Patent foramen ovale (PFO) closure reduced the risk for recurrent ischemic stroke in most young and middle-aged adults with cryptogenic stroke but increased the risk for atrial fibrillation (AF) in a substantial minority.<\/p>\n
Results of a new meta-analysis indicated that a standardized classification system may help clinicians better differentiate patients who stand to benefit from PFO closure from those at an increased risk for harm.\u00a0<\/p>\n
Using the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, investigators found that patients with strokes classified as probable or possibly related to PFO experienced fewer recurrent strokes than AF events after closure.\u00a0<\/p>\n
Meanwhile, patients classified as unlikely to have a PFO-related stroke saw no decrease in stroke risk, but rather, a significant increase in AF, including late-onset and clinically serious cases.<\/p>\n
\u201cThese findings reinforce that PFO closure should generally be avoided in patients in the unlikely category, among whom causes net harm. In contrast, PFO closure generally confers net benefit in both probable and possible patients,\u201d co-first author Jeffrey L. Saver, MD, Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, University of California, Los Angeles, told Medscape Medical News<\/em>.<\/p>\n The study was published online on January 26 in JAMA Neurology<\/em>.\u00a0<\/p>\n A PFO is a small opening between the heart\u2019s atria and is present in approximately 25% of the general population. In younger patients with cryptogenic stroke, transcatheter PFO closure can reduce the risk for recurrent stroke. However, the procedure carries a known risk for AF, which itself is associated with stroke.<\/p>\n Although randomized trials show an average 60% reduction in recurrent stroke with PFO closure, distinguishing causative from incidental PFOs in clinical practice has been challenging.<\/p>\n Other considerations include vascular risk factors and the presence of undiagnosed AF at the time of the initial stroke.<\/p>\n To address this challenge, the PASCAL system, which combines the Risk of Paradoxical Embolism (RoPE) score with high-risk echocardiographic features such as large shunt size and atrial septal aneurysm, was developed. Previous analyses have validated PASCAL as a predictor of closure efficacy, the investigators noted.\u00a0<\/p>\n For the current analysis, the researchers aimed to assess the benefits and harms of PFO closure across PASCAL groups over a 5\u2011year period. They also sought to examine the timing and severity of AF events that occur beyond the early postprocedure period.<\/p>\n The investigators conducted a secondary analysis of individual participant data from the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium. The dataset included six phase 3 randomized trials comparing transcatheter PFO closure plus antithrombotic therapy vs antithrombotic therapy alone for secondary stroke prevention. The trials took place between 2000 and 2017 at hospitals in North America, Europe, Australia, Brazil, and South Korea.<\/p>\n The analysis included 3740 participants aged 18-60 years (mean age, 45 years) who had a documented PFO and a recent cryptogenic ischemic stroke. Of these participants, 1889 were randomly assigned to closure and 1851 to medical therapy alone; 55.0% were men and 45.0% were women.\u00a0<\/p>\n The primary efficacy endpoint was recurrent ischemic stroke. The primary safety endpoint was first\u2011ever AF detected beyond the periprocedural period (more than 45 days after randomization).<\/p>\n The investigators classified patients using the PASCAL system as probable (n = 1382), possible (n = 1811), or unlikely (n = 547) to have a PFO-related stroke. They used Kaplan-Meier and Cox proportional hazards models to estimate absolute and relative risks over a 5-year follow-up period.<\/p>\n Among the 121 recurrent ischemic stroke events, 32.2% occurred in the PFO closure group and 67.8% in the medical therapy group. In the probable group, closure lowered absolute 5\u2011year stroke risk by 2.5% with a 1.3% increase in postperiprocedural AF. The hazard ratio (HR) for recurrent stroke in this group was 0.10 (P<\/em> < .001).<\/p>\n Patients in the possible group saw a net benefit: closure reduced stroke risk by 3.4% with a 1.1% increase in late-onset AF (HR, 0.38; 95% CI, 0.22-0.65; P<\/em> < .001). In the unlikely group, closure did not reduce stroke risk (HR, 1.14; 95% CI, 0.53-2.46; P<\/em> = .74) but was associated with a substantial 4.6% absolute increase in late-onset AF (P<\/em> = .03).<\/p>\n Of the 112 AF events recorded, 83.9% occurred in the closure group and 16.1% in the medical group. In the probable and possible groups, AF strongly clustered within the first 90 days.\u00a0<\/p>\n In the unlikely group, AF had an even higher cluster from years 3-5 with 41.9% of events classified as severe compared with 12.9% and 22.0% in the probable and possible groups, respectively.<\/p>\n \u201cTwo aspects of the findings regarding postprocedural [AF] were surprising to us and important to management,\u201d Saver said. \u201cFirst, in unlikely patients, new onset of AF continues to occur 3-5 years after closure while in probable and possible patients, new onset of AF plateaus around at the end of year 1 post-closure. Second, new onset AF is not only more frequent in unlikely patients but also more severe.\u201d<\/p>\n There appears to be a trade-off between stroke prevention and procedural risk across the PASCAL categories.<\/p>\n Over 5 years, among 1000 PASCAL probable patients, PFO closure would prevent 27 recurrent strokes and cause13 cases of late-onset AF. In the possible group, closure would prevent 34 strokes and cause 11 AF events. Among patients in the unlikely group, closure would result in four additional strokes and 46 more AF events.\u00a0<\/p>\n \u201cAmong young and middle-aged patients with PFO and otherwise cryptogenic stroke, the PASCAL classification algorithm distinguished the four of every five patients in the probable and possible groups with net benefit and the one of every five patients in the unlikely group with net harm from closure,\u201d Saver said.<\/p>\n The findings show that PFO closure provides net benefit for patients classified as PASCAL possible, even though their relative risk reduction is more modest than in PASCAL probable patients. Importantly, their absolute benefit \u2014 most relevant for clinical decision-making \u2014 was comparable, said co-first author David M. Kent, MD, MS, told Medscape Medical News<\/em>. Kent is Director of the Tufts Predictive Analytics and Comparative Effectiveness Center and Professor of Medicine, Neurology, and Clinical and Translational Science at Tufts Medical Center\/Tufts University School of Medicine in Boston.<\/p>\n He emphasized that PASCAL possible patients appear to benefit from treatment similarly to this group \u2014 a \u201cmarked distinction to the PASCAL unlikely patient, who get no benefit and are subject to increase procedure-related harm.\u201d<\/p>\n The investigators found the study has several limitations, including incomplete data on recurrent AF after initial detection, limited functional outcome data for recurrent stroke, and limited generalizability to patients excluded from the trials. The analysis focused on AF and did not reanalyze other serious adverse events or cost implications.<\/p>\n Despite the limitations, Kent and his colleagues believe \u201cthese findings should be incorporated in clinical practice guidelines \u2014 as they have already been in Europe \u2014 to help better target closure worldwide. We also feel that there might be opportunities to apply our novel analytic approach to other interventions to develop evidence for more personalized decision making elsewhere.\u201d<\/p>\n The PASCAL system can help clinicians carefully weigh the benefits of stroke reduction against the risk for AF when considering PFO closure in patients classified as PASCAL possible or unlikely.<\/p>\n Commenting on the study, Matthew I. Tomey, MD, FAHA, chair of the American Heart Association\u2019s Cardiovascular Intervention Science Committee and Associate Professor of Medicine at the Mount Sinai Fuster Heart Hospital in New York City, acknowledged that the findings support the use of tools such as PASCAL to help guide patient selection.<\/p>\n \u201cIn the context of the six randomized trials analyzed in this study, both \u2018probable\u2019 and \u2018possible\u2019 relatedness of an unexplained stroke to a PFO corresponded with benefit for reduction of recurrent ischemic stroke,\u201d he said.<\/p>\n Tomey, who was not involved in the study, emphasized that closure should generally be avoided when a PFO is unlikely to be the cause of stroke.\u00a0<\/p>\n \u201cEqually compelling is the lack of efficacy seen in the \u2018unlikely\u2019 group,\u201d he said. \u201cBalanced against the concurrent significant device-related increase in AF, patients for whom attribution of stroke to a PFO is \u2018unlikely\u2019 should rarely, if ever, undergo PFO closure for purpose of secondary stroke prevention.\u201d<\/p>\n He added that the excess risk for AF seen after closure is likely real and clinically meaningful.\u00a0<\/p>\n \u201cThe clear signal toward more AF with closure versus medical therapy across multiple randomized trials supports a causal relationship,\u201d Tomey said.<\/p>\n While stroke is often more disabling than AF, the severity of these events can widely vary, and patients may value them differently. Overall, Tomey believes that \u201cdiscussion should be transparent and frank to facilitate shared decision-making.\u201d<\/p>\n Saver reported receiving advisor fees from Abbott during the conduct of the study; additional advisor fees from Aeromics, Amgen, Aronora, Bayer, Biogen, Boehringer Ingelheim, BrainQ, BrainsGate, Medtronic USA, Roche, Stream Medical, and Occlutech; and holding stock options in MindRhythm, Neuronics Medical, and Rapid Medical. Kent reported having no relevant financial relationships. Tomey reported having no relevant financial relationships.<\/em><\/p>\n<\/div>\n Patent foramen ovale (PFO) closure reduced the risk for recurrent ischemic stroke in most young and middle-aged adults with cryptogenic stroke but increased the risk for atrial fibrillation (AF) in a substantial minority. Results of a new meta-analysis indicated that a standardized classification system may help clinicians better differentiate patients who stand to benefit from […]<\/p>\n","protected":false},"author":1,"featured_media":16973,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_daextam_enable_autolinks":"","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[2],"tags":[],"class_list":["post-16972","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/diyhaven858.wasmer.app\/wp-content\/uploads\/2026\/02\/dt-260202-transcatheter-aortic-valve-implantation-800x450.jpg","jetpack_sharing_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/posts\/16972","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/comments?post=16972"}],"version-history":[{"count":0,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/posts\/16972\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/media\/16973"}],"wp:attachment":[{"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/media?parent=16972"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/categories?post=16972"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/diyhaven858.wasmer.app\/index.php\/wp-json\/wp\/v2\/tags?post=16972"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Understanding PFO and Stroke Risk<\/h2>\n
A Look at PFO Causal Likelihood<\/h2>\n
Stroke Reduction vs AF Risk<\/h2>\n
Balancing Potential Benefits and Harms<\/h2>\n
![\"photo](\"https:\/\/img.medscapestatic.com\/vim\/live\/professional_assets\/medscape\/images\/thumbnail_library\/ht-260202-david-m-kent-120x156.jpg\")
Clinically Meaningful Findings<\/h2>\n
![\"photo](\"https:\/\/img.medscapestatic.com\/vim\/live\/professional_assets\/medscape\/images\/thumbnail_library\/ht-260202-dr-matthew-tomey-120x156.jpg\")
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<<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"