Thus, the require- ment that the stroke be cryptogenic is equivalent to nonlacunar stroke of undetermined source, or ESUS. Furthermore, clinical judgement is required because many strokes in the ESUS category may not have a definite cause but other lower-compet- ing-risk conditions such as a proximal large artery Analysis of observa- indicates that younger patients with- out other vascular risk factors are more likely to have PFOs that are related to their stroke. Similarly, the anatomic characteristics of the PFO need to Figure 5. Patent foramen ovale (PFO) and ischemic stroke management guide. Colors correspond to Class of Recommendation in Table 3. CT indicates computed tomography; DVT, deep vein thrombosis; LP, lumbar puncture; MRI, magnetic resonance imaging; MRV, magnetic resonance venography; RoPE, Risk of Paradoxical Embolism; and TIA, transient ischemic attack. CLINICAL STATEMENTS AND GUIDELINES Kleindorfer be considered in decision-making (see text under Recommendations 2 and 3). in which the comparator was antiplatelet therapy and long-term follow-up from an earlier trial555 in which the comparator was antiplatelet or anticoagulation therapy found a benefit of device closure. There is evidence that patients with high-risk anatomic features, including larger shunt size (defined variably), particularly an atrial septal aneurysm, are more likely to benefit from device closure.563 The individual patient level meta-analysis of the first 3 trials552 found slightly greater benefit among patients with these char- acteristics, but the differences did not approach statistical significance. In contrast, the RESPECT showed significant interactions between treatment and both larger shunt size (>20 micro- bubbles) and atrial septal aneurysm, with benefit shown only when either was present. 