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Research Article: Association between patent foramen ovale and anxiety: a prospective study with deep learning-assisted analysis of contrast echocardiography

Date Published: 2026-09-30

Abstract:
To prospectively investigate the association between patent foramen ovale (PFO), detected via agitated saline contrast echocardiography (ASCE), and anxiety using a deep learning approach. This prospective study consecutively enrolled 161 participants between July 15, 2025 and October 31, 2025. Participants were stratified into ASCE-negative (n=58) and ASCE-positive (n=103) groups based on the examination results. All participants underwent ASCE and anxiety assessment using the Self-Rating Anxiety Scale (SAS). An artificial intelligence model was developed using a 10-fold cross-validation approach on the 103 ASCE-positive videos to predict anxiety scores. The primary endpoint was the association between PFO and anxiety, while the deep learning model was evaluated as a secondary/exploratory endpoint. Statistical analyses, including logistic regression, were performed with statistical significance set at p<0.05. Compared to the ASCE-negative group, the ASCE-positive group exhibited significantly higher anxiety levels (SAS score: 45.0 vs. 38.0, p<0.001) and a higher prevalence of anxiety (32.0% vs. 5.2%, p<0.001). Logistic regression identified a strong association between ASCE-positive status and anxiety (adjusted odds ratio=8.64, p<0.001), with no clear dose-dependent relationship across shunt grades. The imaging-only deep learning model achieved a mean absolute error (MAE) of 5.76 ± 0.12 and an R² of 0.46 ± 0.03 across cross-validation folds. After incorporating clinical and sociodemographic confounders, the model’s performance improved to an MAE of 5.15 ± 0.10 and an R² of 0.59 ± 0.02. This prospective study confirms a significant association between PFO and anxiety and demonstrates the feasibility of using ASCE-based deep learning models to predict anxiety risk, although clinical application requires external validation.

Introduction:
The clinical overlap between cardiovascular and neuropsychiatric disorders, particularly in patients with patent foramen ovale (PFO), represents a significant but underexplored challenge in the general hospital setting. PFO, a persistent fetal interatrial communication, is present in approximately 25% of the adult population. While its role in cryptogenic stroke and migraine is well-established ( 1 – 3 ), a growing number of clinical observations suggest a potential, yet poorly defined, link between PFO and mood…

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