Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Spain.
Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Research Center, Montreal Heart Institute, Montreal, Canada.
Rev Esp Cardiol (Engl Ed). 2022 Sep;75(9):717-726. doi: 10.1016/j.rec.2021.12.001. Epub 2022 Jan 20.
Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm.
Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months.
Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months.
In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF.
在隐源性卒中(CrS)患者中,确定亚临床心房颤动(AF)的生物标志物最具意义。我们旨在评估 CrS 伴 AF 患者与持续窦性心律患者的循环microRNA(miRNA)谱。
在 64 例连续接受出院前植入式监测的 CrS 患者中,选择了 18 例患者(9 例伴 AF,9 例持续窦性心律)进行高通量 754 种 miRNA 的测定。还筛选了 9 例同时患有中风和 AF 的患者,以提高 miRNA 选择的产量。在独立队列中复制了差异表达的 miRNA(n=46)。将生物标志物按中位数分层,并纳入逻辑回归分析,以评估其与 6 个月和 12 个月时 AF 的关系。
在 AF 患者和非 AF 患者之间有 8 种 miRNA 表达差异。在复制队列中,miR-1-3p,一种参与心脏心律失常发生的基因调节剂,是唯一在 CrS 伴 AF 患者中显著高于窦性心律患者且与 AF 负荷有一定关联的 miRNA。高(=高于中位数)miR-1-3p 血浆值,加上左心房射血分数低,与 6 个月和 12 个月时的 AF 存在独立相关。
在该队列中,CrS 伴随后发生 AF 的患者的血浆 miR-1-3p 水平升高。我们的结果初步表明,miR-1-3p 可能是一种新的生物标志物,与临床参数一起,有助于识别 CrS 伴隐匿性 AF 风险高的患者。