TCD compares favorably with TEE for detecting right-to-left shunting, which is usually the result of PFO, now a potential target for device closure. A pooled analysis of the OXVASC (Oxford Vascular Study) data with data from 2 previous smaller studies of bubble-TCD in patients 50 years of age found an association between right-to-left shunting and cryp- togenic TIA or nondisabling stroke (OR, 2.35 [95% A pooled analysis of a systematic literature review found that TCD had a sensitivity of (95% CI, 85.5 96.1) compared with TEE (gold stan- dard) for detection of right-to-left shunting.57 Knowledge Gaps and Future Research Randomized trials have provided compelling evidence of specific therapies for specific subsets of patients with ischemic stroke, for example, anticoagulation in the subset of patients with AF and low risk of hemorrhage. Diagnosing these mechanistically related risk factors is an important part of the early evaluation of stroke to opti- mize prevention of recurrent stroke. New risk factors for stroke are being discovered through observational stud- ies, but several knowledge gaps exist relating to the rela- tive importance of testing to identify uncommon or rare conditions associated and potentially causally linked with recurrent stroke. The less prevalent a comorbid condition is among patients with stroke, the more challenging it is to execute successfully a well-powered clinical trial to provide high levels of evidence justifying the diagnostic testing. There are several clinical conditions associated with ischemic stroke for which trial evidence would be helpful to guide therapy: To better prevent cardioembolism, it would be helpful to have trials that clarify optimal duration of heart rhythm monitoring, determine the clinical significance of brief episodes of AF, and define the precise role of cardiac CT/MRI and microembolus detection with TCD. 