Factors associated with high-risk patent foramen ovale in ischemic stroke patients: SAFAS study

Persistent foramen ovale (PFO) contributes to embolic stroke of undetermined source (ESUS) and is associated with stroke recurrence, although the exact mechanism of ischemic events is not fully understood. Several biomarkers have been developed for the prediction of AF after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO. We sought to determine how biomarkers may aid in the diagnosis of PFO. The SAFAS study was a prospective single-center study that included all patients hospitalized between March 31, 2018, and January 18, 2020, in the stroke department of the Dijon University Hospital for ischemic stroke without obvious cause and without a history of atrial fibrillation.PFO was defined according to the CLOSE study: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within 3 cardiac cycles after right atrial opacification). Of the 240 patients included in SAFAS, 226 had complete PFO data, and 25 (11%) had high-risk PFO. Compared with patients without PFO, patients with high risk PFO were significantly younger (59 ± 14 vs. 70 ± 15, P = 0.001), had less frequent previous hypertension (32% vs. 59%, P = 0.011), and more frequent cerebellar territory involvement (28 vs. 8%, P = 0.010). In addition, they had a higher left ventricular ejection fraction (65 ± 9 vs. 59 ± 10, P = 0.006), and a lower left atrial index volume (24 ± 9 vs. 32 ± 15,P = 0.029). Regarding the new biomarkers tested in the SAFAS study, after ROC curve analysis for thresholds definition, PFO patients more often had galectin-3 < 9.5 ng/mL (54% vs. 27%, P = 0.010), ST2 < 13,380 pg/mL (46% vs. 24%, P = 0.026), GDF-15 < 1209 ng/mL (54% vs. 27%, P = 0.009) and osteoprotegerin < 1133 pg/mL (83% vs. 58%, P = 0.016). After multivariate backward stepwise logistic regression, osteoprotegerin < 1133 pg/L (OR (95%CI) 7.1 (1.5–33.1), P = 0.012) and cerebellar territory involvement (OR (95%CI) 4.2 (1.1–15.6), P = 0.035) were independently associated with PFO. Our results suggest that data from clinical presentation, biomarkers, and brain imaging are associated with PFO in a cohort of patients with ischemic stroke. Cerebellar location and low osteoprotegerin levels may help to better select the population that should benefit from intensive screening for high-risk PFO.