PFO-associated Stroke Research Articles

Stroke recurrence after transcatheter PFO closure in patients with cryptogenic stroke.

Patent foramen ovale (PFO) closure is recommended for secondary prevention of cryptogenic stroke. However, data on long-term results are limited. We aimed to evaluate safety and efficacy of transcatheter PFO closure and predict neurologic recurrence. Data from patients undergoing PFO closure between 2010 and 2015 was collected to assess the combined endpoint of transient ischemic attack (TIA), stroke, or death from stroke at short- and long-term follow-up. 330 patients were included, mean age was 49 (±12) years and 55.5% were male. Before PFO closure, 86% experienced a stroke and 19% multiple neurological events. Procedure-related complications occurred in 2.4% of patients. Over a median follow-up of 10 years, the combined endpoint occurred in 3.6%, with a recurrence rate of 0.38 per 100 patient-years. Freedom from the combined endpoint at 5 and 10 years was 97.5% and 96.2%, respectively. New-onset atrial fibrillation was detected in 3%. The Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.68; p=0.032), the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system (adjHR: 0.37; p=0.042), and a history of prior neurological events (adjHR: 9.94; p<0.001) were independent predictors of future recurrent neurologic events. Age, sex, and cardiovascular risk factors did not influence outcomes. In this real-world cohort, transcatheter PFO closure was associated with low long-term recurrence of neurologic events, especially cryptogenic strokes. The RoPE score, the PASCAL score and history of previous neurological events were predictive of recurrent events. This study supports the safety and efficacy of PFO closure for secondary prevention of cryptogenic strokes, and underscores the importance of patient selection.

High Risk PFO-Associated Stroke: Proposed Algorithm for Better Risk Stratification.

High Risk PFO-Associated Stroke: Proposed Algorithm for Better Risk Stratification.

Symptomatic carotid webs and patent foramen ovale: RoPE score in competing stroke etiologies

BackgroundPatent foramen ovale (PFO)-associated stroke is diagnosed more frequently in young patients with infrequent vascular risk factors and embolic appearing infarcts. The risk of paradoxical embolism (RoPE) score is used to identify PFO-associated stroke. Patients with symptomatic carotid artery web (CaW) share a very similar risk profile and these lesions are frequently overlooked. In this study, we evaluate the RoPE score profile in patients with suspected symptomatic CaW. MethodsRetrospective analysis of prospectively collected data of patients with symptomatic CaW as the presumed cause of stroke presenting to 2 comprehensive stroke centers from 2014 to 2021. CaW was diagnosed using computed tomography angiography (CTA) of the neck & head. Shunt study was done using a transthoracic, transesophageal, and/or transcranial-Doppler with bubbles. RoPE score ≥7 was considered high. ResultsSeventy-five patients had stroke from a symptomatic ipsilateral CaW. Mean age was 49.7±11.2 years and 74.7 % were females. Median RoPE score was 7 [5–8], and 52.0 % had a high RoPE score. PFO was detected in 13.3 % of the patients and 20.5 % within the high RoPE score group. Ten percent of the cases would have been misclassified as PFO-associated strokes based on RoPE score. ConclusionHigh RoPE scores were observed in the majority of patients with CaW-attributed stroke, and it should not be used to differentiate CaW- versus PFO-associated stroke. Careful extracranial internal carotid artery evaluation for CaW is warranted in cryptogenic strokes, including in PFO positive patients before defining stroke etiology.

Morphological Features of Patent Foramen Ovale Compared Between Older and Young Patients With Cryptogenic Ischemic Stroke.

The morphology of a patent foramen ovale (PFO) with a high-risk for cryptogenic ischemic stroke (CS) is an important factor in the selection of patients for transcatheter closure, but the morphological features of PFO in older patients with a history of CS are less known because the most data are obtained from younger patients. The study included 169 patients who had a history of CS and PFO. The prevalence of high-risk morphologies of PFO assessed by transesophageal echocardiography was compared between patients aged ≥60 years and patients aged <60 years. We also assessed the presence of septal malalignment of PFO on the aortic wall. The probability of CS due to PFO was evaluated using the PFO-Associated Stroke Causal Likelihood classification system. Patients aged ≥60 years had a significantly higher prevalence of atrial septal aneurysm than patients aged <60 years. The prevalence of large right-to-left shunt, long-tunnel of PFO, or Eustachian valve or Chiari's network was similar between patients aged ≥60 years and <60 years. Septal malalignment was observed more frequently in patients aged ≥60 years than in those <60 years old. Nearly 90% of patients aged ≥60 years were classified as 'possible' in the PFO-Associated Stroke Causal Likelihood classification system. High-risk morphologies of PFO are common in older patients with a history of CS, as well as in younger patients.

Comparison of Simultaneously Performed Transcranial Doppler and Transthoracic Echocardiogram in Patients with Suspected Patent Foramen Ovale

Background: Patent foramen ovale (PFO) is a distinctive aetiology of cryptogenic stroke. The established benchmark for diagnosing PFO is the transoesophageal echocardiography with agitated saline or ‘bubble’ (TOE-b) study. Transcranial Doppler with bubble (TCD-b) or transthoracic echocardiography with bubble (TTE-b) examinations are common initial screening tests for PFO. However, the degree of concordance and discordance between the results of these two approaches remain unclear. Methods: In this prospective observational study, individuals presenting with suspected PFO-associated stroke between 2018 and 2021 underwent simultaneous TCD-b and TTE-b examinations within a joint neuro-cardiovascular laboratory to assess rates of concordance and discordance between TCD-b and TTE-b results. Additionally, data from any subsequent TOE-b studies were gathered. Results: Twenty-two patients were included. Ten patients (45%) exhibited concordantly negative findings and seven patients (32%) had concordantly positive results. Discordant outcomes were recorded in five patients (23%). Subsequently, a subset of seven patients (32%) underwent TOE-b, which confirmed the presence of right-to-left shunts. Among these cases, TCD-b consistently and accurately identified right-to-left shunts in all instances. In contrast, four out of these seven cases exhibited negative TTE-b results. Conclusion: This study indicates that there is significant discordance between TCD-b and TTE-b results (five of 22; 23%). Additionally, the results suggest that TCD-b might be a more effective screening test for detecting PFO compared with TTE-b.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Trigger factors in patients with a patent foramen ovale-associated stroke: A case-crossover study.

Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke. The ODYSSEY study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18-49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the RR of potential trigger factors for PFO-associated stroke. Overall, 1043 patients completed the questionnaire and had an ischemic stroke, of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke, the RR was 26.0 (95% CI 8.0-128.2) for fever, 24.2 (95% CI 8.5-68.7) for flu-like disease, and 3.31 (95% CI 2.2-5.1) for vigorous exercise. In conclusion, flu-like disease, fever, and vigorous exercise may convert an asymptomatic PFO into a stroke-causing PFO in young adults. The raw and anonymized data used in this study can be made available to other researchers on request. Written proposals can be addressed to the corresponding author and will be assessed by the ODYSSEY investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data are shared.

Abstract TP249: A Real World Study of PFO Closure in Young Patients With Ischemic Stroke

Introduction: Over the past decade, the concept of Patent Foreman Ovale (PFO)-related stroke has been evolving. Current guidelines recommend PFO closure in young patients who had a non-lacunar ischemic stroke of undetermined cause and related to a high-risk PFO. Whereas there remains a discrepancy in patient selection for PFO closure among providers and institutions in real-world practice. The retrospective study comprehensively examined patient characteristics, clinical assessments, and outcomes among young stroke patients who underwent PFO closure to gauge the current clinical process in selecting PFO candidates. Methods: Adult ischemic stroke patients (age &gt;18) who underwent PFO closure from 1/2018 to 12/2022 at the single center were identified from the cardiology PFO closure database. Patients were characterized into PFO-Associated Stroke Causal Likelihood (PASCAL)-probable; PASCAL-possible, and PASCAL-unlikely categories for comparison. Descriptive statistics was conducted due to the small sample size. Results: The mean age of qualified 78 patients was 47 years old when receiving PFO closure; the majority were males (64%) and Caucasians (75%). High risk PFO was identified in 55% of patients, and 63% of patients had high Risk of Paradoxical Embolism score ≥7. The patients were determined as PASCAL- probable (53%); PASCAL-possible (33%), and PASCAL-unlikely (15%), respectively. Among all the patients, the rate of successful device implantation was 96.0%, rate of closure related adverse events were 15.8% with post closure atrial fibrillation rate of 7.9%. Compared to PASCAL possible and unlikely patients, PASCAL-probable patients had the highest rate of successful device implantation and the lowest closure-related adverse events rate, including post-procedure atrial fibrillation. During a median follow-up of 3.4 years after PFO closure, three patients (one PASCAL-unlikely and two PASCAL-possible) had a recurrent stroke. Conclusions: The findings of real-world data confirmed that PASCAL-probable patient most likely benefit from PFO closure with the least procedure-related adverse events.

Patent Foramen Ovale Management for Secondary Stroke Prevention: State-of-the-Art Appraisal of Current Evidence.

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features. We also comment on breakthrough developments in patient selection algorithms for PFO closure in relation to the PFO-associated stroke causal likelihood risk stratification system. We further highlight areas for future research in PFO-associated stroke including the efficacy and safety of PFO closure in the elderly population, incidence, and long-term consequences of atrial fibrillation post-PFO closure, generalizability of the results of clinical trials in the real world, and the need for assessing the effect of neurocardiology teams on adherence to international recommendations. Other important knowledge gaps such as sex, race/ethnicity, and regional disparities in access to diagnostic technologies, PFO closure devices, and clinical outcomes in the real world are also discussed as priority research topics.

Heart Brain Clinic: An Integrated Approach to Stroke Care.

Multidisciplinary clinics have been shown to improve care. Patients with patent foramen ovale (PFO)-associated stroke need evaluation by cardiology and neurology specialists. We report our experience creating a multidisciplinary Structural Heart Brain Clinic (HBC) with a focus on patients with PFO-associated stroke. Demographic and clinical data were retrospectively collected for patients with PFO-associated ischemic stroke. Patients with PFO-associated stroke were divided into a standard care group and Heart Brain Clinic group for analysis. Outcome measures included time from stroke to PFO closure and number of clinic visits before decision regarding closure. Nonparametric analysis evaluated differences in median time to visit and clinical decision, while the chi square analysis compared differences in categorical variables between groups. From February 2017 to December 2021, 120 patients were evaluated for PFO-associated stroke. The Structural HBC began in 12/2018 with coordination between Departments of Neurology and Cardiology. For this analysis, 41 patients were considered in the standard care group and 79 patients in the HBC group. During data analysis, 107 patients had received recommendations about PFO closure. HBC patients required fewer clinic visits (p = 0.001) before decision about closure; however, among patients who underwent PFO closure, there was no significant difference in weeks from stroke to PFO closure. Clinicians were more likely to recommend against PFO closure among patients seen in HBC compared with those seen in standard care (p = 0.021). Our data demonstrate that a multidisciplinary, patient-centered approach to management of patients with PFO-associated ischemic stroke is feasible and may improve the quality of care in this younger patient population. The difference in recommendation to not pursue PFO closure between groups may reflect selection and referral bias. Additional work is needed to determine whether this approach improves other aspects of care and outcomes.

Cerebrovascular Events in Older Patients With Patent Foramen Ovale: Current Status and Future Perspectives.

Patent foramen ovale (PFO) closure, along with medical therapy, has emerged as the therapeutic gold standard in younger (<60-year-old) patients with a PFO-related stroke for preventing recurrent events. However, PFO management guidelines lack definite recommendations for older (>60 years) patients with a PFO-related cerebrovascular event, a complex group of patients who were mostly excluded from PFO closure clinical trials. Nevertheless, several studies have shown a higher prevalence of PFO among older patients with cryptogenic stroke, and its presence has been associated with an increased risk of recurrent events. Furthermore, older patients exhibit a higher prevalence of high-risk PFO anatomical features, present inherent age-related risk factors that might increase the risk of paradoxical embolism through a PFO, and have a higher incidence of ischemic events after a PFO-related event. Additionally, observational studies have shown the safety and preliminary efficacy of PFO closure in older PFO-related stroke patients. Yet, higher rates of recurrent cerebrovascular events and new-onset atrial fibrillation were observed in some studies among older patients compared to their younger counterparts. After careful case-by-case evaluation, including the assessment of hidden potential cardioembolic sources of a cryptogenic stroke other than PFO, transcatheter PFO closure might be a safe and effective therapeutic option for preventing recurrent thromboembolic events in patients >60 years with a high-risk PFO-associated stroke. Ongoing trials will provide important insights into the role of PFO closure in the elderly population.

Long-term risk of recurrent cerebrovascular events after patent foramen ovale closure: Results from a real-world stroke cohort.

Patent foramen ovale (PFO)-closure is recommended for stroke prevention in selected patients with suspected PFO-associated stroke. However, studies on cerebrovascular event recurrence after PFO-closure are limited by relatively short follow-up periods and information on the underlying aetiology of recurrent events is scarce. All consecutive patients with a cerebral ischaemic event and PFO-closure at the University Hospital Graz were prospectively identified from 2004 to 2021. Indication for PFO-closure was based on a neurological-cardiological PFO board decision. Patients underwent standardized clinical and echocardiographic follow-up 6 months after PFO-closure. Recurrent cerebrovascular events were assessed via electronical health records. PFO-closure was performed in 515 patients (median age: 49 years; Amplatzer PFO occluder: 42%). Over a median follow-up of 11 years (range: 2-18 years, 5141 total patient-years), recurrent ischaemic cerebrovascular events were observed in 34 patients (ischaemic stroke: n = 22, TIA: n = 12) and associated with age, hyperlipidaemia and smoking in multivariable analysis (p < 0.05 each). Large artery atherosclerosis and small vessel disease were the most frequent aetiologies of recurrent stroke/TIA (27% and 24% respectively), and only two events were related to atrial fibrillation (AF). Recurrent ischaemic cerebrovascular event rates and incident AF were comparable in patients treated with different PFO occluders (p > 0.1). In this long-term follow-up-study of patients with a cerebral ischaemic event who had received PFO-closure with different devices, rates of recurrent stroke/TIA were low and largely related to large artery atherosclerosis and small vessel disease. Thorough vascular risk factor control seems crucial for secondary stroke prevention in patients treated for PFO-related stroke.

Patent Foramen Ovale-associated Stroke and COVID-19 Vaccination.

Background: COVID-19 infection has been associated with paradoxical thromboembolism through a patent foramen ovale (PFO) and ischaemic stroke. Such events have not been reported after COVID-19 vaccination. The aim of the present study was to investigate PFO-associated stroke during the mass COVID-19 vaccination in Slovenia. Methods: This prospective study, conducted between 26 December 2020 and 31 March 2022, enrolled consecutive patients (≥18 years) with PFO-associated stroke referred for a percutaneous closure to a single interventional facility in Slovenia. Results: A total of 953,546 people aged between 18 and 70 years received at least one dose of a COVID-19 vaccine approved by the European Medicines Agency. Of the 28 patients presenting with PFO-associated stroke, 12 patients (42.9%) were vaccinated prior to the event, of whom nine were women and three were men, aged between 21 and 70 years. Stroke occurred within 35 days after vaccination in six patients (50%). Clinical presentation included motor dysphasia, paresis, vertigo, ataxia, paraesthesia, headache, diplopia and hemianopia. At hospital discharge, 11 patients (91.6%) had at least one residual ischaemic lesion. Conclusion: A temporal coincidence of COVID-19 vaccination and PFO-associated stroke has been described. A potential cause-effect relationship may only be hypothesised.

Re-conceptualization of the “Chinese Expert Guidelines for the Prevention of Stroke Associated with Patent Foramen Ovale” for the Management of Perioperative Stroke in Patients with Lung Cancer

The Chinese Heart Journal published the “Chinese Expert Guidelines for the Prevention of Stroke Associated with Patent Foramen Ovale” (hereafter referred to as “the Guidelines”) in 2021. The Guidelines were initiated by Professor Yushun Zhang of the No.1 Affiliated Hospital of Xi’an Jiaotong University, and 55 domestic experts participated in their discussion and formulation. The Guidelines focus on eight key issues in the prevention of stroke associated with patent foramen ovale (PFO), including definition and epidemiology, anatomical features, ultrasound diagnosis, clinical screening, and prevention and treatment of PFO-associated stroke. The prevention and treatment of PFO-associated stroke include pharmacological prevention, prevention of PFO with transcatheter occlusion and transcatheter occlusion of PFO. Patients with PFO are at elevated risk of perioperative stroke. In China, lung cancer ranks first in incidence among malignant tumors. The number of lung cancer surgeries is increasing each year, and the incidence of PFO in the population is approximately 25%. Although perioperative stroke in patients with lung cancer due to the presence of PFO has rarely been reported, given the high disability rate of stroke, incidence of PFO, and incidence of lung cancer, herein, we consider the Guidelines for the management of perioperative stroke in lung cancer. Our aim is to provide further perspectives in decreasing the risk of perioperative stroke in patients with lung cancer and PFO, to improve their quality of life and increase the safety of surgery.

Ischemic stroke associated with patent foramen ovale: hospital database analysis

To analyze clinical and instrumental characteristics of patients with ischemic stroke (IS) due to paradoxical embolism according to the data of hospital registers of Moscow and Perm. A comprehensive study of 114 patients, aged 18 to 55 years, with IS by the mechanism of paradoxical embolism was carried out. All patients underwent clarification of the cause of IS (electrocardiography, ultrasound scanning of the brachiocephalic arteries, CT or MRI of the brain, CT or MR angiography, transthoracic and/or transesophageal echocardiography). The presence of right-left shunt blood flow (RLS) was confirmed by transcranial dopplerography with a bubble test. The clinical significance of patent foramen ovale (PFO) was assessed according to The PFO-Associated Stroke Causal Likelihood Classification System (PASCAL). Clinical and instrumental characteristics of patients with IS due to paradoxical embolism were obtained from two hospital registries. In both groups, the leading trigger for the development of IS was the Valsalva phenomen (>20%), the share of other provoking factors did not exceed 10%. Significant differences between the analyzed groups related to the ultrasonic characteristics of RLS/PFO: patients with a grade 4 shunt predominated in the Research Center of Neurology (RCN) population, while patients with a grade 3 shunt predominated in the City Clinical Hospital (CCH) №4 group. At the same time, there were twice as many patients with aneurysm of the interatrial septum in the CCH №4 group. In accordance with the PASCAL classification, in 93% of RCN patients, PFO can be considered as a probable cause of IS, while in the CCH No. 4 group, a probable causal relationship was traced only in 51% of cases, in 18% of patients, the role of an anomaly in the development of stroke was unlikely. The analysis showed that the primary screening of RLS in a regional vascular center allows classifying PFO as a probable cause of IS in only half of the patients. For a more accurate selection of patients for whom endovascular occlusion of the PFO will be most effective, an in-depth examination in a specialized hospital is recommended.

Selección de pacientes para cierre percutáneo en el ictus isquémico no lacunar criptogénico asociado a foramen oval permeable. Datos del registro cooperativo NORDICTUS

IntroductionThere is an extending use of percutaneous closure of patent foramen ovale (PFO) as therapy for PFO-associated cryptogenic strokes. The aim of our study was to investigate the clinical practice of percutaneous closure of PFO and to analyse the variables for decision-making on the selection of patients for this procedure. MethodA prospective observational multicentric survey was conducted using all the cases of cryptogenic stroke/transient ischemic attack associated with PFO recorded in the NORDICTUS hospital registry during the period 2018-2021. Clinical data, radiological patterns, echocardiogram data and factors related to PFO-associated stroke (thromboembolic disease and paradoxical embolism criteria) were recorded. The indication for closure was analysed according to age (≤/> 60 years) and the characteristics of the PFO. ResultsIn the group ≤60 years (n=488), 143 patients (29.3%) underwent PFO closure. The most influential variables for this therapy were detection of a high-risk PFO (OR 4,11; IC 2,6-6,5, p<0,001), criteria for paradoxical embolism (OR 2,61; IC 1,28-5,28; p=0,008) and previous use of antithrombotics (OR 2,67; IC 1,38-5,18; p=0,009). In the group>60 years old (n=124), 24 patients had PFO closure (19%). The variables related to this option were history of pulmonary thromboembolism, predisposition to thromboembolic disease, paradoxical embolism criteria and high-risk PFO. ConclusionsThe detection of a high-risk PFO (large shunt, shunt with associated aneurysm) is the main criterion for a percutaneous closure-based therapy. Other conditions to consider in the eligibility of patients are the history of thromboembolic disease, paradoxical embolism criteria or the previous use of antithrombotics.

Selection of patients for percutaneous closure in nonlacunar cryptogenic stroke associated with patent foramen ovale. Data from the NORDICTUS cooperative registry

IntroductionThere is an extending use of percutaneous closure of patent foramen ovale (PFO) as therapy for PFO-associated cryptogenic strokes. The aim of our study was to investigate the clinical practice of percutaneous closure of PFO and to analyse the variables for decision-making on the selection of patients for this procedure. MethodA prospective observational multicentric survey was conducted using all the cases of cryptogenic stroke/transient ischaemic attack associated with PFO recorded in the NORDICTUS hospital registry during the period 2018-2021. Clinical data, radiological patterns, echocardiogram data and factors related to PFO-associated stroke (thromboembolic disease and paradoxical embolism criteria) were recorded. The indication for closure was analysed according to age (≤/> 60 years) and the characteristics of the PFO. ResultsIn the group ≤ 60 years (n = 488), 143 patients (29.3%) underwent PFO closure. The most influential variables for this therapy were detection of a high-risk PFO (OR 4.11; IC 2.6-6.5, P < .001), criteria for paradoxical embolism (OR 2.61; IC 1.28−5.28; P = .008) and previous use of antithrombotics (OR 2.67; IC 1.38−5.18; P = .009). In the > 60 years group (n = 124), 24 patients had PFO closure (19%). The variables related to this option were history of pulmonary thromboembolism, predisposition to thromboembolic disease, paradoxical embolism criteria, and high-risk PFO. ConclusionsThe detection of a high-risk PFO (large shunt, shunt with associated aneurysm) is the main criterion for a percutaneous closure-based therapy. Other conditions to consider in the eligibility of patients are the history of thromboembolic disease, paradoxical embolism criteria or the previous use of antithrombotics.

Transcatheter Patent Foramen Ovale Closure in Stroke Patients with Thrombophilia: Current Status and Future Perspectives.

Transcatheter patent foramen ovale (PFO) closure is a safe and effective treatment for secondary prevention after a PFO-associated stroke as demonstrated in multiple large randomized clinical trials. However, these trials excluded a significant proportion of patients who could have benefited from percutaneous PFO closure due to coexisting potential confounders such as additional thromboembolic risk factors, namely thrombophilia. Since scarce and conflicting data existed on such patients, current clinical management guidelines on patients with PFO mainly recommended against PFO closure in patients with thrombophilia and failed to provide any recommendation on the type and duration of antithrombotic treatment after transcatheter PFO closure. In the past 2 years, there has been new evidence supporting transcatheter PFO closure as a clinically meaningful alternative (vs. medical treatment) in this high-risk group of patients, along with additional data supporting the important role of systematic screening for thrombophilia in PFO-associated cerebrovascular events. This review article provides an updated overview of the incidence, clinical characteristics and outcomes of PFO closure in patients with thrombophilia, also commenting on the most appropriate medical treatment after PFO closure and future perspectives in the field.

Monitoring for atrial fibrillation prior to patent foramen ovale closure after cryptogenic stroke.

Patients who had a cryptogenic stroke (CS) suspected to be causally related to a patent foramen ovale (PFO) are candidates for percutaneous PFO closure. In such patients, it is important to screen for atrial fibrillation (AF). Limited guidance is available regarding AF monitoring strategies in CS patients with PFO addressing optimal monitoring technology and duration. To provide a narrative review of cardiac rhythm monitoring in CS patients considered for PFO closure, including current practices, stroke recurrences after CS, findings from monitoring studies in CS patients, and predictors for AF detection published in the literature. To propose a personalized strategy for cardiac monitoring in CS patients, accounting for aspects predicting AF detection. AF detection in CS patients is predicted by age, left atrial enlargement, prolonged PR interval, frequent premature atrial contractions, interatrial conduction block, diabetes, prior brain infarctions, leukoaraiosis, elevated B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and a family history of AF, as well as composed scores (e.g. CHA2DS2-VASc, atrial fibrillation in embolic stroke of undetermined source (AF-ESUS)). The causal role of the PFO may be accounted for by the risk of paradoxical embolism (RoPE) score and/or the PFO-Associated Stroke Causal Likelihood (PASCAL) classification. A personalized approach to AF detection in CS patients is proposed, accounting for the likelihood of AF detection and aimed at obtaining sufficient confidence regarding the absence of AF in patients considered for PFO closure. In addition, the impact of high-risk PFO features on the monitoring strategy is discussed.

Patent Foramen Ovale and Risk of Recurrence in Stroke of Determined Etiology

Patent foramen ovale (PFO) is often found in stroke patients with determined etiologies. PFO may be the actual cause of stroke in some of them. We determined whether the risk of recurrent ischemic stroke differs with PFO status in stroke patients with determined etiologies. This study included consecutive patients with stroke of determined etiology who underwent transesophageal echocardiography. We compared the rates of recurrent cerebral infarction in patients with versus without PFO, and according to PFO-Associated Stroke Causal Likelihood (PASCAL) classification. Of 2,314 included patients, 827 (35.7%) had PFO. During a median follow-up of 4.4 years, cerebral infarction recurred in 202 (8.7%). In multivariate modified Cox regression analyses, recurrence of infarction did not significantly differ between patients with PFO and those without PFO (hazard ratio [HR]= 0.86, 95% confidence interval [CI]= 0.64-1.17, p= 0.339). Interaction analysis showed a significant effect of PFO in patients aged <65 years (adjusted p for interaction=0.090). PFO was independently associated with a decreased risk of recurrent infarction in patients younger than 65 years (HR=0.41, 95% CI=0.20-0.85, adjusted p= 0.016). Patients with probable PFO-associated stroke on the PASCAL classification had a significantly lower risk of recurrent infarction than those without PFO (HR=0.31, 95% CI=0.10-0.97, p= 0.044). Considering the generally low risk of recurrence in PFO-associated stroke, PFO may be the actual cause of stroke in some patients with determined etiologies, especially younger patients or those with PFO features of probable PFO-associated stroke. ANN NEUROL 2022;92:596-606.