Comparison Between the New Gore Septal and Amplatzer Devices For Transcatheter Closure of Patent Foramen Ovale

Transcription

1 2922 MUSTO C et al. Circulation Journal ORIGINAL ARTICLE Official Journal of the Japanese Circulation Society Cardiovascular Intervention Comparison Between the New Gore Septal and Amplatzer Devices For Transcatheter Closure of Patent Foramen Ovale Short- and Mid-Term Clinical and Echocardiographic Outcomes Carmine Musto, MD, PhD; Alberta Cifarelli, MD; Rosario Fiorilli, MD; Francesco De Felice, MD; Antonio Parma, MD; Marco Stefano Nazzaro, MD, PhD; Elena Guerra, MD; Francesca Fiorilli, MD; Roberto Violini, MD Background: The ideal device for percutaneous patent foramen ovale (PFO) occlusion should provide effective closure with long-term biocompatibility and it should have a low profile without interfering with adjacent cardiac structures. Long-term data regarding safety and efficacy of the GORE Septal Occluder (GSO) are lacking. The aim of this study was to investigate the short- and mid-term clinical and echocardiographic outcomes of this device. Methods and Results: Forty-five consecutive patients with clinically significant PFO were treated with GSO and their results were compared with those of 45 consecutive patients treated with Amplatzer PFO device (APO). Primary endpoint was the incidence of 6-month residual right-to-left shunting (rrls). The procedural results and the recurrence of embolic events (REE) at 1 year were also investigated. No differences in terms of embolic risk profile and echocardiographic parameters were observed between the 2 groups. GSO was successfully implanted in all patients without device-related complication. In 2 patients for whom device position was not optimal, the GSO was easily retrieved and a new GSO was successfully repositioned. Immediate moderate severe rrls was similar in 2 groups. No cases of severe 6-month rrls were registered. Two patients (4%) and 1 patient (2%) had moderate 6-month rrls in the GSO and APO group, respectively (P=NS). No cases of REE were registered at 1-year follow-up. Conclusions: GSO appears a valuable alternative to Amplatzer device for PFO occlusion. (Circ J 2013; 77: ) Key Words: Gore septal occluder; Patent foramen ovale; Right-to left shunting Nowadays there are a number of available devices for patent foramen ovale (PFO) closure, 1 3 each with clinical and technical definitive characteristics, but studies examining their comparative safety and efficacy are limited. Double-disk devices are the most commonly used but they raise concerns about long-term erosion, 4 interference with inter-atrial septal dynamics and local/systemic inflammatory reactions. 5 Other types of occluders are more conformable but may be technically challenging to implant or not suitable for the wide variety of PFO anatomy. 6 The ideal device should provide effective closure of the PFO with long-term biocompatibility, be easy to implant and to remove when needed and have a low profile without interfering with adjacent cardiac structures. The GORE Septal Occluder (GSO) is a newly approved device for PFO closure designed to include all these features but data regarding its outcome are limited. Therefore, the aim of the present study was to investigate the short- and mid-term clinical and echocardiographic outcomes of this device in a consecutive series of patients undergoing percutaneous closure of clinically significant PFO. Methods The subjects included 90 patients with a PFO and a positive history of paradoxical embolic events who underwent elective closure of the PFO at San Camillo Hospital, Rome, Italy. From July 2011 to June 2012, 45 consecutive patients were treated by means of a GSO implantation (GSO group). Their results were compared with those of the last 45 consecutive patients treated with the Amplatzer PFO or Amplatzer Cribriform Septal Occluders (APO group) in the period immediately preceding the availability of the GSO device. The choice of device was made Received May 1, 2013; revised manuscript received July 2, 2013; accepted August 1, 2013; released online September 3, 2013 Time for primary review: 36 days Interventional Cardiology Unit, San Camillo Hospital, Rome, Italy Mailing address: Carmine Musto, MD, PhD, Interventional Cardiology Unit, San Camillo Hospital, Via Circonvallazione Gianicolense n. 87, Rome, Italy. cmusto@hotmail.it ISSN doi: /circj.CJ All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 Gore Septal Occluder for Percutaneous PFO Closure 2923 Figure 1. Flow-chart for identification of therapeutic strategy for patients with symptomatic patent foramen ovale (PFO). *Clinical risk factors: ischemic event during Valsalva maneuver, concomitant deep venous thrombosis, concomitant pulmonary embolism, thrombophilia; anatomic risk factors: atrial septal aneurysm, basal right-to-left shunting (RLS), severe (>25 microbubbles) RLS, PFO channel >4 mm. OAT, oral anticoagulation therapy; TIA, transient ischemic attack. independently from septal morphology or physician preference. Patient demographic and procedural data were prospectively collected. An embolic event was considered as being due to paradoxical embolism when the following criteria were fulfilled: (1) clinically and/or imaging confirmed ischemic stroke, transient ischemic attack or peripheral embolism; (2) presence of a PFO with spontaneous or provoked right-to-left shunting (RLS) during contrast transesophageal echocardiography (TEE); (3) exclusion of any other identifiable cardiac, aortic or cerebrovascular cause. Depending on the case, patient workups included a neurological examination, brain computed tomography or magnetic resonance imaging (MRI), extracranial Doppler ultrasonography, 12-lead electrocardiogram (ECG), 24-h blood pressure and ECG monitoring, trans-thoracic echocardiogram (TTE) with a bubble test with and without the Valsalva maneuver, TEE, venous Doppler of lower extremities and hypercoagulable workups (including proteins C and S, anti-thrombin III, anticardiolipin antibodies, homocysteine, factor V Leiden and lupus anticoagulant). The decision-making process regarding the indications for PFO closure is summarized in Figure 1. 7 Echocardiographic Protocols and Definitions The diagnosis of a PFO was made on multiplane TEE. Atrial septal aneurysm (ASA) was defined as the presence of a localized protrusion of the fossa ovalis, with a base width of 15 mm and mobile septum excursion of 10 mm between the 2 atria. Long tunnel was defined as an overlap of the septum primum and septum secundum >10 mm. The presence of spontaneous or provoked RLS was documented on contrast TEE with i.v. injection of 10 ml agitated saline. Bubbles were counted in the left atrium within 3 cardiac cycles after right atrium opacification. Small RLS was defined as 1 9, moderate as and severe as >25 bubbles passing into the left atrium through the inter-atrial septum. Moderate and severe RLS were considered as significant shunts. Device Description and Closure Protocol Patients were included in this study when informed consent had been obtained. The procedures were in accordance with ethics standards of the responsible committee on human experimentation. Two devices were used in this study. The GSO is a doubleumbrella device (W.L. Gore and Associates, Flagstaff, AZ, USA) consisting of a frame of 5 nickel-titanium circular wires covered with eptfe material. The eptfe material has been used in open-heart surgery for several years with a history of proven safety and biocompatibility. This device is fixed in place by an intrinsic locking mechanism that passes through the device from the left atrial to right atrial disc. Available disc sizes range from 15 mm to 30 mm (5-mm increments). The Amplatzer PFO Occluder and Amplatzer Cribriform Septal Occluder (AGA Medical, Golden Valley, MN, USA) are double-umbrella selfexpandable devices made of a nitinol wire mesh. The Amplatzer

3 2924 MUSTO C et al. Table 1. Baseline Subject Characteristics GSO group APO group P-value Female 13 (29) 12 (27) 0.81 Age (years) 42±9 47.5± Age >55 years 5 (11) 4 (9) 1 Thrombophilia 1 (2) 2 (4) 1 Diabetes 0 1 (2) 1 Arrhythmia Embolic index event TIA 32 (71) 29 (64) 0.5 Stroke 13 (29) 16 (36) 0.5 Recurrent events 16 (35) 17 (38) 0.82 Tunnel length (mm) 11±4 12± Long tunnel (>10 mm) 2 (4) 2 (4) 1 Large or spontaneous RLS 15 (33) 12 (27) 0.49 ASA 3 (6) 6 (13) 0.29 Data given as n (%) or mean ± SD. APO, Amplatzer Septal Occluder; ASA, atrial septal aneurysm; GSO, Gore Septal Occluder; RLS, right-to-left shunting; TIA, transient ischemic attack. Table 2. Procedural Data GSO group APO group P-value Procedure success 45 (100) 45 (100) 1 Procedure time (min) 32.3± ± Fluoroscopy time (min) 3.5± ± Balloon sizing required 0 (0) 0 (0) 1 Device removal and repositioning 2 (4) 0 (0) 0.49 Need for second device 0 (0) 0 (0) 1 Device migration 0 (0) 0 (0) 1 Immediate medium/severe RLS 2 (4) 1 (2) 1 Supraventricular arrhythmias 0 1 (2) 1 Air coronary embolism 1 (2) 0 (0) 1 Data given as n (%) or mean ± SD. Abbreviations as in Table 1. Cribriform Septal Occluder is made from 2 equal-sized discs whereas the left atrial Amplatzer PFO Occluder disc is slightly smaller than the right atrial disc. Discs of both devices are connected together by a bond bridge and are available in 18, 25, 30 and 35 mm. The operators were all experienced in the PFO closure technique. All procedures were carried out under local anesthesia and the size of device was selected using intracardiac echographic guidance (AcuNav Diagnostic Ultrasound Catheter; Siemens Medical, CA, USA) 8 without balloon sizing. On the day of implantation 250 mg of i.v. acetylsalicylic acid and a 300-mg loading dose of clopidogrel were given. Following sheath placement in a femoral vein, 100 units/kg body weight of i.v. unfractionated heparin were given. After device implantation all patients received 100 mg aspirin and 75 mg clopidogrel daily for 3 months. Thereafter, clopidogrel was discontinued and aspirin therapy maintained for an additional 3 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. Chest X-ray, for detection of fracture of the device, as well as a bub- bles test during TTE, for detection of residual RLS (rrls) at rest and after the Valsalva maneuver, were performed at 6-month follow-up. rrls was graded according to the definition used for evaluation of the PFO before closure, as described here. In cases of 6-month persistent rrls, contrast TTE was repeated 6 months later. The need for re-intervention for significant rrls or device malalignment was also evaluated. Persistent moderate severe rrls at 6 months was considered the primary endpoint. The incidence of death or recurrence of embolic events (REE) at 1 year was registered. Patients with suspected cerebral REE were re-evaluated by a senior neurologist and brain MRI was repeated. Statistical Analysis Categorical variables were compared using chi-squared or Fisher s exact test when appropriate. Statistical significance was assumed for P<0.05. Parametric variables were compared using 1-way ANOVA. Statistical analysis was performed using SPSS (version 12) and SAS (Fisher s exact test).

4 Gore Septal Occluder for Percutaneous PFO Closure 2925 Figure 2. (A) Unsatisfactory constitution of a 25-mm GORE Septal Occluder (GSO) across inter-atrial septum; (B) easy retrieval of the device inside the sheath; (C) successful implantation of the same 25-mm GSO. Results Subjects Baseline patient characteristics are given in Table 1. No significant differences in terms of embolic risk profile and echocardiographic parameters were observed between the 2 groups. All patients were treated because of a cerebral embolic event and 37% experienced >1 embolic event, 22% were older than 55 years, 30% had a large or spontaneous RLS and 10% had an associated ASA. Procedural and In-Hospital Outcome Procedural data are listed in Table 2. The procedure was successful in all patients and none needed more than 1 device. Procedural and fluoroscopy times did not differ significantly between the 2 groups of patients. In the GSO group a 25-mm device was implanted in all patients. All patients in the APO group received a 25-mm Amplatzer PFO device, except 5 in whom a 25-mm Amplatzer Cribriform septal occluder was used. No case of device embolism was recorded. In 2 patients in the GSO group for whom device position was not optimal, the GSO was easily removed with the retrieval cord and a new GSO was successfully implanted (Figure 2). Immediate moderate severe rrls rates were similar in the 2 groups. No deaths, REE, cardiac tamponade or bleeding complications were observed during hospitalization. One patient in the APO group had a supraventricular arrhythmia, which spontaneously converted to sinus rhythm, and 1 patient in the GSO group had transitory ST-elevation in leads DII, DIII and avf caused by air embolism in the right coronary artery, which spontaneously recovered within a few minutes. Follow-up After discharge all patients were clinically followed up for 1 year; no deaths or REE were recorded in the 2 groups. At 6-month follow-up no cases of severe rrls were observed. Two (4%) and 1 (2%) patients had moderate rrls in the GSO and APO groups, respectively (P=NS; Table 3). One of the 2 GSO pa-

5 2926 MUSTO C et al. Table 3. Outcome at 6-Month Follow-up GSO group APO group P-value Death 0 (0) 0 (0) 1 Stroke 0 (0) 0 (0) 1 TIA 0 (0) 0 (0) 1 Chest discomfort 1 (2) 3 (6) 0.61 Palpitations 1 (2) 3 (6) 0.61 Dyspnea 0 (0) 1 (2) 1 Severe rrls 0 (0) 0 (0) 1 Medium rrls 2 (4) 1 (2) 1 Small rrls 2 (4) 0 (0) 0.49 Device fracture 0 (0) 0 (0) 1 Data given as n (%). rrls, residual right-to-left shunting. Other abbreviations as in Table 1. tients had a late (fifth-sixth cardiac cycle) rrls, probably independent of the device and still present at 1-year follow-up. The 6-month moderate rrls disappeared at 1 year in the other GSO patient and the APO patient. Two cases of small 6-month rrls were registered in the GSO group, both disappeared at 1-year follow-up. Minor complaints, including chest discomfort, palpitations and dyspnea were present at 1-month follow-up in each group but had disappeared, in most patients, at 6-month follow-up. No device fractures were detected 6 months after the procedure. No patient required re-intervention for significant rrls or device malalignment. Discussion This is the first investigation to show that GSO is a safe and effective device for closing clinically significant PFO with a low rate of rrls and without major adverse clinical events at 1-year follow-up. GSO seems to be as safe and effective as the Amplatzer device in this consecutive series of patients. Moreover this new occluder is easy to manage and has a short learning curve. A number of different devices have been tested for percutaneous PFO closure, each with clinical and technical advantages and disadvantages In the present series of consecutive patients with a PFO we found that the clinical results of GSO compare favorably with those of the Amplatzer device. In fact no deaths or REE were registered at 1-year follow-up. The rate of immediate and 6-month rrls was similar between the 2 groups. In the GSO group only 2 patients (4%) had significant immediate rrls that persisted at 6-month follow-up as moderate rrls. At 1-year follow-up the moderate shunting disappeared in 1 patient and persisted in the other. No severe rrls was registered at 6-month echocardiographic follow-up. In the Amplatzer group 1 patient (2%) had significant immediate rrls. This was still present at 6-month and 1-year echocardiographic follow-up as moderate rrls. From these data it may be speculated that PFO occlusion after GSO device implantation could be not instantaneous but progressive. The reasons for the differences in definite occlusion time after device implantation are unclear. The best hypothesis is that the endothelialization process may be faster in more rigid occluders due to their property to button and oppose the septum primum more closely. This process might be delayed with softer devices such as GSO because of the increased separation of the discs. In cases of challenging anatomies such as those with associated ASA, GSO had good performance without 6-month rrls according to a recently published study in which no 1-month rrls was observed in a consecutive series of 20 patients, most of whom had a PFO associated with ASA. 13 In the present series, only 3 patients in the GSO group had a PFO with ASA, therefore the safety and efficacy of this device should be tested in large studies including more patients with a PFO associated with ASA. 14 We did not find any case of GSO wire frame fracture but it should be noted that fractures with the GORE HELEX Septal Occluder were mainly associated with larger devices. 15 GSO devices were easily implanted. The procedural and fluoroscopy times compare favorably with those of most commonly used devices 16 and are lower than those of the Helex device registered in our previously published series of patients 6 despite being in the learning curve of new device implantation. GSO was successfully deployed in all patients. In 2 cases there were concerns about whether the device had properly locked after deployment, therefore the occluder was easily removed from the inter-atrial septum and replaced with a new GSO device. This occurred, however, only during the first implantations of the device. To sum up: the GSO is a very flexible device with a minimal amount of nitinol designed to conform to the contours of the septum without bulky protrusion into the atria. These features may reduce the possibility of cardiac or vascular erosion and perforation while allowing for safe and easy device retrieval. Study Limitations The present study has some limitations. First, it is a small and non-randomized study, although it is a comparison of 2 reallife consecutive clinical series in which the choice of the device was operator independent. Second, the study follow-up was limited to 1 year. Most studies, however, indicate that REE occur early after percutaneous treatment. 17 Third, although we found no differences in the rates of REE, this study did not have sufficient power to show any difference in clinical events. Fourth, because patients who underwent to the PFO closure were treated consecutively, the GSO and Amplatzer devices were implanted at 2 different times. Last, few patient were monitored with an ECG Holter in order to detect asymptomatic post-procedural supraventricular arrhythmias. Conclusions The GSO device seems to be a valuable alternative to the Amplatzer occluders for percutaneous PFO closure. Device- and procedure-related complications are rare and mid-term clinical and echocardiographic results are encouraging. Moreover,

6 Gore Septal Occluder for Percutaneous PFO Closure 2927 GSO is technically very easy to implant and has a short learning curve. Larger and randomized trials are needed in the future to establish the safety and the efficacy of the GSO device. Disclosures The authors report no financial relationships or conflicts of interest regarding the content herein. References 1. Hideaki U, Sadamitsu Y, Hideaki N, Kentarou U, Ryouhei G, Toshihide A, et al. Device closure of atrial septal defect. Circ J 2012; 76: MacDonald ST, Carminati M, Chessa M. Managing adults with congenital hearts disease in the catheterization laboratory: State of the heart. Exp Rev Cardiovasc Ther 2010; 8: Thaman R, Faganello G, Gimeno JR, Szantho GV, Nelson M, Curtis S, et al. Efficacy of percutaneous closure of patent foramen ovale: Comparison among three commonly used occluders. Heart 2011; 97: Cecconi M, Quarti A, Bianchini F, Bucari S, Costantini C, Giovagnoni A, et al. Late cardiac perforation after transcatheter closure of patent foramen ovale. Ann Thorac Surg 2006; 81: e29 e Sigler M, Jux C. Biocompatibility of septal defect closure devices. Heart 2007; 93: Musto C, Cifarelli A, Fiorilli R, De Felice F, Parma A, Pandolfi C, et al. Gore Helex septal occluder for percutaneous closure of patent foramen ovale associated with atrial septal aneurysm: Short and midterm clinical and echocardiographic outcomes. J Invasive Cardiol 2012; 24: Pristipino C, Anzola GP, Ballerini L. Bartorelli A, Cecconi M, Chessa M, et al. Management of patients with patent foramen ovale and cryptogenic stroke: A collaborative, multidisciplinary, position paper. Catheter Cardiovasc Interv 2013; 82: Kim NK, Park SJ, Shin JI, Choi JY. Eight-French intracardiac echo- cardiography: Safe and effective guidance for transcatheter closure in atrial septal defect. Circ J 2012; 76: Taaffe M, Fischer E, Baranowsky A, Majunke N, Heinisch C, Leetz M, et al. Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder). Am J Cardiol 2008; 101: Rigatelli G, Dell Avvocata F, Ronco F, Giordan M, Cardaioli P. Patent ovale foramen transcatheter closure: Results of a strategy based on tailoring the device to the specific patient s anatomy. Cardiol Young 2010; 20: von Bardeleben RS, Richter C, Otto G, Himmrich L, Schnabel R, Kampmann C, et al. Long term follow-up after percutaneous closure of PFO in 357 patients with paradoxical embolism: Difference in occlusion systems and influence of atrial septum aneurysm. Int J Cardiol 2009; 134: Zhang CJ, Huang YG, Huang XS, Huang WH, Shen JJ. Transcatheter closure of patent foramen ovale in Chinese patients with paradoxical embolism. Immediate results and long-term results. Circ J 2011; 75: MacDonald ST, Daniels MJ, Ormerod O. Initial use of new Gore septal occluder in patent foramen ovale closure: Implantation and preliminary results. Catheter Cardiovasc Interv 2013; 81: Cifarelli A, Musto C, Parma A, Pandolfi C, Pucci E, Fiorilli R, et al. Long-term outcome of transcatheter patent foramen ovale closure in patients with paradoxical embolism. Int J Cardiol 2010; 141: Fagan T, Dreher D, Cutright W, Jacobson J, Latson L. For the GORE HELEX Septal Occluder Working group. Fracture of the GORE HELEX septal occluder: Associated factors and clinical outcomes. Catheter Cardiovasc Interv 2009; 73: Morgan G, Lee KJ, Chaturvedi R, Benson L. A biodegradable device (BioSTAR) for atrial septal defect closure in children. Catheter Cardiovasc Interv 2010; 76: Martin F, Sanchez PL, Doherty E, Colon-Hernandez PJ, Delgado G, Inglessis G, et al. Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Circulation 2002; 106: