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Propensity-Score Matched Comparison of the Cera PFO Occluder With the Amplatzer PFO Occluder for Percutaneous Closure of Patent Foramen Ovale Without Echocardiographic Guidance
Abstract: Background. Percutaneous patent foramen ovale (PFO) closure has become a routine procedure and was proven to be safe and feasible. In a recently published pooled analysis of randomized trials, percutaneous PFO closure was shown to more effectively reduce recurrent stroke when compared with medical therapy in patients with cryptogenic strokes. However, procedural safety and closure rate are device dependent. Methods. We performed a propensity-score matched comparison of 28 patients undergoing percutaneous PFO closure using the Cera PFO occluder (CPO) with 28 patients who received the Amplatzer PFO occluder (APO). The main endpoints were procedural complications and closure rate at 6 months verified by transesophageal echocardiography. Results. The implantation procedure using the CPO was successful and without complications in all cases. After propensity-score matching, there was no significant difference between groups for the primary endpoint of residual shunt at 6 months (7% in the CPO group vs 4% in the APO group; log-rank test P=.15). Conclusions. With regard to procedural safety and closure rate at 6 months, the performance of the CPO is comparable with the APO in this small patient cohort.
J INVASIVE CARDIOL 2017;29(8):280-284. Epub 2017 May 15.
Key words: atrial septal aneurysm, patent foramen ovale, cerebral ischemia, embolism, secondary stroke prevention
Among young patients (15-49 years) suffering ischemic strokes, the proportion of strokes of unknown origin, also called cryptogenic strokes, is as high as 30%.1 Several past studies have shown that the prevalence of patent foramen ovale (PFO) in people with cryptogenic stroke is notably higher than in the general population (40%-75% vs 20%-25%).2,3 This association has been extended to patients 55 years and older.4
Currently, device implantation with or without echocardiographic guidance is reported to be successful in almost 100% of cases, with a periprocedural complication rate of about 1%.5,6 With Amplatzer-like devices, the incidence of residual shunt is acceptably low. Effective closure can be achieved in about 90% of the patients. PFO closure without transesophageal echocardiography (TEE), ie, with fluoroscopic guidance only, has the advantage of shortening the procedure and therefore reducing costs, without compromising safety or long-term outcome.6
Procedural performance has proven to be device dependent. In numerous studies, the Amplatzer PFO occluder (APO; Abbott Vascular) has proven to be safe and effective, bearing the smallest risk of thrombus formation, device embolization, or residual shunt.7,8 A variety of Amplatzer-like devices have been developed over the past 15 years. Such devices have the potential to reduce costs while maintaining the high level of effectiveness and safety of the original.
The aim of this series was to compare the Cera PFO occluder (CPO; Lifetech Scientific), a nitinol-mesh, double-disc device, with the APO using propensity-score matching.
Methods
Patients. Between April 2013 and March 2014, a total of 30 patients underwent percutaneous PFO closure using the CPO. The indications for PFO closure were transient ischemic attack (TIA) in 7 patients (23%), cerebral vascular ischemia (CVI) in 12 patients (40%), peripheral embolism in 10 patients (33%), and a diving accident in 1 patient (3%).
Twenty-eight patients with complete follow-up data were matched with the same number of patients who received an APO during an earlier period, out of a cohort of 1000 patients treated with the APO devices at the University Hospital of Bern. For matching baseline characteristics like age, sex, and body mass index, PFO size and the presence of an atrial septal aneurysm (ASA) were considered. All patients gave written informed consent for the procedure and the collection of their data for scientific purpose.
Diagnosis. TEE was used to diagnose PFO and ASA. PFO was defined as a flap-like opening in the atrial septum secundum, with the septum primum serving as one-way valve allowing for permanent or transient right-to-left shunt. By injecting an aerated colloid solution into an antecubital vein at the end of a vigorous and sustained Valsalva maneuver, this interatrial valve can be detected. ASA, a congenital saccular flimsiness of the septum primum, was defined by a diameter at the base of 15 mm or greater, with at least a 10 mm excursion into either the left atrium (LA) or right atrium (RA), or a sum of the total excursion into the LA and RA of 10 mm or more.9
The right-to-left shunt, spontaneous or provoked, was semiquantitatively graded according to the amount of bubbles detected in the LA after crossing the interatrial septum on a still frame: grade 0 none; grade 1 minimal (1-5 bubbles); grade 2 moderate (6-20 bubbles); and grade 3 severe (>20 bubbles).2
Cera PFO occluder. The CPO consists of a polyethylene terephthalate (PET) membrane inside a nitinol wire frame coated with titanium nitride. According to the manufacturer, this coating reduces dissolution of nickel ions (from the nitinol wire) and promotes endothelium growth.10 In analogy to the APO,6 the CPO is a self-expandable double-disc device available in the following sizes of right/left discs, respectively: 18/18 mm, 25/18 mm, 30/25 mm, 30/30 mm, and 35/25 mm (Figure 1). It can be delivered using an 8-12 Fr SteerEase delivery sheath (Lifetech Scientific).
Percutaneous PFO closure. The intervention was performed under local anesthesia and procedural visualization was provided by fluoroscopic guidance only.6 However, all patients were examined using contrast TEE before the intervention for delineation of PFO anatomy and grading of severity.
The right femoral vein was punctured and a guidewire was advanced into the RA. The foramen ovale was crossed by a standard-length normal 0.035˝ guidewire alone, or with the help of a catheter (typically a 6 Fr Multipurpose catheter) under fluoroscopic guidance in the anteroposterior view. If a Multipurpose catheter was used, it was exchanged for an 8-12 Fr dedicated SteerEase delivery sheath, and the stretched and compressed CPO was advanced into the LA, screwed onto the tip of a pusher cable. In the LA, the left disc of the CPO was deployed out of the sheath and pulled back against the atrial septum. This was done in a left anterior oblique (LAO) projection showing the disc butting against the septum in profile. Then, the right disc of the CPO was deployed in the RA. After control of the device position by fluoroscopy using a contrast medium injection in an adjusted LAO projection to delineate the 2 discs on either side of the septum without any overlap, the catheter was detached from the CPO and pulled back. The punctured site was manually compressed, typically by the patient, to achieve hemostasis.
Patients were released to full physical activity as early as a few hours after the procedure. A transthoracic contrast echocardiography was performed before discharge in order to document correct and stable device position. Clopidogrel 75 mg once daily for 1 month and acetylsalicylic acid 100 mg once daily for 5 months were prescribed for antithrombotic protection.
Follow-up. The outcome following the intervention was prospectively assessed. A contrast TEE was repeated 6 months after percutaneous PFO closure. In case of a moderate-to-severe residual shunt, the implantation of a second device was recommended. In case of minimal residual shunt, functional closure was assumed, with no need for further medical treatment, reintervention, or repeat control echocardiography. Thereafter, all patients underwent structured telephone interviews, addressing recurrent embolic events, device-related problems, current antithrombotic medication, and health status.
Statistical analysis. Descriptive characteristics of the study populations were summarized as appropriate. Continuous variables were expressed as mean ± standard deviation and were compared using Wilcoxon rank-sum test. Categorical variables were summarized as absolute numbers and percentages and compared with the Chi-squared (χ2) test or Fisher’s exact test. Kaplan-Meier methods were used to estimate event rates at follow-up; comparisons were made using the log-rank test in the propensity-score matched cohort.
We used a propensity-score match to adjust for possible confounders between the patients receiving the CPO vs those receiving the APO. The primary endpoint for the propensity-score analysis was residual shunt at 6 months. Therefore, only the patients with complete follow-up were included for the matching. We performed a 1:1 matched analysis based on the propensity score of each patient. The log odds of the probability that a patient received the CPO were modeled as a function of the identified confounders. The following variables of interest were included in the model: age, sex, body mass index, presence of ASA, size of device of 25 mm, and the grade of shunt before procedure. By using the estimated logits, we initially selected a patient of the CPO group and matched them with a patient in the APO group with the closest estimated logit value. To assess the success of the matching procedure, we evaluated standardized differences of baseline covariates before and after matching. All analyses are two-sided, and α-level of 0.05 was considered significant. All analyses were performed in STATA software, version 13.0 (STATA Corporation). P-values are two tailed.
Results
The baseline characteristics of the entire cohort are summarized in Table 1 (before matching) and Table 2 (after matching). Two well-balanced populations without significant differences in baseline characteristics were obtained. Two patients were excluded: an 82-year-old woman who suffered a severe stroke with important sequelae before PFO closure died 6 months after the intervention and 1 patient was lost to follow-up. Patients were matched according to age, sex, body mass index, presence of ASA, device size of 25 mm, and the preprocedure shunt grade.
In the CPO group, all patients received a 25 mm device. In the APO group, there were 3 patients (11%) with a 18 mm device, 24 patients (86%) with a 25 mm device, and 1 patient (4%) with a 30 mm device. There were no significant differences concerning cardiovascular risk factors, PFO size, presence of ASA, and embolic index events. Fluoroscopy time was also similar among groups (P=.90). All implantation procedures were successful in both groups. In 2 patients, the CPO was the second device implanted after a relevant residual shunt had been detected by TEE 6 months after 35 mm APO implantantion in 1 case, and 30 mm Amplatzer Cribriform septal occluder implantation in the other case. The only procedural untoward events were 2 groin hematomas, which were associated with incidental coronary angiography in 1 patient and inadvertent arterial puncture in the other patient, and did not require any intervention or prolong hospitalization; both patients were in the CPO group.
Echocardiographic outcomes. Contrast TEE at 6 months was performed in 28 patients of the CPO group. All devices were in the correct position and no thrombi were detected. There was residual shunt in 2 CPO patients (7%). Both of these were graded as minimal without need for further action. Complete closure was achieved in 27 APO patients (log-rank test P=.15). One patient in the APO group had a moderate residual shunt, prompting no further action.
Late outcomes. In the 28 patients of the CPO group with follow-up, there was no difference compared with the APO group for the primary outcome of interest of residual shunt at 6 months (log-rank test P=.15).
During follow-up (1.0 ± 0.4 years), 1 death (mentioned above) and no recurrent embolic events were reported in the CPO group, compared with no death and no recurrent embolic events in the APO group.
Discussion
Percutaneous PFO closure with the APO has been proven safe and feasible in numerous studies, with reported complication rates ranging between 0.7%-9.0%. Complete closure rates ranged between 79%-98%, depending on whether transthoracic echocardiography or TEE were used for assessment of residual shunt.11,12 In terms of efficacy, observational studies, recently pooled by Agarwal et al, showed an advantage of PFO closure compared with medical treatment after assumed paradoxical embolism.13 However, due to insufficient statistical power, the superiority of percutaneous PFO closure was not confirmed by the 3 randomized controlled trials published so far, which all missed their primary endpoint.14-16 However, meta-analyses of these randomized data were able to show that, when using the APO, percutaneous PFO closure was superior to medical treatment for secondary prevention of recurrent strokes, suggesting a device-related effect.17-19 As a consequence, comparison between devices is relevant, as design may impact clinical efficacy.
The CPO shares several similarities with the original APO. Both are designed as a double-disc structure18 made of nitinol mesh with a polyester fabric inside each disc. In addition, disc sizes and waist lengths are very similar. The only notable difference is the coating of the CPO nitinol wire frame with titanium nitride. As described by Zhang et al, this coating decreases the dissolution of nickel ion into the patient’s blood stream. It is also meant to accelerate endothelial growth to minimize the risk of thrombotic apposition.10
Kaya et al performed a randomized controlled trial published in 2014 comparing the Cera septal occluder to the Amplatzer septal occluder for percutaneous atrial septal defect closure in more than 400 patients. The authors found similar rates of residual shunt (1.4% in the Cera group vs 1.0% in the Amplatzer group), device embolization (1 in the Cera group vs 4 in the Amplatzer group), and incidence of atrial arrhythmia (4 patients on the Cera group vs 2 in the Amplatzer group) with both device families. No thrombus formation was observed in either group after a mean follow-up of 25 months.20 Overall, the costs associated with the use of the Cera septal occluder were significantly lower than those generated by the implantation of the Amplatzer septal occluder (US $3500 vs US $5600; P<.001).
So far, no direct comparison has been performed between the CPO and the APO for percutaneous PFO closure. This series is the first to compare both devices using propensity-score matching. In addition, it represents the first report of the device without TEE guidance. A 2014 published retrospective analysis first described the outcomes of 11 patients undergoing PFO closure with the CPO device confirming feasibility and safety of the procedure.21 Although limited to a small number of patients, our study shows a similar safety profile as compared with the APO, considered nowadays the gold standard for percutaneous PFO closure. Our data show similar device success and very low complication rates in both groups. In addition, a comparable closure rate at 6 months was observed using TEE.
Although no systematic cost analysis was performed in the current study, PFO closure with the CPO device is expected to be less expensive than the APO device secondary to a lower purchase price.
Study limitations. The observational character and the small sample size are two important limitations of this study. To establish the safety and efficacy of the CPO, a randomized trial with a longer follow-up period is required. Furthermore, the number of patients included did not allow us to draw conclusions about the efficacy of percutaneous device closure.
Conclusion
With regard to procedural safety and closure rate at 6 months, performances of the CPO are comparable to those of the APO in this small patient cohort.
References
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*Joint first authors.
From the Departments of 1Cardiology and 2Neurology, University Hospital of Bern, Bern, Switzerland.
Funding: This study was supported by a grant from Lifetech Scientific.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Windecker reports grant support from Biotronik, Boston Scientific, Bracco Pharmaceuticals, Edwards Lifesciences, Medtronic, Terumo, and Abbott Vascular; personal fees from Boston Scientific and Daiichi Sankyo. Dr Mattle reports speaker’s bureau participation for Abbott Vascular; personal fees from Bayer Healthcare, Biogen Idec, Boston Scientific, Daiichi Sankyo, Medtronic, Neuravi, Novartis, Pfizer, Sanofi, Servier, SwissMedic, and Research Council of Norway. Dr Meier report speaker’s fees from Abbott Vascular. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 23, 2017, final version accepted February 3, 2017.
Address for correspondence: Bernhard Meier, MD, Professor of Cardiology, Cardiovascular Department, University Hospital of Bern, 3010 Bern, Switzerland. Email: bernhard.meier@insel.ch
