Data from isolated case reports and small case series suggest that DOACs or low-molecular-weight hepa- rin may be beneficial in these clinical scenarios, but larger-scale multicenter observational data will be necessary to clarify whether DOACs or low-molecu- lar-weight heparin can be used safely and effectively in these patients.551 The role of empirical oral anticoagulation in patients with cardiomyopathy, reduced EF, and a history of stroke/TIA should also be investigated further in future studies because these patients were largely underrepresented in RCTs of prophylactic oral anti- coagulation in patients with cardiomyopathies and reduced EF. 5.4.5. Patent Foramen Ovale Recommendations for PFO Referenced studies that support recommendations are summarized in online Data Supplements 38 and 39. COR LOE Recommendations In patients with a nonlacunar ischemic stroke of undetermined cause and a PFO, recom- mendations for PFO closure versus medical management should be made jointly by the patient, a cardiologist, and a neurologist, taking into account the probability of a causal role for the PFO. 