Abstract: Aims. Despite rapid progress in device technologies for patent foramen ovale (PFO) closure over the past decade, long-tunnel anatomies still constitute a challenge. The present study investigated the performance of a novel in-tunnel device (Flatstent EF; Coherex Medical) in long-tunnel PFOs. Methods and Results. Three different umbrella devices (n = 61) and the Coherex Flatstent (n = 27) were used for PFO closure. The Flatstent was the preferred device in long-tunnel anatomies. Seven patients with long PFO tunnels underwent “detunnelization” by stepwise inflation of a low-pressure balloon followed by implantation of an umbrella device. Complete occlusion or trivial residual shunting (“clinical” occlusion) was achieved in 93% of the Flatstent and 92% of the umbrella device procedures (P=.92). Device performance in long-tunnel anatomies was in favor of the Flatstent (n = 24) compared with conventional occluders (n = 7), with “clinical” occlusion of 96% vs 86% (P=.24) and procedure time of 44 ± 16 minutes vs 59 ± 21 minutes (P=.04). Furthermore, postprocedural arrhythmias were significantly less frequent after Flatstent implantations (0.0% vs 9.1%; P=.03). Conclusion. In long-tunnel PFOs, the Flatstent device was quicker to deploy, was at least as equally efficacious as umbrella devices, and reduced the incidence of symptomatic arrhythmias following PFO closure.
J INVASIVE CARDIOL 2015;27(9):E190-E195
Key words: patent foramen ovale closure, long-tunnel anatomy, Flatstent, in-tunnel occluder
Patent foramen ovale (PFO) is a common finding in the general population, with a prevalence of about 25%.1 Since an association with conditions like cryptogenic stroke, migraine, or decompression sickness has been assumed,2-4 transcatheter closure has emerged as a potential treatment option for selected patients.5 However, large randomized trials have failed to demonstrate a clinical benefit so far.6-9 Despite these discouraging results, PFO closure is still considered a potential treatment option in selected patients due to several limitations of the previously mentioned investigations. One of the factors suggested to play a major role in the incidence of recurrent clinical events after percutaneous intervention is the closure performance and residual shunting rates of the available closure devices.10-12
PFO morphology is often complex, and certain anatomical features may require distinct approaches and technologies to achieve the best possible results. In fact, a recent study has demonstrated higher complete occlusion rates and a reduction in complications following an anatomically driven device selection strategy compared with a fixed single device strategy.13 In particular, devices with a fixed distance between the right and left atrial components may be problematic in long-tunnel PFOs, whereby there is the potential for both discs to be partially deployed within the tunnel. In these situations, balloon pull-through, detunnelization, or transseptal puncture constitute possible strategies, as described elsewhere.14-16 Over the past decade, in-tunnel devices have been developed that directly target the PFO tunnel.17,18 Whether these devices offer advantages in terms of safety and efficacy in long tunnels has not yet been elucidated. We report our experience with the Coherex Flatstent (Coherex Medical) in long-tunnel PFO anatomies.
All patients who underwent PFO closure between 2010 and 2013 at the UCLH Heart Hospital were included in this analysis. The objective of the present study was to investigate the device performance of the Coherex Flatstent in-tunnel occluder in long-tunnel PFOs.
All patients were referred by neurologists to be considered for PFO closure in the context of cryptogenic stroke, decompression illness, or migraine (Table 1). Nineteen patients (21.6%) underwent device closure due to both conditions, migraine, and cryptogenic stroke/transient ischemic attack (TIA). Diagnosis of PFO with significant right to left shunt was defined as the presence of >25 microbubbles in the left heart after intravenous injection of agitated saline at either rest or post Valsalva.
Shunt quantification. Contrast transthoracic echocardiogram (TTE) was used for PFO screening as well as quantification of right to left shunts and was performed at baseline, 6 weeks, and 1 year after closure in all patients. Atrial shunts were defined as described elsewhere.19 In brief, four shunt grades were distinguished according to the number of bubbles seen in a single still frame in the left heart (grade 1: 1-5 bubbles; grade 2: 5-25 bubbles; grade 3: >25 bubbles; and grade 4: opacification of left-sided chambers). Shunts were assessed at rest, during Valsalva, and with cough.19 A PFO was considered closed after device implantation when no saline bubbles were detected in the left atrium within six cardiac cycles following right atrial opacification. PFOs were considered clinically closed if residual shunts were less than grade 2.
Procedures and assessment of the fossa ovalis. All patients were preloaded with aspirin 300 mg and clopidogrel 300 mg before the procedure. All procedures were performed under transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE) guidance.
After cannulation of the right femoral vein, a soft-tipped guidewire was advanced through the defect and positioned within a left-sided pulmonary vein. All patients received intravenous heparin (100 IU/kg) during the procedure and intravenous antibiotic prophylaxis.
To assess the PFO morphology, a PTS-X compliant sizing balloon (NuMED, Inc) was positioned across the defect. The balloon was gently inflated with dilute contrast under fluoroscopic and echocardiographic guidance until the sites of constraint of the balloon allowed identification of the entrance (right atrial margin), the exit (left atrial margin), and the length (distance between the entrance and exit) of the PFO. Measurements were taken from echocardiographic and fluoroscopic images, using spacing radiopaque markers on the sizing balloon for calibration.
Based on imaging and balloon assessment, the fossa ovalis was specified according to the presence of multiple openings, long-tunnel, interatrial septal (IAS) aneurysm (>10 mm), thick secondary septum (>10 mm), or a combination of these features.20 The PFO morphology was considered to be long tunnel when the length of the tunnel was greater than the dimension of either the entrance or the exit during balloon sizing.14
Device selection. Between 2010 and 2013, four different devices were used. The Gore septal occluder (Gore Medical), the Coherex Flatstent (Coherex Medical), the Occlutech Figulla device (Occlutech GmbH), and the Biostar septal repair system (NMT Medical).
Whenever a long tunnel was identified, patients were treated with the Coherex Flatstent. If the Flatstent was not available, long-tunnel PFOs were “detunnelized” by stepwise inflation of a low-pressure balloon prior to closure with an umbrella device, as described elsewhere.14
The Gore septal occluder is a soft device, composed of a platinum-filled nickel-titanium (nitinol) wire frame covered with expanded polytetrafluoroethylene. There are four available sizes (15, 20, 25, and 30 mm), which are deployed with a single handle control that allows precise positioning. Device selection was based on the balloon-stretched diameter multiplied by a factor of 1.5-2.21
The Flatstent EF is a 0.51-mm thick super-elastic nitinol component. The implant has microtined anchors that extend out from the PFO tunnel and attach to the walls of the left and right atrium. Radiopaque markers allow visualization of the anchors during implantation. The implant is designed to be unsheathed in the PFO tunnel, where it expands laterally. This action brings the walls of the septum primum and the septum secundum into apposition. A polyurethane foam in the intratunnel cells of the Coherex Flatstent is intended to stimulate tissue growth inside the tunnel. A tunnel length of <4 mm was considered a contraindication to Flatstent implantation. The device was available in a 13 mm version for balloon-measured PFO diameters <8 mm and a 19 mm version for balloon-measured PFO diameters 7-12 mm.17
The Occlutech Figulla device consists of a nitinol wire mesh. It is unique because the left atrial disc is designed with a single layer without a hub, minimizing the amount of material in the left atrium. Occluder sizes were selected according to PFO diameter during balloon sizing (diameter ≤8 mm: 16/18 mm device; diameter 9-13 mm: 23/25 mm device; diameter 14-15 mm: 27/30 mm; and diameter ≥15 mm: 31/35 mm device).22
The Biostar septal repair implant is a bioabsorbable device specifically designed for the closure of atrial septal defects and PFOs. The collagen matrix of the device is rapidly incorporated into the atrial septum, which results in a low profile and early sealing of the defect. Finally, the collagen is absorbed and replaced by host tissue. On the basis of the mentioned measurements, a Biostar implant was selected that was approximately 1.5-2 times the balloon-stretched diameter. Devices available during the study period were 23, 28, and 33 mm.23
Complications were assessed immediately after the procedure, and throughout the follow-up period. Patients who complained about palpitations following the procedure were monitored by 72-hour Holter electrocardiograms. Treatment was applied whenever indicated.
Statistical analysis. Continuous variables are expressed as mean ± standard deviation. Categorical data are reported as frequencies. For intergroup comparisons, the Kruskal-Wallis H-test, Mann-Whitney U-test, and Chi-squared test were used where appropriate. A logistic regression analysis was applied to define predictors of shunt reduction for each device. Level of significance was set at P<.05. Statistical analysis was performed using SPSS version 19 for Windows.
Cerebral embolism (85%) and migraine (33%) were the most common indications for PFO closure. Nineteen patients (21.6%) of our study cohort suffered from both conditions. Significant shunting was present in all individuals as demonstrated by preprocedural bubble studies (grade 3 in 31% and grade 4 in 69%). Predefined anatomic features were observed in 56 patients (long tunnel in 31 patients, IAS aneurysm in 25 patients, and both features in 7 patients) (Table 1).
As depicted in Table 2, the Gore septal occluder was used in 35 patients, the Coherex Flatstent in 27 patients, the Occlutech Figulla in 18 patients, and the Biostar device in 8 patients. Twenty-four of all Flatstent implantations were performed in individuals with long-tunnel PFOs and in 3 patients with IAS aneurysms. Seven long-tunnel PFO patients underwent “detunnelization” followed by closure with an umbrella occluder. A combination of IAS aneurysm and long-tunnel morphology was most frequently observed in patients who received the Occlutech Figulla device.
All procedures were guided by ICE (21.6%) or TEE (78.4%). Although procedure times were comparable in all device types, overall radiation dosage was significantly increased in Flatstent implantations (Table 2). However, in long-tunnel PFOs, procedure times were significantly shorter in Flatstent procedures (44 ± 16 minutes vs 59 ± 21 minutes; P=.04), whereas no differences in radiation dosages were observed between Flatstent (n = 24) and umbrella device implantations (n = 7) (2446 ± 2181 Gy•cm² vs 2382 ± 1867 Gy•cm²; P=.95) (Table 3).
Complete occlusion or minor leaking (grade-1 shunt) was achieved in 66 patients (75%) after 6 weeks and 75 patients (85%) after 1 year (P=.01). During short-term follow-up, residual shunts were comparable in all device types. However, after 1 year, the occlusion rates were significantly higher in patients who received the Gore septal occluder (97.1%) compared with the Occlutech (83.3%) and Biostar devices (87.5%) (Table 2).
Predefined anatomical features did not predict residual shunts after 1 year (analyzed for each device) in univariate and multivariate analyses, although the presence of an IAS aneurysm was associated with worse results after 6 weeks (32.0% vs 13.6%, > grade-1 shunt; P=.02) but not after 1 year (9.0% vs 7.6%, > grade-1 shunt; P=.42). The incidence of > grade-1 shunts in long tunnels was comparable to simple anatomies after 6 weeks (13.8% vs 20.0%; P=.48) and 1 year (6.9% vs 8.5%; P=.38).
In a minority of patients with long-tunnel PFO (n = 7), closure was performed by detunnelization followed by implantation of an umbrella device. The detunnelization/umbrella device strategy in long-tunnel PFOs (n = 7) was associated with a 10% reduction in “clinical” occlusion rates when compared with an anatomy-driven device selection strategy with implantation of a Flatstent (Table 3).
Similar occlusion rates between Flatstents (n = 3) and umbrella devices (n = 22) were observed in the presence of IAS aneurysms (100% vs 91% < grade-2 shunt after 1 year; P=.59).
Procedure-associated complications were observed in 11 patients (12.5%) and were due to supraventricular ectopics in 7 patients (8%), atrial fibrillation (AF) in 1 patient (1.1%), and access-related complications in 3 patients (3.4%). Prolonged antiarrhythmic therapy was required in 1 patient who developed AF after implantation of an umbrella occluder. All other complications resolved without sequelae. In general, supraventricular arrhythmias were more frequent after implantation of umbrella devices compared with Flatstents (9.1% vs 0.0%; P=.03) (Table 2). No recurrent cerebrovascular event was observed within the follow-up period.
An anatomic-driven device selection strategy in PFO closure has been associated with favorable results compared with a single device strategy.13,24 Since the available technologies are rapidly expanding, data on device performance in complex PFO anatomies are crucial to further improve this approach. In our series, the Coherex Flatstent was the preferred device for long-tunnel PFOs. Effective closure rates, along with a reduction in symptomatic postprocedural arrhythmias, were observed in Flatstent procedures. Furthermore, procedure times were significantly shorter when compared with umbrella device implantations in long-tunnel PFOs.
Percutaneous PFO closure, first performed in 1989, has evolved in the past decade as a low-risk alternative therapeutic option in selected patients. Studies have shown over 90% closure success rates using a variety of devices.6-9 Despite the reported simplicity of the technique involved in placing the device, occasionally structural variations of the atrial septum increase the difficulty encountered during device deployment. Among various anatomical variations reported in the literature,20 long-tunnel morphologies and IAS aneurysms were frequently observed in the present study. IAS aneurysm merely describes the mobility of the non-muscular part of the septum primum and has been identified as an important risk factor for paradoxical embolism. Initially, this mobility had been considered a risk factor on its own, even in the absence of a PFO. Today, this can no longer be supported.25 It is now generally accepted that closing the defect is all it takes. Stenting the septum primum with a large oversized umbrella device is no longer deemed necessary. Therefore, IAS aneurysm may also represent a target for in-tunnel devices, as performed in 3 of our patients.
Appreciation of long-tunnel anatomies is important, as they have frequently been associated with device malpositioning and high residual shunt grades.26 Although the term “long tunnel’’ is widely used in the PFO literature, there is no uniform definition. Our definition is empiric and describes the morphology of the defect under conditions of stress. While at rest there is no relationship between the entrance or exit and the length of the tunnel, during balloon dilatation the length tends to decrease as entrance and exit increase. This definition accounted for 27% of our patient cohort.
Several strategies that all have their own limitations have been advocated to facilitate the closure of long-tunnel PFOs. First, delivery of the closure device trough a transseptal puncture is associated with an additional risk and has a higher residual shunt rate.27 Second, balloon pull-through to render the septum primum incompetent and improve the final device position may be traumatic and has a lack of control.15 Third, remodeling the PFO tunnel by stepwise inflation of a low-pressure balloon (detunnelization), as performed in 7 patients of the present study, is also traumatic and may fail in particularly long tunnels.14 Consequently, dedicated devices have been developed to simplify and improve long-tunnel closure procedures. For example, the Premere device overcomes variable tunnel lengths with an adjustable device waist. However, in a previous study, it was associated with an increased risk of vascular injury and a prolonged procedure time.28
In our study, the Coherex Flatstent PFO Closure System was used in long-tunnel anatomies. This device was designed to treat only the PFO tunnel and avoid complications associated with implanting larger closure devices in the left atrium. Furthermore, the implant preserves transseptal access for future left atrial procedures. The feasibility and safety of this device have already been demonstrated in a recently published investigation.17
Our results again confirm excellent closure rates despite using the device in so-called “unfavorable” anatomies. In more than 93.0% of our patients who received a Flatstent implantation, the PFO was “clinically” closed after 1 year. These numbers are comparable to our results with the Gore septal occluder, which was associated with 97.0% closure success.
At the other end of the spectrum, “clinical” closure was achieved in only 83% of patients treated with the Occlutech occluder. This is in contrast to a previous study that reported successful closure in 96.0% of patients who were treated with this device. The increased incidence of an IAS aneurysm/long-tunnel combination in our Occlutech group may explain the different findings. Our observation that predefined anatomical features were not associated with PFO closure rates, on the other hand, possibly relates to the limited number of patients.
However, in long-tunnel PFOs, the Coherex Flatstent was associated with favorable results compared with umbrella-device procedures combined with detunnelization, as indicated by shorter procedure times and a trend toward improved closure performance. As different closure rates were due to a lack of shunt regression in the long-tunnel umbrella cohort beyond the 6-week follow-up, disruption of the IAS and inefficient endothelialization following detunnelization may be responsible for this finding. Most importantly, PFO closure is a procedure with “zero tolerance” for complications; therefore, PFO closure must be performed to an exact safety standard. Procedures to remodel the PFO tunnel may bear the risk of additional complications, and therefore the question arises of whether dedicated in-tunnel devices improve the risk-benefit ratio in certain circumstances, such as in the presence of long tunnels.
Irrespective of the occluder used, we did not experience any serious adverse events. Symptomatic postprocedural arrhythmias were significantly less frequent with Flatstents compared to umbrella devices, which is probably due to the lower mass and the in-tunnel design of the device. Except 1 patient who developed AF after implantation of an umbrella device and required prolonged antiarrhythmic treatment, all arrhythmias resolved without sequelae within 1 year. Furthermore, none of the observed vascular complications led to long-term consequences.
Although the radiation dosage was highest in patients who received a Flatstent, no differences compared to umbrella devices were observed when only long-tunnel morphologies were analyzed. However, Flatstent deployment is mainly guided by fluoroscopy because echocardiographic visualization is difficult, resulting in a higher radiation dosage. This may be particularly relevant as interventional PFO closure is mainly considered in younger patients.
Despite excellent results in the current study and others, the Coherex Flatstent is not recommended in patients with a tunnel length of <4 mm, and is therefore not suitable for all PFO types. However, according to our data, it offers significant advantages in long-tunnel PFOs and may therefore be considered complementary in an anatomy-driven device selection strategy.
Our results are important because device performance and residual shunts are considered to play major roles in clinical outcomes, and long-tunnel PFOs still constitute a challenge in PFO closure.
Unfortunately, Coherex Medical has refocused its research and development efforts, and the Flatstent device, which is currently the only CE-marked in-tunnel occluder, is no longer available. Our results should therefore encourage companies to launch similar devices.
Study limitations. This study was limited by the overall sample size, which made outcome comparisons between the groups difficult. However, it allowed sufficient experience to identify differences in terms of device characteristics and to make conclusions regarding the performance of the Flatstent device in long-tunnel PFOs. Only 8 Biostar devices were implanted in our study cohort, and the worse outcome with this occluder may therefore be due to lack of learning experience.
The Coherex Flatstent reduced the incidence of symptomatic arrhythmias following PFO closure in our study, and may be considered the preferred occluder in the presence of long-tunnel anatomies. However, due to the small sample size in the present study, larger investigations are necessary to confirm our results. Since the Flatstent is no longer available, the development of alternative in-tunnel devices should be encouraged.
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From the 1Charitè Berlin, Campus Benjamin Franklin, Department of Cardiology, Berlin, Germany; and 2University College London, The Heart Hospital, Department for Structural Heart Intervention.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Mullen reports personal fees from NMT Medical, Edwards Lifesciences, and Medtronic, Inc. Prof Landmesser reports personal fees from St. Jude Medical. The remaining authors report no disclosures regarding the content herein.
Manuscript submitted November 17, 2014, provisional acceptance given December 16, 2014, final version accepted February 9, 2015.
Address for correspondence: Markus Reinthaler, Charitè Berlin, Campus Benjamin Franklin, Department of Cardiology, Hindenburgdamm 30, 12200 Berlin, Germany. Email: email@example.com