Patent foramen ovale and cryptogenic stroke: contemporary evidence and treatment

Introduction: Patent foramen ovale (PFO) is a common anatomical variant in the adult circulation. It is a channel allowing communication between the left and right atria and is a remnant of the foetal circulation. In approximately 25% of the population, this channel persists into adulthood. PFO has been proposed as a potential pathophysiological mechanism for cryptogenic stroke.

Areas covered: This review will examine the contemporary evidence for both the association between cryptogenic stroke and PFO and the management of this condition. The authors hope to provide a comprehensive overview of the current evidence and best practice in relation to PFO closure. In addition, the authors will propose some potential avenues for future research in this controversial area and try to predict how PFOs in cryptogenic stroke will be managed in the near future.

Expert commentary: In carefully selected patients with cryptogenic stroke, PFO closure represents an evidence based treatment option for the prevention of further ischemic neurological events. A multidisciplinary approach is necessary to ensure appropriate patient selection for the procedure. This should include a vascular neurologist/stroke physician and an interventional cardiologist with an interest in PFO closure.     

心腔内超声在卵圆孔未闭封堵术中的应用

目的探讨心腔内超声(ICE)在经导管卵圆孔未闭(PFO)封堵术中的应用价值。方法应用ICE观察86例PFO的解剖形态及周围结构，测量PFO通道的直径和长度，监测与引导封堵过程、伞释放后位置，并通过彩色血流显像和超声造影判断有无残余分流。结果ICE清晰地观察到各种形态的PFO，86例中有85例封堵成功，1例失败。结论ICE指导经导管封堵PFO是一种安全、有效、简便和创伤小的方法。     

经胸和经食管超声心动图诊断卵圆孔未闭的对比研究

目的 对比研究经胸超声心动图TTE和经食管超声心动图TEE对卵圆孔未闭(patent foramen ovale，PFO)的诊断方法和诊断价值，及对卵圆孔未闭的临床意义。方法 运用经胸及经食管超声心动图检查，诊断卵圆孔未闭24例，根据患者有无合并其他心脏疾患及合并的心脏疾患的血流动力学特点将患者分为卵圆孔未闭组及卵圆孔开放组。结果 经胸超声心动图通过CDFI观察房水平的穿隔血流对卵圆孔未闭的诊断准确率为58．3％。经食管超声心动图检查能对所有患者做出正确诊断。卵圆孔未闭组可见卵圆孔瓣上缘与继发隔之间裂缝，CDFI显示源于卵圆孔瓣与继发隔交界边缘处的穿隔血流；卵圆孔开放组可见卵圆孔瓣上缘与继发隔之间出现回声缺失，但卵圆孔瓣尚完整，CDFI于缺口处探及垂直于房间隔的穿隔分流束。结论 经食管超声心动图是目前卵圆孔未闭诊断金标准的首选方法。卵圆孔未闭可导致反常栓塞，应予以积极治疗。     

中青年隐源性DWI阴性急性缺血性脑卒中合并卵圆孔未闭两例

该文报道2例中青年隐源性弥散加权成像(DWI)阴性急性缺血性脑卒中合并卵圆孔未闭男性患者,均为38岁,急性起病,以轻度神经功能缺损症状就诊,既往无脑血管病危险因素,以左侧肢体功能障碍为主要表现,DWI均阴性,经颅多普勒超声发泡检查和经食管心脏彩色多普勒超声检查发现卵圆孔未闭,其后均接受抗血小板、调脂等治疗,好转出院后随访显示2例均接受了卵圆孔未闭封堵治疗,均痊愈。应通过该2例的诊治过程提高对局灶性神经功能缺损合并卵圆孔未闭的认识,当患者出现局灶性神经功能缺损,即使DWI阴性亦不能排除急性缺血性脑卒中,应积极进行危险因素筛查,尤其是在中青年隐源性患者中,应高度重视卵圆孔未闭的检测及治疗,减少卵圆孔未闭所致的脑卒中及卒中复发。     

Patent foramen ovale in patients with tension headache: is it as common as in migraineurs? An age- and sex-matched comparative study

The association of patent foramen ovale (PFO) and atrial septal aneurysm (ASA) with migraine headache attack (MHA) has been clearly shown. The same findings have been recently demonstrated also in cluster headache. Although tension-type headaches (TTH) are the most common kind of headache, their association with these atrial septal abnormalities has never been studied before. The study was conducted to clarify whether there was a significant association between the presence of such atrial septal abnormalities and tension headache, when compared with migraineurs. One hundred consecutive patients with migraine and 100 age- and sex-matched subjects with TTH and 50 healthy volunteers with no headache were enrolled in the study and underwent a complete transesophageal echocardiographic study with contrast injections at rest and with the Valsalva maneuver. There was no significant difference between the age and the sex of the participants of the three groups. The overall prevalence of PFO was 23% in patients with TTH and that of large PFOs was only 11%. The 23% prevalence of PFO in patients with TTH was not statistically different from 16% found in our normal control group. Furthermore, we found a significantly higher prevalence of PFO in migraineurs (50%) when compared with patients with tension headache (p < 0.001). This was also true for the collective presence of large PFOs and ASAs (35%) (p < 0.001). Although atrial septal anomalies have an association with MHA, they do not have a significant association with TTH.     

经颅多普勒发泡试验筛查缺血性卒中合并卵圆孔未闭的应用价值

目的探讨经颅多普勒发泡试验(c-TCD)筛查缺血性卒中合并卵圆孔未闭(PFO)的应用价值。方法收集我院神经内科450例缺血性卒中患者,均给予经食管心脏超声(TEE)、右心声学造影、c-TCD检查。观察c-TCD、TEE联合经右心声学造影检查PFO的阳性率。将TEE联合经右心声学造影检查结果视为PFO诊断的"金标准",计算c-TCD的阳性预测值、阴性预测值、灵敏度、特异度及准确率。结果 TEE联合经右心声学造影检查显示,阳性为72例,阳性率为16.00%,即450例患者中,PFO的发生率为16.00%;c-TCD检查显示,65例清晰可见微栓子信号,阳性率为14.44%,c-TCD与TEE联合经右心声学造影检查阳性率比较差异无统计学意义(P>0.05);c-TCD相对于TEE联合经右心声学造影的阳性预测值为96.92%、阴性预测值为97.66%、灵敏度为87.50%、特异度为99.47%、准确率为97.56%、一致性Kappa值为0.837。结论 c-TCD在筛查诊断缺血性卒中合并PFO中具有灵敏度、特异度、准确率高的特点,且无创、安全,易于患者接受,可考虑将c-TCD作为PFO的无创初筛手段,针对阳性患者再进一步做TEE+经右心声学造影检查确诊,以减轻患者的痛苦。     

High prevalence of patent foramen ovale in migraine with aura

In this study we evaluated the presence of patent foramen ovale (PFO) in a cohort of 25 consecutive patients suffering from migraine with aura (MA) during an attack presenting to the emergency ward of an Italian hospital. Patients underwent brain magnetic resonance imaging (MRI) with contrast medium, routine coagulation tests, contrast transcranial echocolour–coded sonography (c–TCCS) and transoesophageal echocardiography (TEE). Of the enrolled patients, 88.7% showed a PFO according to the c–TCCS test, whereas only in 72% TEE confirmed the presence of PFO. This discordance could be due to the fact that c–TCCS is more sensitive even with shunts with minimal capacity also located in the pulmonary vasculature. After surgical treatment of the PFO, MA disappeared within two months. Also, the treatment with warfarin as well as with acetylsalicylic acid and flunarizine was able to dramatically reduce the frequency of migraine attacks. These data indicate a higher prevalence of PFO in MA vs. normal population (OR=2.92) and could suggest that the presence of arteriovenous (AV) shunts could represent a trigger for MA attacks as well as for stroke, but more studies are needed to confirm this preliminary hypothesis.     

脑卒中合并卵圆孔未闭临床及文献分析

目的:探讨脑卒中合并卵圆孔未闭(PFO)患者的临床特征。方法:回顾性分析2002年1月²012年11月我院收治的及万方数据库和中国医知网报道的脑卒中合并PFO患者41例的临床资料。结果:本组患者年龄<55岁35例(85.4%),有少量吸烟史9例,高血压5例,高血脂1例,糖尿病2例;左侧大隐静脉瓣膜功能不全1例,下肢深静脉血栓6例,髋关节置换术后2例;卵圆孔缺损直径≥2 mm者26例(86.7%);头颅MRI示皮质下白质额叶区、顶叶区梗死各12例。结论:脑卒中合并PFO患者发病年龄偏小,多无常规脑血管病危险因素,卵圆孔缺损直径≥2 mm易发病,确诊需经食管超声心动图、经颅多普勒超声造影等辅助检查。     

The potential role of the left atrial septal pouch in cryptogenic stroke

The left atrial septal pouch (LASP) is an anatomic variant of the atrial septum that forms a blind-ending pouch, communicating exclusively with the left atrium (LA). Case reports have demonstrated thrombus within LASP and in the setting of cryptogenic stroke. Initial epidemiologic results are mixed, one study showing and others not showing an association between LASP and cryptogenic stroke. Additional investigation should take place to determine the clinical significance of LASP and what interventions are required to prevent ischemic stroke in at-risk individuals.     

Percutaneous closure of patent foramen ovale: a case series and literature review

Patent foramen ovale (PFO) is an anatomical variant of the interatrial septum with an overall prevalence of 27% in autopsy studies. PFOs have a potential role in causation of stroke, platypneaorthodeoxia, decompression sickness, right to left shunt and migraine headaches. Data regarding percutaneous closure of PFO in low volume tertiary care centers is lacking. Retrospective review of 14 percutaneous PFO closures done in our facility from March 2005 to August 2006 was performed for efficacy of procedure and safety. All patients received clopidogrel for a period of 3 months, and aspirin and subacute bacterial endocarditis prophylaxis for 6 months. Mean age of the study population was 54 years. Fifty percent (7 of 14) of patients experienced an atrial septal aneurysm and 14% (2 patients) exhibited a hypercoagulable state. The indication for closure in 13 patients was transient ischemic attacks or strokes, while one patient had persistent hypoxia due to a severe right to left shunt at PFO. Patients received either a CardioSEAL or Amplatzer device. Deployment rate was 100%. All patients completed a minimum of 6 months of follow-up, with a mean follow-up time of 14.9 +/- 7.6 months. No immediate or late bleeding complication occurred in any patient. One patient developed paroxysmal atrial fibrillation and one patient developed thrombotic complications at 7 months post-procedure secondary to the progression of her anal carcinoma and subsequently died. Pending the results of the four large randomized trials that are enrolling patients, percutaneous closure of PFO for cryptogenic strokes is an attractive alternative to lifelong anticoagulation with relatively few complications, even in low volume centers. There are many challenges in the management of this subset of patients, the foremost being the selection of a target patient population. Role of PFO in migraines is less clear.     

不明原因缺血性脑卒中患者卵圆孔未闭和主动脉粥样硬化斑块的对比研究

目的 应用经食管超声心动图(TEE)探查卵圆孔未闭(PFO)及主动脉内粥样硬化复杂斑块(CA)并分析PFO及CA在不同年龄组与特发性缺血性脑卒中(CIS)的关系,寻找CIS的原因.方法 研究对象包括经TEE检查的229例CIS患者为病例组;314例无脑卒中病史但行TEE的患者作为对照组.对比分析这两组患者的不同年龄组PFO及主动脉内不同部位CA的发生率.结果 (1)与对照组相比,CIS患者的PFO发生率在年龄＜55岁及≥55 岁患者中均明显增高.(2)CA的发生率在年龄＜55岁及≥55 岁中差别均不明显.(3)多元回归分析显示 PFO 与2个年龄组CIS的发生均独立相关.结论 在导致CIS的可能致病因素中卵圆孔未闭较主动脉复杂斑块更有预测意义,而TEE检查是CIS病因诊断的可行手段.     

Lower patent foramen ovale detection with transthoracic echocardiography in atrial fibrillation

Background Patent foramina ovale (PFO) are small defects within the atrial septum that may play a role in paradoxical embolism, stroke and migraines. The relationship between PFO and atrial fibrillation (AF) has not been formally studied. We prospectively studied patients with a history of AF, versus those without (controls), in order to compare PFO prevalence among them. Methods Sixty-one patients with AF and forty-one controls completed the study, all undergoing transthoracic echocardiography using agitated saline microbubbles and a Valsalva maneuver. Results In the control group, 12/41 participants (29.2%) had PFOs compared to 5/61 (8.2%) in the AF group (P < 0.01). PFO positive patients within the entire study population demonstrated greater leftward inter-atrial septal shifting (82% vs 49%, P < 0.05). There was also reduced leftward inter-atrial septal shift observed within the AF group compared to controls (32/61 (52%) vs 31/41 (76%), P < 0.05). Conclusion This study is the first to demonstrate an apparent lower rate of PFO in patients with AF, using bubble contrast echocardiography.     

Enhancement of hypoxemia by right-to-left atrial shunting in severe asthma

We report two cases of severe hypoxemia due to right-to-left shunt in acute asthmatic patients. During acute asthma, the transmural right atrial pressure can be higher than left atrial pressure during inspiration and then induce a right-to-left shunt through inter-atrial communication leading to hypoxemia. Contrast echography as well as Doppler analysis can easily confirm the diagnosis.     

超声心动图诊断卵圆孔未闭

卵圆孔未闭（PFO）在成人的发生率约20%~25%,其与年轻患者的隐源性卒中、短暂性脑缺血发等多种疾病有关。超声心动图在PFO的诊断、经皮封堵术中监测及术后随访中均有重要价值。本文对PFO的超声心动图诊断做一综述。     

Prevalence of patent foramen ovale in a large series of patients with migraine with aura, migraine without aura and cluster headache, and relationship with clinical phenotype

A relationship between migraine and patent foramen ovale (PFO) has been observed in relatively small series of patients so far. Furthermore, the exact mechanism underlying such an association remains unknown. In the present study we determined the prevalence of PFO by contrast–enhanced transcranial Doppler (TCD) in a group of 260 patients with migraine with aura (MA+), 74 patients with migraine without aura (MA–), and 38 patients with cluster headache (CH). One–hundred–sixty–one MA+subjects (61.9%), 12 MA–subjects (16.2%), and 14 CH–subjects (36.8%) were PFO–carriers. The association was independent on the frequency of migraine attacks and complexity of aura. Finally, among the 15 patients who had a history of at least one migraine attack occurring during a Valsalva maneuver only one subject turned out to be PFO–carrier. Our findings confirm previous observations of a link between MA+, CH, and PFO. They also suggest that such an association is independent on migraine clinical phenotype and is probably unrelated to the pathogenic mechanism of paradoxical embolism.     

偏头痛与卵圆孔未闭关系的研究

目的：探讨先兆性偏头痛、无先兆性偏头痛患者和正常人卵圆孔未闭（ PFO）发生率的差异。方法采用经颅多普勒超声（TCD）检测先兆性偏头痛组（29例）、无先兆偏头痛组（31例）和正常对照组（26名） PFO的发生率,比较各组差异。记录治疗前偏头痛患者的头痛频率、头痛发作日数和头痛程度等,并分析其与PFD分流量大小的相关性。结果先兆性偏头痛组、无先兆偏头痛组和正常对照组PFO发生率分别为72％、45％和31％,先兆偏头痛组PFO发生率较正常对照组高（ P＝0.008）,无先兆偏头痛组较正常对照组高,但比较差异尚无统计学意义（ P＝0.491）;PFO大小与头痛频率、头痛发作日数呈正相关（P均＜0.05）。结论先兆偏头痛患者的PFO发生率较高,提示此两种疾病可能有共同的病理学发病机制。     

Migraineurs with patent foramen ovale have larger right-to-left shunt despite similar atrial septal characteristics

The objective of the study was to assess differences in proportion of large right-to-left shunt (RLS) and atrial septal characteristics between migraineurs and non-migraineurs referred for transcatheter closure of patent foramen ovale (PF0). This retrospective study took place in a large metropolitan medical centre. The patients were migraineurs with aura (n=52), migraineurs without aura (n=19) and non-migraineurs (n=149). RLS was evaluated before closure using bilateral power m-mode transcranial Doppler at rest and after calibrated, sustained Valsalva manoeuvre, and graded with a validated 0–5 scale. Intracardiac echocardiography was used to assess atrial septal characteristics. Migraineurs had a higher proportion of large RLS (Grade IV or V) than nonmigraineurs at rest and after calibrated Valsalva (rest, p=0.04; Valsalva, p=0.01). Atrial septal characteristics were similar between groups. Migraine is associated with larger RLS at rest and strain; however migraine status does not predict PFO characteristics.     

Contrast Transthoracic Echocardiography Using 50% Glucose as a Contrast Agent for Screening of a Patent Foramen Ovale

A patent foramen ovale (PFO) is considered a risk factor for neurologic events. The goal of the study described here was to assess the feasibility, advantages, diagnostic sensitivity and accuracy of contrast transthoracic echocardiography examination (cTTE) using 50% glucose as a contrast agent in comparison with the use of agitated saline as contrast to screen for PFO. In our study, we found that the peak time, effective duration and duration of microbubbles produced by 50% glucose were all longer than those produced by the physiologic saline. The sensitivities for detection of PFO with cTTE using physiologic saline and 50% glucose as contrast were 83% (20/24) and 100% (24/24), respectively. TEE suggested a PFO in 24 patients in two groups. Use of 50% glucose as a contrast agent in cTTE examination enables ultrasound technicians to easily observe the right-to-left shunt across the PFO. However, the sensitivities for detection of PFO with cTTE using 50% glucose did not statistically significantly differ from those for physiologic saline.