Imaging of the intracranial vasculature to detect atherosclerotic stenosis of a major intracranial artery 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 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. Compared with alternatives, anticoagulation probably increases major bleeding.319 Each of these 6 trials had 1 methodological features with a high risk of bias identified, including lack of blinding of participants and personnel, lack of blinding of outcome assessments, incomplete outcome data, and selective See Tables LXXV through LXXVII in online Data Supplement 1. Routine imaging of the intracranial vasculature to detect atherosclerotic stenosis of a major intracranial artery to guide selection of antithrombotic or intracranial endovascular treatment for prevention of recurrent stroke is not well established. (See knowledge byte following 6.2, recommendation 2.) IIb B-NR New recommendation. 6.3. Cardiac Evaluation 6.3.1. Electrocardiographic Monitoring COR LOE New, Revised, or Unchanged Cardiac monitoring is recommended to screen for atrial fibrillation and other potentially serious cardiac arrhythmias that would necessitate emergency cardiac interventions. 