Background

Embolic stroke of undetermined source (ESUS) accounts for approximately 17% of strokes according to recent meta-analyses. Diagnostic management aims to ascertain or rule out comorbidities that may be adjudicated as cause of stroke and include standard long-term cardiac monitoring, cerebral artery ultrasound, and echocardiography. Depending on findings, secondary prevention involves anti-thrombotic management by anti-platelet or anticoagulation treatment. More recently, transesophageal echocardiography has gained attention to diagnose possible patent foramen ovale (PFO), in case of which interventional PFO closure has been demonstrated to be superior to anti-platelet therapy alone. However, as PFO remains a common finding in up to 25% of the population, it remains unclear if all patients with ESUS and PFO do equally benefit from PFO closure.

Methods

We have formed an interdisciplinary team involving the cardiology and neurology departments, and have developed and established a standardized diagnostic and treatment algorithm for the management of patients with ESUS (Figure). In our single center study, we aim to prospectively enroll all patients presenting with ESUS into management guided by this algorithm. Following ESUS and standard diagnostic work-up, we stratify patients by age to receive additional transesophageal echocardiography for assessment of PFO. In all patients, we aim to obtain long-term cardiac monitoring by implantation of an implantable cardiac monitor (ICM). Depending on the individual risk profile, we subject patients to different treatment regimens. In those age ≥60 years or without PFO, we aim for ICM registration up to 36 months. Patients receive anti-platelet therapy until the detection of atrial fibrillation. In those <60 years and with PFO, we aim for PFO closure within three to six months. Until then, we collect extended electrocardiographic information. ICM follow-up extends until 36 moths to facilitate diagnosis of atrial fibrillation and eventually switch from anti-platelet to anticoagulation therapy.

Results

Started on January 1^st, 2018, to date, we have enrolled 114 patients presenting at a mean age of 66 years. The proportion of males was 63.2% (n=72). In 60.0%, we have successfully implanted an ICM. Of those <60 years at inclusion, we have detected a PFO in 24 (50%), of which a subset has undergone PFO closure within 6 months of cardiac monitoring. In turn, atrial fibrillation as presumed cause of stroke was detected in 4 patients during extended ICM and electrocardiogram monitoring. The rate of stroke recurrence was 3%, a rate comparable to large clinical trials.

Conclusion

The current publicly available consensus documents for work-up and treatment of patients with ESUS with or without PFO leaves unaddressed questions. Our prospective observational cohort study will help to shed light on several of these unmet needs, including the detection rate of atrial fibrillation in younger ESUS patients, the rate of atrial fibrillation following PFO closure, and the differences in stroke recurrence depending on anti-thrombotic management.