發(fā)布時間：2018-07-13 19:11

【摘要】：第一部分慢性心力衰竭患者死亡風(fēng)險(xiǎn)預(yù)警和生活質(zhì)量評估的意義背景：慢性心力衰竭(CHF)是各種心臟疾病的最后階段。隨著我們國家冠心病發(fā)病率的上升和整體人群壽命的延長,CHF的發(fā)病率和就診率也在逐年提高,繼而因?yàn)樾牧λソ邔?dǎo)致的死亡率增加和心功能差造成的生活質(zhì)量下降越來越受到人們的關(guān)注。作為慢性疾病管理的代表,積極治療疾病的同時,其病情評估和死亡風(fēng)險(xiǎn)的預(yù)警也屬于其中重要的內(nèi)容,近些年來不斷有新的指標(biāo)或量表出現(xiàn),我們在實(shí)踐中去驗(yàn)證和評價是非常有必要的。在CHF的評估指標(biāo)中,傳統(tǒng)指標(biāo)紐約心功能分級和左室射血分?jǐn)?shù)(LVEF)之后,我們又有了腦鈉肽(BNP)和腦鈉肽前體氨基端片段(NT-proBNP);心臟自主神經(jīng)功能評估,過去應(yīng)用竇性心率震蕩(HRT)、心率變異性(HRV),現(xiàn)在有了心率減速力(DC);急性生理與慢性健康評分(APACHE)已有近30年歷史,已更新至第四版,結(jié)合不同國家和疾病種類的差異,最新一版評分正面臨著本土化的改良；過去明尼蘇達(dá)心力衰竭生存質(zhì)量量表(MLHF)得到了廣泛認(rèn)可,現(xiàn)在也有了中國改良版。新指標(biāo)的廣泛應(yīng)用讓我們更好的認(rèn)識CHF,有利于CHF的管理,減少心血管事件的發(fā)生,促進(jìn)CHF患者的恢復(fù),提高患者的生活質(zhì)量。目的：探討CHF患者不同時期各種死亡風(fēng)險(xiǎn)預(yù)測指標(biāo)和生活質(zhì)量評估的變化情況方法：前瞻性納入慢性心力衰竭失代償期(DCHF)患者268例,收集患者一般情況、心衰病因和病史,入院前3天和出院前3天內(nèi)分別進(jìn)行M型超聲心動圖、NT-proBNP、動態(tài)心電圖、APACHE評分、MLHF評分等指標(biāo)監(jiān)測。患者或家屬入院后即開始行CHF健康宣教,并納入慢性疾病管理,加強(qiáng)指導(dǎo)和隨訪,于患者出院后1月和出院后3個月兩次隨訪患者,再次記錄一般情況,同時再次行MLHF評分,比較以上監(jiān)測指標(biāo)在CHF患者病情加重和轉(zhuǎn)歸后發(fā)生的變化。結(jié)果：最終我們共納入患者219例,出院前病情好轉(zhuǎn)210例,未愈4例,死亡5例。住院期間調(diào)查顯示患者對所患疾病或伴隨疾病的知曉率較高,但健康自我管理的理念相對薄弱,藥物依從性差,尤其體現(xiàn)在β受體阻滯劑和ACEI (ARB)應(yīng)用方面,入院前主動復(fù)診的患者比例較低。患者的M型超聲心動圖結(jié)果(LVEF、左室舒張末直徑和左房直徑)在DCHF患者住院轉(zhuǎn)歸前后無明顯變化(p0.05)；HRV和DC在治療后各項(xiàng)指標(biāo)明顯升高,比較有統(tǒng)計(jì)學(xué)意義(p0.05)；免疫檢測指標(biāo)NT-pro-BNP、APACHE評分和MLHF評分在治療后明顯降低,比較有統(tǒng)計(jì)學(xué)意義(p0.05)；住院期間經(jīng)過醫(yī)務(wù)人員的慢病宣教后,患者的健康學(xué)習(xí)意識明顯提高,服用藥物的依從性和達(dá)標(biāo)率較前明顯增加,CHF的健康自我管理項(xiàng)目除外戒煙和監(jiān)測血糖外,運(yùn)動、飲食和血壓、脈搏、體重監(jiān)測都較入院前明顯提高,比較有統(tǒng)計(jì)學(xué)意義(p0.05)。出院后慢病管理期間有3例患者死亡,有4例患者中途失訪。對照出院1個月和3個月的各項(xiàng)指標(biāo),在患者健康自律,醫(yī)務(wù)人員督促的慢病管理模式下,以上各項(xiàng)指標(biāo)無明顯變化(p0.05),戒煙和血糖監(jiān)測有反彈的趨勢。結(jié)論：預(yù)測DCHF死亡風(fēng)險(xiǎn)的單項(xiàng)指標(biāo)和綜合指標(biāo)在病情轉(zhuǎn)歸前后都有一定的變化,各有優(yōu)勢,監(jiān)測的方便性和指導(dǎo)價值不同,總體上綜合指標(biāo)對死亡的預(yù)測價值較高；在慢病管理下的CHF患者,自我管理能力明顯提高,MLHF評分明顯下降。第二部分心率減速力對慢性心力衰竭失代償期患者死亡風(fēng)險(xiǎn)的預(yù)警價值背景：DCHF因?yàn)橛休^高的死亡風(fēng)險(xiǎn),一直是心血管病臨床研究的重點(diǎn)。發(fā)生心血管事件前患者的血流動力學(xué)情況和神經(jīng)內(nèi)分泌狀態(tài)在其發(fā)病原因中占有很大比重,因此深入研究CHF與自主神經(jīng)的關(guān)系勢在必行。作為自主神經(jīng)檢測的臨床指標(biāo),德國Georg Schmidt教授在HRT基礎(chǔ)上開發(fā)出來的DC無疑為我們帶來了新的希望。DC被證實(shí)主要反映了迷走神經(jīng)的功能,隨著人們認(rèn)識到迷走神經(jīng)在CHF中發(fā)揮著更重要的作用,DC檢測的價值更加明顯。作為第一個可以量化區(qū)別迷走神經(jīng)和交感神經(jīng)的指標(biāo),其到底與CHF患者心血管事件發(fā)生的關(guān)系如何?與患者的心功能狀況的關(guān)系如何?是否優(yōu)于過去的常用自主神經(jīng)評價指標(biāo)HRV?是否與整體死亡風(fēng)險(xiǎn)評分APACHE評分一致?這些問題都有待多中心、大規(guī)模的研究,有待大家在實(shí)踐中總結(jié)。作為中國的研究者,郭繼鴻教授將DC的概念引入中國,目前DC檢測已與動態(tài)心電圖融合到了一起,郭教授建議我們中國醫(yī)生也應(yīng)當(dāng)充分利用這一優(yōu)勢,積極實(shí)踐,總結(jié)經(jīng)驗(yàn),為我們國家心源性猝死(SCD)的預(yù)警和防治做出自己的貢獻(xiàn)。目的：探討DC對DCHF患者死亡風(fēng)險(xiǎn)的預(yù)警價值。方法：選擇74例DCHF患者,通過動態(tài)心電圖和APACHE評分對患者治療前后的病情進(jìn)行評估,動態(tài)心電圖重點(diǎn)分析DC和HRV,比較DCHF患者在不同心功能分級下DC、HRV、APACHE評分的區(qū)別,分析心功能分級、DC、HRV、 APACHE評分間的相關(guān)性,比較DC、HRV和APACHE評分預(yù)警患者死亡風(fēng)險(xiǎn)的ROC曲線下面積(AUC)。結(jié)果：DC和HRV各時域指標(biāo)：RR間期總體標(biāo)準(zhǔn)差(SDNN)、5min RR間期平均值的標(biāo)準(zhǔn)差(SDANN)、相鄰RR間期差值的均方根(RMSSD)在DCHF患者治療前低于正常值,治療后各指標(biāo)明顯升高,治療前后比較有統(tǒng)計(jì)學(xué)意義(t=5.518,3.075,2.814,3.109, p0.05); APACHE評分在DCHF患者治療前高于正常值,治療后評分明顯下降,治療前后比較有統(tǒng)計(jì)學(xué)意義(t=4.072,p0.05)。不同心功能分級下DC、HRV (SDNN、SDANN、RMSSD)、APACHE評分各自的比較都有統(tǒng)計(jì)學(xué)意義(F=11.33,10.76,12.08,12.45,10.98,p0.05),DC和HRV各指標(biāo)隨心功能下降而降低,APACHE評分隨心功能下降而升高。DC與HRV各指標(biāo)(SDNN、SDANN、RMSSD)均呈正相關(guān)(r=0.601,0.588,0.457,p0.05)；DC與APACHE評分呈中度負(fù)相關(guān)(r=-0.639,p0.05)。心力衰竭時心功能分級與DC與相關(guān)性的分析：DC與心功能分級呈中度負(fù)相關(guān)(r=-0.571,p0.05)。APACHE評分與心功能分級呈中度正相關(guān)(r=0.653,p0.05),HRV各指標(biāo)(SDNN、SDANN、RMSSD)與心功能分級呈低度相關(guān)(r=-0.385,-0.290,-0.418,p0.05)。預(yù)測DCHF患者死亡風(fēng)險(xiǎn)的價值：APACHE評分DCSDANN (AUC=0.905,0.795,0.717), DC的預(yù)測價值為中度。結(jié)論：DC和HRV在DCHF時隨心功能下降明顯下降,APACHE評分在DCHF時隨心功能下降呈反向升高,DC和APACHE評分與心功能的相關(guān)性較高。DC與病情危重評價的綜合指標(biāo)APACHE評分相關(guān)性較好,其與同樣反映自主神經(jīng)紊亂的HRV相關(guān)性也較好,其作為單項(xiàng)指標(biāo)預(yù)警DCHF患者死亡風(fēng)險(xiǎn)有較高的價值。第三部分參松養(yǎng)心膠囊對慢性心力衰竭患者自主神經(jīng)功能紊亂調(diào)節(jié)的評價背景：CHF患者存在嚴(yán)重的自主神經(jīng)功能紊亂,過去認(rèn)為是心臟重構(gòu)時交感神經(jīng)作用被加強(qiáng),現(xiàn)在認(rèn)為是主要是迷走神經(jīng)的作用被弱化了。隨著評估自主神經(jīng)功能狀態(tài)的無創(chuàng)指標(biāo)的發(fā)展,我們有了新的和連續(xù)心率減速力(DRs),其通過分析動態(tài)心電圖整合心電信號,能定量反映迷走神經(jīng)功能。臨床研究發(fā)現(xiàn)應(yīng)用β受體阻滯劑可降低CHF的猝死風(fēng)險(xiǎn),其最主要的作用機(jī)制就是通過抑制交感神經(jīng)而達(dá)到改善自主神經(jīng)功能紊亂的目的。一方面單純抑制交感神經(jīng)的后果就是可造成負(fù)性肌力作用,另一方面在用藥時機(jī)和達(dá)標(biāo)時間上因?yàn)闈撛诘膯栴},而導(dǎo)致臨床上應(yīng)用受到很大限制,因此,探討新的藥物或手段來調(diào)節(jié)自主神經(jīng)功能成為我們的研究方向。傳統(tǒng)中成藥參松養(yǎng)心膠囊對于調(diào)節(jié)自主神經(jīng)功能有很好的療效,它有多靶點(diǎn)、雙向調(diào)節(jié)作用的優(yōu)點(diǎn),這不僅成為它的優(yōu)點(diǎn),甚至引起了抗心律失常藥物治療領(lǐng)域?qū)χ委熇砟畹姆此�。由于過去在CHF患者中較少的應(yīng)用參松養(yǎng)心膠囊,另外有新的評價指標(biāo)出現(xiàn),本文擬通過應(yīng)用DRs來評價CHF時參松養(yǎng)心膠囊和美托洛爾片對自主神經(jīng)功能紊亂的調(diào)節(jié)作用,為CHF患者自主神經(jīng)功能紊亂的治療尋找一種更有效的方法。目的：評價參松養(yǎng)心膠囊對CHF患者自主神經(jīng)功能紊亂的調(diào)節(jié)作用。方法：將臨床確診為CHF的99例患者隨機(jī)分為參松養(yǎng)心組(n=53)和美托洛爾組(n=46),用藥前和用藥1月后分別行動態(tài)心電圖,計(jì)算DRs,比較兩種藥物對DRs的調(diào)節(jié)作用,評價參松養(yǎng)心膠囊對CHF患者自主神經(jīng)功能的調(diào)節(jié)作用和預(yù)防猝死的價值。結(jié)果：兩組患者治療前后DRs各指標(biāo)DR2、DR4、DR8的變化基本一致,治療后兩組患者猝死風(fēng)險(xiǎn)明顯降低。結(jié)論：參松養(yǎng)心膠囊對CHF患者自主神經(jīng)功能的調(diào)節(jié)作用與美托洛爾片基本相當(dāng),其適應(yīng)證和患者耐受性更優(yōu)于美托洛爾片。
[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.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R541.6

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