Patent Foramen Ovale (PFO)

A patent foramen ovale (PFO) is a small opening between the upper chambers of the heart that failed to close after birth. It is present in roughly one in four adults and causes no symptoms in the vast majority of people. However, in certain situations — particularly unexplained stroke in younger adults — a PFO can allow blood clots or other material to pass directly from the venous to the arterial circulation, bypassing the lungs entirely. Understanding when a PFO matters, and what to do about it, has been transformed by a generation of randomized trials completed in 2017.

Table of Contents

  1. What Is Patent Foramen Ovale?
  2. Embryology: Why the Foramen Ovale Sometimes Stays Open
  3. How Common Is PFO? Prevalence and Anatomy
  4. Right-to-Left Shunting: The Mechanism Behind PFO Complications
  5. Clinical Associations: Stroke, Migraine, and Diving Risks
  6. Diagnosis: Echo, Bubble Studies, and TCD
  7. When to Close a PFO: The Pivotal Trials and Decision Framework
  8. What to Expect: The Closure Procedure and Recovery
  9. Research Papers
  10. Connections
  11. Featured Videos

What Is Patent Foramen Ovale?

The word patent simply means open. The foramen ovale is a natural opening in the wall between the heart's two upper chambers — the right and left atria — that every human fetus needs in order to survive. In most people this opening seals shut within the first few months after birth. In about one in four adults, it never fully closes, leaving a flap-like channel that can intermittently allow blood to pass from the right atrium to the left atrium without first going to the lungs.

On its own, a PFO is not a disease. The vast majority of people who have one will live their entire lives without ever knowing it is there. A PFO only becomes medically relevant when it creates a pathway for material — a blood clot, air bubble, or fat droplet — to bypass the lungs and travel directly into the arterial circulation, a phenomenon called paradoxical embolism.

PFO size is classified by the width of the tunnel it creates:

Larger PFOs and those accompanied by a redundant, floppy interatrial septum (called an atrial septal aneurysm, or ASA) carry higher risk of clinically significant right-to-left shunting.

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Embryology: Why the Foramen Ovale Sometimes Stays Open

To understand why a PFO can persist into adulthood, it helps to understand why the foramen ovale exists in the first place. During fetal life, the lungs are collapsed and filled with amniotic fluid — they perform no gas exchange. Instead, the placenta oxygenates the blood. The fetal heart faces an unusual challenge: it must route the richest, most oxygenated blood directly to the brain and body while bypassing the non-functional lungs almost entirely.

The foramen ovale is nature's elegant solution. The interatrial septum develops from two overlapping sheets of tissue — the septum primum (the first partition to grow, arriving from the top of the atrium) and the septum secundum (a thicker, crescent-shaped ridge that grows alongside it). The septum secundum develops a gap — the foramen ovale — and the thinner septum primum acts as a one-way flap over this gap. Because right atrial pressure is higher than left atrial pressure in the fetus (the lungs are not pumping blood back to the left side), oxygenated blood returning from the placenta flows through the inferior vena cava, bounces off a ridge of tissue called the Eustachian valve, and is funneled through the foramen ovale into the left atrium, then into the left ventricle and out to the brain and body.

At birth, everything changes in an instant. The infant takes its first breath, the lungs expand and fill with air, pulmonary vascular resistance drops dramatically, and blood begins flooding the pulmonary circulation. Left atrial pressure rises and exceeds right atrial pressure. This pressure reversal presses the septum primum flap against the foramen ovale, sealing it shut — first functionally, within minutes of birth, and then anatomically, as the two layers fuse together over the following weeks to months.

In approximately 25–30% of people, this fusion never completes. The septum primum flap remains unsealed, leaving a potential channel — the patent foramen ovale — that can open whenever right atrial pressure momentarily exceeds left atrial pressure.

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How Common Is PFO? Prevalence and Anatomy

PFO is strikingly common. Autopsy studies and high-quality imaging data consistently show that 25–30% of the general adult population has a PFO. That means roughly one in four people walking around has an unsealed foramen ovale. Among young adults who suffer an unexplained ischemic stroke, the rate rises to 40–50% — nearly double the background prevalence — which is one reason PFO has attracted so much research interest as a potential stroke cause.

Several anatomical features influence how clinically significant a PFO is likely to be:

It cannot be overstated: the overwhelming majority of people with a PFO will never have a stroke, never have symptoms, and never need any treatment. PFO is a normal anatomical variant. The challenge for clinicians is identifying the minority in whom it is genuinely causative.

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Right-to-Left Shunting: The Mechanism Behind PFO Complications

Under normal resting conditions, left atrial pressure is slightly higher than right atrial pressure, so the septum primum flap stays pressed shut and no blood crosses through the PFO. The problem arises during transient spikes in right atrial pressure that can reverse this gradient and force the flap open.

Common everyday activities that transiently raise right atrial pressure and can open a PFO include:

During these moments — typically lasting only seconds — right-to-left shunting (RLS) occurs through the PFO. In most people this is harmless because there is nothing in the venous circulation dangerous enough to cause problems when it reaches the arteries. But in certain circumstances, hazardous material can be present in the venous blood at exactly the wrong moment:

The concept of paradoxical embolism was first described in the 19th century but remained theoretical until echocardiography made it possible to visualize the PFO and demonstrate right-to-left shunting in living patients.

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Clinical Associations: Stroke, Migraine, and Diving Risks

Cryptogenic Stroke — The Most Important Association

An ischemic stroke is called cryptogenic when no cause can be identified after thorough evaluation — no atrial fibrillation, no large-artery disease, no small-vessel disease, no cardiac source of embolism from a structural lesion. Cryptogenic stroke accounts for roughly 25–40% of all ischemic strokes and is particularly common in younger adults under 60 years of age.

PFO is found in approximately 40–50% of young cryptogenic stroke patients, compared with 25% of the general population. This doubled prevalence strongly suggests that PFO is causally responsible in a meaningful subset, but the challenge has always been distinguishing a PFO that caused the stroke from a PFO that is merely a bystander.

A PFO is most likely to be the true cause of a cryptogenic stroke when all of the following apply:

The RoPE score (Risk of Paradoxical Embolism) was developed to quantify how likely a given PFO is to have caused a cryptogenic stroke. It awards points for younger age, absence of traditional vascular risk factors (hypertension, diabetes, prior stroke history), and presence of a cortical infarct on imaging. Higher RoPE scores indicate that the PFO is more likely causative and that closure will likely be more beneficial.

Migraine with Aura

There is a well-documented epidemiological link between PFO and migraine with aura. PFO is found approximately twice as often in migraine-with-aura patients compared with the general population, and several mechanisms have been proposed — paradoxical passage of serotonin or other vasoactive platelet products, microemboli triggering cortical spreading depression, or shunting of hypoxic venous blood to the cerebral circulation.

Despite this intriguing association, the MIST randomized trial of PFO closure versus medical therapy for migraine prevention was negative — closure did not significantly reduce migraine frequency or severity compared with sham procedure. PFO closure is not approved or recommended for migraine prevention. Some patients do report improvement in migraines after PFO closure performed for stroke prevention, but this cannot be reliably predicted in advance.

Decompression Illness in Scuba Divers

During a scuba dive, nitrogen dissolves into tissues and blood under pressure. During ascent, if the diver rises too quickly, nitrogen comes out of solution and forms bubbles in the venous circulation. Normally these venous nitrogen bubbles are filtered by the pulmonary capillaries and expelled with each breath. In a diver with a PFO, however, a Valsalva maneuver during ascent can open the PFO and allow nitrogen bubbles to pass directly into the arterial circulation, causing neurological decompression sickness — a far more serious form than musculoskeletal "bends."

Divers with a PFO have been shown to have approximately five times the risk of neurological decompression illness compared with divers without PFO. Professional or technical divers (who dive more frequently and deeper) are strongly advised to undergo PFO evaluation. Closure is recommended for divers with documented decompression illness who wish to continue diving.

Platypnea-Orthodeoxia Syndrome

Platypnea-orthodeoxia is a rare but dramatic syndrome in which patients experience breathlessness and a fall in blood oxygen levels specifically when they stand up, which relieves when they lie down — the opposite of most cardiopulmonary conditions. In patients with PFO, standing causes a positional shift in the heart and inferior vena cava that preferentially directs venous blood toward the PFO, increasing right-to-left shunting in the upright position. Transcatheter PFO closure is highly effective and often curative in this condition.

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Diagnosis: Echo, Bubble Studies, and TCD

Diagnosing a PFO requires both demonstrating the anatomical opening and proving that it allows right-to-left shunting. Several complementary tools are available, each with different strengths.

Transthoracic Echocardiography (TTE) with Bubble Study

The agitated saline (bubble) study is the cornerstone of PFO diagnosis. A mixture of saline, air, and the patient's own blood is agitated to create microbubbles and injected into a peripheral vein. The patient performs a Valsalva maneuver (bears down) and then releases it. In a normal heart, microbubbles fill the right atrium and right ventricle but are filtered by the pulmonary capillaries and never appear on the left side. When a PFO is present, bubbles appear in the left atrium within three cardiac cycles of opacifying the right atrium — the timing distinguishes a true intracardiac shunt from a pulmonary arteriovenous malformation, where bubbles take five or more cycles to cross.

TTE with bubble study is widely available and non-invasive but has moderate sensitivity of approximately 50–60% for detecting PFO. Acoustic windows can be suboptimal, and the interatrial septum is often difficult to visualize clearly.

Transesophageal Echocardiography (TEE) with Bubble Study — Gold Standard

TEE positions the ultrasound probe in the esophagus, immediately behind the heart, giving exquisite visualization of the interatrial septum and left atrium. TEE with bubble study is the gold standard for PFO diagnosis and characterization. It accurately measures tunnel length, shunt grade, and the presence and size of an atrial septal aneurysm — all factors that influence management decisions. The main limitations are that it requires sedation, is semi-invasive, and patients must fast beforehand.

Transcranial Doppler (TCD) with Bubble Study

TCD detects microbubbles (microembolic signals, or MES) in the middle cerebral artery after intravenous agitated saline injection. It is the most sensitive technique for detecting any right-to-left shunting. TCD can be performed in an outpatient office setting, is well tolerated, and provides excellent quantification of shunt size. Its limitation is that it cannot localize the site of shunting — it cannot distinguish a PFO from a pulmonary AVM or other intracardiac defect. TCD is particularly useful for screening and for quantifying shunt size when TEE is not available or tolerated.

Additional Workup

When PFO is discovered in a patient with cryptogenic stroke, further testing is usually warranted to complete the evaluation:

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When to Close a PFO: The Pivotal Trials and Decision Framework

For many years, the question of whether to close a PFO after cryptogenic stroke was genuinely unresolved. Early trials were negative or inconclusive. Then, in 2017, three major randomized trials published simultaneously in the New England Journal of Medicine changed practice.

The Three Pivotal 2017 Trials

The CLOSE trial (Mas JL et al., PMID 28461067) randomized 663 patients aged 16–60 with recent cryptogenic stroke and PFO with either large shunt or atrial septal aneurysm to percutaneous closure, antiplatelet therapy, or anticoagulation. At a median follow-up of 5.3 years, the stroke rate was 0.4% in the closure group versus 6.0% in the antiplatelet group — a striking absolute risk reduction of 5.6 percentage points. No strokes occurred in the anticoagulation group, but that arm was not powered for definitive comparison.

The REDUCE trial (Sondergaard L et al., PMID 28460856) randomized 664 patients aged 18–59 with cryptogenic stroke to PFO closure plus antiplatelet therapy versus antiplatelet therapy alone. Ischemic stroke recurred in 1.4% of the closure group versus 5.4% of the medical therapy group at a median follow-up of 3.2 years, representing a 77% relative risk reduction.

The RESPECT Extended follow-up (Carroll JD et al., PMID 28460366) reported long-term results of 980 patients followed for a median of 5.9 years. The originally neutral RESPECT trial became significantly positive at extended follow-up: percutaneous closure reduced the risk of recurrent ischemic stroke by 62% compared with medical therapy alone.

Earlier trials — including CLOSURE I (Furlan AJ et al., PMID 23663127) using an earlier-generation device — had been negative, likely due to suboptimal device design and patient selection. The 2017 trials used the Amplatzer PFO Occluder with more rigorous patient selection criteria.

Current Recommendations

Based on these trials, percutaneous PFO closure is now recommended for secondary stroke prevention in patients meeting all of the following criteria:

For patients who do not meet these criteria — older patients, those with small PFOs, or those in whom another stroke mechanism is plausible — antiplatelet therapy (aspirin) or anticoagulation (in selected cases) remains the first-line approach. The decision should be made by a multidisciplinary team including a cardiologist with expertise in structural heart disease and a neurologist.

The RoPE Score in Practice

The RoPE score assigns points based on age, presence of cortical infarct, and absence of traditional vascular risk factors. Scores range from 0 to 10. A patient who is 30 years old, has a cortical stroke on MRI, no hypertension, no diabetes, and no prior stroke history might score 9 — meaning the PFO is highly likely to be causative and closure is strongly favored. A 58-year-old with hypertension, diabetes, and a deep lacunar infarct might score 3 — meaning the PFO is probably incidental and treatment should focus on vascular risk factor control.

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What to Expect: The Closure Procedure and Recovery

The Device

The Amplatzer PFO Occluder (Abbott) received FDA approval in 2016 and is the device used in virtually all randomized trials demonstrating benefit. It consists of two nitinol wire mesh discs connected by a short waist. The right atrial disc is larger than the left atrial disc. When deployed, the two discs straddle the interatrial septum and sandwich the PFO closed, held in place by the tissue on either side. Over the following three to six months, the heart's own tissue grows over the device, permanently sealing it in place.

The Procedure

PFO closure is performed in a cardiac catheterization laboratory. Patients are usually under moderate sedation (conscious sedation or general anesthesia) with TEE or intracardiac echocardiography (ICE) guidance to monitor device placement in real time. The procedure takes approximately 30–60 minutes:

  1. A catheter is inserted through a vein in the groin (femoral vein) and advanced into the right atrium under fluoroscopic (X-ray) guidance.
  2. The catheter is guided through the PFO into the left atrium.
  3. The left atrial disc is deployed and pulled back against the left side of the septum.
  4. The right atrial disc is deployed on the right side of the septum.
  5. Imaging confirms correct positioning, no significant residual shunt, and no impingement on surrounding structures.
  6. The device is released and the catheter withdrawn.

Technical success — defined as device deployment without major complications — is achieved in over 95% of cases. Patients are typically discharged the same day or after one night of observation.

Post-Procedure Medications

Until the device is fully covered with tissue (usually six months), patients take aspirin plus clopidogrel (dual antiplatelet therapy) to reduce the risk of clot formation on the device surface. After six months, most patients continue aspirin alone indefinitely, though individual plans vary by physician and patient factors.

Risks and Side Effects

PFO closure is considered a low-risk procedure, but as with any invasive intervention, complications can occur:

Long-Term Outlook

For appropriately selected patients — young adults with cryptogenic stroke and high-risk PFO features — PFO closure is highly effective at preventing recurrent stroke. In the pivotal trials, the absolute risk of recurrent stroke in the closure group was less than 1–2% over five or more years of follow-up, compared with 5–6% in the medical therapy group. Patients can generally return to normal activities, including exercise, within a few days to weeks. Most professional and recreational divers can return to diving after confirmed closure at follow-up bubble study, typically six months after the procedure.

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Research Papers

The following peer-reviewed publications form the evidence base for understanding and managing patent foramen ovale.

PubMed Topic Searches

  1. PFO closure and cryptogenic stroke — PubMed
  2. Paradoxical embolism and PFO — PubMed
  3. PFO and decompression illness in divers — PubMed
  4. RoPE score and PFO — PubMed
  5. Amplatzer PFO Occluder outcomes — PubMed
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Connections

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