Abstract
BACKGROUND: Right-to-left shunt (RLS) is closely associated with migraine and cryptogenic stroke (CS), but single diagnostic techniques have limitations in accurately identifying RLS. This study aimed to evaluate the incremental value of characteristics of RLS in patients with migraine and CS via multi-modal echocardiography and explore independent risk factors between patients with migraine and CS. METHODS: A retrospective study enrolled 455 RLS patients (281 with migraine, 174 with CS) with diagnosis of migraine and CS between May 2022 and July 2024. Contrast-enhanced transcranial Doppler (c-TCD) and/or contrast-enhanced transthoracic echocardiography (c-TTE) were performed to screen RLS, subsequently contrast-enhanced transesophageal echocardiography (c-TEE) combined with real-time three-dimensional (RT-3D) volume imaging examination were followed. RLS was semi-quantitatively graded as I grade (1-10 microbubbles/frame), II grade (11-30 microbubbles/frame), or III grade (>30 microbubbles/frame or left atrial filling). The size and echo intensity of microbubbles were defined by comparison with the microbubbles in the right heart. The χ(2) test was used for group comparisons for categorical variables the Mann-Whitney U test was used for continuous variables. Univariate and multivariate logistic analyses were performed to identify independent risk factors. RESULTS: Compared with TEE, c-TEE and RT-3D c-TEE examination could improve the detection rate of RLS and identify RLS origination, including patent foramen ovale-right-to-left shunt (PFO-RLS), physiological pulmonary-right-to-left shunt (P-RLS), pulmonary arteriovenous fistula (PAVF) and their combination types. The proportion and types of RLS between the migraine and CS groups was significantly different (χ(2)=9.4, P<0.01). Some ultrasonic imaging characteristics of RLS showed significant differences. The CS group exhibited a notably greater PFO height compared to the migraine group {1.7 [interquartile range (IQR), 0.8] vs. 1.3 (IQR, 0.9) mm, P<0.001}, whereas the migraine group had a larger atrial septal swing amplitude [12.7 (IQR, 2.3) vs. 11.2 (IQR, 2.3) mm, P<0.001]. Additionally, the proportion of color-Doppler flow imaging (CDFI) blood flow convergence was higher in the CS group than in the migraine group (54.8% vs. 42.4%, P<0.05). Regarding RLS grading, the CS group had a significantly higher incidence of grade III RLS (57.3% vs. 40.5%), while the migraine group showed a higher incidence of grade I RLS (36.6% vs. 26.1%). Significant disparities were also observed between the two groups in terms of the size, echo intensity and occurrence of RLS microbubbles (all P<0.05). Multivariate logistic analysis identified PFO tunnel height as an independent risk factor for CS (β=0.517, P=0.005), while atrial septal swing amplitude served as an independent risk factor for migraine (β=0.312, P<0.001). CONCLUSIONS: Multi-modal echocardiography can identify the types and characteristics of RLS accurately, which may provide incremental value for clinical decision-making.