Does early passage of many bubbles consistent with an interatrial shunt indicate a large patent foramen ovale (PFO)?

Interpretation of Agitated Saline Contrast Study in Patent Foramen Ovale Assessment

Early passage of many bubbles during an agitated saline contrast study strongly indicates a large patent foramen ovale (PFO). The presence of "many bubbles" with early passage across an interatrial shunt represents a large PFO with significant right-to-left shunting, which carries higher clinical risk compared to small PFOs.

Quantification of PFO Size by Bubble Study

The size of a PFO is typically classified based on the number of microbubbles that cross the interatrial septum:

• Small PFO: 3-19 microbubbles
• Large PFO: ≥20 microbubbles 1

The REDUCE trial specifically defined PFO shunt sizes as 2:

• Moderate: 6-25 microbubbles
• Large: >25 microbubbles

Clinical Significance of Large PFOs

Large PFOs with significant right-to-left shunting have important clinical implications:

1. Higher stroke risk: Patients with large shunts (≥20 microbubbles) have a significantly higher risk of subsequent neurologic events (31%) compared to those with small shunts (0%) 1

2. Treatment implications: The CLOSE trial demonstrated that PFOs associated with large interatrial shunts (>30 microbubbles within three cardiac cycles) had better outcomes with closure versus medical therapy alone 2

3. Paradoxical embolization risk: Large PFOs increase the risk of death (relative risk 2.4), ischemic stroke (relative risk 5.9), and peripheral arterial embolism (relative risk 15) in patients with conditions like pulmonary embolism 2

Diagnostic Approach

The gold standard for PFO assessment is transesophageal echocardiography (TEE) with bubble study 3, but transthoracic echocardiography (TTE) with bubble study is commonly used for initial screening:

• Timing: Early passage is defined as bubbles appearing in the left atrium within 3-4 cardiac cycles of right atrial opacification 3
• Quantification: Count the maximum number of microbubbles in the left heart in any single frame after contrast injection 1
• Provocative maneuvers: Valsalva maneuver should be performed to increase sensitivity by temporarily increasing right atrial pressure 3

Clinical Management Implications

The finding of a large PFO has significant management implications:

• Cryptogenic stroke patients ≤60 years: Consider PFO closure, particularly with high Risk of Paradoxical Embolism (RoPE) scores >6 3
• Presence of atrial septal aneurysm: Increases embolic risk and strengthens the case for closure 2
• Antiplatelet vs. anticoagulation: Antiplatelet therapy is standard for most cryptogenic strokes, but anticoagulation may be considered with concurrent venous thromboembolism 3

Potential Pitfalls in Interpretation

• False positives: Pulmonary arteriovenous malformations can also cause right-to-left shunting with positive bubble studies
• Incidental findings: PFOs are common in the general population (25-27%) 2, 4 and may be incidental rather than pathogenic
• Patient selection: Bubble studies are frequently performed in patients who have readily identifiable causes of stroke and whose PFO is likely incidental 5

Remember that while the finding of many bubbles with early passage indicates a large PFO, clinical context remains crucial for determining its significance and appropriate management strategy.