Embolic Protection Devices: Are Filters Silent Stroke Predictors? CRT 2010 Embolic Protection Devices: Are Filters Silent Stroke Predictors? Michael Wholey, MD, MBA Central Cardiovascular Institute 2/23/10 8:50- 9:00 AM

Michael H. Wholey, MD DISCLOSURES I have no real or apparent conflicts of interest to report. I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference carotid stenting and filter devices.

Financial Disclosures I have no financial interests in this area.

Basic Questions 1. Are Carotid Embolic Protection Devices Helpful ?

Some questions are intuitive.

What Would This Large (Calcified) Embolic Particle Do In the Cerebral Circulation If It Had Not Been Captured ?

How Often Is There Visable Debris in the Filter Basket ? Ouriel et al 90 Angioguard 54% Lupatelli 96 Trap/EPI 21% Sprouse 279 60% Bosiers 100 EPI 57% Reimers 84 3 types 53% Angelini 37 84% There was an increased risk of visible debris found with hypertension, hypercholesterolemia, stent diameter >9 mm, and any neurologic event Collected material consisted of lipid-rich macrophages, fibrin material, and cholesterol clefts.

Carotid Stenting With and Without Protection Symptomatic Pts Asymptomatic Pts 6.04% 3.97% 2.70% 1.75%

CAS with and without DP Author With DP Results Without DP Reduction Zahn Eur Heart J. 2004 Sep;25(17):1550-8. 668 (45%) 2.1% Stroke and Death 676 (55%) 4.9% Stroke and Death 57% Castriota Endovasc Ther. 2002 Dec;9(6):786-92. 150 (55%) 0.7% Stroke 125 (45%) 2.4% Stroke 79% EVA-3 Stroke. 2004 Jan;35(1):e18-20. 58 8% Stroke 15 27% Stroke 70% KASTROP Stroke. 2003 Mar;34(3):813-9. 896 (literature review) 1.8% Stroke and Death 2537 5.5% Stroke and Death 67% Roubin 6.9% Stroke and Death 74% * All Statistically significant

Basic Questions 1. Are Carotid Embolic Protection Devices Helpful ? 2. Are Distal Protection Devices Silent Predictors for Stroke ?

Silent Cerebral Ischemia with DPD Jaeger et al. The Angioguard filter device was effectively employed in 16 of 20 pts New ipsilateral cerebral lesions were visualized by DW-MRI in 3 of the 20 procedures No new permanent neurologic deficits occurred. Cardiovasc Intervent Radiol 2001 Jul-Aug;24(4):249-56 Schluter et al 42 consecutive patients using six types of cerebral protection systems New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures J Am Coll Cardiol. 2003 Sep 17; 42(6): 1007-13

Silent Ischemia with DP METHODS: 67 CAS were performed with EPI The mean length of the procedure was 22.2 minutes (range 8-110). All patients had a cerebral MRI done in the 3 days before CAS and a DW-MR was done the day after. RESULTS: 30-Day Events: 3 TIA’s, 1 minor stroke (1.5%) on day 21, but no major stroke, death or MI DW-MRI after CAS showed 26 new silent ischemic lesions in 11 asymptomatic patients (16.4%). 6 Pts , they were multiple (range 2-5). Location: 21 ipsilateral MCA, 4 in the posterior fossa, and 1 in the contralateral MCA. Gonzales Neurol Res. 2005;27 Suppl 1:S79-83.

Diffusion Weighted MRI Post CAS New ischemic foci were observed in 17.3% of the patients undergoing neuroprotected CAS. Appearance of new ischemic lesions were only significantly related to the occurrence of TIA but not to the number of MES registered or other variables. Incidence of new brain lesions after carotid stenting with and without cerebral protectionA. Kastrup, T. Nagele and K. Groschelet al. Stroke 2006; 36:2312-6.. 

MRI Diffusion Weighted Studies in Post Endarterectomy Postoperative DWI revealed ipsilateral ischemic lesions in 15 patients (17%). In seven of these patients a brain infarction was diagnosed on the T1-MRI during follow-up. A significant correlation between the number of DWI lesions (p=0.031) as well as the volume of DWI lesions (p=0.023) and definite infarction was found. Symptomatic patients preoperatively showed significantly more DWI lesions (p=0.036) and cerebral infarcts (p=0.003) Wolf et al Frequency, Clinical Significance and Course of Cerebral Ischemic Events after Carotid Endarterectomy Evaluated by Serial Diffusion Weighted Imaging European Journal of Vascular and Endovascular Surgery, Volume 27, Issue 2, Pages 167-171

Silent Cerebral Ischemia Detected by Diffusion-Weighted MRI After Carotid Endarterectomy A Preoperative brain DWI of a 74-year-old woman with an asymptomatic high-grade carotid stenosis on the right side. B, Postoperative brain DWI demonstrating a single new hyperintensity in the ipsilateral subcortical temporal region (arrow), which was highly suggestive of a perioperative embolusAsymptomatic Courtesy of Alain Barth (Stroke. 2000;31:1824.)

Diffusion Weighted CAS Studies Author Patients Stroke & Death MRI Findings(ipsilateral) Kastrup et al 139 Protected 4.3% 49% 67 Unprotected 7.5% 67% Piñeroa et al 162 protected 28 pts (17.3%) single foci 13 pts (8%) multiple foci Wolf et al. 88 Protected 2.3% 15 (17%) Gossetti et al 50 CAS 50 CEA 4% 2% 24 (44%) 2 (4%) Schnaudigel et al 1363 CAS 753 CEA -- 37% 10%

So what does this silent ischemia mean ? Are our filters truly effective ? Are we releasing too many small particles? Failing to capture (and hang on) to larger ones?

So what does this silent ischemia mean ? Are our filters truly effective ? Are we releasing too many small particles? Failing to capture (and hang on) to larger ones? Procedural Questions ? Too much manipulations in the aortic arch ? Evidenced by the incidence of post fossa and contralateral hits Excessive Time of procedures

Basic Questions 1. Are Carotid Embolic Protection Devices Helpful ? 2. Are Distal Protection Devices Silent Predictors for Stroke ? 3. Are all Distal Protection Devices the Same ?

Four appproved DPFs (Spider RX, FilterWire EZ, RX Accunet, and FiberNet) were evaluated in a pulsatile programmable piston pump circulated a blood analog at a time-varying flow rate representative of the human common carotid artery. A silicone carotid bifurcation having average human dimensions was used for the carotid flow model. Microspheres ranging from 40 to 900 µm were injected to simulate embolization. The longitudinal vascular impedance was calculated as the ratio of the time-varying pressure gradient across the DPF to the time-varying flow rate in the internal carotid artery.

In Vitro Study

In Vitro Study: Capture Efficiency -RX Accunet had the highest capture efficiency (99.4%) and Spider RX had the lowest (78.1%). -Spider RX missed the largest average number of small particles (14.6) and RX Accunet missed the fewest small particles (0.2). -All 4 DPFs missed a similar average number of medium sized particles (range 0.1–0.4). -All DPFs captured all large particles.

In Vitro Study: Vascular Impedance An increase in longitudinal vascular impedance indicated an increase in pressure gradient and decrease in flow rate. -Spider RX had the smallest increase in longitudinal vascular impedance in EF closely followed by FilterWire EZ . -FiberNet had the largest increase in longitudinal vascular impedance for both EF and FF.

In Vitro Study of the Filters Results: Capture Efficiency: RX Accunet had the highest capture efficiency (99.4%) and Spider RX the lowest (78.1%). Vascular Impedance: Spider RX increased the longitudinal vascular impedance the least after deployment (+23%), while FilterWire EZ increased the longitudinal vascular impedance the least after particles were injected (+29%). FiberNet increased longitudinal vascular impedance the most (+84%).

What is the debris ? The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 micron) and lipoid masses (7 to 600 micron). Martin et al. Stroke 2001 Feb;32(2):479-84 The 22 to 667 particles aspirated per patient, mean 203 micron)…included fibrous plaque debris, lipid or cholesterol vacuoles, and calcific plaque fragments Whitlow et al. Stroke 2002 May;33(5):1308-14

Potential Problems with Distal Protection Inability to deliver or deploy the device  Large device profile  Lack of steerability  Excessive vessel tortuosity Device-induced complications  Injury to the internal carotid artery from the guidewire or protection device  Embolization due to passage of the device through the lesion Cerebral ischemia  Patient intolerance due to balloon occlusion  Filters may become packed with debris causing flow limitations Incomplete capture or retrieval of debris  Pores in filter may allow passage of small particulate debris  Burden of debris may overwhelm the protection device  Incomplete apposition of device to carotid wall may allow embolization Embolization into proximal branches  External carotid (ophthalmic artery)

Potential Problems with Distal Protection Inability to deliver or deploy the device  Large device profile  Lack of steerability  Excessive vessel tortuosity Device-induced complications  Injury to the internal carotid artery from the guidewire or protection device  Embolization due to passage of the device through the lesion Cerebral ischemia  Patient intolerance due to balloon occlusion  Filters may become packed with debris causing flow limitations Incomplete capture or retrieval of debris  Pores in filter may allow passage of small particulate debris  Burden of debris may overwhelm the protection device  Incomplete apposition of device to carotid wall may allow embolization Embolization into proximal branches  External carotid (ophthalmic artery)

Common Filter Problem: Spasm

Problems with Filters: Dissection

Full Basket Following Advancement Across Lesion

Basic Questions 1. Are Carotid Embolic Protection Devices Helpful ? 2. Are Distal Protection Devices Silent Predictors for Stroke ? 3. Are all Distal Protection Devices the Same ? 4. Are Proximal Occlusion Devices Better?

Conclusions There exists differences among the various carotid filters Filters and the inability to capture embolic debris can help lead to silent cerebral ischemia detected by diffusion-weighted MRI