White Matter Lesions in Young-Middle Aged Migraineurs with Patent Foreman Ovale: A Case-Control Study

Background:White matter lesion(WML)is common in aging brain and is associated with cognitive impairment and dementia.However,recent studies reported an association between patent foramen ovale(PFO)and WML in migraineurs,especially in young,middle-aged migraineurs.Our retrospective,case-control study aims to describe the clinical characteristics of WML in this population and to explore potential risk factors.Methods:226 patients with migraine and PFO were consecutively initially screened.Relevant factors were selected by the least absolute shrinkage and selection operator(LASSO)regression and multivariable logistic regression model.A Nomogram was employed to visualize the prediction model conveniently.The discrimination and calibration abilities were evaluated using the Receiver Operating Characteristic(ROC)curve,the Hosmer-Lemeshow test,and calibration curves.Results:One hundred and nineteen participants were ultimately enrolled in our study,with a median age of 36.9±12.7 years and 80.7%of females.Brain magnetic resonance imaging MRI showed 67(56.3%)patients had WML,whereas 52(43.7%)patients were categorized into the non-WML group.LASSO regression screened out potential variables and subsequent multivariate analysisfinally identified age,mean platelet volume,andfibri-nogen(FIB)as independent predictive factors of WML.The area under the ROC curve(AUC)was 0.807.Hos-mer-Lemeshow test and calibration curve verified a consistency between the predicted and actual probability.Conclusion:The predictive nomogram established and validated in our study may assist clinicians in screening WML among young middle-aged migraineurs with PFO and developing individualized preventive and treatment strategies.

Multiple paradoxical embolisms caused by central venous catheter thrombus passing through a patent foramen ovale: A case report

BACKGROUND To date,this is the first case of a paradoxical embolism(PDE)that concurrently manifested in the coronary and lower limb arteries and was secondary to a central venous catheter(CVC)thrombus via a patent foramen ovale(PFO).CASE SUMMARY Here,we report a case of simultaneous coronary and lower limb artery embolism in a PFO patient carrier of a CVC.The patient presented to the hospital with acute chest pain and lower limb fatigue.Doppler ultrasound showed a large thrombus in the right internal jugular vein,precisely at the tip of the CVC.Transthoracic and transesophageal echocardiography confirmed the existence of a PFO,with inducible right-to-left shunting by the Valsalva maneuver.The patient was administered an extended course of anticoagulation therapy,and then the CVC was successfully removed.Percutaneous PFO closure was not undertaken.There was no recurrence during follow-up.CONCLUSION Thus,CVC-associated thrombosis is a potential source for multiple PDE in PFO patients.

Safety and Efficacy of Biodegradable Patent Foramen Ovale Occluder in Patients with Migraine:A Clinical Trial

Background:Transcatheter closure of patent foramen ovale(PFO)has been widely accepted as a highly effective way to treat high-risk PFO-related diseases.However,traditional non-degradable occluders made of metal alloys will permanently exist in the body,resulting in thrombosis,valve damage,hemolysis,arrhythmia,or other complications.The biodegradable PFO occluder developed by Shanghai Mallow Medical Instrument Co.,Ltd.,China can be fully absorbed and degrade into nontoxic ingredients,reducing postoperative complications.Objectives:To study the safety and efficacy of biodegradable PFO occluders in treating PFO.Methods:This single-center clinical trial collected 30 patients treated with a biodegradable PFO occluder.The follow-up period lasted 12 months to analyze the echocardiographic characteristics and headache relief through HIT-6 scores.Results:The immediate success rate was 100%,with no intraoperative severe occlusion-related complications.The contrast transcranial Doppler(cTCD)at 12 months showed that all patients’right-to-left shunts(RLS)were grade I or 0 with no serious postoperative complications,indicating the overall success rate was 100%.The biodegradable PFO occluder mostly degraded six months after the occlusion.Conclusion:PFO closure with a Mallow biodegradable occluder is safe and effective and has no severe complications.

Platypnea-Orthodeoxia Syndrome in an Elderly Patient Treated with Percutaneous Patent Foramen Ovale Closure: Report of a Case and Review of the Literature

Introduction: Platypnea-Orthodeoxia syndrome is characterized by dyspnea and hypoxia in the upright position, usually improving in the supine position. Two components are required: an interatrial or intrapulmonary shunt, and a functional component. Diagnosis is made by contrast ultrasonography. We report a case of Platypnea-Orthodeoxia syndrome revealed by positional dyspnea in an 87-year-old patient. The aim of this study is to describe the clinical, therapeutic and evolutionary profile of this syndrome. Case Presentation: This is an 87-year-old patient with a history of pulmonary embolism (PE) and stroke. He was seen for dyspnea and desaturation in orthostatism, revealing a patent foramen ovale (PFO). Progression was favorable after closure of the PFO. Conclusion: Platypnea-Orthodeoxia syndrome may be presented as simple exertional dyspnea. The clinician should check for improvement in symptoms and/or oxygenation during decubitus. Definitive treatment consists of percutaneous closure of the shunt.

Novel way of patent foramen ovale detection and percutaneous closure by intracardiac echocardiography:A case report

BACKGROUND Patent foramen ovale(PFO)is the most common congenital heart disease and is associated with several diseases,including stroke and migraine.PFO diagnosis involves transoesophageal echocardiography,transthoracic echocardiography,and transcranial Doppler.Recent studies have shown that intracardiac echocardiography(ICE)can be used to diagnose and guide percutaneous transcatheter closure.CASE SUMMARY A 70-year-old male presented with paroxysmal dizziness and limb weakness for the past 3 mo.Magnetic resonance imaging revealed a history of stroke,and a bubble test revealed the presence of PFO.The patient was then transferred to our hospital for PFO closure.Under ICE guidance,the separation of the septum primum and septum secundum was unclear;we then used a Swartz catheter to confirm PFO by applying physical pressure on the right part of the atrial septum without using any contrast.The ICE continuously and clearly guided the procedure.CONCLUSION ICE can guide PFO closure in patients with a history of stroke.When PFO is not evident under ICE,a Swartz catheter can be used.

川芎内生菌Pseudeurotium ovale代谢产物研究

通过大孔树脂柱层析、凝胶柱层析和高效液相色谱等方法对川芎中分离得到的内生菌Pseudeurotium ovale的代谢物进行分离纯化,从中分离得到5个化合物,并通过核磁共振和质谱等波谱学技术手段确认所有化合物的结构,其中包含一个新的化合物4-methoxy-3-methyl-6-(1 E,3 E)-1,3-pentadien-1-yl-2 H-pyran-2-one(1)和四个首次从中分离得到的已知化合物:(2 E,4 E)-1-(2,6-dihydroxy-3,5-dimethylphenyl)-2,4-hexadien-1-one(2)、2-deoxy-sohirnone C(3)、trichodimerol(4)、3,7-dihydroxy-1,9-dimethyl-dibenzofuran(5)。体外抗炎活性测试表明化合物1可抑制经脂多糖(LPS)处理的RAW 264.7细胞中NO、IL-6和TNF-α等炎症因子的分泌。

Clinical relevance of atrial septal aneurysm and patent foramen ovale with migraine

AIM To test the potential association between atrial septal aneurysm(ASA) and migraine in patent foramen ovale(PFO) closure patients through an observational, singlecenter, case-controlled study.METHODS We studied a total of 450 migraineurs who had rightto-left shunts and underwent PFO closure in a retrospective single-center non-randomized registry from February 2012 to October 2016 on the condition that they were aged 18-45 years old. Migraine was diagnosed according to the International Classification of Headache Disorders, 3^(rd) edition and evaluated using the Headache Impact Test-6(HIT-6). All patients underwent preoperative transesophageal echocardiography, contrast transthoracic echocardiography, and computed tomography or magnetic resonance imaging examinations, with subsequent fluoroscopy-guided PFO closure. Based on whether they have ASA or not, the patients were divided into two groups: A(PFO with ASA, n = 80) and B(PFO without ASA, n = 370). Baseline characteristics and procedural and follow-up data were reviewed. RESULTS Compared to group B, group A had an increased frequency of ischemic lesions(11.3% vs 6.2%, P = 0.038) and migraine with aura(32.5% vs 21.1%, P = 0.040). The PFO size was significantly larger in group A(P = 0.007). There was no significant difference in HIT-6 scores between the two groups before and at the oneyear follow-up after the PFO closure [61(9) vs 63(9), P = 0.227; 36(13) vs 36(10), P = 0.706].CONCLUSION Despite its small sample size, our study suggests that the prevalence of ASA in PFO with migraine patients is associated with ischemic stroke, larger PFO size, and migraine with aura.

Patent foramen ovale closure reduces recurrent stroke risk in cryptogenic stroke:A systematic review and metaanalysis of randomized controlled trials

AIM To investigate if patent foramen ovale(PFO) closure device reduces the risk of recurrent stroke in patients with cryptogenic stroke.METHODS We searched five databases-Pub Med,EMBASE,Cochrane,CINAHL and Web-of-Science and clinicaltrials.gov from January 2000 to September 2017 for randomized trials comparing PFO closure to medical therapy in cryptogenic stroke.Heterogeneity was determined using Cochrane's Q statistics.Random effects model was used.RESULTS Five randomized controlled trials with 3440 patients were included in the analysis.Mean follow-up was 50 ± 20 mo.PFO closure was associated with a 41% reduction in incidence of recurrent strokes when compared to medical therapy alone in patients with cryptogenic stroke [risk ratio(RR): 0.59,95%CI: 0.40-0.87,P = 0.008].Atrial fibrillation was higher with device closure when compared to medical therapy alone(RR: 4.97,95%CI: 2.22-11.11,P < 0.001).There was no difference between the two groups with respect to all-cause mortality,major bleeding or adverse events.CONCLUSION PFO device closure in appropriately selected patients with moderate to severe right-to-left shunt and/or atrial septal aneurysm shows benefit with respect to recurrent strokes,particularly in younger patients.Further studies are essential to evaluate the impact of higher incidence of atrial fibrillation seen with the PFO closure device on long-term mortality and stroke rates.

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated metaanalysis of randomized trials

BACKGROUND A few randomized clinical trials(RCT) and their meta-analyses have found patent foramen ovale closure(PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear.AIM To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs.METHODS Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke(IS), transient ischemic attack(TIA), a composite of IS, TIA and systemic embolism(SE), mortality, major bleeding,atrial fibrillation(AF) and procedural complications were the major outcomes.Random-effects model was used to perform analyses.RESULTS Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC,compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95%confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55(0.32-0.93); P = 0.02] and increased the AF risk [4.79(2.35-9.77); P < 0.0001]. No statistical difference was observed in the risk of TIA [0.86(0.54-1.38); P = 0.54],mortality [0.74(0.28-1.93); P = 0.53] and major bleeding [0.81(0.42-1.56); P = 0.53]between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm.CONCLUSION In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.

Closing patent foramen ovale in cryptogenic stroke:The underscored importance of other interatrial shunt variants

Recent trials and metanalysis even not fully conclusive and still debated,at least suggested that mechanical device-based closure of patent foramen ovale(PFO)is more effective than medical therapy in prevent recurrence of stroke. In a proportion ranging from 20% to nearly 40% of patients in literature,PFO is associated to atrial septal aneurysm(ASA):ASA is a well-known entity often associated with additional fenestration. Additionally small atrial septal defects("Flat ASD") can present with signs of paradoxical embolism and cannot be easily detected by transthoracic echocardiography or even by transesophageal echocardiography and are usually discovered by intracardiac echocardiography at the moment of transcatheter closure. This evidence might change potentially the anatomical diagnosis from PFO to fenestrated ASA or as we called it to "hybrid defect",being a bidirectional flow through a small ASD or/and an additional fenestration,often present. Despite the differences in anatomy,pathophysiology and haemodynamic paradoxical embolism may occur in both entities and also may be the first appearance of fenestrated ASA. Because some overlapping do really exist between PFO and hybrid defects,which are often not clearly differentiable by standard diagnostic tools,it is likely that a proportion of patients evaluated for potential transcatheter closure of PFO had actually a different anatomical substrate. These different anatomical and pathophysiologic entities have not been address in any of the previous trials,potentially having an impact on overall results despite the similar mechanical treatment. Neurologists and general cardiologists in charge of clinical management of PFOrelated cryptogenic stroke should be aware of the role of hybrid defects in the pathophysiology of paradoxical embolism- mediated cerebral ischemic events in order to apply the correct decision- making process and avoid downgrading of patients with paradoxical embolism-related interatrial shunt variants different from PFO.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging

BACKGROUND Cardiogenic embolism caused by patent foramen ovale(PFO)is a common etiology of cryptogenic stroke(CS),particularly in young and middle-aged patients.Studies about right-to-left shunt(RLS)detection using contrast-enhanced transcranial Doppler(c-TCD)are numerous.According to the time phase and number of microbubbles detected on c-TCD,RLS can be classified and graded.We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS.AIM To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD.METHODS We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital.In total,111 PFO-related CS patients were divided according to whether RLS was permanent(microbubbles detected both at resting state and after the Valsalva maneuver)or latent(microbubbles detected only after the Valsalva maneuver)on c-TCD.Each group was subdivided into small,mild and large RLS according to the grade of shunt on c-TCD.A normal control group was composed of 33 patients who suffered from simple dizziness.Intragroup and intergroup differences were analyzed in terms of clinical,laboratory and diffusion-weighted imaging lesion characteristics.The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed.RESULTS In 111 patients with PFO-related CS,68 had permanent RLS and 43 had latent RLS.Clinical characteristics and laboratory tests were not significantly different among the permanent RLS,latent RLS and normal control groups.The proportion of patients with multiple territory lesions in the permanent RLS group(50%)was larger than that in the latent RLS group(27.91%;P=0.021).Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group(30.23%vs 8.82%,P=0.004).Permanent-large and latent-large RLS were both more likely to be related to multiple(P_(trend)=0.017 and 0.009,respectively),small(P_(trend)=0.035 and 0.006,respectively)and cortical(P_(trend)=0.031 and 0.033,respectively)lesions.The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography(r=0.758,P<0.001).CONCLUSION Distribution of the infarct suggested the possible type of RLS.Multiple,small and cortical infarcts suggest large RLS induced by a large PFO.

Paradoxical embolus straddling patent foramen ovale demonstrated by computed tomographic pulmonary angiography

An elderly gentleman presented to the emergency department with a recent history of dyspnoea, collapse and transient neurological symptoms. He was noted to be hypoxic with a significantly elevated D Dimer. A computer tomography pulmonary angiogram demonstrated a large embolus with a further filling defects within the left and the right atria, abutting the interatrial septum. Suspicion of a paradoxical pulmonary embolus was raised and the patient subsequently underwent echocardiography which confirmed a patent foramen ovale(PFO). He was commenced on warfarin therapy. In patients with elevated right heart pressure, a PFO can be unmasked and give rise to cerebral emboli. Clinical suspicion should be raised in patients with pulmonary emboli or deep venous thrombosis if there is a concomitant history of focal neurological symptoms.

Influence of High-Velocity Blood Flow on Right-to-Left Shunt in Patients with Patent Foramen Ovale during the Valsalva Maneuver

In this study, we investigated the changes in the right-to-left shunt (RLS) of the patent foramen ovale (PFO) at different phases of the Valsalva maneuver and analyzed the possible mechanisms. The study population consisted of 57 patients with symptoms highly suggestive of a PFO. These patients had been diagnosed with apsychia, migraine with aura, cerebral infarction, transient ischemic attack (TIA), and cerebral ischemia with unknown cause. Routine echocardiography was performed in all patients to rule out a cardiac malformation. Contrast-transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) were used to visualize and quantify the RLS. The standard apical four chamber view was used to observe the changes of E peak, A peak, and velocity-time integral (VTI) ratio of tricuspid blood flow during the strain phase and release phase of the Valsalva maneuver. Paired t-test was used to compare E peak, A peak, and VTI ratio of tricuspid blood flow during the different phases. The right-to-left shunt across the PFO (PFO-RLS) was graded in the two phases and compared by Kruskal-Wallis test. Compared with the strain phase of the Valsalva maneuver, the parameters of E, A, and VTI in diastolic period in patients with PFO-RLS at the release phase were significantly increased [54.30 ± 13.65 cm/s vs 100.35 ± 21.11 cm/s, 42.21 ± 12.32 cm/s vs 57.30 ± 18.88 cm/s, 10.34 ± 3.27 cm/s vs 19.58 ± 4.56 cm/s, respectively], and the difference was statistically significant. The positive consequence of PFO-RLS, as diagnosed by c-TTE with the Valsalva maneuver at the release phase of the Valsalva maneuver, was significantly higher than that at the strain phase of the Valsalva maneuver. At the beginning of release phase of the Valsalva maneuver, decreased intrathoracic pressure led to increased venous backflow into the right atrium. Thus, high-velocity blood flow rapidly pushed the PFO open, which resulted in a significant increase in the PFO-RLS. Therefore, the increase of the PFO-RLS during the Valsalva maneuver is caused by the impact of high-velocity blood flow the PFO.

Left atrial dysfunction in elderly patients with patent foramen ovale and atrial septal aneurysm

Objective Recently it has been suggested that, in patients with large patent foramen ovale （PFO） and atrial septal aneurysms （ASA）, a certain amount of left atrial （LA） dysfunction may be active as an alternate mechanism promoting arterial embolism. Following this hypothesis, elderly patients, being more susceptible to atrial chambers stiffness, should present a more severe LA dysfunction profile. We sought to evaluate the grade of LA dysfunction in elderly patients submitted to transcatheter PFO closure. Methods We retrospectively enrolled 28 consecutive patients with previous stroke （mean age 674-12.5 years, 18 females） referred to our centre for catheter-based PFO closure after recurrent stroke. Baseline values of LA passive and active emptying, LA conduit function, LA ejection fraction, and spontaneous echocontrast （SEC） in the LA and LA appendage were compared with those of 50 atrial fibrillation patients, as well as a sex/age/cardiac risk matched population of 70 healthy controls. Results Pre-closure elderly subjects demonstrated significantly greater reservoir function as well as passive and active emptying, with reduced conduit function and LA ejection fraction, when compared to healthy and younger patients. After closure in elderly patients, LAparameters did not return completely to the levels of healthy patients, whereas LA dysfunction in younger subjects returned normal. Conclusions This study suggests that elderly patients have more severe LA dysfunction than younger patients, which affects the LA remodelling after closure.

Hypoxemia without persistent right-to-left pressure gradient across a patent foramen ovale:A clinical challenge

Patent foramen ovale (PFO) closure for systemic hypoxemia is controversial. The first systematic, albeit retrospective, study was recently presented which showed good procedural and clinical success for PFO closure for this indication. We present a case of acute right to left intra-cardiac shunt across PFO where the shunting is not persistent. Hence making a decision on PFO closure based on the aforementioned promising trial may not have been the right decision for the patient. This case highlights that the decision on PFO closure for such indication needs to be individualized. We also review the sparse literature on PFO closure for this indication and discuss how the decision making for such indication needs to be individualized.

Percutaneous closure of patent foramen ovale: “Closed” door after the last randomized trials?

Patent foramen ovale(PFO) percutaneous closure has previously been an accepted intervention for the prevention of recurrent cryptogenic stroke on the basis of observational studies. However, randomized trials have been lacking until now. Three recently published randomized trials(CLOSURE I, PC and RESPECT) do not demonstrate the superiority of this intervention versus optimal medical therapy, therefore making this practice questionable. Nonetheless, these trials have had certain pitfalls, mainly a lower than initially estimated number of patients recruited, therefore lacking sufficient statistical power. On the other hand, different closure devices were used in the three trials. In two of them(PC and RESPECT), the Amplatzer PFO Occluder was used and the STARflex device was used in the other one(CLOSURE I). Taken altogether, a meta-analysis of these three trials does not demonstrate a statistically significant benefit of percutaneous PFO closure(1.9% vs 2.9%; P = 0.11). However, if we analyze only the PC and RESPECT trials together, in which the Amplatzer PFO Occluder was used, a statistically significant benefit of percutaneous PFO closure is observed(1.4% vs 3.0%, P = 0.04). In conclusion, our interpretation of these trials is that the use of a dedicated, specifically designed Amplatzer PFO device could possibly reducethe risk of stroke in patients with PFO and cryptogenic stroke. This consideration equally applies to patients who have no contraindications for anticoagulant or antithrombotic therapy.

Thrombus straddling a patent foramen ovale and pulmonary embolism:A case report

BACKGROUND Venous thromboembolism is a common vascular syndrome presenting as deep vein thrombosis and/or pulmonary embolism.Thrombus has the possibility of migrating into the left circulation via patent foramen ovale in certain extreme circumstances.Thrombus straddling a patent foramen ovale is a direct evidence of this scenario.However,the confirmed cases of thrombus in transit are still rare.CASE SUMMARY A 32-year-old man suffered from recurrent syncope and intermittent dyspnea for 1 wk.Transthoracic echocardiography confirmed a thrombus straddling the patent foramen ovale,and thrombi were also found in the bilateral pulmonary artery by computed tomography.The man underwent inferior vena cava filter placement and thrombolysis with alteplase.Echocardiography showed the absence of thrombi in both the right atrium and left atrium 2 d after hospitalization.The man was discharged to home on warfarin without any complications 2 wk later.CONCLUSION Scrutinizing intracardiac thrombi provides measurable value in pulmonary embolism as closure of patent foramen ovale may be considered in certain patients.Early intervention plays a critical role in thrombus straddling a patent foramen ovale.A sedentary lifestyle may predispose young adults to thromboembolism,even if there are no other risk factors.

Patent foramen ovale closure in non-lacunar cryptogenic ischemic stroke:where are we now?

Patent foram ovale(PFO)is the most common anatomical cause of an interarterial shunt.It is usually asymptomatic but may cause paradoxical embolism and is a risk factor for non-lacunar cryptogenic cerebral ischemia in young adults.Although the first clinical trials did not show a significant superiority of PFO closure in the secondary prevention of cerebral ischemia as compared with standard antithrombotic treatment,six subsequent randomized clinical trials(CLOSURE I,PC Trial,RESPECT,CLOSE,REDUCE,and DEFENSE-PFO)performed in a sample of cryptogenic stroke in patients aged 60 years or younger provided evidence of a significant reduction of recurrent cerebral ischemia after percutaneous PFO closure.However,the use of percutaneous PFO closure cannot be generalized to the entire population of patients with cerebral ischemia and PFO,but it is indicated in highly selected patients with non-lacunar cryptogenic cerebral infarction with a large right-to-left shunt,an atrial septal aneurysm and no evidence of atrial fibrillation,as well as in association with antithrombotic treatment for an optimal secondary prevention of cerebral ischemia.

Should we consider patent foramen ovale and secundum atrial septal defect as different steps of a single anatomo-clinical continuum？

1 Introduction Isolated atrial septal defects （ASD） represent 7% of all cardiac anomalies and can present at any age. Adolescents and adults with simple congenital heart disease such as isolated atrial septal defects are more likely to reach adult age without being diagnosed. Secundum ASD （sASD） is by far the most common type, occurring in 1/1500 live births, with 65% to 75% involving females, On the other hand, patent foramen ovale （PFO） represents an endemic variant in the normal population with a prevalence of 25%-27%. These two entities appear so different that is difficult to fred a conjunction ring： nevertheless we use the same philosophy for the treatment, Indeed, device-based closure has been proved to be effective in both settings.

Percutaneous Patent Foramen Ovale Closure versus Medical Therapy in Cryptogenic Stroke: An Update Meta-Analysis of Randomized Controlled Trials

Objectives: Concerns regarding the real efficacy of transcatheter patent foramen ovale (PFO) closure versus medical therapy in patients with cryptogenic stroke remained unresolved. We performed a meta-analysis using the randomized controlled trials on the efficacy and safety of transcatheter PFO closure in patients with cryptogenic stroke. Methods: Web of Science, EMBASE, PubMed, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs). The primary outcome was recurrent stroke and transient-ischemic attack (TIA). Original data, hazard ratio (HR) with 95% confidence interval (95% CI) were abstracted to calculate a pooled effect size. Results: Our meta-analysis showed benefit with device closure when compared with medical therapy with an HR of 0.54 (95% CI: 0.39 - 0.74, P = 0.108) in the intention-to-treat cohort, 0.44 (95% CI: 0.24 - 0.82, P = 0.103) in the per-protocol populations, and 0.43 (95% CI: 0.31 - 0.60, P = 0.019) in the as-treated populations. There was a significantly higher incidence of new-onset atrial fibrillation in PFO closure patients (OR = 4.53, 95% CI: 2.58 - 7.97, P = 0.094). PFO Patients with an atrial septal aneurysm benefit from device closure (OR = 0.39, 95% CI: 0.22 - 0.69, P = 0.053). Patients with a substantial PFO shunt benefit the greatest with device closure with a pooled OR of 0.27 (95% CI: 0.14 - 0.56, P = 0.525). Conclusions: The meta-analysis concluded that PFO closure was associated with significantly lower risk of recurrent stroke in PFO patients with cryptogenic stroke than with medical therapy alone. The benefit of PFO closure was greater in patients with a substantial shunt and atrial septal aneurysm. PFO closure was associated with higher rates of new-onset atrial fibrillation.