A Comparison Between Gore Cardioform and Amplatzer Septal Occluder for Percutaneous Closure of Patent Foramen Ovale Associated With Atrial Septal Aneurysm: Clinical and Echocardiographic Outcomes

Objectives. To evaluate the short- and long-term clinical and echocardiographic outcomes of the percutaneous closure of the patent foramen ovale (PFO) with an atrial septal aneurysm (ASA) using 2 different devices. Methods. We enrolled 100 patients with PFO and ASA. Fifty consecutive patients had transcatheter closure of the PFO with the Gore Cardioform septal occluder (GSO) (Gore Medical) and a second group of 50 consecutive patients with the Amplatzer PFO occluder (APO) (Abbott). A clinical and transthoracic echocardiographic follow-up was performed at 1, 3, 6, and 12 months after the implant procedure. The primary endpoint was the incidence of moderate-to-severe residual right-to-left shunting (rRLS) at the 6-month follow-up. The procedural results and the recurrence of embolic events at 1 year were also investigated. Results. The procedure was successful in all patients. The immediate postprocedural moderate-to-severe rRLS incidence was similar between the 2 groups (GSO 14% vs APO 12%; P=NS) as well as the incidence of moderate-to-severe rRLS at the 6-month follow-up (GSO 4% vs APO 4%; P=non-significant). In only 1 patient of the GSO group, there was a persistent moderate rRLS at the 1-year follow-up. The 6-month and 1-year complete occlusion rate for all subjects was 93% and 96%, respectively. No devices embolized and no death or recurrent embolic events were observed during hospitalization through the 1-year follow-up. Conclusions. GSO and APO devices appear to be safe and effective devices for the percutaneous closure of a PFO with ASA, showing similar results for the presence of rRLS at the 6-month follow-up, complete occlusion rate, and clinical embolic recurrences.

J INVASIVE CARDIOL 2021;33(11):E857-E862. Epub 2021 October 15.

Key words: Amplatzer septal occluder, atrial septal aneurysm, Gore Cardioform septal occluder, intracardiac echography, patent foramen ovale, residual right-to-left shunting

The most recent randomized clinical trials on cryptogenic stroke and patent foramen ovale (PFO) percutaneous closure have highlighted the benefit of the percutaneous interventions as compared with medical therapy,^1-5 especially in those patients with additive anatomical risk factors.^6-9 The combination of the PFO with an atrial septal aneurysm (ASA) is associated with a higher risk of left thromboembolic events.^10,11 The presence of an ASA requires a thorough echocardiographic analysis of interatrial septal morphology in order to select the most appropriate device to achieve the maximum effectiveness and minimum device-related complications. The rate of residual right-to-left shunting (rRLS) is variable among different device types and it has been associated with an increased incidence of recurrent embolic events.^12,13 Recently, a new percutaneous suture-mediated PFO closure system without the use of an implantable device, the NobleStitch EL system (Heartstitch), has been introduced in interventional practice.^14,15 Despite the remarkable advantages, more clinical trials are needed to investigate the feasibility and efficacy of this new deviceless technique in complex anatomy PFO.^16,17 The Gore Cardioform septal occluder (GSO) (Gore Medical) and the Amplatzer PFO closure device (APO) (Abbott) are approved and well-investigated devices for PFO closure, although their use has not been systematically studied in patients with PFO and ASA. The aim of the present study is to investigate the short- and long-term clinical and echocardiographic outcomes of the GSO and APO devices in a consecutive series of patients with clinically significant PFO associated with an ASA.

A total of 100 patients with a positive history of a paradoxical embolic event in the presence of a PFO associated with an ASA were enrolled in this study. The patients underwent elective closure of the PFO at the Interventional Cardiology Unit of San Camillao Hospital in Rome, Italy. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in a priori approval by the institution’s human research committee. Among the subject population, 50 consecutive patients were treated by means of GSO implantation and their results were compared with those of 50 consecutive patients treated with APO devices. Accordingly, the implant device selected was based independently on physician preference.

Patient demographic and procedural data were prospectively collected. An embolic event was classified as a paradoxical embolism when the following criteria were fulfilled: (1) presence of PFO with spontaneous or provoked right-to-left shunting (RLS) during contrast transesophageal echocardiography (TEE); (2) clinically and/or radiographically confirmed ischemic stroke or transient ischemic attack or peripheral embolism; (3) exclusion of any other identifiable cardiac, aortic, or cerebrovascular causes. Each case was evaluated individually and patient workups included neurological examination, brain computed tomography, or magnetic resonance imaging (MRI) to detect radiological signs of cerebral ischemia; extracranial Doppler ultrasonography to investigate the presence of RLS; 12-lead electrocardiography, 24-hour blood pressure, and electrocardiography monitoring to exclude supraventricular arrhythmias; agitated saline contrast transthoracic echocardiogram (TTE) (bubble test) with and without the Valsalva maneuver and TEE to confirm the presence of a patent foramen ovale; venous Doppler of lower extremities to exclude deep vein thrombosis; and hypercoagulable workups (including protein C and S, antithrombin III, anticardiolipin antibodies, homocysteine, factor V Leiden and lupus anticoagulant).

Echocardiographic protocols and definitions. The diagnosis of a PFO with RLS was made by a multiplane TEE probe and an accurate evaluation of the interatrial septum as well as right and left atria. An ASA was defined by the presence of a localized protrusion of the fossa ovalis with a base width ≥15 mm and mobile septum excursion ≥10 mm. A long tunnel was defined as a ≥10 mm measured overlap of the septum primum and the septum secundum. Lipomatous hypertrophy of the atrial septum was defined by the presence of ≥15 mm septum secundum hypertrophy. The presence of the Chiari network and Eustachian valve were also evaluated. During the bubble study, 10 mL of agitated saline contrast were injected intravenously and bubbles were counted in the left atrium during 3 cardiac cycles after right atrium opacification. A small RLS was defined as 1-9 bubbles observed in the left atria during 3 cardiac cycles, moderate RLS was measured as 10-20 bubbles, and severe RLS was determined by >20 bubbles. Moderate and severe RLS were regarded as significant shunts.

Device description and closure protocol. The physicians performing the intervention were all experienced with the PFO closure technique. Two devices were used in this study. The GSO consists of 2 soft and conformable circular discs with 5 independent petal wires in a frame covered in a thin layer of ePTFE. The wire frame is made of a nickel-titanium metal alloy with a platinum core. The GSO device is available in 20, 25, and 30 mm options. The Amplatzer PFO occluder and Amplatzer Cribriform occluder (Abbott) are self-expandable devices made of nitinol wire mesh. The Amplatzer Cribriform Occluder is made from two equal sized discs, whereas the left atrial Amplatzer PFO Occluder disc is slightly smaller than the right atrial disc. The discs of both devices are connected together by a bond bridge and are available in 18, 25 and 35 mm.

All procedures were carried out under local anesthesia and the device size was chosen by intracardiac echocardiography (ICE) (AcuNav diagnostic ultrasound catheter; Siemens Medical) guidance, without intention to balloon size. On the day of implantation, 250 mg of intravenous acetylsalicylic acid and a 300 mg loading dose of clopidogrel were administered. Following sheath placement in a femoral vein, 100 U/kg body weight of intravenous unfractionated heparin was administered. After device implantation, all patients received aspirin 100 mg daily and clopidogrel 75 mg daily for 3 months. Thereafter, clopidogrel was discontinued and aspirin therapy maintained for an additional 9 months. Standard bacterial endocarditis prophylaxis was recommended for 12 months.   

Follow-up. Patients were prospectively followed with clinical examination and TTE at 1, 3, 6, and 12 months after the procedure. At the 6-month follow-up, a bubble study was completed with TTE for detection of rRLS at rest and after the Valsalva maneuver. Any rRLS was graded according to the definition used for the evaluation of the PFO prior to closure, as described above. In cases of rRLS at 6-month evaluation, contrast TTE was repeated 6 months later. Death or recurrent embolic events at 1 year were considered clinical endpoints, whereas the 6-month persistence of moderate-to-severe RLS was considered the echocardiographic endpoint. Patients with suspected cerebral recurrent embolic events were re-evaluated by a senior neurologist and a brain MRI was repeated. The need for reintervention due to significant rRLS or device malalignment was also evaluated.

Statistical analysis. Categorical variables are compared by a Chi-squared or Fisher’s exact test, when appropriate. Statistical significance was assumed with a P-value <.05. Parametric variables were compared by one-way analysis of variance. Statistical analysis was performed using the SPSS, version 12, and SAS (Fisher’s exact test) software.

Patient population. Baseline characteristics of patients in each group are outlined in Table 1. No significant differences in terms of embolic risk profile and echocardiographic parameters were observed among the 2 groups. The study population shows high-risk characteristics for recurrent embolic events and challenging anatomies since all patients had a PFO with ASA, 49% had a long tunnel, and 15% had a hypertrophic septum secundum. The vast majority of the population had a large or spontaneous RLS (72%), 21% had >1 embolic event, and another 21% were diagnosed with a thrombophilic state.

Procedural and in-hospital outcome. The procedural data are outlined in Table 2. The procedure and fluoroscopy times were similar in the GSO and APO groups. The procedure was successful in all patients and none required an additional device to achieve placement. In the GSO group, a 25 mm device was implanted in 40 patients (80%) and a 30 mm device in 10 patients (20%). In the APO group, a 25 mm device was implanted in 39 patients (78%) and a 25 mm multifenestrated device was implanted in the remaining 11 patients (22%). In the GSO group, 2 devices required repositioning after the initial deployment due to unsatisfactory placement in the septum. Closure was then achieved using the initial device. Immediate moderate-to-severe RLS was similar in the GSO group compared with the APO group (14% vs 12%, respectively; P=non-significant). No death, recurrent embolic events, cardiac tamponade, or retroperitoneal hematoma were observed during hospitalization. One patient in the APO group and 1 patient in the GSO group showed a supraventricular arrhythmia and spontaneously converted back to sinus rhythm. Moreover, 1 patient in the APO group showed transitory ST-segment elevation in leads DII, DIII, and aVF caused by an air embolism in the right coronary artery, which spontaneously resolved within a few minutes.

Follow-up. The 6-month follow-up data are outlined in Table 3. After discharge, all patients were clinically followed for 1 year. No deaths or recurrent embolic events were recorded among the 2 groups. The 6-month occurrence of a moderate-to-severe rRLS was the same in the 2 groups (4%). Particularly, at 6-month follow-up, no cases of severe rRLS were observed in the APO group, whereas 1 patient (2%) in the GSO group showed severe provocable rRLS (P=.66) (Table 3). A contrast TEE was repeated 6 months later and the RLS decreased from severe to moderate grade. This patient was clinically followed, and he is still on clopidogrel 75 mg/day. Moderate 6-month rRLS was present in 1 GSO patient and 2 APO patients. A contrast TTE was repeated 6 months later in all 3 patients and the degree of rRLS was reduced from moderate to small. At 6 months, a small rRLS was observed in 2 GSO patients and 1 APO patient (P=.49). A contrast TEE was repeated at 1 year from the index procedure showing complete occlusion in all 3 patients. Complete occlusion of 93% was observed for all subjects from both groups at 6 months and 96% at the 1-year follow-up. Minor adverse events, including chest discomfort, palpitations, and dyspnea, were present at the 1-month follow-up in each group but disappeared in most patients by the 6-month follow-up. No patient required reintervention for device malalignment.

The present study demonstrates that both the GSO and the APO devices are safe and effective for the percutaneous closure of a PFO associated with an ASA, showing a low rate of 6-month rRLS and no clinical adverse events at 1-year follow-up. The simultaneous presence of a PFO and ASA has been correlated with paradoxical embolism through several mechanisms; it may facilitate RLS from the inferior vena cava through the PFO, it could be associated with mechanical atrial dysfunction and atrial fibrillation,¹⁸ or it can lead to thrombus formation.¹⁹ Moreover, the presence of the ASA represents a challenging anatomy for the percutaneous closure of the PFO, regardless of the implantation technique, and it has been associated with a higher rate of rRLS with respect to the PFO occlusion without ASA.²⁰ The results of the present study indicate that the RLS, as the principal mechanism of ASA-related embolism, can be effectively eliminated in the majority of patients. Several studies have reported the feasibility and efficacy of percutaneous PFO closure in the presence of complex anatomical findings,^21-23 but no studies have separately analyzed side by side the efficacy of the 2 most widely used PFO occluder devices for the percutaneous treatment of PFO with ASA. Currently, no dedicated closure device has been developed for this subgroup of patients.

The Noblestich EL system, without a permanently implanted device, represents a new technology overcoming most of the limitations of traditional PFO occluder devices, ie, difficulty to perform a trans-septal puncture for future left-sided interventions (such as left atrial appendage closure, arrhythmia ablation, and mitral valve interventions) and early and late complications related to the implanted closure device (atrial wall erosion, perforation, fracture, migration-embolization, infection, thrombosis, induction of arrhythmias, allergic reactions to nickel).^14,15 However, these limitations are extremely rare, and although this innovative technology is very promising, no conclusive data are reported regarding the feasibility and efficacy of the Noblestich system in challenging anatomies. Indeed, careful analysis of all patients with rRLS treated by the Noblestich technology suggests that in the presence of a wide redundant septum, particularly the septum primum, a single suture might not be sufficient to approximate both septa in order to close the PFO completely. More data, further experience, and long-term follow-up with the technique are needed to investigate this issue more deeply, including the ability to place additional sutures to achieve closure, especially in challenging anatomies.^16,17

The present study, for the first time, directly compares the 2 most used and validated closure devices in patients with both a PFO and an ASA; ie, the APO device, which is more rigid, but extremely safe and effective, as shown by long-term follow-up studies, and the GSO device, which is softer than other devices, with a lower profile and without any bulky protrusion into the atria (Figure 1). These 2 devices were tested in a population with a high risk of recurrent embolic events or rRLS because all patients had a PFO with associated ASA and the vast majority of them had an adjunctive clinical and/or anatomical feature of risk. Nevertheless, we found that the clinical and echocardiographic results of the GSO favorably compare with those of the APO devices. No death or recurrent embolic events were registered at 1-year follow-up. In all patients, the 6-month and 1-year complete occlusion rate was 93% and 96%, respectively. The echocardiographic findings suggested that the occlusion process is not instantaneous, but rather occurs progressively in the months following the procedure. Postprocedural moderate/severe RLS had an occurrence rate of 13% in all patients (14% GSO vs 12% APO), 4% at 6-month follow-up in both groups combined, and 1% at 1-year follow-up (Figure 2). These results suggest that the definite occlusion time is not related to the different characteristics of the 2 devices, but seems to be related to their ability to firmly oppose the septum primum more closely due to the presence of a double-umbrella design. In addition, intraprocedural results were also similar in the 2 groups. The GSO and APO devices were successfully deployed in all patients, and fluoroscopy and procedural times were similar in both groups. Only 2 patients in the GSO group required device repositioning, and were subsequently repositioned and released using the same device. No device embolization was recorded in this series of patients. Thus, based on our experience, it is mandatory to select the appropriate device by utilizing an accurate morphological evaluation with TEE or ICE of the interatrial septum anatomy to minimize device-related complications and to achieve the optimal occlusion in order to reduce as much as possible the rRLS and, consequently, to make the interventions safer and more effective.

Study limitations. The present study has some limitations. First, it is a small, non-randomized study, although it directly enrolled consecutive patients comparing 2 different devices and the device choice was operator independent. Second, the study follow-up was limited to 1 year. Third, although we found no differences in the rates of recurrent embolic events, the study does not have sufficient power to show a statistical difference for those clinical events.

The present study demonstrates that both GSO and APO devices are safe and effective in the percutaneous closure of a PFO with an associated ASA. Device- and procedure-related complications are rare, and long-term clinical and echocardiographic follow-up results are reassuring. Larger studies are needed in the future to establish the most appropriate device and implantation technique in this high-risk cohort of patients.