Diagnostic value of contrast-enhanced ultrasonography for patent foramen ovale detection

Background: Patent foramen ovale (PFO) has been associated with migraine, cryptogenic stroke (CS), and hypoxemia. However, which examination method is most reliable remains controversial. This study sought to investigate the diagnostic value of contrast-enhanced ultrasonography (cU), including contrast-enhanced transcranial Doppler (cTCD), contrast transthoracic echocardiography (cTTE), and contrast transesophageal echocardiography (cTEE), for PFO; and to determine the best diagnostic strategy. Methods: This retrospective observational study included a total of 147 consecutive patients suspected PFO at The First Hospital of Shanxi Medical University between October 2019 and January 2022. The patients also underwent cTCD, cTTE, and cTEE examinations. The standard for the diagnosis of PFO was confirmation of the presence of PFO by color Doppler flow signals or contrast microbubbles (MBs) passing through the foramen ovale. Results: A total of 123 patients were diagnosed with PFO and 24 patients without PFO during the study period. The detectable rates of cTCD, cTTE, and cTEE were 120 (97.56%), 110 (89.43%), and 121 (98.37%), respectively. The sensitivity between cTCD and cTEE for PFO were comparable [97.56%, 95% confidence interval (CI): 92.5% to 99.4% vs. 98.37%, 95% CI: 93.7% to 99.7%; P>0.99], and the sensitivity of both were higher than that of cTTE (89.43%, 95% CI: 82.3% to 94.0%; P=0.02 and P=0.001, respectively). In addition, the specificity of cTEE for PFO was significantly higher than that of cTCD (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001) and cTTE (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001). Further, the semi-quantitative classification ability of cTCD for PFO with right-to-left shunt (RLS) was significantly higher than that of cTTE and cTEE (P=0.02 and P<0.001, respectively), and that of cTTE was significantly higher than that of cTEE (P=0.01). The Spearman analysis showed that the degree of RLS was positively correlated with the inner diameter of the PFO (r=0.695, P<0.001). Conclusions: The combination of cTCD and cTEE may provide a favorable strategy for the diagnosis of PFO.