The Angio-Seal Evolution Registry: Outcomes of a Novel Automated Angio-Seal Vascular Closure Device

ABSTRACT: Objectives. The objective of the study was to assess the efficacy and safety of a novel vascular closure device, the Angio-Seal Evolution (EVCD), in patients undergoing routine cardiac catheterization (CATH) and intervention (PCI) via a retrograde femoral artery access. Background. Successful use of current-generation vascular closure devices is highly dependent on operator methodology. To reduce dependence on operator technique, the EVCD was modified to automate the closure process, specifically the compaction of the extravascular collagen sponge that creates a sandwich under pressure against the intra-arterial anchor. Methods. This was a prospective ten-site registry including 1,004 patients undergoing 1,010 procedures with in-laboratory closure using the EVCD after CATH and PCI. The primary outcome measure was the rate of major vascular complications, and secondary outcomes were deployment success, time to hemostasis and in-hospital rates of minor vascular complications through 30 days. Clinical trial identifier NCT 00817349. Results. There were 575 CATH (56.9%) and 435 PCI (43.1%) closures. Overall deployment success was 99.7%; 99.8% for CATH and 99.5% for PCI. Major vascular complications occurred in 0.4% including 0.2% in CATH and 0.7% in PCI. Minor vascular complications occurred in 2.4%, with 0.5% for CATH and 4.9% for PCI. Conclusions. Automation of the anchor-collagen closure of femoral artery access sites with the Angio-Seal ECVD resulted in excellent efficacy and safety after routine cardiac catheterization and intervention.

J INVASIVE CARDIOL 2010;22:420–426

Key words: vascular complications, propensity analysis, cardiac catheterization, percutaneous coronary intervention

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Vascular closure devices (VCDs) have undergone extensive modifications since their initial clinical introduction for femoral artery closure.¹ Although meta analyses involving early generation VCDs showed that a higher complication rate occurred than with manual compression, propensity analyses of newer generations of VCDs, in particular the Angio-Seal (St. Jude Medical, St. Paul, Minnesota), suggest that their safety and efficacy may be equal or potentially superior.^2,3 However, the application of VCDs has been subject to a significant learning curve, dependent in part on the complexity of placement of the devices as well as individual operator technique.^4,5 In order to simplify use of the device, and decrease operator-dependent variability in device deployment, the Angio-Seal Evolution vascular closure device (EVCD) was developed. This novel device eliminates direct operator compaction of the Angio-Seal anchor-collagen sandwich, and instead automates the process, providing consistent and reproducible compaction forces on the anchor and the collagen thrombosing agent (Figure 1). We hypothesized that this novel device and technique would provide both efficacy and safety for patients undergoing cardiac catheterization (CATH) and intervention (PCI) via a retrograde femoral artery access.

Methods

This was a prospective observational registry of 1,004 consecutive patients (Clinical trial.gov identifier NCT 00817349). Patients undergoing CATH or PCI via retrograde femoral artery access were recruited from ten sites with demonstrated experience in vascular closure device use between November 2008 and June 2009 (Appendix A). A total of 1,424 patients consented to the registry, with 1,004 patients receiving 1,010 devices. In 420 patients, a device was not placed because of unsuitable anatomy (60%) or physician preference (40%). Devices were not deployed in consenting patients if: anatomy was unsuitable for closure per Angio-Seal instructions for use guidelines: 1) The arteriotomy site was below the femoral bifurcation or deemed to be in the external iliac artery; 2) the common femoral artery was Evolution Angio-Seal Closure Device The EVCD has the identical bioabsorbable closure elements that are present in the current VIP Angio-Seal device (St. Jude Medical): an intra-arterial copolymer anchor connected to an extravascular bovine-derived collagen sponge by a bioabsorbable PGA-coated suture that creates an arterial sandwich at the arteriotomy site. The VIP device requires manual compaction of the collagen sponge to complete the hemostatic seal. Compaction of the collagen sponge and completion of the hemostatic seal with the EVCD is achieved automatically during the withdrawal of the device sheath using a novel gear mechanism (Figure 2). In bench-top laboratory testing the gearing mechanism controlling the automated compaction of the EVCD resulted in consistent and less variable compressive sealing forces than were observed with manual compaction of the VIP device in the same model (Figure 1).

Femoral Artery Access Management

Prior to deployment of the EVCD, each operator underwent device training on a model. In addition, a minimum of 5 successful device deployments in patients were required for each operator prior to participation in the registry. A femoral arteriogram was obtained via the arterial sheath before deployment of the EVCD in all patients. At the time of EVCD deployment, the arterial access site was re-prepped. The EVCD was deployed in the cardiac catheterization laboratory in all patients by one of the study investigators. Ambulation was initiated 2 hours after the EVCD was placed, or per institutional standards of practice.

Outcomes Evaluation

Device deployment success was assessed in each patient, as was time to achieve hemostasis. Device success was recorded as successful completion of device deployment. Time to hemostasis was defined as the elapsed time from device deployment to complete cessation of bleeding, and was recorded by the catheterization laboratory staff for each patient. Femoral access sites were assessed after the procedure and prior to discharge by the medical team caring for the patient. The presence of vascular complications was recorded in the chart. Prior to hospital discharge, the patient’s chart was evaluated by clinical research personnel. Each patient was contacted within 30 ± 14 days with a scripted phone interview if a physician follow-up visit was not scheduled. Primary and secondary registry outcomes were prospectively identified. Outcomes measures were patterned after the ACC National Cardiovascular Database Registry (NCDR) definitions for vascular complications. The primary registry outcomes were in-hospital and 30-day rates of major vascular complications: vascular injury requiring repair; permanent access site-related nerve injury; access site bleeding requiring transfusion; new ipsilateral lower-extremity ischemia requiring surgical intervention; retroperitoneal hemorrhage; device-related generalized infection requiring prolonged hospitalization and/or treatment with intravenous antibiotics; or death. Secondary registry outcomes were in-hospital and 30-day rates of in-laborabory device deployment success; time to hemostasis; and in-hospital and 30-day rates of minor vascular complications: access site bleeding requiring ≥ 30 minutes of manual compression to re-achieve hemostasis; ipsilateral hematoma > 10 cm; ipsilateral pseudoaneurysm without intervention; ipsilateral arteriovenous fistulae; ipsilateral deep venous thrombosis; or local access site infection without prolonged hospitalization. All outcomes were evaluated and adjudicated by an independent clinical events committee (Appendix B). Statistical methods. The data were summarized using descriptive statistics such as mean, count and/or standard deviation for continuous variables, and count and/or proportions for categorical variables. Baseline, procedure and complications variables were compared by chi-square or Fisher’s exact test (categorical), or t-test (continuous) as presented when appropriate. SAS, version 9.13 statistical software package (SAS Institute, Inc., Cary, North Carolina) was used for all statistical analysis.

Results

Baseline patient and procedural characteristics. A total of 1,004 patients were enrolled in the registry and underwent 1,010 procedures including 575 CATH and 435 PCI. The baseline clinical characteristics of the patients are shown in Table 1. The average age of the patients was 64.2 ± 11.6 years. 64.2% of all patients were male. Diabetes was present in 31.5% of all patients, while 8.0% of all patients had vascular disease present. 58.9% of the cases were performed for chest pain or stable angina, while 25.3% of the patients underwent a procedure during the index hospitalization for an acute coronary syndrome. The procedural characteristics including medications taken at the time of the procedure are shown in Table 2. Sheath size for CATH ranged from 4–8 Fr, with the majority being 6 Fr (84.5%). Sheath size for PCI ranged from 5–8 Fr, with the majority being 6 Fr (75.6%). 88.2% of patients were taking aspirin and 39.1% clopidogrel prior to procedure; 22.1% of patients received heparin, and 9.3% GP IIb/IIIa inhibitors at the time of the procedure. In the PCI subgroup, 53.1% received bivalirudin, and 43.0% heparin as anticoagulation; 20.7% received a GP IIb/IIIa inhibitor for PCI. A 6 Fr EVCD was used in 98.6% of CATH patients, and in 75.2% of PCI patients. Clinical outcomes. The 30-day rate of major vascular complications, the primary outcome of the registry, is shown in Table 3 for all procedures, as well as the CATH and PCI subgroups separately. The overall rate of major vascular complications was 0.4%, with 0.2% for CATH and 0.7% for PCI. Retroperitoneal bleeding occurred in 1 CATH patient (0.2%) and no PCI patients. Two patients experienced a vascular injury requiring repair, and after an urgent PCI, 1 patient experienced access site-related bleeding requiring transfusion. There were no deaths related to access-site complications. The secondary registry outcomes are shown in Table 4. In-laboratory EVCD deployment success was 99.7% overall, with 99.8% success for CATH and 99.5% success for PCI patients. Hemostasis by device was achieved in 97.8% of all procedures, 99.0% CATH and 96.3% PCI. Time to hemostasis 30 minutes manual compression to re-achieve hemostasis, while this was required in 3.2% of PCI patients. The 30-day rate of minor vascular complications was 2.4% overall, with 0.5% for CATH and 4.9% for PCI patients. The vast majority of minor vascular complications in the PCI patients was the need for manual compression to re-achieve hemostasis (3.2%). No other complications were noted in these patients. Multivariate analysis of outcomes. We performed both univariate and multivariate analysis to evaluate 30-day clinical outcomes in potentially high-risk subgroups of patients in the registry. In univariate analysis, PCI only versus diagnostic CATH only, and 8 Fr procedural sheath size versus all others were significant predictors of any adverse vascular complication at 30 days. Previous CATH, either diagnostic CATH or PCI, use of a VCD previously and a body mass index > 30 were not univariate predictors of any adverse vascular complications. PCI versus diagnostic CATH alone, age in years and previous transient ischemic attack/cerebrovascular accident were independent predictors of any vascular complications at 30 days in multivariate analysis. There was no difference in the rates of any major or minor vascular complications between 6 Fr and 8 Fr devices, and neither device size was an independent predictor of any vascular complication. Learning curve. We assessed the effect of operator experience on clinical outcomes. Successful deployment of the device was 100% (133/133) in operators with ≤ 500 career VCD deployments, and 99.6% (850/853) in those with > 500 career VCD deployments; p > 0.99. For those with ≤ 5 overall EVCD deployments in the registry, deployment success was 99.5% (187/188) while those with > 5 overall EVCD deployments in the registry deployment success was 99.8% (814/816); p = 0.46. Any adverse event occurred in 0.8% (1/133) of those with ≤ 500 career VCD deployments, and 3.2% (27/853) of those with > 500 career VCD deployments; p = 0.16. Any vascular complication occurred in 3.5% (18/514) in the first half of each operator’s EVCD deployments in the registry, and 2.0% (10/490) in the second half of each operator’s EVCD deployments in the registry; p = 0.18.

Discussion

The Angio-Seal Evolution registry is the largest contemporary prospective evaluation of a single VCD following CATH or PCI. The overall high rate of deployment success, 99.7%, was independent of prior VCD deployment experience and indicates that use of the device was adopted quickly and successfully without a substantial learning curve. We observed overall high rates of success and low rates of either major or minor vascular complications up to 30 days post procedure. The device was as effective and safe in patients traditionally at high risk for vascular complications such as women and PCI for ST-elevation myocardial infarction as in those without these characteristics. These observations indicate that automation of closure with a VCD is feasible, associated with a high degree of device success and is associated with excellent safety and efficacy. VCDs were commercially available in the United States in 1994, and have undergone significant modification since then.¹ However, the actual closure method of most of the currently available VCDs requires active operator manipulation and has not substantially changed since their initial conception. Several studies have documented the presence of a significant learning curve with successful use of VCDs, dependent on individual operator technique.^4,5 While individual and institutional experiences have probably shortened this learning curve,⁶ the inherent dependence of most VCDs on operator technique remains. The Angio-Seal device, with both an intra-arterial anchor and an extravascular collagen sponge, lends itself to automation of the arteriotomy closure.⁷ Bench model testing demonstrated that automation of the Angio-Seal closure provided more consistent closure force than observed with manual compaction (Figure 1). Whether this would be associated with higher rates of closure success and fewer vascular complications remained to be tested. However, the results of the Angio-Seal Evolution registry support the concept that a consistent compaction force applied to the collagen anchor and sponge translates into high degrees of device deployment success and low rates of vascular complications. Both the efficacy and the safety of VCDs for femoral artery access-site management have been previously evaluated.^8–10 Device efficacy, particularly in fully anticoagulated PCI patients, has been consistently observed, with successful closure observed in ≥ 95% of patients.^11–13 Measures of device safety, however, have been inconsistent and hampered by the fact that no large randomized trials comparing VCDs and manual compression for arterial access-site management have been performed.¹⁴ Our current understanding of VCD safety has been influenced by three recent publications.^8–10 Unfortunately, these studies reached different conclusions concerning the safety of VCD use, likely due to heterogeneity in study definitions of vascular complications, heterogeneity in study participants and the earliest experience of use of first-generation devices. The registry did not include a manual compression control group due to budgetary constraints. Comparison of the outcomes of the Angio-Seal Evolution device would have allowed a comparison of the relative efficacy and safety of these two strategies. However, given the relatively low rates of overall events, an adequately powered trial would require tens of thousands of patients² and was beyond the scope of this registry or most studies. The reduction in overall rates of vascular complications following CATH and PCI procedures observed in recent studies,^6,15 very limited data on outcomes of new VCD entrants in the closure market^16,17 and the lack of large, contemporary, randomized clinical trials,¹⁴ has made evaluation of the clinical benefits of VCDs challenging. Two recent large single-center observational studies indicated that VCD use, a large portion of which were Angio-Seal, was associated with a reduced hazard of vascular complications in PCI procedures compared to manual compression.^3,6 Evaluation of the StarClose¹⁶ and Mynx devices¹⁷ demonstrated non-inferiority compared to manual compression, but the studies were substantially underpowered to detect meaningful differences in rates of vascular complications compared to manual compression (Figure 3). The rate of major vascular complications observed in this registry is comparable to, or lower than, that observed in the pivotal trials for Perclose (STAND II¹⁸), StarClose (CLIP study¹⁶) and Mynx (FINALE study¹⁷). Definitive comparison of the efficacy of these devices can only be made with an adequately powered trial. However, comparison of rates of major vascular complications from these trials, using similar endpoints, and the observation of the absolute rate of major vascular complications, 1% in PCI patients, supports the concept that the Angio-Seal Evolution closure device is at least as safe as these other devices. Recent studies indicate that bleeding associated with PCI procedures, including significant vascular access-site bleeding, has a substantial adverse effect on outcomes to 1 year.^19,20 Moreover, several recent studies have indicated that use of the trans-radial approach substantially reduces the incidence of access-site bleeding and is associated with better overall net clinical results compared to procedures performed via the femoral artery.^21–23 These observations have spurred interest in switching to the transradial approach from the femoral artery approach for CATH and PCI procedures. However, a substantial learning curve is associated with the transradial approach which limits rapid widespread adoption of this approach.²⁴ The proximity of the femoral artery to the retroperitoneum introduces potential access site-related complications such as retroperitoneal bleeding that are not observed with the transradial approach. However, continued improvement in management of the femoral artery access site, such as observed with the Angio-Seal Evolution device, should help improve the relative safety of procedures performed from the femoral artery. Further studies comparing these two access approaches need to be conducted to more fully address this issue. Study limitations. This study is subject to the limitations of observational studies. Biases in selection of patients may have influenced the study results. However, the goal of the study was to include patients undergoing routine CATH and PCI who would ordinarily undergo closure of the access site at the completion of the procedure. To the extent that this occurred at each study site, the results should be reflective of outcomes in routine practice. All of the investigators and study sites had prior experience in femoral artery closure. Whether the results in this registry would be observed with investigators or sites with less experience remains to be determined. The observation that device deployment success exceeded 99% regardless of prior VCD deployment experience suggests that the device was adopted quickly and successfully without a substantial learning curve. However, it should be noted that these results were obtained by using routine femoral angiography prior to device deployment. Whether similar results would be obtained in the absence of routine femoral angiography is uncertain. Eight French EVCDs were used almost exclusively in PCI patients, who had higher rates of vascular complications than CATH patients. There were no significant differences in the rates of vascular complications between the 6 Fr and 8 Fr EVCDs for PCI patients, but a formal evaluation of the relative safety and efficacy of these two devices will need to be clarified by larger studies. Finally, the relatively low rates of vascular complications observed in the registry reflect surveillance by the clinical team caring for the patient. Whether formal evaluation including ultrasound would have detected more events is possible, but was beyond the scope of this registry.

Conclusions

Automation of VCD deployment with the Angio-Seal Evolution device appears both safe and effective. Because VCD use has been traditionally associated with a substantial learning curve, automation may be part of a next-generation evolution of vascular closure technologies. Acknowledgments. We gratefully acknowledge Tammy Davis for manuscript preparation, and Aruna Hulme and Robin Taylor for data collection and database entry.

References

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Robert J. Applegate, MD^a, Zoltan Turi, MD^b, Naveen Sachdev, MD^c, Abdel Ahmed, MD^d, Arthur Szyniszewski, MD^e, Malcolm Foster, MD^f, Antonis Pratsos, MD^f, Timothy Shapiro, MD^g, Steven Yakubov, MD^h, David Shavelle, MD From ^aWake Forest University School of Medicine, Winston-Salem, North Carolina; ^bCooper University Hospital, Camden, New Jersey; ^cProvidence Heart and Vascular Institute/Providence St. Vincent Medical Center, Portland, Oregon; ^dALTRU Health System, Grand Forks, North Dakota; ^eSaint Joseph Mercy Hospital/Michigan Heart P.C., Ann Arbor, Michigan; ^fBaptist Hospital West, Knoxville, Tennessee; ^gLankenau Hospital, Wynnewood, Pennsylvania; ^hMidOhio Cardiology and Vascular Consultants/Ohio Health Research & Innovative Institute, Columbus, Ohio; ⁱGood Samaritan Hospital, Los Angeles, California. Disclosure: Dr. Applegate discloses that he is a paid consultant for St. Jude Medical and received financial support for the study’s design. Manuscript submitted April 30, 2010, provisional acceptance given May 25, 2010, final version accepted June 7, 2010. Address for correspondence: Robert J. Applegate, MD, Wake Forest University School of Medicine, Section of Cardiology, Medical Center Boulevard, Winston-Salem, NC 27157-1045. E-mail: bapplega@wfubmc.edu