Among patients age 18–65 who have had a cryptogenic ischemic stroke, cryptogenic stroke, TIA, or systemic embolism thought to be secondary to PFO due to absence of other etiologies:

Recommend percutaneous PFO closure

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 risk of paradoxical embolism (RoPE) score of ≥ 7 may identify patients who are likely to receive greater benefit from PFO closure.

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

Recommendation: In patients 18 to 60 years of age with a nonlacunar 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).

Recommendation: In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural AF of 0.33% per year).

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:

1. Regarding indications for PFO closure, follow international/global guidelines.
2. 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. transthoracic echocardiography (TTE), contrast transcranial doppler (TCD), transesophageal echocardiography (TEE), intracardiac echocardiography (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.
3. ESUS patients with significant PFO should undergo PFO closure as early as possible.

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

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.

Interventional PFO closure should be performed in patients aged 16 to 60 years (after extensive neurological and cardiological diagnostic workup) with a history of cryptogenic ischemic stroke and patent foramen ovale, with moderate or extensive right-to-left shunt. (Recommendation level A, Evidence level I).

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

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.