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.     

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.     

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 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.     

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.     

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.     

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.     

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.     

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.     

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.     

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 and migraine

Results from several observational studies indicate an association between migraine and patent foramen ovale (PFO). Several biological mechanisms have been proposed to explain this link, including shared genetic inheritance. However, there is currently insufficient evidence to support a causal link between PFO and migraine. Although the results of uncontrolled observational studies suggest the PFO closure may have a beneficial effect on migraine frequency, a large randomized trial failed to support such a conclusion. Until there is more evidence from ongoing large controlled trials, PFO closure should not be performed in clinical practice for the prophylaxis of migraine.     

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: 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.     

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.     

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.     

Echocardiographic features of PFOs and paradoxical embolism: a complicated puzzle

Patent foramen ovale (PFO) is a residual, oblique, slit or tunnel like communication in the atrial septum that persists into adulthood. It is usually an incidental finding with no clinical repercussions. Nevertheless, recent evidence supports the association between the presence of a PFO and a number of clinical conditions, most notably cryptogenic stroke (CS). There is enough evidence that paradoxical embolism is a mechanism which can explain this association. Patient characteristics and certain echocardiography-derived anatomical and hemodynamic features of PFO provide great assistance in estimating the probability of paradoxical embolism. In this review, we initially describe PFO embryology and anatomy. We extensively present the available data on clinical, anatomical and hemodynamic features of PFOs which have been correlated with increased likelihood of paradoxical embolism and recent evidence of therapeutic management.     

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.     

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.