Medical Policy

This document addresses the transcatheter closure of patent foramen ovale.

Note: This document does not address the percutaneous transcatheter closure of atrial septal defects (ASDs).

Note: Please see the following related document for additional information:

• SURG.00096 Surgical and Ablative Treatments for Chronic Headaches

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

Transcatheter closure of a patent foramen ovale (PFO) using a U.S. Food and Drug Administration (FDA) approved device approved for that indication is considered medically necessary for:

1. The prevention of subsequent stroke in individuals with a history of cryptogenic stroke when either criteria set below are met:
   1. 60 years old and younger and the following:
      1. an atrial septal aneurysm; or
      2. a large interatrial shunt (see definition section)
   2. Any age and the following:
      1. Have failed conventional drug therapy (for example, warfarin); or
      2. Are not candidates for conventional drug therapy.

Not Medically Necessary:

Transcatheter closure of a PFO for the prevention of stroke is considered not medically necessary when the criteria above are not met.

Investigational and Not Medically Necessary:

Transcatheter closure of a PFO is considered investigational and not medically necessary for all other indications (for example, migraines, decompression sickness, and platypnea-orthodeoxia syndrome).

This document describes clinical studies and expert recommendations, and explains whether closure of a patent foramen ovale (PFO) is appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

The foramen ovale is a small hole in the heart frequently present in humans before birth that usually closes naturally soon afterwards. In some people, it stays open, referred to as a ‘patent’ foramen ovale or ‘PFO’, and may lead people with a PFO to have a stroke. Closure of a PFO is commonly done through a procedure that uses a catheter (a thin tube) inserted into a blood vessel and directed into the heart where it is used to implant a device to close the hole. The U.S. Food and Drug Administration (FDA) has approved several devices for this use, including the Amplatzer^™ PFO Occluder, Amplatzer^™ Talisman^™, and GORE^® CARDIOFORM Septal Occluder. These devices have been shown to help lower the risk of stroke in certain people with PFOs.

What the Studies Show

Clinical studies show that closing a PFO may help prevent another stroke in people aged 18 to 60. Some features, like a large hole or a flexible wall between the heart chambers (called an atrial septal aneurysm), make the closure more likely to help. Several studies found fewer strokes after closure than with treatment with medicine alone. However, people who had a PFO closure procedure were more likely to develop irregular heartbeats.

For other conditions, like migraine headaches, decompression sickness, and platypnea-orthodeoxia syndrome (a rare medical condition), studies have not proven that PFO closure helps. In migraines, for example, some people improved, but large studies did not show strong benefits. In divers with decompression sickness or people with platypnea-orthodeoxia syndrome, evidence is limited and uncertain. Also, some people may have side effects like chest pain or palpitations, especially those with nickel allergies reacting to the device.

When is Transcatheter Closure of a Patent Foramen Ovale Clinically Appropriate?

Transcatheter closure of a PFO using an FDA-approved device may be appropriate in these situations:

• The person is 60 years old or younger and has had a cryptogenic stroke and has either:
  An atrial septal aneurysm; or
  A large interatrial shunt
  or
• The person has had a cryptogenic stroke and either:
  Tried standard drug therapy (such as warfarin) but it did not prevent stroke; or
  Cannot take standard drug therapy

When is this not Clinically Appropriate?

Transcatheter closure of a PFO is not considered clinically appropriate when the above criteria are not met. This is because studies have not shown that it improves health in other situations. Better studies are needed to know if it helps in other cases. Unnecessary or unproven procedures can lead to treatment that does not help.

This treatment is also considered investigational and not clinically appropriate for other uses, including for:

• Migraine
• Decompression sickness
• Platypnea-orthodeoxia syndrome

For these conditions, studies have not shown clear benefits, and expert guidelines suggest that more research is needed before this treatment can be recommended.

(Return to Description/Scope)

Summary:

Transcatheter closure of a PFO using occluder devices offers a non-surgical option for preventing recurrent ischemic strokes in individuals, typically aged 18 to 60, who have experienced a cryptogenic stroke due to presumed paradoxical embolism. FDA-approved devices, such as the Amplatzer PFO Occluder, Amplatzer Talisman, and the GORE CARDIOFORM Septal Occluder, have demonstrated safety and efficacy in reducing stroke recurrence in this population. Multiple randomized controlled trials (RCTs) support the benefit of PFO closure over medical therapy alone in selected individuals with high-risk PFO features. However, evidence remains insufficient to support routine use of PFO closure for other conditions such as migraine, transient ischemic attack (TIA), decompression sickness (DS), or platypnea-orthodeoxia syndrome, as randomized trials have shown limited or inconclusive benefit in these populations. Current clinical guidelines emphasize individualized selection and shared decision-making for PFO closure based on stroke etiology and PFO characteristics.

Discussion:

A transcatheter PFO occluder is a permanently implanted device that provides a non-surgical method for PFO closure, blocking clots from passing from the right atrium to the left atrium.

On October 28, 2016, the FDA granted premarket approval (PMA) for the Amplatzer^™ PFO Occluder (Abbott Medical, Plymouth, MN). The device is indicated for percutaneous transcatheter closure of a PFO to reduce the risk of recurrent ischemic stroke in individuals (predominantly between ages 18 to 60 years of age) who have had a cryptogenic stroke due to a presumed paradoxical embolism, as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke. On September 27, 2021, the FDA granted PMA for the Amplatzer Talisman PFO Occluder (Abbott Medical, St. Paul, MN); a line extension of the current Amplatzer PFO Occluder Product Family (Amplatzer Talisman PFO Occluder Product Information, 2021).

In 2013, Carroll conducted the RESPECT trial (NCT00465270), a prospective, multicenter, randomized study that enrolled individuals aged 18 to 60 years with a PFO and history of a cryptogenic stroke. Participants were randomized (1:1) to either the device group with PFO closure using the Amplatzer PFO Occluder or the medical management group with four medical regimens allowed (aspirin alone, Coumadin alone, clopidogrel alone, or aspirin combined with dipyridamole). The primary efficacy endpoint was a composite outcome, which included recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization (for example, death from any cause within 30 days after implantation or 45 days after randomization, whichever occurred later, and in the medical-therapy group, death from any cause within 45 days after randomization). Secondary efficacy endpoints included complete closure of the PFO on the 6-month follow-up transesophageal echocardiography (TEE), the absence of recurrent symptomatic nonfatal ischemic stroke or cardiovascular death, and absence of a TIA. The investigators designed the trial to have 80% power and a 2-sided alpha level of 0.05 to detect a 75% relative risk (RR) reduction (based on the assumption that the 2-year primary endpoint rate would be 4.3% in the medical management group and 1.05% in the closure group). A total of 980 individuals participated with 499 randomly assigned to the closure group and 481 to the medical management group. In the intention-to-treat (ITT) analysis, a total of 25 primary end-point events occurred (9 in the closure group and 16 in the medical management group), all of which were nonfatal ischemic strokes (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22 to 1.11; p=0.08). The rates of recurrent stroke differed in the per-protocol and medical management group (p=0.03) and the as-treated group and medical management group (p=0.007). There was no difference in the rate of serious adverse events between the groups. The authors concluded that:

In patients between 18 and 60 years of age who had had a cryptogenic ischemic stroke, there was no significant benefit of closure of a patent foramen ovale over medical therapy alone in the intention-to-treat analysis. The superiority of closure with the use of the Amplatzer PFO Occluder was shown in two prespecified secondary analyses, with a low rate of associated risks.

In 2017, Saver conducted an exploratory analysis to report long-term results from the RESPECT trial (NCT00465270) that compared PFO closure with Amplatzer PFO Occluder (PFO closure group) to medical therapy alone (that is, aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole) for individuals at risk of recurrence of ischemic stroke who had a cryptogenic stroke. Of the 980 individuals who enrolled in the original trial, 716 (73.1%) were included in the long-term analysis. Median follow-up was 5.9 years with a greater dropout rate in the medical therapy only group. In the ITT population, there were 18 participants in the PFO closure group that had recurrent ischemic stroke and in the medical therapy alone group there were 28 participants. A total of 10 participants in the PFO closure group and 23 participants in the medical therapy alone group had recurrent ischemic stroke of undetermined cause. The authors found that:

The rate of venous thromboembolism in both groups exceeded that in healthy populations, which suggests that persons who have had a cryptogenic stroke and also have a PFO have a mildly elevated long-term risk of venous thromboemboli. In our trial, the lower intensity of antithrombotic therapy, including the less common agents, in the PFO closure group than in the medical-therapy group may have contributed to the higher rate of venous thromboembolism in the PFO closure group.

Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. The relative difference in the rate of recurrent ischemic stroke between PFO closure and medical therapy alone was large (45% lower with PFO closure), but the absolute difference was small (0.49 fewer events per 100 patient-years with PFO closure).

In summary, the authors found that during the follow-up period, participants with a history of cryptogenic stroke due to PFO that underwent PFO closure had a lower rate of recurrent ischemic strokes than those that received medical therapy alone.

In 2017, Mas reported results from the CLOSE study (NCT00562289), a multicenter, randomized (1:1:1), open-label study that evaluated participants who had a recent cryptogenic stroke (if no retinal ischemia): stroke (or retinal stroke) with no identifiable cause other than PFO with or without aspirin, based on a detailed etiological work-up, performed under the neurologist’s responsibility. Participants who enrolled had cryptogenic stroke attributed to PFO, with atrial septal aneurysm (defined as excursion of the septum primum greater than 10 mm on TEE); or large interatrial shunt (defined as presence of more than 30 microbubbles in the left atrium within three cardiac cycles after opacification of the right atrium, based on transthoracic echocardiography [TTE] or TEE). Exclusion criteria included any other cause of stroke associated with PFO, other medical indications for long-term anticoagulant or antiplatelet therapy, or increased bleeding risks. Participants (16 to 60 years of age) were assigned to either PFO closure plus long-term antiplatelet therapy (PFO group; n=238), anticoagulation alone group (n=187), or antiplatelet-only group (n=235); participants that had identified contraindication to anticoagulation therapy or PFO closure were assigned to alternative non-contraindicated treatment or to antiplatelet therapy. There were no reported strokes among the PFO group, 14 strokes occurred among the antiplatelet-only group (HR, 0.03; 95% CI, 0 to 0.26; p<0.001). Procedural complications were reported in 14 (5.9%) participants in the PFO closure group. Among the groups, adverse events did not differ significantly. The authors concluded that: 

In conclusion, among patients 16 to 60 years of age who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure plus long-term antiplatelet therapy than with antiplatelet therapy alone. The effects of oral anticoagulant therapy as compared with antiplatelet therapy on the risk of stroke recurrence could not be determined.

Vaduganathan (2018) conducted a meta-analysis of five RCTs (n=3440) comparing PFO closure (n=1829) versus medical therapy (n=1611) in individuals with recent cryptogenic stroke or TIA. Over a follow-up of 2.0 to 5.9 years, PFO closure reduced the incidence of recurrent stroke or death (0.70 vs. 1.48 events per 100 participant-years; RR, 0.52; 95% CI, 0.29-0.91) and stroke/TIA alone (1.04 vs. 2.00 events; RR, 0.55; 95% CI, 0.37-0.82), with modest between-study heterogeneity. All-cause mortality was similar between groups. Procedural bleeding rates were comparable (1.8% in both groups), but new-onset atrial fibrillation/flutter was significantly more common in the PFO closure group (6.6% vs. 0.7%; RR, 4.69; 95% CI, 2.17-10.12). The authors concluded that PFO closure offers superior stroke prevention compared to medical therapy in selected individuals with cryptogenic stroke, but with a higher risk of post-procedural atrial arrhythmia.

In April 2018, the FDA granted PMA for the GORE CARDIOFORM Septal Occluder (W.L. Gore & Associates, Inc., Flagstaff, AZ), a permanently implanted device indicated in PFO to reduce the risk of recurrent ischemic stroke in individuals (predominantly between 18-60 years of age) who have had a cryptogenic stroke due to a presumed paradoxical embolism, as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke. The device is contraindicated in individuals who are unable to take antiplatelet or anticoagulation therapy. The FDA approval is based on data reported by Sondergaard (2017) from the REDUCE (NCT00738894) study, an international, prospective, randomized (2:1 ratio), controlled, open-label trial that evaluated participants who underwent PFO closure plus antiplatelet therapy (PFO group; n=441) or received antiplatelet therapy alone (antiplatelet-only group; n=223). During a median follow-up of 3.2 years, 6 participants (1.4%) in the PFO group and 12 participants (5.4%) in the antiplatelet-only group had a clinical ischemic stroke (HR, 0.23; 95% CI, 0.09 to 0.62; p=0.002). There was a lower incidence of brain infarctions reported in the PFO group (n=22; 5.7%) versus the antiplatelet group only (n=20; 11.3%). Fewer serious adverse events were reported among the PFO group than the antiplatelet-only group, 23.1% versus 27.9%, respectively. The authors concluded that:

In conclusion, among patients who had cryptogenic stroke most likely attributed to PFO, the risk of recurrent stroke and now brain infarction were significantly lower with closure of the PFO plus antiplatelet therapy than with antiplatelet therapy alone.

Lee (2018) reported results from the DEFENSE PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients with High-Risk Patent Foramen Ovale) trial. The study enrolled 120 participants with history of cryptogenic stroke and high-risk PFO, and participants underwent randomization and were divided between PFO closure group and medication-only group. The study primary endpoint was a composition of stroke, vascular death, or thrombosis in myocardial infarction (TIMI) - defined major bleeding during a 2-year follow-up period. All participants in the PFO group had a successful PFO closure, therefore no event of primary endpoint occurred in the PFO closure group. The primary endpoint occurred in 6 of 60 participants in the medication-only group; 2-year event rate: 12.9% (95% CI), 2-year rate of ischemic stroke: 10.5% (p=0.023). In the medication-only group, the events included ischemic stroke (n=2), and transient ischemic attack (n=1). Nonfatal procedural complications included development of atrial fibrillation (n=2), pericardial effusion (n=1), and pseudoaneurysm (n=1). In summary, the authors concluded that:

In patients who had a recent cryptogenic stroke attributed to PFO with a large PFO, atrial septal aneurysm, or hypermobility, the rate of primary composite endpoint as well as stroke recurrence was lower with combined PFO closure in combination with medication than with medication therapy alone.

In 2020 the American Academy of Neurology (AAN) Guideline Subcommittee provided a practice advisory update summary: Patent Foramen Ovale and Secondary Stroke Prevention. The committee found evidence that PFO may play a role in some individuals with cryptogenic stroke older than 60 years. The subcommittee recommended that:

PFO closure may be offered in other populations, such as for a patient who is aged 60-65 years with a very limited degree of traditional vascular risk factors (for example, hypertension, diabetes, hyperlipidemia, or smoking) and no other mechanism of stroke detected following a thorough evaluation, including prolonged monitoring for atrial fibrillation.

Pristipino (2019) published a multi-society European position paper The Management of Patients with PFO-General approach and left circulation thromboembolism which states:

The position of our societies is to perform percutaneous closure of a PFO in carefully selected patients aged from 18 to 65 years with a confirmed cryptogenic stroke, TIA, or systemic embolism and an estimated high probability of a causal role of the PFO as assessed by clinical, anatomical and imaging features. PFO closure can also be considered in patients >65 or <18 years of age, taking into account on a case-by-case basis the lack of evidence, the age-related confounders and additional risks of interventional and drug therapies.

However, the 2022 Society for Cardiovascular Angiography and Interventions (SCAI) Guidelines for the Management of Patent Foramen Ovale provides the following recommendation:

1.7 In persons with a history of TIA and without a prior PFO-associated stroke, the SCAI guideline panel suggests against PFO closure (conditional recommendation, very low certainty of evidence).
Other considerations:

By definition, TIA patients have normal neuroimaging and no persistent clinical neurologic deficits, so an ischemic etiology for any given neurologic clinical presentation cannot be proven with confidence. Therefore, a suspected TIA cannot be differentiated from complex migraine nor from any other cause of transient neurological symptoms. The guideline panel determined that there is very uncertain benefit from PFO closure in this population. Further research is necessary to ascertain the benefits and harms of closure in this population.

In 2024, the European Stroke Organization (ESO) published guidelines on the diagnosis and management of PFO after stroke. The guideline highlights a lack of validated diagnostic algorithms for PFO detection. ESO notes that while TEE is widely used, its status as the diagnostic gold standard is not evidence-based. ESO recommends PFO closure with antiplatelet therapy in selected individuals aged 18 to 60 with PFO-associated stroke and no other identified cause, using the PASCAL classification system (see definitions), to guide candidate selection, particularly in those with large shunts and atrial septal aneurysm. ESO found insufficient evidence to support closure in individuals under 18 or over 60 and that closure is not recommended in cases of unlikely PFO-related stroke. ESO recommends long-term anticoagulation in individuals with PFO-associated stroke unless anticoagulation is not indicated for other medical reasons (Caso, 2024).

The 2021 American Heart Association (AHA)/American Stroke Association (ASA) Guideline for the Prevention of Stroke in Individuals With Stroke and Transient Ischemic Attack also does not recommend PFO closure outside of individuals with a non-lacunar ischemic stroke (on neuroimaging) of undetermined cause and a PFO.

Farjat-Pasos (2023) published a multicenter study including 1012 consecutive participants that underwent PFO closure after a cryptogenic thromboembolic event between 2001and 2020 in two high-volume tertiary-care centers. Outcomes were compared in participants grouped according to the index event; TIA (n=183 [18%]), and stroke (n=829 [82%]). TIA was defined as a temporary ischemic dysfunction causing transient neurological symptoms lasting < 1 hour and without signs of acute brain damage. Stroke was confirmed with either CT or MRI brain imaging. The diagnoses were confirmed by a neurologist in all cases. The diagnosis of PFO was made by a right-to-left shunt during TEE examination with an agitated saline contrast test with and without Valsalva maneuver. The median follow-up was 3 years, which was completed by 98% of participants. The results showed that there were no significant differences between groups except for a lower Risk of Paradoxical Embolism (RoPE) score in the TIA group (6.1 vs. 6.9 in the stroke group, p<0.001). PFO closure was successful 100% of participants with less than 1% of complications in both groups. There were no differences between groups in the incidence of AF (0.42 vs. 0.73 per 100 participant-years in the TIA and stroke groups, respectively; p=0.266), deep vein thromboses (DVT)/PE (0.16 vs. 0.16 per 100 participant-years in the TIA and stroke groups, respectively; p=0.949), and bleeding events (0.86 vs. 0.71 per 100 participant-years in the TIA and stroke groups, respectively, p=0.599). Additionally, there were no differences in the incidence of neurologic events during long-term follow-up between groups; there was 1 stroke event in the TIA group and 6 in the stroke group (0.08 vs. 0.17 per 100 participant-years, p=0.584). The authors concluded that individuals with cryptogenic TIA presented the same clinical profile as those with stroke except for a slightly lower RoPE score, transcatheter PFO closure was safe for individuals with PFO related TIA, and transcatheter PFO closure in individuals with PFO-related TIA may be as effective as in individuals with a PFO-related stroke as shown by similarly low rates of recurrent thromboembolic events during follow-up. This study was limited due to its retrospective nature. A prospective comparative clinical trial of individuals with a PFO-related TIA who did not undergo PFO closure is needed to appropriately conclude that PFO closure is effective in individuals with a PFO-related TIA. Further comparative RCTs are needed.

PFO closure in individuals with only a history of a TIA (but without a prior cryptogenic stroke) has not been rigorously evaluated; studies directly investigating the effect of PFO closure in individuals with TIA are lacking and currently there is insufficient clinical evidence to support the use of PFO closure for the treatment of TIAs.

Nickel-containing devices, such as the Amplatzer and Gore Cardioform Septal Occluders, are used for transcatheter closure of PFO. Apostolos reported that individuals with nickel hypersensitivity are at increased risk of device syndrome; a composite of symptoms including chest pain, palpitations, migraines, dyspnea, and rash. In a randomized, double-blinded study (n=96), individuals with PFO-related ischemic stroke had higher rates of device syndrome (71.4% vs. 20.6%, p<0.001), particularly migraines and palpitations. Nickel hypersensitivity was identified in 29.2% via patch testing. The analysis showed a 10.5-fold increased risk of device syndrome, with no difference in event rates between devices (Apostolos, 2025).

Decompression Sickness

Decompression sickness/illness (DCS/I), also called generalized barotrauma or The Bends, refers to injuries caused by a rapid decrease in the pressure of either air or water that surrounds an individual. Most commonly DCS occurs in scuba or deep-sea divers, it also can occur during high-altitude ascent or unpressurized air travel. Defects through which there may be transient right-to-left shunting, for example PFO, can increase the risk of paradoxical air emboli in individuals with DCS.

Lee (2023) published a single center prospective study which recruited 100 volunteer adult divers who did > 50 dives per year. TTE, TEE, and transcranial Doppler (each with agitated saline contrast without and with Valsalva maneuver) were performed to determine the presence of a PFO. Participants were divided into high-risk, defined as divers with one of the following conditions: atrial septal aneurysm, hypermobility, PFO size (maximum separation of the septum primum from the secundum) 2 mm or greater, or right-to-left shunt in the resting state during TEE or TCD evaluation, and low-risk groups. Follow-up included a self-reported questionnaire that was blinded examiners to PFO status. The primary outcome measured was the 3-year cumulative incidence of PFO-related DCS (defined as cutaneous or neurological DCS events, DCS symptoms requiring hyperbaric treatment, DCS symptoms within 30 minutes after surfacing, or unexplained death within 2 weeks after diving), to determine the odds ratio of PFO-related DCS. PFO was seen in 68 divers (68%; 37 [54% of all PFOs] high-risk and 31 [46% of all PFOs] low-risk). Mean follow-up was approximately 29 months. The results demonstrated that PFO-related DCS occurred in 12 divers in the PFO group (all cutaneous or neurological, no deaths, and only 1 diver underwent hyperbaric treatment). The incidence of a DCS event per 10,000 dives was 0 in non-PFO divers versus 8.4 in high-risk PFO divers versus 2.0 in low-risk PFO divers (p=0.001). Multivariable analysis showed that high-risk PFO was independently associated with an increased risk for PFO-related DCS (95% CI, 1.95-44.88; p=0.005).

The 2022 SCAI Guidelines for the Management of Patent Foramen Ovale recommendations regarding DCS state:

1.2. In self-contained underwater breathing apparatus (SCUBA) divers with prior decompression illness (DCS) and without a prior PFO-associated stroke, suggests against the routine use of PFO closure to prevent DCS (conditional recommendation, very low certainty of evidence).

The South Pacific Underwater Medicine Society (SPUMS) and UK Diving Medical Committee (UKDMC) recommend screening for atrial shunts (PFO or ASD) in individuals with risk factors such as prior DCS, cryptogenic stroke, migraine with aura, or congenital heart disease (Smart, 2025). The committee recommends screening with bubble contrast TEE with provocative maneuvers, if a shunt is detected, management should be individualized by an experienced diving physician. The committee opined that in cases of shunt-mediated DCS, the safest course is cessation of diving, though conservative diving practices may be an alternative. Divers may consider transcatheter PFO closure to return to unrestricted diving, with shunt resolution confirmed by follow-up echocardiography and cessation of potent antiplatelet therapy (low-dose aspirin permitted) before resuming.

Currently there is insufficient clinical evidence to support the use of PFO closure for the treatment of DCS.

Migraine

Migraine with arura may be associated with PFO and right-to-left cardiac shunting. PFO closure has been evaluated as a treatment. A study by Dowson (2008) investigated PFO closure for migraine in a randomized, double-blind, sham-controlled trial. Individuals that experienced migraine with aura, frequent migraine attacks, had previously failed > or = 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. The primary efficacy measure was cessation of migraine headache 91-180 days post-procedure; 432 participants were screened, 163 (38%) had right-to-left shunts consistent with a moderate or large PFO. Subsequently 147 participants were randomized and followed for 6 months. No significant difference was observed in migraine headache cessation between implant and sham groups (3 of 74 vs. 3 of 73, respectively; p=0.51). The implant group demonstrated a greater reduction in total migraine headache days (p=0.027). Adverse events were reported in both groups, most commonly attributed to trial antiplatelet medication. Serious adverse events occurred in 16 individuals. Procedural complications included pericardial effusion in 2 individuals, 1 of which required percutaneous drainage, and a retroperitoneal bleed in 1 individual in the implant group. The authors concluded that the results confirmed a high prevalence of right-to-left shunts in individuals experiencing migraine with aura, however, no significant effect was found from PFO closure. Larger trials are needed to further investigate the benefits of PFO closure in this population.

Mattle (2016) published the results of a multicenter, randomized control trial (RCT) that investigated the effect of percutaneous PFO closure in individuals that were refractory to medical treatment. Participants were randomized to PFO closure or medical treatment groups, both groups were given ASA 75-100 mg/day for 6 months and clopidogrel 75 mg/day for 3 months. The primary outcome measured was reduction in monthly migraine days during months 9-12 after randomization compared with a 3-month baseline phase before randomization; 107 participants were randomized to treatment with an Amplatzer PFO Occluder (n=53) or control with medical management (n=54). The trial was terminated prematurely due to slow enrolment, 83 participants (40 occluder, 43 control) completed 12-month follow-up. Mean migraine days at baseline were 8 (±4.7 SD) in the closure group and 8.3 (±2.4) in controls. The primary outcome was negative with -2.9 days after PFO closure compared to -1.7 days in control group (p=0.17). PFO closure caused 5 adverse events without permanent sequelae. The authors concluded that in individuals with refractory migraine with aura PFO closure did not reduce overall monthly migraine days.

Liu (2021) published a review that examined the relationship between migraine and PFO to better understand the pathophysiological mechanisms and improve understanding of the risks and benefits of treatment with PFO closure. The incidence of PFO in individuals with migraines varies amongst several studies. Several studies found that migraines with atypical aura were closely associated with PFO, and the presence of right-to-left shunt increased the likelihood of aura attacks. The authors stated:

We consider the PFO having a closer relationship in migraine patients with aura, especially atypical aura, although non-migraine with aura is also correlated with the presence of the PFO. The frequency of headache onset, but not its clinical features, is also correlated with PFO, which seems to suggest that right-to-left shunt may trigger the onset of migraine without directly affecting the migraine symptoms. In addition, the type and size of the foramen ovale are also associated with migraine. Persistent PFO, larger PFO, and complex tissue structures may cause more right-to-left shunt of the blood to increase the incidence of migraine. Taken together, these support the “dose-response” relationship between right-to-left shunt and migraine.

However, in RCTs the results were unremarkable. The authors concluded that the findings did not support PFO occlusion for the improvement of headaches in individuals with migraines, and that PFO closure may carry a small risk of adverse events including stroke, pericardial tamponade, atrial fibrillation and death. 

In 2022, the American Headache Society noted that several clinical trials were conducted to determine if closing a PFO is helpful for migraine, none of the studies showed the PFO closure was significantly effective in reducing migraine in all migraine sufferers. However, a secondary analysis suggested that individuals who had aura with most of their migraines did respond well to PFO closure. They concluded that it is important to note that an association does not indicate causation and that based upon the evidence to date clinical trials do not provide evidence to support PFO closures in migraine sufferers. Further research is needed to better understand the potential role for PFO in migraine.

The 2022 SCAI Guidelines for the Management of Patent Foramen Ovale recommendations include the following:

1.1. In persons experiencing migraines without a prior PFO-associated stroke, the panel suggests against the routine use of PFO closure for the treatment of migraine (conditional recommendation, moderate certainty of evidence).

Currently there is insufficient clinical evidence to support the use of PFO closure for the treatment of migraine headaches.

Platypnea-orthodeoxia syndrome

PFO‐associated platypnea-orthodeoxia syndrome is a rare disorder characterized by orthostatic accentuation of a right-to-left shunt, resulting in both dyspnea (platypnea) and arterial desaturation (orthodeoxia) in the upright position that improves in the supine position.

The 2022 SCAI Guidelines for the Management of Patent Foramen Ovale recommendations regarding platypena-orthodeoxia syndrome state:

1.3. In persons with platypnea-orthodeoxia syndrome (POS) and without a prior PFO-associated stroke, in whom other causes of hypoxia have been excluded, the SCAI guideline panel suggests PFO closure rather than no PFO closure (conditional recommendation, very low certainty of evidence).

Based upon the SCAI conditional recommendation, the very low certainty of evidence, and the lack of rigorous studies investigating the effect of PFO closure in individuals with POS there is insufficient clinical evidence to support the use of PFO closure for the treatment of this condition.

PFO describes the persistence of a component of the fetal circulation between the right and left atrium. Although PFOs are found in 10-15% of adults, they are typically clinically insignificant. However, they may be associated with paradoxical embolus, in which an embolus arising in the venous circulation gains access to the arterial circulation through the PFO.

PFO size is inferred from the degree of right-to-left shunting demonstrated on echocardiography in conjunction with agitated saline contrast (bubble study) based on the number of microbubbles appearing in a single frame in the left atrium either spontaneously or after a Valsalva maneuver within three cardiac cycles after opacification of the right atrium. Methods used to detect a right-to-left shunt associated with PFO include TTE, TEE, and transcranial doppler (TCD). TCD cannot confirm the location of the shunt (intracardiac or extracardiac), identify an atrial septal aneurysm, or rule out other cardioembolic sources. Therefore when TCD is positive, imaging, usually with TEE is performed to visualize the type, site, and size of the shunt.

It is estimated that individuals with a history of PFO and paradoxical embolism have a 3.4% and 3.8% yearly risk of recurrent stroke or transient ischemic attack. Therefore, there has been interest in either open surgery or transcatheter approaches to close the PFO, in individuals with a history of embolic stroke of unknown cause. Treatment alternatives include chronic warfarin therapy, based, in part, on the theory that clotting disorders may be present in individuals with embolic stroke. The Amplatzer PFO Occluder, Amplatzer Talisman PFO Occluder, and GORE CARDIOFORM Septal Occluder have received FDA approval for transcatheter closure of a PFO to reduce risk of stroke in individuals who had cryptogenic stroke due to presumed paradoxical embolism, after a comprehensive clinical evaluation (by neurologist and cardiologist) has been conducted to rule out other causes of stroke. Contraindications for the Amplatzer PFO Occluder include: active endocarditis, untreated infection, other heart defects, or a tumor or blood clot in the vessels along the path of the heart. The GORE HELEX Septal Occluder/ GORE Septal Occluder (W.L. Gore & Associates, Inc., Flagstaff, AZ) provides another potential treatment option for PFO closure in individuals who had a cryptogenic stroke.

In the CLOSE study, Mas (2017) defined cryptogenic stroke or retinal ischemia as follows:

Cryptogenic stroke (or retinal ischemia): with no identifiable cause other than PFO with or without ASA, based on a detailed etiological work-up, performed under the neurologist’s responsibility. The following examinations, which are part of the standard etiological work-up for stroke in young adults, will be performed before randomization:

• At least one of the following arterial investigations, performed in the 30 days following the qualifying event, as a complement to or instead of Doppler ultrasound of supra-aortic vessels and/or transcranial Doppler: (a) MRA (magnetic resonance angiography), with intracranial and extracranial investigation; (b) CT angiography, with intracranial and extracranial investigation; (c) arteriography by catheter, with extracranial and intracranial investigation.
• Biological work-up comprising blood count, ESR, CRP, fasting blood glucose, lipid survey, serum creatinine, ASAT, ALAT, PT, aPTT, antiphospholipid antibodies (at least including screening for circulating anticoagulant and anticardiolipin antibodies)
• Transthoracic and transesophageal echocardiography (see appendix)
• ECG and search for emboligenic arrhythmia: cardiac monitoring at the acute phase of stroke and/or 24h-Holter ECG
• Any other examination necessary to confirm a cause suspected on clinical data and/or the initial etiological work-up.

Ischemic stroke: Sudden onset of focal neurological symptoms with the presence of cerebral infarction in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of the symptoms (less than or greater than 24 hours).

Retinal ischemia: Sudden onset of monocular visual deficit accompanied by objective signs of retinal infarction in the appropriate region of the retina. This diagnosis must be confirmed by the appropriate investigations.

Potential causes of stroke

• Atherosclerosis: presence of stenosis ≥ 30% of an artery supplying the brain or atherosclerosis of the aortic arch (plaque ≥ 4 mm). In the case of arterial occlusion in the appropriate territory, the diagnosis of atherosclerosis will be adopted if the individual presents at least two cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking) OR a history of myocardial infarction or arterial disease of the lower limbs OR an atherosclerotic stenosis (≥ 30%) of another artery supplying the brain OR plaques of the aortic arch.
• Potentially emboligenic heart disease, other than PFO or ASA.
• Small artery disease, defined by the presence of a small deep infarction (< 1.5 cm in diameter) corresponding to the clinical signs, in an individual with chronic hypertension or diabetes OR at least one old small infarction or vascular leukoencephalopathy. Individuals with only one small deep infarction, without hypertension or diabetes, can be included in the study.
• Other defined or probable causes of stroke (not exhaustive):
  • Non-atherosclerotic arterial disease (e.g.: dissection or arteritis)
  • Coagulopathy requiring long-term anticoagulant therapy (> 6 months).
  • Hematological malignancies (e.g.: thrombocythemia)
  • Recent intravenous drug use (in previous 6 months).

Atrial septal aneurysm: Redundant interatrial tissue, encompassing the fossa ovalis, with resulting hypermobility of the septum primum and excursion greater than 10 mm on TEE.

Cryptogenic stroke: Cerebral infarction that despite evaluation is not attributable to other well-established singular etiologies including cardioembolism, large artery atherosclerosis, thromboembolism, or small vessel occlusion.

Decompression Sickness (also known as Decompression Illness, Caisson Disease, or The Bends): Occurs when rapid pressure reduction (for example, during ascent from a dive, exit from a caisson or hyperbaric chamber, or ascent to altitude) causes gas previously dissolved in blood or tissues to form bubbles in blood vessels. Symptoms may include pain, neurologic symptoms, or both, severe cases can be fatal. Risk factors include right-to-left cardiac shunts (Merk Manual Professional, 2023).

Large interatrial shunt: Presence of more than 30 microbubbles in the left atrium within three cardiac cycles after opacification of the right atrium, based on TTE or TEE.

Migraine aura: A “warning stage” that sometimes occurs before the onset of a migraine headache. Aura refers to any number of sensory disturbances including visual, sensorimotor, or dysphasia (Cleveland Clinic 2021).

Patent foramen ovale (PFO): A component of the fetal circulation that consists of a communication between the left and right atria that generally closes after birth; if an opening remains after birth, the possibility of an embolus (blood clot that breaks free in the blood) getting to the brain exists, resulting in a stroke or transient ischemic attack.

PASCAL classification system: a clinical risk stratification tool used to assess the likelihood that a PFO is causally related to a cryptogenic stroke and guide decision-making about whether PFO closure may be beneficial (ESO, 2021).

P - Probability
A - Assessment of
S - Stroke
C - Associated
A - with
L - Large PFO
Risk Categories:
The system classifies patients into three risk levels:

1. Probable PFO-related stroke - Strong clinical and anatomical features support a causal link.
2. Possible PFO-related stroke - Some supportive features, but other causes not fully excluded.
3. Unlikely PFO-related stroke - PFO is likely incidental; other stroke etiologies more plausible.

Platypnea-orthodeoxia syndrome (POS): A rare disorder characterized by both dyspnea (platypnea) and arterial desaturation (orthodeoxia) in the upright position with improvement in the supine position.

Transient Ischemic Attack (TIA): A stroke that lasts only a few minutes. It occurs when the blood supply to part of the brain is briefly interrupted. Symptoms usually occur suddenly and disappear within an hour, although they may persist for up to 24 hours. Symptoms can include numbness or weakness in the face, arm, or leg, especially on one side of the body, trouble seeing in one or both eyes, difficulty with walking, dizziness, confusion or difficulty in talking or understanding speech, loss of balance and coordination (NIH 2024).

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met.

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above for all other diagnoses not listed [with the exception of other atrial septal defects not addressed].

Peer Reviewed Publications:

1. Apostolos A, Gregoriou S, Drakopoulou M, et al. Patent foramen ovale closure in patients with and without nickel hypersensitivity: a randomized trial. Circ Cardiovasc Interv. 2025; 18(4):e015228.
2. Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013; 368(12):1092-1100.
3. Caso V, Turc G, Abdul-Rahim AH, et al. European Stroke Organisation (ESO) guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke. Eur Stroke J. 2024; 9(4):800-834.
4. Dowson A, Mullen MJ, Peatfield R, et al. Migraine intervention with STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation. 2008; 117(11):1397-404.
5. Farjat-Pasos JI, Guedeney P, Houde C, et al. Transcatheter patent foramen ovale closure in patients with Transient Ischemic Attack. Am J Cardiol. 2023; 187:148-153.
6. Kapadia SR. Patent foramen ovale closure: historical perspective. Cardiol Clin. 2005; 23(1):73-83.
7. Kay JD, O’Laughlin MP, Ito K, et al. Five-year clinical and echocardiographic evaluation of the Das Angel Wings atrial septal occluder. Am Heart J. 2004; 147(2):361-368.
8. Kuijpers T, Spencer FA, Siemieniuk RA, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. Brit J Med. 2018; 362:k2515.
9. Lee HJ, Lim DS, Lee J, et al. Decompression Illness in divers with or without patent foramen ovale: a cohort study. Ann Intern Med. 2023; 176(7):934-939.
10. Lee PH, Song JK, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol. 2018; 71(20):2335-2342.
11. Mas JL, Derumeaux B, Guillon E, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Eng J Med. 2017; 377(11):1011-1021.
12. Mattle HP, Evers S, Hildick-Smith D, et al. Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial. Eur Heart J. 2016; 37(26):2029-36.
13. Onorato E, Melzi G, Casilli F, et al. Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure in 256 patients. J Interv Cardiol. 2003; 16(1):43-50.
14. Pristipino C, Sievert H, D'Ascenzo F, et al. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. Eur Heart J. 2019; 40(38):3182-3195.
15. Ries M, Kampmann C, Rupprecht HJ, et al. Nickel release after implantation of the Amplatzer occluder. Am Heart J. 2003; 145(4):737-741.
16. Saver JL, Carrol JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017; 377(11):1022-1032.
17. Sondergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Eng J Med. 2017; 377(11):1033-1042.
18. Vaduganathan M, Qamar A, Gupta A. Patent Foramen ovale closure for secondary prevention of cryptogenic stroke: updated meta-analysis of randomized clinical trials. Am J Med. 2018; 131(5):575-577.
19. Windecker S, Wahl A, Chatterjee T, et al. Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long term risk of recurrent thromboembolic events. Circulation. 2000; 101(8):893-898.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Kavinsky CJ, Szerlip M, Goldsweig AM, et al. SCAI guidelines for the management of patent foramen ovale. J Soc Cardiovasc Angiogr Interv. 2022; 1(4):100039.
2. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack. A guideline from the American Heart Association/American Stroke Association. Stroke. 2021; 52:e364-e467.
3. Liu K, Wang BZ, Hao Y, et al. The correlation between migraine and Patent Foramen Ovale. Front Neurol. 2020; 11:543485.
4. Messe SR, Gronseth GS, Kent DM, et al. Practice advisory update summary: patent foramen ovale and secondary stroke prevention. Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology. 2020; 94:1-10.
5. Smart D, Wilmshurst P, Banham N, et al. Joint position statement on atrial shunts (persistent [patent] foramen ovale and atrial septal defects) and diving: 2025 update. South Pacific Underwater Medicine Society (SPUMS) and the United Kingdom Diving Medical Committee (UKDMC). Diving Hyperb Med. 2025; 55(1):51-55.
6. St. Jude Medical. AMPLATZER Cardiac Plug (ACP) registry-long term follow-up protocol (ACPR). NLM Identifier: NCT01786486. Last updated on June 28, 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT01786486?term=AMPLATZER+AND+left+atrial+appendage&rank=1. Accessed on January 13, 2026.
7. U.S. Food and Drug Administration (FDA). Premarket Approval (PMA). AMPLATZER PFO Occluder. No. P120021. Rockville, MD: FDA. October 28, 2016. Accessible at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P120021. Accessed on January 13, 2026.
8. U.S. Food and Drug Administration (FDA). Premarket Approval (PMA). Amplatzer^™ Talisman^™ PFO Occluder. No. P120021/S020. Rockville, MD: FDA. September 27, 2021. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P120021S020.
9. U.S. Food and Drug Administration (FDA) Premarket Approval (PMA). GORE^® CARDIOFORM Septal Occluder. No. P050006/S060. Rockville, MD: FDA. March 30, 2018. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P050006S060. Accessed on January 13, 2026.
10. W.L. Gore & Associates. Gore^® Helex^® septal occlude/GORE^® CARDIOFORM Septal Occlude for patent foramen ovale (PFO) closure in stroke patients - the Gore REDUCE clinical study (HLX 06-03). NLM Identifier: NCT00738894. Last updated November 20, 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT00738894. Accessed on January 13, 2026.

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member’s contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.