Incremental diagnostic value of combining transthoracic echocardiography and transcranial doppler for detecting patent foramen ovale in cryptogenic stroke

Background/Introduction In patients with cryptogenic stroke (CS), screening for Patent Foramen Ovale(PFO) is essential for the prevention of recurrent stroke. Although transthoracic echocardiography (TTE) and transcranial Doppler (TCD) are widely used as non-invasive screening modalities, the incremental benefit of combining these two approaches remains unclear. Purpose This study aimed to investigate whether combining TTE and TCD improves the diagnostic performance of screening for PFO in patients with CS. Methods Of the 432 consecutive CS patients, 399 underwent integrated screening using TTE and TCD bubble testing within a multidisciplinary Heart–Brain Team approach, followed by TEE as the reference standard. Bubble testing was performed at rest and during the Valsalva manoeuvre (VM). Diagnostic performance, modality concordance, and incremental value were evaluated using ROC analysis, Cohen’s kappa statistics, and sequential logistic regression models. Results PFO was confirmed by TEE in 156 patients (39.1%). Both TTE and TCD demonstrated superior diagnostic performance during the VM compared with rest. Under VM conditions, the discriminatory ability of the two modalities was comparable; however, sequential logistic regression analysis showed a significant incremental gain in predictive value when TCD during VM was added to TTE during VM (χ² increase from 271.4 to 297.2; p<0.0001), supporting complementary diagnostic information. Although agreement during VM was substantial (κ=0.63), 54 patients (14%) exhibited discordant findings, among whom 15 (28%) had TEE-confirmed PFO. Application of an “OR” rule (positive if either test was positive) yielded the highest sensitivity, with only modestly reduced specificity. Conclusion Because clinically relevant PFO is frequently identified among patients with discordant findings, reliance on a single modality may lead to underdiagnosis. A dual-modality screening strategy incorporating an “OR”-based interpretation maximises sensitivity and may facilitate more informed referral for confirmatory testing and subsequent treatment decision-making in patients with cryptogenic stroke.