慢性心力衰竭患者死亡风险的无创性指标预测和干预治疗评价

发布时间：2018-07-13 19:11

【摘要】：第一部分慢性心力衰竭患者死亡风险预警和生活质量评估的意义背景：慢性心力衰竭(CHF)是各种心脏疾病的最后阶段。随着我们国家冠心病发病率的上升和整体人群寿命的延长,CHF的发病率和就诊率也在逐年提高,继而因为心力衰竭导致的死亡率增加和心功能差造成的生活质量下降越来越受到人们的关注。作为慢性疾病管理的代表,积极治疗疾病的同时,其病情评估和死亡风险的预警也属于其中重要的内容,近些年来不断有新的指标或量表出现,我们在实践中去验证和评价是非常有必要的。在CHF的评估指标中,传统指标纽约心功能分级和左室射血分数(LVEF)之后,我们又有了脑钠肽(BNP)和脑钠肽前体氨基端片段(NT-proBNP);心脏自主神经功能评估,过去应用窦性心率震荡(HRT)、心率变异性(HRV),现在有了心率减速力(DC);急性生理与慢性健康评分(APACHE)已有近30年历史,已更新至第四版,结合不同国家和疾病种类的差异,最新一版评分正面临着本土化的改良；过去明尼苏达心力衰竭生存质量量表(MLHF)得到了广泛认可,现在也有了中国改良版。新指标的广泛应用让我们更好的认识CHF,有利于CHF的管理,减少心血管事件的发生,促进CHF患者的恢复,提高患者的生活质量。目的：探讨CHF患者不同时期各种死亡风险预测指标和生活质量评估的变化情况方法：前瞻性纳入慢性心力衰竭失代偿期(DCHF)患者268例,收集患者一般情况、心衰病因和病史,入院前3天和出院前3天内分别进行M型超声心动图、NT-proBNP、动态心电图、APACHE评分、MLHF评分等指标监测。患者或家属入院后即开始行CHF健康宣教,并纳入慢性疾病管理,加强指导和随访,于患者出院后1月和出院后3个月两次随访患者,再次记录一般情况,同时再次行MLHF评分,比较以上监测指标在CHF患者病情加重和转归后发生的变化。结果：最终我们共纳入患者219例,出院前病情好转210例,未愈4例,死亡5例。住院期间调查显示患者对所患疾病或伴随疾病的知晓率较高,但健康自我管理的理念相对薄弱,药物依从性差,尤其体现在β受体阻滞剂和ACEI (ARB)应用方面,入院前主动复诊的患者比例较低。患者的M型超声心动图结果(LVEF、左室舒张末直径和左房直径)在DCHF患者住院转归前后无明显变化(p0.05)；HRV和DC在治疗后各项指标明显升高,比较有统计学意义(p0.05)；免疫检测指标NT-pro-BNP、APACHE评分和MLHF评分在治疗后明显降低,比较有统计学意义(p0.05)；住院期间经过医务人员的慢病宣教后,患者的健康学习意识明显提高,服用药物的依从性和达标率较前明显增加,CHF的健康自我管理项目除外戒烟和监测血糖外,运动、饮食和血压、脉搏、体重监测都较入院前明显提高,比较有统计学意义(p0.05)。出院后慢病管理期间有3例患者死亡,有4例患者中途失访。对照出院1个月和3个月的各项指标,在患者健康自律,医务人员督促的慢病管理模式下,以上各项指标无明显变化(p0.05),戒烟和血糖监测有反弹的趋势。结论：预测DCHF死亡风险的单项指标和综合指标在病情转归前后都有一定的变化,各有优势,监测的方便性和指导价值不同,总体上综合指标对死亡的预测价值较高；在慢病管理下的CHF患者,自我管理能力明显提高,MLHF评分明显下降。第二部分心率减速力对慢性心力衰竭失代偿期患者死亡风险的预警价值背景：DCHF因为有较高的死亡风险,一直是心血管病临床研究的重点。发生心血管事件前患者的血流动力学情况和神经内分泌状态在其发病原因中占有很大比重,因此深入研究CHF与自主神经的关系势在必行。作为自主神经检测的临床指标,德国Georg Schmidt教授在HRT基础上开发出来的DC无疑为我们带来了新的希望。DC被证实主要反映了迷走神经的功能,随着人们认识到迷走神经在CHF中发挥着更重要的作用,DC检测的价值更加明显。作为第一个可以量化区别迷走神经和交感神经的指标,其到底与CHF患者心血管事件发生的关系如何?与患者的心功能状况的关系如何?是否优于过去的常用自主神经评价指标HRV?是否与整体死亡风险评分APACHE评分一致?这些问题都有待多中心、大规模的研究,有待大家在实践中总结。作为中国的研究者,郭继鸿教授将DC的概念引入中国,目前DC检测已与动态心电图融合到了一起,郭教授建议我们中国医生也应当充分利用这一优势,积极实践,总结经验,为我们国家心源性猝死(SCD)的预警和防治做出自己的贡献。目的：探讨DC对DCHF患者死亡风险的预警价值。方法：选择74例DCHF患者,通过动态心电图和APACHE评分对患者治疗前后的病情进行评估,动态心电图重点分析DC和HRV,比较DCHF患者在不同心功能分级下DC、HRV、APACHE评分的区别,分析心功能分级、DC、HRV、 APACHE评分间的相关性,比较DC、HRV和APACHE评分预警患者死亡风险的ROC曲线下面积(AUC)。结果：DC和HRV各时域指标：RR间期总体标准差(SDNN)、5min RR间期平均值的标准差(SDANN)、相邻RR间期差值的均方根(RMSSD)在DCHF患者治疗前低于正常值,治疗后各指标明显升高,治疗前后比较有统计学意义(t=5.518,3.075,2.814,3.109, p0.05); APACHE评分在DCHF患者治疗前高于正常值,治疗后评分明显下降,治疗前后比较有统计学意义(t=4.072,p0.05)。不同心功能分级下DC、HRV (SDNN、SDANN、RMSSD)、APACHE评分各自的比较都有统计学意义(F=11.33,10.76,12.08,12.45,10.98,p0.05),DC和HRV各指标随心功能下降而降低,APACHE评分随心功能下降而升高。DC与HRV各指标(SDNN、SDANN、RMSSD)均呈正相关(r=0.601,0.588,0.457,p0.05)；DC与APACHE评分呈中度负相关(r=-0.639,p0.05)。心力衰竭时心功能分级与DC与相关性的分析：DC与心功能分级呈中度负相关(r=-0.571,p0.05)。APACHE评分与心功能分级呈中度正相关(r=0.653,p0.05),HRV各指标(SDNN、SDANN、RMSSD)与心功能分级呈低度相关(r=-0.385,-0.290,-0.418,p0.05)。预测DCHF患者死亡风险的价值：APACHE评分DCSDANN (AUC=0.905,0.795,0.717), DC的预测价值为中度。结论：DC和HRV在DCHF时随心功能下降明显下降,APACHE评分在DCHF时随心功能下降呈反向升高,DC和APACHE评分与心功能的相关性较高。DC与病情危重评价的综合指标APACHE评分相关性较好,其与同样反映自主神经紊乱的HRV相关性也较好,其作为单项指标预警DCHF患者死亡风险有较高的价值。第三部分参松养心胶囊对慢性心力衰竭患者自主神经功能紊乱调节的评价背景：CHF患者存在严重的自主神经功能紊乱,过去认为是心脏重构时交感神经作用被加强,现在认为是主要是迷走神经的作用被弱化了。随着评估自主神经功能状态的无创指标的发展,我们有了新的和连续心率减速力(DRs),其通过分析动态心电图整合心电信号,能定量反映迷走神经功能。临床研究发现应用β受体阻滞剂可降低CHF的猝死风险,其最主要的作用机制就是通过抑制交感神经而达到改善自主神经功能紊乱的目的。一方面单纯抑制交感神经的后果就是可造成负性肌力作用,另一方面在用药时机和达标时间上因为潜在的问题,而导致临床上应用受到很大限制,因此,探讨新的药物或手段来调节自主神经功能成为我们的研究方向。传统中成药参松养心胶囊对于调节自主神经功能有很好的疗效,它有多靶点、双向调节作用的优点,这不仅成为它的优点,甚至引起了抗心律失常药物治疗领域对治疗理念的反思。由于过去在CHF患者中较少的应用参松养心胶囊,另外有新的评价指标出现,本文拟通过应用DRs来评价CHF时参松养心胶囊和美托洛尔片对自主神经功能紊乱的调节作用,为CHF患者自主神经功能紊乱的治疗寻找一种更有效的方法。目的：评价参松养心胶囊对CHF患者自主神经功能紊乱的调节作用。方法：将临床确诊为CHF的99例患者随机分为参松养心组(n=53)和美托洛尔组(n=46),用药前和用药1月后分别行动态心电图,计算DRs,比较两种药物对DRs的调节作用,评价参松养心胶囊对CHF患者自主神经功能的调节作用和预防猝死的价值。结果：两组患者治疗前后DRs各指标DR2、DR4、DR8的变化基本一致,治疗后两组患者猝死风险明显降低。结论：参松养心胶囊对CHF患者自主神经功能的调节作用与美托洛尔片基本相当,其适应证和患者耐受性更优于美托洛尔片。
[Abstract]:The significance of death risk early warning and quality of life assessment in the first part of chronic heart failure: chronic heart failure (CHF) is the last stage of various heart diseases. With the increase of the incidence of coronary heart disease in our country and the prolongation of the whole population life, the incidence and the rate of CHF are increasing year by year, and then because of heart failure. As a representative of the chronic disease management, as a representative of the chronic disease management, the assessment of the disease and the early warning of the risk of death are also important. In recent years, there are new indicators or scales, and we are in practice. Verification and evaluation are necessary. In the CHF assessment index, after the New York cardiac function classification and the left ventricular ejection fraction (LVEF), we also have the brain natriuretic peptide (BNP) and the brain natriuretic peptide amino terminal fragment (NT-proBNP); the cardiac autonomic nervous function assessment, the use of sinus heart rate oscillation (HRT), heart rate variability (HRV), now. With the heart rate deceleration (DC); the acute physiological and chronic health score (APACHE) has a history of nearly 30 years and has been updated to the fourth edition. The latest edition of the first edition is facing a localized improvement in combination with the differences in different countries and diseases; the past Minnesota heart failure quality scale (MLHF) has been widely recognized and now is also in the middle The extensive application of the new national index allows us to better understand the CHF, be beneficial to the management of CHF, reduce the occurrence of cardiovascular events, promote the recovery of CHF patients and improve the quality of life of the patients. Objective: To explore the changes in the predictors of death risk and the changes of quality of life in different periods of CHF patients: prospective inclusion 268 patients with chronic heart failure decompensation (DCHF), the general situation of patients, the cause and history of heart failure, 3 days before admission and 3 days before discharge, respectively, M echocardiography, NT-proBNP, dynamic electrocardiogram, APACHE score, and MLHF score were monitored. The patients or family members began to conduct CHF health education and included chronic diseases after admission. Management, guidance and follow-up, the patients were followed up in January and 3 months after discharge two times after discharge. Again, the general situation was recorded again, and the MLHF score was performed again. The changes of the above monitoring indexes in the patients with CHF were compared. Results: 219 cases were admitted to the patients, 210 cases were improved before discharge, and 4 cases were not healed, 5 cases of death. During hospitalization, the survey showed that the patient had a higher awareness of the disease or associated disease, but the concept of health self-management was relatively weak, and the compliance of the drug was poor, especially in the application of beta blockers and ACEI (ARB), which were lower than those of the cases before admission. The results of M type echocardiography (LVEF, left ventricle) There was no significant change (P0.05) before and after the hospitalization of DCHF patients. The indexes of HRV and DC were significantly higher after the treatment (P0.05), and the immunoassay index (NT-pro-BNP), APACHE score and MLHF score decreased significantly after treatment (P0.05). After the medical staff's slow disease propaganda and education, the health learning consciousness of the patients was obviously improved, the compliance and standard rate of medication increased obviously. The health self-management items of CHF except smoking cessation and monitoring blood sugar, exercise, diet and blood pressure, pulse and weight monitoring were significantly higher than before admission, and were statistically significant (P0.05). After discharge, there were statistical significance (P0.05). 3 patients died during the management of chronic disease, and 4 cases were lost in the midway. The indexes of 1 months and 3 months were compared with 1 months and 3 months. There was no obvious change in the above indexes (P0.05), and the trend of rebound in smoking cessation and blood glucose monitoring. The standard and comprehensive indexes have certain changes before and after the prognosis of the disease, each has advantages, the convenience and guiding value of monitoring are different. In general, the comprehensive index has a higher predictive value for death. In the CHF patients under the management of slow disease, the self management ability is obviously improved and the MLHF score is obviously decreased. The second part of the heart rate deceleration force is the chronic heart failure. The early warning value of the risk of death in patients with exhaustive decompensation: DCHF has been the focus of clinical research on cardiovascular disease because of the high risk of death. The hemodynamic and neuroendocrine state of the patients before the occurrence of cardiovascular events occupies a large proportion in the cause of the disease. Therefore, the relationship between CHF and the autonomic nervous system is deeply studied. It is imperative. As a clinical indicator of autonomic nerve testing, the DC developed by Professor Georg Schmidt on HRT undoubtedly brings us new hope that.DC has been proved to reflect the function of the vagus nerve mainly. As people realize that the vagus nerve plays a more important role in CHF, the value of DC detection is more obvious. What is the relationship between the first quantifying vagal and sympathetic nerves? What is the relationship with cardiovascular events in patients with CHF? What is the relationship with the heart function of the patient? Is it better than the past common autonomic nerve evaluation index HRV? Is it consistent with the overall death risk score APACHE score? These questions need to be much more As a researcher of China, Professor Guo Jihong introduced the concept of DC into China. At present, DC testing has merged with the dynamic electrocardiogram. Professor Guo suggested that we Chinese doctors should make full use of this advantage, actively practice and summarize the experience for the heart of our country. The early warning and prevention of death (SCD) made its own contribution. Objective: To explore the early warning value of DC for the death risk of DCHF patients. Methods: 74 patients with DCHF were selected to evaluate the patient's condition before and after treatment by dynamic electrocardiogram (ECG) and APACHE score. The dynamic electrocardiogram (ECG) was focused on DC and HRV, and the DCHF patients were compared to DC, H under the classification of the heart function. The difference between RV and APACHE scores, the correlation between the classification of cardiac function, the DC, HRV, and APACHE scores, and the area of ROC curve under the DC, HRV and APACHE scores early warning of the mortality risk of the patients (AUC). The root (RMSSD) was lower than the normal value before the treatment of DCHF patients. The indexes were significantly higher after the treatment (t=5.518,3.075,2.814,3.109, P0.05) before and after treatment; the APACHE score was higher than the normal value before the treatment of the DCHF patients. The scores of the patients were significantly decreased after the treatment, and there were statistically significant (t=4.072, P0.05) before and after treatment (t=4.072, P0.05). The lower DC, HRV (SDNN, SDANN, RMSSD), APACHE scores were all statistically significant (F=11.33,10.76,12.08,12.45,10.98, P0.05), DC and HRV indexes decreased with the decrease of cardiac function, APACHE score decreased with the decrease of heart function. A moderate negative correlation (r=-0.639, P0.05). The analysis of cardiac function classification and DC and correlation in heart failure: DC and cardiac function classification showed moderate negative correlation (r=-0.571, P0.05).APACHE score was moderately positive correlation with cardiac function classification (r=0.653, P0.05), HRV indexes (SDNN, SDANN,) were low related to cardiac function classification. 418, P0.05). The value of predicting the risk of death of DCHF patients: the APACHE score DCSDANN (AUC=0.905,0.795,0.717), and the predictive value of DC is moderate. Conclusion: DC and HRV in DCHF decrease significantly with the decrease of cardiac function, APACHE score in DCHF increases with the decrease of cardiac function. The APACHE score of the re evaluated comprehensive index is better, and it has a better correlation with HRV, which also reflects the autonomic nervous disorder. As a single index, it is of high value for early warning of the death risk of DCHF patients. The third part of Shen Song Yangxin capsule is the evaluation background of the regulation of autonomic nervous dysfunction in patients with chronic heart failure: CHF patients. In the severe autonomic nervous dysfunction, it was thought that the sympathetic action of cardiac remodeling was strengthened in the past. It is now considered that the function of the vagus nerve is weakened. With the development of noninvasive indicators to evaluate the state of autonomic nervous function, we have new and continuous heart rate deceleration (DRs), which through the analysis of the integration of the dynamic electrocardiogram. ECG signals can quantitatively reflect the function of the vagus nerve. Clinical studies have found that the use of beta blockers can reduce the risk of sudden death in CHF. The main mechanism is to improve the autonomic nervous dysfunction by inhibiting the sympathetic nerve. On the one hand, the effect of simply inhibiting the sympathetic nerve is the negative inotropic effect. On the other hand, because of the potential problems in the time of drug use and the time to reach the standard, the clinical application is greatly restricted. Therefore, it is our research direction to explore the new drugs or means to regulate the autonomic nerve function. The advantages of bi-directional regulation not only become its advantages, but also cause a reflection on the concept of treatment in the field of antiarrhythmic drug treatment. Because of the less use of Shen Song Yangxin Capsule in the past CHF patients, and the emergence of new evaluation indicators, this article is intended to evaluate CHF Shen Song Yangxin Capsule and metoprolol tablet by using DRs. The regulation of autonomic nervous dysfunction in order to find a more effective method for the treatment of autonomic nervous dysfunction in CHF patients. Objective: To evaluate the effect of Shen Song Yangxin Capsule on autonomic nervous dysfunction in CHF patients. Methods: 99 patients with clinical diagnosis of CHF were divided into two groups: n=53 and metoprolol group. (n=46), before and after January, the dynamic electrocardiogram was performed and the DRs was calculated respectively. The regulation of two drugs on DRs was compared and the value of the regulation of Shen Song Yangxin Capsule on the autonomic nervous function of CHF patients and the value of sudden death prevention were evaluated. Results: the changes of DR2, DR4, DR8 of each DRs index in the two groups were basically the same before and after treatment, and two groups after the treatment were treated. The risk of sudden death was significantly reduced. Conclusion: the regulation of Shen Song Yangxin Capsule on the autonomic nervous function of CHF patients was basically equal to that of metoprolol. The indications and patient tolerance were better than that of metoprolol.
【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.6

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