Patent Foramen Ovale and Other Cardiopathies as Causes of Embolic Stroke With Unknown Source

In patients with stroke caused by cardiac embolism, the responsible heart diseases include atrial fibrillation, acute myocardial infarction, sick sinus syndrome, valvular disease, and significant heart failure. When there is no clear source of the embolism, the condition is referred to as “embolic stroke with unknown source (ESUS).” Recent studies have shown that the most common cause of ESUS is a right-to-left cardiac shunt through a patent foramen ovale (PFO). However, considering that PFOs are found in up to 25% of the general population, their presence does not necessarily indicate causality. In patients with ESUS associated with a PFO, either anticoagulants or antiplatelets are used for the prevention of future strokes or transient ischemic attacks. However, it currently remains unclear which treatment is superior. Nevertheless, recent randomized clinical trials have shown that percutaneous closure of the PFO more effectively reduces the incidence of recurrent strokes compared to medical therapy alone in patients with PFO-related strokes. This benefit is especially significant when the PFO carries high-risk features, such as a large shunt or the presence of an atrial septal aneurysm. Furthermore, the effectiveness of PFO closure has been well documented in young patients (<60 years) with a high-risk PFO development. In other cases, the therapeutic decision should be made through discussion among neurologists, cardiologists, and patients. Notably, in ESUS patients without a PFO, the underlying heart condition itself may be the source of embolism, with left atrial enlargement being the most important factor. Theoretically, anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) would be an effective therapy in these cases. However, recent trials have failed to show that NOACs are superior to antiplatelets in preventing further strokes in these patients. This may be due to the still uncertain definition of emboligenic cardiopathy and the presence of other potential embolic sources, such as mild but emboligenic arterial diseases. Overall, further research is needed to elucidate the source of embolism and to determine an effective management strategy for patients with ESUS.