Complementary Value of Transthoracic Echocardiography and Transcranial Doppler for Screening in Cryptogenic Stroke

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Abstract Background The optimal noninvasive screening strategy for detecting patent foramen ovale (PFO) in patients with cryptogenic stroke (CS) remains uncertain. Although transthoracic echocardiography (TTE) and transcranial Doppler (TCD) are widely used, whether combining both modalities improves diagnostic performance has not been fully established. Methods Among 432 consecutive CS patients, 399 underwent collaborative screening with both TTE and TCD bubble tests performed by a multidisciplinary Heart–Brain Team, followed by transesophageal echocardiography (TEE) as the reference standard. Bubble tests were conducted at rest and during the Valsalva maneuver (VM). Diagnostic performance, concordance between modalities, and incremental value were evaluated using receiver operating characteristic analysis, Cohen’s kappa statistics, and sequential logistic regression models. Results TEE confirmed PFO in 156 patients (39.1%). Both TTE and TCD demonstrated significantly higher diagnostic accuracy during VM than at rest, with no significant difference in area under the curve between modalities under VM. Sequential logistic regression showed a significant incremental increase in predictive value when TCD during VM was added to TTE during VM (χ² increase from 271.4 to 297.2; p<0.0001). Although overall agreement between TTE and TCD during VM was substantial (κ=0.63), 54 patients (14%) showed discordant results, among whom 15 (28%) had TEE-confirmed PFO. Applying an “OR” rule (positive if either test was positive) significantly improved sensitivity compared with either modality alone, at the expense of modestly reduced specificity. Conclusions Dual screening with TTE and TCD during VM within a Heart–Brain Team framework significantly enhances sensitivity for PFO detection and reduces missed diagnoses in patients with CS. An “OR” rule interpretation represents a practical and clinically effective screening strategy.

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