The IrisFIT Patent Foramen Ovale Closure Device in Patients With History of Cryptogenic Embolization

Abstract: Background. The aim of this study was to assess safety, efficacy, and clinical outcome of the IrisFIT PFO Closure System (Lifetech Scientific) for transcatheter closure of patent foramen ovale (PFO) in patients with a history of cryptogenic stroke, transient ischemic attack (TIA), or peripheral embolization. Patients and Methods. We report the results of 60 consecutive patients undergoing PFO closure with the IrisFIT occluder for secondary prevention of paradoxical embolization. All cases were analyzed for periprocedural and device-related adverse events up to 12 months after implantation. In addition, the patients were evaluated for complete defect closure with transesophageal echocardiography (TEE) after 1 month, 6 months, and (if indicated) 12 months. Mean patient age was 53 ± 14 years and 37 patients (62%) were males. All patients had a history of at least 1 cryptogenic stroke, TIA, or peripheral embolization. Results. Technical success was achieved in all 60 procedures. The mean procedure time was 28 ± 11 minutes. There were no periprocedural or device-related complications up to 12 months after the implant. Successful defect closure at 6 months post device implantation was achieved in 56 cases (93.3%). Within 12 months of follow-up, 2 patients had recurrent TIAs, both with complete PFO sealing at the last TEE prior to the event. Conclusion. The IrisFIT PFO Closure System can be used safely and with high technical success for secondary prevention of cryptogenic stroke or peripheral embolization.

J INVASIVE CARDIOL 2019;31(11):319-324. Epub 2019 September 15.

Key words: cryptogenic stroke, paradoxical embolism, patent foramen ovale

The patent foramen ovale (PFO) is a gateway for venous emboli to the systemic (arterial) circulation, potentially causing strokes or peripheral embolization, decompression illness, and ischemic cerebral lesions in divers, and migraine with aura.^1,2 Larger PFO size, a greater right-to-left shunt, and the presence of an atrial septal aneurysm (ASA) appear to increase the risk of paradoxical embolism.^3-6 Percutaneous PFO closure has proven its safety and efficacy compared with medical treatment in randomized trials.^7-9 Therefore, current international treatment recommendations deem PFO closure the first-line therapy in patients with cryptogenic embolization.¹⁰ Importantly, procedural success (closure rate) and complications (device-related thrombus formation or new-onset atrial fibrillation) appear to be device dependent.^11,12

Continuous improvement in device designs in order to minimize the risk of typical occluder-associated complications is desirable to maximize the beneficial effects of transcatheter PFO closure. Therefore, we report the results of a postmarket analysis of the IrisFIT PFO Closure System (Lifetech Scientific). This occluder was designed to maintain the advantages of classic double-disc closure systems while further mitigating typical device-related complications, such as insufficient PFO closure, thrombus formation, or erosion.

Methods

This is a single-center postmarket analysis of the IrisFIT PFO Closure System to evaluate the acute and intermediate-term performance of the device. The study was designed in accordance with the principles of the Declaration of Helsinki and approved by the local ethics committee.

Device description. The IrisFIT occluder is a self-expandable tritium nitride (TiN)-coated nitinol double-disc device with a slim waist (Figure 1). A nitinol wire mesh builds the right atrial disc with an expanded polytetrafluoroethylene (ePTFE) membrane inside. The left atrial disc is designed with a nitinol anchor that consists of six braided arms that carry an ePTFE patch on the outside. A flexible nitinol wire waist connects both discs and allows varying angles between the two discs so that the occluder can adapt to variable anatomy. Furthermore, the waist carries polyester fibers on the right atrial side to facilitate early defect closure after implantation. The device is available in three sizes ranging from 18 mm to 30 mm depending on the diameter of the right atrial disc (Table 1). The diameter of the left atrial disc ranges from 18 mm to 25 mm. While a 10 Fr sheath is recommended for implantation of the 18 mm device, the two bigger devices require a 12 Fr sheath.

All patients provided written informed consent prior to study participation. Patients were selected according to the inclusion and exclusion criteria. Eligible patients were at least 18 years old, had a history of at least one episode of cryptogenic stroke, transient ischemic attack (TIA), or peripheral embolization, and were found to have a PFO eligible for treatment with the IrisFIT occluder. Exclusion criteria were insufficient heart tissue for secure anchoring of the occluder (tunnel length <1 mm), an anatomy in which the occluder affects intracardiac structures (eg, aortic root, pulmonary vein), active endocarditis, intracardiac mass, history of arrhythmia, and inability to take or comply with aspirin, clopidogrel, or antibiotic prophylaxis for 6 months following the procedure.

Percutaneous PFO closure was performed under local anesthesia at the puncture site with mild sedation for transesophageal echocardiography (TEE). After femoral venous access, the PFO was directly crossed with a guidewire or using a 5 Fr multipurpose catheter, which was advanced into the left upper pulmonary vein. Subsequently, 10,000 IU of heparin were administered and a stiff guidewire was positioned in the left upper pulmonary vein to perform balloon sizing. The device was chosen such that the device diameter was at least twice the size of the defect. The balloon catheter was then removed and a 10 or 12 Fr delivery sheath (depending on the device size) was advanced into the left atrium. Then, the device chosen was advanced through the sheath to its distal tip placed in the left atrium. While maintaining the position of the device, the sheath was pulled back to deploy the left atrial disk. Under TEE and fluoroscopic guidance, the expanded left atrial disk was retracted together with the sheath to the atrial septum. Under verification of septal bearing, the sheath was further pulled back to deploy the right atrial disk. After verification of successful occluder position by both TEE and fluoroscopy, the device was released by unscrewing the delivery cable from the right atrial hub.

Antiplatelet therapy to prevent thrombus formation included 100 mg of aspirin daily for 6 months and 75 mg of clopidogrel daily for at least 3 months. Endocarditis prophylaxis was also recommended for 6 months after device implantation.

Follow-up examinations were performed before discharge and at 1 month, 6 months, and 12 months post implantation, and included a TEE at 1 month and 6 months to evaluate for residual shunting using agitated saline as contrast medium at rest and during Valsalva maneuver. The shunt grade was evaluated with TEE using the following classifications: no shunt (0 bubbles); mild shunt (1-10 bubbles); moderate shunt (10-20 bubbles); or severe shunt (>20 bubbles). The last follow-up was performed at 12 months post implantation. This was at least a telephone call, but included an office visit including echocardiography (with transthoracic echocardiography [TTE] or TEE) whenever possible. In cases of adverse events (such as recurrent hospitalization for neurological or peripheral embolic complications) since the previous patient contact, all records were ordered and a neurological assessment was initiated if necessary.

Definitions. The primary study objectives were the safety and efficacy analyses. Safety was defined as implantation without any adverse device-related effect during the procedure and up to 12 months post procedure. Efficacy was defined as the accurate device placement without migration or malfunction of the occluder and successful closure of the PFO. Procedural success was defined as proper positioning of the occluder at TEE evaluation 6 months post implantation with no/trivial to small shunt.

Statistical analysis. Statistical analysis was performed on an intention-to-treat principle. Nominal and categorical variables are displayed as frequencies and percentages. Continuous variables are expressed as mean ± standard deviation. All data were analyzed using BiAS for Windows, version 10.04 (Epsilon Verlag).

Results

Between January and September 2015, PFO closure for secondary prevention of paradoxical embolization was performed in 60 patients with implantation of the IrisFIT occluder. Mean patient age was 53 ± 14 years (range, 18-88 years) and 37 (62.0%) were males. Patient characteristics are displayed in Table 2. Of the 60 patients, a total of 44 (73.3%) had experienced prior strokes, 13 (21.6%) had prior TIAs, and 5 (8.3%) had prior peripheral embolizations. Six patients (10.0%) had already experienced multiple embolic events.

The mean PFO diameter using balloon sizing, as determined by the diameter of the balloon upon changing the shape of the PFO from slit-like to circular, was 8.0 ± 2.7 mm. An 18 mm device was implanted in 13 patients (21.6%), a 25 mm device was implanted in 45 patients (75.0%), and a 30 mm device was used in 2 patients (3.3%). The primary safety endpoint for successful device implantation was met in all 60 patients (100%). All devices showed good maneuverability and all of the attempted devices could be delivered correctly. An occluder never had to be removed or exchanged for another occluder in this study population. The ease of device delivery and implantation was reflected in a short mean procedure time of 28 ±11 minutes (range, 15-75 minutes). Furthermore, there were no periprocedural complications, such as device migration or embolization, cardiac effusion, or thromboembolic complications.

Five patients experienced minor complications before discharge; 3 patients had local hematomas at the puncture site and 2 patients developed atrial fibrillation. One patient with atrial fibrillation was successfully treated with beta-blockers, while the other had to undergo electric cardioversion and thereafter stayed in sinus rhythm.

At 30-day follow-up exam, a total of 53 patients (88.3%) were examined with TEE and 6 (10.0%) with TTE. Testing for residual shunt was done at rest and with Valsalva. Complete closure of the defect was seen in 45 patients (75.0%), while 9 patients (15.0%) had small residual shunts, 2 (3.3%) had moderate residual shunts, and 3 (5.0%) had severe residual shunts (Table 3). In 1 of the severe residual shunt cases, we had noted a second defect during the index procedure. In this patient, device implantation was performed with the intention of covering both defects; the severe shunt was in the second defect, with no shunt through the PFO. Therefore, we implanted a second 18 mm device within 6 months. One patient missed echocardiographic evaluation after 30 days and could only be contacted by phone for clinical follow-up. At 6-month follow-up, a total of 13 patients (21.7%) were evaluated with TTE, all of whom had completely closed defects at 30-day follow-up. Forty-six patients (76.7%) underwent TEE. At this time, a total of 54 PFOs (90%) were successfully closed (including the patient who missed the 30-day follow-up). Small, moderate, and severe shunts remained in 2 patients each. Thus, the aforementioned performance endpoint — proper occluder position at TEE after 6 months without or trivial to small shunt — was met in 56 patients (93.3%). After 12 months, additional TEE was done in the 4 patients with moderate and severe shunts at 6-month follow-up exam. One of these patients only had a minor shunt with <10 bubbles crossing the PFO under Valsalva maneuver; the 3 remaining patients had severe shunts requiring implantation of a second device.

Echocardiographic examinations showed no device-associated thrombus formation, device migration, or embolization in any patient. Hence, the predefined safety criteria were fulfilled.

Clinical follow-up showed new onset of atrial fibrillation in 3 patients (5%), all within 30 days of the implantation and all treated successfully with beta-blockers (Table 4). Within 12 months of follow-up, two patients (3.3%) had recurrent TIAs. There were no residual shunts in the TEEs preceding the events in either patient. One of the latter patients had TIAs at 3 months and 8 months post implantation. Recurrent diagnostic work-up in this patient revealed cerebral vasculitis resulting in an immunosuppressive therapy. The other patient who had a TIA was 1 of the 4 patients in whom atrial fibrillation had occurred within the first month post implantation. Holter electrocardiography in this case did not reveal further episodes of atrial fibrillation. There was no thrombus formation either on the device or in the left atrium or appendage, or spontaneous echo contrast during TEE.

Discussion

The net benefit of transcatheter PFO closure depends on complete or near-complete elimination of the right-to-left shunt and the risk of device- or procedure-related complications. The most serious complication, device erosion, can lead to myocardial perforation, cardiac tamponade, and death. More commonly, thrombus formation or atrial fibrillation may occur. The latter offsets the efficacy of PFO closure in the secondary prevention of embolic complications. Closure and complication rates appear to be device dependent.^11-14

The present study focused on the safety, performance, and efficacy of the IrisFIT PFO occluder in 60 consecutive patients referred for PFO closure. All patients underwent successful device implantation without any periprocedural medical or technical complications. With the exception of atrial fibrillation that may or may not have been related to the procedure or device, there were no adverse events within 12 months of follow-up. Therefore, the primary safety endpoint was met in all patients. With regard to device performance, all devices were placed successfully during the first attempt without device migration or malfunction. At 6-month follow-up exam, complete closure and mild residual shunts were seen in 54 patients (90.0%) and 2 patients (3.3%), respectively.

The favorable safety and efficacy profile may be related to the device design. The system allows easy handling during the implantation, reflected by a short mean procedural time of 28 ± 11 minutes. The waist that connects both discs was developed to allow rotational freedom between the two discs, as well as articulation (Figure 2). This facilitates tension-free adjustment to the individual interatrial anatomy, potentially minimizing tilting and shearing forces and erosion risk.^15,16 In addition, the frame of the left atrial disc has also been designed to reduce the risk of mechanical complications. It consists of six arms, each of which has a guidewire-like atraumatic tip (Figure 1C). Each arm is braided from multiple wires, so that a fracture in a single wire does not affect the stability of the arm and the device. Another potential advantage of the left atrial disc design is the absence of a hub protruding into the left atrium, as a protruding hub may be a nidus for thrombus formation.^17,18 Elimination of a hub, low device profile, and the ePTFE patch that covers the frame of the left atrial disc may accelerate endothelialization and defect closure. In this context, there was no device-associated thrombus formation in any of the patients.

The closure rate of the IrisFIT PFO occluder compares well with other devices. Depending on the device, follow-up methods, timing, and study definitions, closure rates between 50% and 100% have been reported.^13,19 The Amplatzer PFO occluder was used in the RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment) trial, which is the only randomized trial demonstrating superiority of device closure compared with medical therapy. The 6-month complete closure rate was 72.7%, with an effective 6-month closure rate of 93.5% (effective closure was defined as complete closure or minimal residual shunt).²⁰ The favorable complete closure rates with the IrisFIT PFO occluder may be related to several features, including the high anatomic adaptability of the two discs, the good biocompatibility resulting in fast endothelialization, and the fibers attached to the waist on the right atrial side. These fibers are located in the PFO tunnel and may promote closure (similar to fibers used for deliberate blood vessel embolization). In addition, the device flexibility is improved because the nitinol filaments of the right atrial disc are thinner than in other occluders, allowing favorable deformation and adaptation to the anatomy (for example, more conical shapes are possible in long tunnel anatomy).

Furthermore, the TiN coating that covers all nitinol parts increases the biocompatibility and thereby the endothelialization of the IRISFit device, as this alloy reduces the corrosion and thus the release of potentially allergenic nickel ions into the blood. Zhang et al²¹ were able to show that TiN coating allowed faster endothelialization compared with conventional nitinol occluders.

In our analysis, five patients (8.3%) — all of whom had no prior history of atrial fibrillation — developed it after implantation. Atrial fibrillation occurred during hospitalization for PFO closure in 2 patients (3.3%) and after discharge but within 30 days of the procedure in 3 patients (5.0%). The events consisted of a single episode lasting <48 hours in 4 patients, resolving either spontaneously or with cardioversion. One patient reported an episode lasting longer than 48 hours. No recurrences were reported and there was no new-onset atrial fibrillation beyond 30 days of implantation. The reported incidence of atrial fibrillation following PFO closure varies from 0.7%-19.0%,^22-26 depending on the examined number of patients and the device type.²⁷ A meta-analysis of randomized trials also proved that PFO closure reduces recurrent events compared with medical therapy, but is associated with a higher risk of atrial arrhythmias.²⁸ In an analysis of 1349 patients who underwent transcatheter PFO closure, Staubach et al²⁷ reported an atrial fibrillation of 3.9% (53 patients). The majority of these events (62.3%) occurred within 4 weeks of the procedure, while 15.0% occurred between 4 weeks and 6 months post procedure. In an analysis of 1062 patients who underwent device closure of interatrial communications, Spies et al²⁹ reported new-onset atrial fibrillation in 8.0% of patients during a median follow-up of 20 months. The annual incidence was 2.5% and 4.1% in patients with PFO and atrial septal defects, respectively. The clinical significance of these short, mostly one-time arrhythmic episodes remains unclear. Wallenborn et al³⁰ analyzed recurrent events in 1930 patients who underwent PFO closure, and could not show atrial fibrillation as a significant risk factor for recurrent embolic events in patients with transcatheter PFO closure. It is also not clear if the atrial fibrillation is only related to the procedure or device itself or if it is an incidental finding that may have led to the first embolic event without having been recognized. Burow et al²⁵ performed a study comparing 40 patients with cryptogenic stroke and PFO closure versus 70 patients with stroke of known cause other than atrial fibrillation. There was no difference in the incidence of new-onset atrial fibrillation within 6 months post cerebral ischemia (15% vs 16%; P=.77).

Study limitations. The present study has several limitations. First, it is a postmarket analysis of the IrisFIT PFO occluder without comparison versus a control group of patients who underwent closure with other occluders. Hence, the favorable results are subject to selection bias. Second, the sample size is small and there was no control group of patients who did not undergo closure. Therefore, statements regarding clinical efficacy (ie, regarding its efficacy in stroke prevention) cannot be made. Third, it is a single-center analysis. These results can therefore not be guaranteed in other settings. Last, TEE and bubble testing with Valsalva were performed for evaluation of defect closure under conscious sedation. Therefore, the residual shunt rates may be under-estimated.

Conclusion

The IrisFIT PFO occluder performs well in patients with PFO and cryptogenic embolic events. PFO closure with this device leads to a high rate of successful closure and is associated with low acute and postprocedural complication rates.

References

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From the ¹CardioVascular Center Frankfurt, Frankfurt, Germany; and ²Anglia Ruskin University, Faculty of Medical Science, Chelmsford, United Kingdom.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors’ institution has ownership interest in or has received consulting fees, travel expenses, or study honoraria from the following companies: Abbott, Access Closure, AGA, Angiomed, Arstasis, Atritech, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, CSI, EndoCross, EndoTex, Epitek, Evalve, ev3, FlowCardia, Gore, Guidant, Guided Delivery Systems, InSeal Medical, Lumen Biomedical, HLT, Kensey Nash, Kyoto Medical, Lifetech, Lutonix, Medinol, Medtronic, NDC, NMT, OAS, Occlutech, Osprey, Ovalis, Pathway, PendraCare, Percardia, pfm Medical, Rox Medical, Sadra, SJM, Sorin, Spectranetics, SquareOne, Trireme, Trivascular, Velocimed, and Veryan.

Manuscript submitted February 20, 2019, provisional acceptance given March 4, 2019, final version accepted May 9, 2019.

Address for correspondence: Horst Sievert, MD, CardioVascular Center Frankfurt CVC, Seckbacher Landstrasse 65, 60389 Frankfurt, Germany. Email: info@cvcfrankfurt.de