The characteristics and prevalence of patent foramen ovale in Japanese people: a study using material from forensic autopsies.

Racial and ethnic differences in the prevalence of patent foramen ovale have been suggested, but there are insufficient data to confirm the situation. Studies have also not investigated detailed morphological changes in the fossa ovalis by age. This study therefore aimed to clarify the characteristics of the fossa ovalis and determine the frequency of patent foramen ovale in Japanese people, using materials from forensic autopsies. A total of 359 hearts were obtained during forensic autopsies (from 223 males and 136 females, aged from 0 to 94 years). Overall, prevalence of patent foramen ovale was 12.5%, but it was significantly higher among those under 20 years old (66.7% in males, 38.5% in females). The area of the fossa ovalis linearly increased with age in both sexes. The prevalence of patent foramen ovale was lower in Japanese adults than previously found in either White or Black people. The ratio of the area of the fossa ovalis to the heart weight was nearly constant.

Atrial Fibrillation After Patent Foramen Ovale Closure: Incidence, Pathophysiology, and Management.

This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at <5%, varies based on monitoring methods. The review delves into the challenging task of precisely estimating AF incidence, given subclinical AF and diverse diagnostic approaches. Notably, a temporal pattern emerges, with peak incidence around the 14th day after closure and a subsequent decline after the 45th day, mimicking general population AF trends. The pathophysiological mechanisms behind post PFO closure AF remain elusive, with proposed factors including local irritation, device-related interference, tissue stretch, and nickel hypersensitivity. Management considerations encompass rhythm control, with flecainide showing promise, and anticoagulation tailored to individual risk profiles. The authors advocate for a personalized approach, weighing factors like age, comorbidities, and device characteristics. Notably, postclosure AF is generally considered benign, often resolving spontaneously within 45 days, minimizing thromboembolic risks. Further studies are required to refine understanding and provide evidence-based guidelines.

Comparison of atrial septal defect and patent foramen ovale in cryptogenic strokes.

OBJECTIVES: Paradoxical embolism from right-to-left shunt through atrial septal defect (ASD) and patent foramen ovale (PFO) is a well-accepted cause of "cryptogenic" strokes (CS). To better understand the pathogenic role of ASD, we compared ASD patients with CS having a high and low likelihood of being PFO-related. METHODS: In the Acute Stroke Registry and Analysis of Lausanne, we calculated prevalence of PFO and ASD in CS patients undergoing echocardiography, and calculated odds ratios (OR) when compared to non-CS. Using the Risk of Paradoxical Embolism (RoPE) score, we divided CS PFO patients in high (HL-PFO, RoPE 8-10) and low-likelihood (LL-PFO, RoPE 0-4) PFO-related stroke. We then performed univariate comparison of epidemiological, clinical and radiological variables of ASD patients with both PFO groups. RESULTS: Among all CS, prevalence of ASD and PFO were 1.3% and 36.8% respectively. When compared to non-CS, ASD and PFO were associated with CS (OR of 5.2, CI= 1.6-16.6, and 2.8, CI= 2.1-3.8). Compared with HL-PFO, ASD patients were older, more often female, had more cardiovascular risk factors and silent strokes. Compared with LL-PFO, ASD patients were younger, more often female, and had less risk factors. No differences were found for clinical and radiological characteristics and clinical outcome. CONCLUSION: ASD is a rare stroke risk factor for CS. Since characteristics of such patients lie in-between high and low-likelihood paradoxical PFO-strokes, a thorough work-up for other stroke mechanisms is warranted. Individual evaluation of the likelihood of the ASD being causative for stroke may be preferable over routine ASD closure.

Does Atrial Septal Anatomy Still Matter in the Etiological Evaluation of Ischemic Stroke Beyond the Age of 60?

BACKGROUND: Patent foramen ovale (PFO) is causally associated with stroke in some patients younger than 60 years, especially when it is large or associated with an atrial septal aneurysm (ASA). After 60 years of age, this association is less well understood. We assessed the relationships between detailed atrial septal anatomy and the cryptogenic nature of stroke in this population. METHODS AND RESULTS: We reviewed all patients aged 60 to 80 years admitted to our stroke center for ischemic stroke who underwent contrast echocardiography between 2016 and 2021. The atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection (ASCOD) classification was used to reevaluate the etiological workup. Associations between cryptogenic stroke and (1) PFO presence or (2) categories of PFO anatomy (nonlarge PFO without ASA, nonlarge PFO with ASA, large PFO without ASA, and large PFO with ASA) were assessed using logistic regression. Among 533 patients (median National Institutes of Health Stroke Scale score=1), PFO was present in 152 (prevalence, 28.5% [95% CI, 24.9-32.5]). Compared with noncryptogenic stroke, cryptogenic stroke (n=218) was associated with PFO presence (44.5% versus 17.5%; P<0.0001). Among patients with a PFO, septal anatomy categories were associated with cryptogenic stroke (P=0.02), with a strong association for patients with both large PFO and ASA (38.1% versus 14.5%, P=0.002). CONCLUSIONS: PFO presence remains strongly associated with cryptogenic stroke between 60 and 80 years of age. Large PFO, ASA, and their association were strongly associated with cryptogenic stroke in this age group. Our results support performing contrast echocardiography even after 60 years of age, although the optimal secondary prevention therapy in this population remains to be determined in randomized trials.

Predictors of recurrent cerebral ischemia after patent foramen ovale closure: A single center observational study.

OBJECTIVES: Transcatheter patent foramen ovale closure lowers recurrent stroke in patients with cryptogenic stroke or transient ischemic attack with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathophysiology remains largely unknown. We sought to evaluate the prevalence of recurrent ischemic neurological events and to assess its predictors after transcatheter patent foramen ovale closure. METHODS: We enrolled consecutive patients who underwent patent foramen ovale closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. Clinical and procedure-related features were collected for each patient. The incidence of recurrent ischemic neurological events was assessed at follow-up. RESULTS: We enrolled a total of 169 patients with mean Risk of Paradoxical Embolism score at hospital admission of 6.4 ± 1.5. The primary indication was previous cryptogenic stroke (94 [55.6 %] subjects), followed by transient ischemic attack (75 [44.4 %]). Among patients with complete outcome data (n= 154), after a median follow-up of 112 months, recurrent cerebral ischemia occurred in 13 [8.4 %], with an annualized rate of 0.92/100 patients. The presence of obesity [OR 5.268, p = 0.018], Risk of Paradoxical Embolism score < 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/ transient ischemic attack after patent foramen ovale closure. CONCLUSIONS: The presence of obesity, Risk of Paradoxical Embolism score < 7 and migraine were independent positive predictors of recurrent ischemic neurological events after patent foramen ovale closure.

Retinal arterial occlusion and patent foramen ovale: A case study-based review.

PURPOSE: To identify all reported cases of retinal artery occlusion (RAO) associated with patent foramen ovale (PFO) in the literature and present a similar case of CRAO from our clinic. METHODS: PubMed database was searched for studies reporting RAO in individuals with PFO. Relevant data were tabulated and reviewed. We estimated each case's Risk of Paradoxical Embolism (RoPE) score. RESULTS: 23 cases of CRAO (n=10; including ours), BRAO (n=10), and CILRAO (n=3) were reviewed. Most cases were under 50 years of age (78.3%). The reported predisposing factors were: hypertension (26.1%), migraine (17.3%), smoking (13.0%), recent immobilization (13.0%), strenuous exertion (8.7%), pregnancy (8.7%), and diabetes (4.3%). A high RoPE score (≥7; suggestive of paradoxical embolism via PFO) was estimated for 71.4% of patients. In most cases, the neurological and cardiovascular examinations, laboratory studies, and imaging were unremarkable, except for the PFO±atrial septal aneurysm (present in 21.7%). In only 28.6% of cases, transthoracic echocardiography (TTE) (± saline contrast) could visualize the PFO; transesophageal echocardiography (TEE) was necessary to detect the PFO in 71.4%. Approximately one-half of the patients underwent percutaneous closure of the PFO; no complications or subsequent acute ischemic events ensued. The visual prognosis was poorer for CRAO than for BRAO or CILRAO. CONCLUSION: Timely diagnosis, acute management, and ensuring urgent initiation of stroke workup in cases with RAO or transient monocular vision loss are crucial. Clues to a possible paradoxical embolism as the cause include the absence of known cardiovascular risk factors, young age, migraine, recent immobility, vigorous exercise, and pregnancy.

Prevalence of atrial septal defects and patent foramen ovale in a cohort of sudden cardiac death patients undergoing autopsy.

BACKGROUND: Patent foramen ovale (PFO) and atrial septal defects (ASD) have been described in up to 30 % of subjects in autopsy series but contemporary data are scarce. It is important to confirm the prevalence of ASD/PFO in the general population given the potential associated stroke risk and the increasing availability of intervention via PFO closure. METHODS: A state-wide prospective out-of-hospital cardiac arrest registry (OHCA) identified all patients aged 1 to 50 years who experienced OHCA in Victoria, Australia from April 2019 to April 2022 and subsequently underwent autopsy with a cardiac cause of death identified. Autopsy was performed including visual description of any ASD and identification of probe patency of foramen ovale. RESULTS: A total of 517 patients underwent autopsy in the setting of sudden cardiac death; 36 patients (6.9 %) had a probe-patent foramen ovale, 2 patients (0.4 %) had secundum ASD, and 2 patients (0.4 %) had both a PFO and ASD (1 of whom had undergone percutaneous repair of both lesions). Twelve patients (2.3 %) had a prior history of cerebrovascular accident either recorded on medical history or detected on neuropathological examination; however none of these patients had a PFO or ASD. CONCLUSIONS: The combined rate of PFO and ASD in a cohort of 517 patients undergoing autopsy was 7.9 %. None of these patients had experienced a cerebrovascular accident. This rate of PFOs appears lower than earlier reports and raises the possibility that the relative risk of an associated stroke could be higher than previously estimated.

Chronic ischemic lesions and presence of patent foramen ovale in young adults with embolic stroke of undetermined source: Results of the young ESUS patient registry.

BACKGROUND: Chronic ischemic lesions (CILs) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS: This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from October 2017 to October 2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either magnetic resonance imaging (MRI) or computed tomography (CT)). RESULTS: Overall, 535 patients were enrolled (mean age = 40.4 (standard deviation (SD) = 7.3) years, 238 (44%) female). CILs were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (interquartile range (IQR) = 1-2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (relative risk (RR) = 0.17 (0.05-0.61)). In Y-ESUS with PFO, CILs were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% p< 0.001). CONCLUSION: One in seven Y-ESUS patients has additional CIL. CILs were associated with several vascular risk factors, lower probability of a pathogenic PFO, and lower stroke recurrence.

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.

Cardiovascular Outcomes and Readmissions of Atrial Fibrillation Among Patent Foramen Ovale Occluder Device Recipients: A Propensity Matched National Readmission Study.

Patent foramen ovale (PFO) occluder devices are increasingly utilized in minimally invasive procedures used to treat cryptogenic stroke. Data on the impact of Atrial Fibrillation (AF) among PFO occluder device recipients are limited. The Nationwide Readmissions Database was queried between 2016 and 2019 to identify PFO patients with and without AF. The 2 groups were compared using propensity score matching (PSM) and multivariate regression models. The outcomes included in-hospital mortality, acute kidney injury (AKI), Mechanical circulatory support use (MCS), Cardiogenic shock (CS), acute ischemic stroke, bleeding, and other cardiovascular outcomes. Statistical analysis was performed using STATA v. 17. Out of 6508 Weighted hospitalizations for PFO occluder device procedure over the study period, 877 (13.4%) had AF compared to 5631 (86.6%) who did not. On adjusted analysis, PFO with AF group had higher rates of MCS (PSM, 4.5% vs 2.2 %, P value = 0.011) and SCA (PSM, 7.6% vs 4.6 %, P value = 0.015) compared to PFO with no AF. There was no statistically significant difference in the rate of in-hospital mortality (PSM, 5.4% vs 6.4 %, P value = 0.39), CS (PSM, 8.3% vs 5.9 %, P value = 0.075), AKI (PSM, 32.4% vs 32.3 %, P value = 0.96), bleeding (PSM, 2.08% vs 1.3%, P value = 0.235) or the readmission rates among both cohorts. Additionally, AF was associated with higher hospital length of stay (9.5 ± 13.2 vs 8.2 ± 24.3 days, P-value = 0.012) and total cost ($66,513 ± $80,922 vs $52,013±$125,136, 0.025, P-value = 0.025) compared to PFO without AF. AF among PFO occluder device recipients is associated with increased adverse outcomes, including MCS use and SCA, with no difference in mortality and readmission rates among both cohorts. Long-term follow-up needs further studies.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke.

INTRODUCTION: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. METHODS: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. RESULTS: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). CONCLUSIONS: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

Incidence of atrial fibrillation in cryptogenic stroke with patent foramen ovale closure: protocol for the prospective, observational PFO-AF study.

INTRODUCTION: After closure of patent foramen ovale (PFO) due to stroke, atrial fibrillation (AF) occurs in up to one in five patients. However, data are sparse regarding the possible pre-existence of AF in these patients prior to PFO closure, and about recurrence of AF in the long term after the procedure. No prospective study to date has investigated these topics in patients with implanted cardiac monitor (ICM). The PFO-AF study (registered with ClinicalTrials.gov under the number NCT04926142) will investigate the incidence of AF occurring within 2 months after percutaneous closure of PFO in patients with prior stroke. AF will be identified using systematic ICM. Secondary objectives are to assess incidence and burden of AF in the 2 months prior to, and up to 2 years after PFO closure. METHODS AND ANALYSIS: Prospective, multicentre, observational study including 250 patients with an indication for PFO closure after stroke, as decided by interdisciplinary meetings with cardiologists and neurologists. Patients will undergo implantation of a Reveal Linq device (Medtronic). Percutaneous PFO closure will be performed 2 months after device implantation. Follow-up will include consultation, ECG and reading of ICM data at 2, 12 and 24 months after PFO closure. The primary endpoint is occurrence of AF at 2 months, defined as an episode of AF or atrial tachycardia/flutter lasting at least 30 s, and recorded by the ICM and/or any AF or atrial tachycardia/flutter documented on ECG during the first 2 months of follow-up. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee 'Comité de Protection des Personnes (CPP) Sud-Méditerranéen III' on 2 June 2021 and registered with ClinicalTrials.gov (NCT04926142). Findings will be presented in national and international congresses and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04926142.

Sex Differences in Patients With Cryptogenic Cerebrovascular Events Undergoing Transcatheter Closure of Patent Foramen Ovale.

Background Scarce data exist on sex differences in patients with cryptogenic cerebrovascular events undergoing patent foramen ovale (PFO) closure. This study aimed to determine the sex differences in clinical profile, procedural characteristics, and long-term outcomes of patients with cryptogenic cerebrovascular events undergoing PFO closure. Methods and Results A retrospective cohort was used, including 1076 consecutive patients undergoing PFO closure because of a cryptogenic cerebrovascular event. Patients were divided into 2 groups: 469 (43.6%) women and 607 (56.4%) men. The median follow-up was 3 years (interquartile range, 2-8 years). Women were younger (46±13 versus 50±12 years; P<0.01) and had a higher risk of paradoxical embolism score (6.9±1.7 versus 6.6±1.6; P<0.01). Procedural characteristics and postprocedural antithrombotic therapy were similar. At follow-up, there were no differences in atrial fibrillation (women versus men: 0.47 versus 0.97 per 100 patient-years; incidence rate ratio [IRR], 0.55 [95% CI, 0.27-1.11]; P=0.095; adjusted P=0.901), stroke (0.17 versus 0.07 per 100 patient-years; IRR, 2.58 [95% CI, 0.47-14.1]; P=0.274; adjusted P=0.201), or transient ischemic attack (0.43 versus 0.18 per 100 patient-years; IRR, 2.58 [95% CI, 0.88-7.54]; P=0.084; adjusted P=0.121); nevertheless, women exhibited a higher incidence of combined ischemic cerebrovascular events (0.61 versus 0.26 per 100 patient-years; IRR, 2.58 [95% CI, 1.04-6.39]; P=0.041; adjusted P=0.028) and bleeding events (1.04 versus 0.45 per 100 patient-years; IRR, 2.82 [95% CI, 1.41-5.65]; P=0.003; adjusted P=0.004). Conclusions Compared with men, women with cryptogenic cerebrovascular events undergoing PFO closure were younger and had a higher risk of paradoxical embolism score. After a median follow-up of 3 years, there were no differences in stroke events, but women exhibited a higher rate of combined (stroke and transient ischemic attack) cerebrovascular events and bleeding complications. Additional studies are warranted to clarify sex-related outcomes after PFO closure further.

Decompression Illness in Divers With or Without Patent Foramen Ovale : A Cohort Study.

BACKGROUND: In previous studies, the prevalence of patent foramen ovale (PFO) has been reported to be higher in scuba divers who experienced decompression illness (DCI) than in those who did not. OBJECTIVE: To assess the association between PFO and DCI in scuba divers. DESIGN: Prospective cohort study. SETTING: Tertiary cardiac center in South Korea. PARTICIPANTS: One hundred experienced divers from 13 diving organizations who did more than 50 dives per year. MEASUREMENTS: Participants had transesophageal echocardiography with a saline bubble test to determine the presence of a PFO and were subsequently divided into high- and low-risk groups. They were followed using a self-reported questionnaire while blinded to their PFO status. All of the reported symptoms were adjudicated in a blinded manner. The primary end point of this study was PFO-related DCI. Logistic regression analysis was done to determine the odds ratio of PFO-related DCI. RESULTS: Patent foramen ovale was seen in 68 divers (37 at high risk and 31 at low risk). Patent foramen ovale-related DCI occurred in 12 divers in the PFO group (non-PFO vs. high-risk PFO vs. low-risk PFO: 0 vs. 8.4 vs. 2.0 incidences per 10 000 person-dives; P = 0.001) during a mean follow-up of 28.7 months. Multivariable analysis showed that high-risk PFO was independently associated with an increased risk for PFO-related DCI (odds ratio, 9.34 [95% CI, 1.95 to 44.88]). LIMITATION: The sample size was insufficient to assess the association between low-risk PFO and DCI. CONCLUSION: High-risk PFO was associated with an increased risk for DCI in scuba divers. This finding indicates that divers with high-risk PFO are more susceptible to DCI than what has been previously reported and should consider either refraining from diving or adhering to a conservative diving protocol. PRIMARY FUNDING SOURCE: Sejong Medical Research Institute.

Association of patent foramen ovale with epilepsy: A hospital-based case-control study.

OBJECTIVE: This study aimed to investigate the proportion of patent foramen ovale (PFO) in people with epilepsy (PWE) compared to controls without epilepsy and to assess whether PWEs with and without PFO exhibit distinctive clinical features. METHODS: This is a case-control study conducted in a hospital. Contrast transthoracic echocardiography with a venous microbubble bolus and provocative maneuvers (Valsalva and coughing) were used to identify PFO and its right-to-left shunt (RLS) among 741 PWEs and 800 controls without epilepsy. The risk of having PFO in PWEs was explored using multiple matching methods and logistic regression with adjusted congenital factors that may affect the occurrence of PFO. RESULTS: The proportion of PFO in PWEs and controls was 39.00% and 24.25%, respectively. After 1:1 propensity score matching, the risk of suffering PFO in PWEs was 1.71 times (OR, 1.71; 95% CI, 1.24-2.36) higher than that in controls. PWEs also had a higher risk of having a high RLS grade (ßepilepsy = 0.390, P < 0.001). Among clinical characteristics of PWEs, migraine, and drug-resistant epilepsy showed significantly different distributions between those without RLS and those with RLS grade I to III. PWEs with PFO had higher risk of suffering from migraine and drug-resistant epilepsy (OR in migraine, 2.54, 95% CI, 1.65-3.95; OR in drug-resistant epilepsy, 1.47, 95% CI, 1.06-2.03). SIGNIFICANCE: The proportion of PFO was found to be higher in PWE than in controls without epilepsy, especially in patients with drug-resistant epilepsy, suggesting potential relationship between the two disorders. Large multicentric study will be needed to confirm this finding.

New-onset atrial fibrillation after percutaneous patent foramen ovale closure: a meta-analysis.

BACKGROUND: The exact incidence and predictors of new-onset atrial fibrillation (AF) after percutaneous closure of patent foramen ovale (PFO) are unknown. OBJECTIVE: We sought to find post-procedural AF incidence rates and differences due to different screening strategies and devices. METHODS: A systematic search was conducted in Cochrane, MEDLINE and EMBASE. Controlled trials fulfilling the inclusion criteria were included into this meta-analysis. The incidence of new-onset AF was the primary outcome. Further parameters were surveillance strategy, device type, AF treatment and neurological events. New AF was determined as early onset within one month after implantation and late thereafter. RESULTS: 8 controlled trials and 16 cohort studies were eligible for quantitative analysis. 7643 patients received percutaneous PFO closure after cryptogenic stroke or transient ischaemic attack, 117 with other indications, whereas 1792 patients formed the control group. Meta-analysis of controlled trials showed an AF incidence of 5.1% in the interventional and 1.6% in the conservative arm, respectively (OR 3.17, 95% CI 1.46-6.86, P = 0.03, I2 = 55%). 4.7% received high-quality surveillance strategy with Holter-ECG or Loop recorder whereby AF incidence was overall higher compared to the low-quality group with 12-lead ECG only (3.3-15% vs. 0.2-4.3%). Heterogeneous results on time of AF onset were found, limited by different follow-up strategies. CardioSEAL and Starflex seemed to have higher AF incidences in early and late onset with 4.5% and 4.2%, respectively. CONCLUSION: Percutaneous PFO closure led to higher AF post-procedural incidence compared to the conservative strategy. Heterogeneity in surveillance and follow-up strategy limited the generalizability. TRIAL REGISTRATION: Registered on PROSPERO (CRD42022359945).

Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study.

AIMS: Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure. METHODS AND RESULTS: A Danish nationwide cohort study was conducted. During 2008-2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5-10] in the PFO closure cohort, 3.1% (95% CI: 2.0-4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8-1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3-4.0) within the first 3 months and 0.7 (95% CI: 0.3-1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21-125) within the first 3 months and 2.5 (95% CI: 1.2-5.0) thereafter. CONCLUSION: Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.

Comparison of Sex-Based In-Hospital Procedural Outcomes and Hospital Readmission Frequency After Patent Foramen Ovale Occluder Device Placement: A Propensity Matched National Cohort.

Patent foramen ovale (PFO) occluder device has been shown to reduce the chance of recurrent stroke. Per guidelines, stroke is higher in females but procedural efficacy and complications based on sex difference is understudied. The nationwide readmission database (NRD) was used to create sex cohorts using ICD-10 Procedural code for elective PFO occluder device placement performed during the years 2016-2019. The 2 groups were compared using propensity score matching (PSM) and multivariate regression models that matched for confounders to report multivariate odds ratio (mOR) for primary and secondary cardiovascular outcomes. Outcomes included in-hospital mortality, acute kidney injury (AKI), acute ischemic stroke, postprocedure bleeding, and cardiac tamponade. Statistical analysis was performed using STATA v. 17. A total of 5818 patients who underwent PFO occluder device placement were identified, of which 3144 (54.0%) were females, and 2673 (46.0%) were males. There was no difference in periprocedural in-hospital mortality, new onset acute ischemic stroke, postprocedural bleeding, or cardiac tamponade between both sexes undergoing occluder device placement. AKI incidence was higher in males compared to females after matching for CKD (mOR = 0.66; 95% CI [0.48-0.92]; P = 0.016) this can be procedural or can be secondary to volume status or nephrotoxins. Males also had a higher length of stay (LOS) at their index hospitalization (2 days vs 1 day) which led to slightly higher total hospitalization cost ($26,585 vs $24,265). Our data did not show a statistically significant difference in the readmission LOS trends between the 2 groups at 30, 90, and 180 days. This national retrospective cohort study of PFO occluder outcomes shows similar efficacy and complication rates between sexes, with the exception of AKI incidence which was higher in males. AKI occurrence was high in males that can be limited due to unavailability of data about hydration status and nephrotoxic medications.

[Ischemic stroke associated with patent foramen ovale: hospital database analysis]. / Ishemicheskii insul't, assotsiirovannyi s otkrytym oval'nym oknom: analiz dannykh gospital'nykh registrov.

OBJECTIVE: 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. MATERIAL AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.