Cardiology Department, University Hospital, 14, rue Paul-Gaffarel, 21079 Dijon cedex, France; Pathophysiology and Epidemiology of Cerebro-Cardiovascular diseases (EA 7460), Faculty of Health Sciences, université de Bourgogne, université de Bourgogne Franche-Comté, Dijon, France.
Cardiology Department, University Hospital, 14, rue Paul-Gaffarel, 21079 Dijon cedex, France.
Rev Neurol (Paris). 2024 Jan-Feb;180(1-2):33-41. doi: 10.1016/j.neurol.2023.05.007. Epub 2023 Sep 28.
Persistent foramen ovale (PFO) contributes to cryptogenic stroke 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 atrial fibrillation after stroke, but there are currently only limited data on their potential value for the diagnosis of PFO-related stroke.
This 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 systematically screened by transthoracic echocardiography and images were reviewed by an independent cardiologist blinded from clinical data. PFO was defined according to the CLOSE trial criteria: PFO associated with interatrial septal aneurysm or significant interatrial shunt (> 30 microbubbles in the left atrium within three cardiac cycles after right atrial opacification). The potential association of PFO-related stroke with biomarkers of cardiac fibrosis and inflammation such as galectin-3, GDF-15, ST-2, osteoprotegerin and NT-proBNP was tested using multivariate backward stepwise logistic regression.
Of the 240 patients included in the SAFAS study, 229 had complete echocardiographic data, and 23 (10%) had PFO-related stroke. Patients with PFO-related stroke were significantly younger (58±14 vs. 69±14, P<0.001), had less frequent previous arterial hypertension (30 vs. 60%, P=0.008), and more frequent cerebellar territory involvement (26 vs. 9%, P=0.014) compared to the other patients. In addition, they had less frequently left atrial dilatation (left atrial index volume>34mL/m [9 vs. 35%, P=0.009]). After ROC curve analysis for definition of thresholds, PFO-related stroke patients more often had galectin-3<9.5ng/mL (59 vs. 27%, P=0.002), ST2<13380pg/ml (23 vs. 50%, P=0.007), GDF-15<1200ng/mL (59 vs. 27%, P=0.002), osteoprotegerin<1133pg/mL (82 vs. 58%, P=0.033) and NT-proBNP<300pg/mL (88 vs. 55%, P=0.009). After multivariate analysis, only galectin-3<9.5ng/mL (OR [95% CI] 3.4 [1.18; 9.8], P=0.024) and osteoprotegerin<1133pg/L (OR [95% CI] 5.0 [1.1; 22.9], P=0.038) were independently associated with PFO-related stroke.
Patients in whom cryptogenic stroke is attributed to a significant PFO have a specific clinical and biological phenotype. Low levels of galectin-3 and osteoprotegerin may help identify patients with PFO-related strokes.
永存性房间隔缺损（PFO）可导致隐源性卒中，并与卒中复发相关，尽管其缺血事件的确切机制尚未完全阐明。已有多种生物标志物被开发用于预测卒中后房颤，但目前仅有有限的数据表明其对诊断 PFO 相关卒中具有潜在价值。
这是一项前瞻性单中心研究，纳入了 2018 年 3 月 31 日至 2020 年 1 月 18 日期间因无明显病因且无房颤病史而在第戎大学医院卒中科住院的所有缺血性卒中患者。通过经胸超声心动图系统筛查 PFO，并由独立于临床数据的心脏病专家对图像进行审查。根据 CLOSE 试验标准定义 PFO：PFO 伴有房间隔瘤或明显的房间隔分流（右心房显影后 3 个心动周期内左心房内出现>30 个微泡）。使用多元逐步逻辑回归对 PFO 相关卒中与心脏纤维化和炎症的生物标志物（半乳糖凝集素-3、GDF-15、ST-2、骨保护素和 NT-proBNP）的潜在相关性进行了检验。
在 SAFAS 研究中，纳入了 240 例患者，其中 229 例患者具有完整的超声心动图数据，23 例（10%）患者存在 PFO 相关卒中。与其他患者相比，PFO 相关卒中患者明显更年轻（58±14 岁 vs. 69±14 岁，P<0.001），既往动脉高血压发生率更低（30% vs. 60%，P=0.008），且更常累及小脑区域（26% vs. 9%，P=0.014）。此外，他们的左心房扩张程度较轻（左心房指数容积>34mL/m[9% vs. 35%，P=0.009]）。对 PFO 相关卒中的定义阈值进行 ROC 曲线分析后，PFO 相关卒中患者更常出现半乳糖凝集素-3<9.5ng/mL（59% vs. 27%，P=0.002）、ST2<13380pg/ml（23% vs. 50%，P=0.007）、GDF-15<1200ng/mL（59% vs. 27%，P=0.002）、骨保护素<1133pg/ml（82% vs. 58%，P=0.033）和 NT-proBNP<300pg/ml（88% vs. 55%，P=0.009）。多变量分析后，仅半乳糖凝集素-3<9.5ng/mL（OR[95%CI]3.4[1.18;9.8]，P=0.024）和骨保护素<1133pg/L（OR[95%CI]5.0[1.1;22.9]，P=0.038）与 PFO 相关卒中独立相关。
归因于明显 PFO 的隐源性卒中患者具有特定的临床和生物学表型。低水平的半乳糖凝集素-3 和骨保护素可能有助于识别 PFO 相关卒中患者。
