MIGRAINE EPIDEMIOLOGY, CLINICAL PRESENTATIONS, AND COMORBIDITY

A patent foramen ovale (PFO) is a frequent remnant of embryological development with clinical importance in thromboembolism, paradoxical embolism, stroke, platypnea-orthodeoxia, decompression sickness, and migraine headache. The proposed mechanisms of stroke with PFO include paradoxical embolization, in situ thrombosis within the canal of the PFO, associated atrial arrhythmias, and concomitant hypercoagulable states. Prospective trials using aspirin treatment to reduce recurrent stroke showed a significant recurrence of neurologic events in patients with a PFO and atrial septal aneurysm. Use of warfarin anticoagulation does not further reduce recurrent stroke rates compared with antiplatelet therapy. Both surgical and catheter-based modes of closure have been shown to decrease the rate of subsequent embolic events substantially. Successful closure, defined by transesophageal echocardiography, appears to predict freedom from subsequent embolic events. To our knowledge, no randomized trials comparing anticoagulation with surgical or catheter-based closure have been performed.     

Patent foramen ovale and stroke

A patent foramen ovale (PFO) is a frequent remnant of embryological development with clinical importance in thromboembolism, paradoxical embolism, stroke, platypnea-orthodeoxia, decompression sickness, and migraine headache. The proposed mechanisms of stroke with PFO include paradoxical embolization, in situ thrombosis within the canal of the PFO, associated atrial arrhythmias, and concomitant hypercoagulable states. Prospective trials using aspirin treatment to reduce recurrent stroke showed a significant recurrence of neurologic events in patients with a PFO and atrial septal aneurysm. Use of warfarin anticoagulation does not further reduce recurrent stroke rates compared with antiplatelet therapy. Both surgical and catheter-based modes of closure have been shown to decrease the rate of subsequent embolic events substantially. Successful closure, defined by transesophageal echocardiography, appears to predict freedom from subsequent embolic events. To our knowledge, no randomized trials comparing anticoagulation with surgical or catheter-based closure have been performed.     

Secondary prevention of cerebral ischemia in patent foramen ovale: systematic review and meta-analysis

BACKGROUND: Therapy for patent foramen ovale (PFO), found with increased frequency in the setting of stroke in the young, is controversial. We compiled a synthesis of the literature on therapeutic options for PFO and stroke. METHODS: Searching MEDLINE (1966 to 1999), published abstracts, and bibliographies of primary and review articles, we identified five retrospective cohort studies that compared at least two different treatment options (antiplatelet therapy, warfarin, or surgery). Outcomes data on mode of therapy and recurrent stroke were abstracted, and pooled analysis was done using a random effects model. RESULTS: Warfarin was superior to antiplatelet therapy in preventing recurrent ischemic events (odds ratio [OR] 0.37; 95% confidence interval [CI], 0.23 to 0.60). Surgical PFO closure was comparable to warfarin treatment (OR 1.19; 95% CI, 0.62 to 2.27). CONCLUSION: Available data suggest that warfarin is superior to antiplatelet therapy and comparable to surgical PFO closure for the prevention of recurrent cerebral ischemic events from paradoxical embolism.     

Thrombus in transit within a patent foramen ovale: An argument for consideration of prophylactic closure?

Recurrent pulmonary embolism (PE) in prothrombotic patients with patent foramen ovale (PFO) is not considered a setting for elective PFO closure. We describe a 35-year-old woman with known PFO, recurrent PE on warfarin, and Klippel-Trenaunay syndrome-a condition with predisposition for thromboembolism-who suffered concurrent saddle PE and devastating stroke with further impending paradoxical embolus across the PFO. Optimal management in patients with biatrial thromboembolus caught in transit across PFO is challenging. Patients with recurrent PE, prothrombotic states, and PFO should be considered for PFO closure. Prompt diagnosis of impending paradoxical embolus with echocardiography and consideration of surgical removal and PFO closure are critical.     

Closing the gap on patent foramen ovale and cryptogenic stroke

Introduction: The treatment options for prevention of recurrent of cryptogenic stroke in patients with patent foramen ovale (PFO) have been intensely debated in the recent decades. The suggested options were percutaneous closure of PFO versus medical therapy. However, up to these date there is a controversy regarding the indication of percutaneous closure. Multiple meta-analysis and recent randomized control trials showed the benefit of PFO closure when compared with medical therapy alone.

Areas covered: The article reviews the prevalence, physiology, diagnosis and treatment options of PFO after cryptogenic stroke. Furthermore, it will discuss the results of randomized control trials that compared the PFO closure to medical therapy.

Expert opinion: The association between PFO and unexplained cryptogenic stroke has been well established in the multiple studies. The diagnosis and management of PFO might be challenging in some cases. Although multiple studies showed that PFO closure is associated with lower rates of recurrent stroke in patients presenting with cryptogenic stroke, the indication and patient selection for this intervention are not well established yet in the guidelines.     

PFO closuRE and CryptogenIc StrokE (PRECISE) registry: a multi-center, international registry

Background

The Premere? PFO closure device has a special design for closure of patent foramen ovale (PFO) including a flexible distance and angulation between the right and left disc providing minimal septal distortion. The primary objective of the study was to determine the degree of risk for stroke or transient ischemic attack (TIA) in patients after Premere? PFO closure device implantation.

Methods

In this multicenter, prospective observational registry, patients with a clinical indication for PFO closure were included. Patients had a history of stroke or TIA with right to left shunt. Follow-up visits were scheduled according to routine clinical practice.

Results

In 23 centers from 10 countries, 267 patients with successful device implantation were included. Assessment of right to left shunt after device implantation revealed no residual shunt in 71?%, small shunts in 16.8?%, and moderate or large residual shunts in 5.6 and 6.5?%. With common clinical practice, use of Coumadin or heparin decreased from 27?% pre- to 3?% post-implantation, while use of acetylsalicylic acid or thienopyridines increased from 64 to 95?% and 27 to 80?%, respectively; 18?% of patients were discharged with anti-platelet monotherapy. Mean follow-up was 11?±?9?months (range 1–24?months). There was no stroke or TIA. During follow-up, there was one sudden death. Atrial fibrillation occurred in five (1.9?%) patients. One (0.4?%) patient with a thrombophilic diathesis developed a thrombus.

Conclusions

In this prospective, international, multicenter PRECISE registry, the use of the Premere? PFO closure device for closure of PFO after stroke or TIA resulted in good clinical results with no recurrent event.     

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.     

Percutaneous closure of patent foramen ovale: safe and effective but underutilized

With three recently published randomized trials on patent foramen ovale (PFO) closure, the concept of PFO closure to reduce recurrent strokes has been proven; however, PFO closure is currently only considered for secondary prevention. Given the potential devastating consequences of a PFO-related event, we advocate screening for and closure of a PFO for primary prevention in high-risk populations. Such populations include patients who are suffering from a disease that is associated with PFO (e.g., migraine) or patients with high-risk hobbies/professions (e.g., weight-lifters, frequent-flyers, and deep sea divers). Looking at young people with a remaining average life expectancy of 50 years, we have to close 2.4 PFOs to prevent one stroke. This should support a more proactive attitude toward PFO screening and closure.     

卵圆孔未闭介入封堵预防隐源性脑卒中复发

目的 探究卵圆孔未闭(PFO)封堵治疗的安全性、有效性,进一步讨论介入封堵治疗PFO的临床意义。方法 选取2019年1-7月我院行PFO介入封堵术的PFO患者90例,术前所有患者均行经胸超声心动图右心声学造影（cTTE）及经食道超声心动图（TEE）证实为卵圆孔未闭并存在右向左分流。封堵成功即刻予床旁经胸超声心动图（TTE）,观察封堵器及分流情况。术后3个月,行cTTE及颅脑CT。结果 所有患者均成功置入封堵器,即刻经胸超声心动图证实封堵器位置正常,二、三尖瓣功能正常,未见残余分流,均未出现术中、术后并发症。术后随访3个月,58.9%患者头痛症状完全消失,34.4%患者头痛症状明显改善,发作频率较前明显减少,总的有效率为93.3%。术前27例一侧肢体麻木乏力患者中19例术后肢体麻木乏力症状完全消失,8例肢体麻木乏力症状虽未完全消失但较前不同程度缓解;术前8例恶心呕吐患者,术后症状完全消失。术后3个月复查经胸壁超声心动图右心声学造影示阳性率为5.6%（5/90）。术后3个月复查颅脑CT,提示本研究中90例患者均未发现新发梗死灶,再发脑卒中发生率为0%。结论 介入封堵治疗PFO可明显缓解患者临床症状,解除患者痛苦,减少分流量,降低脑卒中的再发风险,是一种安全、有效的治疗方法,对PFO的治疗具有指导意义。     

Paradoxical emboli in children and young adults: role of atrial septal defect and patent foramen ovale device closure

OBJECTIVE: To describe a multicenter experience with patent foramen ovale (PFO) and atrial septal defect (ASD) device closure for presumed paradoxical emboli in children and young adults (<35 years old). PATIENTS AND METHODS: Medical records were reviewed of patients who had device closure of an ASD or PFO, who were younger than 35 years, and who had a history of presumed paradoxical embolus between January 1999 and August 2005 at Mayo Clinic, Rochester, Minn, University of Parma, Parma, Italy, and Loyola University Medical Center, Maywood, Ill. RESULTS: Forty-five patients fulfilled the inclusion criteria. Median patient age was 29.0 years (range, 5.0-34.9 years), and 23 patients (51%) were male. Clinical diagnoses included the following: stroke, 30 (67%); transient ischemic attack, 13 (29%); myocardial infarction, 1 (2%); and renal infarct, 1 (2%). Overall, 42 patients (93%) had a PFO, and 3 (7%) had an ASD. Seventeen patients had known cardiovascular disease risk factors: tobacco use (10 patients), hypercoagulable states (7 patients), systemic hypertension (3 patients), and hyperilpidemia (2 patients). No major procedural complications occurred. Median follow-up evaluation was performed at 5.3 months (range, 2.5-40.0 months). Forty-four patients (98%) had no recurrent neurologic events and no residual atrial shunt by contrast transthoracic echocardiography. CONCLUSIONS: Cryptogenic ischemic events occur in young patients and have serious sequelae. The potential for paradoxical embolization through a PFO or an ASD should be assessed in all such patients. In our short-term follow-up, device closure was a safe alternative therapeutic option for children and young adults with presumed paradoxical emboli.     

Cryptogenic stroke and patent foramen ovale

A stroke of unknown etiology is commonly referred to as cryptogenic and is diagnosed in a considerable patient population of especially young age. Numerous case-control studies revealed a strong and consistent association between cryptogenic stroke and the presence of a patent foramen ovale. This relationship corroborates paradoxical embolism as likely stroke mechanism in this patient population. In approximately twenty-five percent of patients with cryptogenic stroke, the patent foramen ovale is accompanied by an atrial septal aneurysm, which considerably heightens the risk for recurrent neurological events. Therapeutic measures for secondary prevention in this patient population encompass medical treatment with antiplatelet agents or anticoagulants and surgical or percutaneous closure of patent foramen ovale. Currently, randomised clinical studies compare medical treatment with closure of patent foramen ovale to determine the most effective treatment strategy in this patient population.     

Patent foramen ovale transcatheter closure device thrombosis

The role of patent foramen ovale (PFO) in patients with cryptogenic stroke (stroke of unknown cause) remains controversial, although an association seems likely in younger patients with atrial septal aneurysms and PFO. The mechanism of cryptogenic stroke in these patients is presumed to be paradoxical embolism via right-to-left shunt across the PFO. The available options for treatment include medical therapy with antiplatelet or anticoagulant therapy or closure of the PFO surgically or with use of transcatheter PFO closure devices. We describe 2 cases of bilateral device thrombosis associated with use of a transcatheter PFO closure device (CardioSEAL). To our knowledge, only 1 other case of thrombosis associated with use of this device has been reported.     

Use of an echocardiographic contrast agent to establish safety of cardioversion in a patient with a ligated left atrial appendage

Transesophageal echocardiographic-guided cardioversion is a safe, accepted technique to minimize risk of stroke and embolic events when electrically converting atrial fibrillation to normal sinus rhythm. The presence of thrombus in the left atrial appendage (LAA) is a contraindication to performing cardioversion in these patients. For patients with a surgically ligated LAA, thrombus may be more prevalent and may still represent an embolic risk because of incomplete closure of the LAA. We report use of an echocardiographic contrast agent in a patient with a thrombus in a ligated LAA to determine safety of cardioversion.     

封堵卵圆孔未闭预防卒中的国外发展及中国现状

经过近20年的争议和大量研究,封堵卵圆孔未闭(patent foramen ovale,PFO)在卒中二级预防中的作用已经明确.本文从循证医学证据入手,回顾近年来国内外经导管封堵PFO预防卒中的研究成果,旨在明确能从封堵治疗中获益的PFO人群.     

Patent foramen ovale: a nonfunctional embryological remnant or a potential cause of significant pathology?

A patent foramen ovale (PFO) is an embryological remnant found in 27% of adults. It is a potential right-to-left intracardiac shunt. Shunting may be the result of reversal in the interatrial pressure gradient or abnormal streaming of blood in the right atrium. The pathologic consequences of right-to-left shunting include hypoxemia and paradoxical embolism. PFO may exacerbate preexisting hypoxemia or be its primary cause. Paradoxical embolism through a PFO is well documented. Its role in cryptogenic stroke remains controversial. A PFO may be detected by both invasive and noninvasive techniques. Contrast transesophageal echocardiography with provocative maneuvers is the diagnostic method of choice allowing visualization of the shunt. Patients with cryptogenic stroke should be screened for a PFO. If detected, noninvasive studies for deep vein thrombosis are recommended. Treatment must be tailored to the presentation. Surgical or transcatheter closure is recommended for hypoxemia. Prevention of venous embolism (air or thrombus) with or without closure of the PFO is recommended for paradoxical embolism.     

Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism

OBJECTIVE: To review our experience with, and profile the safety and efficacy of, the Amplatzer PFO (patent foramen ovale) occluder (APO) and Amplatzer septal occluder (ASO) used to close PFO and/or atrial septal defect (ASD) in patients with paradoxical embolism (PE). PATIENTS AND METHODS: Between April 1998 and November 2002, 103 patients at the Mayo Clinic in Rochester, Minn, and Scottsdale, Ariz, mean age 52.4 years, with presumed PE (transient ischemic attack [n=22], stroke [n=77], or peripheral emboli [n=4]) underwent transcatheter device closure of PFO (n=81), ASD (n=12), and ASD/PFO (n=10) with 106 devices (APO [n=22] or ASO [n=84]). RESULTS: All devices deployed successfully, and no patients died. Procedural complications included atrial fibrillation (n=2), vessel injury (n=3), profound sinus node dysfunction (n=1), and device embolization with successful retrieval (n=1). At 3 months, 7 of 95 monitored patients had trivial residual shunt; at 12 months, 2 of 28 monitored patients had trivial residual shunt. Three patients had recurrent events--2 transient ischemic attacks and 1 retinal artery occlusion--at a mean +/- SD follow-up of 8.3 +/- 8.1 months (range, 1-34 months). None of these 3 patients had residual shunt or evidence of intracardiac thrombus. The average annual recurrence of all events was 3.6% at 23 months. The overall mean +/- SD freedom from recurrence of all events was 98.9% +/- 1.2% and 83.8% +/- 10.2% at 12 and 29 months of follow-up, respectively. CONCLUSIONS: Transcatheter device closure of PFO and/or ASD with use of APO/ASO in patients with presumed PE is effective and safe. Recurrent events may occur in the absence of a residual shunt.     

Patent foramen ovale (PFO): is there life before death in the presence of PFO?

Patent foramen ovale (PFO) is an embryologic remnant with incomplete postnatal adhesion of the cardiac atrial septum primum and secundum. After birth, the prevalence of PFO decreases from about 35% at young to approximately 20% at old age. PFO has been associated with numerous conditions such as decompression illness in divers, migraine, high‐altitude pulmonary oedema, cerebrovascular and coronary ischaemia, and obstructive sleep apnoea syndrome. PFO is the cause of intermittent atrial right‐to‐left shunt, and it can be the source of cardiac paradoxical embolism. So far, randomized controlled trials have not documented a reduced rate of cerebrovascular recurrent events in patients receiving PFO device closure as compared to those on medical treatment. The purpose of this article was to critically evaluate evidence on the pathophysiologic, clinical as well as prognostic relevance of PFO.     

Clinical evaluation of a novel occluder device (Occlutech<Superscript>®</Superscript>) for percutaneous transcatheter closure of patent foramen ovale (PFO)

Background

We investigated the safety, feasibility and usefulness for closure of PFO with the new nitinol meshwire PFO-occluder device (Occlutech Figulla^®-single layer occluder) with an unique braiding technology which allows a 50% reduction of meshwork material on the left atrial side in combination with a greater flexibility as compared to the Amplatzer^® occluder device.

Methods

The retention discs of the new PFO Occlutech Figulla^® single layer device (23/25 mm) are connected by a 3 mm waist in the centre with only one right atrial side hub. The left atrial disc is a single flat layer covered by an ultrathin polyethylene terephthalate (PET) patch. We investigated the safety, feasibility and usefulness for closure of PFO in a multicenter clinical trial. Indications for closure included cryptogenic stroke with evidence of a patent foramen ovale in transesophageal echocardiography (PFO max. diameter 13 mm according to sizing balloon). The device was implanted in 36 patients (mean age 57, 18–80 years) by means of fluoroscopy and transesophageal echocardiography (TEE) using a 9 French delivery sheath and employing a femoral vein approach. Both acetylsalicylacid 100 mg/d (6 months) and clopidogrel 75 mg/d (3 months) were administered post interventional. A transthoracal (TTE) and transesophageal echocardiography follow-up examination was performed after 1, 2 and 6 months (TTE day 30 and 180; TEE day 60).

Results

The device was successfully implanted in 36 pts. In one patient PFO implantations was attempted but not crossed with a guide wire. Perioperativly there were no major in-hospital-adverse events or complications thromboembolism, occluder dislodgement, infection or myocardial infarction. One patient had transient atrial fibrillation 2 h after implantation, which terminated medically after 12 h. TEE studies in the remaining 35 pts (one pt was unwilling to further participate) showed a residual shunt in 8.6% (3/35) after 60 days and a left-to-right shunt in 2.6% (1/35) of pts. After 180 days one pt with severe arteriosclerotic heart disease and A.carotic stenosis revealed a stroke without evidence of cardioembolic origin or devices thrombosis.

Conclusions

The novel Occlutech Figulla^® PFO N single layer device appears to be safe, feasible and useful for PFO closure despite a 50% reduction of the meshwire, no distal hub and an improved flexibility of the left atrial disc.

     

To close or not to close: contemporary indications for patent foramen ovale closure

Introduction: Patent foramen ovale (PFO) is a common congenital cardiac abnormality and that has been associated with several disease processes including transient ischemic attacks (TIA), stroke, migraine headaches with aura, decompression sickness, platypnea-orthodeoxia syndrome, and shunt induced cyanosis. Controversy exists regarding closure of PFO as a therapeutic treatment modality for these disease processes. This review addresses the contemporary clinical indications for PFO closure.

Areas covered: We conducted a comprehensive literature search of contemporary research studies focusing on randomized trials and meta-analyses comparing medical therapy and device closure of PFOs for the treatment of PFO associated clinical syndromes. We synthesized this literature into a review addressing indications for PFO closure in stroke, TIA, migraine headaches with aura, decompression sickness, platypnea-orthodeoxia syndrome, and shunt induced cyanosis.

Expert commentary: Because in many PFO associated conditions it can be difficult to determine the degree to which the PFO is a causative factor in the disease process, we recommend a comprehensive diagnostic evaluation to exclude other obvious etiologies of PFO associated conditions before implicating the PFO and proceeding with closure. However in the properly selected patient population there is growing clinical experience and experimental evidence suggesting that closure of PFO is a safe and effective treatment modality.     

Saline contrast and colour Doppler transoesophageal echocardiography in detecting a patent foramen ovale and right-to-left shunts in stroke patients

Summary. A paradoxical embolism due to right-to-left shunt through a patent foramen ovale (PFO) can be responsible for stroke and other ischaemic cerebral events. We studied the usefulness of saline contrast transoesophageal echocardiography after the Valsalva manoeuvre in detecting PFO and right-to-left shunts in 28 adult patients without known reason for a recent stroke. The results were compared with conventional transthoracic colour Doppler and with transoesophageal colour Doppler techniques. A PFO was found in 24 patients (86%) of our selected study population, whereas in four patients no PFO was found. A PFO with left-to-right shunt could be diagnosed by transthoracic colour Doppler echocardiography in only one case. A PFO with left-to-right shunt was found by transoesophageal colour Doppler echocardiography in 17 patients (61%), but in only three of them was a right-to-left shunt detected, even after the Valsalva manoeuvre. In contrast, a PFO with right-to-left shunt could be detected in 21 patients (75%) by using saline contrast transoesophageal echocardiography with the Valsalva manoeuvre. However, the method was unable to detect three cases of PFO with only left-to-right shunt, which were detected by colour Doppler transoesophageal echocardiography. In conclusion, our results show that saline contrast transoesophageal echocardiography with the Valsalva manoeuvre greatly improves the echocardiographic detection of PFO with right-to-left shunts in stroke patients.