When is an echo with bubble study (contrast echocardiogram) recommended in a stroke patient with suspected cardiac source of embolism, such as patent foramen ovale (PFO)?

When to Perform Echo with Bubble Study in Stroke Patients

Perform an echocardiogram with bubble study (agitated saline contrast) in stroke patients when you suspect a cardiac source of embolism, specifically when evaluating for patent foramen ovale (PFO) in cryptogenic stroke patients, particularly those younger than 60 years of age. 1

Primary Indications for Bubble Study

Cryptogenic Stroke Evaluation

• Order a bubble study when the stroke remains unexplained after ruling out other causes including atrial fibrillation (via prolonged rhythm monitoring), large artery atherosclerosis (via carotid imaging), and aortic atherothrombosis or left atrial clot (via appropriate imaging). 1
• The American Heart Association recommends this evaluation specifically for embolic stroke of undetermined source (ESUS), where transesophageal echocardiography (TEE), cardiac CT, or cardiac MRI might be reasonable to identify possible cardioaortic sources or transcardiac pathways for cerebral embolism (Class 2b, Level C-LD). 1

Age-Based Considerations

• Prioritize bubble studies in younger patients (< 55-60 years) as the association between PFO and cryptogenic stroke is more convincingly demonstrated in this age group. 1
• PFO prevalence reaches 45.9% in young cryptogenic stroke patients compared to lower rates in older patients. 1
• The American College of Cardiology specifically recommends TEE with higher sensitivity for PFO detection in younger adults with unexplained cerebrovascular events. 1, 2

Diagnostic Approach Algorithm

Initial Screening Method

• Start with transthoracic echocardiography (TTE) with agitated saline contrast as the initial non-invasive screening method, which is rated "Appropriate" by the American College of Cardiology and has improved sensitivity with second harmonic imaging. 2
• The bubble study detects PFO by demonstrating right-to-left transit of contrast microbubbles within 3-4 cardiac cycles of right atrial opacification. 1, 2
• Perform Valsalva maneuver during contrast injection to transiently increase right atrial pressure and enhance sensitivity for PFO detection. 1

When to Escalate to TEE

• Proceed to transesophageal echocardiography (TEE) with bubble study when TTE is positive or inconclusive and you are contemplating PFO closure, as TEE provides superior visualization of atrial septal anatomy, shunt size, and presence of atrial septal aneurysm. 1, 2
• TEE remains the gold standard for detailed anatomical assessment before any planned intervention. 2

Alternative Screening Option

• Transcranial Doppler (TCD) with embolus detection might be reasonable to screen for right-to-left shunt in patients where PFO closure would be contemplated (Class 2b, Level C-LD). 1

Clinical Scenarios Warranting Bubble Study

High-Yield Scenarios

• Cryptogenic stroke in patients < 60 years with no identified stroke mechanism after comprehensive workup. 1
• Patients with Risk of Paradoxical Embolism (RoPE) score > 5-8 who lack classic atherosclerotic risk factors (hypertension, hyperlipidemia, diabetes, older age). 1
• Presence of deep venous thrombosis or pulmonary embolism suggesting potential paradoxical embolization mechanism. 1, 3

Special Consideration: Massive Pulmonary Embolism

• Screen for PFO with bubble study in patients with massive or submassive PE for risk stratification, as PFO presence increases mortality risk 2.4-fold and stroke risk 5.9-fold (Class IIb, Level of Evidence C). 1
• The presence of PFO with PE creates risk for paradoxical embolization and warrants consideration of aggressive therapeutic options. 1

Important Caveats and Pitfalls

Avoid Inappropriate Testing

• Do not routinely order bubble studies in patients with already-identified stroke etiology such as atrial fibrillation (8.7% of patients inappropriately screened) or significant carotid stenosis ≥70% (9.2% inappropriately screened). 4, 5
• Studies show that 62.3% of bubble studies are performed in non-cryptogenic stroke patients, yielding no management change in the vast majority. 5
• Avoid bubble studies in patients > 60 years with multiple vascular risk factors where atherosclerotic mechanisms are more likely and PFO is likely incidental. 4

Additional Cardiac Sources to Evaluate

• Remember that bubble studies also help identify other embolic sources including atrial septal defects, cardiac tumors (myxoma, papillary fibroelastoma), valve vegetations, atrial thrombi, and pulmonary arteriovenous malformations. 1
• Late appearance of bubbles (beyond 3-4 cardiac cycles) suggests pulmonary arteriovenous malformations rather than PFO. 1

Risk Stratification Features

• Document shunt size and presence of atrial septal aneurysm as these features increase embolic risk and influence management decisions, though shunt size estimation may be unreliable. 1, 3
• Atrial septal aneurysm (>10mm excursion from centerline) is present in 2.5% of patients and often associated with increased embolic risk. 1, 3

Safety Considerations

• The procedure carries a very low complication rate (0.1% TIA risk), but this warrants informed consent. 4