Extravascular Closure for Patients with High-Risk Femoral Anatomy

Methods

Study design and endpoints. We performed a single-center, multiple-operator, prospective registry enrolling 98 patients who met the inclusion criteria of non-ideal femoral anatomy or increased bleeding risk. The treatment cohort was obtained from 619 consecutive patients undergoing diagnostic coronary angiography via the femoral approach at the University of Vermont between November, 2006 and November, 2007. All patients provided written, informed consent to participate. The inclusion criteria were any of the following:

• femoral artery is calcified (opacification of femoral artery without contrast dye);

• femoral access is in the profunda femoris or superficial femoral artery;
• femoral access is at the bifurcation of the profunda and superficial femoral arteries;
• femoral artery stenosis of 30–70%;
• femoral artery diameter 4–5 mm (as judged compared to a 6 Fr sheath with external diameter of 2.5 mm);
• patients with access of the same femoral artery within the prior 8 weeks;
• patient within 24 hours of fibrinolytic therapy;
  
• patient with platelet count < 100,000 or hematocrit < 28%.

The most common reasons for exclusion were non-high-risk femoral anatomy (n = 251, 48%) and coronary intervention procedure (n = 210, 40%). In 11 cases, the patient was deemed not able to ambulate within 60 minutes due to clinical reasons (i.e., severe left main disease awaiting bypass surgery). In 23 cases, the patient received an extra bolus heparin or bivalirudin for an intravascular ultrasound procedure and was excluded, although preprocedural use of heparin or bivalirudin infusion was not a contraindication to enrollment.
In 10 cases, exclusion was due to the sheath being at or above the inferior epigastric artery, and in 8 cases, the Starclose VCD was not used at the discretion of the physician. The management strategy and outcomes of patients not included in the registry were not recorded. Patients with external iliac artery sheath insertions were excluded due to concerns about potential failure for clip-based closure in the deeper external iliac artery; these high-risk punctures were managed with caution including manual compression, cessation of anticoagulation, prolonged bed rest and occasional cautious use of VCDs.
The primary study endpoint was device success defined as final hemostasis using the Starclose VCD alone or with adjunctive compression of < 5 minutes and freedom from major vascular complications. Secondary study endpoints included procedural success with the Starclose device (final hemostasis using any method and freedom from major vascular complications) and in-hospital major or minor vascular complications. Efficacy endpoints included the time to hemostasis (elapsed time between sheath removal and first observed hemostasis), time to ambulation (elapsed time between sheath removal and time when the subject stood and walked at least 20 feet without re-bleeding), and time to discharge from the hospital. Major and minor complications were defined according to the CLIP trial⁵ and are listed in Table 3; major vascular complications included any vascular injury requiring intervention, new ipsilateral ischemia, access site-related bleeding requiring transfusion, infection or nerve injury.
Each investigator in the study performed at least 25 successful Starclose femoral artery closures prior to enrolling in this registry. This was to avoid potentially higher rates of complications related to operators still in the “learning curve” for a VCD.⁷ The Starclose closure procedure was performed according to the instructions in the IFU (www.abbottvascular.com/ifu) and is demonstrated in Figure 1. All patients signed an informed consent describing off-label utilization of the Starclose device if femoral anatomy or clinical characteristics met criteria for non-ideal closure risk. The study was approved by the institutional review board at University of Vermont/Fletcher Allen Health Care.
Femoral access and angiography. Femoral access was performed after locating the probable location of the common femoral artery via fluoroscopy to identify the femoral head.^8–10 Ultrasound guidance was not used in this registry. Femoral angiography was performed as per our usual clinical practice; intra-arterial nitroglycerin was not given, thus spasm of the femoral artery cannot be excluded as a potential cause of mild-to-moderate stenosis in some of these patients.
Data collection and analysis. Clinical, laboratory, angiographic and demographic data were collected during the index hospitalization. Quantitative femoral angiography was performed on all patients using both digital calipers and an automated edge detection algorithm (Philips Medical Systems, Bothell, Washington). The femoral artery reference diameter and minimum lumen diameter were determined using an automated edge detection program with the sheath as the reference. Cineangiography was adequate for quantitative assessment in 99% of patients in the cohort. All patients underwent femoral angiography in the 30º ipsilateral projection to assess the femoral anatomy and puncture site location. If the insertion point of the sheath could not be determined with a 30º RAO projection, a 30º LAO projection was used. Determination of sheath insertion distance from the bifurcation of the superficial femoral/profunda femoris arteries was made using digital calipers.
Data are presented as mean ± standard deviations. The study was designed to have a maximum enrollment ≤ the diagnostic arm of the CLIP pivotal Starclose approval trial (n = 136) during 12 months of consecutive enrollment (n = 98 patients from October 2006–October 2007). The study endpoints were compared to the CLIP trial which used the same device in a lower-risk diagnostic catheterization population. Student’s t-tests were used to evaluate significance in outcomes as compared to the CLIP trial. A p-value < 0.05 was considered significant.

Results

A total of 98 patients were enrolled in this registry from 619 consecutive patients during the 12-month period. The average age was 64 years old and the majority were males (65%) undergoing outpatient procedures (86%). Approximately one-third of patients had more than one inclusion criteria, with sheath insertion at the bifurcation (37%), femoral stenosis (30%) or femoral calcification (24%) being the most common inclusion criteria (Table 1). These were followed in order of descending frequency by small femoral artery diameter 4–5 mm (9%), sheath below the bifurcation (9%), prior access in the ipsilateral femoral artery within 8 weeks (4%), platelet count < 100,000 or hematocrit < 28% (3%), and fibrinolytic therapy within 24 hours (2%). While not a specific high-risk inclusion criteria, it is noteworthy that 18% of patients in this registry were significantly obese (body mass index [BMI] > 35.0) with a maximum BMI of 59.0 (weight 323 lbs).
Angiographic characteristics. All patients had a 6 Fr arterial sheath. Figure 2 shows examples of high-risk femoral closure due to moderate arterial stenosis or bifurcation sheath insertion site. The femoral arterial reference vessel diameter was 7.0 ± 2.0 mm in diameter, similar to the results of a prior large angiographic study of femoral anatomy.⁸ The minimum lumen diameter for the entire cohort was 6.1 ± 1.99 mm and reflects the inclusion of many high-risk patients due to nonstenotic indications (low sheath insertion, calcification). The minimum lumen diameter among patients included due to femoral arterial disease was 4.61 ± 1.56 mm consistent with mild-to-moderate femoral arterial disease. Patients with femoral arterial diameters < 4.0 mm were excluded by the protocol due to safety concerns. Thus, femoral stenoses were mild-to-moderate by quantitative angiography (35.3 ± 5.13%) (Table 2).
Device efficacy and safety. Despite high risk for femoral closure, there was 100% procedural success and 94% device success in the registry (Table 3). Eighty-seven of the 98 patients required compression of < 1 minute, with 15–60 seconds of compression used commonly to manage tract oozing. Failure to attain device success in 6% of the patient cohort was entirely due to the inability of the operator to attain early complete hemostasis within 5 minutes of device deployment. Five cases of device failure were due to persistent bleeding after Starclose deployment that required manual compression of 5–30 minutes in duration, although hemostasis was achieved without further sequelae. There was also 1 case of re-bleeding after successful device closure and initial hemostasis that required 30 minutes of manual compression (minor complication). There were no major vascular complications.
Ambulation at 60 minutes after device closure was a pre-specified endpoint of the study; only one-third of patients ambulated at 60 minutes due to patient preference and/or sedation effects. On the other hand, 90% (n = 88) of patients ambulated within 90 minutes. The average time to ambulation (78.1 ± 47.3 minutes) was significantly reduced using this protocol as compared to a similar population studied in the CLIP diagnostic trial (p < 0.001) (Table 4).

Discussion

The major concerns of femoral artery closure after cardiac catheterization are cost and complications.¹¹ The risk of complications may be stratified by the presence of risk factors such as peripheral vascular disease¹² as well as other clinical risk factors associated with bleeding complications.¹³ While the overall risk of vascular complications after diagnostic cardiac catheterization is 0.5–1.7%, it is significantly increased in patients with peripheral vascular disease.^2,12,14,15 In this pilot registry, we demonstrated a very high rate of safety and efficacy with the use of an extravascular closure device after diagnostic catheterization despite the presence of multiple high-risk features.
Comparison to prior studies. Prior studies of patients with peripheral vascular disease suggest an increased relative risk of vascular complications of 40–89%, with absolute rates of vascular complications of 2.6–8.9%.^12,16–20 Patients with peripheral vascular disease have been excluded from the pivotal VCD trials, thus the role of VCD in patients with high risk is largely undefined. The presence of femoral artery calcification, bifurcation sheath insertion, smaller femoral arteries and mild-to-moderate femoral stenosis present a heightened concern for mechanical complications associated with VCDs. For example, the presence of an intra-arterial anchor or suture may be associated with plaque shift and femoral compromise requiring urgent surgery due to limb ischemia.²¹
On the other hand, there is a theoretical benefit to extravascular closure methods in such high-risk situations as a mechanism for avoiding plaque shift. To date, one extravascular closure device has been studied among patients with high-risk anatomy; in a single-center registry of 45 patients receiving the Angiolink staple-mediated closure device (Medtronic, Inc., Minneapolis, Minnesota), success and complications looked promising.¹⁷ Our results are consistent with this prior study and suggest that extravascular closure with a clip-based device may be especially promising among patients with high-risk features. Alternative strategies for management of high-risk femoral anatomy require further study. For example, it is possible that a low rate of complications and successful early ambulation could also be achieved with an alternative strategy utilizing smaller (4 or 5 Fr) catheters in conjunction with relatively brief manual compression.²²
Caution is required in extrapolating the Starclose results to all extravascular closure devices; prior experience with an extravascular delayed closure device (Vasoseal, Datascope Corp., Mahwah, New Jersey) has been associated with an increased risk of vascular complications compared to manual compression.2 Furthermore, we note that our study required fluoroscopic identification of landmarks for access: the use of any vascular closure device is likely to be safest when access has been successfully attained in the common femoral artery. Thus, meticulous technique and attention to fluoroscopic markers of the ideal “landing zone” are required regardless of closure device utilization.^8–10
VCD and early ambulation. Unlike, the CLIP study (which left ambulation time to the discretion of the operators),⁵ all study patients were encouraged to ambulate 20 feet 1 hour after initial hemostasis. Patients in this high-risk registry had significantly shorter times to ambulation than patients in the randomized CLIP trial. This difference is due to our protocol-based goal of early ambulation (within 60 minutes) after successful closure. Despite high-risk features, extravascular closure with the Starclose device allowed greater than 90% of patients to ambulate < 90 minutes after their closure device insertion. Thus, there was a significant improvement in time to discharge when compared to the diagnostic arm of the CLIP trial. It is of practical interest, however, that two-thirds of our study patients did not actually want to ambulate in the first 60 minutes after completing their procedure. Thus, while theoretically beneficial to have patients ambulate immediately after an invasive procedure, it may be more practical to emphasize the achievement of 90-minute ambulation times to be consistent with patient preferences.
Study limitations. Our study is limited by its single-arm registry design and cannot comment on the relative efficacy of manual compression or other closure devices in patients with a high risk for vascular complications. This study was not powered as a noninferiority trial compared to historic controls, and definitive statements regarding device safety in high-risk populations would require larger, multicenter, randomized trials. Our results are promising given the historical rate of vascular complications in these higher-risk patients.
We note that enrollment was challenging due to the strict inclusion criteria (only 16% of accepted patients were actually enrolled in the registry). Based upon the results of this current registry, enhanced enrollment of even higher-risk patients (those with full anticoagulation undergoing percutaneous coronary intervention or peripheral vascular intervention) may allow a larger patient population to be studied and compared to alternative strategies.

Conclusions

The results of this prospective registry study suggest that the Starclose VCD is safe and effective for arteriotomy closure after diagnostic catheterization in high-risk patient subsets with an increased risk of bleeding or non-ideal common femoral artery anatomy. Further multicenter study is warranted to definitively determine the broad applicability and safety of this extravascular closure device in patients at high risk for vascular complications.

References

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