Project description: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.
Project description:Patent foramen ovale (PFO)-related stroke is increasingly recognized as an important etiology of ischemic embolic stroke-accounting for up to 50% of strokes previously considered 'cryptogenic' or with an unknown mechanism. As a 'back door to the brain,' PFO can allow venous clots to enter arterial circulation via interatrial right-to-left shunting, potentially resulting in ischemic stroke. We observe that clinically, PFO-related stroke affects women of childbearing age, and that pregnancy-owing to major changes in hemocoagulative, hormonal, and cardiovascular parameters-can enhance stroke risks. However, no systematic study has been performed and little is known regarding complications, pregnancy outcomes and treatment for PFO-related stroke during pregnancy. To identify and characterize the complications and clinical outcomes related to PFOs during pregnancy, we performed a literature review and analysis from all reported cases of pregnancy with PFO-related complications in the medical literature from 1970 to 2015. We find that during pregnancy and post-partum, PFO is associated with complications affecting multiple organs, including the brain, heart and lung. The three principal complications reported are stroke, pulmonary emboli and myocardial infarction. In contrast to other pregnancy-related stroke etiologies, which peak during later pregnancy and postpartum, PFO-related stroke peaks during early pregnancy (first and second trimester-60%), and most patients had good neurological outcome (77%). In patients with PFO with recurrent stroke during pregnancy, additional key factors include high-risk PFO morphology (atrial septal aneurysm), larger right-to-left shunt, multiple gestation and concurrent hypercoagulability. Compared to strokes of other etiologies during pregnancy, most PFO stroke patients experienced uneventful delivery (93%) of healthy babies with a good clinical outcome. We conclude with recommended clinical treatment strategies for pregnant patients with PFO suggested by the data from these cases, and the clinical experience of our Cardio-Neurology Clinic.
Project description:Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.
Project description:IntroductionPatent foramen ovale (PFO) closure prevents recurrent ischemic stroke in selected patients with a cryptogenic stroke. Trial results tend to be generalized to daily practice, often extending original trial inclusion criteria. This may result in unnecessary closure without benefit, but with risk of complications. We therefore introduced a standardized and structured evaluation by an interdisciplinary Heart-Stroke Team (HST). Our aim was to investigate the proportion of actual PFO closure of all referred patients with a cryptogenic stroke, after evaluation by the HST.Patients and methodsWe conducted a single-center, retrospective cohort study. Patients with an assumed cryptogenic ischemic stroke or transient ischemic attack (TIA) and a PFO who were referred for PFO closure were analyzed. As part of the HST approach, all patients underwent a standardized work-up, first to demonstrate the ischemic event on neuroimaging, second to evaluate all potential causes of stroke and finally, to assess the possible relation between the PFO and stroke. Outcome was the proportion of patients treated with PFO closure after referral.ResultsA total of 195 patients were included. In 124 patients (64%) PFO closure was advised. Fourty-two (22%) patients had a clear alternative cause of stroke and in 13 (7%) patients the initial stroke diagnosis could not be confirmed.ConclusionAfter careful analysis of patients referred for PFO closure a relationship between the PFO and stroke could not be demonstrated in 32% of referrals, and 3% preferred best medical treatment over percutaneous closure. This stresses the need for a complete neurovascular work-up and multidisciplinary assessment.
Project description:Patent foramen ovale (PFO) is a common congenital heart defect that can contribute to cryptogenic stroke, particularly in younger patients lacking traditional risk factors. The present study describes the case of a 14-year-old male patient who experienced an acute ischemic stroke without identifiable atheroembolic risk factors. Comprehensive diagnostic imaging revealed a marked right-to-left shunt through a PFO, identified as the probable cause of the stroke. The patient was treated with dual antiplatelet therapy and subsequently underwent successful percutaneous PFO closure. At 6 months following the procedure, the patient exhibited notable neurological recovery. The present case report highlights the critical need for evaluating PFO as a potential etiology of cryptogenic stroke in younger populations, emphasizing the advantages of a multidisciplinary approach and timely intervention in preventing recurrent events.
Project description:Background and purposePatent foramen ovale (PFO) is significantly associated with cryptogenic stroke (CS). However, even in patients with CS, a PFO can be an incidental finding. We sought to estimate the probability that a PFO in a patient with CS is incidental.MethodsA systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus control subjects with stroke of known cause. Using simple assumptions and Bayes' theorem, we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus control subjects in different age populations, with or without atrial septal aneurysms, and were used to summarize across studies the probability that a PFO in CS is incidental.ResultsThe summary OR (95% CIs) for PFO in CS versus control subjects was 2.9 (CI, 2.1 to 4.0). The corresponding ORs for young and old patients (< or >or=55 years) were 5.1 (3.3 to 7.8) and 2.0 (>1.0 to 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28% to 39%) in age-inclusive studies, 20% (16% to 25%) in younger patients, and 48% (34% to 66%) in older patients. These probabilities were much lower when an atrial septal aneurysm was present.ConclusionsIn patients with otherwise CS, approximately one third of discovered PFOs are likely to be incidental and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an atrial septal aneurysm, suggesting the importance of patient selection in therapeutic decision-making.
Project description:ObjectiveSystematic reviews suggest that patent foramen ovale closure (PFOc) is performed percutaneously with low complication rates. We did a network meta-analysis (NMA) comparing devices for PFO closures, evaluating safety and efficacy of transcatheter PFOc in preventing neurological events in patients with stroke when compared with medical therapy (MT), and assessing risk of atrial fibrillation (AF).MethodsWe searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) identifying six randomized controlled trials from 2012 until December 2019. We performed a Bayesian NMA; number-needed-to-treat and number-needed-to-harm were derived by applying the estimated odds ratios (ORs). The likelihood of being helped or harmed (LHH) was evaluated to estimate the risk-effectiveness balance.ResultsThe 3560 patients allocated to PFOc were less subject to a stroke than patients with MT. The overall ORs of PFOc versus MT were 0.41 with fixed-effects, and 0.22 with random-effects model. NMA proves that PFOc induces AF episodes significantly higher than MT, even when analysis is limited to only new episodes of "serious AF." LHH (0.68 fixed-effects, 0.79 random-effects) showed that strokes saved are less than cases of AFs added. By considering only serious AF, strokes saved are higher than serious AFs induced by the PFOc (LHH was 3.46 and 4.00 respectively).ConclusionsNMA supported PFOc in patients with cryptogenic stroke, confirming that devices are better than MT, but increase the risk of AF by over 2/4 times (serious or unserious AF). Considering serious AFs (real risky clinical condition), patients have more advantages in being treated, since LHH is ≥ 3-4.
Project description:Interventional patent foramen ovale (PFO) closure should be performed in patients aged 16 to 60 years (after extensive neurological and cardiological diagnostic work-up) with a history of cryptogenic ischaemic stroke and patent foramen ovale, with moderate or extensive right-to-left shunt. In patients with cryptogenic ischaemic stroke and patent foramen ovale, who reject a PFO closure, there is no evidence of superiority of oral anticoagulation over antiplatelet therapy. Therefore, secondary prevention should be performed with aspirin or clopidogrel. Atrial fibrillation, pericardial tamponade, and pulmonary embolism are reported complications during and after implantation of an occluder. However, these events are so rare that they should not influence the recommendation for implantation. This article is an abridged and translated version of the guideline published in Nervenarzt: Diener, HC., für die Deutsche Gesellschaft für Neurologie (DGN), Grau, A.J. et al. Nervenarzt (2018) 89: 1143. 10.1007/s00115-018-0609-y.
Project description:ObjectiveTo examine the relative impact of three management options in patients aged <60 years with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, antiplatelet therapy alone and anticoagulation alone.DesignSystematic review and network meta-analysis (NMA) supported by complementary external evidence.Data sourcesMedline, EMBASE and Cochrane CENTRAL.Study selectionRandomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke.Review methodsWe conducted an NMA complemented with external evidence and rated certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsTen RCTs in eight studies proved eligible (n=4416). Seven RCTs (n=3913) addressed PFO closure versus medical therapy. Of these, three (n=1257) addressed PFO closure versus antiplatelet therapy, three (n=2303) addressed PFO closure versus mixed antiplatelet and anticoagulation therapies and one (n=353) addressed PFO closure versus anticoagulation. The remaining three RCTs (n=503) addressed anticoagulant versus antiplatelet therapy. PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years (RD): -87, 95% credible interval (CrI) -100 to -33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD -20, 95% CrI -27 to -2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, 95% CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared with antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD -71, 95% CrI -100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, 95% CrI -5 to +65, moderate certainty).ConclusionsIn patients aged <60 years, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.Prospero registration numberCRD42017081567.
Project description:ObjectiveWe examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation.MethodsThe Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings.ResultsA total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use.ConclusionBoth antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.