Chapter 34 Access Site Closure Devices What We Need to Know

Chapter 34 Access Site Closure Devices What We Need to Know SATYAJEET SURYAWANSHI SHIRISH (M.S.) HIREMATH As the ageing population continues to rise, to manage their cardiovascular health, there is a corresponding increase in the number of percutaneous radiologic and endovascular procedures. According to the United States Census Bureau, there will be 71 million people above the age of 65 years, and 19.5 million above the age of 80, i.e. a 7% and 50% rise in 2030 compared with year 2000, respectively. Cardiovascular disease is the number one cause of death in the USA. Consequently, there is a constant drive to develop innovative methods and devices that enable interventionalists to achieve diagnostic or therapeutic goals while reducing procedure-related risks and enhancing patient satisfaction, and performing outpatient procedures. One area of percutaneous vascular interventions, which has received intense focus in the past decade relates to technologies to achieve rapid and effective control of femoral arterial access, which is traditionally accomplished by manual compression. These vascular closure devices (VCD) have been used in several studies and are shown to be associated with reduced time of haemostasis, early patient ambulation, decrease in hospitalization rate, better staff utilization and most importantly improvements in patient outcomes 1. However, the use of these VCDs is associated with certain shortcomings and therefore the interventionalists are required to have a complete understanding of how these devices work and what are their potential complications. Minor and major complications with these devices have been reported to range from 1.5% to 9% (see ref 2). The introduction of Seldinger technique in 1953 presented a unique problem. The punctures made in the common femoral artery for gaining vascular access required to be closed. Manual compression was the first method used for addressing this problem and still remains the gold standard for this purpose. Manual compression is performed with sustained pressure over the puncture site for 15 20 min followed by bed rest for an additional 6 h. This technique is generally sufficient in achieving groin haemostasis in the majority of patients undergoing percutaneous coronary interventions (PCI), with a few exceptions like obese patients and those with orthopaedic comorbidities. However, with increased use of various anticoagulation regimens during PCI, including antiplatelet glycoprotein IIb/IIIa Inhibitors, achieving haemostasis may be a challenge. With time as the treatment field demanded bigger holes and physicians became busier, novel solutions to the problem needed to be explored. Early 1990s saw the inception of the VCDs and since then the market has been growing exponentially. Global estimates in 2013 suggested it to be closed to approximately $1 billion. Various factors have been involved in driving this growth, such as increasing competitiveness in the economic landscape of health care. Devices like these have found increasing acceptance, as they can free up the highly skilled medical personnel for other responsibilities. Quick haemostasis achieved with these devices leading to shortened duration of immobilization and early ambulation and outpatient discharge following PCI is the primary advantage attributed to VCD. The patient comfort and satisfaction are also important considerations in the wide adoption of these devices 1. Significant advances have occurred in the past decades in vascular closure technologies leading to several important design features that merit consideration when choosing a VCD. There is no ideal device; each one has its own inherent problems. This is due to lack of superiority of VCD over manual compression, concern for cost and lack of reimbursement. Ideally, a closure device should be 267

268 SECTION IV Interventional Cardiology simple to use without cumbersome deployment mechanism and should be safe. The activation of the device closure mechanism should be reliable and consistent with low complication rates comparable to traditional manual compression methods. The utilization of a closure device should not incite significant inflammatory reaction in the surrounding tissue. The latter feature allows procedural safety if postinterventional repeat puncture or surgical access is necessary. Lastly, an ideal device must be cost-effective. Costeffectiveness is a tough issue to decipher; it depends not only on cost but also on reimbursement, on the reduction of cost related to complications as well as comparison to what mechanism of external compression is used as manual compression. This chapter provides an overview of the VCDs currently in use, referencing mostly The Society of Interventional Radiology quality improvement guidelines for their use 3. The principles and important considerations behind the use of VCDs are discussed and the most popular VCDs are described. The comprehensive list with brief description is provided in Tables 34-1 34-4. RECENT LITERATURE Two most recent randomized controlled trials (RCT) have been pivotal in their impact on the use of VCDs in clinical practice. The Journal of the American Medical Association published the Instrumental Sealing of ARterial puncture site CLOSURE device versus manual compression (ISAR-CLOSURE) trial results in the November 2014 issue 4. In this large, multicentre trial conducted in more than 4500 patients across Germany, the comparative efficacies of manual pressure versus closure using the FemoSeal (St. Jude Medical, ) or the Exoseal VCD (Cordis Corporation) were studied. The patients were randomly assigned in 1:1:1 ratio to any of the three groups. The primary end point studied was the incidence of the complications at the vascular access site (a composite of haematoma 5 cm, pseudoaneurysm, arteriovenous fistula, access site related major bleeding, acute ipsilateral leg ischaemia, need for vascular surgical or interventional treatment, or local infection at 30 days). The study reported access site related vascular complications in 6.9% of VCD patients versus 7.9% of manual compression patients. These findings thus confirmed the noninferiority of VCDs compared to manual compression. An additional finding was that the time to haemostasis and closure device failure was significantly higher in the Exoseal group as compared to the FemoSeal group. The other RCT, as mentioned earlier, Percutaneous Endovascular Aortic Aneurysm Repair (PEVAR) trial (Endologix, ) was designed and conducted to assess the safety and effectiveness of percutaneous endovascular aortic aneurysm repair with the use of a 21-F stent graft system and either a 6- or 10-F suture-mediated closure system 5. The study compared percutaneous access with open surgical femoral exposure using a noninferiority trial design. The randomization was set at 2:1 for percutaneous access or open femoral exposure in a total of 151 patients. The 6-F Perclose ProGlide device (Abbott Vascular) was used in 50 patients, and the 10-F Prostar XL device (Abbott Vascular) was used in 51 patients. The primary trial end point was defined as technical success without vascular complications at 30 days. The results showed that when compared with open surgical femoral exposure, the VCD use was associated with shorter procedure time, shorter time to haemostasis, decreased blood loss and groin pain. The study, thus, confirmed noninferiority of VCDs as compared to femoral exposure and the benefit was sustained for 6 months. In none of the patients, conversions to open femoral repair was required. Recently, the Society of Interventional Radiology has again released quality improvement guidelines pertaining to VCD use 3. The committee has confirmed that the existing evidence, derived predominantly from cardiac interventional procedures, demonstrates high success rates of VCDs, regardless of device mechanism. However, this should be interpreted cautiously as these observations may not be applicable to interventional radiology procedures, because of inherent technical differences in the procedures and the use of larger sheaths which may be associated with greater risk in these patients. TYPES OF VCDs BASED ON THEIR MECHANISMS OF ACTION VCDs are usually best understood based on their mechanisms of action. There are three main categories: Active approximators: They act by physically closing the arteriotomy with the use of a suture or a Nitinol clip. Passive approximators: They act by deploying a plug, sealant or gel at the arteriotomy site without actively closing the arteriotomy. External haemostatic devices: These are placed on top of the skin and achieve haemostasis by providing mechanical pressure at the arteriotomy site or by accelerating the clotting cascade.

Chapter 34 Access Site Closure Devices What We Need to Know 269 TABLE 34-1 FDA-APPROVED ACTIVE VASCULAR CLOSURE DEVICES Device Category Device Name Manufacturer Puncture Size (F) Comments Clip or staple StarClose SE Abbott Vascular 5, 6 Second generation; extravascular Nitinol clip approximates arteriotomy site Suture Perclose A-T Abbott Vascular 5 8 Percutaneous deployment of a braided polyester suture with a pretied knot around the arterial puncture site Perclose ProGlide Abbott Vascular 5 21 Percutaneous deployment of a monofilament polypropylene suture with automatic knot formation; two devices and a preclose technique are required for sheath sizes 8 F Prostar XL Abbott Vascular 8.5 10 Percutaneous braided polyester suture delivered, designed for use after procedures requiring larger procedural sheaths ACTIVE APPROXIMATORS Active approximators act on the principle as is used in surgical closure of an arteriotomy. The site is physically closed and there is no need of any manual compression. Anticoagulation is not a concern with the use of these VCDs and a procoagulant plug is also not required. As a result, groin scarring and discomfort related to inflammation are not a concern with this device class. Suture-Based Devices The earliest developed VCDs were actually the suture-based devices. In these devices, percutaneous sutures are deployed on either side of the arteriotomy site which are tied to form a surgical knot to achieve arterial haemostasis. The knot is tied by a built-in mechanism within the closure device or it could also be tied manually if necessary. As no proteinaceous biomaterial is left behind in the puncture tract, no bioresorption or inflammatory soft tissue reaction is associated with this closure technology. Thus, repeat arterial access or immediate surgical exploration of the same artery if required, can be performed safely, which offers an additional advantage. Some of these suture-based closure devices include Perclose (Abbott Vascular Devices, Redwood City, CA), X-Site (Datascope, Montvale, NJ) and SuperStitch (Sutura, Fountain Valley, CA). The Perclose device is the prototypical suturebased VCD. After being approved in 1997, it has been revised several times over the years. The changes that have been made in the device recently include deployment of a pretied knot, use of monofilament suture, and a new mechanism to cut the suture. ProStar XL is indicated for 8.5- to 10-F closure. Perclose ProGlide can accommodate 5- to 21-F arteriotomies, making it a popular device in this category due to its versatility in closing small and large arteriotomy sites. Suture-based active approximators have several advantages. The arteriotomy is physically closed, so accessing the site again is not a problem in cases that require the same and also, anticoagulation is not required with the use of these devices. The main limitations of these devices are the learning curve required to master the technique of use and luminal distortion as is seen secondary to suture closure. Nonetheless, the recent PEVAR trial results have shown that with these VCDs, when multiple devices are used to preclose, even large arteriotomies can be safely closed. Clip-Based Devices The StarClose SE (Abbott Vascular) acts by deploying a 4-mm Nitinol clip over the arteriotomy site and requires a sheath exchange. However, no biomaterial is left behind intravascularly and hence no local inflammatory reaction occurs. The main limitation is an inability to evaluate immediately adjacent structures with magnetic resonance imaging, as the metallic clip remains in place indefinitely. PASSIVE APPROXIMATORS Passive approximators act by deploying a plug, sealant or gel at the arteriotomy site without actively closing the arteriotomy. The plug is deployed on top of the arteriotomy and thus though the arteriotomy site is not physically closed, arterial haemostasis is achieved by the expanding plug in the subcutaneous tissues, and acceleration of the

270 SECTION IV Interventional Cardiology TABLE 34-2 FDA-APPROVED COLLAGEN-BASED PASSIVE VASCULAR CLOSURE DEVICES Device Name Manufacturer Puncture Size (F) Comments Angio-Seal St. Jude Medical 5/6, 7/8 Device deploys an absorbable collagen plug to close the arteriotomy site, secured in place by intraluminal anchor and absorbable suture; new delivery mechanism allows for one-handed and decreased variability VASCADE vascular closure system (VCS) Cardiva Medical, 5 7 Bioabsorbable femoral access closure system leaves no permanent components behind; combines collapsible disc technology and thrombogenic resorbable collagen patch in an integrated design clotting cascade by the collagen in the plug. If the plug is not collagen based, haemostasis is achieved solely by the expanding plug on top of the arteriotomy. Collagen Plugs Devices that utilize collagen to achieve haemostasis are primarily based on bovine biodegradable products to augment thrombus formation. The haemostatic formation of collagen-based closure devices is based on two biochemical reactions. This exogenous collagen material forms an extracellular lattice, which triggers a haemostatic cascade by promoting platelet aggregation, adherence and activation 6. Secondly, upon contact with blood, the collagen expands its physical mass resulting in mechanical occlusion of the vessel puncture site and tissue tract 7. Because of the degradable nature of these proteinaceous bioproducts, the resorption of these collagens may lead to varying degrees of inflammatory processes in the surrounding soft tissue 8. In vivo studies have shown that collagen plugs are resorbed within 4 weeks. One of the most widely used VCDs in the clinical practice today is Angio-Seal (St. Jude Medical, ). The device uses an intravascular anchor to secure an extravascular collagen plug on top of the arteriotomy site. All the components of the VCD, including the intravascular anchor, are fully absorbed within 60 90 days. The intravascular footplate used to secure the plug atop the arteriotomy is a unique feature of the device; however, it represents both a strength and limitation of this VCD. It limits the possibility of a re-entry if required within 90 days postprocedure. The footplate secures the plug, encouraging haemostasis without the need for compression. When deployed, the combination of anchor, collagen plug and absorbable suture effectively sandwiches the puncture site between the anchor and the extravascular collagen plug to seal the arterial puncture site. However, the footplate is an intraluminal device, making distal embolization a possibility. Additionally, angiographic confirmation of the puncture site is necessary, as the device should not be deployed in the external iliac artery, superficial femoral artery or profunda femoris artery. Another consideration to avoid the use of this device is in peripheral vascular disease patients and vessels less than 5 mm in diameter. The VASCADE vascular closure system (Cardiva Medical, ) is another bioabsorbable femoral access closure system but it is extravascular. It has a dual mechanism of action, both mechanical and physiological. This dual mechanism is achieved by integrating a thrombogenic resorbable collagen patch with a collapsible disc. The RESPECT IDE trial, which was a multicentre, prospective, randomized trial of 420 patients, compared the use of manual compression versus VASCADE. The study demonstrated that the VCD achieved rapid haemostasis and was associated with a much lower complication rate (1.1%). The FemoSeal VCD is similar to the Angio-Seal device because it also has an intravascular anchor plate; however, the main difference between the two is that unlike the Angio-Seal device which has an extravascular collagen plug being anchored to the intravascular footplate, the FemoSeal VCD has an extravascular locking disk which is secured in place by an absorbable filament attached to the intravascular footplate. The device is not yet approved by the US Food and Drug Administration. The VasoSeal (St. Jude Medical, St. Paul, MN) is a closure device utilizing a purified bovine collagenbased plug to achieve haemostasis at the arterial punctured site. Since the FDA approval, there have been a total of four different platforms of VasoSeal which include (1) VasoSeal Vascular Hemostasis Device (VHD), (2) VasoSeal ES (Extravascular Security), (3) VasoSeal Low Profile and (4) VasoSeal Elite. Both VasoSeal Elite and ES utilize a temporary J-shaped locator segment, which is deployed so the collagen

Chapter 34 Access Site Closure Devices What We Need to Know 271 plug is deposited on the outer surface of the vessel wall along the puncture tract. The main difference between the Angio-Seal and VasoSeal is that the latter device does not possess any intraluminal components, while an Angio-Seal deploys an intraluminal plug to achieve haemostasis. Following the VasoSeal device deployment, patients only need to have bed rest for 1 h before they can be ambulatory. Repeat arterial puncture can be performed after 6 weeks of deployment of the VasoSeal device. Because this device deploys an extraluminal collagen plug, femoral artery calcification or peripheral artery disease is not considered a contraindication for VasoSeal deployment. Also, there is no need for a femoral angiogram prior to deployment. However, the VasoSeal device is contraindicated in obese patients, due to device length limitations 8, 9. Sealant- or Gel-Based Devices X-Seal VCD (Essential Medical, ) is a new entrant to the category of sealant-/gel-based VCDs. The device has recently received CE Mark approval. The same company is developing a platform that will be suitable for closure of an 18-F arteriotomy. First-in-man studies in a small number of patients with large-bore arteriotomy have been successfully conducted with the device producing rapid haemostasis and good clinical and angiographic results. The Mynx (Cardinal Health) family of devices are sealant-based VCDs that act by deploying a polyethylene glycol sealant to the extravascular space over the arteriotomy site. The sealant conforms to the arteriotomy site, thereby sealing the vessel. There is no coagulation enhancement feature as is seen with collagen-based plug devices. The device employs a new grip sealant that tends to increase the sealant volume by up to 300% when the device is deployed. A major benefit with this VCD is that sheath exchange is not required for deploying this. MynxGrip device has also recently been approved for closing femoral veins. Yet another VCD, the Mynx Ace device, is a new entrant in this category and features an easy-to-use delivery system. The Exoseal VCD has a similar mechanism, as it works by deploying a polyglycolic acid plug over the arteriotomy site. However, it differs from the Mynx device in that visual indicators guide deployment and thus tactile feedback is not needed. This is associated with a shorter operator learning curve. The FastSeal VCD acts by deployment of a bioabsorbable plug at the arteriotomy site through the 6- or 7-F procedural sheath. The plug then expands intravascularly and the sheath can then be withdrawn. The plug produces haemostasis by locking itself into place at the arteriotomy site. The intravascular component gets absorbsed in 2 3 weeks, and the extraluminal component is absorbsed in approximately 2 months. The product is under firstin-man studies and has not yet received CE Mark or US Food and Drug Administration approval. The company is also working on developing a version of this device suitable for 18-F arteriotomy closure. Compression-Assist Devices Passive approximators such as compression-assist devices do not depend on a clip, plug or a retained suture for achieving vessel closure. The Axera 2 access system (Arstasis) is one such device. It acts by TABLE 34-3 FDA-APPROVED SEALANT- OR GEL-BASED VASCULAR CLOSURE DEVICES Device Name Manufacturer Puncture Size (F) Comments Mynx Ace Cardinal Health 5 7 Grip Technology sealant actively adheres to the artery for secure mechanical closure; Grip Technology is completely extravascular and dissolves within 30 days; new delivery system uses 1-, 2-, 3-button approach for consistent deployment MynxGrip Cardinal Health 5 7 Grip Technology at the distal end of the original Mynx sealant adheres to and seals the arteriotomy while expanding to fill the tissue tract; the Grip Technology sealant is completely extravascular and dissolves within 30 days; indicated for femoral arteries and veins Exoseal Cordis Corporation 5 7 Device deploys polyglycolic acid plug through existing sheath into the extravascular space FISH Morris Innovative, 5 8 Device uses an extracellular matrix closure patch premounted onto the CombiClose FISH ControlClose Morris Innovative, access sheath through which intervention is performed 6, 7 Device use an extracellular matrix closure patch premounted onto the access sheath through which intervention is performed

272 SECTION IV Interventional Cardiology TABLE 34-4 FDA-APPROVED COMPRESSION-ASSIST VASCULAR CLOSURE DEVICES Device Name Cardiva Catalyst II Cardiva Catalyst III Axera 2 access device Manufacturer Puncture Size (F) Comments Cardiva Medical, 5 7 Intravascular disk left in place under tension to create haemostasis; after haemostasis is achieved, the disk is removed Cardiva Medical, 5 7 Intravascular disk left in place under tension to create haemostasis; device has protamine coating to locally neutralize heparin; after haemostasis is achieved, the device is removed Arstasis, 5, 6 Access to femoral artery is achieved with a micropuncture kit; Axera 2 access device is then used to create an access tract with a longer and shallower trajectory; brief compression is held for a few minutes creating a low angle (10º 15º) arteriotomy to achieve haemostasis. When using this device, the femoral artery access is achieved using a 19-gauge needle in a conventional manner. However, with the use of Axera 2 device, this conventional arteriotomy is converted to a shallow access through which the procedure is performed. The sheath is removed after the procedure is completed and manual pressure is maintained over the site. Increased arterial wall overlap due to the shallower angle hastens haemostasis which is further assisted by tract compression resulting from the expansive, radial force generated by the pulsatile blood flow through the artery. Another category of compression-assist VCDs includes devices such as Catalyst II and Catalyst III (Cardiva Medical, ). These devices have an intravascular Nitinol disk which is attached to an 18-gauge Nitinol wire. Once the procedure is completed, the disk is introduced into the artery and a gentle traction is applied to the wire which brings the disk and the arteriotomy in apposition. The device is then left in place for approximately 30 min to achieve haemostasis and is then removed in its entirety. Additionally, these devices are also coated with substances that promote clot formation at the arteriotomy site. For example, Catalyst II is coated with kaolin and chitosan that activate the clotting cascade and cause platelet aggregation, whereas Catalyst III is coated with protamine sulphate that neutralizes heparin. These devices can be delivered through sheaths ranging in sizes from 5 F to 7 F. EXTERNAL HAEMOSTATIC DEVICES The VCDs in this category include patches or pads that promote coagulation and devices that manually exert pressure on the arteriotomy. If required, these devices can also be used in concert with other VCDs. External manual haemostatic devices are increasingly being used due to the growing use of transradial access at several centres. Transradial access has several advantages over transfemoral access, including significantly lower cost of a radial haemostatic device compared with femoral VCDs. Also, unlike femoral access, there are no ambulation restrictions after radial access, regardless of VCD use. This approach is also of significant value in coagulopathic patients in whom a retroperitoneal or groin haematoma could lead to significant morbidity and mortality. However, radial access is not appropriate for all patients. Some of the case scenarios where radial access is likely not appropriate include need for a sheath size 6 F and tall patients or those in whom lower extremity intervention is needed, because catheter length can become an issue. Additionally, radial access is also not desriable in patients where the perfusion of the hand is entirely dependent on radial artery, as a radial artery occlusion could have devastating consequences in such patients. Currently, there are several external haemostatic devices suitable for achieving haemostasis after radial puncture such as TR Band, Terumo Interventional Systems; Safeguard Radial and Merit Medical. THE FUTURE VCDs are an evolving group of devices with continued developments and advancements. Currently, the focus is on developing devices that can safely and efficiently close large calibre femoral arteriotomies, which has become an urgent requirement given the rapid growth of transcatheter aortic valve repair and percutaneous endovascular aneurysm repair procedures. However, despite the clinical efficacy of available closure devices, interventionalists must be cognizant of the fact that there is a definite learning curve with all VCDs. There is no

Chapter 34 Access Site Closure Devices What We Need to Know 273 one single device that is ideally suited for all patients. Familiarity with different devices will be helpful in using certain devices in different clinical situations. For instance, the need for immediate percutaneous access or operative groin intervention may favour the use of a closure device, which does not utilize certain collagen-based plugs as the risk of soft tissue inflammation and operative scarring may be significant. The current available arterial closure devices have made this technology an essential component of endovascular clinical practice. Interventionalists should consider all patients undergoing percutaneous arterial procedure as candidates for closure device application. Institutions should have their own algorithm for VCD use, putting concerns of safety, expertise and cost into perspective. As early ambulation and patient comfort remain important goals of any vascular interventional procedure, it is necessary for the endovascular physician to possess a detailed knowledge of a variety of VCDs so that the above objectives can be met in a range of patients and clinical situations with varying anatomic and procedural details, as well as coagulation parameters. REFERENCES 1. Nikolsky, E., Mehran, R., Halkin, A., Aymong, E. D., Mintz, G. S., Lasic, Z., et al. ( 2004 ). Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: A meta-analysis. Journal of the American College of Cardiology, 44, 1200 1209. 2. Koreny, M., Riedmüller, E., Nikfardjam, M., Siostrzonek, P., & Müllner, M. ( 2004 ). Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: Systematic review and meta-analysis. JAMA, 291, 350 357. 3. Sheth, R. A., Walker, T. G., Saad, W. E. Dariushnia, S. R., Ganguli, S., Hogan, M. J., et al. ( 2014 ). Quality improvement guidelines for vascular access and closure device use. Journal of Vascular and Interventional Radiology, 25, 73 84. 4. Schulz-Schüpke, S., Helde, S., Gewalt, S., Ibrahim, T., Linhardt, M., Haas, K., et al. ( 2014 ). Comparison of vascular closure devices vs manual compression after femoral artery puncture: The ISAR-CLOSURE randomized clinical trial. JAMA, 312, 1981 1987. 5. Nelson, P. R., Kracjer, Z., Kansal, N., Rao, V., Bianchi, C., Hashemi, H., et al. ( 2014 ). A multicenter, randomized, controlled trial of totally percutaneous access versus open femoral exposure for endovascular aortic aneurysm repair (the PEVAR trial). Journal of Vascular Surgery, 59, 1181 1193. 6. Gargiulo, N. J. III., Veith, F. J., Ohki, T., Scher, L. A., Berdejo, G. L., Lipsitz, E. C., et al. ( 2007 ). Histologic and duplex comparison of the Perclose and Angio-Seal percutaneous closure devices. Vascular, 15, 24 29. 7. Abbott, W. M., & Austen, W. G. ( 1975 ). The effectiveness and mechanism of collagen-induced topical hemostasis. Surgery, 78, 723 729. 8. Hoffer, E. K., & Bloch, R. D. ( 2003 ). Percutaneous arterial closure devices. Journal of Vascular and Interventional Radiology, 14, 865 885. 9. Cleveland, G., Hill, S., & Williams, S. ( 2003 ). Arterial puncture closure using a collagen plug, II. (VasoSeal). Techniques in Vascular and Interventional Radiology, 6, 82 84.