Vascular Closure Techniques Femoral Approach Clifford J Kavinsky, MD, PHD Professor of Medicine and pediatrics Associate Director, Center for Congenital and Structural Heart Disease Rush University Medical Center Number of coronary interventions per annum in excess of 500,000 and >1,000,000 worldwide Major complications related to site of peripheral access including hematoma, bleeding, arteriovenous fistula, pseudo aneurysm occur with rates of 1.5%-9%. 20-40% of these patients require surgical repair. According to recent data from the ACC National cardiovascular data registry fewer then 2% of cases performed from the radial access site.

How to Improve Safety Take time to do puncture right Use fluoroscopy and/or ultrasound Angiogram every femoral puncture Diagnostic catheterization associated with 3.4% rate of serious vascular complications.

Local Complications of FA Access: 2-10% Hematoma (1-12%) Pseudoaneurysm (1-6%) AV fistula (<1%) Vessel laceration (<1%) Free bleeding Intimal dissection Ante- or retro-grade Acute vessel closure (<1%) Thrombosis (small artery lumen) Retroperitoneal hemorrhage (0.1 - 0.9%) Thickening of the perivascular tissues Neural damage Infection Venous thrombosis Pericatheter clot Montreal Heart CCI 3/2001 1.8%/4% (7,953/3,868) The local complications of femoral artery access have remained relatively high. The availability of vascular closure devices have not had any significant affect on these numbers. There are multiple reasons for continuing vascular access morbidity that will be discussed in detail in the following slides. Complications persist despite availability of vascular sealing devices.

Why Complications of Manual Closure Persist Puncture technique Sheath management Adjunctive drug therapy Sicker population Age, gender, comorbidity Coexistent vascular disease Inherent limitations of technique Adjunctive drug therapy also accounts for some elements of closure complications.

How to Decrease Risk of Complications Puncture over the lower half of the femoral head above the bifurcation of the CFA and below the lowest excursion of the Inferior epigastric artery, and above the inguinal ligament. With puncture above the inguinal ligament, the external iliac artery moves away from the skin and the track passes through layers of muscle and fascia en route to the artery. Passage of a VCD may be impeded by the fascia and muscle. Courtesy of Zoltan Turi

Femoral Head and the CFA Bifurcation 55.5% 22% 17% 4.0% 1.5% Above center of head At center of head Below center of head At inferior border Below inferior border n=200 V IV III II I In our 200 patients, the femoral bifurcation occurred below the femoral head in only some 55% of patients. Puncture at the level of the upper-inner quadrant of the femoral head on the other hand would avoid the bifurcation in all except 1.5% of the population. Number of patients I: 111 II: 44 III: 34 IV: 8 V: 3

Consequences of Low Arterial Puncture “Low” puncture into the SFA and PF: Pseudoaneurysm 2° inability to compress AV fistula Thrombosis - embolism Occlusion with large sheaths Primarily due to Low stick Inadequate compression time Aggressive anticoagulation The consequences of low puncture, as seen above, include pseudoaneurysm, in particular because the bifurcation vessels do not course over bone, and therefore manual compression tends to be less effective.

High Puncture “High” puncture of the femoral artery: Increases risk of retroperitoneal bleeding High puncture is most commonly associated with retroperitoneal bleeding. Unlike low puncture, external soft tissue compression does not occur, and there is a predisposition to uncontrolled blood loss, particularly in the setting of full anticoagulation.

Predictors of Complications Age (>70) Female sex Diabetes Body Surface Area (<1.6 m2 Sheath size Renal failure or Cr > 2mg/dL Emergent Procedure Periprocedural use of Glycoprotein IIb/IIIa inhibitors Comorbidities Multilesion and more complex lesion interventions Use of intra-aoortic balloon pump A list of factors that appear to be associated with increased complication rates is listed here. Glyocoprotein IIb/IIIa inhibitors have not consistently been shown to increase bleeding, although this may reflect the associated decrease in heparin dose when these drugs is used. A red star is placed next to several variables that can only be addressed if a femoral angiogram is performed during the catheterization. Piper WD et al 2003, Am Heart J 145:1022

The Promise of Vascular closure Devices Patient comfort and convenience Decreased Time to hemostasis Early ambulation Shorter hospital stay First used in the united states in 1995. First approved was VasoSeal device. Second was the Prostar XL device (Abbott Vascular). Since that time numerous devices have been introduced and the VCD market has experienced substantial growth. Decreased overall procedure-related hospital costs Decreased complication rates

Closure Device Market $1 billion $900 $800 $700 $600 $500 $400 $300 Most of the VCD use lies with adult interventional the overwhelming majority of devices being used in the setting of coronary diagnostic and interventional procedures. However, as we move further in the area of percutaneous interventions with the use of larger vascular access sheaths, pediatric cardiologists have shown interest in this technology. Estimated 825 millinon in 2010 Estimated to be 1 billion dollar market in 2012 Despite this only 38% of the 9.6 million catheterization procedures done globally utilize VCDs $300 $200 $100 $0 00 01 02 03 04 05 06 10 13 Medtech Insight.

VCDs-The Promise Meta-analysis of 30 randomized trials Efficacy Shorter time to hemostasis- mean difference 17 min Decreased duration of bedrest- mean difference 10.8 hours Decreased hospital length of stay- mean difference 0.6 days Koreny, Riedmuller and Nikfardjam et al., JAMA. 2008;291:350-357

VCDs-The Promise Decreased Vascular Complication rate Pseudo aneurysm Arteriovenous fistula Retroperitoneal hematoma/hemorrhage Femoral artery dissection Bleeding Femoral artery thrombosis Many feel that the complications relate to VCDs can in some cases be additive to that of manual compression particularly as it relates to RPH

Complications Specific to VCDs Device-related: Embolization Infection Vessel obstruction Direct mechanical Injection into vessel Bleeding Mechanical secondary to device Secondary to early sheath pull A fair assessment of the complication rates associated with VCD’s has been challenging. A number of complications are seen with manual compression of course, but some of the complications above are arguably additive. Nevertheless, it is clear that some complications are additive to manual compression.

Sterile Technique Groin infections after vascular closure devices are particularly severe. This groin infection is an example; these are far worse than any groin infection I have seen after manual compression. Meticulous attention to sterile technique is advisable – we reprep the area, place fresh towels and reglove, and have a low threshold for giving antibiotics or avoiding closure device use in immune compromised patients. Courtesy Dr. John Eidt, UAMS.

VCDS-Reduced Complications Lack of large randomized trials compared VCDs to std. manual hemostasis Multiple different devices Lack of homogeneous endpoints Small sample size Operator experience Level of anti-coagulation and adjunctive pharmacotherapy Selection bias

Complication Rate Nikolsky et. al. JACC 2004;44:1200 Dx studies Heterogeneity test P-value 0.1 0.2 0.5 1.0 2.0 5.0 10.0 OR (95% CI) 1.44 [0.43, 4.82]† 0.66 [0.18/, 2.38]* 0.0003 0.16 Dx studies 1.11 [0.94, 1.33]* 1.35 [0.87, 2.11]* 0.22 0.15 PCI studies 1.83[1.15,2.90]† 1.15 [0.67, 1.98]* 0.001 0.43 Both Dx+PCI studies In an attempt to salvage some utility from the existing series, two large meta-analyses were published in 2004, one by Koreny and colleagues and the other by Nikolsky et al. The results were similar: some subgroup advantage in favor of manual compression, although the results generally straddle the null hypothesis. The solid squares above refer to the randomized studies in the literature. The studies being analyzed are in general of poor quality. 1.34 [1.01, 1.79]† 1.30 [0.90,1.87]* <0.0001 0.19 All studies Favors Closure Device Favors Manual Compression Nikolsky et. al. JACC 2004;44:1200

Propensity Score Analysis Graph of propensity score adjusted odds ratio of the incidence of any vascular complication for all VCDs compared to the incidence of vascular complications after manual compression Single center non-randomized retrospective study of 21,841 patients from 1998-2003 (angioseal, perclose and vasoseal) Appelgate et.al.,CCI 2006, 67:556

Compilation of Meta- and Propensity Analyses Meta analyses by Koreny et al, Nikolsky et al and propensity analyses by Appelgate et al and Resnic et al comparing VCDs and Manual compression. The meta-analyses suffered from weak underlying studies. The propensity analyses may not fully compensate for variables that may have influenced patient selection for VCDs. In general, the data suggest parity or superiority with VCDs, with the exception of the Koreny et al study which had a strong trend in favor of manual compression. Only Resnic shows a statistically significance in favor of VCDs. Turi,Z., Endovascular Today 2008,7:28

Vascular Closure Devices Active Closure mechanically secures arteriotomy effects closure either through approximation of margins or mechanical fixation of a “plug” Passive Closure devices which assist with compression (clamps), assist or enhance coagulation, and sealants

Current FDA-Approved VCDs Caputo RP, 2012 Card Int Today 6:70

Anchored Plugs Active Approximation Angio-Seal (St.Jude Medical) Angio-Seal combines both active and passive properties. Anchored plugs leave a resorbable anchor inside the arterythat is tethered by a polymer filament to an extravascular collagan plug applied directly over the arteriotomy.Resorb in 60-90 days.Have 50% of the VCD market. They combine the potential benefits (and also potential downsides) of a collagen plug in the tissue track with the predictability of successful closure that an anchored closure provides. The anchor itself is also a potential liability, particularly in patients with peripheral vascular disease. Angio-Seal, shown above, is currently the most commonly used closure device, in part because of a short learning curve, and relatively high efficacy. Handicapped by two properties. 1) the anchor placed inside the vessel produces a transiently visible filling defect in the arterial lumen and is occasionally obstructive. 2) it leaves a mass of collagen inside the tissue tract and a suture that extends from the arteriotomy to near the skin surface providing a potential nidus for infection. re-puncture should be done with caution during the first three months. Collagen Thrombosing agent Advantages- High success rate, short learning curve, short deployment time Disadvantages-vascular occlusion, potential infection

Perclose (Abbott Vascular) Suture-Mediated active approximation Suture mediated closure has approximately 20%of the Market share. Delivers 2 needles through the anterior wall opf the artery. Needles are deployed through a intra-arterial footplate, engaging a non-biodegradeable polypropylene suture that is then pulled back through the arterial wall. Suitable for closure using 5-8 French access. Prostar XL uses four needles and two sutures and is approved for use in 8.5 F to 10 French arteriotomies. Has a longer learning curve and has a definite skill set to using it successfully

Preclosure Balloon Aortic Valvuloplasty-12F PVAD 15 – 18 F Percutaneous Valve Technology 18 - 24 F Endovascular Aneurysm Repair 12 – 24 F Has become an important tool for vascular access management in some of the procedures using large sheath such as TAVR, BAV, endovascular stent placement. In these settings one to two devices are deployed after vascular access is obtained using a standard size introducer sheath. The needles are deployed and the sutures harvested and set to the side for the duration of the procedure. At the end the knots are secured and hemostasis is obtained.

Preclosure Success Rates N = 279 20 56 30 45 67 25 36 Patients n = 258 Success = 93.8% Lee WA et al: J Vasc Surg 2007

StarClose SE (Abbott Vascular) Active Approximation Deployed through procedure sheath. Effects active closure through deployment of a disc-shaped nitinol clip that actively approximates the edges of the arteriotomy. Permanent implant 19.4% market share

Passive Approximation Vascular Sealants MynxGrip ExoSeal (Cordis) Mynx (AccessClosure)- uses a biopolymer (polyethylene glycol) deployed while a small balloon tamponades the puncture site while the sealing agent is deployed. The sealant rapidly expands in the tissue tract and attracts blood which the coagulates. Dissolves in 30 days. Exoseal (cordis) –also uses a sealant (polyglycolic acid). Delivers through existing sheath. Just completed testing in pivotal trial. Eclipse trial looked at 400 patients 50% Dx and 50%Int. success rate of 89% Unknown whether they are superior to collagen matrix AccessClosure

No footprint devices Passive approximation Catalyst II (Cardiva Medical) Cardiva Medical (Mountain View California) Unique device in the world of VCDs-relies on a nitinol disc inside the artery along with a spring mechanism to maintain traction at the arteriotmy site inside the vessel until hemostasis occurs. The shaft of the device is coated with two proprietary agents which promote coagulation and thrombosis. Advantages-No foreign body No thrombosing or sealing agents

Closure Begins with Access Axera Device( Arstasis ) Femoral Introducer Sheath and Hemostasis A new class of devices has entered the VCD world. Best described as “closure begins with access” or CBA. Not to be confused with suture-mediated preclosure which has been around for over 10 years and has had considerable success. Now two true CBA devices have appeared on the scene. FISH (femoral Introducer sheath and hemostasis, Morris innovative research) uses small intestinal submucosa wrapped around the introducer sheath which is deployed as the sheath is removed. The device is FDA approved. Arstasis device (Modesitt) . Device creates a dissection plane in the femoral artery at the time of access to create a self-sealing mechanism as the sheath is withdrawn. No foreign body left behind Morris Innovative, Inc.

Topical Hemostatic Patches Passive Approximation NON-INVASIVE patch assisted hemostasis. Whole variety on the market. Patches coated with clot promoting substance i.e. murine Chitin (murine biopolymer, Chito-Seal),poly-D-glucosamine, poly-N-acetyl glucosamine(Clo-Sur PAD), Thrombin and carboxy-methyl-cellulose (D-stat),Calcium alginates (Neptune), woven poly-N-acetylglucomaine isolated from murine algae (Syvek), Advantages-non-invasive, no foreign body, no risk of infection or vascular damage. Disadvantages- no carefully controlled trials. High failure rate in heavily anti-coagulated patients. Chito-Seal, Clo-Sur P.A.D., D-Stat, Neptune, Stasys, Syvek

Which Device to Use? Patient and Vessel specific Heavily anti-coagulated- invasive active approximation Diseased vessel- passive approximation Residual oozing- thrombosing sealing agent or topical hemostatic patch Operator experience/competence

The Importance of Operator Experience 10 8 6 % 4 2 Failure rate with a suture-mediated closure device. An additional major problem in these studies is the role of the physician and institutional learning curve. The data above show a failure rate of 9% with one device in the first 50 cases declining to approximately 3% after 930 cases; with an inflection point in the 350 to 450 patient range. Some studies compare experiences with as few as 6 devices against several hundred with another device. The fact that the learning curve is this extensive is of course in itself an important drawback of some of the closure devices. 25 75 150 250 350 450 550 650 750 850 930 Patients Balzer et al. CCI 2001; 53: 174

Learning Curve With Angio-Seal 3.5 % 14 % Retrospective study of frequency and groin complications when Angio-Seal used in 252 patients by a single operator. 66% interventional case, 34% Diagnostic. First 50 patients-14% failure, subsequent 202 patients-3.5% non-deployment. Warren, Warren and Miller, CCI 1999, 48:162

Moral of the Learning Curve Learn one or two devices and learn them extremely well Consider an additional device for special circumstances Remember that manual compression is always an option

Figure-of-8 for Venous Access Closure

AHA Recommendations Use of VCDs is reasonable after invasive cardiovascular procedures performed via the femoral artery to achieve faster hemostasis, shorter duration of bedrest, and possibly improved patient comfort VCDs should not be used routinely for the specific purpose of reducing vascular complications in patients undergoing invasive cardiovascular procedures via the femoral artery approach Patel et al 2010 Circ 122:1882

Thank you