What is being assessed when a Transthoracic Echocardiogram (TTE) with bubble study is ordered?

What is Being Assessed with a TTE Bubble Study

A TTE with bubble study is primarily ordered to detect right-to-left shunts, specifically intracardiac shunts like patent foramen ovale (PFO) and intrapulmonary shunts such as pulmonary arteriovenous malformations (PAVMs). 1

Primary Clinical Indications

Detection of Intracardiac Shunts (Patent Foramen Ovale)

• The most common reason for ordering a bubble study is to identify PFO in patients with cryptogenic stroke, where paradoxical embolism through the PFO may be the underlying mechanism. 1, 2
• The American Heart Association recommends bubble studies to identify patients who might benefit from PFO closure to prevent recurrent stroke. 1
• TTE with agitated saline has 76-87% sensitivity for detecting PFO, making it an excellent first-line screening test. 3, 4

Detection of Pulmonary Arteriovenous Malformations

• Bubble studies are essential for diagnosing PAVMs, particularly in patients with hereditary hemorrhagic telangiectasia (HHT). 5, 1
• TTE with agitated saline demonstrates 98-99% sensitivity for detecting PAVMs, making it the primary screening modality. 5, 1
• The test does not provide information about PAVM size or location, but effectively identifies the presence of intrapulmonary shunting. 5

How the Test Distinguishes Between Shunt Types

Timing of Bubble Appearance

• Bubbles appearing in the left atrium within 3-4 cardiac cycles indicate an intracardiac shunt (PFO), as they pass directly from right to left heart without traversing the pulmonary capillary bed. 5, 6
• Bubbles appearing after 5 or more cardiac cycles (typically 3-8 cycles) indicate an intrapulmonary shunt (PAVM), as they must pass through abnormal pulmonary vascular connections. 5, 6
• The 4th cardiac cycle rule most optimally differentiates PFO from intrapulmonary shunts. 6

Quantification of Shunt Severity

• A semi-quantitative grading system assesses shunt size: Grade 0 (no bubbles), Grade 1 (<30 bubbles), Grade 2 (moderate filling), Grade 3 (complete left atrial opacification). 5
• Shunts with >20 bubbles are considered large and clinically significant, correlating with higher risk of cerebral complications. 5
• Higher grades (2 and 3) in PAVM patients have positive predictive values of 0.21 and 0.87 respectively for requiring treatment. 5

Additional Clinical Applications

Risk Stratification in Pulmonary Embolism

• The American Heart Association recommends bubble studies for risk-stratifying patients with massive or submassive pulmonary embolism (Class IIb recommendation). 1, 7
• The presence of PFO significantly increases risk of death, stroke, and peripheral arterial embolism through paradoxical embolism in PE patients. 1, 7

Evaluation of Pulmonary Hypertension

• 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 help identify intracardiac shunts that may contribute to or complicate pulmonary hypertension. 1

Assessment of Unexplained Hypoxemia

• Bubble studies help distinguish between cardiac and non-cardiac causes of dyspnea and hypoxemia when clinical findings are ambiguous. 1
• This is particularly valuable in patients with lung disease where standard imaging may be limited. 1

Congenital Heart Disease Evaluation

• Bubble studies verify the presence of shunts in known or suspected congenital heart disease and help differentiate between intracardiac and extracardiac shunts. 1

Technical Considerations and Limitations

Procedure Enhancement

• The Valsalva maneuver significantly increases the number of bubbles shunting (from 10±11 to 20±19 bubbles) and should be performed during the study. 8
• The Valsalva maneuver increases right atrial pressure, promoting right-to-left shunting and improving diagnostic sensitivity. 8, 4

When to Consider TEE Instead

• TEE provides higher sensitivity (51%) compared to TTE (32%) for detecting shunts and should be considered when TTE is non-diagnostic. 1, 2
• TEE is preferred when evaluating the atrial septum for PFO closure planning, as it provides accurate assessment of secundum atrial septal defect size and rim length. 1
• Common reasons for false-negative TTE include poor image quality and left-sided valve lesions. 4

Safety Profile

• Adverse events including air embolism are rare with TTE bubble studies, occurring in <1% of cases. 5

Common Pitfalls to Avoid

• Do not assume all positive bubble studies represent PFO—timing of bubble appearance is critical to distinguish intracardiac from intrapulmonary shunts. 6
• Poor acoustic windows can lead to false-negative results—patients with significant lung disease may require TEE for definitive evaluation. 1, 4
• Inadequate Valsalva maneuver reduces sensitivity—proper patient coaching and technique are essential. 8, 4
• The bubble study should not be ordered routinely in all patients with lung disease without clinical suspicion of cardiac involvement. 1