Transcatheter Closure of Patent Foramen Ovale Associated with Atrial Septal Aneurysm with Amplatzer Cribriform Septal Occluder

ABSTRACT: Objective. We sought to evaluate the short- and long-term outcomes of Amplatzer Multi-Fenestrated Septal Occluder Cribriform (AMF) device use in the percutaneous closure of patent foramen ovale (PFO) associated with atrial septal aneurysm (ASA). Background. Since patients with PFO, associated with ASA, are at higher risk of embolic events (EE), the AMF device might offer advantages in this subgroup of patients. Methods. Overall, 38 consecutive patients, with both PFO and ASA, underwent percutaneous closure of the defect with the AMF device, and the results were compared to those in 38 patients with PFO and ASA treated with the Amplatzer PFO device (APO). Death due to embolism, stroke or transient ischemic attack (TIA) were considered recurrent EE. Pre- and post-intervention shunting and 6-month residual shunting were evaluated echocardiographically with intravenous contrast injection. Results. The procedure was successfully completed in all patients in both groups. No procedure-related complications were observed during hospitalization. Immediate closure was achieved in all patients in the AMF group, whereas 3 patients in the APO group showed a small residual shunt. Residual shunting was observed at 6 months in 2 patients in the APO group. No recurrence of EE was recorded in the AMF group. Recurrent TIA was observed in 3 patients in the APO group; 2/3 patients had a small residual shunt following the procedure and at 6-month follow up. Conclusion. The AMF device might offer advantages in terms of rate of EE recurrence or residual shunt compared to the APO device in PFO patients associated with ASA. J INVASIVE CARDIOL 2009;21:290–293 Key words: Amplatzer Cribriform septal occluder, patent foramen ovale, congenital heart disease in adults Atrial septal aneurysm (ASA) has been associated with neurological events and patients with both patent foramen ovale (PFO) and ASA are at greater risk of recurrent stroke with a three- to five-fold increased risk of recurrence compared to patients with PFO alone.1–3 ASA can facilitate paradoxical embolism because, due to highly mobile atrial septal tissue, which may increase the PFO diameter leading to a more frequent and wider opening of an otherwise small channel,4,5 it may promote right-to-left shunting (RLS) by redirecting the flow from the inferior vena cava toward the PFO6 and, furthermore, because it has been considered a nidus for local thrombus formation and, subsequently, embolization.7 Treatment of patients with PFO associated with ASA has not yet been systematically studied. Various devices have been used for PFO closure8–12 and the use of a novel septal occluder device, the Amplatzer multi-fenestrated septal occluder cribriform (AMF) in consecutive patients with PFO, has been recently described with favorable results in terms of ease-of-use and effectiveness of immediate closure of PFO.13 The aim of the present study was to evaluate the short- and long-term outcomes of transcatheter closure of PFO, associated with ASA, in a consecutive series of patients using the AMF device and to compare the findings with those in patients with both PFO and ASA treated with the Amplatzer PFO occluder (APO) for secondary prevention of embolic events (EE). Methods Study population. Between January 2007 and April 2008, 38 consecutive patients with both PFO and ASA and with ≥ 1 paradoxical cerebral embolic event underwent elective closure of the PFO using the Amplatzer multi-fenestrated septal occluder Cribriform device. To evaluate the effectiveness of the AMF device for PFO closure, we compared these results with those in 38 consecutive patients with both PFO and ASA who had undergone percutaneous transcatheter PFO closure with the Amplatzer PFO occluder device, shortly before availability of the AMF device. The study protocol was approved by local ethics committee and all patients gave written informed consent to the investigation. The cerebrovascular event was considered the result of a paradoxical embolism when the presence of the PFO and a spontaneous or provoked right-to-left shunt (RLS) was identified by transesophageal contrast echocardiography (TEE) in association with clinically and/or radiographically confirmed ischemic stroke or transient ischemic attack (TIA) and with no other evidence of a cardiac, aortic or cerebrovascular disorder. All patients underwent thorough and meticulous evaluation to exclude any other causes of systemic embolism. Patient evaluation, depending upon the case, included neurological examination, brain computed tomography (CT) or magnetic resonance imaging (MRI), extracranial Doppler ultrasonography, 12-lead electrocardiogram (ECG), 24-hour blood pressure and ECG monitoring, two-dimensional (2-D) echocardiography with microbubbles test with and without the Valsalva maneuver, TEE, Doppler of lower extremities to exclude deep vein thrombosis and hypercoagulable workups (proteins C and S, antithrombin III, anticardiolipin antibodies, homocysteine, factor V Leiden and lupus anticoagulant). Echocardiographic definitions. All echocardiographic evaluations, prior to the transcatheter PFO closure, were made with a multiplane TEE probe, using 10 ml of agitated saline solution as contrast agent to study the exact anatomy of the interatrial septum. PFO was defined as a flap-like opening in the atrial septum secundum, with the septum primum serving as a one-way valve allowing permanent or transient right-to-left shunt. Atrial septal aneurysm was defined as the presence of a localized protrusion of the fossa ovalis, with a base width ≥ 15 mm and mobile septum excursion ≥ 10 mm into the left or right atrium.14 Quantification of PFO shunt volume, as determined by contrast injection at rest and during the Valsalva-maneuver, was defined. A “small” shunt volume was defined as 3–20 bubbles and a “large” shunt volume as > 20 bubbles passing the PFO into the left atrium. Implantation procedure and AMF device description. Transcatheter PFO closure has been described in detail elsewhere.15 The procedure was carried out under intracardiac echocardiography (ICE) (AcuNav Diagnostic Ultrasound Catheter, Siemens Medical, California), TEE and transthoracic (TTE) guidance. On the day of implantation, 250 mg acetylsalicylic acid and amoxicillin were administered intravenously (IV). Three doses of amoxicillin were administered, 2 days after the procedure for prophylaxis of bacterial endocarditis. Following sheath placement in the right femoral vein, heparinization was performed with 100 units/kg body weight of unfractionated heparin. The position of the device was confirmed by chest X-ray and the degree of the shunting was quantified by TTE before discharge. For prophylaxis of EE, after device implantation, patients were treated with acetylsalicylic acid (300 mg) for 6 months. Standard bacterial endocarditic prophylaxis was recommended for 12 months. The Amplatzer multi-fenestrated septal occluder is a percutaneous transcatheter device used for the closure of multi-fenestrated atrial septal defects, but it would be more efficacious and safer than other devices, especially in high risk patients such as those with PFO associated with ASA. The Amplatzer multi-fenestrated septal occluder is a self-expandable, double disc device made with nitinol wire mesh. The device is made from two equal sized discs, linked together by a 3 mm connecting waist. In order to improve closure, the discs are filled with polyester fabric which is securely fastened to each disc by polyester thread. Follow up. Patients in the two groups were observed at follow up, which included clinical examination and echocardiography with TTE at 1, 6 and 12 months after the procedure and yearly thereafter. Moreover, chest X-ray, for the detection of eventual fracture of the device, as well as TTE or transcranial Doppler (ce-TCD) with IV contrast injection, for detection of residual shunting, at rest and after the Valsalva maneuver, were performed at 6-month follow up. Residual shunting was graded according to the definition used for evaluation of the PFO prior to closure, as described above. All patients and family physicians were instructed to inform us of any change in clinical status. Death due to cerebrovascular embolism, stroke or TIA were considered recurrent EE. Patients with suspected recurrence of cerebrovascular EE were reexamined by a neurologist and a brain imaging study was performed. Follow-up data included also the eventual need of reintervention for significant residual shunt or device malalignment. Statistical analysis. Descriptive statistics were calculated for demographic characteristics, the duration of follow-up and rate of cerebral EE recurrence. Values are expressed as mean ± SD. Comparisons were made with paired t-test and χ2 analysis. A p-value of Results Patient population. Demographic data are outlined in Table 1. Indications for transcatheter PFO closure included only TIA or stroke and no statistically significant differences were observed in the two groups in terms of echocardiographic parameters and embolic risk profile. Overall, 11 patients were over 55 years of age at the time of percutaneous atrial septal defect closure, 6 in the AMF group and 5 in the APO group, moreover 11 patients had > 1 cerebrovascular event, 4 in the AMF group and 7 in the APO group, respectively. The vast majority of the patients demonstrated large TEE baseline RLS in both groups. Procedural and in-hospital outcome. The procedural data are outlined in Table 2. In all patients the procedure was completed successfully. No device migration or need for a second device was observed in either group. Of the 38 patients in the AMF group, 30 (79%) were submitted to PFO closure under ICE guidance and 8 (21%) under TEE guidance, whereas in the APO group, the procedure was carried out under ICE, TEE and TTE guidance in 26 (68%), 10 (26%) and 2 (6%) patients, respectively. The 25 mm Amplatzer Cribriform device was used in 36 patients (95%) and the 35 mm device in the remaining 2 patients (5%). The size of the Amplatzer device in the APO group was 18 mm, 25 mm and 35 mm in one (3%), 32 (84%) and 5 (13%) patients, respectively. The PFO diameter, assessed echocardiographically, was 12 ± 11 mm and 12 ± 10 mm in the AMF and APO group, respectively. The measurement of PFO diameter, by a balloon catheter, was required in 7 patients, all of them belonging to the APO group (p Discussion Previous reports demonstrated that transcatheter PFO closure is a safe and efficacious technique using a variety of transseptal devices in patients with paradoxical embolism.8,10–12 Although a report has recently been published on a small series of patients treated with the Amplatzer cribriform septal occluder device including only 8 patients with associated ASA13 and demonstrating its safety and effectiveness in the PFO closure, the present study is the first to systematically investigate patients with PFO associated with ASA treated with the Amplatzer cribriform septal occluder device. The present investigation demonstrates that: 1) transcatheter closure of PFO, using the AMF device, is safe also in high risk patients such as those with associated ASA; 2) procedural success and complications are similar to those following treatment of PFO with ASA using the Amplatzer PFO occluder; 3) the AMF group showed a lower rate of recurrent EE and residual RLS compared to the APO group. Patients with ASA + PFO are at higher risk of stroke and recurrence of stroke compared to patients presenting only PFO, and secondary prevention, with anticoagulant agents or acetylsalicylic acid appear to be insufficient to protect against recurrent EE.2 Furthermore, patients with residual shunt, at the time of the procedure, may be at higher risk of recurrent EE compared to those with immediate complete occlusion.16,17 Possible explanations for persistence of residual shunt following transcatheter PFO closure include the use of a device which is too small for the defect, inability of the device used to adequately conform to the defect, leakage through the device, septal mobility limiting adequate fusion of the device to the tissue or trauma to the septal tissue after the device implantation. It has recently been observed that the presence of an ASA is predictive of a residual shunt after placing an Amplatzer PFO occluder device.18 In our study population, recurrent EE occurred in 3 patients, all of whom belonged to the APO group. Moreover, 2 of these 3 patients showed a small RLS after the procedure and 1 had > 1 cerebrovascular event at baseline. Recurrent EE and immediate RLS were not observed in the AMF group, thus suggesting that this device might provide more complete occlusion compared to the APO device in patients with PFO + ASA. The AMF device may make “buttoning” the septum primum and the septum secundum together easier with its arms opposed tightly together and may be more efficient than the double-disk devices that have an additional center occluder, such as the Amplatzer secundum atrial septal defect occluder or double-umbrella devices, achieving a more complete closure and, consequently, a lower rate of residual RLS. Otherwise, an ideal device for PFO closure is a device that does not interfere with other important adjacent cardiac structures. The Cribriform septal occluder device is very similar to the Amplatzer PFO device, but it differs in that it has discs of equal diameter instead of an 18 mm left atrial disc, as is present in the PFO device. The possibility that the larger left atrial disc could increase cardiac erosion or perforation needs to be taken into consideration. Most perforations or erosions have been described in the oversized ASD device setting.19 Device size is based on the length of the aortic and superior vena cava rim. A device with a radius equal or smaller than the shortest measured rim is recommended. The most important feature in establishing the exact sizing of the device is to avoid overriding of the device discs around the aorta or tenting of the atrial roof. The recommendation is that the rims be comprised between 7–9 mm. Moreover, by using AMF device particularly in the presence of PFO associated with ASA, the measurement of the PFO size with a balloon catheter can be spared, thus avoiding the risk of increasing the PFO diameter. In our opinion, it is mandatory that the interventional cardiologists’ team has a thorough knowledge of transesophageal or intracardiac echocardiography in order to study the correct anatomy of the interatrial septum and to choose a device of an appropriate size in order to avoid device-related complications. Study limitations. Results of the present study still show several limitation. For example, the study is not randomized. It is possible that some of the recurrent EE, observed during the first 6 months of follow up likely occurred before complete endothelialization and could, therefore, have been secondary to embolism from the device despite adequate antiplatelet therapy. It is possible that 6 months of residual RLS is underestimated, since some patients, in both groups, were evaluated by TTE. The small sample size of our study population and the small number of recurrent EE observed did not allow us to identify predictors of recurrent events following device implantation. Conclusion Trancatheter closure of PFO with the Amplatzer Cribriform Septal Occluder device is a safe and effective procedure also in high-risk patients such as those with associated ASA presenting with paradoxical embolism. The results of the present study suggest that the Amplatzer Cribriform Septal Occluder device is easy to use and may lead to more complete closure of the defect and a lower rate of EE at short- and long-term follow up, compared to the Amplatzer PFO occluder device. Randomized trials on a large series of patients are needed to confirm these preliminary findings and to better address the incidence of late adverse events, particularly mechanical damage of adjacent cardiac structures. From the Interventional Cardiology Unit, S. Camillo Hospital, Rome, Italy. The authors report no conflicts of interest regarding the content herein. Manuscript submitted January 2, 2009, and accepted February 13, 2009. Address for correspondence: Carmine Musto, MD, Interventional Cardiology Unit, S. Camillo Hospital, Circonvallazione Gianicolense 87, 00151 Rome, Italy. E-mail: c.musto@jumpy.it

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