Robot-Assisted Transcranial Doppler Versus Transthoracic Echocardiography for Right to Left Shunt Detection

Mark N Rubin, Ruchir Shah, Thomas Devlin, Teddy S Youn, Michael F Waters, John J Volpi, Aaron Stayman, Colleen M Douville, Ted Lowenkopf, Georgios Tsivgoulis, Andrei V Alexandrov, Mark N Rubin, Ruchir Shah, Thomas Devlin, Teddy S Youn, Michael F Waters, John J Volpi, Aaron Stayman, Colleen M Douville, Ted Lowenkopf, Georgios Tsivgoulis, Andrei V Alexandrov

Abstract

Background: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce.

Methods: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed per local standards. The primary outcome was rate of RLS detection by raTCD versus TTE.

Results: A total of 154 patients were enrolled, 129 evaluable (intent to scan) and 121 subjects had complete data per protocol. In the intent to scan cohort, mean age was 60±15 years, 47% were women, and all qualifying events were diagnosed as ischemic stroke or transient ischemic attack. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%; absolute difference 43.4% [95% CI, 35.2%-52.0%]; P<0.001). On prespecified secondary analysis, large RLS was detected by raTCD in 35 subjects (27%) versus 13 (10%) by TTE (absolute difference 17.0% [95% CI, 11.5%-24.5%]; P<0.001). There were no serious adverse events.

Conclusions: raTCD was safe and ≈3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and patent foramen ovale detection without the need for an experienced operator to perform the test. Pending confirmatory studies, TCD appears to be the superior screen for RLS compared with TTE (funded by NeuraSignal).

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT04604015.

Keywords: echocardiography; embolic stroke; embolism; ischemic stroke; patent foramen ovale; robotics; ultrasound.

Conflict of interest statement

Disclosures Drs Alexandrov, Rubin, Tsivgoulis, and Volpi have received payment as consultants to the study sponsor. C. Douville has received travel support from the study sponsor. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
BUBL patient recruitment diagram. SOC indicates standard of care; TCD, transcranial Doppler; and TTE, transthoracic echocardiography.
Figure 2.
Figure 2.
A transthoracic echocardiogram (TTE) and robot-assisted transcranial Doppler (raTCD) in one of the study subjects with a negative TTE and a strongly positive raTCD. The 4-chamber apical view of the TTE demonstrates opacification of the right atrium and ventricle (on the left of the figure) with agitated saline contrast and none of those bubbles crossing into the left atrium or ventricle, suggesting the absence of a right to left shunt (RLS). In stark contrast, one can see on the right part of the figure that many bubbles, generating the white streaks seen on the raTCD—enough to fill entire cardiac cycles—indicating a large RLS. In the setting of discrepancy, the positive raTCD study is to be trusted as TTE is subject to false negative and the pattern of the result of raTCD does not suggest false positive. Please see Video S2 for audio and visual detail.

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