For what indications is a bubble study (contrast echocardiography) performed?

Bubble Study Indications

A bubble study (agitated saline contrast echocardiography) is primarily performed to detect right-to-left shunts, including patent foramen ovale (PFO) and pulmonary arteriovenous malformations (PAVMs), with critical applications in cryptogenic stroke evaluation, pulmonary hypertension assessment, and congenital heart disease diagnosis. 1

Primary Clinical Indications

Cryptogenic Stroke Evaluation

• Bubble studies are essential for evaluating cryptogenic stroke patients where PFO may be the source of paradoxical embolism, directly impacting decisions about PFO closure to prevent recurrent stroke 1, 2
• This represents one of the most important clinical applications, as identifying a PFO changes management from medical therapy alone to potential device closure 3

Detection of Intracardiac Shunts

• The test identifies patent foramen ovale, which standard echocardiography cannot reliably detect without contrast 2
• Bubble studies verify the presence of shunts in known or suspected congenital heart disease and help differentiate between intracardiac versus extracardiac shunts 1
• Transthoracic echocardiography (TTE) with agitated saline serves as the initial screening test due to its non-invasive nature, wide availability, and minimal risk 1

Pulmonary Arteriovenous Malformation Diagnosis

• Transthoracic contrast echocardiography demonstrates 98-99% sensitivity for detecting PAVMs, making it an essential diagnostic test for patients suspected of having these lesions 4, 1
• This is particularly important in patients with hereditary hemorrhagic telangiectasia, where PAVMs are common 1, 3
• The test quantifies right-to-left shunting before and after PAVM treatment 4
• A semiquantitative grading system (grades 0-3 based on bubble appearance in left atrium) correlates with PAVM diagnosis, with higher grades associated with larger shunts and cerebral complications 4

Pulmonary Hypertension and Pulmonary Embolism Assessment

• Pulmonologists routinely screen for shunts when evaluating patients with elevated right ventricular systolic pressure (RVSP > 45 mmHg) as part of comprehensive pulmonary hypertension assessment 1
• Bubble studies are recommended for risk-stratifying patients with massive or submassive pulmonary embolism (Class IIb recommendation), as the presence of PFO significantly increases risk of death, stroke, and peripheral arterial embolism through paradoxical embolism 1, 2
• The test helps identify intracardiac shunts that may contribute to or complicate pulmonary hypertension management 1

Unexplained Hypoxemia

• Bubble studies help distinguish between cardiac and non-cardiac causes of dyspnea when clinical and laboratory findings are ambiguous 1
• This is particularly valuable in patients with pulmonary disease who may have poor transthoracic windows, as the subxiphoid/subcostal view can usually visualize the heart well despite hyperinflated lungs 1

Technical Approach and Timing Considerations

Choice Between TTE and TEE

• TTE with agitated saline is the initial screening test, but TEE should be considered when TTE is non-diagnostic, when higher sensitivity is needed, or when detailed anatomical assessment is required for procedural planning 1
• TEE provides significantly higher sensitivity (51%) compared to TTE (32%) for detecting shunts 1, 2, 3
• TEE offers superior visualization of the atrial septum and is preferred when evaluating for PFO closure planning, as it provides accurate assessment of secundum atrial septal defect size and rim length comparable to CT 1

Distinguishing Intracardiac from Extracardiac Shunts

• The traditional "3-to-5 beat rule" for timing of bubble appearance has limited specificity and should not be used as the sole criterion for differentiating intracardiac from extracardiac shunts 5
• Microbubbles appearing after 3-8 cardiac cycles in the left atrium after initial right chamber opacification suggest intrapulmonary shunt, but early appearance does not definitively exclude PAVM 4, 5
• TEE with contrast can help locate PAVMs based on visualization of contrast emanating from specific pulmonary venous ostia, though this is limited when multiple PAVMs are present 4

Important Safety Considerations and Caveats

Risk of Paradoxical Embolism

• Ischemic cerebrovascular complications can occur during bubble studies in patients with cardiac or pulmonary shunts, though the true incidence remains unknown 6
• Events have been reported during or within 5 minutes of the procedure, occurring exclusively in patients with PFO, PAVM, or both 6
• Adverse events including air embolism occur in <1% of cases 4

Technical Limitations

• TEE has specific blind spots including limited visualization of the right ventricular outflow tract, pulmonary valve, distal right pulmonary artery, proximal left pulmonary artery, and apical-anterior septum 1
• The examination may be unsuccessful in 3-5% of patients due to inability to tolerate the probe, and another 4-5% require general anesthesia 1
• TEE is semi-invasive, requires conscious sedation, and has a mortality rate of 0.0098% and complication rate of 0.88% 1

When NOT to Order

• The bubble study should not be ordered routinely in all patients with lung disease without clinical suspicion of cardiac involvement 1
• There is no role for resting TTE without contrast in PAVM evaluation, though it does allow assessment of intracardiac shunts and cardiac function 4