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Device Guide

This Device Guide offers a searchable, comprehensive listing of the available interventional cardiology devices in the United States.

The Spectrum of PFO Closure Devices

A closer look at current technology as the indications for PFO closure become clearer.

By Narbeh Melikian, BSc, MB BS, MD, FRCP; and Philip A. MacCarthy, BSc, MB BCh, PhD, FRCP
 

Patent foramen ovale (PFO) is a tunnel-like passage in the interatrial septum formed by failure of postnatal fusion of the septum primum and secundum. Persistent PFO is estimated to occur in approximately 20% to 25% of the adult population. Despite its high prevalence, the clinical significance of a persistent PFO remains an area of intense debate. Over the years, PFO has been implicated in multiple clinical conditions for which closure has been proposed, including cryptogenic stroke,1 migraine,2 decompression sickness,3 platypnea-orthodeoxia syndrome,3 and paradoxical cardiosystemic embolization.3

Nonetheless, the recently published multicenter RESPECT trial, which randomly assigned patients with a proven PFO and ischemic stroke, transient ischemic attack, or systemic thromboembolism to PFO closure or medical therapy, is the only study that has conclusively demonstrated a medium-term clinical benefit from PFO closure.4,5 In 2016, in response to this study, the US Food and Drug Administration (FDA) approved the use of the Amplatzer PFO occluder device (Abbott Vascular) in patients with cryptogenic stroke.

The recent results of the REDUCE and CLOSE clinical trials, presented at the European Stroke Organization Conference, showed positive outcomes using PFO occlude devices in the treatment of PFO. In the REDUCE trial, 664 patients with previous embolic cryptogenic stroke were randomized to PFO closure using Gore & Associates’ septal occluder devices or antiplatelet therapy. Results showed that PFO closures were significantly superior to medical therapy at 3.4 years, had a 76.6% relative risk reduction in recurrent clinical stroke, and a 49.6% relative reduction in silent ischemia via brain imaging. Higher rates of atrial fibrillation were reported in the device closure arm, most of which were periprocedural.6

The CLOSE trial enrolled 663 patients who suffered a recent cryptogenic stroke and had a PFO with either an atrial septal aneurysm or a large shunt. Patients were then randomized into three groups: PFO closure using one of the CE Mark–approved PFO devices in addition to antiplatelet therapy, chronic oral anticoagulation, or chronic antiplatelet therapy. PFO closures with antiplatelet therapy better reduced the risk of recurrent stroke, with an absolute risk reduction of 4.9%, compared with antiplatelet therapy alone. Like REDUCE, the CLOSE trial also reported a significantly higher incidence of atrial fibrillation.7 For more detailed coverage of the REDUCE and CLOSE data, please see page 26.

There are currently multiple commercially available PFO occluders with different design features.

SELF-EXPANDING DOUBLE-DISC PFO OCCLUDERS

Self-expanding double-disc PFO occluders make up the bulk of the clinically used PFO occluders and utilize a simple common principle to close a PFO. They consist of two self-expanding left and right atrial discs or anchoring devices that are attached through a central waist. Once in position, a combination of mechanical influences and fibrous encapsulation leads to closure of the PFO.

Closure involves three simple stages. First, the PFO is crossed using a guidewire advanced from the right atrium. A compliant balloon is then often used to measure tunnel dimensions to guide the size of the occluder. However, on occasion, balloon sizing can enlarge the PFO, and therefore, some cardiologists omit this stage. This is followed by deployment of the device by sequential unfolding of the left (distal) and right (proximal) atrial discs. Closure should ideally be guided by transesophageal echocardiography or intracardiac ultrasound and can be performed under conscious sedation or general anesthesia. Nonetheless, some experts continue to use fluoroscopy alone.8

Amplatzer PFO Occluder

The Amplatzer occluder is the only device that has FDA approval for PFO closure in the context of cryptogenic stroke. It is made of two nitinol woven discs with integral Dacron patches and a fixed short waist (Figure 1). The Dacron patches are designed to stimulate endothelialization. The device comes in multiple sizes with the right atrial disc being larger than the left atrial disc. The exceptions are the smallest 18-mm device, which has equally sized biatrial discs, and the other “cribriform” devices.

Figure 1. The Amplatzer PFO occluder.

Figure 2. The Figulla Flex II PFO occluder.

Figulla Flex II PFO Occluder

The design of the Figulla II PFO occluder (Occlutech AB) is technically very similar to the Amplatzer device, with minor design differences. Notable differences are a lower-profile left atrial disc, absent hub on the left atrial side, and hinged attachment to the delivery cable (Figure 2). The changes are designed to achieve optimal alignment of the atrial septum during deployment and reduce long-term complications, such as device erosion. There is a polyethylene patch inside each disc to support immediate closure. Like the Amplatzer occluder, this device is also nitinol based.

Cardioform Septal Occluder

Figure 3. The Cardioform septal occluder.

The Cardioform Septal Occluder (Gore & Associates) is a flexible, retrievable, double-disc device with a petal design made of a nitinol frame covered by expanded polytetrafluoroethylene to facilitate rapid endothelialization (Figure 3). The Cardioform septal occluder showed clinical success rates of 89% to 100% in initial and further experience of a small cohort.9-11 The efficacy of Cardioform occluder was similar to the Amplatzer occluder, with a low risk of a major adverse event, such as fracture or embolization, and no difference in procedural time. As of now, no erosion has been described, even in deficient aortic rims12; however, large registries may lack the tools to detect this rare event. The Cardioform septal occluder is suitable for secundum atrial septal defect < 18 mm. In the United States, the Cardioform occluder is indicated for the treatment of atrial septal defects; in the United Kingdom, it is approved for use in atrial septal defects and PFO.

Other Double-Disc Occluders

Figure 4. The Intrasept occluder.

Over the years, multiple other double-disc occluders have been designed, but few have had significant clinical success and most have been withdrawn from clinical use. One such device was the Intrasept (Cardia Inc.) consisting of an articulating central post that joins distal and proximal end caps made of sails and umbrellas. The device is designed to allow close alignment in patients with different septal configurations (Figure 4).

The CeraFlex (Lifetech Scientific) is another double disc occluder. It is designed to minimize thromboembolic complications as it has no distal left disc hub. The titanium nitride coating accelerates endothelization and significantly reduces release of nickel in comparison to other traditional uncoated devices. Furthermore, it has a flexible delivery cable capable of rotating through 360º to ensure the device is not under tension during deployment.

OCCLUDERS PLACED WITHIN THE PFO TUNNEL

Figure 5. The Flatstent occluder.

This group of devices is inserted directly into the PFO tunnel and stabilized though two adjustable left and right atrial anchors bringing the septum primum and secundum in close apposition.13 The rationale underpinning this design is to minimize the amount of material exposed to the circulation and thus reduce device-related complications, such as thrombus formation, atrial arrhythmias, and erosion. In addition, the absence of large metallic discs allows for future septal punctures in case of potentially invasive left heart procedures. The FlatStent occluder (Coherex Medical, Inc.) is a commercially available device that utilizes this principle, and recent evaluation has indicated that it is particularly suited for closure of PFOs with long tunnels (Figure 5).14

BIOABSORBABLE PFO OCCLUDERS

The development of completely or partially bioabsorbable PFO occluders is an ongoing area of intense research.15 These devices have a basic self-expanding double-disc design and are deployed in a similar manner to standard metallic double-disc occluders. However, because the polymer constituting the discs (and struts in selected designs) is resorbed and replaced by native tissue, there should theoretically be a reduced chance of thrombosis, arrhythmia, and device erosion.

A number of bioabsorbable devices have been evaluated clinically, but early results suggest these devices have a higher degree of residual shunt when compared with more widely used devices such as the Amplatzer occluder.16 There are currently no bioabsorbable devices in routine clinical use.

Another Novel Device

The HeartStitch occluder (Sutura, Inc.) utilizes complex SuperStitch technology, as used in femoral vascular closure devices, to suture the septum primum and secundum. Similar to other devices where there is no or minimal implantable material, the chances of thrombosis, arrhythmia, and erosion should be reduced.

CONCLUSION

Over the past 2 decades, a large array of devices has undergone evaluation for PFO closure. However, it is only in the past 12 months that the Amplatzer PFO occluder has been given FDA approval for routine clinical use. As the indications for PFO closure are becoming more clear, there is a trend away from permanent deployable devices toward bioabsorbable materials or novel technologies that minimize the use of foreign material. Inherent advantages of such technologies are reduced thrombogenicity, avoidance of device-related complications, and maintenance of normal or near-normal native interatrial septum anatomy, as well as the ability to access the left atrium for potential future intervention.

1. Khan AR, Abdulhak AAB, Sheikh MA, et al. Device closure of patent foramen ovale versus medical therapy in cryptogenic stroke. A systematic review and meta-analysis. JACC Cardiovasc Interv. 2013;12:1316-1326.

2. Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine: a quantitative systematic review. Cephalalgia. 2008;28:531-540.

3. Irwin B, Ray S. Patent foramen ovale: assessment and treatment. Cardioavsc Ther. 2012;30:e128-e135.

4. Meier B, Kalesan HP, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368:1083-1091.

5. Kent DM, Dahabreh IJ, Ruthazer R, et al. Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials. J Am Coll Cardiol 2016; 67: 907-917.

6. Kasner SE, Sondergaard L, Rhodes JF, Thomassen L. PFO closure in the Gore REDUCE clinical trial: primary results. Presented at: The European Stroke Organisation Conference; May 16-18, 2017; Prague, Czech Republic.

7. Mas JL. Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence results. Presented at: The European Stroke Organisation Conference; May 16-18, 2017; Prague, Czech Republic.

8. Dattilo PB, Kim MS, Carroll JD. Patent foramen ovale. Cardiol Clin. 2013;31:401-415.

9. Freixa X, Ibrahim R, Chan J, et al. Initial clinical experience with the GORE septal occluder for the treatment of atrial septal defects and patent foramen ovale. EuroIntervention. 2013;9:629-635.

10. Lombardi M, Tagliente MR, Pirolo T, et al. Feasibility and safety of a new generation of gore septal occluder device in children [published online ahead of print April 9, 2014]. J Cardiovasc Med (Hagerstown).

11. Nyboe C, Hjortdal VE, Nielsen-Kudsk JE. First experiences with the GORE Septal Occluder in children and adults with atrial septal defects. Catheter Cardiovasc Interv. 2013;82:929-934.

12. Smith B, Thomson J, Crossland D, et al. UK multicenter experience using the Gore septal occluder (GSO) for atrial septal defect closure in children and adults. Catheter Cardiovasc Interv. 2014;83:581-586.

13. Aral M, Mullen M. The Flatstent versus conventional umbrella devices in the percutaneous closure of patent foramen ovale. Catheter Cardiovasc Interv. 2015;85:1058-1065.

14. Reinthaler M, Aggarwal SK, Mert A, et al. Closure of long-tunnel PFOs with the Coherex Flatstent EF: a tailored approach. J Invasive Cardiol. 2015;27:e190-195.

15. Mullen MJ, Hildick-Smith D, De Giovanni JV, et al. BioStar Evaluation Study (BEST): a prospective, multicentre, phase I clinical trial to evaluate the feasibility, efficacy, and safety of the BioStar bioabsorbable septal repair implant for the closure of atrial-level shunts. Circulation. 2006;114:1962-1967.

16. Van den Branden BJ, Post MC, Plokker HW, et al. Bioabsorbable closure device. Safety and efficacy at 6-month follow-up. JACC Cardiovasc Interv. 2010;3:968-973.

Narbeh Melikian, BSc, MB BS, MD, FRCP
Cardiology Department
King’s College Hospital
Denmark Hill
London, United Kingdom
Disclosures: None.

Philip A. MacCarthy, BSc, MB BCh, PhD, FRCP
Cardiology Department
King’s College Hospital
Denmark Hill
London, United Kingdom
+ 44 (0)20 3299 9000; philip.maccarthy@nhs.net
Disclosures: None.

 

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About Cardiac Interventions Today

Cardiac Interventions Today (ISSN 2572-5955 print and ISSN 2572-5963 online) is a publication dedicated to providing comprehensive coverage of the latest developments in technology, techniques, clinical studies, and regulatory and reimbursement issues in the field of coronary and cardiac interventions. Cardiac Interventions Today premiered in March 2007 and each edition contains a variety of topics in a flexible format, including articles covering various perspectives on current clinical topics, in-depth interviews with expert physicians, overviews of available technologies, industry news, and insights into the issues affecting today's interventional cardiology practices.