Patent foramen ovale closure: past,present and future

Patent foramen ovale (PFO) is a common congenital abnormality that has been implicated in a number of disease processes, including cryptogenic stroke and migraine headaches. Medical treatment for these processes is often considered inadequate and mechanical closure of the PFO is an attractive, albeit controversial, alternative. PFO closure has become common practice in many centers, although recent guidelines limit its indication to certain subsets of patients. This review first focuses on the anatomy, physiology and pathophysiology of PFO, and then reviews the currently available and experimental devices for PFO closure, as well as the present clinical data pertaining to them. Finally, we present our perspective of the PFO closure, with regard to its current use and future directions.     

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.     

Patent Foramen Ovale: Pivotal Role of Transesophageal Echocardiography in the Indications for Closure,Assessment of Varying Anatomies and Post-procedure Follow-up

Patent foramen ovale (PFO) is present in 15%–30% of the general population and has been associated with various pathologic states, including cryptogenic stroke, platypnea–orthodeoxia syndrome, decompression sickness and migraine with auras. Transesophageal echocardiography (TEE) has a major role in the diagnostic evaluation of PFO, as well as in the post-procedural assessment after transcatheter closure. The goals of this article were to synthesize the echocardiographic transesophageal techniques required for accurate PFO diagnosis and careful anatomic assessment of its anatomic variants, to focus TEE indications for device closure as complementary to clinical indications and to assess the role of TEE in the post-procedure follow-up.     

Patent foramen ovale and migraine--bringing closure to the subject

There is increasing interest in the relationship between migraine and patent foramen ovale (PFO). PFO is more common in migraineurs with aura, and migraine with aura is more prevalent in patients with PFO. Retrospective analyses of PFO closure for stroke prevention and decompression illness in divers have suggested that migraineurs with and without aura may derive significant benefit from PFO closure, but to date no prospective, randomized, sham-controlled study to confirm this has been completed. Herein we review published data regarding the relationship between migraine and PFO and discuss the rationale, justification, and important factors to consider in the conduct of prospective, controlled, clinical trials designed to evaluate the efficacy and safety of percutaneous device closure of PFO for migraine prevention.     

Patent foramen ovale closure in post‐CVA/TIA patients: psychological distress,quality of life and optimism

Background: Patent foramen ovale (PFO) is common in asymptomatic adults, but imposes higher risk for transient ischaemic attack (TIA) or cerebral vascular accident (CVA). Trans‐catheter closure of the PFO is now a common procedure in patients after cryptogenic CVA or TIA. No studies to date have assessed the psychological aspects of PFO closure. Aims: To assess the level of psychological distress, quality of life and optimism in patients post‐PFO closure in comparison with healthy age‐matched controls. Methods: A total of 89 patients who had undergone trans‐catheter PFO closure and 60 age‐matched controls were enrolled in the cross‐sectional study. They answered demographic, health, quality of life, anxiety and depression and optimism questionnaires. Results: PFO patients and controls reported similar levels of quality of life, depression and anxiety, although the study group reported a higher level of optimism. An age × group effect appeared for depression, indicating that older controls were significantly more depressed than their counterparts in the study group and than the younger participants in both groups. Optimism significantly accounted for the variance of depression, anxiety and quality of life, and age significantly accounted for depression and quality of life, while group also significantly accounted for depression. Conclusions: Post‐PFO closure patients enjoy good psychological well‐being and quality of life, and are more optimistic, which supports the view of optimism as a situational trait.     

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.     

Intra-atrial thrombus after surgical closure of patent foramen ovale.

Patent foramen ovale (PFO) represents a potential path for paradoxical embolism and is associated with cryptogenic stroke. It has been suggested that because a PFO represents a repairable lesion (by surgical or transcatheter methods), repair may be the optimal treatment to prevent recurrent stroke. This report describes a patient with recurrent neurologic and peripheral embolic events, which occurred approximately 6 months after the surgical closure of a PFO. The diagnosis of an intra-atrial thrombus with a small residual PFO was made by subsequent transesophageal echocardiography. Thrombus formation at the closure site needs to be considered in a patient with recurrent embolic events after closure of a PFO.     

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.     

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.     

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.     

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.     

Two-dimensional echocardiography using second harmonic imaging for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies

Right-to-left shunting (RLS), usually through a patent foramen ovale (PFO), has been associated with migraine, cryptogenic stroke and hypoxemia. With emerging observational studies and clinical trials on the subject of PFO, there is a need for accurate diagnosis of PFO in patients being considered for transcatheter closure. While transesophageal echo (TEE) bubble study is the current standard reference for diagnosing PFO, transthoracic echo with second harmonic imaging (TTE-HI) may be a preferable screening test for RLS due to its high accuracy and non-invasiveness. The aim of this meta-analysis was to determine the accuracy of TTE-HI compared to TEE as the reference. A systematic review of Medline, Cochrane and Embase was done for all the prospective studies assessing for intracardiac RLS using TTE-HI compared to TEE as the reference; both TTE-HI and TEE were performed with a contrast agent and a maneuver to provoke RLS in all studies. A total of 15 studies with 1995 patients fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TTE-HI were 91 and 93 % respectively. Likewise, the positive and negative likelihood ratios were 13.52 and 0.13 respectively. TTE-HI is a reliable, non-invasive test with proficient diagnostic accuracies. The high sensitivity and specificity of TTE-HI make it a useful initial screening test for RLS. If the precise anatomy is required, then TEE can be obtained before scheduling a patient for transcatheter PFO closure.     

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.     

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.     

超声心动图在卵圆孔未闭封堵中的应用及卵圆孔未闭分流方向的探讨

目的探讨超声心动图在卵圆孔未闭(PFO)治疗中的应用价值.方法 7例封堵治疗PFO患者,术前经胸(TTE)或经食管超声心动图(TEE)明确PFO诊断,术中TTE和X线引导监护,术后TTE随访;并对157例PFO分流方向进行统计分析.结果 7例PFO封堵患者右向左分流的确诊方法:TTE 1例,TEE 4例,TTE或TEE 右心声学造影各1例.术后TTE随访PFO分流消失.157例TTE诊断的PFO以左向右分流表现为主,少数右向左分流和双向分流者多伴其他心脏结构和功能改变.结论超声心动图在PFO封堵术中具有多方面重要作用.TEE及声学造影诊断PFO右向左分流的敏感性高于单纯TTE.常规TTE检查PFO多表现为左向右分流,而非理论定义的右向左分流.     

Current evidence for closure of a patent foramen ovale for cryptogenic stroke prevention

A patent foramen ovale (PFO) has long been implicated as a potential mechanism for cryptogenic stroke (CS), which accounts for up to 40% of all cases of ischaemic stroke. Although there is a strong association between a PFO and CS, there is less evidence that percutaneous closure of the defect, as opposed to medical therapy with antithrombotics or anticoagulants, is the most effective form of secondary prevention. The aim of this review is to examine the evidence comparing percutaneous closure with medical therapy, with a particular focus on three recently published randomised controlled trials.     

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。     

经胸超声心动图在卵圆孔未闭封堵术中的应用

目的 探讨经胸超声心动图（TFE）在卵圆孔未闭（PFO）封堵术中的应用价值。方法回顾性分析43例PFO患者在封堵术前、术中及术后的TTE图像特征。结果 TTE在术前可清晰显示PFO的大小、形态和分流方向,能帮助介入医师选择合适的封堵器;术中可准确地评价PFO患者封堵器的位置、形态及其与周边的临近结构关系;术后可有效地监控PFO患者预后情况。结论 TTE在PFO封堵术前确诊、术中引导、监护及术后随访均具有重要的作用。     

Patent foramen ovale: assessment, clinical significance and therapeutic options

Foramen ovale plays an important function in the fetus but is of no physiologic significance after birth and closes in most individuals. In about one fourth of the population, however, foramen ovale remains open for life and has been associated with cerebrovascular accidents, especially in younger patients, presumably through paradoxical embolism. Patent foramen ovale (PFO) has also been associated with hypoxia, migraine headaches and neurologic findings of decompression illness in scuba divers. Availability of transesophageal echocardiography and its frequent use in the management of patients with stroke has lead to frequent detection of PFO. In addition, the recent development of devices and techniques for percutaneous closure of PFO has resulted in widespread enthusiasm for such interventions, even when a clear etiologic role for PFO may not be established. In the United States, the Federal Drug Administration (FDA) has approved two such devices through compassionate investigational device exemption without adequate data from large randomized clinical studies. Other such devices are undergoing evaluation in clinical trials. Expert opinions have been helpful for clinical decision making in management of patients with PFO associated with stroke, hypoxia, decompression sickness and migraine headaches.     

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.