[Management of patent foramen ovale in non-cardiac surgery]. / Gestione della pervietà del forame ovale nella chirurgia non cardiaca.

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.

Outcomes Following Patent Foramen Ovale Percutaneous Closure According to the Delay From Last Ischemic Event.

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.

Emergent pulmonary thromboembolectomy and atrial septal aneurysmectomy for intracardiac impending paradoxical embolism: An en bloc approach to prevent clot embolism and facilitate repair.

Although a patent foramen ovale (PFO) is relatively common, confirmed reports of thrombus entrapped within a PFO are uncommon. Management of impending paradoxical embolism (IPE), also called a thrombus in transit, lacks consensus but includes systemic anticoagulation (e.g., heparin), systemic thrombolysis, or surgical thrombectomy. We present a case of IPE diagnosed with intraoperative transesophageal echocardiography (TEE) as well as a novel en bloc approach to atrial septal aneurysmectomy to minimize embolism and facilitate repair of the interatrial septum. Timely use of intraoperative TEE may aid in diagnosis and help guide the surgical approach to minimize embolic risk with an IPE.

Stroke Prevention in Patients with Patent Foramen Ovale.

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.

Secondary stroke prevention in patients with patent foramen ovale.

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.

Interventional prevention of paradoxical embolism as the gold standard: End of discussion?

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.

Concomitant acute myocardial infarction and acute pulmonary embolism caused by paradoxical embolism: a case report.

BACKGROUND: Due to its low incidence and diverse manifestations, paradoxical embolism (PDE) is still under-reported and is not routinely considered in differential diagnoses. Concomitant acute myocardial infarction (AMI) and acute pulmonary embolism (PE) caused by PDE has rarely been reported. CASE PRESENTATION: A 45-year-old woman presented with acute chest pain and difficulty with breathing. Multiple imaging modules including ECG, echocardiography, emergency cardioangiogram (CAG), and CT angiography of the pulmonary arteries showed acute occlusion of the posterolateral artery and acute PE. After coronary aspiration, no residual stenosis was observed. One month later, a bubble study showed inter-atrial communication via a patent foramen ovale (PFO). The AMI in this patient was finally attributed to PDE via the PFO. PFO closure was performed, and long-term anticoagulation was prescribed to prevent recurrent thromboembolic events. CONCLUSIONS: PDE via PFO is a rare etiology of AMI, especially in patients with concomitant AMI and PE. Clinicians should be vigilant of this possibility and close the inter-atrial channel for secondary prevention.

Efficacy and safety of percutaneous patent foramen ovale closure in patients with a hypercoagulable disorder.

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.

Concomitant fat embolism syndrome and pulmonary embolism in a patient with patent foramen ovale.

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.

Historia natural del cierre percutáneo de foramen oval permeable / Natural history of patent foramen ovales closure

INTRODUCCIÓN: El cierre percutáneo del foramen oval permeable (FOP) se ha posicionado como el tratamiento de elección para la prevención secundaria de pacientes con infartos encefálicos (IE) criptogénicos asociados a FOP. OBJETIVO: Revisar los cierres de FOP realizados en nuestra institución, evaluando las características clínicas y del procedimiento, los resultados a mediano plazo luego del procedimiento y la tendencia en el número de intervenciones durante el período estudiado. MÉTODOS: Se incluyeron 101 pacientes consecutivos en que se realizó cierre de FOP, con una mediana de seguimiento de 4,6 años. Se analizaron las características basales de los pacientes, la indicación del cierre de FOP, el éxito del procedimiento y la presencia de shunt residual en ecocardiografía al año. Se realizó una encuesta telefónica estructurada a todos los pacientes, en la cual se preguntó por nuevo IE o crisis isquémica transitoria (CIT), otros eventos cardiovasculares y la presencia de sangrados. El seguimiento fue completado en el 95%. Se calculó el puntaje RoPE ("Risk of Paradoxical Embolism") el cual provee una estimación de la posibilidad de que ese IE se haya debido al FOP y del riesgo de repetir un nuevo IE en caso de no cerrar el FOP para cada paciente. RESULTADOS: La edad promedio fue de 49,1±13,7 años, con 53% mujeres. Sólo en 3 pacientes se diagnosticó una trombofilia. En 96 pacientes la indicación fue para prevención de embolía paradojal e IE (74% IE, 17% CIT y 4% embolía periférica), mientras que en 5% por síndrome de ortodeoxia/platipnea. El cierre de FOP fue exitoso en todos los pacientes. Shunt residual en ecocardiograma al año se observó en 5% - ninguno de estos pacientes presentó un nuevo evento encefálico durante el seguimiento. Se registraron 2 nuevos IE (4 IE por 1000 pacientes/año) y 1 nueva CIT (2 CIT por 1000 pacientes/año) en el seguimiento, con un promedio de presentación de 3,6 años post procedimiento. Esta tasa de eventos fue significativamente menor a lo predicho por el puntaje RoPE en nuestra cohorte. Se observó un marcado aumento en el número de procedimientos desde el año 2017 en adelante. CONCLUSIONES: En nuestra cohorte, el cierre de FOP fue un procedimiento exitoso y seguro. Se asoció a una baja tasa de nuevos eventos cerebrales, marcadamente menor a lo estimado por el puntaje de riesgo actualmente disponible (RoPE).

INTRODUCTION: The percutaneous closure of a patent foramen ovale (PFO) has been established as the preferred treatment for those with an ischemic stroke (IS) and associated PFO. AIMS: To review the PFO closure experience at our institution, characterizing the patients and procedures, mid-term results and the trend in the number of interventions during the study period. METHODS: One hundred and one consecutive patients undergoing PFO closure were included, with a median follow-up of 4.6 years. Baseline demographics, PFO closure indications, procedural success rates and residual shunt at 1-year were recorded. A telephonic survey was performed to complete follow-up, asking for new IS or transient ischemic attacks (TIA), other cardiovascular events and bleeding. Follow-up was completed by 95%. The RoPE score was calculated for each patient, providing an estimate of the chance a given IS being due to a PFO and the risk of a new event when the defect is not closed. RESULTS: Mean age was 49.1±13.7 years and 53% were females. Whereas the indication for PFO closure was paradoxical embolism in 96 patients (74% IS, 17% TIA and 4% peripheral embolism), in 5 it was for platypnea-orthodeoxia syndrome. All patients had a successful PFO closure procedure. Residual shunt at 1 year was found in 5% - yet, none of these patients experienced a new stroke during the study period. During follow-up there were 2 new IS (4 IS per 1,000 patients/year) and 1 new TIA (2 TIA per 1,000 patients/year), with a mean incidence time of 3.6 years after the procedure. This rate of new events was significantly lower than the one predicted by the RoPE score. From 2017 onwards, there was a marked increase in the number of procedures performed at our institution. CONCLUSION: In this cohort, PFO closure was a successful and safe procedure. It was associated to a low rate of new cerebral events during mid-term follow-up, markedly lower than the RoPE predicted rate.

The Closure of Patent Foramen Ovale in Preventing Subsequent Neurological Events: A Bayesian Network Meta-Analysis to Identify the Best Device.

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.

Modified percutaneous suture-mediated patent fossa ovalis closure for prevention of cerebral ischemic events.

Percutaneous suture-mediated transcatheter patent fossa ovalis (PFO) closure has been shown to be an effective and safe technique with self-evident advantages due to the lack of a permanent device heart implant. The success of this novel technique relies on an optimal catch of the interatrial septa, especially the septum primum which is floppier than the bulkier muscular septum secundum. We hypothesized that double suture of septum primum would further improve the efficacy of the procedure by increasing the surface contact between the septa when the septum primum is bent into the right atrium. We have provided proof of this concept by implementing a modified technique in two patients with PFO and cerebral ischemic events.

Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale.

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.

Transcatheter Closure of Patent Foramen Ovale: Randomized Trial Update.

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.

SCAI expert consensus statement on operator and institutional requirements for PFO closure for secondary prevention of paradoxical embolic stroke: The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.

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.

The Fragility Index in Randomized Controlled Trials for Patent Foramen Ovale Closure in Cryptogenic Stroke.

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.

Anticoagulation in patients with Embolic Stroke of Unknown Source.

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.

Patent foramen ovale and cryptogenic stroke: diagnosis and updates in secondary stroke prevention.

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.