1. Transcatheter closure of patent foramen ovale with the Spider TM PFO Occluder:Initial Clinical Experience Department of Cardiology, Guangdong Cardiovascular Institute Dr Yigao Huang, Dr Caojin Zhang

2. Patent foramen ovale (PFO) is quite common, with prevalence estimates from 10% to 35% of patients as determined by ultrasound and autopsy studies, respectively. The prevalence decreases gradually with increasing age, from 34.3% during the first three decades to 20.2% during the ninth decade. 1.Hagen PT, Scholz DG, Edwards WD. Mayo Clin Proc. 1984,59(1):17-20. 3. Fisher DC, Fisher EA, Budd JH,et al. Chest. 1995,107(6):1504-9. 2. Konstadt SN, Louie EK, Black S,et al. Anesthesiology. 1991,74(2):212-6. 4. Stendel R, Gramm HJ, Schröder K,et al. Anesthesiology. 2000,93(4):971-5. Background

3. FPrevalence of PFO is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. FThe increased risk for recurrent thromboembolic events can be avoided by percutaneous closure of PFO, surgical closure or permanent oral anticoagulation.

4. 1.Taaffe M, Fischer E, Baranowski A,et al. Am J Cardiol. 2008,101(9):1353-8. FTranscatheter closure of PFO is a promising alternative to surgical closure or anticoagulation therapy. FCurrently,several devices are used for PFO closure, such as Amplatzer occluder, Helex occluder, and CardioSEAL-STARflex occluder.

5. The aim of the present study was to evaluate the safety, feasibility and usefulness for closure of PFO with a new PFO occluder - the Spider TM PFO Occluder(Lifetech Scientific (Shenzhen) Co.Ltd,China.).

6. The Spider TM PFO Occluder

7. Animal experiment

8. Material and methods FGuangxi BA-MA Mini-pigs were selected. (provide by Guangxi University,Animal technology college) FThe fossa ovalis is punctured to establish the animal model of PFO. FThe Spider TM PFO Occluder was chosen to occlude PFO under guidance of fluoroscopy. FAfter occlusion, mini-pigs were sacrifized at month 1, 2 ， 3 and 6 for gross inspection and microscopic inspection.

9. FPuncture right femoro iliac vein after dissection FPosition 8 F femoral arterial sheath FPerform pulmonary arterial angiography FPuncture atrial septum and position left atrial wire FExchange to 10 F long sheath FPosition occluder(16 mm) The procedure of animal experiment

10. F12 Guangxi BA-MA Mini-pigs were selected to complete this experiment. weight: 28.2 ±3.8 kg Fprocedure time ： 66.75±38.58 min FX-ray exposure time: 22.09±13.38 min Results

11. The animal model of patent foramen ovale

12. The left atrium disc of the Spider TM PFO Occluder after implantation

13. The right atrium disc of the Spider TM PFO Occluder after implantation

14. The microscopic inspection at 1 month after occlusion (micro× 100)

15. The microscopic inspection at 2 months after occlusion (micro× 100)

16. The microscopic inspection at 3 months after occlusion (micro× 100)

17. The microscopic inspection at 6 months after occlusion (micro× 200)

18. Results FNo vegetation, thrombosis, broken strut, or erosion was found on the surface of all devices. FThe PFOs were completely occluded,observed by TTE from 1 to 6 months after occlusion.  The surface of the device was almost fully covered 1 month after occlusion. The left and right discs of the occluder were primarily covered by accretionary collagenous fibers and endothelial layers which are gradually thickening.

19. Clinical trial

20. Patient Population FBetween January 2006 and September 2008 F25 patients with a PFO underwent percutaneous PFO closure. FThe presence of a PFO was confirmed by transthoracic echocardiography(TTE) and/or transesophageal echocardiography (TEE) with a spontaneous or provocable (Valsalva manoeuvre) right-to-left shunt (RLS) FAll patients gave written informed consent before the implantation procedure.

21. Degree of right-to-left shunt FSpontaneous or provoked right-to-left shunt was semi- quantitatively graded according to the amount of bubbles detected in the left atrium after crossing the interatrial septum on a still frame: grade 0 = none, grade 1 = minimal (1–5 bubbles), grade 2 = moderate (6–20 bubbles), grade 3 = severe (>20 bubbles).  The PFO size was additionally determined by multiplane two-dimensional TEE as recently reported by Schuchlenz et al.

27. Percutaneous PFO closure FThe procedure was performed under local anaesthesia. FThe chosen PFO occluder was mounted on the delivery system and loaded into the transseptal sheath, with care taken to prevent air embolism. FThe occluder was advanced through the sheath into the left atrium until the left atrial part of the device was unfolded.After that, the whole unit was withdrawn under fluoroscopic and echocardiographic guidance against the interatrial septum. After it was determined that the device was in the correct position, the introducer sheath was further withdrawn, while constant tension was applied on the delivery cable until the right atrial part of the device unfolded. FOptimal placement of the device was assured by TTE and the absence of a residual shunt after deployment by color flow Doppler and micro-bubble administration.

28. Set up the track

29. The procedure was performed under fluoroscopic guidance

30. The procedure was performed under echocardiographic guidance

31. The occluder is well positioned and shaped after the occlusion

32. Post interventional Treatment  All patients were treated with aspirin 100 mg once daily for 6 months, at which time the medication was stopped unless required for another indication.

33. Follow-Up Evaluation FA two-dimensional TTE, chest X-ray and routine-ECG was performed at 24 hours after transcatheter PFO closure. FPatients were followed-up prospectively by TTE and/or TEE and clinically at 24 hours, 1 month, 3 months, 6 months, and 12 months after device implantation and yearly thereafter. FIncluding extensive neurological (by a neurologist experienced in cerebrovascular diseases) and medical examination with a 12-lead ECG and a TTE and/or TEE at rest and during Valsalva-Maneuver. FFollow-up events included death, recurrent neurological or peripheral thromboembolic events, and the need of reintervention for significant residual shunt or device malalignment.

34. Results 25 cases with PFO were diagnosed by TTE or TEE male ： 10cases ； female ： 15cases; mean age 35.1±13.8 years, range, 15 to 56 years

35. 3 patients with brain embolism after more than 4 months 3 patients after thrombolytic therapy for a snake-like thrombus on PFO 6 patients (2 male,4 female) with a repeated migraine history. 8 patients with platypnea-orthodeoxia syndrome One patient with decompression sickness 4 cases without any symptoms (by physical examination)

36. 22 patients had an ASD like closure (the catheter passed through the PFO directly) 3 patients needed an atrial septum puncture

37. All 25 cases procedure were successful. Procedure time ( pass PFO) :37±45min X-ray exposure time ： 17±34min 3 procedure time( AIS puncture) ： 153 、 90 and 73min ， respectively X-ray exposure time: 121 、 40 and 26 min ， respectively TTE or TEE examination after operation 24 － 48 hours: The position and shape of the occluders were good Results

38. FThere were no deaths or no complications (i.e. air embolism or thromboembolism, bleeding, occluder dislodgement, infection,myocardial infarction or others) during the procedure. F Seven patients had frequent atrial premature beats or transient atrial tachycardia during implantation, which terminated medically after implantation.

39. All patients have completed clinical follow- up at least 6 months(25 ± 11,6-39 months). No complications No migraine Blood examination: Homocytology shows no abnormality Renal function shows no abnormality Liver function is normal Follow-up

40. The Spider TM PFO occluder is the first device made in China. The Spider TM PFO occluder have some special characters : 1. Conventional Right Atrial Disc. 2. Left Atrial Disc is a ePTFE membrane with four or six braided ceramic deposit anchors, which may minimize risk of thrombus formation. 3.An active link between the Left Atrial Disc and the Right Atrial Disc allows the Left Atrail Disc to conform to the anatomy of atrial septum. Discussion

41. 1.Taaffe M, Fischer E, Baranowski A, et al. Am J Cardiol. 2008,101(9):1353-1358. 2.Spies C, Khandelwal A, Timmemanns I,et al. Catheter Cardiovasc Interv. 2008,72(7):966-70. 3.Luermans JG, Post MC, Plokker HW,et al. Neth Heart J. 2008,16(10):332-6. FThe summary conclusion of the present study is that the interventional PFO closure ｗ ith the Spider TM PFO occluder is a safe and effective technique with a high success rate. FOur data is in good agreement with previous studies using different transcatheter occluder systems.

42. Spider TM PFO occluder is a good choice for a transcatheter PFO closure If the catheter passes directly through PFO to create the path, a relative small size device can be selected. If it is difficult for catheter passing the PFO (over 20 minutes), the method of puncturing the atrial septum should be used, and a relative larger size device will be selected.

43. FFirstly, our patient population was a selected cohort referred to our institution for percutaneous PFO closure and might differ from other series published. FSecondly, the number of our patient population was smaller than other studies’. Limitations of our study

44. Conclusion FTranscatheter closure of PFO with the Spider TM PFO Occluder is a safe and effective therapeutic option. FTo further evaluate this strategy, randomized trials comparing this device with other devices and therapies have to be performed

45. Guangdong General hospital