Quantitative Analysis of Pulmonary Right-to-Left Shunts and Patent Foramen Ovale via Agitated Saline Contrast Transesophageal Echocardiography: Associations With Migraine, Cryptogenic Stroke, and Transient Ischemic Attack.

BACKGROUND: Growing evidence associates patent foramen ovale right-to-left shunt (PFO-RLS) with conditions including migraine, cryptogenic stroke (CS), and transient ischemic attack (TIA). However, the potential role of pulmonary right-to-left shunt (P-RLS) remains unclear. This study aimed to characterize PFO-RLS and P-RLS using contrast transesophageal echocardiography (cTEE) and analyze their distinct features and intrinsic associations with migraine and CS/TIA.

METHODS: 302 patients with clinically suspected right-to-left shunt (RLS) contrast transesophageal echocardiography (cTEE) between October 2019 and January 2025 were retrospectively analyzed. Target Symptom Group included patients presenting with migraine, cryptogenic stroke (CS), and/or transient ischemic attack (TIA); all other patients comprised the Comparison Group. cTEE was performed to detect and quantitatively evaluate both patent foramen ovale right-to-left shunt (PFO-RLS) and pulmonary right-to-left shunt (P-RLS). We conducted stratified analyses to assess the relationships of PFO-RLS and P-RLS individually with the presence of target symptoms. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with the Target Symptom Group.

RESULTS: All 302 patients were successfully examined using TTE and cTEE. cTEE revealed 165 cases of PFO-RLS and 217 cases of P-RLS. Stratified analyses showed no statistical significance of P-RLS among patients with varying degrees of PFO-RLS between the positive symptom and other symptoms group. PFO-RLS was statistically significant between the two groups in patients with varying degrees of P-RLS. Pulmonary vein shunt and PFO shunt were significantly associated with positive symptoms (p < 0.05) in the univariate analysis; however, only PFO shunt was an independent risk factor in the multivariate analysis (OR 1.363, p < 0.05). Patients with moderate-to-severe dual shunts had the highest proportion(76.5%) of positive symptoms. Further analysis showed no significant interaction (p > 0.05).

CONCLUSION: cTEE has a good diagnostic value for determining the source of RLS microvesicles. PFO-RLS causes migraine and CS/TIA; the more shunts there are, the more severe the symptoms. Current grading system for right-to-left shunt does not take microbubble size into consideration, although P-RLS is more common, it does not cause severe symptoms. A PFO shunt alone is an independent risk factor for migraine and CS/TIA.