Patent Foramen Ovale: Causes, Diagnosis, and Treatment

A patent foramen ovale, usually called a PFO, is a small flap-like opening between the two upper chambers of the heart that every human has before birth but that fails to seal shut in roughly one in four adults. It is not a disease you “catch” or a defect caused by something that went wrong during pregnancy; it is a leftover piece of normal fetal anatomy that simply never completed its natural closure. Most people who have one will never know it and never need treatment. The opening becomes medically relevant only when it allows blood clots or other material to cross from the right side of the heart to the left, potentially reaching the brain or other organs.

Why the Opening Exists in the First Place

Before birth, a fetus does not breathe with its lungs. Oxygen arrives through the placenta and umbilical cord, meaning blood has no reason to make the full trip through the lungs the way it does after delivery. To keep things efficient, fetal circulation includes several built-in shortcuts. One of the most important is the foramen ovale, a window between the right and left atria that lets oxygen-rich blood coming from the placenta flow directly into the left side of the heart and out to the body. The foramen ovale works together with another bypass called the ductus venosus, and together these structures form a key distribution system that routes the best-oxygenated blood where the developing fetus needs it most, particularly the brain and heart muscle.¹

At birth, a baby takes its first breath and the lungs fill with air. Blood pressure on the left side of the heart rises as blood now flows through the lungs and returns to the left atrium. That increased left-sided pressure pushes a thin flap of tissue, the septum primum, against the thicker septum secundum, effectively sealing the foramen ovale shut like a one-way valve. In mouse models, which mirror human cardiac development, this functional closure happens within the first week of life, and true tissue fusion between the two septal layers occurs over the following weeks to months.² In humans, the timeline is similar in concept but longer: some studies suggest tissue fusion can take months or even years, and in about a quarter of people it never happens at all. When that flap stays unsealed, the result is a PFO.

Why Some PFOs Never Close

The honest answer is that researchers do not fully understand why the foramen ovale closes in some people and stays open in others. Animal research and limited human genetic data point to a robust genetic component, but no single gene has been identified as the culprit.³ There is likely a spectrum: some people are born with a septum primum that is just too small or too floppy to stay pressed against the septum secundum, while in others the overlap between the two layers may be minimal. Because PFO is so common and almost always harmless, there has been relatively little pressure to pin down the genetics the way there has been for rarer congenital heart defects. What we can say is that having a PFO does not mean something went “wrong” developmentally. It is better understood as one end of normal anatomical variation.

When a PFO Becomes a Problem

The vast majority of people with a PFO live their entire lives without a single symptom. The opening sits there, functionally irrelevant, because normal left-sided heart pressure keeps the flap pressed shut most of the time. Problems arise when the pressure balance tips. Anything that briefly raises pressure on the right side of the heart, such as straining, coughing, or bearing down during a bowel movement, can momentarily open the flap and allow a small amount of blood to cross from right to left. If a blood clot happens to be sitting in the venous system at that moment, it can slip through the PFO, bypass the lungs where it would normally get trapped, and travel to the brain or another organ. This is called paradoxical embolism, and it is considered the primary way a PFO causes stroke.⁴

Strong support for this mechanism comes from studies of patients with pulmonary embolism, a condition in which clots form in the veins and travel to the lungs. Among those patients, the rate of recent stroke is higher in people who also have a PFO, which makes sense if clots are crossing through the opening before they reach the lungs.⁵

How the Valsalva Maneuver Opens the Flap

The Valsalva maneuver, the act of bearing down against a closed airway, is central to PFO physiology and diagnosis. When you strain, intrathoracic pressure rises. That increased pressure makes it harder for venous blood to return to the right heart, so the right atrium briefly empties out. Meanwhile the left ventricle keeps pumping, so left-sided pressures stay relatively high. At this stage, the PFO flap stays shut. The key moment comes right after the strain is released. Intrathoracic pressure drops suddenly, and the pooled venous blood rushes back into the right atrium all at once, causing a transient spike in right atrial pressure that exceeds left atrial pressure. That reversal pops the flap open, and anything in the right atrium, including a clot, can cross over.⁶ This is why doctors specifically look for a history of straining or coughing right before the onset of stroke symptoms when they suspect a PFO-related event.

Exercise can compound the effect. In stroke patients who had undergone PFO closure, researchers showed that vigorous physical exertion combined with a Valsalva strain could temporarily resurrect a right-to-left shunt even after the device was in place, though the clinical significance of this finding remains uncertain.⁶

Features That Raise the Risk

Not all PFOs carry the same level of risk. Two anatomical features stand out. The first is shunt size: a larger opening allows more blood to cross. The second is the presence of an atrial septal aneurysm, or ASA, a condition in which the tissue between the atria is abnormally mobile and bulges back and forth. When both features are present together, the risk of stroke climbs substantially. A meta-analysis found that PFO patients with an accompanying ASA had roughly three and a half times the odds of cryptogenic stroke compared to PFO patients without one.⁷

This distinction matters for treatment decisions too. An analysis pooling data from three major closure trials found that the benefit of closing a PFO was greatest in patients who had both a large shunt and an ASA. In that subgroup, the absolute risk of recurrent stroke dropped by about five and a half percentage points over two years compared to medical therapy. Patients with a small shunt and no ASA saw almost no measurable benefit from closure.⁸ The same analysis validated a clinical scoring tool called the RoPE score, which estimates the likelihood that a given patient’s PFO is actually the cause of their stroke rather than an innocent bystander. The higher the score, the more likely closure will help.

Conditions Linked to PFO Beyond Stroke

Stroke gets the most attention, but PFO has been linked to several other conditions, each with varying strength of evidence.

Migraine with aura: The association here is striking. Among migraine patients who experience aura, the reported prevalence of PFO ranges from roughly 46% to as high as 88%, compared with 16% to 35% in migraine patients without aura.⁹ The theory is that small venous substances, possibly micro-clots or vasoactive chemicals, bypass the lung filter through the PFO and trigger aura. Despite the epidemiological link, clinical trials of PFO closure for migraine have produced mixed results, and closure is not currently a standard migraine treatment.
Decompression sickness in divers: Scuba divers with a PFO face a higher risk of decompression sickness because nitrogen bubbles that form in venous blood during ascent can cross through the opening into the arterial circulation instead of being filtered out by the lungs.¹⁰ Some dive medicine specialists now recommend screening for PFO in divers who have experienced unexplained decompression illness, and transcatheter closure has been reported to reduce recurrence in those with large shunts.
Platypnea-orthodeoxia syndrome: This rare but dramatic condition causes breathlessness and low oxygen levels when a person sits or stands upright, with improvement upon lying down. In select patients, a PFO allows deoxygenated blood to shunt into the left atrium when upright, and closing the PFO can resolve the symptoms entirely.¹¹

How PFO Is Diagnosed

A PFO cannot be detected with a standard physical exam or a routine electrocardiogram. Diagnosis relies on imaging that can visualize or infer the passage of blood (or a contrast agent) from the right side of the heart to the left.

The most common first step is a transthoracic echocardiogram with a “bubble study.” A saline solution is agitated to create tiny microbubbles and injected into a vein while the patient performs a Valsalva maneuver. If bubbles appear in the left atrium within a few heartbeats, a right-to-left shunt is present. This test is noninvasive and widely available, but its sensitivity depends heavily on technique, particularly how well the patient performs the Valsalva and how high-quality the bubble injection is. A high-quality bubble injection has been identified as the single most important factor in detecting a larger shunt across all echocardiographic methods.¹²

Transesophageal echocardiography, where an ultrasound probe is passed into the esophagus for a closer view of the heart, provides better anatomical detail and is considered the reference standard for confirming PFO and measuring shunt size. Newer three-dimensional transesophageal techniques have shown the ability to reclassify a meaningful proportion of patients. In one study, applying a 3D protocol changed the diagnosis in about one in ten patients and increased the number classified as having a definite PFO from 13% to 23%.¹³

For screening purposes, contrast-enhanced transcranial Doppler is an attractive option. Rather than imaging the heart directly, it detects microbubbles arriving in the brain’s blood vessels after injection. A recent meta-analysis found that this method has about 95% sensitivity and 90% specificity for PFO detection when compared to transesophageal echocardiography, making it a strong first-line screening tool.¹⁴ A negative result on transcranial Doppler meaningfully lowers the chance that a clinically significant PFO is present, while a positive result usually prompts confirmatory transesophageal imaging to map the anatomy before any treatment decision. The Valsalva maneuver during any of these tests is essential; without it, false-negative results are common.¹⁵

Medical Treatment After a PFO-Related Stroke

When a patient has a stroke attributed to a PFO but is not a candidate for closure, or when the stroke risk is judged to be low, the standard approach is long-term medication to prevent blood clots. The two main options are antiplatelet drugs like aspirin and oral anticoagulants like warfarin or newer direct oral anticoagulants. You might expect anticoagulants to be clearly better, given that the underlying mechanism involves clots, but the evidence is surprisingly murky. A large individual-patient-data meta-analysis comparing the two approaches found no statistically significant difference in the combined rate of stroke, transient ischemic attack, and death.¹⁶ The CLOSE trial did show a numerically lower stroke rate with anticoagulants compared to antiplatelets, but the numbers were small.¹⁷ In practice, the choice often depends on each patient’s bleeding risk, tolerance of long-term medication, and physician preference.

Closure Devices and Their Benefits

The most definitive treatment for a high-risk PFO is transcatheter closure. A small device, typically a double-disc structure made of a nickel-titanium alloy called nitinol, is threaded through a vein in the groin up to the heart and deployed across the opening. The discs sandwich the septal tissue, and over months the body’s own tissue grows over the device, permanently sealing the gap.

Multiple randomized trials have now shown that closure reduces the risk of recurrent stroke compared to medication alone in appropriately selected patients. The RESPECT trial, one of the largest, found that PFO closure roughly halved the rate of recurrent ischemic stroke over long-term follow-up.¹⁸ A systematic review encompassing several trials confirmed a consistent reduction in both stroke and transient ischemic attack rates with closure, and found that overall mortality was similar between the two approaches, underscoring that closure is generally safe.¹⁹

The key qualifier is “appropriately selected.” European guidance on PFO management emphasizes a two-axis framework: how likely is it that the PFO actually caused the clinical event, and how likely is the event to recur? Patients in whom both probabilities are high are the strongest candidates for closure. When both are low, medication alone is reasonable. For everyone in between, the decision requires shared conversation between the patient and a multidisciplinary team.²⁰

Risks of Closure

PFO closure is a relatively low-risk procedure, but it is not risk-free. The most discussed complication is new-onset atrial fibrillation. Earlier studies estimated the incidence at roughly 3% to 7%, but more recent work using more rigorous monitoring has pushed that figure as high as 21%, suggesting that many cases were simply going undetected before.²¹ The reassuring side of this is that post-closure atrial fibrillation tends to peak around two weeks after the procedure and typically resolves on its own within about 45 days. It is generally considered a temporary irritation from the device sitting against the atrial tissue rather than a permanent heart rhythm problem.²² When it does not resolve spontaneously, rhythm-control medications can be used, and anticoagulation is tailored to the individual patient’s risk profile.

A less common but increasingly recognized issue involves nickel sensitivity. Because most closure devices are made of nitinol, individuals with a nickel allergy can develop systemic reactions after implantation, including chest pain, palpitations, headaches, shortness of breath, and skin rashes. The incidence of device-related symptoms appears to be higher in nickel-sensitive patients than in the general closure population.²³ Management is largely trial-and-error, involving corticosteroids, antihistamines, or in stubborn cases, removal of the device. Some centers now screen for nickel allergy before closure, though there is no universal protocol.

PFO in Divers

Recreational and professional divers occupy a unique niche in PFO medicine. During a dive, nitrogen dissolves into the blood under pressure. On ascent, that nitrogen comes out of solution and forms tiny bubbles in the venous circulation. In most people, these bubbles travel to the lungs and are harmlessly exhaled. In a diver with a PFO, however, the bubbles can cross into the arterial side and cause decompression sickness, which can range from joint pain and skin rashes to neurological injury. A screening and risk-stratification approach using echocardiography has been shown to reduce the occurrence of decompression sickness in divers found to have a PFO, and transcatheter closure has been reported to help those with large shunts.¹⁰ Not every diver with a PFO needs closure; conservative measures like slower ascent rates and shallower dive profiles can reduce risk. But for serious divers who have already had decompression illness and are found to have a significant right-to-left shunt, closure is a reasonable option to discuss with a cardiologist experienced in dive medicine.

Should You Be Screened for PFO?

Given that about one in four people has a PFO, you might wonder whether everyone should be tested. The short answer is no. Screening the general population would identify millions of PFOs that will never cause harm, generating anxiety and potentially leading to unnecessary procedures. The current approach is event-driven: you get tested if you have had a stroke without an obvious cause (cryptogenic stroke), unexplained decompression sickness, or one of the rarer associated syndromes. Even among younger stroke patients, a PFO is sometimes found incidentally and turns out to be unrelated. Tools like the RoPE score help clinicians sort out which PFOs are culprits and which are bystanders.⁸ If you have not had any of these events, discovering a PFO on a scan done for another reason is not a call to action. It is a common anatomical finding, comparable to learning you have a freckle on the inside of your heart.