目的 探讨常规治疗无效的心力衰竭（心衰）伴心房颤动（房颤）患者应用注射用重组人脑利钠肽（新活素）治疗后血清半乳糖凝集素-3（Gal-3）、结缔组织生长因子（CTGF）水平变化及其与房颤复发的相关性。方法 选取2018年4月—2020年4月邢台市第三医院收治的148例经常规治疗无效的心衰伴房颤患者作为研究对象，所有患者均给予注射用重组人脑利钠肽治疗，具体用法为500 μg注射用重组人脑利钠肽＋50 mL 0.9%氯化钠注射液，先采用负荷剂量1.5～2.0 μg·kg^-1静脉推注3～5 min，之后以0.007 5～0.015 0 μg·kg^-1·min^-1静脉滴注24～72 h，根据患者体质量调节负荷量和静脉滴注速率。评价治疗效果，检测并比较治疗前、用药30 min、用药24 h、用药结束后患者的心率、收缩压、舒张压、血氧饱和度、24 h尿量，检测并比较患者治疗前、治疗后7 d、治疗后30 d的左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）、左心房内径（LAD）、左室射血分数（LVEF）和血清N-末端脑利钠肽前体（NT-proBNP）、超敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）、Gal-3、CTGF水平，记录患者治疗过程中不良反应发生情况，随访治疗后3个月的房颤复发情况。根据治疗后3个月房颤复发情况将入选患者分为复发组（n=27）和未复发组（n=121），比较两组患者治疗前血清Gal-3、CTGF水平，应用Pearson相关分析进行线性相关性分析，单因素和多因素Logistic回归分析患者治疗后房颤复发的相关危险因素。结果 148例心衰伴房颤患者中有122例（82.43%）用药24 h内转复为窦性心律。与治疗前比较，患者用药30 min、用药24 h后、用药结束后的心率、收缩压、舒张压均明显降低，血氧饱和度和24 h尿量明显增加，差异有统计学意义（P<0.05）；治疗后7 d、治疗后30 d患者的LVEF明显升高，LAD、LVEDD、LVESD和血清NT-proBNP、hs-CRP、TNF-α、Gal-3、CTGF水平均明显降低，差异有统计学意义（P<0.05）。Pearson相关性分析结果显示，心衰伴房颤患者的血清Gal-3、CTGF水平与NT-proBNP和心功能指标LAD、LVEDD、LVESD、LVEF均有明显相关性（P<0.05）。复发组与未复发组患者年龄、病程、LAD、LVEF及治疗前NT-proBNP、hs-CRP、TNF-α、Gal-3、CTGF水平比较均有显著性差异（P<0.05），Logistic回归分析显示，LAD、病程时间、NT-proBNP、hs-CRP、TNF-α、Gal-3、CTGF水平均是影响房颤复发的危险因素。结论 应用注射用重组人脑利钠肽治疗心力衰竭伴房颤效果确切，不良反应发生率低，其能及时有效缓解患者呼吸困难症状，降低血清NT-proBNP和炎症因子水平，明显改善心功能指标和全身炎症状态，此外其还能明显降低血清Gal-3、CTGF水平。血清Gal-3、CTGF水平与NT-proBNP和心功能指标呈明显相关性，这2个指标可作为心衰伴房颤患者治疗后房颤复发的预测指标。

Objective To investigate the changes of serum galectin-3 (Gal-3) and connective tissue growth factor (CTGF) levels and their correlation with the recurrence of atrial fibrillation in patients with heart failure and atrial fibrillation who failed to respond to conventional treatment. Methods Total 148 patients with heart failure with atrial fibrillation treated in Xingtai Third Hospital from April 2018 to April 2020 were selected as the research object. All patients were treated with Recombinant Human Brain Natriuretic Peptide for Injection, with a specific usage of 500 μg Recombinant Human Brain Natriuretic Peptide for Injection + 50 mL diluent (0.9% Sodium Chloride Injection), the loading dose was 1.5-2.0 μ g ·kg^-1 was injected intravenously for 3-5 min, followed by 0.007 5-0.015 0 μg·kg^-1·min-1 intravenous drip for 24-72 h, and the load and intravenous drip rate were adjusted according to the patient's body mass. Treatment effect was evaluated. The heart rate, systolic blood pressure, diastolic blood pressure, blood oxygen saturation and 24 h urine volume of patients were detected and compared before treatment, 30 min after treatment, 24 h after treatment, and the end of treatment. The left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left atrial diameter (LAD), left ventricular ejection fraction (LVEF), serum levels of N-terminal pro brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α), Gal-3, and CTGF were detected and compared before treatment, seven days after treatment and 30 days after treatment. The occurrence of adverse reactions during treatment and the recurrence of atrial fibrillation three months after treatment were recorded. According to the recurrence of atrial fibrillation three months after treatment, the selected patients were divided into recurrence group (n=27) and non recurrence group (n=121). The levels of serum Gal-3 and CTGF were compared between two groups before treatment. Pearson correlation analysis was used for linear correlation analysis, and univariate and multivariate Logistic regression analysis were used to analyze the risk factors of atrial fibrillation recurrence after treatment. Results Total 122 (82.43%) of 148 patients with heart failure and atrial fibrillation were converted to sinus rhythm within 24 h. Compared with before treatment, the heart rate, systolic blood pressure and diastolic blood pressure decreased significantly 30 min after treatment, 24 h after treatment, and the end of treatment, and the blood oxygen saturation and 24 h urine volume increased significantly (P < 0.05). LVEF, LAD, LVEDD, LVESD and serum NT-proBNP, hs-CRP and TNF-α increased significantly seven and 30 days after treatment. The levels of Gal-3 and CTGF decreased significantly (P < 0.05). Pearson correlation analysis showed that the levels of serum Gal-3 and CTGF were significantly correlated with NT-proBNP and cardiac function indexes LAD, LVEDD, LVESD and LVEF (P < 0.05). There were significant differences in Age, course of disease, LAD, LVEF, NT-proBNP, hs-CRP, TNF-α, Gal-3 and CTGF before treatment in recurrent group and non recurrent group (P < 0.05). Logistic regression analysis showed that LAD, duration of disease, NT-proBNP, hs-CRP and TNF-α, Gal-3 and CTGF are risk factors for the recurrence of atrial fibrillation. Conclusion Recombinant Human Brain Natriuretic Peptide for Injection is effective in the treatment of heart failure with atrial fibrillation, and the incidence of adverse reactions is low. It can timely and effectively alleviate the symptoms of dyspnea, reduce the levels of serum NT-proBNP and inflammatory factors, significantly improve the indexes of cardiac function and systemic inflammation, and significantly reduce the levels of serum Gal-3 and CTGF. Serum Gal-3 and CTGF levels were significantly correlated with NT-proBNP and cardiac function indexes. These two indexes can be used as predictors of atrial fibrillation recurrence in patients with heart failure and atrial fibrillation after treatment.

R972

邢台市重点研发计划项目（2020ZC178）