The paradox of platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra-cardiac or intra-pulmonary) combined with a functional component that promotes positional right-to-left shunting. We describe the rare occurrence of a patient with platypnoea-orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line-associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.

Amplatzer or Figulla Flex II Occluder: a comparative study of outcomes after transcatheter patent foramen ovale closure.

OBJECTIVES: Percutaneous closure of a patent foramen ovale (PFO) for the prevention of recurrent paradoxical thromboembolic events has been shown to be safe and effective in randomized controlled trials. However, it remains uncertain if differences in the structure and design of the occluder devices impact the outcomes. The aim of this study was to compare results of percutaneous PFO closure using 2 widely used double-disc occluders. METHODS: Consecutive patients who underwent percutaneous PFO closure with the Abbott Amplatzer occluder (APO) or the Occlutech Figulla-Flex-II occluder (OPO) at the Heart Center Lucerne between February 2017 and December 2022 were included in a registry. The primary endpoint was effective closure of the PFO, defined as a residual shunt grade 0 or 1, assessed by contrast echocardiogram at 6-month follow-up. Secondary endpoints included procedural efficacy/safety and major adverse cardiovascular events during the hospital stay and at 6-month follow-up. RESULTS: One hundred ninety-three consecutive patients (mean age 51.7 ± 12.5 years; 39% women; Risk of Paradoxical Embolism (RoPE) score = 7, IQR = 6-8) underwent percutaneous PFO closure with the APO (120 patients, 62.2%) or the OPO (73 patients, 37.8%). Main indications for closure were crypotogenic stroke in 168 patients (87.1%) and peripheral embolism in 13 patients (6.7%). At baseline, right-to-left shunt (RLS) greater than or equal to grade 2 was present in 189 patients (97.9%). Immediate procedural success was 99.5%. In 1 patient, an air embolism occurred during positioning of the APO occluder with transient chest pain and electrocardiogram changes, but without further sequelae to the patient. At 6-month follow-up, effective closure was achieved in 185 patients (95.8%; APO: 96.6% vs OPO: 94.5%, P = .30). Rates of atrial fibrillation and recurrent thromboembolic events were 4.2 and 0.5%, respectively. CONCLUSIONS: PFO closure is safe and effective when performed with either the self-expanding Abbott Amplatzer or Occlutech Figulla Flex II PFO occluder.

The association between patent foramen ovale and unexplained syncope in pediatric patients.

BACKGROUND: Patent foramen ovale (PFO) is associated with transient ischemia attack (TIA) or stroke, paradoxical embolism, and migraines. PFO closure decreases the recurrent incidence of cerebral ischemic events and reduces the incidence of syncope in adults. However, whether PFO is associated with syncope in pediatric patients has not been investigated. METHODS: 1001 pediatric patients (aged 4 to 17 years, mean age 10.31 ± 2.61 years, 519 males) who complained of unexplained syncope, palpitation, headache, dizziness and chest pain and were hospitalized in the Syncope Ward, The Second Xiangya Hospital, Central South University between January 2013 and April 2022 were recruited. Children with definite etiology of syncope, neurological, cardiogenic, psychological and other system diseases were excluded. PFO was measured by transthoracic echocardiography and right-heart contrast echocardiography was performed to identify the presence of right-to-left shunting. The demographic data and medical records were retrospectively reviewed and analyzed. RESULTS: 276 cases were included in the simple syncope group, 379 cases in the headache/dizziness group, 265 cases in the chest pain group, and 81 cases in the palpitation group. The incidence of PFO between the four groups was insignificant (4.71%, 4.74%, 4.15%, 6.17%, respectively, P = 0.903). Multivariate Logistic regression demonstrated that PFO is not associated with the increased risk of syncope (P = 0.081). CONCLUSION: PFO may not increase the risk of syncope in pediatric patients. Further study may include a large and multicenter sample to investigate the association between PFO and unexplained syncope.

Embolic stroke of undetermined source: Focusing on atrial cardiopathy and patent foramen ovale.

BACKGROUND: Atrial cardiopathy(AC) and patent foramen ovale (PFO) are two etiologies of embolic strokes of undetermined source (ESUS). We aimed to explore the relationship between them in ESUS. METHODS: A total of 1146 participants were included from January 2019 to June 2022, which included the ESUS group and non-embolic stroke which includes LAA(large arterial atherosclerosis) + SAO(small artery occlusion) group. AC was defined as the presence of at least one of the following: PTFV1(P-wave terminal force in lead V1) > 4000 µV*ms in the electrocardiograms, NT-proBNP(N-terminal probrain natriuretic peptide) > 250 pg/mL in laboratory tests or LAD(left atrial diameter) > 3.8 cm for women and > 4.0 cm for men in cardiac ultrasound. The presence of PFO was assessed by transthoracic echocardiography, transcranial Doppler ultrasound, transesophageal echocardiography or cardiac MRI. PFO was considered pathogenic if the RoPE score was 7 to 10. RESULTS: The prevalence of AC and PFO was higher in the ESUS group than the LAA + SAO group. The prevalence of AC was lower in ESUS patients with pathogenic PFO (37.9%) than those without PFO (68.4%) and with incidental PFO (64.0%) (p = 0.006). The prevalence of pathogenic PFO was lower in ESUS patients with AC than those without AC (6.0% vs. 17.8%, p = 0.006). The AUC(area under the curve) of PTFV1 for predicting ESUS was 0.724 [95%CI (0.686-0.762), p < 0.05)], indicating that PTFV1 the most valuable AC biomarker. CONCLUSIONS: The prevalence of AC is inversely related to the prevalence of pathogenic PFO in ESUS patients. PTFV1 was the most valuable index to predict ESUS among the AC biomarkers.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

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.

Transient Ischemic Attack in a 22-Year-Old NCAA Division I Baseball Athlete: A Case Study.

CONTEXT: A healthy, 22-year-old, male NCAA Division I baseball shortstop was experiencing confusion, chest pain, and tightness during an off-season intersquad scrimmage. The patient did not have any significant medical history or mechanism of head injury. After initial evaluation from the athletic trainer, the patient's cognitive status began to quickly decline. The emergency action plan was put in place rapidly and referred the patient to the local emergency clinic. CASE PRESENTATION: Upon arrival at the emergency department, an electrocardiogram was performed to rule out myocardial infarction or stroke. The first electrocardiogram results returned negative for any cardiac pathology, but a stroke alert was called. The patient was then transported to a level II trauma center due to continual cognitive decline. The patient was diagnosed with transient ischemic attack (TIA) secondary to an undiagnosed patent foramen ovale (PFO) that would later be diagnosed with further evaluation 2 months after the initial TIA incident. After multiple diagnostic and laboratory tests, the PFO went undetected until a 2D echocardiogram was performed and evaluated by a cardiologist. MANAGEMENT AND OUTCOMES: After the confirmation of the congenital defect, surgical intervention was performed to correct the PFO using catheterization. Despite multiple preparticipation examinations, electrocardiograms, and examination of past family history, the PFO went undetected until the patient experienced symptoms of TIA. The discovery of PFO in this 22-year-old athletic individual is unusual because traditional screening techniques (electrocardiogram and preparticipation examinations) failed to detect the congenital defect. CONCLUSIONS: Due to the emergent and timely actions of the athletic trainer, the patient has made a full recovery and is able to compete fully in athletic events. This case study amplifies the need for athletic trainers at all sporting events, updated and reviewed emergency action plans, rapid recognition of TIA in athletic individuals, and return-to-play protocol for an athletic individual after TIA.

Factors associated with patent foramen ovale-related stroke: SAFAS study.

BACKGROUND: Persistent foramen ovale (PFO) contributes to cryptogenic stroke and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke. METHODS: This study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation. PFO was systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression. RESULTS: Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m2 [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke. CONCLUSION: Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes.

Platypnea-Orthodeoxia Syndrome Caused by Patent Foramen Ovale with Right-To-Left Shunt.

BACKGROUND Patent Foramen Ovale (PFO) is an important part of fetal circulation. It allows the oxygenated blood from the umbilical cord to bypass the lungs. PFOs usually close after birth due to the sudden change of the hemodynamics associated with the expansion of the lungs however they are known to persist in about 25% of the total population. One of their rare manifestations is Platypnea-Orthodeoxia Syndrome (POS) that presents as dyspnea upon assuming an upright position, which improves upon recumbency, accompanied by hypoxemia. CASE REPORT We report a case of a 63-year-old man, known to have systemic lupus erythematosus (SLE) and positive anti-phospholipid antibodies but with no prior thrombotic events, admitted with symptoms of SARS-COV2 infection, and developed symptoms of Platypnea-Orthodeoxia Syndrome during his hospitalization, further evaluation by a transthoracic echocardiography revealed he had PFO with a right-to-left shunt which was treated successfully with percutaneous device closure. CONCLUSIONS Platypnea-Orthodeoxia Syndrome (POS) can be associated with various cardiac defects resulting in right-to-left shunts and other non-cardiac pathologies such as pulmonary AV malformations, lung parenchymal diseases and hepatopulmonary syndrome. In cases of cardiac right-to-left shunts Contrast-enhanced Transthoracic Echocardiography (TTE) can effectively diagnose Platypnea-Orthodeoxia Syndrome, and percutaneous closure has shown to be an efficacious treatment option in alleviating the symptoms. This case report highlights the necessity of actively exploring the possibility of PFOs with right-to-left shunts in patients exhibiting POS symptoms, while considering other potential aetiologies.

An unusual approach for platypnea-orthodeoxia syndrome due to isolated pulmonary arteriovenous malformations.

A 27-year-old man presented to the emergency department with complaints of syncope, dyspnea, and fatigue. Physical examination revealed left-sided mild hemiparesis, platypnea, and continuous murmur on right middle lobe lung auscultation.

Patent Foramen Ovale-Related Hypoxemia After Bilateral Lung Transplant.

A 64-year-old man with interstitial pulmonary fibrosis and a small patent foramen ovale with right-to-left shunting underwent bilateral lung transplant without closure of the patent foramen ovale. Postoperatively, the patient remained persistently hypoxemic with partial response to high-flow oxygen. Investigations revealed the presence of a large patent foramen ovale with right-to-left shunting on echocardiography and a shunt fraction of 21% on cardiac catheterization. Two months after the lung transplantation, primary surgical repair of the patent foramen ovale was performed with immediate improvement in oxygenation. Three years postoperatively, the patient remained oxygen independent.

The predictive value of abnormal electrocardiogram for patent foramen ovale: A retrospective study.

BACKGROUND AND HYPOTHESIS: The objective of this study was to identify the characteristics of electrocardiogram (ECG) in adult patients with patent foramen ovale (PFO) and to analyze the predictive value of the characteristics of ECG for PFO in adult patients. METHODS: Retrospectively, 267 patients who had undergone ECG, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) with agitated saline contrast echocardiography in our hospital, were recruited continuously from January 2021 to March 2023. Electrocardiographs were analyzed to investigate the presence of right bundle branch block (RBBB) and crochetage R wave. RESULTS: The ratio of crochetage R wave in inferior leads in patients with PFO was 45.3% and 21.2% without PFO. There were 17 (6.4%) patients with coexistence of crochetage R wave and RBBB, including 13 (6.5%) patients with PFO and four (6.1%) patients without PFO. The accuracies of TTE, crochetage R wave, and RBBB were 0.637, 0.535, and 0.314, respectively. A combination of crochetage R wave and RBBB demonstrated a sensitivity of 0.507 and a specificity of 0.758. When TTE, crochetage R wave, and RBBB were combined, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 0.712, 0.801, 0.439, 0.813, and 0.420, respectively. Logistic regression analysis revealed a correlation between PFO and the presence of crochetage R wave (odds ratio [OR]: 3.073, 95% confidence interval [CI]: 1.601-5.899, p < 0.001), and also a combination between crochetage R wave and RBBB (OR: 3.220, 95% CI: 1.720-6.028, p < 0.001). CONCLUSIONS: Crochetage R wave in ECG was associated with PFO. Crochetage R wave, especially combined with RBBB and TTE, may be helpful in the early detection of patients with PFO.

Orthodeoxia Platypnea Syndrome in the Setting of Cholangiocarcinoma: A Case Report.

Platypnea-orthodeoxia syndrome is a rare cause of positional hypoxemia and dyspnea. We present the case of a 54-year-old man with right-to-left shunting through a patent foramen ovale in the setting of metastatic cholangiocarcinoma resulting in platypnea-orthodeoxia syndrome. The shunt was originally not visualized on cardiac magnetic resonance imaging but later detected with transesophageal echocardiography. This case highlights the importance of complimentary multimodality cardiac imaging in the diagnosis of both common and uncommon disorders.

[Thromboembolic diseases from a cardiological point of view]. / Thromboembolische Erkrankungen aus kardiologischer Sicht.

Thromboembolic disease is associated with a high mortality. It can be divided into two groups: embolism from a venous and embolism from an arterial side. This article gives an overview on thromboembolic disease (with a focus on pulmonary embolism and ischemic stroke) from a cardiologist's perspective.The therapeutic options for acute pulmonary embolism range from anticoagulation to fibrinolysis to interventional recanalization and surgery. The deciding factor for choice of therapy is the risk of early death. Besides clinical parameters, laboratory markers like cardiac troponin and right ventricular function on echocardiography or CTPA (computed tomography pulmonary angiography) are used to determine the early mortality risk. In hemodynamically instable patients, immediate thrombolysis is required, whereas patients with intermediate and low risk can be treated with anticoagulation. Interventional recanalization is currently being studied in patients at risk for development of CTEPH (chronic thromboembolic pulmonary hypertension) or an intermediate risk of early mortality.In ischemic stroke, early interdisciplinary workup involving a cardiologist is paramount. Post stroke screening should include monitoring for arrythmias (especially atrial fibrillation) and transthoracic echocardiography as well as sonography of extra- and intracranial arteries. If no embolic source can be detected (embolic stroke of undetermined source), transesophageal echo can be helpful to detect intracardiac shunts like patent foramen ovale (PFO) or intracardiac tumors. Post stroke care includes secondary prevention measures like risk factor modification and lipid lowering therapy as well as anticoagulation. In high risk for paradoxical embolization, interventional PFO closure can be performed. Interventional closure of the left atrial appendage (LAA) can be discussed in patients with both high thromboembolic and bleeding risk.

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).

Management of patent foramen ovale in embolic stroke of undetermined source patients: Malaysian experts' consensus.

INTRODUCTION: About 20 to 40% of ischaemic stroke causes are cryptogenic. Embolic stroke of undetermined source (ESUS) is a subtype of cryptogenic stroke which is diagnosed based on specific criteria. Even though patent foramen ovale (PFO) is linked with the risk of stroke, it is found in about 25% of the general population, so it might be an innocent bystander. The best way to treat ESUS patients with PFO is still up for discussion. MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities. RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.

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.