Article Text
Abstract
Background Angioseal, an arteriotomy closure device (ACD), functions as a collagen plug that physically closes arteriotomy sites and can simultaneously induce platelet activation and aggregation. When used ‘on-label’, the safety and efficacy profile of Angioseal is superior compared with those of other ACDs. However, Angioseal is sometimes deployed in less than ideal situations. Therefore, we sought to assess the safety and efficacy of ‘off-label’ Angioseal use in patients undergoing femoral arteriotomies.
Methods We performed a retrospective review of all femoral arterial angiograms executed at our institution between 2008 and 2014. Patients whose femoral punctures did not fit the criteria for on-label Angioseal use were included, and were dichotomized based on vascular closure (off-label Angioseal vs manual compression).
Results Of the 521 patients (1023 angiograms) reviewed, 303 (58.2%) patients had off-label Angioseal groin punctures. Mean patient age was 46.2±14.0 years, and 113 were men. 234 patients (77%) had off-label Angioseal deployment while 69 (22%) individuals received manual pressure, serving as controls. Demographic and procedural variables were nearly identical between the two groups but the Angioseal group comprised mostly patients that underwent neurointerventional procedures and thus received intraprocedural heparinization (41%) more often than the manual compression group (19%). The overall rate of major complications associated with off-label Angioseal deployment was low (<0.85%), and clinical complications were not independently associated with Angioseal use (OR 0.76 (95% CI 0.06 to 8.86); p=0.69).
Conclusions Off-label use of Angioseal was found to be safe and was not associated with an increased complication rate in our cohort.
- Artery
- Angiography
- Standards
- Technique
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Introduction
Arteriotomy closure devices were first introduced in the 1990s with the aim to decrease time for hemostasis, ambulation times, and patient discomfort.1 There are active and passive vascular closure devices, and Angioseal is an active vascular closure device that employs a collagen plug that not only physically closes the arteriotomy site but also induces platelet activation and aggregation when deployed. Angioseal use is recommended in a femoral artery measuring 5 mm or less in patients over 18 years of age.2 However, its use in arteriotomies at the inferior epigastric level or at the bifurcation, and in arteriotomies on the same side of a previously deployed Angioseal within 90 days, is not advised.3
When following these recommendations, the use of Angioseal has been shown to have a safety and efficacy profile superior to other active vascular closure devices while resulting in decreased time for ambulation and fewer postprocedural complications.4–6 However, when these conditions are not met, manual compression is most often employed to avoid thromboembolic complications.
In everyday practice, Angioseal is sometimes deployed in less than ideal situations in which its use has not been studied and is therefore not recommended. Thus we sought to perform a retrospective review to evaluate the safety and efficacy of Angioseal when used in off-label circumstances.
Methods
We performed a retrospective review of 521 patients (1023 consecutive angiograms) between 2008 and 2014. All patients with available femoral angiograms were evaluated. Every femoral angiography was analyzed for femoral artery diameter at the site of puncture, and the site of puncture: inferior to the bifurcation, at the bifurcation, in the common femoral artery, and at or above the inferior epigastric artery origin (figure 1). The use of femoral artery access for a procedure within 90 days of a prior ipsilateral puncture was recorded. All images were reviewed by an investigator who was blinded to the use of a closure device. Procedures with femoral angiographic runs of suboptimal quality (ie, motion artifact, angles that did not allow interpretation of vascular anatomic landmarks) were excluded.
Groin puncture technique
All procedures were performed by either the neurointerventional attending or a neurointerventional fellow. According to the institutional protocol, groin punctures were performed after femoral artery palpation and fluoroscopic evaluation to confirm the position over the femoral head. When the femoral pulse was impalpable, or if access failed after three sticks on a palpable pulse, ultrasound guidance was used. A micropunture kit was utilized for all angiograms. A 21 g needle was inserted and small amplitude brisk advancements were made to avoid a double wall puncture. Once access is achieved, a microwire is inserted, and fluoroscopy is used to confirm wire placement in the aorta. After confirmation, a microdilator is inserted, and a lymphangiogram tube is connected to the microdilator, at which point an ipsilateral oblique magnified three frames per second run is performed. If the common femoral artery bifurcation and the origin of the inferior epigastric artery are not properly visualized, a run in contralateral oblique is performed. All diagnostic procedures were performed with a 5 F sheath closed by a 6 F Angioseal. All interventional procedures were performed with an 8 F sheath with an 8 F Angioseal.
Inclusion and exclusion criteria
All patients whose femoral punctures did not fit the criteria for on-label Angioseal use were included. These included: (1) diameter of the vessel at the level of the puncture <5 mm; (2) puncture below or at the level of the femoral bifurcation, or puncture at the level or above the inferior epigastric artery origin; (3) age <18 years; and (4) punctures performed in individuals within 90 days of prior ipsilateral punctures in which an Angioseal had been used. The included patients had characteristics that would classify them as an off-label Angioseal puncture. These patients where dichotomized into off-label Angioseal use versus manual pressure. Manual pressure cases occasionally had adjunctive use of hemostatic patches or FemoStop (St Jude Medical, Sweden).
The decision to perform manual compression or utilize the Angioseal closure device off-label was made at the discretion of the neurointerventionalist based on perioperative factors (ie, heparin or antiplatelet therapy), patient factors (ie, patient body mass index), and mental status (ie, ability to hold lower extremity still).
Additional procedural variables
Other procedural variables recorded included type of procedure (diagnostic vs intervention), use of double antiplatelet therapy and/or full heparinization or anticoagulation, and lateralization of puncture (right or left). The presence of stenosis at the site of prior Angioseal use, and/or the presence of atherosclerosis on common femoral angiography runs, were noted. Demographic variables were collected, including age and gender.
Complications
Records were reviewed for clinical and radiologic complications. All cases in which CT of the pelvis, CT of the groin, or ultrasound of the groin were performed were noted. The presence of major complications, such as retroperitoneal hematomas, severe acute lower extremity ischemia, as well as minor complications, such as infections, pseudoaneurysms, or severe pain, were also recorded. There were no reported device failures.
Statistical analysis
Continuous variables are reported as mean±SD. Categorical variables are reported as proportions. Between group comparisons for continuous/ordinal variables were made using the Student's t test or Mann–Whitney U, test as appropriate. Categorical variables were compared by χ2 or Fisher exact test, as appropriate. Correlation coefficients were calculated with Spearman or Pearson, as appropriate. Significance was set at p<0.05. Multivariate logistic regression analysis for predictors of SIG was performed for variables at the 0.1 level of significance on univariate analysis, using a variable selection method. This study was approved by the local institutional review board.
Results
Demographic and procedural variables
Of the 521 patients whose angiograms we reviewed (n=1023 consecutive angiograms), 303 (58%) were off-label Angioseal groin punctures and were included in the analysis. Mean age (of the 303 patients) was 46.2±14.0 years and 113 were men. Two hundred and thirty-four (77%) patients had an off-label Angioseal deployed while 69 (22%) individuals received manual pressure, serving as controls.
Comparison of demographic and procedural variables between the two groups is described in table 1. The two groups had similar demographic profiles. The most common puncture site was in the common femoral artery (44%, figure 2A), followed by puncture at the bifurcation (29%, figure 2B), inferior to the bifurcation (17%, figure 2C), and at or above the inferior epigastric artery (10%). The Angioseal group comprised mostly patients that underwent neurointerventional procedures, and thus received intraprocedural therapeutic heparinization more often on univariate analysis. Moreover, punctures at the level of the inferior epigastric artery or higher were more common in the control group.
Complications
The off-label use of Angioseal was not associated with increased complications compared with manual pressure for patients considered to have off-label Angioseal puncture profiles. The overall rate of major complications associated with off-label Angioseal deployment was low (<0.85%) (table 2). Utilization of imaging studies due to the patient's symptomatology was low and not statistically different between groups. When taking into account the variable ‘any complications’ into the multivariate regression model, clinical complications were not found to be independently associated with off-label use of Angioseal (OR 0.76 (95% CI 0.06 to 8.86); p=0.69).
Although there were no significant bleeding complications, two patients suffered complications related to the use of Angioseal. One patient was found to have a femoral artery dissection following a diagnostic angiogram with Angioseal deployment at the level of the bifurcation. A second patient had an infected groin with abscess formation diagnosed and treated on postoperative day (POD) 5 after Angioseal was deployed in a small femoral artery (3.7 mm). Other minor clinical complications encountered were persistent oozing from the groin site after a diagnostic angiogram and pain at the site of Angioseal deployment. Both patients had workup imaging revealing no significant pathology, and both recovered uneventfully. There were no thromboembolic complications recorded.
The first complication was observed after an Angioseal was deployed at the level of the bifurcation for a diagnostic angiogram in a patient in their 60s. A 5 F sheath with a 6 F Angioseal was used. Shortly after the procedure, the patient complained of severe groin pain and pulses were not palpable. A lower extremity ultrasound and abdominopelvic CT angiography was ordered. The ultrasound showed a right external iliac artery high grade occlusion. However, at the time of CT angiography, which showed a small dissection of the posteromedial aspect of the right common femoral artery, the pulse had returned. The dissection was not flow limiting and therefore was managed conservatively. The patient had no clinical signs or symptoms of lower extremity ischemia at the follow-up visit.
The second complication was observed in which the Angioseal had been deployed in a patient after a diagnostic angiogram whose common femoral artery diameter was <3.7 mm. A 5 F sheath with a 6 F Angioseal was used, as above. There were no immediate complications after the procedure. On POD 5, the patient developed pain, swelling, and erythema at the puncture site along with a palpable soft collection. An ultrasound showed a 2.6×1.8 cm collection consistent with an abscess. The patient underwent a bedside incision and drainage, and was placed on antibiotics with resolution of the collection on follow-up imaging.
Other minor complications were encountered in a patient that complained of severe pain at the groin site after a diagnostic angiogram and in a patient that had persistent oozing from the groin site associated with severe unrelenting pain. Workup imaging for both patients was negative and they recovered on POD 1.
Discussion
To our knowledge, this study is the largest retrospective study to examine the safety and efficacy of the off-label use of Angioseal. The main finding of our study is that the use of Angioseal in these conditions is safe and not associated with an increase in complication rates.
Most arteriotomy closure devices decrease time for hemostasis, time for ambulation, and patient discomfort when compared with manual compression. Although many of these devices are available today, not all employ the same mechanism of closure and thus do not share a similar safety and efficacy profile. There are active and passive arteriotomy closure devices available. Active arteriotomy devices are used to mechanically close the arteriotomy site while passive devices serve to augment natural hemostasis at the arteriotomy site. Several mechanisms are available for mechanical closure at the arteriotomy site with arteriotomy closure devices. A collagen plug inserted at the arteriotomy site is used with the Vasoseal, Angioseal, and Duett Pro systems, while suturing of the arteriotomy site can be achieved with Prostar, Perclose, Xsite, and Super stitch.
Our practice is to perform a femoral angiogram using the micropuncture kit to evaluate the location of the puncture site prior to inserting the sheath. If the puncture site does not meet the criteria for the recommended use of Angioseal, then we either pull out the microdilator, hold pressure for 5 min, and restick using the anatomical information from the angiogram; proceed with placement of the sheath followed by Angioseal placement at the culmination of the procedure; or proceed with placement of the sheath followed by manual compression.
Manual compression serves as the standard of care for non-ideal situations, especially with punctures below the bifurcation, and in this study we looked to evaluate Angioseal in those ‘less than ideal’ circumstances. Therefore, it was chosen as a control arm in this study as opposed to on-label Angioseal because it represents the reality of a clinical scenario when puncturing the femoral artery.
Our retrospective look at our experience with the off-label use of Angioseal demonstrates that it maintains a low complication rate (<1%), even in less than ideal circumstances. Despite being used in patients undergoing interventional procedures, where full heparinization is more commonly employed, the off-label use of Angioseal was demonstrated to be safe and effective. However, concerns related to the use of a closure device that leaves an intraluminal (biodegradable) part exist and have not been thoroughly investigated.
Study limitations
Limitations of our study include those that are inherent with a retrospective review, including misclassification of femoral runs secondary to poor femoral runs or views, and that outcome assessments were based on reviews of charts in which documentation, at times, was scarce. Furthermore, as this was a retrospective chart review study without routine screening ultrasound after each procedure, there is a possibility that smaller complications, such as minor groin hematomas not requiring transfusion or minute groin site pain, may have gone unnoticed. Clinical and radiographic notes were carefully reviewed to minimize the chance of overlooked complications, although important limitations to our study are those inherent in retrospective reviews.
Additionally, although our sample was large, the outcomes under review were only a few, and thus we are unable to make absolute statements regarding safety and efficacy. One study examined the off-label use of Angioseal, specifically looking at its use at sites anatomically above and below the common femoral artery. Based on their chart review of 62 included patients, no postoperative or long term complications were reported in the off-label use category.7 Another study looked at the use of the 8 F Angioseal system compared with 9 F and 12 F sheaths, and with their cohort (n=42) there was 100% successful postoperative hemostasis. A complication rate of 4.1%, including one postoperative hematoma and one asymptomatic pseudoaneurysm, was documented.8 Our study, however, is the largest chart review to date in the literature, and has looked at the broadest definition of ‘off-label’ for Angioseal use, and thus our results cannot be compared with data from other centers to support or contradict our findings.
Conclusions
These data suggest that off-label use of Angioseal is safe and is not associated with an increased complication rate. Further study may be warranted to elucidate the safety of off-label Angioseal using larger patient cohorts.
Footnotes
Contributors GP, BMS, SSS, DCH, SS, and IS contributed to the design, data collection, statistical analysis, and drafting of the manuscript. DRY, MSE, and ECP provided manuscript oversight and administrative support. All authors critically reviewed the manuscript and approved its final submission.
Competing interests None declared.
Ethics approval The study was approved by the local institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Available on request.