• before birth, the atrial septum is formed by two leaves. After birth, the pressure rises in the left atrium, and the two leaves fuse together
  • in 1/3 of people, the leaves do not fuse, and a different-sized opening called a patent foramen ovale (PFO) or foramen ovale apertum (FOA) persist
  • PFO causes a right-to-left shunt – blood can flow from the right atrium directly into the left atrium, bypassing the pulmonary circulation
  • various particles in the blood can bypass the pulmonary circulation together with the blood and enter the systemic circulation (paradoxical embolism)
    • small blood clots released from the veins of the lower limbs and pelvis
    • gas bubbles (formed during rapid decompression in scuba divers or administered by IV injections)
    • certain hormones (serotonin in migraine with aura?)
  • PFO alone does not cause hemodynamic problems
  • PFO is not the only cause of right-to-left shunting:
    • intracardiac shunts (90%) – patent foramen ovale (PFO), atrial septal defects
    • extracardiac shunts (10%) – mostly pulmonary AV shunts
    • combination of extra- and intracardiac shunts is possible
Patent Foramen Ovale (PFO)

PFO and cryptogenic stroke

  • patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), though the pathogenicity of discovered PFO in the setting of CS is typically unclear
    • the prevalence of PFO is approx. 25% in the general population and up to 46% in patients with CS
  • PFO is occasionally associated with the following conditions:
    • atrial septal aneurysm (ASA) /  hypermobile atrial septum – defined as excursion ≥ 10-15 mm from the midline Atrial septal aneurysm on TEE Patent Foramen Ovale (PFO) and Atrial Septal Aneurysm (ASA)
    • atrial septal defect
  • PFO-related stroke mechanisms:
    • paradoxical embolization from peripheral veins
    • embolization of a thrombus formed directly within the PFO canal
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Diagnostic evaluation

PFO detection

Contrast-enhanced transesophageal echocardiography (cTEE)

  • 2D or 3D + bubble test – sensitivity and specificity between 89-95%
  • information on PFO shape and size and associated pathologies (ASA, septal hypermobility, LAA thrombus, etc.)
  • disadvantages:
    • invasive nature of the procedure; some patients may not tolerate it
    • lower sensitivity for small PFOs
Patent Foramen Ovale on TEE with positive bubble test

TCD/TCCD bubble test

  • non-invasive screening method → see here
  • detects all right-to-left shunts (cardiac and extracardiac)
  • sensitivity and specificity reported over 90%
TCD/TCCD bubble test with proof of right-to-left shunt (grade II-IV)

Cardiac MRI/CTA

  • can be performed in patients who cannot tolerate TEE
  • provides information on potential thrombi and other pathology
  • may also be useful for monitoring PFO occlusion
Patent foramen ovale on cardiac CTA
Postcontrast MRI with detection of right-to-left shunt after contrast agent administration (left image). Amplatzer occluder on cardiac MRI (right image)

Other methods

Doppler ultrasound / MR venography

  • detection of a possible source of embolism in pelvic and lower extremity veins
Right-sided deep vein thrombosis on the utrasound examiantion
MR venography showing thrombosis of the right femoral vein. Large arrow shows hypointense thrombus, small arrow edema.


  • normal levels:  0.068-0.494 mg/L
  • level <0.5 mg/L makes DVT unlikely but not impossible
  • false-positive results are common


  • primary prevention: PFO closure not indicated
  • secondary prevention:  consider antiplatelet or anticoagulant therapy and PFO closure
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PFO and migraine

  • a higher prevalence of PFO has been reported in patients with migraine with aura than in patients with migraine without aura or patients without migraine (48% vs. 23% and 20%, respectively).
  • the causal association remains unclear
  • some small non-randomized trials have reported a reduced incidence of migraine after PFO closure
  • randomized trials MIST  (Starfix, 2016) and PREMIUM (Amplatzer, 2017) did not show a preventive effect
    • MIST –  primary outcome: migraine regression in 3 of 74 (occlusion) vs. 3 of 74 (control), significant complications (SAEs) in 16 of 74 patients
    • PREMIUM – primary outcome: 45/117 (Amplatzer) vs. 33/103 (control)
  • in conclusion, it is less likely that PFO plays a role in the development of migraine headache
  • the role of PFO in the development of ischemic stroke in migraineurs has not been determined yet
    • patients with both migraine and stroke had larger shunts than patients with migraine without stroke, patients without migraine with stroke, and controls 
    • concerning the white matter hyperintensities (WMH), overall WMH did not differ by PFO presence; however, juxtacortical WMHs are more frequently found in patients with migraine and right-to-left shunting
    • these findings suggest that incidental PFO may increase the risk of ischemic stroke in migraineurs

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Patent foramen ovale (PFO)
link: https://www.stroke-manual.com/patent-foramen-ovale-pfo/