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Practice Guideline
. 2024 Dec;9(4):800-834.
doi: 10.1177/23969873241247978. Epub 2024 May 16.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke

Valeria Caso  1 , Guillaume Turc  2 , Azmil H Abdul-Rahim  3   4   5 , Pedro Castro  6 , Salman Hussain  7 , Avtar Lal  7 , Heinrich Mattle  8 , Eleni Korompoki  9 , Lars Søndergaard  10 , Danilo Toni  11 , Silke Walter  12 , Christian Pristipino  13
Affiliations
Practice Guideline

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke

Valeria Caso et al. Eur Stroke J. 2024 Dec.

Abstract

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Keywords: PFO closure; Patent foramen ovale; anticoagulation; antiplatelets; atrial fibrillation; stroke.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Risk of bias of individual studies included in the analysis of PICO 1.1 using the QUADAS-2 tool.
Figure 2.
Figure 2.
Risk of bias summary for PICO 1.1.
Figure 3.
Figure 3.
Random-effects meta-analysis comparing the assessment of a right-to-left shunt with c-TCD to c-TOE as a reference test in patients with ischaemic stroke, TIA, silent infarcts migraine and other neurological diseases. Pooled sensitivity 0.96 (95% CI: 0.93–0.98). Pooled specificity 0.90 (95% CI: 0.83–0.95).
Figure 4.
Figure 4.
Area under the summary receiver operating characteristic curve (sROC), reflecting the diagnostic accuracy for c-TCD and ROC curve displaying the average value of sensitivity of c-TCD over all possible values of specificity. The area under the ROC curve (AUC) is 0.96.
Figure 5.
Figure 5.
Risk of bias of individual studies used for the analysis of PICO 1.2 using the QUADAS-2 tool.
Figure 6.
Figure 6.
Risk of bias summary.
Figure 7.
Figure 7.
Random-effects meta-analysis comparing the assessment of a right-to-left shunt with c-TTE to c-TOE as a reference test. Pooled sensitivity: 0.71 (95% CI: 0.50–0.86). Pooled specificity: 0.99 (95% CI: 0.93–1.00).
Figure 8.
Figure 8.
Area under the summary receiver operating characteristic curve (sROC), reflecting the diagnostic accuracy for c-TTE and ROC curve displaying the average value of sensitivity of c-TTE over all possible values of specificity. The area under the ROC curve (AUC) is 0.71, indicating an overall modest diagnostic accuracy of c-TTE.
Figure 9.
Figure 9.
Study-level meta-analysis of the risk of recurrent ischaemic stroke in patients with PFO-associated stroke and randomised to PFO closure versus medical therapy alone (updated from Turc et al., JAHA 2018 and Mas et al.).
Figure 10.
Figure 10.
Risk of ischaemic stroke (only one study included).
Figure 11.
Figure 11.
Risk of death (only one study included).
Figure 12.
Figure 12.
Risk of TIA (only one study included).
Figure 13.
Figure 13.
Risk of major bleeding.
Figure 14.
Figure 14.
Risk of bias of randomised controlled trial (outcomes: Ischaemic stroke, Death, TIA, Major bleeding).
Figure 15.
Figure 15.
Risk of bias of randomised controlled trials.
Figure 16.
Figure 16.
Risk of stroke recurrence restricted to RCTs (antiplatelets vs anticoagulants) stroke recurrence.
Figure 17.
Figure 17.
Risk of major bleeding restricted to RCTs (antiplatelets vs anticoagulants).
Figure 18.
Figure 18.
Risk of composite outcome (stroke/TIA/death) restricted to RCTs (antiplatelets vs anticoagulants).
Figure 19.
Figure 19.
Risk of TIA restricted to RCTs (antiplatelets vs anticoagulants) TIA.
Figure 20.
Figure 20.
Risk of death restricted to RCTs (antiplatelets vs anticoagulants) death.
Figure 21.
Figure 21.
Risk of bias assessment (ROBINS-I tool) of observational studies reporting data on dual antiplatelet therapy versus single antiplatelet therapy for reducing the risk of recurrent stroke after PFO closure.
Figure 22.
Figure 22.
Dual antiplatelet therapy versus single antiplatelet therapy and risk of recurrent stroke.
Figure 23.
Figure 23.
Dual antiplatelet therapy versus single antiplatelet therapy and risk of MI.
Figure 24.
Figure 24.
Meta-analysis of the incidence of AF after PFO closure in patients who underwent long-term cardiac monitoring.
See this image and copyright information in PMC

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