Embolic Protection Device

Disease State & Pathology

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Image: Surrounding tissues of implanted EPD

The Embolic Protection Device (EPD) functions as a biotextile device to capture and remove debris and emboli from the bloodstream during balloon angioplasty, stenting, or percutaneous surgical procedures in the carotid arteries and coronary saphenous vein.  Such procedures are known as carotid artery stenting (CAS) and carotid endarterectomy (CEA).  Carotid artery stenting (CAS), as a viable therapy to treat carotid disease and stroke prevention, is growing.  Continuous advances in angioplasty techniques and the development of low-profile, flexible, tapered nitinol stents designed specifically for carotid applications have made CAS a viable alternative to CEA.  One of the limitations of carotid stenting is the risk of liberating embolic particles during the procedure that could cause a stroke or compromise cognitive function.  Physicians are looking for better solutions to achieve optimal protection while performing carotid procedures.  These procedures remove plaque and thrombus from the internal or luminal arterial wall of atherosclerotic patients.  Atherosclerosis is the buildup of fats, cholesterol, and other substances (plaque) in or on the artery walls.  Distal embolization results from this plaque formation, causing blockages, which travel from their origin to a different site in the body.  These emboli in effect block the flow of blood throughout the body and may result in tissue damage or mortality.  Emboli which occur in the brain are a direct cause of stroke, while those that occur in the heart directly influence heart attacks.  Other sites of typical embolic occurrence are the lower extremities and pulmonary tissues.  By filtering debris and emboli, the EPD contains and removes these undesirable materials, while allowing blood cells to pass through.  It reduces the risk of arterial or pulmonary blockage (occlusion), infarcts, stroke, and heart attacks secondary to the intervention.

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Image: Diseased site requiring EPD intervention

Implantation Site & Protocol

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Image: Implantation protocol of EPD

The EPD, which resembles a butterfly net, is pre-placed on a wire downstream prior to surgery.  It is attached to a balloon angioplasty catheter, which is used to deploy an arterial stent.  The stent is expanded by the balloon catheter, thus creating a larger vessel for the placement of the Embolic Protection Device.  Upon deployment, the EPD expands creating a filter that collects debris and emboli.  It is most commonly used for applications in which veins are 2.5-5.5mm in diameter.  Following the completion of the surgical procedure, the EPD is removed, having collected materials considered to be detrimental to the success of the procedure, and ultimately the health of the patient.

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Image: Balloon stenting for EPD delivery

Manufacturers

MEDTRONIC® – FiberNet™ Embolic Protection System

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Image: FiberNet Embolic Protection System

The Medtronic® 3-D FiberNet Embolic Protection System is designed to provide protection from embolic debris during surgical procedures.  Screen Shot 2015-04-12 at 6.31.37 PMThe filter features capillary channel PET (polyethylene terephthalate) fibers that move fluids and capture particles efficiently.  The three-dimensional design of the fibers allows for cover of a high surface area that provides conformity to the irregular vasculature of the vessel wall.  It also provides a 360 degree apposition that increases stability and minimizes vasospasm.  The device can capture debris as small as 40 microns and has a significantly higher filter efficiency than a traditional wire and basket device.

http://www.peripheral.medtronicendovascular.com/videos/fibernet/index.htm

W.L. GORE – GORE® Embolic Filter

EPD

Image: GORE Embolic Filter

The GORE® Embolic Filter features a unique diamond frame that expands the safety of embolic protection during carotid interventions in an easy-to-use solution.  The diamond frame provides optimal wall apposition leading to superior filter efficiency, even in tortuous vessels with small landing zones and tight curves.  To take full advantage of improved filter efficiency, the filter is designed for enhanced lesion cross-ability and reliable retrieval.  The diamond frame is is surrounded by a braided ePTFE filter containing 100 micron pores.  A conformable, hydrophilic heparin-coated ePTFE filter bag with unconstrained distal attachment provides large filter capacity while accommodating small landing zones with tight curves.

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Image: Dimensions of GORE EPD system

Clinical Studies

W.L. GORE – GORE® Embolic Filter

While the GORE® Embolic Filter is similar in many ways to other currently available filters, it has been designed to provide optimal vessel wall apposition.  Bench tests suggest that the wall apposition may provide improved filter efficiency, thereby minimizing embolization of particles downstream and potentially decreasing adverse clinical effects.  In addition, preclinical testing suggests that the GORE® Embolic Filter has improved deliverability, including torque ability and lesion cross that may improve the ability of the system to access and treat tight lesions in tortuous anatomy.  Thus, the purpose of this multi-center clinical study is to assess the safety and effectiveness of the GORE® Embolic Filter when used to provide cerebral embolic protection during carotid artery angioplasty and stenting.

A clinical trials study was conducted by the Food & Drug Administration (sponsored by W.L. Gore and Associates) over a time period from 2008-2012.  It included patients of middle and older age for the purpose of testing device and clinical success.  Device success defined as the number of participants with Technical Success using the GORE Embolic Filter (i.e., the GORE® Embolic Filter device was delivered, placed, and retrieved as outlined in the Instructions for Use).  Clinical success defined as GORE® Embolic Filter and carotid stent success in the absence of death, emergency endarterectomy, repeat thrombolysis of the target vessel, and stroke.  Clinical success will be evaluated from procedure through 24-48 hours post-procedure.  This study was conducted at a maximum of 40 medical institutions across the United States and enrolled approximately 250 participants.  The principal investigator was Dr. William A. Gray, M.D. of Columbia University.

Study Results:

Gore® Embolic Filter in Carotid Stenting for High Risk Surgical Subjects (EMBOLDEN)

Reference to the Clinicaltrials.gov website, with ID# NCT00766493. This Study was Completed.

Number of Participants: 250

Average Age: 74.7 ±9.4

Range: (51.3 – 92.6)

  • History of Diabetes: 87
  • History of Hypertension: 236
  • History of Ischemic Stroke:
  • None: 200
  • One: 34
  • Two: 12

Primary Study: Composite Major Adverse Event (MAE) Rate of death, myocardial infarction, and stroke at 30 days post procedure

  • Participants analyzed: 234
  • One or more MAE: 10
  • Death: 2
  • Myocardial Infarction: 1
  • Stroke: 7
  • Major stroke: 1
  • Ischemic Stroke: 1
  • Minor Stroke: 6
  • Ischemic minor Stroke: 6

Secondary Study: Device Success as defined as the number of participants with technical success using the GORE embolic protection system (i.e. Embolic filter device was delivered, placed, and retrieved as outlined in the instructions for use.

  • Participants analyzed: 250
  • Device Success: 241

Secondary Study: Clinical Success as defined by GORE Embolic Filter and carotid stent success in the absence of death, emergency, endarterectomy, repeat PTA/ thrombolysis of the target vessel, and stroke or MI as determined by the clinical event committee. Evaluated from procedure through 24-48 hours post procedure.

  • Participants analyzed: 250
  • Clinical Success: 233

Secondary Study: Access Site complications, defined as the presence of a large hematoma (>5cm or requiring treatment or prolonged hospitalization), fistula or pseudoaneurysm formation, retroperitoneal bleeding or the need for surgical repair postprocedure.

  • Participants analyzed: 250
  • Access Site Complications: 6

Secondary Study: Neurologic events at 30 days post-procedure, including transient ischemic attacks (TIAs) 30 day time frame

  • Participants analyzed: 250
  • Neurologic Events: 16

Total, Serious adverse events: #Participants affected / at risk    56/250 = 22.4%

MEDTRONIC® – FiberNet Embolic Protection System

A clinical trials study was conducted by the Food & Drug Administration (sponsored by Medtronic, Inc., previously Lumen Biomedical) over a time period from 2006-2008.   This study was conducted with an enrollment of approximately 30 participants.  The study was designed to demonstrate the performance and safety of the Medtronic, Inc. (Lumen Biomedical, Inc.) FiberNet™ Embolic Protection System as an adjunctive device during carotid artery percutaneous intervention using a carotid stent in high surgical risk patients.  These patients experience symptomatic with atherosclerotic stenosis ≥ 50% or asymptomatic with atherosclerotic stenosis ≥ 70% of the carotid artery.  The principal investigator was Dr. J. Michael Bacharach, M.D., of the North Central Heart Institute.

Study Results:

EPIC US Feasability Study: Use of the FiberNet® Embolic Protection Device in Carotid Artery Stenting

Reference to the Clinicaltrials.gov website, with ID# NCT0034515. This Study was Completed and rated as a success, but the data was not released.

Estimated Enrollment: 30

Primary Outcome Measures: Rate of all death, all stroke and myocardial infarction within 30 days of the procedure

Secondary Outcome Measures: all death and all stroke rates; non-stroke neurological even rates; technical success rates; procedural success rates; access site complication rates

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Image: Clinical results of GORE EPD

Surface Treatments

The two most recommended surface treatments for improving the efficiency of an embolic protection device are the application of an organically-based silica gel coating and the use of an anticoagulant medication finish.  Several key surface and mechanical properties of an embolic protection device/system are: porosity, bending flexibility/stiffness, bursting strength, thrombogenicity, thickness, tensile strength, and hydrophobicity, among others.  While several of these properties are determined through the material structure (i.e. braided), some properties are influenced by surface modifications of the product.  Each of these properties provides essential function to the product through filtration of emboli.

An organically-based silica gel is applied to the metal or polymer that composes a filter prior to filter formation.  Such gel promotes hydrophobicity and serves to further reduce pore size, as well as decrease the likelihood of complete filter blockage occurrence.  This allows for the smooth flow of small platelets and other blood components, while filtering plaque, debris, and other emboli.

An anti-platelet/coagulant drug such as serves the purpose of further breaking up partially clotted platelets that mistakenly move through the filter.  Drugs, such as Clopidogrel or Heparin, provide an additional opposition to the thrombogenic nature of arterial stenting and the likelihood of thrombus formation.  Such coating also allows blood to flow at a greater ease through the filter without a combination of platelets and plaque forming an embolus within.

Sterilization Procedures

There are three common commercial sterilization techniques used among the current range of commercial embolic protection devices: electron beam sterilization, Ethylene Oxide sterilization, and gamma irradiation.  In order to be successful in the sterilization of an embolic protection device/system, the given sterilization method must not degrade the selected polymer materials and not damage the surrounding tissue and immune response.

Electron beam sterilization involves the use of mostly high energy electrons to break DNA chains in organisms such as bacteria, resulting in microbial death.  This process is deemed environmentally friendly, and is also able to be used following final packaging as electrons have the ability to pass through package units.  As this process is quick, compatible with many materials, reliable, and does not require quarantine following processing, electron beam sterilization provides significant advantages when compared to other forms of sterilization.  Also, unlike both gamma rays and ethylene oxide gas, electron beam sterilization does not make use of radioactive or hazardous materials.  Proper sterilization is ensured through the efficient conversion of rf power to an accelerating gradient as well as a standard of electron pulse repetition rates ranging up to 500 pulses per second; therefore, ensuring a stable sterilization process in continuous use.

Similar to electron beam sterilization, gamma irradiation as a sterilization technique consists of passing electromagnetic rays through a multitude of materials to kill bacteria through the means of breaking covalent bonds of bacterial DNA.  Gamma irradiation serves to provide a number of benefits economically, as well as overall sterility.  It can be applied safely under controlled operating parameters, and does not yield heat stress to subjects of radiation.  It should also be noted that there is no residual radioactivity following irradiation of products, although the strength of gamma radiation provides the potential to degrade polymer structures and surface coatings.  To ensure a sterile product, historical dose mapping is used to test the amount of radiation delivered to total sterilization of the end product.  This ensures that a standardized level of radiation has been accepted for delivery resulting in proper sterilization with minimal damage to materials.

Cold (or chemical) sterilization and ethylene oxide (ETO) sterilization are also used in sterilizing biomaterials for medical devices.  These methods of sterilization require hazardous solutions and conditions, which result in growing environmental and health concerns.  Due to these concerns and the time invested in eliminating traces of ETO and chemicals present on the products after processing, there is considerable pressure to reduce and ultimately eliminate the use of these processes as acceptable sterilization methods for medical devices and biotextile materials.

Business Strategy

The business strategy for embolic protection devices is aimed towards medical professionals dealing with coronary, carotid/neurological, and peripheral artery procedures.  Most marketing for these devices involves proving the effectiveness of a particular product over another in terms of filter efficiency.  In other words, a surgeon is more likely to use the most effective embolic protection device as it will reduce complications presented by the release of emboli during surgery.  Embolic protection devices have been forecasted to reach a revenue of $540 million in 2015 with a compound annual growth rate of 14.6% through the period of 2009-2015.  North America accounts for almost 40% of the global embolic protection device industry while Europe claims almost 30%.  In the eastern hemisphere, it is determined that China leads over India, South Korea, and Russia in terms of global value, while India shows the largest potential for growth.  Balloon occlusion devices are projected to provide for a majority of market value in 2015, followed by catheter occlusion and filter devices.  In terms of procedures performed, coronary interventions lead over carotid/neurology and peripheral artery procedures.

Potential Limitations & Improvements

MEDTRONIC® – FiberNet™ Embolic Protection System

  • High crossing profile
  • Difficult to steer during procedure
  • Delivery/retrieval catheters may embolize
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Table: Comparison of EPD filter efficiency

W.L. GORE – GORE® Embolic Filter

  • High crossing profile
  • Too stiff for some tortuous vessels
  • May clog with debridement
  • Delivery/retrieval catheters may embolize
  • May not capture all debris

Alternative Therapies & Techniques

Current EPD uses are consistent in the vascular arteries and tissues to prevent the movement of blood clots and emboli from moving to the neural/cerebral arteries, thus resulting in stroke or loss of cognitive function; however, there is a new desire to extend this treatment to other arterial applications in the body.  Several studies have researched advanced techniques to improve blood flow in the lower extremities.  These include the use of embolic protection devices/systems to promote healthy blood flow in the femoral artery, renal artery, among others.

References

  1. “FiberNet – Carotid Package – Embolic Protection System, Medtronic.” Web.
  2. “Current update of cerebral embolic protection devices.” Mousa, Albeir Y. et al. Journal of Vascular Surgery, Volume 56, Issue 5, 1429 – 1437.
  3. “GORE® Embolic Filter.” Web.
  4. “GORE® Embolic Filter in Carotid Stenting for High Risk Surgical Subjects (EMBOLDEN).” Web.
  5. “EPIC US Feasibility Study: Use of the FiberNet® Emboli Protection Device in Carotid Artery Stenting.” Web.
  6. Lin, J.; Chen, H.; Fei, T.; Zhang, J. (2013). “Highly transparent superhydrophobic organic–inorganic nanocoating from the aggregation of silica nanoparticles.” Colloids and Surfaces A: Physicochemical and Engineering Aspects 421: 51.
  7. Buddy D. Ratner, Chapter I.1.5 – Surface Properties and Surface Characterization of Biomaterials, Biomaterials Science (Third Edition), 2013, Pages 34-55.
  8. Buddy D. Ratner and Allan S. Hoffman, Chapter I.2.12 – Physicochemical Surface Modification of Materials Used in Medicine, Biomaterials Science (Third Edition), 2013, Pages 259-276.
  9. Martin, J. Understanding gamma sterilization. BioPharm International, 25(2)
  10. David Hill, Chapter 18 – Sterilization, Design Engineering of Biomaterials for Medical Devices, 1998, P ages 305-317.
  11. “Medical Device Sterilization: What Manufacturers Need to Know.” MDDI RSS. Web.
  12. “Ethylene Oxide (EtO) Sterilization Process.” Web.
  13. “Embolic Protection Devices (EPD) – Emerging Markets 2009-2015.” Web.
  14. “Global Embolic Protection Devices (EPD) – Market Growth Analysis, 2009-2015.” Web.
  15. D. Christopher Metzger, Embolic Protection in Carotid Artery Stenting: New Options, Techniques in Vascular and Interventional Radiology, Volume 14, Issue 2, June 2011, Pages 86-94.
  16. White, C. J. (2014). Carotid artery stenting. Journal of the American College of Cardiology, 64(7), 722-31.

Final Version

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11 thoughts on “Embolic Protection Device

  1. This blog provides a great overview for your product. The images are appealing and I think the videos are great in helping to explain implantation. If possible, you all should provide more information about the materials to make this product and the structure of those materials. Also, you should provide results of clinical studies.

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  2. This is a great start to a blog. The information is presented is easily understood and well organized.

    Like

  3. The information on this page is very good at showing how the device works and its purpose, but there is not much information on how it is fabricated, which as textile majors we are most interested in. The business strategy section is very interesting and shows that we have to always remember that the biotextiles industry is a business therefore in every decision business considerations must be made.

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  4. The organization of the blog is very good. It is easy to follow and the pictures are helpful. The information that has been added so far is clear and grammatically correct.

    Like

  5. This page is excellent. It has the right balance between pictures and text. It looks like this page was extremely well thought out and organized. The pictures definitely draw the attention of the viewer.

    Like

  6. The layout, pictures, and video are great, but some more information could be added such as alternatives to this operation/product and the sterilization technique used.

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  7. Awesome presentation with the visuals and formatting. Maybe add in more material to make the text parts longer. Also, sources should be added.

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  8. Lots of good information but you need to add a list of sources. Organization and overall presentation of information is very professional

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  9. I love all the charts and images used to help understand the device. Bold headings may help with organization of the page! Great job guys!

    Like

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