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1、卵圆孔未闭封堵术:争论与发展May 9, 2009,Andrew D. Michaels, MD, MAS, FACC, FAHA Director, Cardiac Catheterization Laboratory and Interventional Cardiology University of Utah, Salt Lake City, Utah,胎儿循环,胎儿期,氧合血液由脐静脉经下腔静脉进入右房 血流由下腔静脉经过Eustachian 瓣流到卵圆窝.,出生后房间隔发育,宫内 出生后,Hagen, Scholz. Mayo Clin Proc 1984; 59: 17-20.,

2、人口的75 人口 的25%,PFO相关临床综合症,体位相关呼吸困难 Platypnea orthodeoxia 减压病/高原性肺水肿 脑血管事件/TIA 偏头痛,Platypnoea Orthodeoxia,罕见 直立体位引起的呼吸困难,伴有低氧血症 机制:右向左房间分流,Aigner et al. Eur J Cardiothor Surg 2008; 33: 268. Medina et al. Circulation 2001; 104: 741.,Platypnea Orthodeoxia,1949年至今已有文献报道近100例 PFO 常伴有: 主动脉瘤 胸廓畸形 肺切除术后 约50例

3、已接受封堵术,减压病,对230名 无症状潜水者进行研究 27% 有PFO 需要减压舱治疗者: 19% 有PFO 2% 无 PFO,Torti et al. Eur Heart J 2004; 25: 1014-20.,隐匿性脑卒中,40岁男性,突发失语 既往史无特殊. 无明显脑卒中病因. TEE: 发现房间隔瘤与 PFO. 常见伴发症: 50% 隐匿性脑卒中患者有 PFO. 推测机制: 静脉血栓反常性体循环栓塞症. PFO 通道内原位血栓形成造成栓塞,血栓流经 PFO,首例 PFO伴血栓形成报道于1876. 既往通过超声心动图及术中见到嵌顿于PFO的血栓. 但无法观察到小栓子的流程。,服用阿司

4、匹林的PFO患者脑血管事件/TIA复发率较高,Mas et al. NEJM 2001; 345: 1740-6.,581 名患者有隐匿性脑卒中 均接受阿司匹林治疗,华法林阿司匹林复发性脑卒中研究,Mohr et al. NEJM 2001; 345: 1444-51.,N=2206 缺血性脑血管事件 (56% 腔梗; 25%隐匿性; 13% 大血管性) 随机接受阿司匹林325mg 或华法林治疗 结论: 抗血小板及抗凝治疗有效(无效)率相当。,药物治疗 vs. PFO封堵术,Windecker et al. JACC 2004; 44: 750-8.,308名 隐匿性脑卒中伴PFO患者 随机接

5、受药物治疗或PFO封堵术治疗,药物治疗 vs. PFO 封堵术:观察性研究的荟萃分析,Khairy et al. Ann Int Med 2003; 139: 753-60.,1年脑卒中/TIA 复发率,死亡/脑卒中/TIA 事件/100 人年,PFO 封堵器,PFO,ASD,Amplatzer PFO,STARFlex,Amplatzer ASO,CardioSEAL,Helex,Amplatzer Cribiform ASD,左房伞植入,右房伞植入,植入前,植入后,偏头痛与PFO的关系,12人口患有偏头痛 (女性18% ; 男性6% ) 偏头痛患者中 存在PFO的占: 48%的偏头痛伴视觉

6、先兆 1 23%的偏头痛不伴视觉先兆 20% 正常人 隐匿性脑卒中伴PFO患者中偏头痛发生率 52% 有偏头痛伴视觉先兆2 71% 封堵术后症状缓解3 偏头痛患者较正常人MRI检查病变阳性率高13倍4,Anzola. Neurology 1999;52:1622-5. Sztajzel. CV Diseases 2002;13:102-6. Wilmshurst. Lancet 2000;356:1648-51. Kruit. JAMA 2004;294:427-34.,卵圆孔未闭与偏头痛之间可能的病理生理相关性,经过PFO的微小栓子可引起偏头痛. 体液因子(如5HT) 免受肺降解,引起偏头痛

7、.,MIST研究结果,Dowson A, et al. Circulation 2008; 117: 1397-404.,术前,术前,术后,术后,P value,手术组 (n=74),假手术组(n=73),偏头痛随机临床试验,NMT Medical closed MIST II (January 24, 2008). PREMIUM (AGA Medical) 及 ESCAPE (St Jude Medical) 仍在进行中.,PFO 封堵器技术现况与展望,目前封堵器技术的局限性 大型,永久性植入物. 远期并发症:心率失常,炎症,糜烂,血栓形成,过敏反应. 未来的封堵器技术 小型封堵器. 生物

8、可吸收(BioSTAR). 可缝合封堵器. 射频消融.,Mullen et al. Circulation 2006; 114: 1962-7.,结论,目前隐匿性脑卒中的药物治疗疗效欠佳. 研究提示存在高危复发脑卒中的亚组. 尚无随机临床试验支持任何药物治疗 经皮 PFO封堵术可能成为隐匿性脑卒中预防的主要干预手段. 安全. 非随机临床试验资料提示对可有效预防脑卒中. 有待关于脑卒中与偏头痛的进一步临床研究结果.,结论,Patent Foramen Ovale Closure:Controversies and Accomplishments May 9, 2009,Andrew D. Mic

9、haels, MD, MAS, FACC, FAHA Director, Cardiac Catheterization Laboratory and Interventional Cardiology University of Utah, Salt Lake City, Utah,Fetal Circulation,During fetal life, oxygenated blood returning from the umbilical vein enters the RA through the IVC. Blood flow is directed by the Eustachi

10、an valve from the IVC to the fossa ovalis and through the PFO.,Post-Natal Septal Development,In Utero After Birth,Hagen, Scholz. Mayo Clin Proc 1984; 59: 17-20.,75% of Population 25% of Population,Clinical Syndromes Associated with PFO,Platypnea orthodeoxia Decompression sickness/high-altitude pulmo

11、nary edema CVA/TIA Migraine,Platypnoea Orthodeoxia,Uncommon syndrome Dyspnea induced by upright posture, with associated hypoxemia Mechanism: right-to-left interatrial shunting,Aigner et al. Eur J Cardiothor Surg 2008; 33: 268. Medina et al. Circulation 2001; 104: 741.,Platypnea Orthodeoxia,100 case

12、s in literature since 1949 PFO associated with: Aortic aneurysm Chest deformity Post-pneumonectomy 50 have undergone device closure,Decompression Sickness,230 asymptomatic divers surveyed 27% had a PFO Decompression chamber required: 19% with a PFO 2% without a PFO,Torti et al. Eur Heart J 2004; 25:

13、 1014-20.,Cryptogenic Stroke Case,40 yo man with sudden aphasia. No medical history. No obvious cause of stroke. TEE: atrial septal aneurysm and PFO. Associations: 50% of people with cryptogenic stroke have a PFO. Presumed mechanism: Paradoxical embolism of venous thrombus. In-situ thrombosis within

14、 PFO tunnel with embolization.,Thrombus in transit through PFO,First case of PFO with thrombus described in 1876. Thrombus caught in PFO has been seen by echo and at surgery. However, passages of small emboli are impossible to prove.,Higher CVA/TIA Recurrence Rate in Patients with PFO + ASA,Mas et a

15、l. NEJM 2001; 345: 1740-6.,581 patients with cryptogenic stroke All treated with aspirin,Warfarin-Aspirin Recurrent Stroke Study,Mohr et al. NEJM 2001; 345: 1444-51.,N=2206 with ischemic CVA (56% lacunar; 25% cryptogenic; 13% large vessel) Randomized to ASA 325mg vs Warfarin Conclusion: Antiplatelet

16、 and anticoagulant therapy equally (in)effective,Medical Therapy vs. PFO Closure,Windecker et al. JACC 2004; 44: 750-8.,N=308 with cryptogenic CVA and PFO Randomized to medical therapy or PFO closure,Medical Therapy vs. PFO Closure:Meta-Analysis of Observational Studies,Khairy et al. Ann Int Med 200

17、3; 139: 753-60.,Recurrent CVA/TIA 1-Year,Death/CVA/TIA Events/100 pt yrs,PFO Devices,PFO,ASD,Amplatzer PFO,STARFlex,Amplatzer ASO,CardioSEAL,Helex,Amplatzer Cribiform ASD,Left Atrial Disc Deployment,Right Atrial Disc Deployment,Pre,Post,Association Between Migraine and PFO,Migraine headache affects

18、12% of population (18% F; 6% M) Incidence of PFO in patients with migraine 48% if migraine with aura1 23% if migraine without aura 20% in controls Incidence of migraine in cryptogenic stroke with PFO 52% had migraine with aura2 71% had suppression post-closure3 Migraine patients have 13 times higher

19、 incidence of MRI lesions4,Anzola. Neurology 1999;52:1622-5. Sztajzel. CV Diseases 2002;13:102-6. Wilmshurst. Lancet 2000;356:1648-51. Kruit. JAMA 2004;294:427-34.,Potential Pathophysiologic Association Between PFO and Migraine,Microembolism through PFO triggers migraine. Humoral factors (i.e., sero

20、tonin) escape pulmonary degradation, triggering migraine.,Published MIST Results,Dowson A, et al. Circulation 2008; 117: 1397-404.,Baseline,Baseline,Post,Post,P value,Implant (n=74),Sham (n=73),Migraine Randomized Clinical Trials,NMT Medical closed MIST II (January 24, 2008). PREMIUM (AGA Medical) and ESCAPE (St Jude Medical) still enrolling.,Current and Future PFO Device Technologies,Limitations of Current Device Technol

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