Safety and Efficacy of the New Angio-Seal Evolution Closure Device: A Single-Center Experience

ABSTRACT: Background. The Angio-Seal Evolution (ASE) is a novel vascular closure device (VCD) engineered to reduce the individual skills needed for deployment. A clinical comparison of ASE with manual femoral compression (MC) has never been reported. Methods and Results. A total of 451 consecutive patients treated by ASE following cardiac catheterization were compared with 451 propensity-score matched controls treated by MC. Early failure of ASE and in-hospital major vascular complications (any retroperitoneal hemorrhage, limb-threatening ischemia or surgical repair) and minor vascular complications (any groin hematoma ≥ 5 cm or pseudoaneurysm) following ASE deployment were prospectively assessed. Early failure of ASE was rare (1.8%). In the two groups, the major vascular complication rate was similar [odds ratio (OR), 2.5; 95% confidence interval (CI), 0.5–13.0; p = NS]. However, patients treated by ASE showed a significantly higher risk for minor vascular complications (OR, 2.2; 95% CI, 1.1–4.3; p = 0.029). In comparison to successful deployment, early ASE failure was associated with a very high risk for both major (OR, 15.7; 95% CI, 1.56–158.7; p = 0.002) and minor (OR, 6.1; 95% CI, 1.2–31.8; p = 0.015) vascular complications. Conclusion. In a large, single-center experience, early ASE failure was rare and the rate of major vascular complications following ASE deployment was similar to controls. However, an excess of minor vascular complications (generally large groin hematomas) was observed in patients treated by ASE. Our study confirms that early ASE failure is an important risk factor for severe vascular complications.

Vascular closure devices (VCD) are a major advance in interventional cardiology. They facilitate early patient ambulation^1,2 and may prevent puncture-site complications in patients treated by potent anticoagulant and antiplatelet drugs.^3–7 Along with a widespread diffusion of these devices, reports of complications have emerged⁸ and routine use of these devices has been questioned.⁹

The Angio-Seal Evolution (ASE; St. Jude Medical, Minneapolis, Minnesota) is a novel collagen-plug VCD. The device has been engineered to automate the compaction of the collagen plug, which was operator-dependent in the previous Angio-Seal models. This process should reduce user variability and standardize the deployment forces among different users. Data from a recently published registry suggest a low incidence of vascular complications following ASE deployment.¹⁰ However, this study provided no clinical comparison of ASE with manual compression (MC), the gold standard for femoral hemostasis. Thus, we planned a prospective evaluation of the efficacy and safety of ASE, comparing it with MC.

Methods

From May 2009 to December 2009, a total of 1,021 patients underwent cardiac catheterization and/or percutaneous coronary intervention (PCI) at our institution. In 538 patients, the femoral approach with a 6 French (Fr) arterial sheath was employed. Cardiac catheterization was performed using standard techniques. As part of our routine practice, a femoral angiogram via the arterial sheath was obtained at the end of the procedure. Patients did not undergo VCD deployment if: 1) the arteriotomy site was at or below the femoral bifurcation; 2) the common femoral artery was < 5 mm in diameter; or 3) extensive calcification or plaque burden was present in the common femoral artery. In each patient without angiographic contraindication, hemostasis by ASE was attempted. ASE deployment was performed according to the standard recommended technique. As is routine in our Cath Lab, antibiotic prophylaxis was performed by oral amoxicillin 2 g administered 1 hour before cardiac catheterization. In patients with a history of allergic reaction to beta-lactam drugs, intravenous gentamicin 1.5 mg/kg was used. In cases of urgent cardiac catheterization, intravenous ampicillin 2 g or intravenous gentamicin 1.5 mg/kg were administered immediately before the procedure. In 87 patients, femoral angiography contraindicated ASE deployment. Thus, the final cohort of patients treated by ASE (ASE group) contained 451 patients. These patients were prospectively evaluated for the occurrence of the following endpoints:

1. Early failure of ASE: defined as failure in achieving hemostasis following ASE deployment in the Cath Lab, requiring more than 10 minutes additional MC or Femostop;
2. Major vascular complications: defined as any retroperitoneal hemorrhage, limb-threatening ischemia, or surgical repair occurring in-hospital following cardiac catheterization; and
3. Minor vascular complications: defined as any groin bleeding, groin hematoma ≥ 5 cm, pseudoaneurysm, or arteriovenous fistula occurring in-hospital following cardiac catheterization.

As is routine at our institution, a groin check was made 1 hour and 6 hours following the procedure and prior to discharge. In case of groin hematoma or new femoral bruit detection, an ultrasound evaluation of the groin was performed. The presence of hematoma, pseudoaneurysm or arteriovenous fistula was assessed and recorded, as well as the B-mode measurements of hematomas. The patient charts were evaluated by a clinical research nurse and outcomes were entered into a dedicated database. To serve as a control group, we selected a propensity-score matched population of 451 patients treated by MC following cardiac catheterization (MC group). To minimize bias, controls were selected among 561 consecutive patients who underwent cardiac catheterization from January 2007 to May 2007, when VCD were not routinely used in our Cath Lab. In these patients, routine MC of the femoral artery was performed, pulling the sheath only after an activated clotting time of ≤ 160 seconds was achieved. The clinical charts of the MC group were evaluated and the occurrence of any endpoints previously defined was registered and entered into the database by a clinical research nurse. Femostop (RADI Medical Systems, Inc., Uppsala, Sweden), a pneumatic compression device, was used when hemostasis was not adequate despite MC or ASE deployment. Ambulation was routinely initiated 2–4 hours after ASE deployment and 6–8 hours after MC. The study was approved by the Local Institutional Review Board and all patients gave written consent to the investigation. Statistical analysis. Descriptive statistics (means and standard deviations for continuous factors, frequency counts and relative frequencies for categorical factors) were computed by closure type (MC group versus ASE group). Comparison between groups for continuous variables was performed by unpaired t-test (in case of parametric distribution) or Mann-Whitney U-test (in case of non-parametric distribution), as appropriate. Univariate associations between treatment type and patient features and outcomes were examined using two-way contingency tables; significance of associations were assessed using the Chi-squared test or the Fisher exact test, as appropriate. Patient outcomes were expressed as odds ratios (OR) and 95% confidence intervals (CI). To estimate associations between closure type and complications in a setting adjusted for possible within-subject correlation as well as important concomitant risk factors, multivariate logistic regression analysis was employed. A p-value of < 0.05 was required to reject the null hypothesis. As patients with unsuccessful deployment of ASE showed increased risk of complications in several reports, prespecified subgroup analysis of patients with and without early ASE failure was planned. This statistical analysis was performed using the SPSS statistical software package version 16.0. Propensity score matching. The logistic model, which included patient background characteristics [age, sex, body mass index (BMI), diabetes, hypertension, high blood cholesterol, smoking, peripheral artery disease, presence of acute coronary syndrome, PCI and drug classes affecting coagulation and platelet function (aspirin, clopidogrel, sodium-heparin, low molecular weight heparin, abciximab, tirofiban, eptifibatide, thrombolytics)] was used to generate a propensity score for each individual in the dataset. Propensity-score matching was performed using a 5-digit, greedy 1:1 matching algorithm^11,12(Parsons, Black). This statistical analysis was performed with the SAS statistical software package, version 9.1 (SAS Institute, Inc., Chicago, Illinois).

Results

Figure 1 describes the process of patient selection and cross-matching. The clinical features of ASE and MC groups were similar, as expected in propensity-score matched cohorts (Table 1). The clinical outcomes of the two groups are summarized in Table 2. Early failure of ASE was a rare event, occurring in 8 patients (1.8%). ASE and MC groups had similar rates of major vascular complications (1.1% versus 0.4%, respectively; OR, 2.52; 95% CI, 0.49–13.04; p = NS), but the ASE group showed higher rates of minor vascular complications (5.5% versus 2.7%, respectively; OR, 2.15; 95% CI, 1.07–4.33; p = 0.029). Only 1 patient (treated by ASE) died from a cause directly correlated to a major vascular complication (massive retroperitoneal bleeding). The clinical features and outcomes of patients with early ASE failure are summarized in Tables 3 and 4. These patients showed a severely increased risk of major (OR, 15.68; 95% CI, 1.55–158.70; p = 0.002) and minor vascular complications (OR, 6.09; 95% CI, 1.16–31.83; p = 0.015). The results of the logistic regression analysis are summarized in Figure 2. Vascular complications were significantly and independently correlated to the presence of obesity (defined as BMI ≥ 30 kg/m²) and peripheral vascular disease. ASE deployment and early ASE failure showed a trend for correlation with vascular complications, but did not reach statistical significance. Finally, data concerning the effects of the operator experience on clinical outcomes are summarized in Table 5. ASE were deployed at our institution by 6 skilled operators. The number of ASE implanted, rate of successful deployment and rate of vascular complications were similar among the 6 operators. To assess the presence of a learning curve effect, we compared the vascular complications occurring in the first 50% versus the second 50% of the career of each operator and we observed no significant difference (12 vascular complications in the first 50% of deployments versus 13 vascular complications in the second 50% of deployments; p = NS).

Discussion

The present study demonstrated that, in an unselected population treated by cardiac catheterization and/or PCI in a high volume Cath Lab, the novel ASE device had a low rate of early hemostasis failure and a rate of major vascular complications similar to femoral compression. However, patients treated by ASE showed an increased incidence of minor vascular complications. The pre-specified subgroup analysis confirmed that ASE failure is an important risk factor for the occurrence of major and minor vascular complications in the first 24 hours after cardiac catheterization and/or PCI. Prior studies demonstrated VCD efficacy in reducing the time to ambulation for patients undergoing cardiac catheterization^1,2 and in decreasing the rates of vascular complications in high-risk PCI patients.^4–7 However, other studies^13,14 and a meta-analysis¹⁵ suggested that VCD could actually increase the risk of vascular complications, such as hematomas, pseudoaneurysms and limb-threatening ischemia. Moreover, comparison trials^16–19 and meta-analyses^20,21 highlighted significant differences among individual VCD. One of the most important drawbacks of VCD is the complexity of their deployment and the dependence on operator skill. ASE is a novel collagen plug-based VCD, engineered specifically to automate the compaction of the collagen plug, which was a manual process in previous Angio-Seal models. The automatic compaction eliminates multiple steps in the deployment process, removes user variability and standardizes deployment forces among different users. Applegate et al recently published the results of the Angio-Seal Evolution Registry,¹⁰ reporting a very low incidence of vascular complications following ASE deployment. Unfortunately, this study did not provide a clinical comparison of ASE with femoral compression, the gold standard for femoral artery hemostasis. Our study upheld that early hemostasis failure following ASE deployment is a rare event and demonstrated that ASE was not associated with increased rates of major vascular complications when compared to patients treated by femoral compression. However, we did observe an excess of minor vascular complications in the patient population treated by ASE. Thus, our results support the position recently expressed in the American Heart Asssociation Scientific Statements by Patel et al,²² which considered VCD in Class IIa when employed to achieve faster hemostasis, shorter duration of bed rest and improved patient comfort, but in Class III when used to reduce vascular complications in patients undergoing invasive cardiovascular procedures via the femoral artery approach. The use of VCD should therefore be carefully weighed against the risk of increased complications and their routine employment should depend on a correct acknowledgement of their risk/benefit profile. Another interesting result of our study is that early failure of ASE identified a cohort of patients with a very high risk of both major and minor vascular complications, a concept that was recently highlighted by Bangalore et al.²³ The recognition that early VCD failure is a risk factor for ominous vascular complications is a crucial issue. In our experience, an insidious link between early ASE failure and the subsequent occurrence of severe vascular complications was observed. In fact, none of the patients with early ASE failure had uncontrollable post-procedural bleeding requiring immediate surgery, but each of them developed a large groin hematoma or pseudoaneurysm in the first 24 hours after cardiac catheterization, often requiring surgical repair. Thus, when early ASE failure occurs, patients should be closely monitored, possibly with repeated groin checks and serial complete blood counts, and should be evaluated expeditiously by CT-angiography and surgical repair if active bleeding is suspected. The importance of early ASE failure as a risk factor for severe bleeding, as well as the efficacy of diagnostic options and therapeutic interventions to prevent such complications, should be addressed by future investigations. Finally, we observed no significant learning curve effect for ASE deployment. Several studies have suggested that VCD results could, at least in part, depend on operator skill.^24,25 While individual and institutional experiences have probably shortened this learning curve,²⁶ some grade of dependence on operator technique remains. In order to simplify VCD deployment and to decrease the operator-dependent variability, the novel ASE was engineered to eliminate the operator-dependent compaction of the anchor-collagen sandwich and to provide consistent and reproducible compaction forces on the anchor and collagen sponge. The results of our study support the concept that a consistent compaction force applied to the collagen anchor and sponge translates into high degrees of device deployment success with homogeneous results across different users. Study limitations. The present study has several limitations. First of all, hemostasis by ASE or femoral compression was not based on blinded and random assignment; therefore, the results may be confounded by other factors. Although this is unlikely to occur, given the broad spectrum of characteristics collected in our study and taken into account by the propensity-score matching, we cannot exclude residual confounding by unmeasured factors.²⁷ Furthermore, vascular complications experienced outside the hospital were not formally monitored. Anecdotal experience in previously published series indicates that late infection is a rare but severe complication in patients undergoing closure with various VCD.^3,28,29 However, the design of our study does not allow us to formally measure this complication rate in our patient cohorts. Finally, the definition of large groin hematoma has been a subject of debate and the choice of a cut-off of ≥ 5 cm, as well as the methods of hematoma measurement, could be questionable. In the meta-analysis by Nikolsky et al,²⁰ the presence of a very wide-ranged criteria for the definition of groin hematoma was remarked and authors did not consider groin hematoma as a primary endpoint to avoid bias. Also, in a recent study by Bangalore et al, groin hematomas larger than 5 cm were considered a minor complication.²³ Thus, in the present study, we decided to consider groin hematoma to be a component of the minor vascular complication endpoint and the cut-off was chosen to be 5 cm. This cut-off could explain the difference of our results with those from the Angio-Seal Evolution Registry,¹⁰ which reported a very low incidence of vascular complications following ASE deployment, but considered as a vascular endpoint only groin hematomas larger than 10 cm. However, the Angio-Seal Evolution Registry lacks a control group with MC, making a comparison with the results of our study very challenging.

Conclusion

The novel ASE device showed a low rate of early failure and major vascular complications, similar in comparison to femoral compression. However ASE deployment was associated with an excess of minor vascular complications (generally large groin hematomas). Our results confirm that early ASE failure represents a condition of high risk for both major and minor vascular complications and suggests strict clinical monitoring for patients in whom ASE deployment was not successful. Acknowledgments. We gratefully acknowledge the efforts of Maria Grazia D’Ulisse, Anna Federzoni, Chiara Clementi, Maria Teresa Bausani, Adele Mandrino, Pierangelo Rizzotti and Roberta Sandri for their expertise and support in the Cath Lab and data collection.

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From the Department of Cardiology, Maggiore della Carità, Novara, Italy. The authors report no conflicts of interest regarding the content herein. Manuscript submitted November 29, 2010, provisional acceptance given January 3, 2011, final version accepted January 12, 2011. Corresponding author: Alessandro Lupi, MD, Ospedale Maggiore della Carità, Cardiologia 2, Cso Mazzini 18, 28100, Novara, Italy. E-mail: lupialessandro1@tin.it