A phase II randomized trial comparing dabigatran and warfarin in patients with mechanical heart valves (RE-ALIGN [Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients After Heart Valve Replacement]) was stopped prematurely after enrollment of 252 patients because of an excess of thromboembolic and bleeding events in the dab- At this point, there is no published randomized study evaluating the safety and effi- cacy of other DOACs in patients with mechanical heart valves, and warfarin remains the only recom- mended oral anticoagulant in these patients. Knowledge Gaps and Future Research Rheumatic mitral valve disease often results in left atrial structural changes and adverse remodeling, which predisposes to thromboembolic complica- tions also when in sinus rhythm, a condition that has been defined as atrial cardiomyopathy.496,497 In patients with ischemic stroke or TIA who have rheumatic mitral valve disease without AF and no other likely cause for their symptoms (eg, carotid stenosis), the role of oral anticoagulation has not been adequately investigated. Patients with a bioprosthetic aortic or mitral valve are typically managed with antiplatelet therapy. If an ischemic stroke or TIA occurs in these patients despite adequate antiplatelet, the benefit of switch- ing to oral anticoagulation with warfarin or a DOAC is unknown and warrants further investigation. In patients with IE, small observational series sug- gest a role for routine neurovascular imaging studies (CT or MRA) to screen for mycotic aneurysms, which can potentially influence the treatment plan.498,499 Further larger studies are needed to determine whether routine neurovascular imaging to screen for mycotic aneurysms in IE improves outcomes. 