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Background: An echocardiogram or transcranial Doppler (TCD) bubble study to test for a right-to-left shunt (RLS) is a standard component of an ischemic stroke workup. Because the pathway for an intracradiac RLS, such as a patent foramen ovale (PFO), is more direct, it has been proposed that the late appearance of a RLS suggests an extracardiac pathway. We sought to characterize a cohort of ischemic stroke patients with late RLS (LRLS) on TCD.Methods: We searched the medical record of a Comprehensive Stroke Center for patients with ischemic stroke who had a TCD and echocardiogram bubble study during 2011-2013. LRLS was defined as TCD bubbles appearing more than 18 cardiac cycles after contrast injection. TOAST stroke etiology classification was performed by a vascular neurologist blinded to TCD results.Results: 124 patients met inclusion criteria, of which 67/124 (54%) had RLS on TCD; and 32/67 (48%) had LRLS. In the 35/67 patients with normal RLS on TCD, 23% did not have RLS on echocardiography, consistent with prior reports of TCD’s superiority for detecting RLS. In the 32/67 patients with LRLS on TCD, 56% were negative for RLS by echocardiography. In the cohort of 124 patients, the percentage of TOAST classification 4 (stroke of other determined cause) was 26%, while in the 32 patients with LRLS the percentage of TOAST 4 was significantly higher at 52%(p=0.005) (Table 1). The increase in TOAST 4 in LRLS patients was created by an even distribution of decreases in the other TOAST categories. The most common TOAST 4 stroke etiology in LRLS patients was PFO with concurrent deep venous thrombosis.Conclusion: This preliminary data supports prior studies that have shown superiority of TCD over echocardiography for detection of RLS, and challenge the prevailing notion that extracardiac shunt, such as pulmonary AVM, is the most common cause of LRLS in ischemic stroke patients. This subgroup of patients warrants further research to clarify mechanisms of ischemic stroke in patients with RLS.