本文選題：急性心肌梗死 + 新發(fā)房顫��； 參考：《復(fù)旦大學(xué)》2013年博士論文

【摘要】：第一部分急性心肌梗死患者新發(fā)房顫預(yù)測因素的前瞻性臨床研究 目的：通過對急性心肌梗死患者的前瞻性臨床觀察研究,尋找新發(fā)房顫的預(yù)測因素并對其預(yù)測價(jià)值進(jìn)行評估。 方法：連續(xù)入選2011年9月至2012年4月收住復(fù)旦大學(xué)中山醫(yī)院心內(nèi)科心臟監(jiān)護(hù)室的急性心肌梗死(AMI)患者。在監(jiān)護(hù)室治療期間對所有入組患者進(jìn)行24小時持續(xù)心電監(jiān)測,根據(jù)住院期間是否出現(xiàn)新發(fā)房顫將患者分為房顫組和非房顫組。分析比較兩組患者臨床特征,實(shí)驗(yàn)室指標(biāo),心臟超聲檢測指標(biāo)以及冠狀動脈介入治療等方面的特征和差異,尋找AMI患者病程中出現(xiàn)新發(fā)房顫的預(yù)測因素并對其預(yù)測價(jià)值和準(zhǔn)確性進(jìn)行評估。 結(jié)果：(1)本組研究中AMI患者住院期間出現(xiàn)新發(fā)房顫的比例為9.6%,ST段抬高型心肌梗死(STEMI)與非ST段抬高型心肌梗死(NSTEMI)患者間無明顯差異(17/165比15/169,P0.05)。房顫組患者具有高齡(72.16±11.61歲比66.23±11.14歲,P=0.009),入院心率偏快(89.44±26.61bpm比78.07±15.43bpm, P0.001),身高較低(1.64±0.08m比1.67±0.08m,P0.05)的特征。有高血壓病的患者在急性心肌梗死期間更容易罹患房顫(84.4%比64.2%,P=0.029)。房顫組患者吸煙率低于非房顫組(28.1%比52.6%,P=0.009)。另外,房顫組患者中繼往有腦卒中(21.9%比9.6%,P=0.063)及慢性腎功能不全(9.4%比2.3%,P=0.060)病史的患者比例明顯高于非房顫組,但差異未達(dá)到統(tǒng)計(jì)學(xué)意義。兩組患者入院血壓、心梗類型及部位、糖尿病病史、血脂代謝異常病史以及既往PCI治療史無明顯差別；在危險(xiǎn)分層及評估比較中,房顫組患者Crusade評分明顯高于非房顫組(P=0.002),CHA2DS2-VASc評分顯著升高(P=0.009);兩組患者實(shí)驗(yàn)室指標(biāo)比較發(fā)現(xiàn),房顫組患者白細(xì)胞計(jì)數(shù)(P=0.008)、紅細(xì)胞分布寬度(P=0.037)、cTnT峰值(P=0.029)明顯高于非房顫組患者。另外,房顫組患者腎小球?yàn)V過率較低(P=0.002),而入院24小時內(nèi)血漿NT-proBNP水平明顯高于非房顫組患者[2295.00(1263.25-4694.50) pg/mL比653.95(193.85-2100.00)pg/mL, P0.001],住院期間NT-proBNP峰值亦明顯高于非房顫組患者[(3915.00(2242.00-6550.50) pg/mL比1184.00(435.28-3134.25) pg/mL, P0.001];兩組患者超聲檢測結(jié)果比較發(fā)現(xiàn),房顫組患者左心房內(nèi)徑明顯大于非房顫組患者(42.63±5.65mm比39.72±4.66mm,P=0.001)。房顫組患者與非房顫組患者間其他實(shí)驗(yàn)指標(biāo)及心臟超聲檢測結(jié)果無明顯差異；兩組患者冠狀動脈病變特點(diǎn)及介入治療特點(diǎn)比較發(fā)現(xiàn),房顫組患者中接受再血管化治療的比例明顯低于非房顫組(56.3%比79.1%,P0.01),而兩組患者冠脈病變血管支數(shù)、罪犯血管分布比例以及介入治療術(shù)終病變血管TIMI血流評分無明顯差別；房顫組患者于非房顫組患者間住院期間藥物治療策略無顯著差異。(2)多因素Logistic回歸分析發(fā)現(xiàn),入院心率(OR1.024,95%CI1.003-1.046, P=0.028),左心房內(nèi)徑(OR1.091,95%CI1.008-1.184, P=0.031),入院24小時內(nèi)NT-proBNP水平(OR1.988,95%CI1.029-3.845, P=0.041)和住院期間NT-proBNP峰值(OR2.745,95%CI1.326-5.683, P=0.007)是AMI患者出現(xiàn)新發(fā)房顫的獨(dú)立危險(xiǎn)因素；(3)利用入院24小時內(nèi)血漿NT-proBNP水平預(yù)測急性心肌梗死患者新發(fā)房顫的ROC曲線下面積為0.717±0.046,P0.001,最佳預(yù)測臨界值為1100pg/mL,其預(yù)測急性心肌梗死患者新發(fā)房顫的敏感度和特異性分別為81.2%和61.3%。根據(jù)最佳預(yù)測臨界值將入組患者分為高、低NT-prpBNP組,比較發(fā)現(xiàn)高NT-proBNP組患者住院期間新發(fā)房顫的比例明顯增高(26/144,18.1%比6/190,3.2%,P0.001)。結(jié)論：過快的入院心率、增大的左心房內(nèi)徑、明顯升高的入院24小時血漿NT-proBNP水平以及住院期間血漿NT-proBNP峰值是AMI患者新發(fā)房顫的獨(dú)立危險(xiǎn)因素,可用于預(yù)測AMI患者的新發(fā)房顫,可用于指導(dǎo)患者危險(xiǎn)分層及早期預(yù)防治療。 第二部分合并新發(fā)房顫的急性心肌梗死患者血流動力學(xué)、神經(jīng)內(nèi)分泌和炎癥反應(yīng)激活特點(diǎn)及短期預(yù)后的前瞻性臨床研究 目的：分析合并新發(fā)房顫的急性心肌梗死患者血流動力學(xué)、神經(jīng)內(nèi)分泌和炎癥反應(yīng)激活特點(diǎn),觀察新發(fā)房顫對患者短期預(yù)后的影響。 方法：入選2011年9月至2012年4月收入復(fù)旦大學(xué)中山醫(yī)院心內(nèi)科心臟監(jiān)護(hù)室的急性心肌梗死患者共59例,其中病程中出現(xiàn)新發(fā)房顫患者25例為病例組,未出現(xiàn)房顫患者34例為對照組。住院期間,采用NICOM無創(chuàng)心排儀對患者進(jìn)行一次24小時持續(xù)血流動力學(xué)監(jiān)測,比較兩組間差異；同時,測定并比較房顫組患者與非房顫組患者入院后第一天及第三天血管緊張素Ⅱ,腎素、醛固酮、腫瘤壞死因子α、白介素-6、髓過氧化物酶及骨保護(hù)素水平,比較房顫組與非房顫組患者間差異；對入組患者進(jìn)行出院后90天隨訪,主要觀察指標(biāo)為心血管不良事件,包括心源性死亡、再次心肌梗死、再次住院、病變血管再次介入治療以及腦卒中。評估房顫對AMI患者短期預(yù)后的影響。 結(jié)果：(1)房顫組與非房顫組患者心輸出量、心臟指數(shù)、心功率及每搏輸出量均無明顯差異,但房顫組患者每博輸出量變化率較非房顫組患者增高(15±2.8%比11.9±2.9%,P0.001),主動脈血流速度峰值顯著下降(136.1±48.5比172.1±65.5,P=0.034)。兩組患者其他血流動力學(xué)監(jiān)測指標(biāo)無明顯差異：(2)兩組患者神經(jīng)內(nèi)分泌及炎癥反應(yīng)激活特點(diǎn)比較發(fā)現(xiàn),房顫組患者血管緊張素ⅠI[71.49(57.57-79.62)pg/mL比58.96(50.42-62.67)pg/mL, P=0.010]、腫瘤壞死因子a[1.35(0.93-2.03)pg/mL比0.03(0.03-0.28)pg/mL, P0.001]、髓過氧化物酶[4.04(2.10-6.21)ng/mL比1.97(0.80-3.37),P=0.028]及NT-proBNP水平(3041.0(1525.0-5021.0)pg/mL比674.5(198.9-2242.0)pg/mL, P0.01)均明顯高于非房顫組。另外,房顫組患者骨保護(hù)素水平明顯高于非房顫組患者,但差異未達(dá)到統(tǒng)計(jì)學(xué)意義[(17181.5(13347.8-24684.3)pg/mL比14581.0(9692.5-19566.0) pg/mL,P=0.065)。兩組患者間腎素、醛固酮、白介素-6水平無明顯差異。Spearman相關(guān)分析發(fā)現(xiàn)腎素、血管緊張素Ⅱ、腫瘤壞死因子α以及髓過氧化物酶與患者NT-proBNP水平明確相關(guān)；(3)對兩組患者進(jìn)行出院后90天短期隨訪,結(jié)果顯示房顫組患者短期心血管不良事件發(fā)生率明顯高于非房顫組患者(8/32,32%比3/32,8.8%,P=0.04),且以心源性死亡為主要不良結(jié)局。Kaplan-meier生存分析對顯示房顫組患者無事件生存率明顯低于非房顫組患者,且以心源性死亡為主要不良事件類型。 結(jié)論：(1)合并新發(fā)房顫的AMI患者無創(chuàng)血流動力學(xué)監(jiān)測結(jié)果與非房顫組患者無明顯差別,僅每博輸出量變異率和主動脈血流速度存在差異；(2)AMI患者出現(xiàn)新發(fā)房顫早期神經(jīng)內(nèi)分泌和炎癥反應(yīng)激活明顯,且伴隨起病時間而逐漸增強(qiáng)；(3)新發(fā)房顫與AMI患者90天預(yù)后明確相關(guān),病程中出現(xiàn)新發(fā)房顫的急性心肌梗死患者其90天無事件生存率較竇性心律患者低。心源性死亡是并發(fā)新發(fā)房顫的AMI患者短期不良心血管事件的主要類型。 第三部分血漿NT-proBNP對急性心肌梗死患者新發(fā)房顫預(yù)測價(jià)值的回顧性臨床研究 目的：探討N末端B型腦利鈉肽前體(NT-proBNP)對急性心肌梗死患者新發(fā)房顫的預(yù)測價(jià)值。 方法：采用回顧性臨床研究的方法,自2008年1月至2010年12月收住復(fù)旦大學(xué)附屬中山醫(yī)院心臟監(jiān)護(hù)室的患者中入選AMI患者268例,按照患者住院期間是否出現(xiàn)新發(fā)房顫將患者分為房顫組(n=36)和非房顫組(n=232)。比較兩組間差異,分析評估入院24小時內(nèi)血漿NT-proBNP水平對急性心肌梗死患者新發(fā)房顫的預(yù)測價(jià)值和準(zhǔn)確性。 結(jié)果：(1)AMI患者住院期間出現(xiàn)新發(fā)房顫的比例為13.4%,STEMI與NSTEMI患者間無明顯差異；(2)房顫組患者NT-proBNP水平明顯高于非房顫患者[(2166(1571-4871)pg/mL比707(347-1759)pg/mL, P0.001)],平均年齡較大,但左心室射血分?jǐn)?shù)(55.74%±11.02%Vs.60.14%±9.56%,P=0.015),血紅蛋白含量(123.00±14.90g/mL Vs.132.66±15.42g/mL, P=0.001)和腎小球?yàn)V過率(69.39±20.41ml/min/1.73m2Vs.79.52±21.59ml/min/1.73m2, P=0.009)均低于非房顫組患者；(3)對房顫常見危險(xiǎn)因素進(jìn)行校正后多因素Logistic回歸分析顯示,明顯升高的血漿NT-proBNP水平是AMI患者新發(fā)房顫的獨(dú)立危險(xiǎn)因素(OR4.918,95%CI1.662-14.549, P=0.004)。(4)利用入院24小時內(nèi)患者血漿NT-proBNP預(yù)測新發(fā)房顫的ROC曲線下面積為0.811,95%可信區(qū)間為0.753-0.868,P0.001；以入院24小時內(nèi)血漿NT-proBNP水平≥796pg/mL作為臨界值來預(yù)測AMI患者新發(fā)房顫的敏感度和特異性分別為100%和53.4%,所有在病程中出現(xiàn)新發(fā)房顫的患者入院血漿NT-proBNP水平均高于796pg/mL; 結(jié)論：血漿NT-proBNP水平可獨(dú)立預(yù)測急性心肌梗死患者新發(fā)房顫的發(fā)生,可用于患者危險(xiǎn)分層及指導(dǎo)早期預(yù)防治療。
[Abstract]:Part one prospective clinical study of predictors of new onset atrial fibrillation in patients with acute myocardial infarction
Objective: To evaluate the predictive value of new atrial fibrillation (AF) by prospective clinical observation of acute myocardial infarction (AMI).
Methods: the patients who received acute myocardial infarction (AMI) from the Department of Cardiology, Zhongshan hospital, Fudan University from September 2011 to April 2012, were enrolled in the cardiac monitoring room of the Department of Cardiology, Zhongshan hospital. During the intensive care unit, all the patients were monitored continuously. The patients were divided into atrial fibrillation group and non atrial fibrillation group according to whether there were new atrial fibrillation during the hospitalization. The characteristics and differences of clinical features, laboratory indicators, echocardiographic indicators and coronary intervention in the two groups were compared, and the predictive factors for the emergence of new atrial fibrillation in the course of AMI patients were evaluated and their predictive value and accuracy were evaluated.
Results: (1) in the study, the proportion of new onset atrial fibrillation in AMI patients was 9.6%, there was no significant difference between ST segment elevation myocardial infarction (STEMI) and non ST elevation myocardial infarction (NSTEMI) patients (17/165 than 15/169, P0.05). The patients in atrial fibrillation group had a higher age (72.16 + 11.61 years than 66.23 + 11.14 years, P=0.009), and the hospitalized heart rate was faster (89.44). 26.61bpm was 78.07 + 15.43bpm, P0.001), and the height was lower (1.64 + 0.08m than 1.67 + 0.08m, P0.05). Patients with hypertension were more likely to suffer from atrial fibrillation (84.4% to 64.2%, P=0.029) during acute myocardial infarction. The rate of smoking in atrial fibrillation group was lower than that of non atrial fibrillation group (28.1% to 52.6%, P=0.009). The ratio of 21.9% to 9.6%, P=0.063) and chronic renal insufficiency (9.4% to 2.3%, P=0.060) was significantly higher than that in the non atrial fibrillation group, but the difference was not statistically significant. The hospitalized blood pressure, the type and location of myocardial infarction, the history of diabetes, the history of abnormal blood lipid metabolism and the history of PCI treatment were not significantly different in the two groups, and in the risk stratification and evaluation. In the comparison, the Crusade score in the atrial fibrillation group was significantly higher than that in the non atrial fibrillation group (P=0.002), and the CHA2DS2-VASc score increased significantly (P=0.009). The two groups of patients showed that the leukocyte count (P=0.008), the red cell distribution width (P=0.037) and the peak value of cTnT (P=0.029) were significantly higher in the atrial fibrillation group than in the non atrial fibrillation group. In addition, the renal fibrillation group was kidney. The small pellet filtration rate was lower (P=0.002), and the plasma NT-proBNP level was significantly higher than that of the non atrial fibrillation group (1263.25-4694.50) pg/mL ratio (193.85-2100.00) pg/mL, P0.001], and the peak value of NT-proBNP (3915 (2242.00-6550.50) pg/mL ratio 1184 (2242.00-6550.50) pg/mL ratio 1184 (435.28-3134.25) during the 24 hours of admission. P0.001]; two groups of patients with ultrasound examination showed that the left atrial diameter of the atrial fibrillation group was significantly greater than that of the non atrial fibrillation group (42.63 + 5.65mm ratio 39.72 + 4.66mm, P=0.001). There was no significant difference between the other experimental indexes and the echocardiographic results between the patients of atrial fibrillation group and the non atrial fibrillation group; the coronary artery lesion characteristics and intervention in the two groups of patients were not significantly different. It was found that the rate of revascularization in the patients with atrial fibrillation was significantly lower than that in non atrial fibrillation group (56.3% to 79.1%, P0.01), but there was no significant difference in the number of vessels in the two groups, the proportion of the blood vessels in the offender's vessels and the TIMI blood flow score of the end of the interventional therapy. There was no significant difference in the drug treatment strategy during the hospital. (2) multiple factor Logistic regression analysis found the hospitalization heart rate (OR1.024,95%CI1.003-1.046, P=0.028), the left atrium diameter (OR1.091,95%CI1.008-1.184, P=0.031), the NT-proBNP level (OR1.988,95% CI1.029-3.845, P=0.041) and the NT-proBNP peak during the hospitalization (OR2.745,95%CI1.326-5) during the hospital (OR2.745,95%CI1.326-5). .683, P=0.007) is an independent risk factor for the emergence of new atrial fibrillation in AMI patients; (3) the area of the ROC curve under the ROC curve of the patients with acute myocardial infarction is 0.717 + 0.046, P0.001, and the best predictive critical value is 1100pg/mL, using the plasma NT-proBNP level within 24 hours of admission. The sensitivity and specificity of the new onset atrial fibrillation in patients with acute myocardial infarction are measured. 81.2% and 61.3%., respectively, were divided into high and low NT-prpBNP groups based on the best predicted critical values. The ratio of new onset atrial fibrillation in the high NT-proBNP group was significantly higher (26/144,18.1% than 6/190,3.2%, P0.001). Conclusion: the fast admission heart rate, the increased left atrium diameter, and a significantly increased admission of 24 hours of hospitalization. Plasma NT-proBNP levels and plasma NT-proBNP peaks during hospitalization are independent risk factors for new atrial fibrillation in AMI patients, which can be used to predict new atrial fibrillation in AMI patients and can be used to guide patients with risk stratification and early preventive treatment.
A prospective clinical study on hemodynamics, neuroendocrine and inflammatory response activation characteristics and short-term prognosis in the second part of patients with acute myocardial infarction with new atrial fibrillation
Objective: to analyze the hemodynamic, neuroendocrine and inflammatory activation characteristics of patients with acute myocardial infarction with new atrial fibrillation, and to observe the effect of new atrial fibrillation on the short-term prognosis of patients.
Methods: a total of 59 patients with acute myocardial infarction in the Department of Cardiology, Zhongshan hospital, Zhongshan hospital from September 2011 to April 2012, were enrolled in the cardiac monitoring room of the Department of Cardiology, Fudan University. Among them, 25 cases of new atrial fibrillation were found in the course of the disease, and 34 patients without atrial fibrillation were used as the control group. During the period of hospitalization, the patients were held for 24 hours with a NICOM noninvasive heart arrangement. Continuous hemodynamic monitoring was used to compare the differences between the two groups. At the same time, the levels of angiotensin II, renin, aldosterone, tumor necrosis factor alpha, il--6, myeloperoxidase and osteoprotegerin were measured and compared between the atrial fibrillation group and the non atrial fibrillation group at the first and three days after admission, and the differences were compared between the atrial fibrillation group and the non atrial fibrillation group. The patients were followed up 90 days after discharge. The main indicators were cardiovascular adverse events, including cardiogenic death, re myocardial infarction, rehospitalization, re interventional therapy and stroke. The effect of atrial fibrillation on the short-term prognosis of AMI patients was evaluated.
Results: (1) there was no significant difference in cardiac output, cardiac index, cardiac power and per stroke output in atrial fibrillation group and non atrial fibrillation group, but the change rate of per Bo output in atrial fibrillation group was higher than that of non atrial fibrillation group (15 + 2.8% / 11.9 + 2.9%, P0.001), and the peak of aortic blood flow rate decreased significantly (136.1 + 48.5, 172.1 + 65.5, P=0.034). Two groups were affected. There were no significant differences in other hemodynamic monitoring indexes: (2) compared with the activation characteristics of neuroendocrine and inflammatory reaction in the two groups, the angiotensin I I[71.49 (57.57-79.62) pg/mL of atrial fibrillation group was compared with 58.96 (50.42-62.67) pg/mL, P=0.010], a[1.35 (0.93-2.03) pg/mL ratio 0.03 (0.03-0.28) pg/mL, P0.001], and medullary The ratio of oxide enzyme [4.04 (2.10-6.21) ng/mL to 1.97 (0.80-3.37), P=0.028] and NT-proBNP (3041 (1525.0-5021.0) pg/mL ratio 674.5 (198.9-2242.0) pg/mL, P0.01) were significantly higher than that in non atrial fibrillation group. In addition, the level of osteoprotegerin in patients with atrial fibrillation was significantly higher than that in non atrial fibrillation group, but the difference was not statistically significant [(17181.5) (13347.8-24684.3). G/mL was compared to 14581 (9692.5-19566.0) pg/mL, P=0.065). There was no significant difference between the two groups of patients with renin, aldosterone, and interleukin -6, the.Spearman related analysis found that renin, angiotensin II, TNF - alpha, and myeloperoxidase were clearly associated with the patients' NT-proBNP level; (3) two groups of patients were followed up for 90 days after discharge. The results showed that the incidence of short term cardiovascular events in patients with atrial fibrillation was significantly higher than that in non atrial fibrillation group (8/32,32% 3/32,8.8%, P=0.04), and.Kaplan-meier survival analysis with cardiac death as the main adverse outcome was significantly lower than that of non atrial fibrillation group, and cardiac death was the main adverse event in the patients with atrial fibrillation. Event type.
Conclusions: (1) the noninvasive hemodynamic monitoring results of AMI patients with new atrial fibrillation were not significantly different from those in the non atrial fibrillation group. There was a difference in the rate of variation of output per blot and the velocity of aortic blood flow; (2) the activation of neuroendocrine and inflammatory reactions in the early onset atrial fibrillation was obvious in AMI patients and increased with the onset time; (3) The 90 day prognosis of new onset atrial fibrillation is clearly related to the 90 day prognosis. The 90 day non event survival rate of patients with acute myocardial infarction with new atrial fibrillation in the course of the disease is lower than that of the sinus rhythm patients. Cardiac death is the main type of short term adverse cardiovascular events in patients with AMI patients with new atrial fibrillation.
The third part of the retrospective study of plasma NT-proBNP in predicting the incidence of new onset atrial fibrillation in patients with acute myocardial infarction
Objective: To investigate the predictive value of N terminal B type natriuretic peptide precursor (NT-proBNP) in patients with acute atrial fibrillation (AMI).
Methods: 268 patients with AMI were selected from January 2008 to December 2010 with a retrospective clinical study. The patients were divided into atrial fibrillation group (n=36) and non atrial fibrillation group (n=232) according to whether the patients had new atrial fibrillation during the period of hospitalization during the period of hospitalization. The difference between the two groups was compared and evaluated. The predictive value and accuracy of plasma NT-proBNP level in 24 hours of acute myocardial infarction patients with new onset atrial fibrillation.
Results: (1) the proportion of new onset atrial fibrillation in AMI patients was 13.4%, and there was no significant difference between STEMI and NSTEMI patients. (2) the NT-proBNP level in patients with atrial fibrillation was significantly higher than that of non atrial fibrillation patients [(2166 (1571-4871) pg/mL ratio 707 (347-1759) pg/mL, P0.001)], and the average age was larger, but the left ventricular ejection fraction (55.74% + 11.02%Vs.60.14% + 9.56%,) P=0.015), the content of hemoglobin (123 + 14.90g/mL Vs.132.66 + 15.42g/mL, P=0.001) and glomerular filtration rate (69.39 + 20.41ml/min/1.73m2Vs.79.52 + 21.59ml/min/1.73m2, P=0.009) were lower than those in non atrial fibrillation group. (3) multiple factor Logistic regression analysis after correction of common risk factors for atrial fibrillation showed a significant increase in plasma NT-pro BNP level is an independent risk factor for new atrial fibrillation in AMI patients (OR4.918,95%CI1.662-14.549, P=0.004). (4) the area of the ROC curve under the ROC curve of the patient's plasma NT-proBNP in the hospital within 24 hours of admission is 0.753-0.868, P0.001, and the plasma NT-proBNP level > 796pg/mL as the critical value within 24 hours of admission as the critical value. The sensitivity and specificity of new atrial fibrillation in AMI patients were 100% and 53.4% respectively. The average NT-proBNP water in all patients with new onset atrial fibrillation in the course of the disease was higher than that of 796pg/mL.
Conclusion: plasma NT-proBNP level can independently predict the occurrence of new onset atrial fibrillation in patients with acute myocardial infarction, and can be used for risk stratification and early prevention and treatment.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R542.22;R541.7

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