Acute Evaluation of the Mynx‚Ñ¢ Vascular Closure Device during Arterial Re-Puncture in an Ovine Model

ABSTRACT: Background. The Mynx™ vascular closure device (VCD) (AccessClosure, Inc., Mountain View, California) is used for extravascular closure of the common femoral artery (CFA) after diagnostic or interventional endovascular procedures. Although it is common clinical practice to re-puncture a CFA, for some VCDs, acute repuncture is discouraged, while for other VCDs the safety of direct re-puncture through a previously placed VCD is still in question. The objective of this preclinical study was to evaluate the acute performance of the Mynx device where direct re-puncture has occurred through the hydrogel sealant, followed by delivery of a second Mynx device to close the re-access puncture site. Methods. Two ovine models with a total of 24 punctures (12 sets of puncture and re-puncture) were used for this study. Success was measured utilizing angiographic and observational endpoints. Results. There was no evidence of hydrogel sealant prolapse into the artery, distal embolization of sealant following repuncture, groin site bleeding or hematoma. Successful hemostasis was achieved in all punctures (mean activated clotting time = 357 secs) with the exception of a minor (non-clinically significant) contrast extravasation in the tissue tract, which resolved with 2 minutes of adjunctive compression. Conclusion. Arterial re-puncture in an ovine model directly through a recently placed Mynx closure device and subsequent re-closure with a second Mynx device can be successfully accomplished. J INVASIVE CARDIOL 2009;21:283–285 Patients who have undergone coronary or peripheral endovascular procedures requiring arterial access often require repeat endovascular procedures within days or hours of the first procedure. This scenario may necessitate re-access at the same site of entry, most commonly the femoral artery. One common method of avoiding a re-stick through a recently closed arteriotomy is to obtain arterial access through the contralateral femoral artery. However, this may not be a viable option in some patients due to severe peripheral vascular disease, tortuous anatomy, the existence of prior closure devices or other disqualifying issues. In cases where a vascular closure device (VCD) has been used in the first procedure, re-access at the same site is often considered dangerous due to the potential for closure device embolization, displacement, bleeding or other post-procedural complications. The Mynx™ VCD (AccessClosure, Inc., Mountain View, California) consists of a delivery catheter with an intravascular balloon component and a coaxial delivery cartridge with a synthetic, non-coagulative, polyethylene glycol (PEG) hydrogel sealant loaded at the tip. The extravascular deployment of hydrogel sealant is designed to immediately seal the arteriotomy and rapidly expand in the tissue tract promoting hemostasis. The hydrogel is subsequently reabsorbed within 30 days of implantation. The primary objective of this animal study was to assess the acute safety and effectiveness of the Mynx device where acute re-puncture and re-access and ultimately repeat closure has occurred through the hydrogel sealant of a previously deployed Mynx device. The criteria for acute safety and effectiveness were determined by angiographic endpoints obtained after the second Mynx device was deployed, as well as direct observation of the groin site. Success was measured by: 1) angiographic assessment of hemostasis at the access site demonstrating lack of contrast extravasation post Mynx deployment; 2) lack of hydrogel prolapse into the artery; 3) assessment of the angiographic patency of the vasculature distal to and at the site of vascular access; 4) the absence of angiographic evidence for intravascular hydrogel or distal embolization of sealant after repuncture; and 5) visualized bleeding or hematoma at the groin site post Mynx deployment. Materials and Methods The animal protocol was designed by the investigators under an animal research proposal approved by the Institutional Animal Care and Use Committee. The study was performed in accordance with the standard operating procedures (SOPs) of the animal lab (LyChron, LLC, Mountain View, California). Two male ovine (Suffolk sheep), obtained from certified vendors identified by the test facility and weighing over 100 kg, were utilized for this study. The animals were euthanized per laboratory protocol at the end of the study. The following exclusion criteria were included to ensure that the vessel selection and closure procedures closely mimicked the current human clinical practice: vessel diameter 120 mmHg, presence of thrombus at the treatment site. The animals were medicated beginning 48 hours preprocedure with daily aspirin 325 mg. The animals fasted 12 hours prior to the procedure and were sedated, prepared and anesthetized according to the animal lab SOP. The baseline ACT was measured and heparin was administered during the procedure to achieve and maintain an ACT between 250 – 450 seconds. The MAP was maintained as needed with vasodilators and vasopressors (lactated ringer solution, phenylephrine and/or dobutamine) between approximately 80 and 120 mmHg at the time of the Mynx deployment. Papaverine and/or nitroglycerine were administered if angiographic evidence for vasospasm was identified. For each puncture set, single-wall arterial vascular access was performed using a Seldinger technique. For subsequent sets on the ipsilateral side, intra-arterial access was obtained distal to the previous puncture site. The operator collected depth and angulation measurements in order to facilitate through-and-through re-puncture. A total of 6 punctures (3 sets of puncture and re-puncture) were performed at each groin site, for a total of 24 punctures (12 sets) in both ovine models. A 6 Fr Cordis sheath (Cordis Corp., Miami Lakes, Florida) was used for each access. Using standard interventional technique, a 6 Fr guide catheter was placed from the contralateral leg as required to perform baseline angiographic assessments of the ipsilateral leg (Figure 1). Each femoral access site was closed utilizing the Mynx device per the procedural steps in the instructions for use. The time of sheath insertion and initial Mynx deployment was recorded. Direct visualization of the groin site was completed to assess for bleeding or hematoma. A minimum of 30 minutes elapsed prior to performing the re-puncture. Angiography was performed prior to re-puncture to assess hemostasis at the puncture site (Figure 2). Utilizing a roadmap angiogram, a skin staple placed at the site of initial puncture and depth and angulation measurements as guiding tools, arterial re-access and sheath insertion were targeted and obtained through the previously deployed Mynx sealant. Angiography at the groin site and angiography of distal runoff was performed to confirm hemostasis, lack of sealant prolapse and lack of distal sealant embolization (Figure 3). The access site was then re-closed with a Mynx device. Visualization of the groin site was completed to assess for bleeding or hematoma, and angiography was performed to confirm hemostasis (Figure 4). Arterial access and closure were performed by a single operator. Results Two ovine models were utilized for this study. Both were over 100 kg (134 kg and 139 kg). A total of 24 punctures (12 sets of puncture and repuncture) were performed, with 6 punctures (3 sets) at each groin. All 24 insertions were single, anterior wall punctures, with the exception of one that was also a posterior wall stick. This resulted in minor extravasation of contrast posterior to the vessel that resolved with 2 minutes of adjunctive compression. Excluding the posterior wall stick, all punctures and re-punctures were performed successfully and without difficulty. The mean common femoral artery vessel size was 7.39 mm (range 6.4–8.9 mm). Vessels that were measured during arterial spasm were not included in the analysis. Vessel measurements for the last three punctures with the second animal were not documented due to the need for inotropic support (with hypotension, the vessel measured approximately 5 mm). The hemodynamic instability was not related to vascular access, bleeding or any issue directly or indirectly related to the study. The mean ACT was 357 seconds (range 259–426 seconds). The MAP was 105.4 (range 71–116). The time-to re-puncture was measured by the difference in the time of hemostasis of the initial puncture and the time of re-puncture. The result was a mean of 36 minutes (range 28–51 minutes). Successful hemostasis was achieved in all punctures with the exception of a minor (clinically insignificant) contrast extravasation in the tissue tract post Mynx deployment, which occurred in 1 of 24 Mynx deployments (4%) and resolved with 2 minutes of adjunctive compression. A flow disturbance was detected angiographically distal to a single re-puncture, which did not change after repeat closure. At follow-up necropsy, this was found to be a dissection. There was no angiographic evidence of hydrogel sealant prolapse into the artery at the site of puncture/re-puncture in any of the 24 closures. There were no cases of distal embolization of sealant following re-puncture. All punctures were free of visible bleeding or hematoma at the groin site. Protocol deviations that occurred during the procedure included: one back-wall stick, an initial puncture occurring out of sequence before the previous re-puncture, and failure to take vessel measurements of the final three punctures due to hemodynamic instability of the animal. Epinephrine and dopamine were administered in an attempt to stabilize the animal for completion of the study. Discussion The unavoidable need for repeat intra-arterial access at a site of recent puncture is a common circumstance for the endovascular physician. In some cases, fear of device dislodgment, embolization or access site bleeding has led operators to avoid use of a VCD in patients due to a perceived risk of requiring short-term re-puncture. Thus, there is a clinical need for a VCD that allows safe and effective initial arterial closure, re-access and re-closure without distal embolization or device dislodgement, bleeding or other vascular compromise. In this preclinical study using the PEG-based vascular closure device (Mynx) in an ovine model, we have demonstrated that one can safely and effectively use this device for arterial closure and repeat closure after a second sheath placement positioned directly at that initial site. Unlike a collagen-based device, the PEG sealant used in the Mynx device has minimal column strength, thus allowing a Seldinger needle or arterial sheath to pass through the sealant without introducing it into the target artery. Furthermore, the non-inflammatory nature of the PEG sealant allows for placement of two Mynx devices in one anatomic locale without a heightened level of concern for post-deployment inflammatory infiltrate. While this investigation is preclinical in non-atheromatous ovine vessels, proof of concept has been established that should be re-examined in a real-world clinical circumstance. Study limitations. This investigation utilized non-atherosclerotic vessels in a lean ovine model, which may not be characteristic of all patients undergoing repeat endovascular procedures. The ease and effectiveness of re-puncture in a more obese human population as well as patients with a wider range of hemodynamic circumstances is unknown. The acute nature of the study did not allow for other potential factors, such as increased risk of infection, which can be associated with chronic human conditions and recurrent procedures. A total of 24 punctures (12 sets of puncture and re-puncture) were performed. Although efforts were made to re-puncture directly through the previously placed Mynx device, an exact re-puncture may not have occurred on each set. This was a single-arm study utilizing the Mynx device without randomization or the use of a control. Future clinical studies among multiple investigators and devices would provide more data in regard to the safety and efficacy of the Mynx device compared to other VCDs in real-world clinical setting. In this preclinical study in an ovine model, arterial re-puncture directly through a recently placed hydrogel-based closure device and subsequent re-closure with a second such device can be accomplished without sealant prolapse or embolization, angiographic bleeding or visible hematoma. These findings require confirmation in a clinical study. Conclusions In this preclinical study in an ovine model, arterial re-puncture directly through a recently placed hydrogel-based closure device, and subsequent re-closure with a second such device can be accomplished without sealant prolapse or embolization, angiographic bleeding or visible hematoma. These findings require confirmation in a clinical study. ____________________________ From the *Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, §Access Closure, Inc, Mountain View, California, and the £Division of Cardiology University of Florida, Gainesville, Florida. Disclosures: Dr. Garasic is a consultant for and has an equity interest in Access Closure, Inc. Ms. Marin is an employee of Access Closure, Inc. Dr. Anderson has no conflict of interest to declare. Manuscript submitted December 2, 2008, provisional acceptance given December 30, 2008, final version accepted February 9, 2009. Address for correspondence: Joseph M. Garasic, MD, Division of Cardiology, Massachusetts General Hospital, 55 Fruit Street, GRB-8, Boston, MA 02114. E-mail: jgarasic@partners.org

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