When to order an echocardiogram (echo) with bubble study in a stroke workup?

From the Guidelines

An echocardiogram with bubble study should be ordered in stroke workup when there is suspicion of a right-to-left cardiac shunt, particularly a patent foramen ovale (PFO), as a potential cause of cryptogenic stroke, as recommended by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

Key Points to Consider

• This test is most appropriate for patients under 60 years of age who have had an ischemic stroke or transient ischemic attack (TIA) with no identified cause after initial evaluation including brain imaging, vascular imaging, and cardiac rhythm assessment.
• The bubble study is particularly indicated when the stroke pattern suggests an embolic source but standard evaluations (carotid ultrasound, standard echocardiography, and cardiac monitoring) have not revealed a source.
• Specific scenarios warranting this test include patients with cryptogenic stroke who have risk factors for paradoxical embolism such as deep vein thrombosis, pulmonary embolism, history of prolonged immobility, or Valsalva-provoking activities preceding the stroke.
• The test involves injecting agitated saline solution intravenously while imaging the heart to detect bubbles crossing from the right to left atrium, indicating a shunt.
• If a PFO is detected and deemed clinically significant, treatment options including antiplatelet therapy, anticoagulation, or PFO closure may be considered based on individual patient factors and stroke recurrence risk, as supported by studies such as the one published in 2021 1.

Diagnostic Evaluation

• The American Heart Association/American Stroke Association recommends a diagnostic evaluation for gaining insights into the etiology of and planning optimal strategies for preventing recurrent stroke, with testing completed or underway within 48 hours of onset of stroke symptoms 1.
• Echocardiography with or without contrast is reasonable to evaluate for possible cardiac sources of or transcardiac pathways for cerebral embolism in patients with cryptogenic stroke, as stated in the 2021 guideline 1.

Detection of Right-to-Left Shunting

• Transcranial Doppler (TCD) with embolus detection might be reasonable to screen for right-to-left shunt in patients with ischemic stroke or TIA in whom patent foramen ovale (PFO) closure would be contemplated, as suggested by the 2021 guideline 1.
• TCD has a sensitivity of 96.1% and specificity of 92.4% compared with TEE (gold standard) for detection of right-to-left shunting, as reported in a pooled analysis of a systematic literature review 1.

From the Research

Indications for Echocardiogram with Bubble Study in Stroke Workup

• The decision to order an echocardiogram with bubble study in a stroke workup should be based on the presence of cryptogenic stroke or transient ischemic attack (TIA) in patients ≤ 60 years old 2, 3.
• Patients with a readily identifiable cause of stroke, such as atrial fibrillation or carotid stenosis ≥ 70%, may not require a bubble study as the detection of a patent foramen ovale (PFO) is likely to be incidental and may not alter management 4.
• A transcranial Doppler (TCD) bubble test can be used as a non-invasive screening tool to detect right-to-left shunt (RLS) and select patients for further evaluation with transesophageal echocardiography (TEE) 5, 6.
• The combination of TCD bubble test and carotid ultrasound can be used to guide the indication of TEE in young patients with stroke, with a high negative predictive value for therapy-relevant TEE findings 3.

Patient Selection

• Patients with cryptogenic acute ischemic stroke or TIA ≤ 60 years old should undergo a TCD bubble test and carotid ultrasound to screen for PFO and atherosclerosis 3.
• Patients with a positive TCD bubble test and/or carotid ultrasound showing atherosclerosis should undergo TEE to confirm the presence of a PFO or aortic atheroma 3.
• Patients with a negative TCD bubble test and no carotid atherosclerosis may not require TEE, as the likelihood of therapy-relevant findings is low 3.

Clinical Predictors of Right-to-Left Shunt

• Activity at the time of stroke onset equivalent to a Valsalva maneuver, isolated cortical infarction, and posterior circulation involvement are significantly associated with the presence of an RLS 6.
• A high-grade shunt on the TCD bubble contrast study, a longer length of the tunnel, and the presence of an interatrial septal aneurysm are also associated with an increased risk of paradoxical embolism 6.