Quantitative assessment and clinical value of right-to-left shunt in patent foramen ovale using three-dimensional transesophageal echocardiography combined with right-heart contrast: a prospective study.

Background: A patent foramen ovale (PFO) is a common congenital cardiac condition characterized by a persistent communication between the right and left atria, which can facilitate a right-to-left shunt (RLS). This study aimed to determine the diagnostic accuracy, reproducibility, and prognostic value of PFO shunt volume quantified by three-dimensional transesophageal echocardiography (3D-TEE) combined with right-heart contrast echocardiography. Methods: In this prospective study, 100 patients with suspected PFO were prospectively enrolled and allocated in a 7:3 ratio to a training cohort (n=70) and a validation cohort (n=30). Each participant underwent two-dimensional transthoracic echocardiography (2D-TTE), two-dimensional transesophageal echocardiography (2D-TEE), and 3D-TEE. The total shunt volume (V_total) was calculated using voxel-based grey-scale integration. The optimal cut-off value was determined in the training set with the Youden index and then applied to the validation set. A multi-modality "hard reference" standard served as the diagnostic gold standard for method comparison. Reproducibility was evaluated with intraclass correlation coefficients (ICCs). All patients were followed for 36 months; stroke or transient ischemic attack (TIA) risk was analyzed with Kaplan-Meier curves and Firth-penalized Cox models, and changes in migraine frequency and residual shunt volume were recorded. Results: Eight baseline 3D structural indices, including tunnel length, slit width, leaflet excursion and shunt volume, showed no significant difference between cohorts (P>0.05). V_total, V_peak and t_dur demonstrated excellent repeatability (ICC =0.91-0.94; coefficient of variation 6.96-8.27%). The optimal threshold of 22.93 µL yielded an area under the curve (AUC) of 0.92 in the training set and 0.89 in the validation set (DeLong, P=0.27), with a sensitivity of 92%, specificity of 89%, and a diagnostic odds ratio (DOR) of 89.78, outperforming 2D-TTE and 2D-TEE. Kaplan-Meier analysis showed a 3-year stroke/TIA-free survival of 79% for shunt volume ≥22.93 µL versus 96% below the threshold (12 events, log-rank P=0.01); V_total ≥23 µL remained an independent predictor [hazard ratio (HR) =5.27, P=0.04]. Migraine frequency fell significantly over follow-up (P=0.001), and residual shunt volume at six months was lower after closure than with medical therapy (P<0.001). Conclusions: 3D-TEE with right-heart contrast precisely quantifies PFO shunt volume; a threshold of 22.93 µL is reproducible and predicts both diagnostic status and long-term outcomes, supporting its use in stroke risk stratification, closure decision-making and therapeutic monitoring.