Helex Septal Occluder for Closure of Atrial Septal ...

Helex Septal Occluder for Closure of Atrial Septal Defects Larry A. Latson, MD,* Evan M. Zahn, MD,† and Neil Wilson, MD‡

Address * Department of Pediatric Cardiology – M41, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. E-mail: [email protected] † Miami Children’s Hospital, 3200 SW 60th Court, #104, Miami, FL 33155, USA. ‡ Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ, Scotland. Current Interventional Cardiology Reports 2000, 2:268–273 Current Science Inc. ISSN 1523–3839 Copyright © 2000 by Current Science Inc.

The HELEX Septal Occluder (W.L. Gore and Associates, Flagstaff, AZ) is a new device with many desirable characteristics. These include direct placement of the delivery catheter across the septal defect without the need for a long sheath; rounded, flexible and atraumatic shape; easy deployment while maintaining the ability to withdraw the device back into the delivery system at any time prior to release; safety cord to allow for removal of the device even after release from the formed elements of the delivery system; and highly biocompatible expanded polytetrafluoroethylene (ePTFE) covering. The design of the device has been thoroughly tested by computer modeling, in vitro testing, and in vivo evaluations in an animal model of atrial septal defect (ASD). Early human experience in Europe for ASD and patent foramen ovale (PFO) indications has been encouraging. Food and Drug Administration (FDA) trials in the United States are anticipated this year.

Introduction There has been a remarkable evolution of devices for transcatheter ASD and PFO closure since the early 1980s [1••,2]. As experience has been gained with a number of devices, certain characteristics are becoming recognized as desirable features [3]. From the standpoint of the implanting physician the device should be forgiving of errors. In this respect, perhaps the most important feature is the ability to get a partially (or fully) deployed device out of the patient easily if the size or position is not acceptable. A device that can be completely released from any rigid portions of the delivery system and yet be tethered temporarily so that it will still be under control if it should embolize adds significantly to the safety of the procedure and the comfort level of the physician. Ease and speed of the procedure are also important. From the patient’s standpoint, the

ideal device should be minimally thrombogenic, relatively atraumatic, and pose no risk of late erosion or penetration of any vascular walls. In general, this suggests that the device be relatively flexible and probably rounded in shape. The structure of the device should provide support spread over the largest area possible. This constraint favors devices that are supported around the circumference of the occluding membrane rather than by arms that radiate from the center to a small number of points around the circumference. Because these devices are life-long implants, they should be composed of materials that are thoroughly biocompatible. A new device, the HELEX Septal Occluder, embodies these characteristics more fully than other devices that have been used to date. The HELEX device is new enough that little has been published or presented about the device. Detailed publications are in preparation, but summary data from the authors’ experiences are presented in this article.

Device Description The HELEX Septal Occluder is composed of a single length of 0.012-in diameter nitinol wire covered by an ultra thin membrane of expanded ePTFE (Fig. 1). In its final occlusive configuration in the body, the device forms two round, flexible disks that straddle the atrial septum. For delivery, the flexible frame is elongated around a central mandrel and pulled into a 9F catheter, which can be manipulated directly across the ASD or PFO. All of the device except for the central locking mechanism is covered by ePTFE membrane so only a small amount of nitinol wire is uncovered in the vascular system. The nitinol is specially processed to reduce nickel leaching. The ePTFE has been specially formulated with a microporous structure to allow for cellular ingrowth.

Device Delivery Because of the flexibility of the materials, the HELEX Septal Occluder is designed to be delivered through a specially designed delivery catheter without the need for a long transseptal sheath. The occluder is packaged with the HELEX in its final occlusive (relaxed) configuration preattached to the delivery system components (Fig. 2). For delivery, the central mandrel around which the device forms itself is extended in a stepwise fashion to elongate the frame and the device is pulled into the delivery cathe-

Helex Septal Occluder for Closure of Atrial Septal Defects • Latson et al.

Figure 1. Shows the smallest (15 mm) and largest (30 mm) HELEX devices in their final configuration but still attached to the delivery catheter. The device in the bottom right has been partially withdrawn into the delivery catheter. The device can be seen to have a helical configuration around the central mandrel. The mandrel can be further extended to elongate the device and allow withdrawal into the delivery catheter. The middle eyelet, which separates the left and right atrial disks of the device, can be seen.

ter. The catheter has a standard NIH-type curve with an atraumatic radiopaque tip. After the system is thoroughly flushed, the catheter is inserted through a standard 9F short sheath in the femoral vein and advanced directly across the septal defect. The device can also be delivered through a long transseptal sheath, but direct delivery reduces the procedure time and eliminates the possibility of embolization of small amounts of air that have plagued devices requiring a long delivery sheath. With the catheter tip in the left atrium, deployment is achieved by repeatedly advancing the device a small distance out of the tip of the delivery catheter via the “frame control catheter” and then pulling back slightly on the mandrel to allow the frame to configure itself. When the left atrial portion of the device has been completely deployed, a center eyelet is easily seen at the end of the catheter and a flat disk is seen in the left atrium (Fig. 3). The entire system is then withdrawn slightly until the left atrial disk contacts the atrial septum. At this point, the device can be seen on fluoroscopy to move with the heart. In addition, the operator can feel the traction on the delivery catheter and the position can be confirmed by transesophageal or transthoracic echocardiography. The device is then held in place against the atrial septum by maintaining the position of the mandrel. The right atrial portion of the device is uncovered by withdrawing the delivery catheter toward the inferior vena cava. The frame control catheter is then advanced and the right atrial portion of the device can be seen on fluoroscopy to configure itself into a second flat disk. The position of the device can be reconfirmed by echocardiography. If there are any concerns

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about proper positioning, the device can be withdrawn back into the delivery catheter by repeatedly extending the mandrel a small distance and withdrawing the frame control catheter as was done in the initial loading of the device into the delivery catheter outside of the patient. When it is determined that both sides of the device are in the appropriate position, the device can be released from the formed components of the delivery system. The delivery catheter is re-advanced to the device to hold it in place. The red safety cap at the end of the catheter is then removed to allow for slack in the safety cord, which remains looped through the device after the other portions of the delivery system have been detached. The mandrel is then withdrawn completely out of the delivery system. This action releases the final curved portion of the wire frame that locks the two disks firmly into their final configuration (Fig. 4). The delivery system can then be withdrawn slightly so that the device is completely free except for the safety cord. At this point, the device can be thoroughly evaluated in its final configuration with no tension on the atrial septum for correct positioning and evaluation of the size of any residual leak. If the device is felt to be in an acceptable position, the guide catheter is held against the device and the frame control catheter is carefully withdrawn, making sure that the free end of the safety cord at the end of the catheter is moving easily. When the frame control catheter is fully removed, the device is completely free of any attachments. Prior to removal of the safety cord, the device can be retrieved by refastening the free end of the safety cord with the red cap and then pulling the frame control catheter. This pulls the device back into the delivery catheter. If retrieval is performed with the safety cord after the lock has been released, the retrieved device will, unfortunately, not be normally configured. The operator can see and feel the membrane pull off of the lock and the membrane is “unzipped” or unlocked from its normal threaded position on the central portion of the wire. Thus, the final fail-safe mechanism does provide protection from embolization and the opportunity to remove the device if it is suboptimally oriented after release from the formed elements of the delivery system, but the device becomes no longer usable if it must be retrieved at this point.

Preclinical Testing Component materials testing The design and materials of the HELEX device were tested extensively prior to initial human implantations [4••]. In the design phase of the study, computer modeling was used to insure that there would be little or no risk of fracture of the support wire of the device. Finite element analysis was used to determine the maximal stress that would be expected under physiologic conditions with the final configuration of the device. Fatigue testing was then performed on the nitinol wire for over 2.1 billion cycles, to be certain that when the wire was exposed to the maximal expected

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Pediatric Interventional Cardiology Figure 2. Details of the HELEX delivery system. The HELEX is packaged pre-attached to the delivery system as illustrated. The device is withdrawn into the (black) delivery catheter by advancing the mandrel in a stepwise fashion to elongate the device and pulling on the (gray) control catheter. The control catheter is attached to the proximal eyelet of the device by the safety or retrieval cord and is used to advance or withdraw the wire frame during deployment. The distal end of the safety cord is attached to the distal end of the control catheter and the cord is threaded through the proximal eyelet, then through the lumen of the control catheter. The proximal end of the safety cord exits the control catheter and is held tightly by the red safety cap until time for release of the device.

Figure 3. Fluoroscopic view of delivery of the HELEX device in a dog model. The left atrial (LA) disk has been fully deployed and has formed itself into a flat disk in the left atrium. The system has been withdrawn so that the LA disk is against the septal wall. The central, or middle, eyelet can be readily seen fluoroscopically and demarcates the left atrial and right atrial portions of the HELEX device.

stresses it would not fracture. In addition, intact devices were installed in a tester, which exposed intact devices to over 400 million cycles of differential pressure between the two sides. These tests confirmed that no device fractures occurred under expected physiologic conditions.

Figure 4. Fluoroscopic view of the completely deployed HELEX device in a dog model. A transesophageal echo probe is seen (far right). The wire frames of the left atrial (LA) and right atrial (RA) disks are configured into their desired shape and are in relatively parallel planes. The central wire latch can be seen threaded through the middle and right atrial eyelet.

Concern has been raised about the possibility of leaching of small amounts of nickel from nitinol-based devices. Although only the eyelets and locking loop of the nitinol wire frame of the HELEX device are exposed to the vascular system (the remainder of the nitinol wire is completely covered by ePTFE), tissue-leaching studies were performed. These confirmed that the amount of nickel leached from the nitinol wire used in this device is essentially equal to


the levels of detectable nickel present as background in the animals’ normal tissue. In most human applications, ePTFE is considered to be the best tolerated synthetic material for intravascular conduits and patches. The formulation of ePTFE used in this device was designed to have a pore size that would allow for ingrowth of normal cellular components. Initial testing of the material was performed by sewing patches of the material to the atrial wall of dogs. Histologic evaluations confirmed that like more commonly used forms of ePTFE, the material used in the HELEX device causes a bland tissue reaction. The material is relatively rapidly covered by a layer of fibrous connective tissue, and the fibrous connective tissue is covered by endothelial-like cells [4••].

Acute animal testing Initial in vivo tests were performed in a dog model of ASD created by using a 10-mm hole punch pushed through the atrial septum from the left atrial appendage in a closed heart operation [5••]. During the early portions of the animal studies, numerous minor modifications were made to the delivery system in order to improve its performance and safety characteristics. Some of these modifications included changing the size and material of the delivery catheter, changing the material of the mandrel, and changing the manufacturing and sterilization processes to insure consistent performance of the delivery system. In addition, the safety features of the device were evaluated and were found to perform as expected. Devices were partially deployed and then withdrawn back into the delivery catheter numerous times. The safety cord feature of the device was finalized and shown to be capable of reliably removing the device if desired. In addition, numerous devices were allowed to embolize intentionally to the left and right side of the heart or were removed from the normal position on the atrial septum with a snare catheter after complete release from the safety cord. It was also found that the device would move through the heart with no apparent trauma because of its flexibility and rounded shape. It was found to be relatively easy to snare a portion of the device with a standard gooseneck snare and pull it into a long sheath. Often the device could be pulled into a 9F sheath, but in some instances, a 10F sheath would have allowed easier retrieval.

Chronic animal studies A total of 24 animals underwent placement of devices under sterile conditions for long-term safety, efficacy, and biocompatibility studies [6]. After implantation, all animals were observed for any unusual symptoms by veterin a r i a n s. Tr a n s e s o p h a g e a l e c h o c a r d i o g r a m s a n d fluoroscopic evaluations were performed at 24 hours, 2 weeks, 1 month, and then every other month until the time of sacrifice at 30 to 45, 90, or 180 days post-implant.

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Immediately prior to retrieval of the devices for gross and histologic evaluations, extensive testing of device efficacy was performed on each animal. Transesophageal echocardiography was used to evaluate for leaks by color Doppler. Right atrial angiography and contrast echocardiography were performed to further test for any evidence of right-toleft shunting (Fig. 5). A left thoracotomy was then performed and a catheter was inserted directly into the left atrium. Angiography and epicardial left atrial contrast echocardiography were performed to evaluate for residual left-to-right shunting. The hearts and lungs were then removed en block. The lungs, brain, and kidneys were removed and evaluated grossly and by light microscopy for evidence of thromboemboli and tissue infarction. The hearts were perfusion-fixed to allow for better assessment of the spatial relationships of the device in the fluid-filled configuration of the heart. Although the shape of the atrial septum in the dog is somewhat different from the shape of the septum in humans, this animal model provides a good method of evaluating histologic response and provides an initial evaluation of the likely efficacy of the device. Of the 24 animals used for chronic studies, only one had evidence of any residual leak by the most sensitive evaluation methods (left atrial contrast echocardiography and angiography). One animal died 4 days after device implantation but was found to have bacterial pneumonia with no evidence of infection around or related to the device. No animals were found to have gross or microscopic evidence of thromboembolic lesions in the brain, lungs, or kidneys. No animal had any clinical evidence of arrhythmias. On gross evaluation, all devices were adherent to the atrial septum or atrial wall at points of contact by 30 days post-implantation. Larger devices were not completely flat against portions of the atrial septum because they abutted the coronary sinus, crista terminalis, or the walls of the atrium. Even in animals with overly large devices, there was no evidence of erosions or effusion. Smaller devices had a very low profile with excellent apposition to the atrial septum (Fig. 6). Microscopic evaluations showed nearly complete coverage of the material of the devices by a layer of fibrous connective tissue within 45 days post-implantation. The atrial chamber surface of the layer of fibrous connective tissue was multifocally to locally extensively covered by a layer of spindloid endothelial-like cells beginning at 30 days post-implantation. There was no inflammatory response to the materials of the device at any of the time frames. Regions of the devices that were not flat against the atrial septum (areas not in contact with the septum), were covered by the same layer of fibrous connective tissue and endothelial-like cells as the regions that were in contact with the atrial septum. Final microscopic evaluations of the devices implanted for 1 year are pending. The gross appearance of these devices was similar to those at 6 months with continued maturation of the covering tissue layer.

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were felt to be secondary to embolization of small air bubbles that occurred when the delivery catheter was used through a long sheath (because of multiple ASDs). This incident emphasizes the advantage of the normal delivery process for the HELEX, which does not require a long sheath. Most of the patients with ASD had trivial residual leaks immediately after implantation but only one patient with PFO had a leak detected in the catheter laboratory. At 1-month follow-up, 24 of 26 patients (93%) had complete echocardiographic closure of their atrial defect and two patients had trivial leaks.

Conclusions

Figure 5. Right atrial (RA) angiogram in a dog model of an atrial septal defect. A transesophageal echo probe can be seen on the far right. An injection has been performed in the low right atrium. There is no angiographic evidence of any right-to-left shunting. LA—left atrial.

Figure 6. View of left atrial side of the HELEX device 90 days after implantation in dog model. The device lies flat on the septal surface with only the distal eyelet protruding. The device is adherent to the septum and covered completely by a thin fibrous connective tissue layer with an endothelial-like covering.

Initial Human Experience Initial human implants have been performed by Dr. Neil Wilson in Glasgow, Scotland, and then by Dr. Horst Sievert in Frankfurt, Germany. As of December 1999, a total of 26 devices were implanted in 28 patients attempted. Nineteen of the patients had an ASD and nine had a PFO and a previous presumed paradoxical embolus. In two patients with ASD, deployment of a HELEX device was attempted but could not be accomplished because of lack of the appropriate sized device or inability to attain a suitable position of the device. The only complications that occurred in the early human experience were one groin hematoma and one incidence of transient ST segment elevation. The ECG changes

Current reviews of the most widely used transcatheter ASD occlusion devices are included in this issue of the journal. All of the devices are designed to fold into a catheter or sheath and then expand to a final occlusive shape. The delivery techniques, materials, and final shapes of the devices vary widely. Reasonable clinical success has been obtained with currently available devices, but problems have also been encountered. Although deaths from transcatheter closure device implantations appear to be rare, some major complications have occurred. These include embolization of all or part of a device, thromboembolic events, creation of atrioventricular block, fractures of supporting structures, perforation of atrial walls or valves, and at least one case of endocarditis [6–8,9••,10,11]. Some devices have relatively complex methods of delivery and others are very straightforward to deliver. Some devices are difficult or impossible to remove after partial or full deployment and others can be removed relatively easily until just before release. Materials for the different devices vary widely and the choice of materials may affect such characteristics as durability and propensity for thrombus formation. The HELEX Septal Occluder is a new transcatheter device used to close ASD and PFO that is just beginning human trials. The device has a number of design characteristics that the authors feel provide significant advantages over currently available devices. The steps required prior to delivery of the device have been minimized. The device is preassembled to the delivery system and the delivery catheter is designed to be placed directly across the septal defect without the need for a long sheath. The device is delivered in a controlled stepwise fashion, and the ability to withdraw the device back into the delivery system after deployment of both left and right atrial portions of the device is maintained. In addition, there is a safety cord to allow for removal of the device even after release from the formed elements of the delivery system. The device is flexible and has a rounded shape to minimize the possibility of trauma to cardiac structures. The use of ePTFE to cover the device enhances confidence in the biocompatibility of the components. Extensive preclinical evaluations have demonstrated the durability and biocompatibility of the basic design. A large number of animal evaluations have contrib-


uted to refinement of the delivery system and confirmation of the safety and efficacy of the device for up to 1 year. Very early human experience has demonstrated the effectiveness of the safety features of the device and has shown complete occlusion of atrial defects in 93% of patients within 1 month with only trivial leaks in the remainder. There are tentative plans to begin FDA-approved trials in the United States this year.

References and Recommended Reading Recently published papers of particular interest are highlighted as: • Of importance •• Of major importance 1.•• Latson LA: Per-catheter ASD closure. Pediatr Cardiol 1998, 19:86–93. Review of the history and early results of various transcatheter ASD occlusion devices. 2. O’Laughlin MP: Catheter closure of secundum atrial septal defects. Tex Heart Inst J 1997, 24:287–292. 3. Latson LA, Kapitan JM, Prieto LR, et al.: Preliminary results of a removable internal frame transcatheter ASD occlusion device. The Second World Congress of Pediatric Cardiology and Cardiac Surgery, Honolulu, Hawaii, May 11–15, 1997. 4.•• Latson LA, Wilson N: A new transcatheter ASD closure device. American College of Cardiology 48th Annual Scientific Session, New Orleans, Louisiana, March 7–10, 1999. Abstract detailing the in vitro and early in vivo results of the HELEX device (termed the GORE Septal Defect Closure Device at the time this abstract was written).

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5.•• Zahn EM, Latson L, Wilson N: In vivo implantation and follow up testing of a new nitinol ePTFE septal occlusion device [abstract]. Cath Cardiovasc Diagn 1999, 47:124. Details the early in vivo evaluations of the HELEX device in a chronic animal model of ASD. 6. Hoepp HW, Deutsh HJ, La Rosee K, et al.: Transcatheter closure of atrial-septal defects and patent foramen ovale in adults: optimal anatomic adaptation of occlusion device. Am Heart J 1999, 138(5 Pt 1):941–949. 7. La Rosee K, Deutsch HJ, Schnabel P, et al.: Thrombus formation after transcatheter closure of atrial septal defect. Am J Cardiol 1991, 84:356–359. 8. Bullock AM, Menahem S, Wilkinson JL: Infective endocarditis on an occluder closing an atrial septal defect. Cardiol Young 1999, 9:65–67. 9.•• Sievert H, Babic UU, Hausdorf G, et al.: Transcatheter closure of atrial septal defect and patent foramen ovale with ASDOS device (a multi-institutional European trial). Am J Cardiol 1998, 82:1405–1413. Review of the experience with the ASDOS device in 200 patients. Particularly worrisome findings noted in this study included thrombus formation in nine patients, cerebral thromboembolism in one patient, late atrial wall perforation in three patients, frame fractures in 14% of patients, and endocarditis in two patients. 10. Hausdorf G, Schneider M, Find C, et al.: Transcatheter closure of atrial septal defects within the oval fossa: medium-term results in children using the “ASDOS” technique. Cardiol Young 1998, 8:462–471. 11. Schenck MH, Sterba R, Foreman CK, et al.: Improvement in noninvasive electrophysiologic findings in children after transcatheter atrial septal defect closure. Am J Cardiol 1995, 76:695–698.