Efficacy and Safety of the Nitinol Clip-Based Vascular Closure Device (Starclose) for Closure of Common Femoral Arterial Cannulation at or Near the Bifurcation: A Propensity Score-Adjusted Analysis

ABSTRACT: Objectives. To evaluate the efficacy and safety of the nitinol clip-based closure device (Starclose®, Abbott Vascular, Santa Clara, California) in patients with femoral arterial cannulation at the common femoral artery bifurcation. Background. Femoral artery puncture at the bifurcation of common femoral artery is a relative contraindication for the use of vascular closure devices with intravascular components, and patients with bifurcation cannulation were excluded from the pivotal trials of these devices. The nitinol clip-based closure device (Starclose) is extravascular and is sometimes used in such patients; however, the efficacy and safety of this approach is unknown. Methods. We evaluated consecutive patients undergoing deployment of a Starclose device following a coronary procedure via the femoral artery approach. Quantitative femoral angiographic analyses were performed using a hand caliper. The distance of the artery puncture site from the bifurcation was recorded in each patient. Any arterial cannulation ≤ 3 mm from the bifurcation was categorized as a bifurcation cannulation (as the outer diameter of the nitinol clip of Starclose is 4 mm). Results. Among 1,096 patients who underwent deployment of a Starclose device, 217 (20%) were within 3 mm of the bifurcation. Starclose deployment at the bifurcation was not associated with a significant increase in the risk of any (0.9% vs. 1.0%; p = 0.892) major (0.0% vs. 0.3%; p = 0.389) or minor vascular complications (0.9% vs. 0.7%; p = 0.711) compared to deployment for non-bifurcation cannulations (both for diagnostic and percutaneous coronary interventional procedures). The results were unchanged in both a regression model adjusted for a propensity score (41 baseline covariates) as well as a propensity score-matched cohort (217 bifurcation cannulations vs. 217 non-bifurcation cannulations). Conclusion. In a select group of patients, vascular closure using a extravascular closure device (Starclose) appears to be safe for arterial cannulations at or near the bifurcation.

J INVASIVE CARDIOL 2011;23:194–199

Key words: bifurcation; complications; Starclose®; vascular closure devices

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Femoral arterial access is the most common method of vascular access for coronary angiography and percutaneous coronary intervention (PCI) in the United States. Vascular closure devices (VCDs) have emerged as an effective alternative to traditional mechanical compression after cardiac catheterization and have the potential to reduce the time to hemostasis, facilitate early patient mobilization, decrease hospital length of stay and improve patient satisfaction.^1–6 However, not all patients are candidates for VCD use. Precaution is advised in the presence of femoral artery atherosclerotic disease, extreme obesity, in situations where the artery is small (diameter < 4–5 mm) and in the presence of low or high arterial punctures or bifurcation cannulation.⁷ The concern with VCDs with an intravascular component (like the Angio-Seal® device, St. Jude Medical, St. Paul, Minnesota) for closure of bifurcation cannulation is the anchor catching on the bifurcation, difficulty in positioning the device correctly or collagen deposition into the vessel.⁷ As such, patients with bifurcation cannulation were excluded from the pivotal device approval studies.⁷

Common femoral bifurcation cannulation is nevertheless seen in a small proportion of patients undergoing coronary angiography and intervention. Given the paucity of data, VCDs are not routinely used in such patients resulting in manual compression as the technique of choice for achieving hemostasis. However, devices such as Starclose^® (Abbott Vascular, Santa Clara, California) which are predominantly extravascular are attractive in this setting. The efficacy and safety of such devices for bifurcation punctures are not well defined.

The objective of the present study was to evaluate the efficacy and safety of the Starclose device in patients with femoral artery cannulation at or near the bifurcation.

Methods

Study population. We prospectively evaluated consecutive patients undergoing cardiac catheterization (either diagnostic or PCI) via femoral access at the Brigham and Women’s Hospital between January 1, 2006, and June 30, 2009. Patients who received a nitinol clip-based closure device (Starclose) were selected for the study, as these were most likely to be used (if any) for any common femoral artery cannulation at or near the bifurcation, at our institution. Patients who required an intra-aortic balloon pump placement during the cardiac catheterization procedure were excluded from the study. Informed written consent was obtained from all patients and the study was approved by the institutional review board.

Data collection. A prospective catheterization laboratory database, based on the American College of Cardiology (ACC)-National Cardiovascular Data Registry (NCDR) definitions, was used to record clinical and procedural elements for each patient.⁸ Patients were prospectively followed up for the occurrence of in-hospital vascular complications which were reviewed and adjudicated by board-certified interventional cardiologists.

Cardiac catheterization protocol. Diagnostic coronary catheterization and PCI were performed according to standard guidelines. Unless contraindicated, all PCI patients received aspirin, clopidogrel and weight-adjusted heparin therapy (or bivalirudin) as per the standard ACC/American Heart Association (AHA) recommendations. Periprocedural glycoprotein IIb/IIIa inhibitors were used at the discretion of the treating physician. Anatomical landmarks were identified by preprocedure fluoroscopy, and vascular access was obtained through single-wall common femoral arterial puncture.

Vascular closure device protocol. Femoral angiography was performed in all patients prior to VCD deployment. An ipsilateral oblique view was used in all cases. At the operator’s discretion, additional views were obtained if there was significant vessel overlap or in cases of uncertainty of the site of the femoral arterial cannulation with one view.

The type of VCD used and the decision to use a VCD was left to the operator’s discretion. The Starclose device was deployed using standard technique as described by the FDA-approved instructions for use.⁹ Briefly, the Starclose is a nitinol clip-based active approximator which is predominantly extraluminal. Given that there are no significant intravascular components, it is thought to be relatively safe for closure of bifurcation cannulations, though not marketed for this indication. Ambulation was advised 2–4 hours after closure device deployment. Local lidocaine with epinephrine injection was used as needed to stop oozing from the arteriotomy site.

Quantitative femoral angiography. Quantitative femoral angiography was performed in all patients using hand caliper by observers blinded to patient outcomes. The distance of the artery puncture site from the bifurcation was recorded for each patient. Any arterial cannulation ≤ 3 mm from the bifurcation was categorized as a bifurcation cannulation (as the outer diameter of the nitinol clip of Starclose is 4 mm) (Figure 1). Analysis also included evaluation of presence of atherosclerosis in the external iliac artery, common iliac artery, common femoral artery, superficial femoral artery and the profunda femoris artery at the bifurcation. We also measured the size of the above arteries. The presence of atherosclerotic plaque was determined by the presence of any luminal irregularities on the femoral angiography.

Outcome measures. Patients were followed up for the occurrence of in-hospital vascular complications. Vascular complications included: groin bleeding (defined as blood loss at the access site resulting in blood transfusion, increased length of stay, or drop in hemoglobin >3 g/dL), hematoma (size ≥ 5 cm), pseudoaneurysm (confirmed by ultrasonography), arteriovenous fistula (confirmed by ultrasonography), retroperitoneal hemorrhage (confirmed by computed tomographic scan), limb ischemia (loss of peripheral pulse requiring vascular or surgical evaluation), or any case requiring vascular access-related surgical intervention. Major vascular complication was defined as any retroperitoneal hemorrhage, limb ischemia or any vascular access-related surgical intervention. Minor vascular complication was defined as any groin bleeding, hematoma (≥ 5 cm), pseudoaneurysm or arteriovenous fistula. “Any” vascular complication was defined as either a major or minor vascular complication.

Statistical analysis. All analyses were carried out using standard statistical package (SPSS for Windows, Version 16.0, SPSS Inc., Chicago, Illinois). Patients were divided into two groups:  bifurcation puncture versus not based on the results of the quantitative femoral angiography. Continuous variables were reported as mean value ± standard deviation (SD). Patient groups were compared using the Student t-test (for normally distributed variable) or the Wilcoxon rank-sum test (for other variables) for continuous variables and the chi-square test or Fisher’s exact tests for categorical variables.

An unadjusted analysis was performed to evaluate the risk of vascular complications based on the location of the femoral arterial puncture site (bifurcation versus not). A regression model adjusted for propensity score was performed to adjust for baseline variables. Propensity score is the conditional probability of having an exposure given a set of measured baseline covariates^10,11 Propensity scores were estimated using a non-parsimonious multivariable logistic regression model.¹² In the model, bifurcation puncture was used as the dependent variable, and the 41 baseline characteristics displayed in Figure 2 were entered as covariates. The logistic regression score was then modeled into a multivariate regression analysis to evaluate the risk of vascular outcomes with bifurcation cannulation. The discriminatory power of the logistic models was measured using the area under the receiver-operator curve, and goodness of fit was measured with the Hosmer-Lemeshow C statistic. P-value was considered significant at < 0.05.

For the propensity score matching, we used a one-to-one (Greedy) matching protocol without replacement, using a caliper width of 0.6 of the standard deviation. The propensity score matching matched 217 patients with bifurcation punctures (100% of the bifurcation puncture patients) with 217 patients without bifurcation punctures (20% of the 1,096 patients without bifurcation puncture) who had similar propensity scores. We estimated absolute standardized differences for all of the covariates between participants to assess pre-match imbalance and post-match balance.¹³ Absolute standardized differences directly quantify balance in the means (or proportions) of covariates across the groups and are expressed as percentages of pooled SDs. An absolute standardized difference of 0% on a covariate indicates no between-group imbalance for that covariate, and values < 10% indicate inconsequential imbalance.¹³ Unadjusted analysis for the risk of vascular outcomes was then performed on this matched cohort. Additional adjustment to significant baseline variables (post-matching) was performed. The discriminatory power of all of these logistic models was measured using the area under the receiver-operator curve. P-value was considered significant at < 0.05.

Results

Among the study cohort of 1,096 patients who underwent Starclose device deployment, the frequency of puncture at or near the bifurcation was 20% (217 patients).

Baseline characteristics. Among the study cohort of 1,096 patients who underwent Starclose deployment, bifurcation puncture was present in 217 patients (20%) and no bifurcation puncture in 879 (80%) patients. The baseline clinical and procedural characteristics of patients with and without bifurcation punctures are summarized in Table 1. Patients with bifurcation puncture were more likely to be older, men, those who underwent a PCI procedure and those with usage of bivalirudin as the anticoagulant regimen compared to patients without bifurcation puncture (Table 1). Of note, nearly half of the bifurcation punctures were in patients undergoing PCI.

Matched cohort. The propensity score-matching matched 217 patients with bifurcation punctures (100% of the bifurcation puncture patients) with 217 patients without bifurcation punctures (20% of the 879 patients without bifurcation puncture) who had similar propensity scores. The baseline characteristics were well matched except for a greater frequency of glycoprotein IIb/IIIa use in the bifurcation puncture patients (Table 1). The absolute standardized differences pre- and post-matching are summarized in Figure 2. Compared to pre-match, there were only two variables with an absolute standardized difference > 10% post-match, indicating adequate match (Figure 2).

Quantitative femoral angiography. Quantitative femoral angiography using hand calipers was performed on all patients. Of the 1,096 patients, 18 (1.6%) had atherosclerotic plaque in the external iliac artery, 34 (3.1%) in the common femoral artery, 32 (2.9%) in the superficial femoral artery, 33 (3.0%) in the profunda femoris artery, but only 6 (0.5%) had any significant narrowing at the bifurcation. This was not different in those who had bifurcation cannulation versus those without. The mean diameter of the artery at the site of arterial puncture was 6.5 ± 2.4 mm in those with a bifurcation puncture versus 6.8 ± 2.4 mm for others (p = 0.140). Similarly, the diameter of the external iliac artery was similar between the two groups (7.7 ± 2.4 mm vs. 7.7 ± 2.4 mm; p = 0.731). Most of the arterial cannulation was in the common femoral artery (76%), while a few were in the profunda femoris (6%) and superficial femoral arteries (18%).

Vascular outcomes. For the overall cohort, the risk of vascular complications with Starclose was low (any vascular complication 1%, major 0.3%, minor 0.7%). The incidence of vascular complications was higher in patients undergoing PCI compared to those who underwent diagnostic coronary angiography only, although this was not statistically significant — any vascular complication (1.5% vs. 0.7%; p = 0.194), major (0.3% vs. 0.3%; p = 1.000) or minor vascular complication (1.3% vs. 0.4%; p = 0.115). Compared to patients with Starclose deployment for a non-bifurcation cannulation, deployment for a bifurcation cannulation was associated with similar risk of any major or minor vascular complications (Figure 3). The risk of vascular complications were similar in a regression model adjusted for the propensity score (Table 2). Of note, the C-statistic of the model improved with adjustment for propensity score for all the outcomes tested (Table 2). The incidence of any vascular complication as a function of distance of the arteriotomy site from the bifurcation of the common femoral artery is shown in Figure 5. The incidence increased with greater distance from the bifurcation, with lowest rate between 7 to 12 mm.

Similarly, in the propensity score matched cohort, compared to patients with Starclose deployment for a non-bifurcation cannulation, deployment for bifurcation cannulation was associated with a similar risk of any, major or minor vascular complications (Figure 4). The results were consistent after adjusting for baseline variables (Table 2).

In addition, the rate of any vascular complications varied with the site of arteriotomy with the lowest rate in the common femoral artery (6/826 patients; 0.7%), followed by profunda femoris artery (1/66 patients; 1.5%), superficial femoral artery (3/195 patients; 1.5%) and external iliac artery (1/5 patients; 20%).

For the overall cohort, the length of hospital stay was considerably lower in patients with bifurcation puncture compared to patients without bifurcation puncture.

Discussion

This study assessed the efficacy and safety of Starclose device deployment for femoral artery cannulation at or near the bifurcation. The results of the present study showed that in this select group of patients, Starclose deployment in patients with bifurcation puncture was associated with similar low risk of vascular complications compared to deployment in patients without bifurcation puncture.

VCDs and bifurcation femoral artery cannulation. VCDs are being increasingly used in patients after cardiac catheterization, as they reliably shorten the time to hemostasis compared with manual compression, and thus allow earlier patient ambulation.³ In addition, sheath removal can be done immediately compared to manual compression, even in patients undergoing PCI.¹⁴ VCDs can also allow improved patient satisfaction and comfort related to the avoidance of prolonged sheath insertion and manual compression.^14,15 The data on reduction of vascular complications with these devices are controversial.¹⁶ Nevertheless, VCDs are not for all patients, and caution is required when considering the use of these devices in patients with peripheral vascular disease, extremely obese patients, those with small femoral arteries (diameters < 4–5 mm), those with arterial cannulation at or below the bifurcation. Apart from the above patient- and artery-specific factors, factors related to the mechanism of action of VCDs should also be taken into consideration, i.e., presence of an intravascular component of the closure device. In devices with a significant intravascular component, such as the Angio-Seal device, usage is not recommended for bifurcation punctures, as there is a risk of obstruction by the intravascular portion of the device of the smaller branches typically involved in bifurcation punctures. Moreover, accurate alignment of the intravascular part might be difficult due to the complex angles at the site of bifurcation. In addition, there is also a risk of deployment of the collagen plug intravascularly. Thus, access-site closure in patients with bifurcation punctures continues to be a challenge and most sites of this type are compressed manually. 

Devices that do not have any significant intravascular component (like Starclose or Mynx™ [AccessClosure, Inc., Mountain view, California]) are especially attractive in this group of patients. However, avoiding bifurcation puncture should be a priority, as it not only reduces vascular complications but also permits usage of VCDs. Fluoroscopic guidance, as used in our study, is increasingly employed and is a recommended technique for femoral artery puncture. The technique employs visualization of the femoral head under fluoroscopy in a posterior-anterior projection and by starting the skin puncture at the level of the lower border of the head of femur with an eventual goal of arterial cannulation at the center of the head of femur. However, even with this technique, bifurcation punctures cannot be completely avoided. This is due to variability in the site of femoral artery bifurcation in reference to the femoral head. Dotter et al¹⁷ found that the femoral artery bifurcation was 2–66 mm below the femoral head. Though in a majority of cases (approximately 77%) the bifurcation is below the level of the femoral head, in approximately 23% of cases the femoral artery bifurcation site is higher,¹⁸ potentially resulting in a bifurcation puncture. The use of ultrasound guidance has the potential to reduce such punctures, but routine ultrasound-guided puncture is not widespread.

In patients with bifurcation punctures, the results of the present study showed that the use of a primarily extravascular device like the Starclose is safe and efficacious. The risk of vascular complications was low and comparable to the rates that of manual compression found in the literature. The study had low rates of peripheral vascular disease and moderate-to-severe atherosclerosis on femoral angiography. Moreover, it appears that the risk of any vascular complications increased with increasing distance from the bifurcation, implying a greater risk of vascular complications with high arterial cannulations. In addition, our results are concordant with other studies showing that the lowest risk of any vascular complications involves femoral arterial cannulation in the common femoral artery.

Study limitations. The data are from a single, high-volume center with an institutional policy of routine VCD use, and hence the generalizability of our study to other centers is limited. Despite the institutional policy for deployment of VCDs and the propensity analysis reported, unadjusted biases may still remain in this observational data set. We evaluated consecutive patients who underwent Starclose deployment and did not compare the results with patients who underwent manual compression alone or with other devices such as the Mynx. However, the rate of vascular complication was low and comparable to that seen with manual compression alone. The rate of complications was rather low in the study both for diagnostic or PCI procedures. In this study we evaluated in-hospital outcomes only, and hence late complications may be underestimated.

Conclusions

In a selected group of patients undergoing either diagnostic or interventional coronary procedures, the use of an extravascular closure device (Starclose) is associated with similar rates of any major or minor vascular complications in patients with or without bifurcation arterial cannulation.

References

1. Chevalier B, Lancelin B, Koning R, et al. Effect of a closure device on complication rates in high-local-risk patients: Results of a randomized multicenter trial. Catheter Cardiovasc Interv 2003;58:285–291.
2. Gerckens U, Cattelaens N, Lampe EG, Grube E. Management of arterial puncture site after catheterization procedures: Evaluating a suture-mediated closure device. Am J Cardiol 1999;83:1658–1663.
3. Kussmaul WG 3rd, Buchbinder M, Whitlow PL, et al. Rapid arterial hemostasis and decreased access site complications after cardiac catheterization and angioplasty: Results of a randomized trial of a novel hemostatic device. J Am Coll Cardiol 1995;25:1685–1692.
4. Nasu K, Tsuchikane E, Sumitsuji S. Clinical effectiveness of the Prostar XL suture-mediated percutaneous vascular closure device following PCI: Results of the Perclose AcceleRated Ambulation and DISchargE (PARADISE) Trial. J Invasive Cardiol 2003;15:251–256.
5. Slaughter PM, Chetty R, Flintoft VF, et al. A single center randomized trial assessing use of a vascular hemostasis device vs. conventional manual compression following PTCA: What are the potential resource savings? Cathet Cardiovasc Diagn 1995;34:210–214.
6. Ward SR, Casale P, Raymond R, et al. Efficacy and safety of a hemostatic puncture closure device with early ambulation after coronary angiography. Angio-Seal Investigators. Am J Cardiol 1998;81:569–572.
7. https://www.sjm.com/_MediaAssets/documents/angioseal_evo_ifu.pdf. Accessed Feb 22, 2010. Angio-Seal Evolution Vascular Closure Device: Instructions for Use.
8. Brindis RG, Fitzgerald S, Anderson HV, et al. The American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR): Building a national clinical data repository. J Am Coll Cardiol 2001;37:2240–2245.
9. https://www.abbottvascular.com/en_US/content/document/Starclose_eIFU.pdf. Accessed Feb 22, 2010.Starclose vascular closure system: Instructions for use.
10. Rosenbaum P, Rubin D. The central role of propensity score in observational studies for causal effects. Biometrika 1983;70:41–55.
11. Rubin D. Using propensity score to help design observational studies: Application to the tobacco litigation. Health Serv Outcomes Res Methodol 2001;2:169–188.
12. Ahmed A, Husain A, Love TE, et al. Heart failure, chronic diuretic use, and increase in mortality and hospitalization: An observational study using propensity score methods. Eur Heart J 2006;27:1431–1439.
13. Normand ST, Landrum MB, Guadagnoli E, et al. Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: A matched analysis using propensity scores. J Clin Epidemiol 2001;54:387–398.
14. Duffin DC, Muhlestein JB, Allisson SB, 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.

15. Martin JL, Pratsos A, Magargee E, et al. A randomized trial comparing compression, Perclose Proglide and Angio-Seal VIP for arterial closure following percutaneous coronary intervention: The CAP trial. Catheter Cardiovasc Interv 2008;71:1–5.
16. Nikolsky E, Mehran R, Halkin A, et al. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: A meta-analysis. J Am Coll Cardiol 2004;44:1200–1209.
17. Dotter CT, Rosch J, Robinson M. Fluoroscopic guidance in femoral artery puncture. Radiology 1978;127:266–267.
18. Turi ZG. An evidence-based approach to femoral arterial access and closure. Rev Cardiovasc Med 2008;9:7–18.

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From *New York University School of Medicine, New York, New York and §Brigham and Women’s Hospital, Boston, Massachusetts.
This work was funded in part by NIH R01-LM008142. This work was pre- sented in part at the 2010 Annual Scientific Session of the American College of Cardiology, Atlanta, Georgia. Dr. Resnic is a consultant to St. Jude Medical and has received grant support from the Medicines Company. The other authors report no conflicts of interest related to the content herein.
Manuscript submitted January 3, 2011, provisional acceptance given Feb- ruary 7, 2011, final version accepted February 18, 2011.
Address for correspondence: Frederic S. Resnic, MD, MSc, Director, Car- diac Catheterization Laboratory, Division of Cardiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. Email: fresnic@partners.org