: p=0.0059) 12
  14. 14. Performance assessment: in vitro testing Hendriks et al. [14] • Investigate the effect the presence of Angioguard, RX Accunet (Abbott Vascular), FilterWire EZ, Spider RX has on pressure gradient • 5 mm ID tube • Blood-mimicking fluid Schematic of bench-top flow loop used by Hendriks. • Input pressure 70 mmHg, 200 mL/min outflow • Results: – Angioguard had the largest pressure gradient (8.80 mmHg) – Significant correlation between flow rate and pressure gradient (r=-0.77, p<0.01) 13
  15. 15. Results from our laboratory Performance assessment: in vitro testing • We have conducted numerous in vitro experiments using several different flow models Flow models: • – Finol [15-17] curved tube patient-specific – Gaspard [18,19] average dimensions, – Siewiorek [20-26] normal and stenosed 14
  16. 16. Results from our laboratory Finol et al. [15-17] • Performance evaluation and wall apposition assessment – 3 tubes curved to have sinusoidal geometry with 3 different IDs: 5.0, 5.5, 6.0 mm • Represent range of vessel sizes one specific size of EPF can treat – Distilled water working fluid – Constant flow rate Q = 360 mL/min; P = 85 mmHg – Microspheres diameter = 297 – 1000 μm Schematic of bench-top flow loop using a straight silicone tube as the flow model. 15
  17. 17. Results from our laboratory Finol et al. [15-17] • Wall apposition assessment – Microspheres cannot pass through pores verify pore size Confocal image projection • – Zeiss LSM 510 Meta laser confocal microscope – 5x FLUAR objective – Numerical aperature = 0.5 (B) (C) (A) Confocal image projection verifying the pore size reported by the manufacturer: (A) Angioguard XP, (B) FilterWire EZ, (C) RX Accunet. 16
  18. 18. Results from our laboratory Finol et al. [15-17] • Wall apposition assessment – Percentage of area not covered by EPF to vessel cross-section Photograph in coronal plane • – EOS Digital Rebel XT Camera – Any portion of filter not flush against wall was colored in red (A) 0.65% (C) (B) 0.075% 4.2% Embolic protection filters shown in the coronal plane of the vessel phantom: (A) Angioguard XP, (B) FilterWire EZ, and (C) RX Accunet. Gaps between the device basket and the arterial wall are shown in red. 17
  19. 19. Results from our laboratory Finol et al. [15-17] • Performance evaluation Percentage of particles missed (RA) – Particles must pass through gaps in wall – Vessel ID (mm) EPFs with highest RA have highest wall apposition – 5.0 5.5 6.0 Angioguard XP Min (mg) 8.76 ± 1.41 9.93 ± 3.27 11.52 ± 4.36 MA (mg) 0.66 ± 0.92 1.08 ± 1.48 1.64 ± 1.22 RA (%) (7.5) (10.9) (14.2) FilterWire EZ Min (mg) 8.08 ± 1.71 8.38 ± 1.93 — MA (mg) 0.08 ± 0.17 0.05 ± 0.12 — RA (%) (1.0) (0.6) — RX Accunet Min (mg) 7.22 ± 0.89 9.58 ± 2.34 10.15 ± 3.78 MA (mg) 0.30 ± 0.06 0.02 ± 0.08 0.14 ± 0.25 RA (%) (4.2) (0.2) (1.4) Continuous data are expressed as mean ± standard deviation. Min: mass of injected microspheres, MA: mass of emboli collected at inline filter A (does not include emboli lost during retrieval of the device), RA: percentage of missed particles to the originally injected microsphere 18 mass (MA/Min) in parenthesis.
  20. 20. Results from our laboratory Gaspard et al. [18,19] • Performance evaluation of RX Accunet Epoxy resin of patient-specific carotid artery geometry – 0.9% saline solution working fluid – Constant flow rate Q = 700 mL/min; P = 95-100 mmHg – Microspheres diameter = 200, 116, 200/116/49 μm – FM 3 ECA PT 3 Carotid flow Pressure Fluid FM 1 valve model reservior CCA Pulse PT 1 FM 2 dampener ICA PT 2 Pressure Pump valve In-line LEGEND filters direction of flow silicone tubing PT pressure transducer FM flow meter Schematic of bench-top flow loop with inset a patient-specific carotid geometry as the flow model. 19
  21. 21. Results from our laboratory Gaspard et al. [18,19] • Performance evaluation of RX Accunet Percentage of particles missed – 200 μm: larger than pore size, 116 μm: approximately same as pore size, 49 μm: smaller – than pore size 200 μm 116 μm 200/116/49 μm Min (mg) 3.71 ± 0.47 4.25 ± 0.69 3.39 ± 0.31 MA (mg) 0.04 ± 0.03 0.06 ± 0.09 0.07 ± 0.06 RA (%) (1.1) (1.9) (2.1) Min = mass of injected particles flowing in the ICA (mg). MA = mass of emboli in the ICA (mg). RA = % of emboli. Data are expressed as mean ± standard deviation and as a percentage of the originally injected particle mass in the ICA in parenthesis. MICA does not include emboli lost during retrieval of the device. Vascular resistance R* – ( ) PCCA − PICA 200 μm 116 μm 200/116/49 μm QICA R* = FF R* +296% +302% +280% ( ) PCCA − PICA Vascular resistance measurements are expressed as a ratio of the pressure QICA gradient in the ICA to the flow rate in the ICA. The percentage values IC indicate the change in vascular resistance in the ICA for FF (final filter condition) with respect to IC (initial condition). 20
  22. 22. Results from our laboratory Gaspard et al. [18,19] • CFD modeling – CAD geometry of patient-specific carotid artery imported into Gambit 2.2 and pre-meshed w/o device – Customized Gambit GUI generated with native scripting language; parametric control of device location and basket pore size – Pore size range 40 – 200 μm; fractional deployment range 70 – 100% – Fractional deployment is the ratio of inlet cross-section of device to ICA cross-section at deployment site Pre-meshed carotid artery and device embedded within the ICA. Gambit GUI for device geometry and mesh generation. 21
  23. 23. Results from our laboratory Gaspard et al. [18,19] • CFD modeling – Pre-meshed carotid geometry ≈ 115,000 hexahedral and tetrahedral elements; device geometry and ICA distal segment: 600,000 – 1.2x106 tetrahedral elements – Actual pore size used in this study: 110 μm; fractional deployment set at 70, 85 and 100% Mesh refinement for device is a function of number and size of pores. 22
  24. 24. Results from our laboratory Gaspard et al. [18,19] • Fluid properties – ρ = 1.05 g/cm3 – μ = 3.85 cP Boundary conditions • Uniform inlet CCA velocity of 0.41 m/s (corresponding to 700 mL/min) – Operating pressure of 100 mmHg – Zero gauge pressure at ICA and ECA outlets – No slip at arterial wall and solid boundaries of EPF basket – Device deployed inside ICA. 23
  25. 25. Results from our laboratory Gaspard et al. [18,19] • Computational simulations (A) indicate up to 17x increase in the local velocity of the flow exiting the basket pores with respect to the CCA inlet • Significant pressure drop in the ICA across the device suggestive of “slow-flow” 7 m/s (B) condition observed in vivo 0 (A) Wall pressure distribution and (B) velocity vectors of blood through RX Accunet in patient-specific carotid bifurcation geometry for 100% apposition. 24
  26. 26. Results from our laboratory 0 m/s Gaspard et al. [18,19] • Retrograde axial flow obtained in the vicinity of the device at 100% apposition 100% • For 85 and 70% apposition -0.2 0.2 m/s retrograde flow is also obtained within the gap between the device and the arterial wall • QICA:QECA ratios – 0.11:0.89 for 100% -0.5 85% – 0.17:0.83 for 85% 0 m/s – 0.29:0.71 for 70% fractional deployments 70% -0.5 Axial velocity mappings proximal to, at the inlet, and distal to the device. 25
  27. 27. Results from our laboratory Siewiorek et al. [20-26] • Performance assessment Average human dimensions of carotid artery, 70% symmetric stenosis – 36% glycerin / 64% deionized water (μ = 3.5 cP) – Constant flow rate Q = 737 mL/min; P = 80 – 100 mmHg – Microspheres diameter = 200, 300 μm – FM 3 ECA PT 3 Carotid flow Pressure Fluid FM 1 valve model reservior CCA Pulse PT 1 FM 2 dampener ICA PT 2 Pressure Pump valve In-line LEGEND filters direction of flow silicone tubing PT pressure transducer FM flow meter Schematic of in vitro flow-loop system with inset of carotid artery flow model with average dimensions and 70% symmetric stenosis. 26
  28. 28. Results from our laboratory Siewiorek et al. [20-26] • Performance assessment Percentage of particles missed – 200 μm microspheres larger than pore size of device except Spider RX (70-200 μm), which – was tested with 300 μm RX Accunet Emboshield Spider RX FilterWire EZ Angioguard XP 5 mg 5.00 ± 0.00 5.00 ± 0.01 5.00 ± 0.01 4.99 ± 0.01 4.99 ± 0.01 Min (mg) 10 mg 10.0 ± 0.0 9.98 ± 0.03 10.0 ± 0.0 10.0 ± 0.0 — 5 mg 0.12 ± 0.09 1.42 ± 0.31 0.01 ± 0.01 0.20 ± 0.13 1.81 ± 0.72 MICA (mg) 10 mg 1.46 ± 0.51 4.83 ± 0.90 0.16 ± 0.14 0.76 ± 0.35 — 5 mg (2.5) (28.3) (0.06) (3.9) (36.3) RA (%) 10 mg (14.6) (48.4) (1.6) (7.6) — Min = mass of injected particles flowing in the ICA (mg). MICA = mass of emboli in the ICA (mg). RA = % of emboli. Data are expressed as mean ± standard deviation and as a percentage of the originally injected particle mass in the ICA in parenthesis. MICA does not include emboli lost during retrieval of the device. 27
  29. 29. Results from our laboratory Siewiorek et al. [20-26] Performance assessment • ( ) PCCA − PICA – Vascular resistance R* QICA R* = FF ( ) PCCA − PICA QICA IC RX Accunet Emboshield Spider RX FilterWire EZ Angioguard XP 5 mg +40.6% +194% +10.1% +20.5% +45.5% R* 10 mg +57.2% +250% +33.0% +32.7% — Vascular resistance measurements are expressed as a ratio of the pressure gradient in the ICA to the flow rate in the ICA at full filter conditions normalized to the initial condition. 28
  30. 30. Results from our laboratory Siewiorek et al. [20-26] • Design characteristics Apores Porosity: Porosity (φ) is defined as the ratio of porous surface ϕ = – Atotal area to total surface area of the device basket Pore density: Pore density (ρp) is defined as the ratio of the number of pores to total surface – area of the device basket Pseudo-permeability – Device removed from nitinol framework and mounted on microscope slide • Image of entire surface taken with Microfire Microscope digital CCD camera • mounted on Olympus BX51 upright microscope Mosaic images acquired using an automated stage and Neurolucida software • (C) (A) (B) High resolution images of EPF baskets removed from nitinol frame and mounted on microscope slides: (A) Spider RX, (B) FilterWire EZ, (C) RX 29 Accunet.
  31. 31. Results from our laboratory Siewiorek et al. [20-26] • Design characteristics Porosity: Porosity (φ) is defined as the ratio of porous surface area to total surface area of – the device basket pores Pore density: Pore density (ρp) is defined as the ratio of the ρp = – number of pores to total surface area of the device basket Atotal Pseudo-permeability – Device removed from nitinol framework and mounted on microscope slide • Image of entire surface taken with Microfire Microscope digital CCD camera • mounted on Olympus BX51 upright microscope Mosaic images acquired using an automated stage and Neurolucida software • (C) (A) (B) High resolution images of EPF baskets removed from nitinol frame and mounted on microscope slides: (A) Spider RX, (B) FilterWire EZ, (C) RX 30 Accunet.
  32. 32. Results from our laboratory Siewiorek et al. [20-26] • Design characteristics Porosity – Pore density – Pseudo-permeability – Same bench-top flow loop: constant flow rate, straight silicone tube 5.5 mm ID • Six target pressure gradients • Physiologically realistic pressure gradients (independent variable) • Adjust flow rate to match target pressure gradient for initial, empty, and full filter conditions • Pseudo-permeability calculated for empty filter condition from Darcy equation for a • straight tube: K: permeability [mm2] Q μL μ: dynamic viscosity = 3.5 cP K= ⋅ L: thickness of membrane = 50-85 μm ΔP A A: cross-sectional area of vessel = π·r2vessel Q/ΔP: flow rate/pressure gradient = slope of Q-ΔP curve 31
  33. 33. Embolic protection filter overview RX Accunet Spider RX FilterWire EZ Emboshield Angioguard XP Nitinol frame / Nitinol frame / Nitinol frame / Nitinol frame / Material polyurethane Nitinol mesh polyurethane polyurethane polyurethane membrane membrane membrane membrane Pore Size (μm) 115 70 – 200 110 140 100 Crossing 3.5 – 3.7 3.2 3.2 3.7 – 3.9 3.2 – 3.9 Profile (F) One size fits all Size (mm) 4.5, 5.5, 6.5, 7.5 3, 4, 5, 6, 7 3, 4, 5, 6 4, 5, 6, 7, 8 (3.5 – 5.5) Porosity (%) 4.5% 50.4% 12.9% 2.2% 11.3% Pore Density 4.4 10.0 13.6 1.4 14.4 (pore/mm2) Permeability — 0.826 1.879 1.225 0.422 (mm2) Capture 95.1% 99.9% 96.1% 64.6% 63.7% Efficiency (%) Vascular +40.6% +10.1% +20.5% +194% +45.4% Resistance 32
  34. 34. Performance assessment: ex vivo testing Müller-Hülsbeck et al. [27] • Quantify vessel wall damage on ex vivo porcine carotid arteries in bench-top flow loop described previously 0.9% saline solution working fluid – Constant flow rate Q = 700 mL/min – Mean CCA pressure P = 78-80 mmHg – Adverse movement (1 cm up in cranial direction, 2 cm • down, 1 cm up) of Angioguard, FilterWire EX, Neuroshield, Trap, Percusure (distal balloon occlusion) Vessel wall evaluated histologically • Results: • Schematic of bench-top flow loop used by Müller-Hülsbeck. Angioguard generated significantly (p<0.001) less debris – than the other devices (4.75 mg) during placement except for FilterWire EX (p<0.014) Angioguard generated significantly more debris during – device retrieval (2.06 mg) than during placement or adverse movement (1.32 and 1.37 mg respectively, p<0.05) The masses are generated due to device-vessel wall – 33 contact
  35. 35. Performance assessment: ex vivo testing Müller-Hülsbeck et al. [28] • Proof of concept study evaluated capture efficiency of unprotected CAS, protected CAS using Emboshield, and MembraX, a membrane stent with integrated protection • Human carotid cadaveric explants • Results: – Fewest number of embolized plaque Carotid explant used during experimentation. Carotid is connected to bench-top flow loop by CCA and ICA; ECA particles generated during is clamped. unprotected CAS (17 particles), followed by MembraX (10 particles) and protected CAS (37 particles) – Emboshield caused the greatest weight (p=0.011) and number of particles (p=0.054) 34
  36. 36. Performance assessment: ex vivo testing Ohki et al. [29] • Capture efficiency of Neuroshield • Human carotid plaques obtained from CEA • Protected CAS simulated • Embolic debris quantified • Results: – Neuroshield captured 88% of total plaque particles embolized during the procedure Schematic of bench-top flow loop used by Ohki. 35
  37. 37. Performance assessment: clinical testing Casserly et al. [30] • Observed via angiograms significant reduction in antegrade flow in the ICA proximal to the EPF – Termed “slow-flow” Use multivariate logistic regression to identify predictors and prognosis of • patients who undergo slow-flow Results: • – Slow-flow predictors: recent (<6 months) of stroke or transient ischemic attack, increased stent diameter, increased patient age – Among patients who experienced slow-flow, 30 day stroke and death rate was 9.5% vs 2.9% (p=0.03) It is important to note that a significant percentage of embolic debris is • smaller than the pore size of EPFs and have the potential to occlude diatal capillary beds; thus, “slow-flow” can occur even if the EPF basket is not full 36
  38. 38. Performance assessment: clinical testing Trial Device Endpoint 30 day rate SAPPHIRE [31] Angioguard / Stroke, 4.4% (Stenting and Angioplasty with Protection in Patients at High Risk for Angioguard XP MI, death Endarterectomy) ARCHeR [32] Stroke, RX Accunet 8.3% MI, death (ACCULINK for Revascularization of Carotid in High-Risk Patients) BEACH [33] Stroke, 5.8% FilterWire EX / EZ (Boston Scientific EPI: A Carotid Stenting Trial for High-Risk Surgical MI, death Patients) CABERNET [34] Stroke, 3.8% FilterWire EX / EZ (Carotid Artery Revascularization Using the Boston Scientific FilterWire MI, death and the EndoTex NexStent) CREATE [35] Stroke, 6.2% Spider RX MI, death (Carotid Revascularization with ev3 Arterial Technology Evolution) SECuRITY [36] Stroke, (Registry Study to Evaluate the Neuroshield Bare Wire Cerebral 7.2% Emboshield MI, death Protection System and X-Act Stent in Patients at High Risk for Carotid Endarterectomy) 37
  39. 39. Performance assessment: clinical testing Roffi et al. [37] • Investigate effect of EPF design (Angioguard, FilterWire EZ, Spider) on blood flow impairment • Find predictors of flow impairment: use Student t test for continuous variables, chi-square contingency tables for categorical data • Results: – Flow obstruction occurred more frequently with Angioguard (32.2%) than with FilterWire EZ (6.2%) or Spider (6.7%) – No flow occurred in 13 procedures, all treated with Angioguard It is interesting to note that these results correlate well with our in vitro • experiments – Angioguard had one of the least favorable performance, FilterWire EZ and Spider had more favorable performances 38
  40. 40. Limitations of EPFs Three important questions remain unanswered: • – What is the ideal pore size? – How effective is circumferential basket-vessel wall apposition in tortuous anatomy? – How can capture efficiency be improved? 39
  41. 41. Limitations of EPFs What is the ideal pore size? • – Most filters have pore sizes less than 200 μm • Stroke victims have evidence of occluded arterioles ranging from 50 to 300 μm [38] • Small fragments (<100 μm) may cause late neuronal ischemia [39] • Calcified fragments cause greater levels of infarction than fibrous plaques [40] 40
  42. 42. Limitations of EPFs How effective is circumferential basket-vessel wall apposition in • tortuous anatomy? – Basket-vessel wall apposition is not always complete, particularly in tortuous anatomy – A poorly seated filter basket is not necessarily evident at time of intervention • Can lead treating physician into a false sense of security even though EPF is not functioning as expected 41
  43. 43. Limitations of EPFs How can capture efficiency be improved? • – EPF must be able to capture debris while maintaining antegrade flow – Clinical evidence of exceeded capture efficiency capacity is occluded or thrombosed filter basket – Capture efficiency can be altered by several mechanisms: • Pore density • Filter configuration (shape and length) • Filter membrane composition – One current short-coming of EPFs is embolic capture occurs in only one dimension • FiberNet (Lumen Biomedical), currently in clinical trials, uses a woven polytetrafluoroethylene membrane to capture emboli in two dimensions 42
  44. 44. Limitations of EPFs How can capture efficiency be improved? • – Clinical manifestations of distal embolization due to inadequate pore size and wall apposition may be relatively minor or absent despite pathologic or radiographic evidence of ischemia [41-43] – Silent infarcts may lead to diminished neurocognitive function, vascular dementia and Alzheimer’s disease, while others have shown improvements in cognitive function after CAS [44-46] – Better correlation between in vitro testing and clinical outcomes needs to be established • Although no known difference in complication rates between patients that do and do not exhibit periprocedural hemodynamic depression (systolic blood pressure <90 mmHg and/or heart rate >50 beats/min), it should be decreased for patients with severely calcified plaque lesions [47] 43
  45. 45. Cost-effectiveness Protected CAS is associated with significantly higher total and direct costs than CEA • Decreased procedural and hospital times for CAS do not offset equipment costs • In order for two procedures to be equally cost-effective, major stroke and mortality rate of CAS • must approach that of CEA Study Measure CAS cost CEA cost p-value Total procedural cost US$17,402 US$12,112 p = 0.029 Park et al. [48] Surgical vs angiography suite US$15,407 US$1,953 p = 0.001 supplies Central supply costs (medical and US$4,548 US$338 p < 0.001 Pawaskar et al. [49] surgical supplies) Arrebola-Lopez et al. [50] Average cost €5158 €3963 — Quality adjusted life-years 8.20 8.36 — Kilaru et al. [51] Lifetime cost US$35,789 US$28,772 — 44
  46. 46. Application of technology There are no randomized studies comparing protected and • unprotected CAS – It is unlikely they will be pursued Use of EPFs considered to be standard of care by some [52,53] • Angioguard XP for use with Precise RX Nitinol Self-Expanding • Stent was approved for CAS interventions by the FDA in September of 2006 45
  47. 47. Conclusion Complications resulting from or during CAS have been reduced by • use of EPFs such as Angioguard XP Our own bench-top testing indicates Angioguard XP has • undesirable performance measures Angioguard XP has mixed results in the literature • Future generations of EPFs should be designed to minimized • vascular resistance Pore size and wall apposition have been observed experimentally • to be important characteristics influencing EPF performance in vitro 46
  48. 48. Expert commentary CAS is an evolving field for the treatment of extracranial carotid • artery disease and stroke prevention Improvements in training and devices appear to have led to better • clinical outcomes Further advances are needed to diminish distal cerebral • embolization Angioguard and other EPFs lack sophistication required for more • complex anatomy and plaque morphology More stringent bench-top testing required to address device short- • comings, particularly with pore size, wall apposition, and capture efficiency 47
  49. 49. Five-year view Medical therapy will continue to be the mainstay for stroke • prevention CAS and CEA will continue to be necessary in certain patient • cohorts: – CAS: reserved for high-risk surgical candidates (i.e., recurrent carotid stenosis, prior neck irradiation, contralateral recurrent laryngeal nerve palsy or severe cardiopulmonary disease) – CEA: advocated for standard-risk patients Newer EPFs will become available that allow for capture of all • particulate debris to reduce the short- and long-term sequelae of distal cerebral embolization 48
  50. 50. Acknowledgments • Carnegie Mellon’s Biomedical Engineering Department • Pennsylvania Infrastructure Technology Alliance (PITA) • Samuel and Emma Winters Foundation • NIH T32 Biomechanics in Regenerative Medicine • Justin Crowley and Corey Flynn of Carnegie Mellon’s Department of Biological Sciences and Center for the Neural Basis of Cognition • Mark H. Wholey of Department of Radiology, University of Pittsburgh Medical Center – Shadyside, Pittsburgh, PA • Michael H. Wholey of Department of Radiology, University of Texas Health Sciences Center, San Antonio, TX • Mark K. Eskandari of Division of Vascular Surgery and Department of Radiology, Northwestern Memorial Hospital, Chicago, IL 49
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