This document provides an overview of filter-protected carotid artery stenting. It discusses carotid artery disease and treatment options like carotid endarterectomy and carotid artery stenting. Embolic protection filters are used during carotid artery stenting to prevent plaque and debris from entering the bloodstream and causing strokes. The document summarizes various embolic protection devices and filter designs. It also reviews several in vitro studies that evaluate the capture efficiency and performance of different filter devices using particle models and benchtop flow loops. Overall, the document presents background information on carotid artery disease and stenting and evaluates the performance of embolic protection filters through in vitro testing.

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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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