卵圆孔未闭与隐源性卒中

隐源性卒中占所有缺血性卒中的25％~40％,其病因诊断和治疗一直是临床研究者们努力的方向。其中,卵圆孔未闭（patent foramen ovale, PFO）与隐源性卒中的关系广受争议,一直是研究的热点。病例对照研究表明,与普通人群相比,隐源性卒中患者中PFO患病率显著增高。不过,前瞻性研究显示,单纯PFO并不会增高隐源性卒中发生率,只有在PFO与其他一些高危因素共存时才会显著增高缺血性卒中风险。 PFO的治疗选择包括抗血小板药、抗凝药、经皮介入封堵术和开胸封堵术。近年来,3项比较PFO封堵术与药物预防隐源性卒中复发的大样本临床试验结果已发表,使得卒中二级预防指南得以更新。文章就PFO与隐源性卒中的联系、PFO相关隐源性卒中的高危特征以及二级预防治疗方面的研究进展进行了综述。     

隐源性卒中患者的卵圆孔未闭：评价和二级预防

隐源性卒中(cryptogenic stroke, CS)是使用卒中标准临床检查程序之后, 仍然不能找到确切病因的卒中类型。近年来, 多项研究表明卵圆孔未闭(patent foramen ovale, PFO)与CS关系密切, 其主要发病机制为反常性栓塞。在临床实践中, 多使用超声方法进行PFO筛查。在PFO背景下, CS的二级预防包括药物治疗和PFO封堵术, 但选择何种治疗方式目前仍存在着争议。针对可能存在的PFO进行筛查和评价, 有助于为CS患者制定二级预防策略, 特别是能从PFO封堵术中受益的患者。     

中青年缺血性卒中患者卵圆孔未闭发生情况分析

目的探讨中青年缺血性卒中患者卵圆孔未闭（PFO）的发生情况。方法选择2006年10月—2010年1月,首都医科大学宣武医院门诊或住院的中青年缺血性卒中患者198例,根据经食管超声心动图检查确定是否存在PFO,分为PFO组和无PFO组。其中PFO组125例,无PFO组73例。经食管超声心动图及右心声学造影检查,观察卵圆孔未闭的发生情况。对所有患者行卒中相关危险因素的检查。结果①PFO组患者的年龄低于无PFO组[（37±10）岁,（43±10）岁],差异有统计学意义,P〈0．05。②在卒中相关危险因素比较中,PFO组患者的高血压、糖尿病、吸烟史、高脂血症等比例均低于无PFO组,差异均有统计学意义,P〈0．05。③PFO组中有18例（14．4％）合并房间隔瘤,无PFO组中有5例（6．8％）合并房间隔瘤,PFO组合并房间隔瘤的比例高于无PFO组,差异有统计学意义,P=0．018。④PFO组无任何危险因素的比例高于无PFO组,差异有统计学意义,P〈0．05。结论卵圆孔未闭可能是中青年缺血性卒中患者重要的发病原因。     

卵圆孔未闭与原因不明性卒中

流行病学研究显示,原因不明性卒中患者中的卵圆孔未闭(patent foramen ovale,PFO)患病率显著高于普通人群,二者之间的密切联系支持反常性栓塞为卒中病因的假说.然而,在原因不明性卒中患者中,单纯检测到PFO并不能确立反常性栓塞的诊断.当PFO与其他一些因素共存时,会显著增高缺血性卒中风险.一些研究显示,伴有PFO的原因不明性卒中患者的MRI病灶模式与无PFO者并无显著差异,特别是多发性缺血灶,因此不支持反常性栓塞作为PFO患者卒中病因的理论.PFO的检测方法包括经胸壁超声心动图、经食管超声心动图(transesophageal echocardiography,TEE)和经颅多普勒(transcranial Doppler,TCD).TCD与TEE具有良好的一致性,因此应被推荐为一种简单、无创和可靠的技术,而TEE仅应在经过选择的患者中进行.PFO的治疗选择包括抗血小板药、抗凝药、经皮血管内封堵术和开胸手术.在几项重要的大样本随机对照试验完成之前,对于伴有PFO的原因不明性卒中患者,经皮封堵术仅应考虑用于治疗在接受内科治疗过程中仍然出现复发性事件、对内科治疗存在禁忌证以及某些高危解剖学风险的PFO.     

缺血性卒中相关性卵圆孔未闭的介入治疗

卵圆孔未闭是缺血性卒中的一个新的危险因素，但其具体机制仍不明，许多相关问题尚需进一步探讨。通过对相关文献进行比较，进一步肯定了卵圆孔未闭与缺血性或不明原因的卒中之间有很强的联系。房间隔瘤伴发卵圆孔未闭是脑梗死的危险因素。经皮导管卵圆孔未闭封堵术的应用前景看好，但还需要进行进一步的前瞻性研究。     

卵圆孔未闭与原因不明性卒中

流行病学研究显示,原因不明性卒中患者中的卵圆孔未闭(patent foramen ovale,PFO)患病率显著高于普通人群,二者之间的密切联系支持反常性栓塞为卒中病因的假说.然而,在原因不明性卒中患者中,单纯检测到PFO并不能确立反常性栓塞的诊断.当PFO与其他一些因素共存时,会显著增高缺血性卒中风险.一些研究显示,伴有PFO的原因不明性卒中患者的MRI病灶模式与无PFO者并无显著差异,特别是多发性缺血灶,因此不支持反常性栓塞作为PFO患者卒中病因的理论.PFO的检测方法包括经胸壁超声心动图、经食管超声心动图(transesophageal echocardiography,TEE)和经颅多普勒(transcranial Doppler,TCD).TCD与TEE具有良好的一致性,因此应被推荐为一种简单、无创和可靠的技术,而TEE仅应在经过选择的患者中进行.PFO的治疗选择包括抗血小板药、抗凝药、经皮血管内封堵术和开胸手术.在几项重要的大样本随机对照试验完成之前,对于伴有PFO的原因不明性卒中患者,经皮封堵术仅应考虑用于治疗在接受内科治疗过程中仍然出现复发性事件、对内科治疗存在禁忌证以及某些高危解剖学风险的PFO.     

卵圆孔未闭患者的隐源性卒中

隐源性卒中是指通过目前的常规检查不能明确病因的缺血性卒中。研究显示,卵圆孔未闭可能是隐源性卒中的常见病因,其可能的机制是反常性栓塞。随着影像学技术的发展,越来越多的研究表明卵圆孔未闭与隐源性卒中之间关系密切。文章就卵圆孔未闭患者的隐源性卒中进行了综述。     

经导管封堵卵圆孔未闭预防卒中复发的研究进展

经导管封堵卵圆孔未闭预防卒中复发的有效性和安全性备受争议.随着近几年随机对照试验结果的公布,卵圆孔未闭封堵治疗从争议变为统一.本综述就卵圆孔未闭封堵相关的几项随机对照试验一一讨论,并对卵圆孔未闭封堵治疗获益患者的特征、术后管理等内容进行探讨.     

卵圆孔未闭患者缺血性脑血管病复发情况的分析

目的 观察伴有卵圆孔未闭（PFO）的缺血性卒中或短暂性脑缺血发作患者的复发情况,以了解PFO在脑缺血发生过程中的作用。方法 连续选取2008年3月-2009年3月, 首都医科大学宣武医院神经内科住院的,15-55岁缺血性卒中或短暂性脑缺血发作患者71例进行研究,均行经食管超声心动图检查,其中PFO组49例,非PFO组22例,比较12个月内两组缺血性脑血管病复发情况。结果 随访12个月时PFO组共有8例复发脑缺血,而非PFO组仅有1例复发。（1）PFO组与非PFO组3、6、12个月时复发率分别为6.12%,0;10.20%,4.55%和16.33%,4.55%,差异均无统计学意义（P=0.322,P=0.428,P=0.168）。（2）PFO组患者缺血性脑血管病累计复发率较非PFO组患者具有增高趋势,但差异尚未达到统计学意义（P=0.065）,其OR值为3.76（95%CI：0.834-16.946）,亦未达到统计学意义（P=0.085）。结论 存在PFO的缺血性脑血管病患者的复发率有增高趋势,但尚不能够确定PFO可以增加再发脑缺血的概率。     

卵圆孔未闭不是普通人群中原因不明性卒中的危险因素

为了确定卵圆孔未闭（patent foramen ovale，PFO）是否为原因不明性脑血管缺血事件（cerebrovascular ischemic event。CIE）的危险因素，美国梅奥医疗中心神经科的Pewtty等对明尼苏达州Olmsted县的1072名居民进行了一项病例对照研究，所有居民在1993—1997年期间均做过对比增强经食管超声心动图（transesophageal echocardiography。TIE）。其中519例为从人群中随机选择的无CIE对照者，262例为因心脏病行TIE但无CIE对照者，158例为有明显病因的偶发性CIE患者（非原因不明性）和133例病因不确定的偶发性CIE患者（原因不明性）。     

Electrocardiographic findings in patients with cryptogenic ischemic stroke and patent foramen ovale

Background

A characteristic electrocardiogram (ECG) pattern called crochetage has been described in patients with atrial septal defects. Nevertheless, there are discrepancies regarding its frequency in patients with patent foramen ovale (PFO).

Objective

We analyzed the ECGs of patients who had cryptogenic stroke to study crochetage and other possible patterns in relation to PFO.

Methods

We prospectively included consecutive patients who have had a cryptogenic stroke and are undergoing a right-to-left shunt (RLS) study with transesophageal echocardiography and simultaneous transcranial Doppler. Two blinded and independent cardiologists analyzed the ECGs for crochetage, defined as a notch near the apex of the R wave in inferior limb leads, P wave abnormalities, and right bundle branch block (RBBB).

Results

We studied 104 patients whose mean age was 55.1 ± 12.7 years; 60.6% were men. PFO was detected in 40.4% of patients. Cardiologists recorded crochetage in 26.2% of patients with PFO and 14.5% of patients without PFO (P = .204) and RBBB in 19% and 8% of patients, respectively (P = .132). P wave abnormalities were also detected in 54.8% of patients with PFO and 35.5% of patients without PFO (P = .070). In patients with PFO, biphasic P waves were more frequent in small RLS (P = .006). Although higher frequencies of crochetage in small RLS and RBBB in moderate RLS were detected, these differences did not reach statistical significance (P = .067 and P = .05, respectively).

Conclusion

There is no characteristic ECG pattern to identify the patients with cryptogenic stroke.     

Patent foramen ovale and cryptogenic stroke

The presence of a patent foramen ovale (PFO) has been found to be associated with an increased risk of cryptogenic stroke in many case–control studies. This paper reviews the current understanding of the pathophysiology and diagnosis of PFO, and therapeutic options of patients with PFO and cryptogenic stroke.     

Transcatheter closure versus medical therapy of patent foramen ovale and cryptogenic stroke.

OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of device closure of patent foramen ovale (PFO) versus antiplatelet therapy in patients with cryptogenic stroke (CS). BACKGROUND: There are no controlled data to support the therapeutic value of PFO closure with a device compared to medical treatment in patients with CS. METHODS: We performed a nonrandomized, prospective, patient preference case series comparing the recurrence rate in 92 patients with PFO and CS who were treated either with antiplatelet agents (44 patients) or underwent catheter closure (48 patients) using the Amplatzer PFO occluder (APFOO). All patients completed a 2-year follow-up. RESULTS: PFO closure group. Immediate complete closure (CC) was observed in 44/48 (91%) patients. Four (9%) patients had a minimal residual shunt immediately after the procedure. One patient developed hemopericardium that was successfully managed by pericardiocentesis. No other complication was observed. Follow-up. PFO closure group. Contrast bubble study at 6-month follow-up confirmed CC in all 48 patients. No complications were observed. Antiplatelet therapy group. Three (6%) and 6 (13%) patients had a major and minor hemorrhagic event, respectively. The average incidence of embolic events/year was 0 and 14.75% for the PFO closure group and the antiplatelet therapy group, respectively (P < 0.001). CONCLUSIONS: PFO closure using the APFOO is a rational alternative to medical treatment in patients with CS. Larger randomized clinical trials are required to support the use of this device over the other PFO occluders and medical therapy.     

Management of patients with patent foramen ovale and cryptogenic stroke: A collaborative,multidisciplinary, position paper

Objectives : To organize a common approach on the management of patent foramen ovale (PFO) and cryptogenic stroke that may be shared by different specialists. Background : The management of PFO related to cryptogenic stroke is controversial, despite an increase in interventional closure procedures. Methods : A consensus statement was developed by approaching Italian national cardiological, neurological, and hematological scientific societies. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. Drafts were outlined by specific task force working groups. To obtain a widespread consensus, these drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft, merging all the revisions, was reviewed by the task force and finally approved by scientific societies. Results : Definitions of transient ischemic attack and both symptomatic and asymptomatic cryptogenic strokes were specified. A diagnostic workout was identified for patients with candidate event(s) and patient foramen ovale to define the probable pathogenesis of clinical events and to describe individual PFO characteristics. Further recommendations were provided regarding medical and interventional therapy considering individual risk factors of recurrence. Finally, follow‐up evaluation was appraised. Conclusions : Available data provided the basis for a shared approach to management of cryptogenic ischemic cerebral events and PFO among different Italian scientific societies. Wider international initiatives on the topic are awaited. © 2013 Wiley Periodicals, Inc.     

Impaired endothelial function in patients with cryptogenic stroke and patent foramen ovale is not affected by closure

Introduction

Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS) and migraine with aura (MA). Endothelial dysfunction (ED) is a risk factor for development of cardiovascular disease, but might also be involved in migraine pathophysiology. Short‐term worsening of migraine has been described after closure of PFO. We evaluated endothelial function in patients with CS and PFO, before and after closure of PFO, and in patients with migraine, whether changes in endothelial function was related to a change in migraine frequency.

Material and Methods

Patients with CS and PFO were included; 20 with planned closure of PFO and seven controls on medical treatment only. Endothelial function was assessed by peripheral arterial tonometry (EndoPat^R) and biomarkers of endothelial activation. Patients were followed longitudinally at baseline, day 1, 1 month, and 6 months. A headache diary was used to assess migraine frequency.

Result

Mean age of the cohort was 45.4 years, and migraine prevalence was 50% whereof 84.6% had MA. Median EndoPat^R index (RHI) at baseline was 1.60 (IQR 1.41‐2.00). There was no change in RHI over time, either in closure patients (P = 0.66), nor in controls (P = 0.31), and there was no change in biomarkers of endothelial activation. Three migraine patients experienced worsening of migraine frequency directly after closure.

Discussion

Endothelial function did not change after closure of PFO. Although patients were lacking cardiovascular risk factors, a high proportion had impaired endothelial function. Whether ED can have predictive value, identifying PFO at higher risk for recurrent stroke warrants further investigations.