The efficacy of treatment in reducing the risk of recurrent stroke associated with many of these echocardiographic lesions is unknown, or there is not a treatment that has been shown to be better than standard medical therapy.352 360 Different authors have concluded that routine echocardiography is indicated or contraindicated. Various inconsistent recommendations for selecting which patients with AIS should undergo echocardiography have been made.358,361 363 Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without an obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria. They do not support the routine use of echocardiography in all patients with AIS. See Tables LXXIV and LXXXV in online Data Supplement 1. Echocardiography is reasonable in selected patients as part of a comprehensive evaluation to determine if they meet the eligibility criteria of the RCTs that investigated mechanical closure of PFO for prevention of recurrent stroke. IIa B-R New recommendation. Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without an obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography. Meta-analyses of these trials show a significantly reduced risk of recurrent stroke with mechanical closure compared with medical therapy with a number needed to treat of 131.318 320 A network meta-analysis concluded that, in patients <60 years of age, PFO closure probably confers an important reduction in ischemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events. 