Association of Resting Right-to-Left Shunt With Ischemic Stroke Among Patients Referred for Contrast...

Resting right-to-left shunt (RLS) may represent a persistent functional shunt phenotype compared with provoked-only shunting. However, its association with ischemic stroke among patients clinically referred for contrast-enhanced transthoracic echocardiography (c-TTE)-based RLS assessment remains incompletely characterized. Because such patients are referred according to clinical suspicion rather than population-based screening, findings from this setting require cautious interpretation.

We conducted a single-center retrospective cross-sectional study at Taizhou People's Hospital. Consecutive outpatients and inpatients clinically referred for c-TTE-based RLS assessment between July 2024 and June 2025 were screened. Patients with incomplete key clinical, laboratory, or echocardiographic data were excluded, and analyses were performed on a complete-case basis. Ischemic stroke was identified on the basis of compatible focal neurological symptoms and radiologic evidence of acute infarction. Resting RLS was defined as microbubble passage into the left-sided cardiac chambers without provocation and was graded semiquantitatively from 0 to 3. Multivariable logistic regression was used to examine the association between resting RLS and ischemic stroke status after adjustment for clinically relevant covariates.

Among 1328 consecutive patients clinically referred for c-TTE-based RLS assessment, 717 with complete data were included in the final analytic cohort. Ischemic stroke was present in 161 patients (22.5%), and resting RLS was present in 156 patients (21.8%). Resting RLS was more frequent in patients with stroke than in those without stroke (32.9% vs. 18.5%, p < 0.001). In multivariable analysis, resting RLS was associated with ischemic stroke status (adjusted OR 2.30, 95% CI 1.52-3.50; p < 0.001). When analyzed as an ordinal variable, each one-grade increase in resting RLS was associated with higher odds of stroke status (adjusted OR 1.50, 95% CI 1.23-1.84; P for trend < 0.001). Exploratory ROC analysis showed an AUC of 0.715 for the model including resting RLS.

In this clinically referred complete-case cohort undergoing c-TTE-based RLS assessment, resting RLS and higher resting RLS grade were associated with ischemic stroke status after adjustment for available conventional vascular risk factors. Given the retrospective referral-based design, complete-case selection, and limited availability of medication information, these findings should be interpreted as hypothesis-generating and require prospective validation in broader, systematically evaluated populations.