Patent Foramen Ovale

Article Author:
Troy Hampton
Article Editor:
Heather Murphy-Lavoie
1/13/2020 12:27:41 PM
PubMed Link:
Patent Foramen Ovale


Patent foramen ovale (PFO), part of a group of entities known as atrial septal defects, is a remnant of normal fetal anatomy that abnormally persists into adulthood contributing to inter-atrial, right-to-left shunting of deoxygenated blood and potential for shunting venous thromboembolism to the arterial circulation. This implicates PFO as the underlying pathophysiologic determinant of several conditions including cryptogenic (having no other identifiable cause) stroke, decompression sickness, migraine, platypnea-orthodeoxia syndrome, and acute limb ischemia secondary to emboli.[1]

The majority of patients with a PFO are asymptomatic. The diagnosis is often made after the patient suffers a stroke, migraine-like symptoms or decompression sickness while diving.


The foramen ovale is a tunnel-like space between the overlying septum secundum and septum primum. It closes in 75% of people at birth when the septum primum and secundum fuse. In utero, the foramen ovale is necessary for the flow of blood across the fetal atrial septum. Oxygenated blood from the placenta returns to the inferior vena cava, crosses the foramen ovale, and enters the systemic circulation. In approximately 25% of people, a PFO persists into adulthood. PFOs may be associated with atrial septal aneurysms (a redundancy of the interatrial septum), Eustachian valves (a remnant of the sinus venosus valve), and Chiari networks (filamentous strands in the right atrium). PFOs may serve as either a conduit for paradoxical embolization from the venous side to the systemic circulation or, because of their tunnel-like structure and propensity for stagnant flow, may serve as a nidus for in situ thrombus formation.[2]


Data in 1988 revealed that 30% to 40% of young patients who had a Cryptogenic stoke had a PFO. This percentage compared to 25% in the general population. Since that time, the largest target population studied has been patients of all ages with cryptogenic stroke, in whom the frequency of finding a PFO is often double that of the general population. In this population, an optimal secondary prevention strategy is not well defined. Patients with PFO and atrial septal aneurysm who have experienced strokes seem to be at higher risk for recurrent stroke (as high as 15% per year), and secondary preventive strategies are necessary. In another study, 50% of patients with cryptogenic stroke were found to have right-to-left shunting compared to 15% of the controls. Approximately 2/3rds of divers with undeserved (following safe dive profiles) decompression illness, are found to have a PFO. PFOs are especially common in divers with cerebral, inner ear,  and cutaneous decompression sickness.[3]


PFO is a flap-like opening between the atrial septum secundum and primum at the fossa ovalis. In utero, it serves as a conduit for blood to the systemic circulation. Once the pulmonary circulation increases after birth, the functional PFO starts to close. Anatomical closure of the PFO usually occurs at about 12 months.

PFO primarily increases the risk of stroke from a paradoxical embolism. The risk for a cryptogenic stroke is proportional to the size of the PFO. The presence of an interatrial septal aneurysm in combination with a PFO also increases the risk for an adverse event, perhaps because of increased in situ thrombus formation in the aneurysmal tissue or because PFOs associated with an interatrial septal aneurysm tend to be larger. Despite prior reports concerning paradoxical embolism through a PFO, the magnitude of this phenomenon as a risk factor for stroke remains undefined, because deep venous thrombosis is infrequently detected in such patients. In one study, pelvic vein thrombi were found more frequently in young patients with cryptogenic stroke than in those with a known cause of stroke. This may provide the source of venous thrombi, particularly when a source of venous thromboembolism (VTE) is not initially identified.[4]

History and Physical

The majority of patients with PFO are asymptomatic. However, some may present with migraines-like headaches, stroke or a transient ischemic event. Less common clinical presentations include paradoxical embolism, acute myocardial infarction, systemic embolism and dyspnea at rest.

The physical exam may be remarkable. A faint systolic murmur may be heard on auscultation.


By far the most common circumstance prompting the search for PFO is a cryptogenic stroke. When an etiology is elusive in the work-up for stroke, and there exist no identifiable contributors, the stroke is considered cryptogenic. Evaluation for PFO is then appropriately pursued, particularly in those persons younger than 40 years of age experiencing a stroke. A PFO is usually detected by transthoracic echocardiography, transesophageal echocardiogram (TEE), or transcranial Doppler. TEE is the most sensitive test, especially when performed with contrast media injected during a cough or Valsalva maneuver. Patients with cryptogenic strokes should also be evaluated for the presence of venous thromboembolism (VTE). 

Divers with more than one episode of undeserved decompression illness should undergo evaluation for a right to left shunt. A 2015 diving medicine consensus panel recommended contrasted provocative transthoracic echocardiography for this evaluation, because it has a lower complication rate than TEE and is unlikely to miss a clinically significant PFO. [5]

Treatment / Management

Once the presumptive diagnosis of a cryptogenic stroke caused by a PFO is determined, treatment modalities to prevent recurrent events include antiplatelet or anticoagulant agents, percutaneous device closure, or surgical PFO closure. Device closure is safe and seems to be effective, with a stroke recurrence rate of between 0% and 3.8% per year. The functional closure is usually followed by permanent fusion of the 2 flaps comprising the defective atrial septum. Complete closure occurs in up to 80%, and in an additional 10% to 15% the residual right-to-left shunting appears to be trivial.[6][7][8]

Studies currently demonstrate low recurrent ischemic stroke rates with medical therapy alone. There is some disparity in trials evaluating the superiority of medical and surgical interventions in the prevention of recurrent stroke albeit that risk is apparently low in both approaches. Three randomized clinical trials that totaled more than 2000 patients compared closure of the patent foramen ovale with alternative medical treatment. Data from these trials indicated that PFO offered no benefit compared with medical therapy.[9][10]

Other studies have shown that patients with cryptogenic stroke and PFO have relatively low outcome rates with medical therapy with or without device closure and that recurrent stroke rates are lower with percutaneously implanted device closure than with medical therapy alone. One study demonstrated that transcatheter closure was found to be superior to medical therapy in the prevention of recurrent neurological events after cryptogenic stroke, and patients taking coumadin had a lower recurrence rate than did those receiving antiplatelet therapy.

Many single-center studies have been published, most have been retrospective, but all have been observational, often with historical controls. The results of these reports have been summarized in meta-analyses supporting the superiority of device closure, frequently with concomitant antiplatelet therapy, versus medical therapy alone. However, prospective studies are lacking.

Indications for surgery include the following:

PFO that is larger than 25 mm

Failure of the PFO to close by percutaneous method

Inadequate rim at the edge-this can make it difficult for percutaneous closure

The advantages of surgery include 1) no risk of future paradoxical emboli 2) permanent closure ad 3) no need for long term anticoagulation. However, surgery does require open-heart surgery and the usual risks of the procedure.

For percutaneous closure, the FDA has approved the Cardioseal Septal occlusion system and the amplatzer PFO occluder. The procedure is done under fluoroscopic guidance and requires hospital admission. Aspirin or warfarin is required for a minimum of 6 months.

Differential Diagnosis

Atrial septal defect

Ventricular septal defect

Carcinoid syndrome


The prognosis for most patients who undergo closure is excellent. Surgical outcomes have been well established. Percutaneous closure is successful but complications are not uncommon. Embolism, dislodgment, and failure to close the PFO have all been reported. In addition, the percutaneous procedure may be associated with damage to the blood vessels, stroke, thrombus formation, and infective endocarditis.


The usual complications of antiplatelet and anticoagulant therapies include bleeding and intracerebral hemorrhage. Intraprocedural complications utilizing device closure include perforation resulting in tamponade, air embolism, device embolization, and stroke. However, these are all rare events in experienced hands, with rates of less than 1%. Subsequent atrial arrhythmias may occur in 3% to 5% but are transient. Although the rate of development of atrial fibrillation has been 5% to 6% with some devices, they have also been associated with thrombus formation on the device. Late cardiac perforation has been reported with some devices but appears to be rare. In comparisons, atrial fibrillation was more common among closure patients than anticoagulated patients in secondary preventive strategies.[11]

Enhancing Healthcare Team Outcomes

PFO has been identified as the major contributing factor in cryptogenic stroke in 50% of affected young adults and is present in 25% of the general adult population. The identification of PFO, particularly in young cryptogenic stroke patients, is rather easily accomplished via TEE with contrast media. Treatment is aimed at the prevention of a secondary event primarily with antiplatelet or anticoagulation therapy or atrial septal device closure. The risk associated with either treatment is low overall, and the superiority of one therapy over the other is still contested. Accepted device closure treatment is for large PFOs (greater than 25 mm), and in patients with PFOs who have already had a recurrent neurological event. Any identified venous thromboembolic event involving PFO should be treated with anticoagulation, just as pulmonary embolism would be treated.[1]

The management of patent foramen ovale is made by an interprofessional team that consists of a pediatrician, cardiologist, interventional radiologist, and a cardiac surgeon. The decision to treat depends on the presence of symptoms, size, and presence of complications. Today, in high-risk patients percutaneous methods of closure have evolved. Patients should be educated on their treatment options and possible complications of each treatment.

  • Image courtesy S Bhimji MD
    (Move Mouse on Image to Enlarge)
    • Image 8499 Not availableImage 8499 Not available
      Image courtesy S Bhimji MD

  • Image courtesy O. Chaigasame
    (Move Mouse on Image to Enlarge)
    • Image 11286 Not availableImage 11286 Not available
      Image courtesy O. Chaigasame


[1] Pristipino C,Sievert H,D'Ascenzo F,Louis Mas J,Meier B,Scacciatella P,Hildick-Smith D,Gaita F,Toni D,Kyrle P,Thomson J,Derumeaux G,Onorato E,Sibbing D,Germonpré P,Berti S,Chessa M,Bedogni F,Dudek D,Hornung M,Zamorano J, European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. European heart journal. 2018 Oct 25     [PubMed PMID: 30358849]
[2] Teshome MK,Najib K,Nwagbara CC,Akinseye OA,Ibebuogu UN, Patent Foramen Ovale: A Comprehensive Review. Current problems in cardiology. 2018 Sep 8     [PubMed PMID: 30327131]
[3] Detection of right to left shunts in decompression sickness in divers., Kerut EK,Truax WD,Borreson TE,Van Meter KW,Given MB,Giles TD,, The American journal of cardiology, 1997 Feb 1     [PubMed PMID: 9036765]
[4] Zoltowska DM,Thind G,Agrawal Y,Gupta V,Kalavakunta JK, May-Thurner Syndrome as a Rare Cause of Paradoxical Embolism in a Patient with Patent Foramen Ovale. Case reports in cardiology. 2018     [PubMed PMID: 30057826]
[5] Joint position statement on persistent foramen ovale (PFO) and diving. South Paciļ¬c Underwater Medicine Society (SPUMS) and the United Kingdom Sports Diving Medical Committee (UKSDMC)., Smart D,Mitchell S,Wilmshurst P,Turner M,Banham N,, Diving and hyperbaric medicine, 2015 Jun     [PubMed PMID: 26165538]
[6] He YD,Yan XL,Qin C,Zhang P,Guo ZN,Yang Y, Transcatheter Patent Foramen Ovale Closure Is Effective in Alleviating Migraine in a 5-Year Follow-Up. Frontiers in neurology. 2019;     [PubMed PMID: 31803135]
[7] Panagopoulos D,Loukopoulou S,Karanasios E,Eleftherakis N, Recurrent arterial ischemic strokes in a patient with patent foramen ovale and ductus arteriosus: Presentation of our management and review of the literature. Global cardiology science     [PubMed PMID: 31799288]
[8] Mac Grory B,Flood SP,Apostolidou E,Yaghi S, Cryptogenic Stroke: Diagnostic Workup and Management. Current treatment options in cardiovascular medicine. 2019 Dec 3;     [PubMed PMID: 31792625]
[9] Favilla CG,Messé SR, Patent foramen ovale and stroke: current evidence and treatment options. Current opinion in neurology. 2019 Nov 27;     [PubMed PMID: 31789709]
[10] Sposato LA,Spence JD, Patent foramen ovale in patients with atrial fibrillation. International journal of cardiology. 2019 Nov 22;     [PubMed PMID: 31785956]
[11] Giordano M,Gaio G,Santoro G,Palladino MT,Sarubbi B,Golino P,Russo MG, Patent foramen ovale with complex anatomy: Comparison of two different devices (Amplatzer Septal Occluder device and Amplatzer PFO Occluder device 30/35). International journal of cardiology. 2018 Oct 16     [PubMed PMID: 30344060]