Impact of Gender on Femoral Access Complications Secondary to Application of a Collagen-based Vascular Closure Device

ABSTRACT: Background: Vascular complications at the femoral access site continue to be a significant problem after cardiac catheterization procedures. It was the aim of the present study to assess the impact of gender on the incidence of severe femoral access complications following the application of a collagen-based vascular closure device after transfemoral catheterization procedures. Methods: A total of 1294 consecutive patients (977 male, 317 female) underwent closure of femoral access sites with 8F collagen-based vascular closure devices (Angioseal™) immediately after diagnostic or interventional coronary catheterization procedures, independently of the coagulation status. All patients were closely monitored for the occurrence of complications during the following 24 hours. Results: Between male and female patients, there was no difference in the technical performance of the device with successful deployment being achieved in 96.7% and 95.9%, respectively (p=0.60). Severe access complications were found to be significantly higher in female versus male patients (1.6% vs. 0.2%; Odds ratio 7.7, 95% confidence interval 1.5–40.1; p = 0.015), although similar accomplishment of an immediate hemostasis was seen in 92.8% and 92.4% of male and female patients (p=0.98). Conclusion: Women show a significantly increased risk of developing severe femoral access complications secondary to the application of a collagen-based vascular closure device, although the overall incidence of these complications is relatively low. We speculate that the increased risk in women may be related to smaller arterial dimensions, which could be evaluated by femoral angiography prior to deployment of a closure device. J INVAS CARDIOL 2004;16:247–250 Keywords: vascular access complications,catheterization, closure device, femoral, bleeding, female, gender Vascular complications at the femoral access site continue to be a significant problem after cardiac catheterization procedures.^1,2 Previous studies identified procedural and patient-related predictors of local vascular complications, such as the size of the introducer sheath and the intensity and duration of anticoagulant or antiplatelet therapy during and after the procedure.³ Patient-related risk factors include advanced age, presence of peripheral vascular disease, and marked obesity;^3,4 few studies also suggested an increased risk of access complications in women.^4,5 Recently, a variety of suture-based and collagen-based vascular closure devices has been introduced to facilitate management of the femoral access site, to achieve an earlier ambulation and discharge, and to reduce access site complications;^1–3 it remains, however, controversial whether the use of closure devices actually reduces the incidence of local vascular complications. The Angio-Seal™ (St. Jude Medical Inc., St. Paul, Minn.) vascular closure device is a well-established closure device, which uses an intravascular biodegradable anchor and an extra-arterial resorbable collagen plug to achieve local hemostasis after transfemoral catheterization procedures.⁶ In the present analysis, we evaluated the impact of male and female gender on the occurrence of vascular access complications secondary to the application of the Angio-Seal vascular closure device in patients undergoing both, diagnostic and therapeutic cardiac catheterization procedures. Patients and Methods Patient population. All patients scheduled between January 1 and October 31, 2000, for diagnostic cardiac catheterization, percutaneous coronary intervention, or 6-month control angiography (at that time routinely performed following percutaneous coronary intervention) in our cardiac catheterization laboratory were eligible for the study. Patients were included, if written informed consent was obtained prior to the procedure, and they fulfilled the following inclusion criteria: (1) age > 18 years; (2) no severe peripheral vascular disease; (3) no known allergy to bovine products or reabsorbable suture material; (4) no glycoprotein (GP) IIb/IIIa inhibitor therapy; and (5) no development of a large groin hematoma before the end of the procedure. Catheterization protocol. All patients received oral aspirin >= 100mg/d (or 500 mg intravenously in the absence of pre-treatment). In all patients, the Judkins technique via the femoral artery was used. Attention was given to obtaining arterial access with a single puncture of the anterior wall of the femoral artery. Immediately after introduction of a standard arterial sheath of 8 French in diameter and a length of 11 cm (Avanti Introducer, Cordis, Roden, NL), each patient received 50 IU of heparin per kilogram body weight intraarterially for diagnostic procedures. At the time of the study, 8 French arterial sheaths were routinely used in our department as patients are usually referred to our center (tertiary referral center) for planned complex coronary interventions. For coronary angioplasty or extended diagnostic procedures including intravascular ultrasound or Doppler examination, additional 50 IU of heparin per kilogram bodyweight were administered. Immediately after the procedure, the arterial sheath was removed with the patient still on the catheterization table, independently of the coagulation status. An activated clotting time (ACT) was not measured before or after deployment of the closure device. Device description and application technique. The closure device (8 French Angio-Seal™, St. Jude Medical Inc., St. Paul, Minn.) and its application technique have been previously described in detail.6 Before deployment, after the catheterization was finished, repeat sterilization of the puncture site was applied to strictly ensure sterile deployment. The procedure sheath was replaced with a locator system to precisely position the locator sheath within the lumen of the femoral artery. The device insertion system was introduced through the locator sheath, and the anchor was placed against the inner arterial wall. By retraction of the whole application system, anchor and collagen sponge were drawn together, sandwiching the arteriotomy. Finally, the collagen sponge was tamped onto the outer arterial wall to secure the seal. A metallic spring maintained controlled tension and was the taken off in the absence of oozing of blood. No femoral angiogram was performed prior to the deployment of the device. Study endpoint and definitions. The primary endpoint was the incidence of severe complications related to the femoral access site during the in-hospital period. Severe complications were defined as complications with obvious clinical sequelae for the patient: (1) any vascular surgery; (2) peripheral interventional procedures; (3) ultrasound-guided compression (e.g., for pseudoaneurysm); (4) major bleeding; (5) hematoma requiring transfusion or further treatment (e.g., surgery); (6) retroperitoneal hematoma; (7) thrombosis or loss of distal pulses; (8) groin infections requiring intravenous antibiotics; and (9) death related to access site complications. Technical success was defined as successful deployment of the device. Immediate hemostasis was achieved by the absence of bleeding immediately after application of the closure device. Data management. Patient characteristics and details of the catheterization procedure and placement of the closure device were recorded using a standardized protocol, which was filled in by the operator immediately after the procedure. All patients were closely monitored for 24 hours after the procedure. The puncture site was assessed by a physician on the next morning for the following criteria: (1) need for additional manual compression/application of pressure bandages; (2) evidence of active bleeding or infection; (3) hematoma; (4) presence of a bruit or a pulsatile mass; and (5) post deployment pain. In addition, the time to ambulation was recorded. The results of a clinical examination 24 hours after the procedure were also documented on the protocol of each individual patient. Statistical analysis. Comparisons between continuous variables were performed using univariate ANOVA. Comparisons between categorical variables were based on X2 – analysis or Fisher’s exact test. A backward logistic regression model was used, including age, gender, body mass index, type of procedure, duration of procedure, and amount of heparin to test their respective effects on the incidence of complications. All statistical analyses were performed using the SPSS software package (version 10.0, SPSS, Chicago, Ill.). P-values Patient demographics and procedural data. A total of 1294 consecutive patients were analyzed; there were 977 male and 317 female patients. Females were smaller and had a lower body weight than men (Table 1). There was a trend towards higher percentage of diagnostic catheterization procedures in females than in men. Due to the higher body weight, male patients received on average more heparin (8,089 ± 2,398 IU vs. 7,708 ± 2,434 IU; p = 0.015; Table 1). Device performance. Technically successful deployment of the closure device was achieved in 95.8% of all patients, without a significant difference between gender groups (p = 0.603; Table 2). The rate of immediate hemostasis was comparable for both groups (92.8% vs. 92.4%; p = 0.979). Complications. Overall, there were only 7 severe access complications (0.5%) in the total of 1,294 patients: 4 patients suffered from symptomatic stenoses of the femoral artery and had to undergo vascular surgery to relieve limb ischemia; 1 patient required surgical repair of a pseudoaneurysm; 1 patient had a pseudoaneurysm that was successfully treated by ultrasound-guided compression therapy; and 1 patient suffered from a major bleeding and required blood transfusion. The incidence of severe access complications was significantly higher in female than in male patients (1.6% vs. 0.2%; p = 0.015); femoral artery stenoses tended to be more frequent in women {3/317 (0.9%) vs. 1/977 (0.1%); p = 0.077}. All severe complications occurred after coronary interventions. The logistic regression model yielded a 7-fold increased risk for severe access complications for female patients (OR = 7.7; 95% CI 1.5–40.1). Gender was the single remaining variable in the backward selection process, indicating that all other variables had no significant impact on the risk of severe access complications. Discussion The present study suggests that women are at an increased risk of developing severe assess complications secondary to the application of a collagen-based vascular closure device after transfemoral cardiac catheterization procedures, although the overall incidence of severe complications is quite low. So far, manual or mechanical compression with subsequent application of pressure bandages still remains the standard technique for access site management after cardiac catheterization.⁷ Previous studies identified procedural and patient-related predictors of increased femoral access complications following compression therapy; these include severity of anticoagulation and antiplatelet therapy, introducer sheath size, presence of peripheral vascular disease, marked obesity, and female gender.^3–5 So far, there are no studies reporting on predictors of access complications following the use of vascular closure devices, although the mechanisms of achieving local hemostasis obviously differs significantly from traditional compression techniques. In addition, the use of the Angio-Seal collagen-based closure device bears the risk of specific complications that have been observed to occur besides those vascular complications seen also after conventional treatment of the femoral access site.6 These specific complications mainly relate to femoral artery stenoses or occlusions with subsequent claudication or severe limb-ischemia, but may also rarely include local infections which are — once occurred — difficult to treat. Femoral artery obstruction is usually believed to be due to inadvertent intra-arterial placement of the collagen plug, but also cases of anchor migration have been reported.6 In the present study, symptomatic femoral artery stenoses account for 4 of the 7 severe access complications; in all patients, surgical repair had to be performed to relieve limb ischemia. Three of these femoral artery stenoses occurred in women and 1 in a male patient. Schnyder et al.⁷ recently demonstrated that the mean diameter of the common femoral artery (CFA), as assessed by quantitative femoral angiography, is lower in women compared to men (6.0 ± 1.0 mm vs. 7.5 ± 1.2 mm; p 7 Puncture below the bifurcation of the CFA may in turn increase the risk of sheath-related traumatic vessel injury with subsequent development of pseudoaneurysm or arteriovenous fistula, and excessive bleeding.⁷ Since both superficial femoral artery and profunda femoral artery have a smaller diameter than the CFA,⁷ the likelihood of severe luminal obstruction by a closure device component is markedly increased. Schnyder et al.⁷ showed that the length of the CFA is significantly shorter in women compared to men (37.9 ± 12.7 mm vs. 46 ± 17.2 mm; p = 0.0001), which may thus increase the risk of puncturing a femoral vessel other than the CFA with increased risk of subsequent complications, as outlined above. Recently, femoral angiography has been strongly recommended to evaluate femoral anatomy and potential peripheral arterial disease at the puncture site prior to the deployment of a closure device.⁷ In the present study, however, we did not obtain femoral angiograms. The use of femoral angiography may have avoided placement of the closure device in patients with small femoral arteries or inadvertent puncture below the CFA bifurcation and may thus have avoided some of the severe complications observed. However, the total incidence of complications (0.5%) in the present study was lower than in previous studies.^1,8,9 But any comparison with complication rates of other centers is hampered by the fact that — in this context — a generally accepted definition of vascular complications has not been established yet.¹⁰ In addition, the classification of bleeding severity and measurements of hematoma size may still be a matter of substantial bias.¹¹ In the present study, we therefore focused on severe femoral access complications with obvious significant clinical sequelae for the patient, while minor complications (e.g., minor bleedings or hematomas) were not tabulated. Study limitations. Although the present study is one of the largest series, so far, it is limited by the only small number of severe complications. The study was designed as a prospective registry, thereby lacking a control group of patients treated by manual compression. We did not perform routine color-coded Doppler ultrasound examinations to detect minor vascular injury; the incidence of asymptomatic arteriovenous fistulas or pseudoaneurysms may thus have been underreported. We used 8 French arterial sheaths in all patients while today the majority of catheterization procedures is performed using smaller sized sheaths (e.g. 6 French). However, we believe that the majority of the observed complications were related to the use of the closure device (e.g., femoral artery stenosis) rather than to the arterial sheath and may have also occurred despite the use of smaller sized sheaths. All patients were treated with the closure device immediately after conclusion of the catheterization procedure irrespective of the coagulation status; therefore (and in the absence of clinical consequences), measurements of the activated clotting time were not performed. Femoral angiograms were not obtained prior to device placement, but may have avoided placement of the closure device. Clinical implications. The present study suggests that female gender is a risk factor for access complications following application of a collagen-based vascular closure device after cardiac catheterization procedures. The likelihood of symptomatic lumen obstruction by a closure device component may be increased in women because of the smaller arterial dimensions (compared to men). Femoral angiography may be particularly useful in women to evaluate their arterial anatomy prior to closure device deployment in order to avoid complications. Close surveillance after the use of a closure device is mandatory.