What Does a Positive Bubble Study Indicate?

A positive bubble study indicates that blood is crossing from the right side of the heart to the left through an abnormal pathway, known as a right-to-left shunt. Normally, the lungs act as a filter that traps the tiny microbubbles injected during the test, so none should appear on the left side of the heart. When they do, it means something is letting them through, and the most common culprit is a patent foramen ovale, a small flap-like opening between the upper chambers of the heart that never fully closed after birth. But the timing of when those bubbles show up, how many appear, and whether you needed a specific breathing maneuver to provoke them all shape what the result actually means for you.

Why the Lungs Normally Stop the Bubbles

The test works because of a simple size mismatch. When a technician rapidly mixes saline between two syringes and injects it into your vein, the agitation creates microbubbles whose smallest diameter is roughly 24 micrometers. The capillaries in your lungs, where blood picks up oxygen, are smaller than 15 micrometers in diameter.¹ That means normal lung capillaries physically cannot let the bubbles pass. They get trapped and dissolve harmlessly on the right side of the circulation. If bubbles show up on the left side of the heart on echocardiography, something besides normal lung capillaries is carrying them across.

Early Bubbles Versus Late Bubbles

Not all positive bubble studies mean the same thing. The single most important clue is how quickly bubbles appear in the left heart after the right side fills with contrast. Current guidelines generally place the dividing line between three and six cardiac cycles, and research has refined that cutoff further. If bubbles appear in the left heart within the first four cardiac cycles, a patent foramen ovale (PFO) is the most likely explanation; bubbles arriving at or after the fifth cycle point instead toward an intrapulmonary shunt, meaning the abnormal passage is inside the lungs rather than in the heart itself.²

The logic is straightforward. A PFO is a direct hole between the right and left atria, so bubbles can slip through almost instantly. An intrapulmonary shunt, by contrast, requires the bubbles to travel through abnormally dilated vessels in the lung before returning to the left atrium, which takes several extra heartbeats. One case report illustrating the distinction described agitated saline contrast arriving in the left chambers after roughly six cardiac cycles, with the late arrival considered diagnostic of an intrapulmonary shunt rather than a cardiac defect.³ Getting this distinction right matters because the causes, risks, and treatments for cardiac shunts and lung shunts are very different.

The Valsalva Maneuver and Why You Are Asked to Bear Down

During many bubble studies, you will be asked to perform a Valsalva maneuver: essentially bearing down as if straining, then releasing. This is not just a formality. A PFO can be functionally closed most of the time, only opening when pressure conditions briefly favor it. The Valsalva maneuver creates exactly those conditions. During the straining phase, increased chest pressure reduces blood return to the right heart, and left heart filling also drops because less blood comes through the lungs. After you release the strain, blood rushes back into the right atrium from the large veins, and right-sided pressure transiently exceeds left-sided pressure. That pressure reversal pushes the flap of the foramen ovale open, and any microbubbles sitting in the right atrium flood through into the left atrium.⁴

A study that had PFO patients undergo bubble studies both with and without Valsalva found that the strain phase sometimes produced only a few scattered microbubbles crossing through, while the release phase, when right atrial pressure was significantly higher than left atrial pressure, filled the left atrium with a large number of microbubbles.⁴ Without the Valsalva, many PFOs would be missed entirely because the pressure difference needed to open the flap never occurs during quiet rest.

Patent Foramen Ovale as the Most Common Finding

About one in four adults has a PFO that can be detected by careful testing. In most of these people, the opening causes no symptoms whatsoever. It is a leftover from fetal circulation, where blood needed to bypass the lungs since the fetus got oxygen from the placenta. After birth, the flap usually seals shut, but in a large fraction of people it remains open to some degree.

The reason a positive bubble study matters clinically is that a PFO can serve as a conduit for paradoxical embolism. A blood clot that forms in the veins, which would normally travel to the lungs and get filtered there, can instead cross through the PFO into the arterial circulation and lodge in the brain, causing a stroke. Right-to-left shunts, mainly due to PFO, are thought to be responsible for roughly 5% of all ischemic strokes and about 10% of those occurring in young and middle-aged adults.⁵ PFO is considered an important cause of embolic cryptogenic stroke, especially in younger patients, with paradoxical embolism as the underlying mechanism.⁶

Intrapulmonary Shunts and Liver Disease

When bubbles arrive late, the problem usually lies in the lungs rather than the heart. Pulmonary arteriovenous malformations (PAVMs) are abnormal direct connections between pulmonary arteries and veins that let blood, and bubbles, bypass the capillary bed. These are most commonly associated with a hereditary condition called hereditary hemorrhagic telangiectasia, though they can occur for other reasons as well.

The grading of the bubble study can help predict whether a PAVM will actually show up on a CT scan. In one study, none of the patients with a negative bubble study or only a minimal positive result (grade 1) had PAVMs visible on thoracic CT. Among those with a moderate positive result (grade 2), a quarter had PAVMs on CT, while 80% of those with a grade 3 result and all patients with grade 4 had confirmed PAVMs.⁷ The bubble study, in other words, does not just tell you whether something abnormal exists; the amount of contrast that crosses gives clinicians a sense of how significant the abnormality is and whether further imaging is warranted.

Advanced liver disease can also cause a late-positive bubble study through a completely different mechanism. In hepatopulmonary syndrome, the tiny blood vessels in the lungs become abnormally dilated, growing wide enough for microbubbles to pass through without getting trapped. Microbubble contrast echocardiography with a late positive signal enables the detection of this kind of intrapulmonary vascular dilation in patients with end-stage liver disease.⁸ For people being evaluated for liver transplant, a positive bubble study can be the finding that clinches the diagnosis of hepatopulmonary syndrome and changes the urgency of their listing.

How Shunt Size Is Graded and Why It Matters for Treatment

A positive bubble study is not simply positive or negative; the number of bubbles that cross and the context in which they cross influence clinical decisions. For PFO specifically, a large shunt is often defined as more than 20 microbubbles appearing in the left atrium within three cardiac cycles on transesophageal echocardiography. This threshold is significant because the major randomized trials that showed benefit from PFO closure used it as a criterion for intervention in patients who had already had a cryptogenic ischemic stroke.⁹

Clinicians also use clinical scoring tools like the RoPE (Risk of Paradoxical Embolism) score, which combines patient characteristics and imaging features to estimate how likely it is that a detected PFO actually caused the stroke rather than being an incidental finding. Analysis of major closure trials found that the RoPE score’s estimated attributable fraction correlated closely with the benefit patients got from closure, suggesting the score is good at sorting out pathogenic PFOs from innocent bystanders.¹⁰ Higher RoPE scores support the decision to proceed with device closure, while lower scores suggest the PFO may not be the culprit and closing it may not help.¹¹

Different Ways of Running the Test

Bubble studies can be performed through several imaging approaches, each with trade-offs. Transthoracic echocardiography (TTE) is the least invasive: a standard ultrasound probe on the chest wall while agitated saline is injected into an arm vein. It is widely available and inexpensive, but its sensitivity for detecting right-to-left shunts is moderate. A meta-analysis of 35 studies covering more than 4,200 patients found TTE with contrast had a sensitivity of about 73% and a specificity of about 94% compared with transesophageal echocardiography as the reference standard.¹² That means TTE is very good at confirming a shunt when bubbles do cross, but it misses roughly a quarter of shunts that a more sensitive test would catch.

Transesophageal echocardiography (TEE) places the ultrasound probe in the esophagus, directly behind the heart, giving a much clearer view. One study in patients with embolic stroke of undetermined source found TEE achieved a sensitivity of about 95% and the highest overall accuracy among the modalities compared.¹³ The downsides are that it requires mild sedation and involves swallowing the probe, which is uncomfortable. TEE is considered necessary when treatment decisions hinge on the result, because it can visualize the anatomy of the PFO itself and measure features like the size of the opening or the presence of an atrial septal aneurysm.¹⁴

Transcranial Doppler (TCD) takes a different approach entirely. Instead of imaging the heart, it monitors blood flow in the brain’s arteries using a probe on the temple. When microbubbles reach the brain circulation, they produce distinctive “hits” on the Doppler signal. TCD is considered an accurate, easily accessible screening method and an excellent alternative to echocardiography for initial detection, though it cannot tell you the anatomical details of the shunt.¹⁴ The combination of TCD for screening and TEE for anatomical detail provides the most complete diagnostic picture.

False Positives and False Negatives

Bubble studies are not perfect. PFO researchers have used varying criteria to define what counts as a positive study, and there are multiple mechanisms by which saline contrast can produce both false-positive and false-negative results.¹⁵ A false positive can occur if a small amount of contrast is manufactured within the left heart itself due to ultrasound beam interaction with certain blood components, or if a single stray bubble is mistaken for a shunt. False negatives happen more commonly: if the Valsalva maneuver is poorly timed relative to the saline injection, the brief window during which right atrial pressure exceeds left atrial pressure may be missed, and the PFO never opens. Inadequate agitation of the saline, which produces fewer or larger bubbles, can also reduce sensitivity.

Rare vascular anomalies can produce unexpected patterns as well. A persistent left superior vena cava, a congenital variant where an extra vein drains into the coronary sinus instead of the usual route, can cause the coronary sinus to appear dilated on echocardiography and can be confirmed by the characteristic pattern of contrast flow during a bubble study.¹⁶ This is not a right-to-left shunt in the conventional sense, but the unusual contrast pattern may initially be confused with one.

What Happens After a Positive Result

Finding a shunt on a bubble study does not automatically mean you need a procedure. The clinical context determines everything. For someone who has never had a stroke and whose PFO was discovered incidentally, the standard approach is to leave it alone. PFOs are too common for routine closure to make sense in asymptomatic people.

For patients who have had a cryptogenic stroke, the evidence favors closure in the right circumstances. A meta-analysis of all randomized clinical trials comparing PFO closure with medication alone found that closure cut the rate of recurrent stroke by more than half compared with medical therapy.¹⁷ A network meta-analysis similarly found that PFO closure was associated with a reduced risk of recurrent ischemic stroke, though it also noted an increased risk of new-onset atrial fibrillation, a trade-off that comes from the device irritating the heart tissue during healing.¹⁸ The atrial fibrillation risk is generally temporary and often resolves within weeks to months, but it is something patients and their cardiologists weigh against the long-term stroke reduction benefit.

For intrapulmonary shunts caused by PAVMs, treatment usually involves blocking the abnormal vessels with embolization rather than cardiac closure devices. For hepatopulmonary syndrome, the definitive treatment is liver transplantation, after which the pulmonary vascular dilation typically resolves.

How Safe Is the Test Itself

The bubble study is one of the safer cardiac diagnostic procedures. The agitated saline is just salt water with room air, and the microbubbles dissolve within seconds. In a review of 924 bubble studies, only one patient (about 0.1%) experienced a transient ischemic attack as a complication.¹⁹ When commercial ultrasound contrast agents (rather than plain agitated saline) are used for enhanced cardiac imaging, a review of over 5,500 administrations found adverse events in only about 0.25% of cases, with the most common complaints being back pain and headache, and no adverse events among patients known to have intracardiac shunts.²⁰

Connections to Migraine and Diving

Beyond stroke, a positive bubble study showing a PFO has interesting connections to two other conditions that patients often ask about. Migraine with aura has been linked to PFO in multiple studies. Among patients with both cryptogenic stroke and migraine, nearly 80% were found to have a PFO, compared with about 59% of cryptogenic stroke patients without migraine. In those who specifically had frequent aura, 93% had a PFO.²¹ The hypothesis is that small venous blood clots or vasoactive chemicals that would normally be filtered by the lungs can cross through the PFO and trigger migraine events in the brain. That said, trials of PFO closure for migraine alone have produced mixed results, and closure is not currently a standard migraine treatment.

Scuba divers have a particular reason to care about PFO. During ascent, dissolved nitrogen in the blood can form small bubbles. In most people, the lungs filter these out. In a diver with a PFO, nitrogen bubbles can cross into the arterial circulation and cause decompression sickness even after dives that stayed within recommended safety limits. Research has found that PFO plays a significant role in unexplained cerebral decompression sickness in sports divers, though not in spinal decompression sickness.²² Divers who have experienced unexplained neurological decompression illness are sometimes referred for bubble studies, and a positive result may lead to recommendations about conservative dive profiles or, in some cases, PFO closure.

A rarer condition called platypnea-orthodeoxia syndrome, where blood oxygen drops when sitting upright and improves when lying down, can also be diagnosed with the help of a positional bubble study. In one case, a transcatheter bubble test showed minimal right-to-left shunting while the patient was lying on their left side but massive shunting when sitting up, confirming the diagnosis.²³ The positional change alters the geometry of the heart enough to open a shunt that stays closed in other positions, a phenomenon that is easy to miss on a standard supine echocardiogram.