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Background: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly., Aims: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events., Methods: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted., Results: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF., Conclusions: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Patent foramen ovale (PFO) is a remnant of normal fetal anatomy which may persist into adulthood, mostly asymptomatic. In some adults, PFO may result in a potential for shunting venous thromboembolism to the arterial circulation; less frequently it can cause interatrial, right-to-left shunting of deoxygenated blood. The pathogenesis of several medical conditions is related to the presence of PFO. Some randomized clinical trials have shown evidence of benefit for device closure as compared with medical therapy in patients with cryptogenic stroke. The literature reported several cases of carbon dioxide embolism during general laparoscopic surgery and sometimes stroke after laparoscopic or neurosurgery but there are neither prospective studies addressing these issues, nor randomized clinical trials assessing the effectiveness of pharmacotherapy or interventional procedures at decreasing risk. The European position paper suggests routine monitoring in non-cardiac surgery of patients with a PFO and no actual indications for closure. This article aims to further stratify the risk of periprocedural stroke and paradoxical embolism in this category of patients.

Background: Randomised controlled trials evaluating percutaneous closure of patent foramen ovale (PFO) have included only patients with a recent embolic event. We aimed to evaluate outcomes after percutaneous PFO closure according to the delay from the last embolic episode., Methods: This international ambispective cohort included consecutive patients from 2 centres in France and Canada undergoing PFO closure for secondary prevention of a paradoxical embolic event. The primary end point was the composite of stroke or transient ischemic attack (TIA). A logistic regression model was used to evaluate determinants of late PFO closure procedures., Results: A total of 1179 patients (mean age 49 ± 12.7 years; 44.4% female) underwent PFO closure from 2001 to 2021. The median delay from last embolic event to procedure was 6.0 (interquartile range 3.4-11.2) months. The determinants of late PFO closure procedure were the centre (France vs Canada; adjusted odds ratio [aOR] 1.65, 95% confidence interval [CI] 1.25-2.19), year of procedure (since 2018 vs before 2018; aOR 1.43, 95% CI 1.08-1.90), female sex (aOR 1.63, 95% CI 1.28-2.07), and lower risk of paradoxical embolism score (aOR 1.10, 95% CI 1.03-1.19). After a median follow-up of 2.61 (1.13-7.25) years, the incidence rate of first stroke or TIA did not differ between early and late PFO procedures, with 0.51 vs 0.29 events per 100 patient-years, respectively (incidence rate ratio 1.74, 95% CI 0.66-5.08; P = 0.24), and the timing of PFO closure was not associated with the occurrence of stroke or TIA in univariate analysis (hazard ratio 0.54, 95% CI 0.22-1.34) for late vs early closure)., Conclusions: This analysis provides indirect evidence that the delay from the last ischemic event does not affect outcomes after PFO closure for secondary prevention., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Patent foramen ovale (PFO) is widely prevalent and studies have suggested an association with ischemic stroke. In this review, we aim to highlight current management of patients with ischemic stroke in the setting of PFO and discuss some areas of controversy., Recent Findings: Upon reviewing the literature, we have found that the evidence regarding the management of patients with cryptogenic stroke and PFO has come a long way in the past several years, and many uncertainties remain in clinical practice. The Risk of Paradoxical Embolism (RoPE) score helps to predict the probability of a pathogenic PFO, and recent trial data confirms the benefit of closure in carefully selected patients. The benefit of closure in older patients and in patients with alternate, competing mechanisms is still uncertain, and the long-term risks of closure are not known. Finally, the efficacy of direct oral anticoagulants (DOACs) in this patient population as compared to other medical therapy or mechanical closure has not yet been investigated. Randomized data is needed to help answer these questions. PFO closure is a safe and effective strategy in reducing stroke risk in carefully selected patients with cryptogenic stroke in the setting of a PFO. More studies are needed to test optimal medical treatment strategies and the safety and efficacy of PFO closure in patient subgroups not included in prior PFO closure trials., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke reduces the rate of recurrent events. Although presence of thrombophilia increases the risk for paradoxical emboli through a PFO, such patients were excluded from large randomized trials., Objectives: We compared the safety and efficacy of percutaneous PFO closure in patients with and without a hypercoagulable state., Methods: Data from 800 consecutive patients undergoing percutaneous PFO closure in our medical center were analyzed. All patients were independently evaluated by specialists in neurology, cardiology, hematology, and vascular medicine. A post-procedural treatment of at least 3 months of anticoagulation was utilized in patients with thrombophilia. Follow-up events included death, recurrent neurological events, and the need for reintervention for significant residual shunt., Results: A hypercoagulable state was found in 239 patients (29.9%). At median follow-up of 41.9 months, there were no differences in the frequencies of stroke or transient ischemic attack between patients with or without thrombophilia (2.5% in non-hypercoagulable group vs. 3.4% in hypercoagulable group, log-rank test p = 0.35). There were no significant differences in baseline demographics, echocardiographic characteristics, procedural success, or complications between groups., Conclusion: Percutaneous PFO closure is a safe and effective therapeutic approach for patients with cryptogenic stroke and an underlying hypercoagulable state., (© 2021 Wiley Periodicals LLC.)

Paradoxical embolism is one of the predominant causes of cryptogenic stroke and interventional secondary prevention, i.e., closure of the patent foramen ovale (PFO), is a much discussed issue. This review aims to provide a complex perspective on this topic, aggregates and comments on the available data and current guidelines. Several large trials were performed, some of which proved the superiority of PFO closure over pharmacotherapy while others have not. Studies detecting significant superiority of intervention worked with disproportionately high representation of large shunts compared to the general population. Other controversies also remain, such as the lack of comparison of the effect of modern anticoagulant/antiplatelet treatment to PFO closure or the risk of developing unwanted side effects after intervention, and these are discussed in detail. PFO closure is a suitable method for secondary prevention of paradoxical embolism and, therefore, cryptogenic stroke. However, this is only true for carefully selected patient populations and such selection is of the utmost importance in deciding on interventional or conservative treatment.

Purpose of Review: Although a patent foramen ovale (PFO) is an established risk factor for cryptogenic ischemic stroke, strategies for secondary prevention remain controversial. Increasing evidence over the past decade from well designed clinical trials supports transcatheter PFO closure for selected patients whose stroke was likely attributable to the PFO. However, patient selection using imaging findings, clinical scoring systems, and in some cases, thrombophilia testing, is crucial for determining patients most likely to benefit from closure, anticoagulation, or antiplatelet therapy., Recent Findings: Recent studies have found that patients with a high Risk of Paradoxical Embolism (RoPE) score and those with a thrombophilia benefit more from closure than medical therapy (including antiplatelet or anticoagulant therapy) alone. Meta-analyses have demonstrated an increased short-term risk of atrial fibrillation in closure patients, and that residual shunt after closure predicts stroke recurrence. Last, recent data have been inconclusive as to whether patients receiving medical therapy only benefit more from anticoagulation or antiplatelet therapy, so this remains an area of controversy., Summary: Transcatheter PFO closure is an evidence-based, guideline-supported therapy for secondary stroke prevention in patients with a PFO and cryptogenic stroke. However, proper patient selection is critical to achieve benefit, and recent studies have helped clarify those patients most likely to benefit from closure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We present a rare case of a patient with concurrent fat embolism and pulmonary embolism, in a closed femur fracture with patent foramen ovale (PFO). A 24-year-old man was involved in a motor vehicle accident with a closed left midshaft femur fracture. He developed fat embolism syndrome (FES) on day 3 of admission, and plating was performed. The D-dimer concentration was also high, which raised the suspicion of pulmonary artery embolism. Computed tomography pulmonary angiography (CTPA) revealed right inferior lobar pulmonary artery embolism and FES. A transthoracic echocardiogram (TEE) was performed, which showed a PFO. The presence of a PFO in patients with pulmonary embolism increases the risk of systemic embolism. Therefore, we recommend the routine echocardiogram for patients with pulmonary embolism to exclude any cardiac defect in causing right-to-left shunts, which predisposes the patient to paradoxical embolism.

The pathophysiological relationship between elevated serum homocysteine (Hcy) levels and patent foramen ovale (PFO) has not yet been completely clarified. In the present study, we assess the correlation between serum homocysteine levels and the RoPE score in PFO patients. We retrospectively reviewed clinical and instrumental data of 244 subjects referred to a single tertiary center for PFO evaluation and/or treatment between January 2010 and January 2018,stratified as closure and control group, respectively. Patients in the closure group had an higher serum Hcy levels compared to the control group (28.5 ± 8.5 vs 10.2 ± 6.6 μg/dL, p < 0.0001). A significant direct correlation was observed between serum Hcy levels and the RoPE Score in the entire population. A positive significant correlation continued to exist also in the closure and control groups (r = 0.472, p < 0.0001 and r = 0.378, p < 0.0001, respectively). A receiver operating characteristics curve identified the optimal cutoff value of homocysteinemia as a predictor of RoPE score > 7 in the closure group (AUC 0.90, 95% CI 0.81-0.94, p < 0.0001) when 19.5 μg/dL. Multivariate logistic regression analysis demonstrated that an Hcy serum level ≥ 19.5 μg/dL predict an RoPE score > 7 (OR 3.21, 95% CI 2.82-3.26, p < 0.0001) in closed patients independently from the presence of permanent right-to-left (RLS) (OR 2.28, 95% CI 2.01-2.43, p = 0.001) and atrial septal aneurysm (ASA) (OR 3.04, 95% CI 2.64-3.51, p < 0.0001). Serum homocysteine levels in PFO patients are positively correlated with the RoPE score. Moreover, a homocysteinemia ≥ 19.5 μg/dL predicts an RoPE score > 7 independently from the presence of a permanent RLS and a concomitant ASA.

Background: Randomized-controlled trials (RCTs) reported a finding on the safety and efficacy of percutaneous patent foramen ovale (PFO) closure to prevent stroke recurrence. It showed that the Amplatzer (AMP) device appears to be superior to medical therapy (MT) in preventing strokes and episodes of atrial fibrillation (AF), than other devices. We performed a network meta-analysis (NMA) to evaluate the closure of PFO in preventing subsequent neurological events while investigating the results obtained by specific devices., Methods: We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) and identified 6 RCTs until March 2019. We performed an NMA and used pooled ORs. Analyses were done in NetMetaXL1.6-WinBUGS1.4., Results: Six RCTs with 3,560 patients (mean age 45.2-46.2 years) were included in the present NMA. Depending on the device, 4 groups of patients were compared with MT: 1,889 patients undergoing PFO closure were significantly less likely to experience a stroke than 1,671 patients treated with MT (ORs 0.41; 95% Cr.I. 0.27-0.60 with fixed-effects model and ORs 0.22; 95% Cr.I. 0.05-0.70 with random-effects model). The patients with AMP showed a similar risk than those treated with Helex/Cardioform (HLX/CF) or with a group of 11 multiple devices. This suggests the equality between the 2 most currently used devices. When assessing TIA and, for the safety analysis, major bleeding, both models confirm no significant difference between any devices and MT. PFO closure increased the risk of new-onset AF: MT induces AF significantly less than all the devices. In favor of the AMP, there is a reduced number of cases of AF versus MT; however, no device superiority has been established in comparing HLX/CF and other devices in a random effect model., Conclusions: Our NMA provides evidence in favor of PFO closure with all the devices currently in use. We can conclude that these devices are better than MT, but not that 1 device is better than the rest in reducing stroke recurrences and AF episodes in the follow-up., (© 2020 S. Karger AG, Basel.)

A patent foramen ovale (PFO) is found in about one-quarter of all adults, but the prevalence increases to approximately half of those with a history of a so-called cryptogenic stroke. The true efficacy of PFO closure for prevention of recurrent paradoxical embolism has been debated for years, as the early 3 randomized trials did not show a statistically significant benefit of PFO closure over standard-of-care medical therapy. However, 3 recent randomized trials along with the long-term follow-up data from the largest early trial demonstrated superiority of device closure for secondary stroke prevention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: The routine use of percutaneous transcatheter patent foramen ovale closure (PPFOC) to prevent recurrent stroke in patients with cryptogenic stroke is still a matter of debate after completion major randomized controlled trials (RCTs)., Methods: The fragility index of RCTs evaluating effect of PPFOC against medial therapy alone in stroke prevention was calculated to assess the robustness of statistically significant findings., Results: Literature search with PubMed identifies 6 RCTs on PPFOC. Median number of patients who underwent PPFOC and medical treatment were 340 and 229, respectively. Median number of the patients lost to follow-up was 20 in PPFOC and 18 in medical group. Fragility index was 0 for 4 studies. Median fragility index was also 0 for both "stroke" (interquartile range: 0-5.3) and "combined stroke and TIA" (interquartile range: 0-2) endpoints. In all studies except CLOSE, fragility index was smaller than or equal to the number of the subjects lost to follow-up., Conclusions: Recent positive results of PFO closure studies should be interpreted cautiously because of their fragile characteristics. Routine PFO closure should be reserved for prevention of recurrence when suspicion for paradoxical embolism is high. Detailed individualized decision-making is crucial before ordering PPFOC for stroke prevention in patients with cryptogenic embolism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

When warfarin was the mainstay of anticoagulation for the prevention of cardioembolic stroke, the paradigm was essentially "we mustn't anticoagulate anyone unless we prove that the stroke was cardioembolic." Now that direct-acting oral anticoagulants are available, the paradigm should change. The risk of stroke is highest soon after the initial event, particularly in patients with more than one infarction. Direct-acting oral anticoagulants are not significantly more likely than aspirin to cause severe hemorrhage, and it is now clear that patients with paradoxical embolism are better treated with anticoagulant than aspirin. Percutaneous closure of a patent foramen ovale is better than aspirin, but not better than anticoagulant, and some patients with paradoxical embolism may be better treated with anticoagulant than with percutaneous closure, which cannot prevent pulmonary embolism. Patients in whom cardioembolic stroke is strongly suspected should probably be anticoagulated pending the results of investigations such as echocardiography and prolonged cardiac monitoring for atrial fibrillation, and some of them, in whom the suspicion of a cardioembolic source is very strong, should probably be anticoagulated long term, even if such investigations do not confirm a cardiac source.

Until recently, evidence to support Patent Foramen Ovale (PFO) closure for secondary prevention of recurrent stroke has been controversial. Publication of high-quality evidence from randomized clinical trials and the subsequent FDA approval of two devices for percutaneous PFO closure is expected to increase the volume of PFO closure procedures not only in the United States but worldwide. As this technology is disseminated broadly to the public, ensuring the safe and efficacious performance of PFO closure is essential to mitigate risk and avoid unnecessary procedures. This document, prepared by a multi-disciplinary writing group convened by the Society for Cardiovascular Angiography and Interventions and including representatives from the American Academy of Neurology, makes recommendations for institutional infrastructure and individual skills necessary to initiate and maintain an active PFO/stroke program, with emphasis on shared decision making and patient-centered care., (© 2019 Wiley Periodicals, Inc.)

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.

Aims: About one-third of ischemic stroke are cryptogenic. Paradoxical embolism through patent foramen ovale (PFO) has been identified as a possible cause of cryptogenic stroke. Therefore, PFO closure has been considered for secondary prevention of cryptogenic stroke. However, randomized clinical trials (RCTs) comparing PFO closure versus medical therapy led to conflicting results. Our objectives were to examine if PFO closure is superior to medical therapy alone for secondary prevention of cryptogenic stroke and to investigate whether PFO closure is associated with an increased incidence of atrial fibrillation/atrial flutter (AFL)., Methods: The authors systematically searched MEDLINE for RCTs that compared PFO closure with medical therapy. Efficacy outcome was cerebrovascular event (CVE) recurrence and safety outcome was new-onset atrial fibrillation/AFL. The outcomes of interest were investigated according to device type with subgroup analyses and meta-regression., Results: The authors included eight RCTs constituting 4114 patients. Patients who underwent PFO closure had a lower risk of CVE recurrence compared with medically treated patients [relative risk (RR): 0.56; 95% confidence interval (CI) 0.40-0.80; P = 0.001; I = 30%]. This protective effect was consistent across the different device types. Patients who underwent PFO closure developed more frequently atrial fibrillation/AFL (RR 4.96; 95% CI 2.74-8.99; P < 0.00001; I = 0%), which was mainly transient and within 1 month. Atrial fibrillation/AFL risk was consistent according to device types, although marginally significant in the Amplatzer subgroup., Conclusion: PFO closure might have a role in secondary CVE prevention of patients with PFO and cryptogenic stroke. However, it is associated with an increased incidence of new-onset atrial fibrillation/AFL especially within 1 month.

The patent foramen ovale (PFO), given its high prevalence in the general population and especially in patients with cryptogenic stroke, has long generated investigation and debate on its propensity for stroke by paradoxical embolism and its management for stroke prevention. The pendulum has swung for percutaneous PFO closure for secondary stroke prevention in cryptogenic stroke. Based on a review of current evidence, the benefit from PFO closure relies on careful patient selection: those under the age of 60 years with few to no vascular risk factors and embolic-appearing stroke deemed cryptogenic after thorough evaluation. As these data look towards influencing guideline statements and device approvals in the future, patient selection remains the crucial ingredient for clinical decision making and future trials., Competing Interests: Competing interests: KY reports no conflict of interest. SEK reports a research grant from WL Gore & Associates.

Background: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO-associated cryptogenic stroke., Methods and Results: We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I 2 =59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I 2 =42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I 2 =12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I 2 =77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I 2 =14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I 2 =12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference., Conclusions: PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Cryptogenic stroke is the final diagnosis in almost 40% of ischemic acute cerebrovascular events. There is currently no definitive clinical evidence that percutaneous closure of patent foramen ovale (PFO) can prevent the recurrence of stroke or transient ischemic attack (TIA). Identification of the causes of neurologic ischemic syndromes is essential for any strategy intended to prevent the catastrophic consequences of cerebral infarction. Since the initial reports of an unexpectedly high prevalence of PFO in younger patients with cryptogenic stroke in 1988, there has been growing interest and experience in diagnosing and treating these patients, both medically and/or with percutaneous closure, in particular for the potential to eliminate paradoxical embolism via PFO, which is a likely mechanism for stroke in these patients. Selection of the appropriate occluder device is of paramount importance for the success of the procedure. While devices like the Amplatzer™ PFO Occluder (St. Jude Medical), which, based on the extended follow-up of the RESPECT Trial, was approved by the U.S. Food and Drug Administration last year for recurrent stroke prevention, have become generally accepted as being better than medical therapy for patients needing treatment, concerns remain regarding device- and procedure-related complications. NobleStitch™ EL is a novel device that offers a simple non-prosthetic implant method of PFO closure without the inherent risks seen with septal occluders: no risk of device embolization, device thrombosis or late erosion, and probably no risk of arrhythmia. Futhermore, there is no material that would hinder future access to the left atrium and no requirement for anti-coagulation.

Patients with cryptogenic strokes are more likely to have a patent foremen ovale than in the general population. It is speculated that these strokes are due to paradoxical embolism, that is, passage of a venous thrombus across the patent foremen ovale to enter the arterial circulation, resulting in an embolic stroke. Venous thromboembolism is rarely present in these cases of cryptogenic stroke. Thousands of patients with cryptogenic strokes have undergone transcatheter closure of their patent foremen ovale via a variety of devices. The first 3 randomized clinical trials comparing patent foremen ovale closure with medical therapy failed to show a significant advantage of patent foremen ovale closure. Three additional trials reported in 2017 had longer years of follow-up and demonstrated an advantage of patent foremen ovale closure versus medical therapy. Analysis of their data indicated that patent foremen ovale closure in patients with an atrial septal aneurysm in addition to a patent foremen ovale had a very significant decrease in cryptogenic strokes (P < .001). There was no decrease in strokes in patients without an aneurysm of the atrial septum who underwent patent foremen ovale closure (P = .37). Aneurysms of the atrial septum are easily recognized by echocardiography and are present in approximately one-third of patients with patent foremen ovales. These data suggest that closure of patent foremen ovales in patients with an atrial septal aneurysm is indicated. In patients with a patent foremen ovale without an aneurysm of the atrial septum, patent foremen ovale closure is not indicated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A patent foramen ovale (PFO) is a common variant in cardiac anatomy found in 25% to 30% of U.S. adults. While PFOs are a normal part of fetal development and commonly seen in asymptomatic adults, they have been implicated in a variety of pathophysiologic conditions. The most clinically important of these is paradoxical embolization of venous thrombus resulting in stroke or systemic embolism. Various devices can be used to close PFOs via a transcatheter approach to prevent recurrent stroke. Data regarding the safety and effectiveness of these devices is rapidly evolving, with recent long-term results suggesting efficacy in preventing secondary stroke in carefully selected patients. This review discusses historical data on PFO occurrence and treatment, a risk score that can assess the likelihood of a stroke being attributable to a PFO, a variety of other conditions that may be linked to PFOs, and current research regarding the role transcatheter closure plays in their treatment., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Objectives: To describe medium- to long-term follow-up of patients undergoing device closure of patent foramen ovale (PFO) for stroke or transient ischemic attack (TIA)., Background: Transcatheter device closure of PFO continues to be used for secondary prevention of cryptogenic stroke or TIA, but data are lacking regarding long-term outcomes., Methods: We reviewed the Mayo Clinic Rochester PFO database for patients who underwent device closure of PFO for secondary prevention of stroke/TIA from December 2001 to June 2012. Demographic, clinical, procedural, and follow-up data were reviewed. Recurrence rate of stroke/TIA were calculated. Data were analyzed to identify risk factors of recurrent neurologic events., Results: Seven hundred and thirty patients (mean age 53 years; 40% female) were included in our study. Most patients (72%) had cryptogenic stroke as their qualifying event for PFO closure. There were no procedure-related deaths or strokes. The most commonly used device was the Amplatzer Septal Occluder (82%). Median follow-up was 6 years. A 3.9% of patients had documented residual right-to-left shunting at last echocardiogram. Recurrent stroke and/or TIA were reported in 45 patients, (6.3% of patients with follow-up data). Patients who experienced recurrent stroke/TIA were older and had a higher rate of diabetes and hypertension than those who did not. The presence of residual shunt did not correlate with risk of recurrent events., Conclusions: Device closure of PFO can be performed safely with very good long-term resolution of atrial shunting. Recurrent neurologic events after PFO closure may reflect additional comorbid risk factors unrelated to the potential for paradoxical embolism. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

More than 25% of all ischemic strokes per year are cryptogenic, that is, their cause is not determined after an appropriate evaluation. In 1988, it was reported that the incidence of a patent foramen ovale was 30 to 40% in young patients with a cryptogenic stroke compared with 25% in the general population. This led to the suspicion that cryptogenic strokes were due to paradoxical embolism, that is, a venous thrombus crossing a patent foramen ovale to enter the left atrium and then the arterial circulation. Few of the patients considered to have paradoxical embolism were shown to have coexistent venous thromboembolism. This suspicion of paradoxical embolism led to thousands of patients undergoing surgical closure of their patent foramen ovale. Surgical closure was replaced by closure of the patent foramen ovale by a variety of transvenous devices. Others recommended anticoagulant or antiplatelet therapy to prevent recurrent ischemic strokes. Three randomized clinical trials totaling more than 2000 patients compared closure of the patent foramen ovale with medical therapy. All 3 trials reported that closure of the patent foramen ovale provided no benefit compared with medical therapy. Subsequent trials have demonstrated no benefit of anticoagulation compared with antiplatelet therapy in patients with cryptogenic strokes with or without a patent foramen ovale. Patients with cryptogenic strokes should be evaluated for the presence of venous thromboembolism. If venous thromboembolism is present, treatment should be the same as for pulmonary embolism: anticoagulation. If venous thromboembolism is not present, antiplatelet therapy is indicated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study., Methods and Results: Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39-1.32; P=0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33-1.21; P=0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04-0.81; P=0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05-0.68; P=0.011)., Conclusions: PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation., (© 2016 American Heart Association, Inc.)

Patent foramen ovale (PFO) is a slit or tunnel-like communication in the atrial septum occurring in approximately 25% of the population. A wide number of pathological conditions have been linked to its presence, most notably, cryptogenic stroke (CS) and migraine. However, in the setting of a neurological event, it is not often clear whether the PFO is pathogenically related to the index event or an incidental finding. Therefore, a detailed analysis of several clues is needed for understanding PFO's clinical significance, with a frequent case-by-case decision about destination therapy. Indeed, the controversy about PFO's pathogenicity prompted a paradigm shift of research interest from medical therapy with antiplatelets or anticoagulants to percutaneous transcatheter closure, in secondary prevention. Observational data and meta-analysis of observational studies had previously suggested that PFO closure with a device was a safe procedure with a low recurrence rate of stroke. To date, however, recent randomized controlled trials have not shown the superiority of PFO closure over medical therapy. Thus, the optimal strategy for secondary prevention of paradoxical embolism in patients with a PFO remains unclear. Moreover, the latest guidelines for the prevention on stroke restricted indications for PFO closure to patients with deep vein thrombosis and high-risk of its recurrence. Given these recent data, in the present review, we critically discuss current treatment options, pointing out the role of a comprehensive patient evaluation in overcoming PFO closure restrictions and planning the best management for each patient., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Echocardiography is often performed to identify a cardiac source of embolism (CSE) causing transient ischemic attack (TIA). However, the diagnostic yield of echocardiography in TIA remains uncertain, and its role in routine evaluation of TIA is controversial., Methods: Patients with acute TIA were prospectively enrolled at 4 stroke centers. A CSE was defined using the Causative Classification of Stroke system; patent foramen ovale was considered a relevant CSE only if the patient underwent closure or was placed on anticoagulation. Patients with a known CSE at time of admission were excluded from analysis of the yield of echocardiography., Results: A total of 869 patients were enrolled at stroke centers, and 129 had a known CSE at presentation. Of the 740 remaining patients, 603 (81%) underwent echocardiography. A potential CSE was identified in 60 (10%) of these patients. The most common CSEs noted on echocardiography were complex aortic arch atherosclerosis and patent foramen ovale. History of coronary artery disease (P < .001), lack of prior stroke or TIA (P = .007), and presence of acute infarction on magnetic resonance imaging (MRI) (P < .001) were predictors of CSE on echocardiography. The yield of echocardiography was 29% in patients with both history of coronary artery disease and acute infarction on MRI, 14% with one of these features, and 5% with neither of these features (P < .0001). A CSE identified by echocardiography prompted initiation of anticoagulation in 15 of the 603 (2.5%) subjects., Conclusions: Echocardiography demonstrates a relevant CSE in a significant portion of patients with TIA. However, changes in antithrombotic therapy resulting from echocardiography are infrequent., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.

Aims: To compare clinical outcome of Amplatzer PFO (APFO) to Cardia PFO (CPFO) occluder. Percutaneous patent foramen ovale (PFO) closure prevents stroke recurrence in stroke due to paradoxical embolism., Methods and Results: The primary endpoint was a composite of stroke, TIA, or peripheral embolism at follow-up. The secondary endpoint was residual shunt. Outcome was compared among 934 (APFO: 712; CPFO: 222) patients, and in 297 propensity score-matched patients. The primary endpoint occurred in 29 patients (0.71/100 patient-years): four (2%) with the CPFO (0.31/100 patient-years), and 25 (4%) with the APFO (0.89/100 patient-years) (p=0.20). Residual shunt at six months was more frequent with the CPFO (31% versus 9%, p<0.001). No differences in residual shunts were seen at the last available echocardiographic follow-up (9±18 months): APFO 11%, CPFO 14%, p=0.22., Conclusions: This study suggests that PFO closure with APFO or CPFO is equally effective for the prevention of recurrent events. Residual shunt was more frequent at six months with CPFO, but was similar to APFO at later follow-up.

Aims: To evaluate the very long-term risk of recurrent thromboembolic events in patients treated by percutaneous PFO closure., Methods and Results: Between 1998 and 2008, a total of 232 consecutive patients with PFO and a high suspicion of paradoxical embolism were treated by percutaneous closure. The following major events were observed during hospitalisation: implantation failure (one patient) and appearance of an acute left-sided device thrombus requiring surgery (one patient). The primary endpoint of the study was a recurrent embolic event beyond at least five years' follow-up. During a mean follow-up of 7.6±2.4 years, this event occurred in five patients, representing a 0.28% annual/patient risk. Other major complications during follow-up were the following: late thrombus formation on the device (two patients) and transient atrial fibrillation (15 patients). Three patients died during follow-up from cardiovascular causes considered not related to the index procedure. The PFO was judged closed on follow-up echocardiography in 92.3% of patients., Conclusions: Long-term follow-up following percutaneous PFO closure for presumed paradoxical embolism reveals very low recurrence rates. This observation should be put in perspective with recent published randomised trials comparing percutaneous closure and medical therapy.

Introduction: The natural history and therapeutic interventions for secondary prevention after a cerebrovascular event in patients with patent foramen ovale (PFO) are not yet established. This study aims to assess the safety and efficacy of percutaneous PFO closure in a population of patients with ischemic cerebrovascular disease of unknown etiology., Methods: This prospective observational study included patients with a history of cryptogenic transient ischemic attack (TIA) or stroke who underwent percutaneous PFO closure. The effectiveness of the device for the secondary prevention of TIA or stroke was assessed by comparing observed events in the sample with expected events for this clinical setting., Results: The sample included 193 cases of percutaneous PFO closure (age 46.4 ± 13.1 years, 62.2% female) with a mean follow-up of 4.3 ± 2.2 years, corresponding to a total exposure to ischemic events of 542 patient-years. The high-risk characteristics of the PFO were assessed prior to device implantation. There were seven primary endpoint events during follow-up (1.3 per 100 patient-years), corresponding to a relative risk reduction of 68.2% in recurrent TIA or stroke compared to medical therapy alone. The procedure was associated with a low rate of device- or intervention-related complications (1.5%)., Conclusions: In this long-term registry, percutaneous PFO closure was shown to be a safe and effective therapy for the secondary prevention of cryptogenic stroke or TIA., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: Optimal management of patients with persistent foramen ovale (PFO) following cryptogenic stroke or transient ischemic attack (TIA) suspected for paradoxical embolic events is still unclear. PFO closure has the potential benefit of preventing recurrent embolic events and avoiding serious bleeding resulting from long-term anticoagulation. Despite the widespread usage of closure devices, no randomized trial supports the general percutaneous closure approach. In addition, only mid-term, but not long-term, outcomes have been reported until now. The aim of the study is to assess clinical characteristics and long-term clinical outcome of patients undergoing percutaneous PFO closure., Methods: Included in this single-center registry trial were 146 consecutive patients who underwent percutaneous closure of PFO at the University Hospital Frankfurt from 2000 to 2009. Periprocedural outcomes and long-term events were assessed. Follow-up was available in 146 patients (100%) with a mean follow-up of 7.8±3.1 years (cumulative 1148 patient-years)., Results: The cerebroischemic event leading to indicate percutaneous PFO closure was TIA (34.9%), stroke without sequels (38.4%), stroke with sequels (24.7%), amaurosis fugax (N=2; 1.4%), and peripheral emboli (N=1; 0.7%). Only one severe periprocedural complication occurred (device dislocation). The majority of patients (N=143; 97.9%) experienced no further events during follow-up., Conclusion: This "all-comers" population documents the safety of percutaneous PFO closure. The cardiovascular event rate is slightly lower (0.26 per 100 patient years) compared to the recently published randomized trials and maintained persistently low rate for more than 8 years., (Copyright © 2014. Published by Elsevier Ltd.)

Objectives: This study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial., Background: The CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO., Methods: The CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort., Results: In 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001)., Conclusions: These findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Trauma is known to be one of the strongest risk factors for pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin therapy for prevention of PE, but trauma places some patients at risk of excess bleeding. Experts are divided on the role of prophylactic inferior vena cava (IVC) filters to prevent PE., Objective: To perform a systematic review and meta-analysis examining the comparative effectiveness of prophylactic IVC filters in trauma patients, particularly in preventing PE, fatal PE, and mortality., Data Sources: We searched the following databases for primary studies: MEDLINE, EMBASE, Scopus, CINAHL, International Pharmaceutical Abstracts, clinicaltrial.gov, and the Cochrane Library (all through July 31, 2012). We developed a search strategy using medical subject headings terms and text words of key articles that we identified a priori. We reviewed the references of all included articles, relevant review articles, and related systematic reviews to identify articles the database searches might have missed., Study Selection: We reviewed titles followed by abstracts to identify randomized clinical trials or observational studies with comparison groups reporting on the effectiveness and/or safety of IVC filters for prevention of venous thromboembolism in trauma patients., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and abstracted data. For studies amenable to pooling with meta-analysis, we pooled using the random-effects model to analyze the relative risks. We graded the quantity, quality, and consistency of the evidence by adapting an evidence-grading scheme recommended by the Agency for Healthcare Research and Quality., Results: Eight controlled studies compared the effectiveness of no IVC filter vs IVC filter on PE, fatal PE, deep vein thrombosis, and/or mortality in trauma patients. Evidence showed a consistent reduction of PE (relative risk, 0.20 [95% CI, 0.06-0.70]; I(2)=0%) and fatal PE (0.09 [0.01-0.81]; I(2)=0%) with IVC filter placement, without any statistical heterogeneity. We found no significant difference in the incidence of deep vein thrombosis (relative risk, 1.76 [95% CI, 0.50-6.19]; P=.38; I(2)=56.8%) or mortality (0.70 [0.40-1.23]; I(2)=6.7%). The number needed to treat to prevent 1 additional PE with IVC filters is estimated to range from 109 (95% CI, 93-190) to 962 (819-2565), depending on the baseline PE risk., Conclusions and Relevance: The strength of evidence is low but supports the association of IVC filter placement with a lower incidence of PE and fatal PE in trauma patients. Which patients experience benefit enough to outweigh the harms associated with IVC filter placement remains unclear. Additional well-designed observational or prospective cohort studies may be informative.

Aims: Closure of patent foramen ovale following presumed paradoxical embolic stroke remains controversial. The answer to the question as to whether cardiovascular risk factors (CVRF) impact on the recurrence of stroke in patients who have undergone PFO closure remains elusive so far. We aimed to investigate the potential impact of CVRF on the long-term rate of stroke/TIA recurrence in patients treated with an occluder following presumed paradoxical embolic stroke., Methods and Results: 443 patients (mean age: 50.0±12.6 yrs, female: 206 [46.5%]) undergoing percutaneous PFO closure after presumed paradoxical embolic stroke were followed for a median time of 43.0 [interquartile range: 20.0-86.0] months. During the follow-up period a total of 22 (5.0%) strokes/TIAs and 17 (3.8%) deaths were observed. Cox regression analysis identified hypertension, age and the Essen stroke risk score as predictors of recurrent stroke/TIA., Conclusions: This study shows that, in patients with a prior presumed paradoxical embolic stroke, the risk for recurrent stroke/TIA after PFO closure is firmly linked to the presence of CVRF.

Objectives: This study sought to examine the frequency of indications for and the immediate and long-term clinical outcomes of transcatheter closure of patent foramen ovale (PFO)., Background: Transcatheter PFO closure is commonly performed for several indications, including cryptogenic stroke, despite conflicting data regarding the efficacy of this intervention., Methods: We report the outcomes of 800 consecutive patients (52% male, 50 ± 14 years of age) who underwent PFO closure at our institution after multidisciplinary evaluation over a 16-year period., Results: Indications for closure included cryptogenic cerebrovascular event (94%), hypoxemia (2%), peripheral embolism (3%), and migraine headaches (2%). Procedural success was 99% with effective closure obtained in 93% of patients. At a mean follow-up of 42.7 ± 33.4 months, 21 patients suffered a recurrent ischemic neurologic event (12 strokes, and 9 transient ischemic attacks) for an incidence rate of 0.79 events per 100 person-years and freedom from recurrent events of 91.6% at 10 years. There was no device-based difference in the rate of recurrent ischemic neurologic events (p = 0.82). Only Eustachian valve prominence (hazard ratio: 9.04; 95% confidence interval: 2.07 to 39.44; p = 0.0034) was associated with recurrent neurologic events., Conclusions: Transcatheter PFO closure is safe and feasible in patients with several clinical indications. The long-term efficacy of this intervention in patients with paradoxical embolism appears superb in this observational study. Carefully selected patients with features suggestive of paradoxical embolism are the most likely to benefit from PFO closure and should be the focus of future investigation., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the incidence of symptomatic recurrent embolic events after patent foramen ovale (PFO) closure and potential causes for these events., Background: It is well-known that cerebral or other embolic events may occur after PFO closure., Methods: This is a retrospective analysis of consecutive patients who underwent PFO closure for secondary prevention of embolic events at a single institution., Results: 1,930 patients (mean age of 50 ± 13.3 years) underwent transcatheter PFO closure. Complete closure occurred in 92%. The annual recurrence rate of embolic events before PFO closure was 22.4% (785 events in 3,497 patient-years). During follow-up (mean 39 months), 63 recurrent events were documented: 25 strokes, 36 transient ischemic attacks (TIAs), and 2 peripheral embolic events. The overall annual recurrence rate after the procedure was 1% per year (63 events in 6,211 patient-years). The majority of events occurred in patients without residual shunts (54/63). There was no significant association between the presence of a residual shunt and recurrent events [hazard ratio (HR) 1.7; 95% confidence interval (CI) 0.8-3.6, P = 0.16]. The most common cause for recurrent events was atherosclerosis. Nine out of 63 events were considered likely or possible paradoxical embolism due to residual shunt [stroke (2), TIA (5), and peripheral embolism (2)]. After PFO closure, the annual rate of events potentially related to paradoxical embolism was 0.14% (9 events in 6,211 patient-years)., Conclusion: The incidence of symptomatic embolic events after PFO closure is low. Most recurrent events are related to coexistent conditions associated with thromboembolic risk rather than residual shunts., (Copyright © 2012 Wiley Periodicals, Inc.)