BACKGROUND: Contrast echocardiography with agitated saline contrast (ASC) is widely employed to detect the patent foramen ovale (PFO) in patients with ischemic stroke. Second harmonic imaging (SHI) improved the sensitivity to detect microbubbles in the heart. Although large amounts of left heart contrast appearing 4 cardiac cycles or later have been well described in patients with large pulmonary arteriovenous malformations, few study has evaluated the clinical significance of small amounts of late-appearing left heart contrast in patients with stroke. METHODS: In 212 consecutive patients with suspicious of embolic stroke, TTE and TEE with ASC were performed. Semi-quantification and timing of contrast passage were assessed using SHI. If contrast appeared in the left atrium (LA) within 3 cardiac cycles, PFO was diagnosed, while appearance of contrast after 3 cardiac cycles, intrapulmonary shunt was diagnosed. In patients undergoing TEE, we confirmed contrast entering LA from pulmonary vein. Demographic, laboratory and echocardiographic data were compared between patients with intrapulmonary shunt and PFO. RESULTS: Among the 212 patients (mean age 66짹12, female 48.1%), 78 presented a passage of contrast from the right to the left atrium. PFO was diagnosed in 27 patients (12.7%), and intrapulmonary shunt in 51 patients (24.0%). There was no known lung disease in patients with intrapulmonary shunt. Women were less in patients with intrapulmonary shunt compared to PFO (37.3 vs. 74.1%, p=0.007). Among echocardiographic parameters, LA volume was slightly larger in patients with intrapulmonary shunt (34.0짹15.1 vs. 29.4짹9.9mL, p=0.01). The serum level of high-sensitivity C-reactive protein was significantly higher (12.8짹28.5 vs. 1.8짹2.1mg/L, p=0.0003), and there were more patients with elevated BNP level (>100pg/mL, 21.2 vs. 9.1%, p=0.02) in patients with intrapulmonary shunt. CONCLUSION: In patients with stroke, the incidence of intrapulmonary shunt was even higher than PFO with using SHI. Diagnosis of PFO should be made with careful exclusion of intrapulmonary shunt, and the clinical implication of intrapulmonary shunt remained to be investigated.