Mechanical heart valves Bioprosthetic heart valves Chronic myocardial infarction together with low ejection fraction (<28%) Apical akinesia Dilated cardiomyopathy (prior established Wall motion abnormalities (hypokinesia, diagnosis or left ventricular dilatation with an ejection fraction of <40% or fractional shortening of <25%) akinesia, dyskinesia) other than apical akinesia Nonbacterial thrombotic endocarditis Hypertrophic cardiomyopathy Infective endocarditis Left ventricular hypertrophy Papillary fibroelastoma Left ventricular hypertrabeculation/non- compaction Left atrial myxoma Recent aortic valve replacement or coronary artery bypass graft surgery Presence of left ventricular assist device Paroxysmal supraventricular tachycardia Aortic sources of embolism: Complex atheroma in the ascending aorta or proximal arch (protruding with >4 mm thickness, or mobile debris, or plaque ulceration) https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 13/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate The high- and low-risk cardioaortic sources in this table are separated using an arbitrary 2% annual or one-time primary stroke risk threshold. Data from: 1. Ay H, Benner T, Arsava EM, et al. A computerized algorithm for etiologic classi cation of ischemic stroke: the Causative Classi cation of Stroke System. Stroke 2007; 38:2979. 2. Ay H, Furie KL, Singhal A, et al. An evidence-based causative classi cation system for acute ischemic stroke. Ann Neurol 2005; 58:688. 3. Arsava EM, Ballabio E, Benner T, et al. The Causative Classi cation of Stroke system: an international reliability and optimization study. Neurology 2010; 75:1277. 4. Kamel H, Elkind MS, Bhave PD, et al. Paroxysmal supraventricular tachycardia and the risk of ischemic stroke. Stroke 2013; 44:1550. 5. Kirklin JK, Pagani FD, Kormos RL, et al. Eighth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Transplant 2017; 36:1080. Reproduced and modi ed with permission from: Ay H, Furie KL, Singhal A, et al. An evidence-based causative classi cation system for acute ischemic stroke. Ann Neurol 2005; 58:688. Copyright 2005 American Neurological Association. Graphic 60843 Version 11.0 https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 14/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate Risk of Paradoxical Embolism (RoPE) score RoPE Characteristic Points score No history of hypertension 1 No history of diabetes 1 No history of stroke or TIA 1 Nonsmoker 1 Cortical infarct on imaging 1 Age, years 18 to 29 5 30 to 39 4 40 to 49 3 50 to 59 2 60 to 69 1 70 0 Total score (sum of individual points) Maximum score (a patient <30 years with no hypertension, no 10 diabetes, no history of stroke or TIA, nonsmoker, and cortical infarct) Minimum score (a patient 70 years with hypertension, diabetes, prior stroke, current smoker, and no cortical infarct) 0 TIA: transient ischemic attack. From: Kent DM, Ruthazer R, Weimar C, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology 2013; 81:619. DOI: 10.1212/WNL.0b013e3182a08d59. Reproduced with permission from Lippincott Williams & Wilkins. Copyright 2013 American Academy of Neurology. Unauthorized reproduction of this material is prohibited. Graphic 97895 Version 5.0 https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 15/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate PFO prevalence, attributable fraction, and estimated two-year risk of stroke/TIA CS patients with PFO (n = Cryptogenic stroke (n = 3023) 1324) Estimated two-year stroke/TIA Prevalence of PFO- RoPE patients with a PFO, attributable fraction, Number of CS patients with score Number of patients recurrence rate (Kaplan- percent (95% CI)* percent (95% CI)* PFO* Meier), percent (95% CI) 0 to 3 613 23 (19 to 26) 0 (0 to 4) 108 20 (12 to 28) 4 511 35 (31 to 39) 38 (25 to 48) 148 12 (6 to 18) 5 516 34 (30 to 38) 34 (21 to 45) 186 7 (3 to 11) 6 482 47 (42 to 51) 62 (54 to 68) 236 8 (4 to 12) 7 434 54 (49 to 59) 72 (66 to 76) 263 6 (2 to 10) 8 287 67 (62 to 73) 84 (79 to 87) 233 6 (2 to 10) 9 to 10 180 73 (66 to 79) 88 (83 to 91) 150 2 (0 to 4) CI: confidence interval; CS: cryptogenic stroke; PFO: patent foramen ovale; RoPE: Risk of Paradoxical Embolism; TIA: transient ischemic attack. NOTE: 95% CI for PFO prevalence and attributable fraction based on normal approximation to the binomial distribution. From: Kent DM, Ruthazer R, Weimar C, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology 2013; 81:619. DOI: 10.1212/WNL.0b013e3182a08d59. Reproduced with permission from Lippincott Williams & Wilkins. Copyright 2013 American Academy of Neurology. Unauthorized reproduction of this material is prohibited. Graphic 97896 Version 5.0 https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 16/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate Proposed flexible clinical practice approach to classifying patent foramen ovale causal association in patients with embolic infarct topography and without other major stroke sources* RoPE score Risk source Features Low High Very high A PFO and a straddling thrombus Definite Definite High (1) Concomitant pulmonary embolism Probable Highly probable or deep venous thrombosis preceding an index infarct combined with either (2a) a PFO and an atrial septal aneurysm or (2b) a large-shunt PFO Medium Either (1) a PFO and an atrial septal Possible Probable aneurysm or (2) a large-shunt PFO Low A small-shunt PFO without an atrial septal aneurysm Unlikely Possible RoPE: Risk of Paradoxical Embolism; PFO: patent foramen ovale. The algorithm in this table is proposed for use in flexible clinical practice when application of an entire formal classification system is not being conducted. The RoPE score includes points for 5 age categories, cortical infarct, absence of hypertension, diabetes, prior stroke or transient ischemic attack, and smoking. A higher RoPE score ( 7 points) increases probability of causal association. Reproduced with permission from: Elgendy AY, Saver JL, Amin Z, et al. Proposal for updated nomenclature and classi cation of potential causative mechanism in patent foramen ovale-associated Stroke. JAMA Neurol 2020; 77:878. Copyright 2020 American Medical Association. All rights reserved. Graphic 134674 Version 3.0 https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 17/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate Approach to management for a patient with PFO and embolic-appearing ischem without other identified cause This algorithm is intended to provide general guidance to PFO management in patients with a recent emboli ischemic stroke who have a PFO and no other identified cause of stroke. For most patients who are 60 year possible, probable, or definite likelihood by RoPE and PASCAL that the PFO was causally associated with the s percutaneous PFO device closure in addition to antiplatelet therapy. PFO device closure may be temporarily d patients with an indication for short-term anticoagulation. The benefit of PFO device closure is uncertain for of age and for patients with an indication for long-term anticoagulation; in such cases, an individualized app decision-making is appropriate. Patients with ischemic stroke should generally be treated with all available ri strategies including antithrombotic therapy, blood pressure control, low-density lipoprotein (LDL)-lowering th lifestyle modification, as appropriate. For details regarding the evaluation required for a comprehensive stroke evaluation, choice of antithromboti other factors that impact decision-making for PFO management, refer to appropriate UpToDate topics. PFO: patent foramen ovale; DVT: deep venous thrombosis; PE: pulmonary embolism; RoPE: Risk of Paradoxic PASCAL: PFO-associated stroke causal likelihood; ASA: atrial septal aneurysm. https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 18/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate For most patients with an indication for anticoagulation >1 year, PFO closure is not performed, as benefit in uncertain. PFO closure may be an option for selected patients, such as those who experience recurrent embo other identified cause while therapeutically anticoagulated and those who are no longer anticoagulated. An approach to decision-making is based upon patient preferences, risk factors, and comorbidities. Patients who undergo PFO closure (percutaneous or surgical) are treated with antiplatelet agents. We treat to 81 mg/day) plus clopidogrel (75 mg/day) for three months, followed by continued aspirin therapy. For the rare patient who has a concurrent indication for surgical valve intervention, surgical (rather than pe closure is appropriate. If percutaneous PFO closure is not feasible and there is no concurrent indication for c suggest against surgical PFO closure. For most patients >60 years old, PFO closure is not performed since such patients were excluded from tria and the benefit of closure in this setting is unproven. PFO closure may be an option for selected patients >60 as younger patients in this age range who have low estimated atherosclerotic cardiovascular disease risk. An approach to decision-making is based upon patient preferences, risk factors, and comorbidities. Refer to UpToDate topic on cryptogenic stroke. Graphic 138535 Version 1.0 https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 19/20 7/6/23, 12:11 PM Stroke associated with patent foramen ovale (PFO): Evaluation - UpToDate Contributor Disclosures Steven R Mess , MD Equity Ownership/Stock Options: Neuralert Technologies [Stroke monitoring]. Grant/Research/Clinical Trial Support: Biogen [Hemispheric ischemic stroke]; Mallinkrodt, Inc [Nitric oxide and cerebral perfusion]; Novartis [Intracerebral hemorrhage]; WL Gore & Associates [PFO closure for secondary stroke prevention, neurologic outcomes from proximal aortic repair]. Consultant/Advisory Boards: Boston Scientific [steering committee for PROTECTED-TAVR trial of embolic protection during TAVR]; EmStop [embolic protection during TAVR]; WL Gore [DSMB for post marketing study of PFO closure for secondary stroke prevention]. Other Financial Interest: Novo Nordisk [ONWARDS trial event adjudication committee]; Terumo [Patient selection committee, Relay Branch trial]. All of the relevant financial relationships listed have been mitigated. Stephen JD Brecker, MD, FRCP, FESC, FACC Grant/Research/Clinical Trial Support: Medtronic [Transcatheter valves]. Consultant/Advisory Boards: Aortic Innovations LLC [Transcatheter valves]; Medtronic [Transcatheter valves]. Speaker's Bureau: Medtronic [Transcatheter valves]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Heidi M Connolly, MD, FACC, FASE No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/stroke-associated-with-patent-foramen-ovale-pfo-evaluation/print 20/20