AbsorbaSeal™ 5.6.7F vascular closure device: A good laboratory practice chronic study evaluating safety and efficacy in a healthy porcine model

Abstract

Objectives

Vascular closure devices (VCDs) are widely used for arteriotomy closure after percutaneous catheter–based procedures. In comparison to manual compression, VCDs have been associated with shorter time to hemostasis, shorter time to ambulation, and also decreased length of stay. Complexity of deployment, lack of immediate hemostasis, and residual deformity of the arterial wall remain as limitations of current VCDs. The aim of this study was to investigate the AbsorbaSeal™ 5.6.7F vascular closure device, a novel, completely bioabsorbable, intuitive, and easy to use VCD which uses a compressive, “sandwich”-type design comprising a low profile intravascular distal seal and gasket and an extravascular floating foot and proximal seal, in an open infrarenal aortic swine model.

Methods

Eight fully heparinized swine at a good laboratory practices facility underwent AbsorbaSeal™ 5.6.7F VCD closure of three 6F arteriotomies each in the proximal, mid, and distal infrarenal aorta. Two swine underwent harvest at each of four time cohorts: 30, 60, 90, and 120 days. Acute and chronic procedural safety and efficacy, as well as target site vascular remodeling over time, were the primary outcomes evaluated. Secondary outcome measures included local and systemic inflammatory responses, end-organ tissue analysis, and device-related complications through the follow-up periods. Histopathological evaluation was performed by a blinded pathologist. Standard statistical methods were used.

Results

In deployment of 24 AbsorbaSeal™ 5.6.7F VCDs, there were no device-related complications or mortalities. All deployments resulted in rapid arteriotomy seal (100% deployment success), with a mean time to hemostasis (cessation of arterial flow) of 21.5 s (median: 6.5 s) across a mean activated clotting time (ACT) of 356 s. Twenty of the 24 implant sites (83%) attained complete hemostasis within 20 s. Immediate post-implant and pre-termination angiographies at all time points were performed of all swine which demonstrated normal aortic appearance and tissue structure and normal downstream vascular beds. At 30 days, each implant’s intravascular distal seal and gasket were removed from the circulation and completely covered with a smooth neointimal layer. Minimal inflammation and no intimal or luminal thrombus were observed at any site at every time point.

Conclusions

AbsorbaSeal™ 5.6.7F is a safe, effective, and secure VCD that demonstrates rapid hemostasis in a fully heparinized open aortic porcine model. Removal from circulation and complete coverage of the intravascular distal seal and gasket with neointima occurred within 30 days post-implant. Natural transmural vessel healing from the arteriotomy itself with minimal inflammation was noted for each implant at every time point.

Keywords

AbsorbaSeal vascular closure device arteriotomy vascular access manual compression percutaneous catheter–based intervention

Introduction

Many of the procedures in cardiac and vascular surgery that were previously done via an open technique are now able to be accomplished through a less invasive, percutaneous, catheter-based femoral arterial approach.¹ More recently, they have grown to include treatment of cardiac valvular issues and other major vascular procedures.^2,3 However, following percutaneous catheterization, vascular access site (VAS) complications, such as hemorrhage, arterial thrombosis, arterial dissection, and thromboembolism, occur in up to 10% of cases.^4,5 These complications can negatively impact patient health outcomes and have a drastic financial impact on the healthcare system.⁶ In a study done at the University of Michigan Medical Center evaluating patients with post-operative vascular site complications, surgical repair was required in 70% of patients, with 9% of patients needing major vascular reconstruction, 3% of patients requiring lower extremity amputation, and 8% of patients suffering a mortality.⁶

Traditionally, manual compression has been used to achieve hemostasis at the VAS and minimize bleeding. However, manual compression is both time- and labor-consuming, limited in efficacy, and results in prolonged patient immobility and in-hospital stay.⁷ In an attempt to minimize time to hemostasis (TTH) and time to ambulation and shortened hospital length of stay, vascular closure devices (VCD) were developed.⁸ VCDs were first introduced in the mid-1990s and have since become widely used in vascular surgery and other interventional specialties.⁴ In a systematic review of randomized controlled trials evaluating VCDs, it was found that patients with VCD treatment had a 95.7% procedural success rate.⁹ Additionally, patients experienced an overall median time to hemostasis of 5.95 min compared to 22.9 min with manual compression alone.⁹ The challenge with VCDs is they are a very heterogeneous group in their method of delivery/deployment and hemostatic mechanism of action. Indeed, all of the VCDs currently on the market have a significant learning curve with associated complications, do not attain instant hemostasis, and are thus more akin to closure assist devices.¹⁰

The marked shift toward, and numerical growth in, percutaneous endovascular procedures has emphasized the need to create a VCD that is intuitive and easy to use, rapidly deployed, highly effective, and secure in achieving hemostasis, with a low rate of complications.¹¹ In addition, considering the frequent need for future interventions in the same patient, a VCD that sets these vasculopath patients up for future success with positive, natural vascular healing would significantly improve the current field of VCDs.¹⁰

The AbsorbaSeal™ 5.6.7F VCD (CyndRx, LLC, Brentwood, Tennessee) is a completely bioabsorbable, intuitive, and easy to use VCD designed to offer a safe, secure, and highly effective method of sealing vascular punctures.¹⁰ The primary objectives of this study were to determine acute and chronic device safety and efficacy in a porcine open infrarenal aortic deployment model and, importantly, to evaluate vascular remodeling at the target closure site over time. Secondary outcome measures included mid- and long-term complications, the presence and severity of peri-device inflammatory reaction, and bioabsorption of the seal assembly over time.

Methods and materials

Funding and data source

Funding for this study was supplied by CyndRx, LLC. Synchrony Labs (LLC, Durham, North Carolina), an independent lab in compliance with good laboratory practice (GLP) regulations, performed the AbsorbaSeal™ 5.6.7F VCD experimentation (angiography, device harvest, histology, etc.) and data collection. This was accomplished in conjunction with experienced, independent veterinarians and pathologists. IACUC approval was obtained prior to the beginning of the study and animal treatment was performed in humane fashion in accordance with the United States Department of Agriculture Animal Welfare Act. CyndRx, LLC played no role in the harvest of the animals or tissues, data generation and collection, pathologic and histology inquiry, or outcomes of the study.

Study population

The study was performed on eight swine (Oak Hill Genetics, LLC, Ewing, Illinois). This swine model was chosen because of the anatomical and physiological arterial similarity to humans.¹² The study was performed in vivo to accurately capture the anatomical and physiological operative and post-operative reactions. Two swine (n = 2) each were randomly placed into one of four time point cohorts: 30(±3), 60(±2), 90(±3), and 120 (±3) days.

Procedure and AbsorbaSeal™ 5.6.7F device description

The AbsorbaSeal™ 5.6.7F VCD is an intuitive, easy to use, completely bioabsorbable VCD (Figure 1). The seal assembly is made up of a polymer-based intravascular distal seal and gasket and an extravascular floating foot and proximal seal, connected by a stem (Figure 2). A 6F sheath is placed into the target aorta by a typical Seldinger technique.¹³ Upon completion of the primary interventional procedure, the inserter portion of the AbsorbaSeal™ 5.6.7F VCD is placed into and pushed through the hemostatic valve of the dedicated 6F sheath until the inserter locks into place; proper seating of the inserter is indicated by a tactile and audible click. With the inserter properly seated, the seal assembly is advanced distally through the sheath until the handle locks into the sheath hub; again, this is noted by a tactile and audible click. The AbsorbaSeal™ 5.6.7F VCD handle and sheath assembly are then withdrawn until the intravascular portion of the seal (distal seal and gasket) is up against the anterior artery wall; positioning of the intravascular components can be verified easily through tactile resistance or imaging. The deployment slide on the handle is then manually advanced, which secures the floating foot and proximal seal onto the outer vessel wall with a compressive pressure appropriate for hemostasis without causing vessel wall tissue necrosis. When the appropriate compressive force is achieved, the seal assembly separates from the delivery system at the break notch. The intravascular distal seal and the flexible intravascular gasket, which is larger than the arteriotomy, and extravascular floating foot and proximal seal “sandwich” the arteriotomy/vessel wall, providing immediate mechanical hemostasis.

Figure 1.

AbsorbaSeal™ 5.6.7F vascular closure device.

Figure 2.

AbsorbaSeal™ 5.6.7F vascular closure device polymer-based seal design.

Experimental procedure

Placement of the AbsorbaSeal™ 5.6.7F VCDs was done in an operating room with the swine undergoing general anesthesia. Throughout the procedure, the animals and level of anesthesia were monitored by a team of veterinarians. A midline incision was made in the abdomen and carried down to the abdominal cavity. The small intestine and descending colon were reflected upward, and dissection was performed until the infrarenal aorta was completely exposed down to the bifurcation. A contrast-enhanced aortic angiogram with distal runoff was obtained in each animal before placing the first test sheath. The swine were fully heparinized, and an ACT was measured with a goal of maintaining it at greater than 250 s throughout the procedures. Three six Fr catheters were introduced over a wire utilizing a Seldinger technique, one proximally (infrarenal), one in the middle of infrarenal aorta, and one distally but above the aortic bifurcation.¹³

AbsorbaSeal™ 5.6.7F VCDs were implanted through each of the 6F sheaths. Time to hemostasis was documented in seconds after each deployment and removal of the device; no hemostatic adjuncts or compression methods were used in this study. Implant sites were marked proximally and distally with non-absorbable Prolene® sutures. Contrast-enhanced aortic angiograms were performed after deployment of the last VCD in each animal. After assuring hemostasis, abdominal organs were moved back into normal positions and the animals’ incisions were closed using a layered closure with absorbable suture; all animals were then recovered from anesthesia. For all animals, hematology and serum chemistry results were collected prior to the implant procedures and termination studies.

Post-operatively, the swine were kept in a vivarium, and their overall health and incisions were examined daily by veterinarians and the research team. The assigned animals were then euthanized at day 33 (30-day cohort), 60 (60-day cohort), 88 (90-day cohort), or 119 (120-day cohort) days. Prior to euthanasia, contrast-enhanced aortic angiograms of the implant sites and the distal vascular bed were performed using the carotid artery for access. All images were recorded in digital media and archived. The aortas were harvested with approximately 3 cm of vessel proximal and distal to the implant sites. The external and internal portions of the implant were examined. The aorta’s posterior wall was longitudinally incised to allow examination and imaging of each implantation site. For each animal, the most proximal implant was excised and used for subsequent polymer degradation testing, except in one 60-day animal where in vivo polymer degradation resulted in insufficient material for analysis. The middle and distal implants from each animal were used for histopathological evaluation.

Organs which might be affected by implant application (embolization) were harvested and examined grossly and histologically. These included the spleen, kidneys, draining iliac and para-iliac lymph nodes, gluteus medius and gastrocnemius muscles, and samples of the deep dermis from both rear limbs.

Study endpoints

The primary endpoints of this study were to determine acute and chronic device safety and efficacy in a porcine open infrarenal aortic deployment model and, importantly, to evaluate the seal component bioabsorption and vascular remodeling of the target vessel access site over time. Secondary outcome measures included appearance of aortic angiograms with run-off to the distal vascular beds immediately following implantation and just prior to termination studies. As well, evaluation of acute and chronic complications such as device-related dissections, thrombosis and bleeding, and the presence and severity of peri-device inflammatory reaction over time was performed. In addition, end-organ tissues were examined to assess for distant complications associated with the polymer-based seal assembly.

Statistical analysis

Descriptive statistics were reported as means with corresponding standard deviations for continuous variables and percentages for categorical variables. Calculations were performed by use of Microsoft (Redwood, WA) Excel^® software.

Results

Safety and efficacy

Demographic data for the swine population can be found in Table 1. There were no early deaths, device-related dissections, or thrombosis in the study population. Deployment success was 100%. Time to hemostasis was defined as time in seconds from removal of the sheath until hemostasis was confirmed. The overall mean TTH was 21.5 s (median: 6.5 s). TTH at 20 of 24 (83%) implant sites was within 20 s. The peri-deployment ACT averaged 356 s and ranged from 210 s to 1,500 s; there was no observed relationship between ACT and TTH times (Figure 3).

Table 1.

Demographics and clinical characteristics of animal study cohort.

Characteristic	Study cohort (n = 8)
Species	Swine–Sus scrofa domestica
Breed	Domestic swine (Yorkshire or Yorkshire crossbred)
Age	97 days
Gender	Female
Weight range (at day 0)	31.6–37.3 kg

Figure 3.

This histogram demonstrates the relationship between TTH and ACT. TTH: time to hemostasis; ACT: activated clotting time.

Contrast-enhanced angiography, performed at day zero and on all termination study dates (33, 60, 88, and 119 days), demonstrated no thrombosis, device-related dissection, or downstream thromboembolism or other abnormalities (Figure 4). The implants did not alter the luminal cross-sectional area or the shape of the intimal surface of the artery.

Figure 4.

Contrast-enhanced aortic angiograms on day 0 (post-implant) and day 120 (prior to termination study) with three (3) devices in situ (proximal, mid, and distal of infrarenal aorta).

Gross and histologic findings

Gross examination was performed on all implant sites (N = 24), while histopathology was performed on the middle and distal implant sites for all animals. On gross examination, all implants at all time points appeared highly similar. The extravascular components (floating foot and proximal seal) were surrounded by a small amount of fibrous connective tissue. Intravascularly, the distal seal and gasket were covered with normal appearing neointima, including all of the 30-day test sites (Figure 5). Histologically, all implantation sites were highly similar across all time points. At 30 days, all seal components were present with the intravascular distal seal and gasket completely removed from the circulation and covered with full thickness neointima. By 60 days, the distal seal, gasket, and extravascular floating foot were completely bioabsorbed leaving only remnants of the extravascular proximal seal to remodel through 120 days (Figure 6). The histological results represent typical and expected changes to the aortic wall consistent with normal healing at the arteriotomy site with a low reaction to the test article. Endothelial denudation and intimal/luminal thrombus were not observed in any site of each time point. The proliferative response of the aortic wall extended minimally over the intimal surface as segmental thin intimal hyperplasia which did not significantly alter the shape/contour of the intimal surface and did not alter the luminal cross-sectional area. Inflammation was minimal to mild at each site at each time point and confined to the implant and immediate peri-implant area. Small foci of granulomatous inflammation centered on small fragments of the polymer consistent with a lubricious coating were observed at one 30-day site and one 120-day site. There were no gross or histological lesions suggestive of downstream thromboembolism, ischemia, or infarction due to implant material at any time point. The lymph nodes appeared normal in a post-surgical environment. All tissue samples appeared normal for a post-operative animal at all time points without complications after placement of the sheath or VCD.

Figure 5.

Gross pathology of intimal layer of aorta with three (3) AbsorbaSeal™ 5.6.7F vascular closure devices in situ at 30 days post-implant (proximal infrarenal aorta is to the left of the image). Proximal and distal Prolene® suture markers highlighted.

Figure 6.

Histopathology of target vessel closure sites with representative 30-, 60-, 90-, and 120-day micrographs.

Discussion

VCDs have become a common means to close arteriotomies following percutaneous access for endovascular procedures with success driven by efficacy (time to hemostasis) and early ambulation and discharge.¹⁴ VCDs, however, represent a very heterogenous population of devices involving multiple steps prior to deployment, may require hemostatic collagen or other agents as part of the process, and often leave a marked scar and/or foreign body which challenges re-access at that site.^9,15 In the current study, an intuitive and easy to use VCD (AbsorbaSeal™ 5.6.7F) was inserted directly into the aorta of eight heparinized swine at three infrarenal locations (proximal, mid, and distal) with gross and histopathological evaluation at monthly time points over the course of 120 days. AbsorbaSeal™ 5.6.7F VCD achieved complete hemostasis at all sites in an average of 21.5 s (median: 6.5 s), despite the broad range of ACTs (210–1,500 s) and the experimental method of sheath placement directly into the aorta. There were no episodes of lack of seal, death, or device-related vascular complications, and the post-procedure contrast-enhanced aortic angiograms were normal in appearance. As evaluated by an independent pathologist, complete neointimal coverage and thus removal of the intravascular components from the vessel lumen were rapid and present at the first time point investigated, 30 days, for all devices. Minimal-to-mild inflammation was appreciated at each deployment site throughout the study and these histological observations were consistent with normal healing from the arteriotomy procedure. Histologically, bioabsorption by hydrolysis of the polymer-based seal components into H₂O and CO₂ was progressive throughout the study. The AbsorbaSeal™ 5.6.7F VCD proved to be safe, rapidly effective and secure, and appears, by the factors detailed above, to represent a substantial innovation in VCD technology.

Previous VCD studies have been performed such as the current study, but very few evaluate the rapidity of post-deployment removal of intravascular device components from the vessel lumen, acute and chronic impact of device on vessel diameter, and a measure of inflammation. A porcine study examining the closure of 6F arteriotomies with two commonly used VCDs, Angio-Seal^TM and StarClose^TM, which also utilized an independent pathologist, demonstrated an early post-deployment vessel stenosis of 65% with Angio-Seal™ and 50% with StarClose™ as measured by arteriogram, and 59% and 35%, respectively, by ultrasound.¹⁵ On histopathologic exam, both devices tended to generate significant inflammation at the closure site which was measurably greater with the Angio-Seal™ device. In addition to inflammation, Angio-Seal™ deployment resulted in significantly more hemorrhage, luminal thrombosis, and vessel stenosis/thrombus. An additional porcine study demonstrated much the same, with complete occlusion in three of 13 (23%) and a 50% occlusion in one (9%) animal treated with Angio-Seal™.¹⁶ It is hypothesized that the delayed healing and inflammation induced by Angio-Seal™ may be from its collagen component, which generates a foreign body immune response.¹⁵ A study performed by Inoue et al. evaluating stents found that device induced inflammation delayed endothelialization and was linked to delayed arterial healing and thrombosis.¹⁷ This type of inflammatory response to Angio-Seal™ may “result in a chronic process that never allows the artery to return to a quiescent state.”¹⁵ The importance of this finding is in its influence on patient quality of life, especially considering how commonly a repeat trans-arterial procedure is required in vascular and cardiac patients. Prompt natural vessel healing with the AbsorbaSeal™ 5.6.7F VCD, signified by the complete removal from circulation and coverage of the device by full thickness neointima within 30 days, and its subsequent bioabsorption and lack of clinically significant inflammation, may offer considerable short- and long-term advantages including safe re-access of the target artery.⁴ An additional advantage of rapid and generally inert bioabsorption of VCD seal components is that the prolonged presence of a foreign body in the subcutaneous tissues abutting a vascular structure could serve as a nidus for infection, which may lead to the need for debridement and arterial reconstruction.¹⁸

Most previous studies evaluating VCDs focus on patient-related outcomes, typically TTH, complications, and time to ambulation and discharge.⁹ Early metanalyses, one each from 2004 and 2010, concluded that existing evidence suggested an unfavorable safety profile when comparing VCDs with manual compression (MC).^19,20 In a more recent systematic review of 34 randomized controlled trials of VCDs (ex: Angio-Seal^TM, VasoSeal®, FemoSeal™, ProGlide®, etc.) versus MC, VCDs demonstrated significant superiority in the above defined parameters.⁹ The VCD procedural success rate was 95.7%, and the overall median time to hemostasis was 5.95 min for the VCDs and 22.9 min for MC. When comparing the type of procedure and its median time to hemostasis, VCD versus MC was 3.7 min versus 17 min for diagnostic procedures and 7.6 min versus 29.1 min for interventional procedures. The overall device-related complication rate among VCDs in this systematic review was 12.2%. In a single, large randomized trial, the VCD time to hemostasis was significantly better than MC, with a vascular complication rate of 6.9%.²¹ An additional, more recent point of interest is in patient-reported outcomes, specifically quality of life. Non-randomized prospective and retrospective studies have examined quality of life factors comparing MC to vascular closure devices. Follow-up at 30 days post-procedure revealed a preference of VCDs over MC and for those patients who had undergone prior angiograms with MC technique, patients uniformly chose a VCD as the preferred method to hemostasis.²²

Previous clinical data on the use of AbsorbaSeal™ 5.6.7F VCD had been limited until the recent prospective, multi-center CE Mark Trial completed in early 2021.²³ In fifty patients, after Belgian Federal Agency for Medicines and Health Products approval, AbsorbaSeal™ 5.6.7F VCD was used to close 6F arteriotomies. Key inclusion criteria for this study included age >18 years and target vessel lumen > 5 mm with key exclusion criteria being prior target vessel surgery or vascular graft, mean body mass index >35 kg/m², and fibrotic or heavily calcified femoral artery within 10 mm of access site. All primary procedures were interventional cases with 80% retrograde and 20% antegrade access in fully anticoagulated patients. All fifty devices deployed successfully (100% deployment success) with a mean time to arterial hemostasis of 0.0 s (instantaneous). In 13 of 50 (26%) patients, light digital pressure with 4x4 gauze was applied for a mean of 42 ± 32 s for venous/capillary tissue track oozing. With this, the average total time to complete hemostasis (arterial hemostasis plus tissue track oozing) for the trial cohort of 50 patients was 11 ± 25 s. Mean closure procedure time (sheath entry–seal deployment–sheath removal) was 45 ± 16 s. Thus, on average, the total procedure time and groin management required across the entire trial cohort was less than one (1) minute total. There were no device-related complications reported at the CFA access site or with deployment of the AbsorbaSeal™ 5.6.7F VCD. Duplex ultrasound performed post-procedure (N = 50) and 30 days post-operatively (n = 48) demonstrated no hematomas, false aneurysms, or other abnormalities at the CFA entry site for all patients evaluated. Additionally, the CE Mark trial evaluated patient satisfaction measures. Pain scores, as measured on a 10-point scale, were very low acutely (0/10–60%, 1/10–26%, 2/10–12%, 3/10–2%) and at 1-month post-procedure (0/10–96%, 1/10–4%). These clinical data, including a quick procedure time, rapid and complete hemostasis, and lack of device-related complications through follow-up, when matched with the very favorable gross and histological evaluation from the current GLP open infrarenal aortic porcine study, make AbsorbaSeal™ 5.6.7F a very promising VCD that provides solutions to many of the most pressing problems encountered in the current VCD market.²⁴

Limitations and future direction

The limitations of this study include the small, uniform sample size. The sample included eight healthy swine of the similar gender, age, and weight range, as well as the open infrarenal aortic procedure performed. The swine aorta in this study, however, does mimic key clinical characteristics of the common femoral artery in an adult human. The study was performed using only the small bore (6F) version of the AbsorbaSeal™ platform to close an arteriotomy, although the overall AbsorbaSeal™ platform of VCDs is designed to close small to large, arterial and venous punctures. Obviously, a similar experiment cannot be performed in human subjects because it requires histopathology samples from vascular structures.

Conclusion

AbsorbaSeal™ 5.6.7F, a VCD which utilizes an intuitive, easy to use method to deploy a biologically friendly, polymer-based compressive “sandwich” seal with an intravascular distal seal and gasket and an extravascular floating foot and proximal seal, demonstrated strong acute and chronic safety and efficacy with secure and rapid hemostasis in a fully heparinized open infrarenal aortic porcine model. Rapid removal from circulation and complete neointimal coverage of the intravascular components occurred within 30 days. Progressive bioabsorption with minimal inflammation consistent with natural arteriotomy healing was noted at each time point throughout the 120-day study. The AbsorbaSeal™ 5.6.7F VCD demonstrates considerable potential to be a very positive advancement in vascular closure, with significant promise in both clinical and economic value.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by CyndRx, LLC. Otherwise, there was no outside grant funding received.

Ethics statement

The care and use of animals in this study was reviewed and approved by Synchrony Labs’ Institutional Animal Care and Use Committee prior to the start of the study. The treatment of animals was performed in humane fashion and in accordance with the United States Department of Agriculture’s Animal Welfare Act and the conditions specified in the Guide for Care and Use of Laboratory Animals.

Financial disclosure statement

Dr. Bassett and Mr. Lawson are employed by CyndRx, LLC.

Additional authors have nothing to disclose.

ORCID iD

Sullivan A Ayuso

References

Serruys

Morice

Kappetein

, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. New Engl J Med 2009; 360: 961–972.

Leon

Smith

Mack

, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. New Engl J Med 2016; 374: 1609–1620.

Thourani

Kodali

Makkar

, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet 2016; 387(10034): 2218–2225.

Kolluri

Fowler

Nandish

. Vascular access complications: diagnosis and management. Curr Treat Options Cardiovasc Med 2013; 15: 173–187.

Resnic

Wang

Arora

, et al. Quantifying the learning curve in the use of a novel vascular closure device: an analysis of the NCDR (national cardiovascular data registry) CathPCI registry. JACC Cardiovasc Interv 2012; 5: 82–89.

Messina

Brothers

Wakefield

, et al. Clinical characteristics and surgical management of vascular complications in patients undergoing cardiac catheterization: Interventional versus diagnostic procedures. J Vasc Surg 1991; 13: 593–600.

Wong

Bachinsky

Cambier

, et al. A randomized comparison of a novel bioabsorbable vascular closure device versus manual compression in the achievement of hemostasis after percutaneous femoral procedures. JACC Cardiovasc Interv 2009; 2: 785–793.

Noori

Eldrup-Jørgensen

. A systematic review of vascular closure devices for femoral artery puncture sites. J Vasc Surg 2018; 68: 887–899.

Cox

Blair

Huntington

, et al. Systematic review of randomized controlled trials comparing manual compression to vascular closure devices for diagnostic and therapeutic arterial procedures. Surg Technol Int 2015; 27: 32–44.

10.

Benham

Deloose

Callaert

, et al. AbsorbaSeal™ vascular closure device: a novel device for hemostasis following interventional peripheral vascular procedures. Surg Technol Int 2017; 31: 93–99.

11.

Sohail

Khan

Holmes

, et al. Infectious complications of percutaneous vascular closure devices. Mayo Clinic Proc 2005; 80: 1011–1015.

12.

Tsang

Rashdan

Whitelaw

CBA

, et al. Large animal models of cardiovascular disease. Cel Biochem Funct 2016; 34: 113–132.

13.

Higgs

Macafee

Braithwaite

, et al. The Seldinger technique: 50 years on. Lancet 2005; 366: 1407–1409.

14.

Rickli

Unterweger

Sütsch

, et al. Comparison of costs and safety of a suture-mediated closure device with conventional manual compression after coronary artery interventions. Catheter Cardiovasc Interv 2002; 57: 297–302.

15.

Sanghi

Virmani

, et al. A comparative evaluation of arterial blood flow and the healing response after femoral artery closure using Angio-Seal STS Plus and StarClose in a porcine model. J Interv Cardiol 2008; 21: 329–336.

16.

Kabelitz

Nonn

Nolte

, et al. Long term outcome after application of the Angio-Seal vascular closure device in minipigs. PLoS One 2016; 11: e0163878.

17.

Inoue

Croce

Morooka

, et al. Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis. JACC Cardiovasc Interv 2011; 4: 1057–1066.

18.

Johanning

Franklin

Elmore

, et al. Femoral artery infections associated with percutaneous arterial closure devices. J Vasc Surg 2001; 34: 983–985.

19.

Koreny

Riedmüller

Nikfardjam

, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis. JAMA 2004; 291: 350–357.

20.

Biancari

D’Andrea

Marco

, et al. Meta-analysis of randomized trials on the efficacy of vascular closure devices after diagnostic angiography and angioplasty. Am Heart J 2010; 159: 518–531.

21.

Schulz-Schüpke

Helde

Gewalt

, et al. Comparison of vascular closure devices vs manual compression after femoral artery puncture the ISAR-CLOSURE randomized clinical trial. JAMA 2014; 312: 1981–1987.

22.

Duffin

Muhlestein

Allisson

, et al. Femoral arterial puncture management after percutaneous coronary procedures: a comparison of clinical outcomes and patient satisfaction between manual compression and two different vascular closure devices. J Invasive Cardiol 2001; 13: 354–362.

23.

Belgian Federal Agency for Medicines and Health Products . Prospective, multicenter, single arm, pre-CE marked study of the AbsorbaSeal (ABS 5.6.7) vascular closure device. ClinicalTrial.gov identifier, p. CP0040CE NCT04635501.

24.

Hon

Ganeshan

Thomas

, et al. Vascular closure devices: a comparative overview. Curr Probl Diagn Radiol 2009; 38: 33–43.