U.S. and International Stroke Guidelines

Society for Cardiovascular Angiography & Interventions (SCAI) – Guidelines for the Management of Patent Foramen Ovale¹ – 2022

Recommendation: In patients between the ages of 18 and 60 with a prior PFO-associated stroke, the SCAI guideline panel recommends PFO closure rather than antiplatelet therapy alone (strong recommendation, moderate certainty of evidence).

This recommendation is independent of patient anatomy (i.e., presence of ASA, size of shunt). A RoPE score of ≥ 7 may identify patients who are likely to receive greater benefit from PFO closure.

The guidelines were developed by SCAI, with representation from the American Academy of Neurology (AAN).

American Heart Association/American Stroke Association (AHA/ASA)² — 2021

In the 2021 Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack, the AHA/ASA recommend PFO closure in select patients.

Recommendation: In patients 18 to 60 years of age with a non-lacunar ischemic stroke of undetermined cause, despite a thorough evaluation and a PFO with high-risk anatomic features, it is reasonable to choose closure with a transcatheter device and long-term antiplatelet therapy over antiplatelet therapy alone for preventing recurrent stroke. (Recommendation level 2b, level of evidence B-R).

American Academy of Neurology (AAN)³ — 2020

An updated practice advisory from the American Academy of Neurology (AAN) concludes that patent foramen ovale (PFO) closure may be recommended for some patients with a PFO, an embolic-appearing infarct, and no other mechanism of stroke identified. This advisory has been endorsed by the American Heart Association/American Stroke Association, the Society for Cardiovascular Angiography and Interventions, and the European Academy of Neurology.

Recommendation: In patients younger than 60 years with a PFO and an embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (reduction of stroke recurrence) and risks (procedural complication and atrial fibrillation) (Level C).

Japanese Guidance Document⁴ — 2019

The Japan Stroke Society, The Japanese Circulation Society, and Japanese Association of Cardiovascular Intervention and Therapeutics came together to review the evidence on PFO closure and recommend the following when it comes to selecting the appropriate patient for PFO closure:

Indication criteria for percutaneous closure of PFO for the purpose of stroke recurrence prevention:

1. Indispensable condition: Implementation of the intervention will be considered in case of satisfaction of all items described below:
   1. Patients who meet the diagnosis criteria for PFO related cryptogenic stroke
   2. Patients in whom antithrombotic therapy can be conducted during a certain period after percutaneous closure implementation
   3. Patients <60 years of age in principle
   4. Female patients who are not pregnant or do not want to become pregnant within a year
2. Recommendation condition: Implementation of the intervention will be recommended in case of satisfaction of all aforementioned items and any items described below:
   1. The presence of high risk PFO in terms of function/anatomy such as:
      1. Large volume of shunt
      2. Concomitant atrial septal aneurysm (ASA)
      3. Concomitant Eustachian valve (EV)
      4. Concomitant Chiari network
      5. Right-left shunt found at rest (without Valsalva maneuver)
   2. Onset of the aforementioned type of cryptogenic stroke during appropriately conducted antithrombotic therapy.

Australian Guidelines⁵ — 2019

Published by the Stroke Foundation, the Australian guidelines were written by Content Development Working Group, a multi-disciplinary group of physicians involved in stroke care. In summary, the guidelines involving PFO closure state:

Strong Recommendation:

In ischaemic stroke patients aged <60 in whom a patent foramen ovale is considered the likely cause of stroke after thorough exclusion of other aetiologies, percutaneous closure of the PFO is recommended (Turc et al. 2018 [182], Saver et al. 2018 [184]).

German Guidelines⁶— 2018

Physicians from cardiology, internal medicine, and neurology joined together to publish new stroke guidelines related to PFO closure in patients with cryptogenic stroke. The guidelines state that interventional 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. Recommendation level A, Evidence level I.

The British Medical Journal (BMJ)⁷ — 2018

Among patients younger than age 60 who have had a cryptogenic ischemic stroke thought to be secondary to PFO (due to absence of other etiologies):

• Strong recommendation: among patients in whom anticoagulation is contraindicated or declined — to provide PFO closure + antiplatelet therapy, vs antiplatelet therapy alone
• Weak recommendation: among patients who are open to all options — to provide PFO closure + antiplatelet therapy vs anticoagulant therapy
• Weak recommendation: among patients in whom closure is contraindicated or declined — to provide anticoagulant therapy vs antiplatelet therapy

Canadian Guidelines⁸ — 2017

Published in the International Journal of Stroke, the Canadian guidelines were written by a group of physicians on behalf of the Heart and Stroke Foundation Canadian Stroke Best Practice Committees. In summary, PFO guidelines have been updated with the following:

Patent Foramen Ovale

For carefully-selected patients with a recent ischemic stroke or TIA attributed to a PFO, PFO device closure plus long-term antiplatelet therapy is recommended over long-term antithrombotic therapy alone, provided all the following criteria are met:

[Evidence Level A]:

1. Age 18–60 years;
2. The diagnosis of the index stroke event is confirmed by imaging as a nonlacunar embolic ischemic stroke or a TIA with positive neuroimaging or cortical symptoms;
3. The patient has been evaluated by a neurologist or clinician with stroke expertise, and the PFO is felt to be the most likely cause for the index stroke event following a thorough etiological evaluation to exclude alternate etiologies.

Monitoring for Atrial Fibrillation Prior to PFO Closure⁹ - 2022

In patients who have suffered a stroke that may be PFO-associated, it’s important to screen for atrial fibrillation (AF). Given the lack of clear and specific guidance available on the optimal monitoring modality and duration, an expert panel set out to provide a straightforward and personalized approach to AF detection in these patients.

The new framework provides:

• Specific monitoring timelines and modalities that account for patients with varying age and other AF risk factors
• AF monitoring ranges from 72 hours of Holter to 3 months of ICM, depending on the patient

Monitoring duration may be reduced based on presence of high-risk PFO features (i.e. large shunt and/or ASA).

Establishment of the Heart and Brain Team for PFO Closure in Stroke Patients¹⁰ - 2022

Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure. This multidisciplinary team – also known as the Heart and Brain Team – involves several clinical specialties, including neurology and cardiology, as well as the patient.

This review provides insights into the implementation, composition, organization and operation of a heart and brain team, as well as metrics to evaluate the team’s role.

An impactful Heart and Brain team requires upfront networking, implements an organized structure and routinely assesses effectiveness. When done well, patient waiting time and risk of loss to follow up is reduced.

Asian-Pacific Consensus Statement¹¹ — 2020

With most of the evidence on PFO closure being obtained from Caucasian patients, a consensus statement was developed by Asian-Pacific clinical experts, accounting for the specific stroke and bleeding characteristics of Asian-Pacific patients and the specific Asian-Pacific context.

Key aspects of this consensus statement include:

• Regarding indications for PFO closure, follow international/global guidelines.
• Ensure that patients with recent embolic stroke of undetermined source (ESUS) are screened for PFO, using imaging modalities that are readily available in the hospital and on which the staff is best trained and most experienced (e.g. TTE, contrast TCD, TEE, ICE). Contrast TCD is widely available in the Asian-Pacific region and may be used as a first screening tool, followed by confirmation using TEE or TTE with bubble contrast.
• ESUS patients with significant PFO should undergo PFO closure as early as possible.

It was emphasized that clinical evidence for the above aspects should be collected among Asian-Pacific patients.

European Position Paper¹² — 2018

EuroIntervention published a European position paper regarding the management of patients with PFO. The paper was developed by 8 scientific societies and international stroke experts.

Recommendation:

“Position of our societies is to perform percutaneous closure of PFO in carefully selected patients from 18 to 65 years with confirmed cryptogenic stroke, TIA or systemic embolism and estimated high probability of causal role of PFO as assessed by clinical, anatomic and imaging features.”

“The interventional procedure must be proposed to each patient evaluating the individual probability of benefit based on an assessment of both the role of the PFO in the thromboembolic event and the expected results and risks of a lifelong medical therapy.”