心脏术后纤维蛋白原和胶原代谢的变化规律及其与术后心房颤动关系的前瞻性队列研究

Changes of fibrinogen and collagen metabolism after cardiac surgery and their relationship with postoperative atrial fibrillation: A prospective cohort study

目的探索冠状动脉旁路移植术(coronary artery bypass grafting,CABG)和/或心脏瓣膜置换(heart valve replacement,VR)术后外周血液和心包引流液中纤维蛋白原及胶原代谢经典标记物[Ⅰ型前胶原羧基端前肽(PICP)及Ⅰ型胶原羧基末端交联肽(ICTP)]的变化规律,并评价其与心脏术后心房颤动(postoperative atrial fibrillation,POAF)的关系。方法纳入2021年3—6月在北京朝阳医院心脏中心行CABG和/或VR术的患者。分别于术前、术后0 h、6 h、24 h、48 h采集外周血液和心包引流液标本,检测其中的PICP、ICTP、纤维蛋白原水平,并同时收集术前、术中和术后的混杂因素。PICP、ICTP、纤维蛋白原水平采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测。结果纳入患者26例,其中男18例、女8例,平均年龄(64.04±7.27)岁。共收集125例次血液样本,78例次引流液样本。POAF发生率为34.6%。三大因子中,POAF组患者的心包引流液中纤维蛋白原水平在术后48 h内呈现两个高峰(术后0 h、24 h);而窦性心律(SR)组则呈现持续下降的趋势。两组患者心包引流液中纤维蛋白原随时间变化趋势显著不同(P=0.022);血液中的纤维蛋白原,及血液和引流液中的PICP和ICTP则呈现整体下降的趋势,其随时间变化的趋势在两组患者中差异无统计学意义(P>0.05)。单因素分析显示,POAF组患者心包引流液中术后24 h及48 h的纤维蛋白原、术前血液中的纤维蛋白原、术后0 h的PICP及右房长径显著高于或长于SR组。多元回归分析显示,术后24 h心包引流液中的纤维蛋白原≥11.47 ng/mL[OR=14.911,95%CI(1.371,162.122),P=0.026]及右房长径≥46 mm[OR=10.801,95%CI(1.011,115.391),P=0.049]是POAF的独立预测因子。结论本研究发现术后24 h心包引流液中的纤维蛋白原是一种潜在的、新型的、无创的POAF预测因子。研究结果为POAF的发生机制探讨提供了新思路,并为临床POAF的精准预测和预防提供了研究基础。

Objective To investigate the changes of fibrinogen and classical markers of collagen metabolism[carboxy-terminal propeptide of type Ⅰ procollagen(PICP) and carboxy-terminal cross-linked peptide of type Ⅰ collagen(ICTP)] in peripheral blood and pericardial drainage after coronary artery bypass grafting(CABG) and/or heart valve replacement(VR), and to evaluate their relationship with postoperative atrial fibrillation(POAF) after cardiac surgery.Methods Patients who underwent CABG and/or VR in the Heart Center of Beijing Chao-Yang Hospital from March to June 2021 were included. Peripheral blood and pericardial drainage fluid samples were collected before surgery and at 0 h,6 h, 24 h and 48 h after surgery to detect PICP, ICTP and fibrinogen levels, and preoperative, intraoperative and postoperative confounding factors were also collected. PICP, ICTP and fibrinogen levels were measured by enzyme-linked immunosorbent assay(ELISA). Results A total of 26 patients with 125 blood samples and 78 drainage samples were collected. There were 18 males and 8 females with an average age of 64.04±7.27 years. The incidence rate of POAF was34.6%. Among the factors, the fibrinogen level in pericardial drainage showed two peaks within 48 h after operation(0 h and 24 h after operation) in the POAF group, while it showed a continuous downward trend in the sinus rhythm(SR)group, and the change trend of fibrinogen in pericardial drainage was significantly different over time between the two groups(P=0.022). Fibrinogen in blood, PICP and ICTP in blood and drainage showed an overall decreasing trend, and their trends over time were not significantly different between the two groups of patients(P>0.05). Univariate analysis showed that fibrinogen at 24 h and 48 h after pericardial drainage, fibrinogen in preoperative blood, PICP immediately after surgery and right atrial long axis diameter were significantly higher or longer in the POAF group than those in the SR group. Multiple regression showed that fibrinogen≥11.47 ng/mL in pericardial drainage 24 h after surgery(OR=14.911,95%CI 1.371-162.122, P=0.026), right atrial long axis diameter≥46 mm(OR=10.801, 95%CI 1.011-115.391, P=0.049) were independent predictors of POAF. Conclusion This study finds the regularity of changes in fibrinogen and collagen metabolic markers after CABG and/or VR surgery, and to find that fibrinogen in pericardial drainage 24 h after surgery is a potential novel and predictive factor for POAF. The results provide a new idea for exploring the mechanism of POAF,and provide a research basis for the accurate prediction and prevention of clinical POAF.