{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:53:03Z","timestamp":1793109183262,"version":"4.5.0"},"reference-count":79,"publisher":"American Medical Association (AMA)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:sec id=\"ab-jrv250022-1\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>A patent foramen ovale (PFO), an opening between the right and left atria during normal fetal development that fails to close after birth, is present in approximately 25% of all adults. Paradoxical embolism, a venous thromboembolism that travels to the systemic circulation typically through a PFO, accounts for about 5% of all strokes and 10% of strokes in younger patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv250022-2\">\n                    <jats:title>Observations<\/jats:title>\n                    <jats:p>Approximately 50% of patients 60 years or younger with an embolic stroke of undetermined source (cryptogenic stroke) have a PFO, compared with 25% of the general population. The Risk of Paradoxical Embolism (RoPE) score incorporates clinical characteristics (age, history of stroke or transient ischemic attack, diabetes, hypertension, smoking, cortical infarct on imaging) to predict the likelihood that embolic stroke of undetermined source was caused by a PFO. Among patients in the lowest RoPE score category (score &amp;amp;lt;3), PFO prevalence was similar to that in the general population (23%), while PFO prevalence was 77% in patients with a RoPE score of 9 or 10. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system combines the RoPE score and anatomical criteria from echocardiography (large shunt, atrial septal aneurysm) to classify PFO as the \u201cprobable,\u201d \u201cpossible,\u201d or \u201cunlikely\u201d cause of otherwise cryptogenic stroke. PFO closure reduces recurrent ischemic stroke in patients 60 years or younger with cryptogenic stroke. In a pooled analysis of 6 trials (3740 patients), the annualized incidence of stroke over a median follow-up of 57 months was 0.47% (95% CI, 0.35%-0.65%) with PFO closure vs 1.09% (95% CI, 0.88%-1.36%) with medical therapy (adjusted hazard ratio, 0.41 [95% CI, 0.28-0.60]). However, the benefits and harms of closure were highly heterogeneous across the trial populations. In patients categorized as PASCAL \u201cprobable\u201d (ie, younger patients without vascular risk factors and high-risk PFO anatomical features), there was a 90% decreased relative rate of recurrent ischemic stroke after PFO closure at 2 years (hazard ratio, 0.10 [95% CI, 0.03-0.35]; absolute risk reduction, 2.1% [95% CI, 0.9%-3.4%]). PASCAL \u201cunlikely\u201d patients (eg, older patients with vascular risk factors and no high-risk PFO anatomical features) did not have a lower recurrent stroke rate with PFO closure but had higher risk of procedure- and device-related adverse events, such as atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv250022-3\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Patent foramen ovale is present in approximately 25% of all adults and is a common cause of stroke in young and middle-aged patients. The PASCAL classification system can help guide patient selection for PFO closure. Percutaneous PFO closure substantially reduces the risk of stroke recurrence in well-selected patients younger than 60 years after cryptogenic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2025.10946","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T15:00:25Z","timestamp":1753714825000},"page":"1463","source":"Crossref","is-referenced-by-count":53,"title":["Patent Foramen Ovale and Stroke"],"prefix":"10.1001","volume":"334","author":[{"given":"David M.","family":"Kent","sequence":"first","affiliation":[{"name":"Predictive Analytics and Comparative Effectiveness Center, Tufts Medical Center\/Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San 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