本文關鍵詞： 先天性心臟病 肺動脈高壓 肺血管順應性 預后 肺血管順應性 急性肺血管反應試驗 鈣通道阻滯劑 右室內不同步化運動 肺動脈高壓 右心功能 預后　出處：《北京協(xié)和醫(yī)學院》2017年博士論文　論文類型：學位論文

【摘要】：第一部分:肺血管順應性對成人先天性心臟病相關性肺動脈高壓預后預測價值的研究(International Heart Journal.已接收)目的:探討肺血管順應性(pulmonary vascular compliance,Cp)在預測成人先天性心臟病相關性肺動脈高壓患者預后方面的價值。方法:連續(xù)入選2007年1月-2012年12月在阜外醫(yī)院經(jīng)右心導管確診的成人先天性心臟病相關性肺動脈高壓患者,所有患者進行詳細的臨床評估,包括世界衛(wèi)生組織(world health organization,WHO)肺動脈高壓功能分級、六分鐘步行距離、超聲心動圖檢查和血流動力學檢查,收集肝功、腎功、血漿利鈉肽、血氣分析等血液化驗結果。肺血管順應性定義為右心每搏輸出量/(肺動脈收縮壓-舒張壓)。所有患者每隔3-6個月進行電話或門診隨訪,主要隨訪結局事件為全因死亡。結果:研究共納入了 175例成人先天性心臟病相關性肺動脈高壓患者,并根據(jù)臨床分類分為3個組,包括Eisenmenger綜合征112例,小缺損先天性心臟病合并肺動脈高壓20例,左向右分流先天性心臟病矯正術后肺動脈高壓43例。在各個組中肺血管順應性與肺血管阻力均呈反比例關系。肺血管順應性低的患者表現(xiàn)出更差的運動耐力、肝功能、右心功能、血氧分壓和血流動力學狀態(tài)。所有患者平均隨訪時間為67±26個月,隨訪過程中有23人死亡。單因素Cox回歸分析提示與生存相關的危險因素為心率((HR=1.038,p=0.028)、肺血管順應性(HR=1.359,p0.001)、肺血管阻力(HR=0.972,p=0.001)、肺循環(huán)血流量(HR=1.092,p=0.001)和六分鐘步行距離(HR=1.003,p=0.037)。雙變量Cox回歸分析提示肺血管順應性是患者預后的獨立預測因素。受試者工作曲線(receiver operator characteristic curve,ROC)曲線獲得肺血管順應性預測預后的最佳臨界值為1.04ml/mmHg;Kaplan-Meier曲線顯示肺血管順應性小于1.04ml/mmHg的患者的生存率要明顯低于肺血管順應性大于或等于1.04ml/mmHg 的患者。結論:肺血管順應性可以反映成人先天性心臟病相關性肺動脈高壓患者的病情嚴重程度,是患者預后的獨立預測因素。第二部分:肺血管順應性預測特發(fā)性肺動脈高壓患者鈣通道阻滯劑治療長期獲益的研究(Lung.2016;194(4):613-618)目的:探討肺血管順應性(pulmonary vascular compliance,Cp)預測特發(fā)性肺動脈高壓(idiopathic pulmonary arterial hypertension,IP AH)患者能否長期獲益于鈣通道阻滯劑(calcium channel blockers,CCB)治療方面的價值。方法:研究入選2009年1月-2014年12月在阜外醫(yī)院肺血管病中心初診為特發(fā)性肺動脈高壓的患者,通過吸入伊洛前列素進行急性肺血管反應試驗,評估吸藥前和吸藥后的肺血管順應性。肺血管順應性定義為右心每搏輸出量/(肺動脈收縮壓-舒張壓)。急性肺血管反應試驗陽性患者給予CCB治療,并對患者進行至少1年的隨訪,主要隨訪內容為患者癥狀、運動耐力、世界衛(wèi)生組織(world health organization,WHO)肺動脈高壓分級和用藥情況。結果:研究共納入特發(fā)性肺動脈高壓患者308例,其中35例為急性肺血管反應試驗陽性,占11.7%。肺血管順應性與患者WHO肺動脈高壓功能分級、六分鐘步行距離、肺動脈平均壓、肺血管阻力呈明顯相關性(r=-0.363,p0.001;r = 0.333,p0.001;r =-0.514,p0.001;r=-0.739,p0.001)。與陰性患者相比,陽性患者吸藥前的肺血管順應性更高(1.5±0.6ml/mmHg vs.1.1±0.7ml/mmHg,p = 0.003),肺動脈平均壓(49±10mmHg vs.62±17mmHg,p0.001)和肺血管阻力(11.7 ± 4.6 wood單位 vs.17.1 ±8.1wood單位,p0.001)更低。吸藥后陽性患者肺血管順應性提高79%±48%,而陰性患者提高19%±47%,差異有統(tǒng)計學意義(p0.001)。35例陽性患者中有24例長期獲益于CCB治療。長期獲益的患者吸藥后肺血管順應性增加更為明顯(93%± 72%vs.48%±49%,p=0.039)。多因素邏輯回歸結果提示,吸入伊洛前列素后肺血管順應性的增加程度與CCB治療長期獲益相關,是鈣通道阻滯劑治療長期獲益有力的預測因素(OR=1.24,p=0.031)。結論:急性肺血管反應試驗陽性的IPAH患者具有更高的肺血管順應性,急性肺血管反應試驗過程中吸入伊洛前列素后肺血管順應性的增加程度可預測鈣通道阻滯劑治療的長期有效性,有助于篩選CCB治療長期獲益的患者。第三部分:右室內不同步化運動對肺動脈高壓患者右心功能及預后的影響目的:探討右心室內不同步化運動對肺動脈高壓患者右心功能和預后的影響。方法:研究入選150例在阜外醫(yī)院肺血管病中心診斷為肺動脈高壓的患者,所有患者進行詳細的臨床評估,包括世界衛(wèi)生組織(world health organization,WHO)肺動脈高壓功能分級、六分鐘步行距離、右心導管檢查等。通過二維超聲斑點追蹤技術評估右室內不同步化運動,Qlab軟件分析獲取右心室室壁各節(jié)段的應變-時間曲線,并記錄右室游離壁中間段、基底段和室間隔中間段、基底段4個節(jié)段的縱向應變達峰時間(心電圖QRS波起點至應變峰值的時間),計算右室壁4個節(jié)段應變達峰時間的標準差(RV-SD4),以RV-SD418ms作為判斷患者是否存在右室內不同步化運動的標準。三維超聲心動圖測量右心室舒張末容積、收縮末容積,計算右心室射血分數(shù)。所有患者自確診之日起每隔6個月進行電話或門診隨訪,主要隨訪結局事件為全因死亡。結果:RV-SD4與右室收縮末容積、右室舒張末容積、肺血管阻力呈正相關(r=0.566,p0.001;r=0.532,p0.001;r=0.372,p0.001);與三尖瓣環(huán)收縮期位移幅度、右室射血分數(shù)、右室面積變化分數(shù)和心指數(shù)呈負相關(r=-0.394,p0.001;r=-0.336,p0.001;r=-0.427,p0.001;r=-0.420,p0.001)。85例患者存在右室內不同步化運動(RV-SD418ms),占56.7%。與同步化運動組患者相比,右室內不同步化運動患者右室游離壁基底段和室間隔基底段出現(xiàn)收縮延遲,且患者的WHO肺動脈高壓分級更差,右室舒張末容積(150.1±65.1cm3vs.112.2±39.3cm3,p0.001)和收縮末容積(112.1±55.5cm3 vs.75.9±30.9cm3,p0.001)增加,右室射血分數(shù)(25.5%±10.1%vs.33.3%±8.6%,p0.001)和右室面積變化分數(shù)(25.9%±6.2%vs.32.8%± 9.0%,p0.001)降低。血流動力學方面,右室內不同步化運動患者心指數(shù)明顯降低(2.5±0.7 L/min.m2 vs.3.3±1.6L/min.m2,p0.001),而肺血管阻力增加(16.3±8.0wood 單位 vs.11.7±6.1 wood單位,p0.001)。多因素邏輯回歸分析顯示右室收縮末容積增加、右室面積變化分數(shù)和心指數(shù)降低是與右室內不同步化運動相關的影響因素。研究平均隨訪時間為42±16個月,隨訪期間29例患者死亡。ROC曲線獲得RV-SD4預測預后的最佳臨界值為38ms。多因素Cox回歸分析提示RV-SD438ms是患者死亡的獨立預測因素(HR=2.962,p=0.048)。結論:肺動脈高壓患者右心功能減低與右室內存在不同步化運動有關,右室內不同步化運動是肺動脈高壓患者死亡的獨立預測因素。
[Abstract]:The first part: the research on the predictive value of prognosis associated with pulmonary arterial hypertension in adults with congenital heart disease pulmonary vascular (International Heart Journal. received) objective: To investigate the pulmonary vascular compliance (pulmonary vascular, compliance, Cp) in the prediction of adult congenital heart disease patients with pulmonary artery hypertension associated with the value. Methods: consecutive in January 2007 -2012 year in December in Fuwai Hospital after patients associated with pulmonary arterial hypertension in adults with congenital heart disease diagnostic right heart catheterization, all patients underwent a detailed clinical evaluation, including WHO (World Health Organization, WHO) function in pulmonary arterial hypertension grading, six minutes walking distance, echocardiography and hemodynamic examination, collect liver, kidney power, plasma natriuretic peptide, blood gas analysis and blood test results. Pulmonary vascular compliance is defined as rVSV (pulmonary / The systolic blood pressure and diastolic blood pressure). All patients were followed up by telephone or clinic every 3-6 months follow-up, the main outcomes of all-cause death. Results: the study included 175 patients associated with pulmonary arterial hypertension in adults with congenital heart disease, according to clinical classification and divided into 3 groups, including 112 cases of Eisenmenger syndrome small defect, congenital heart disease and pulmonary hypertension in 20 cases, left to right shunt congenital heart disease after surgical correction of pulmonary hypertension in 43 cases. In each group of pulmonary vascular resistance and pulmonary vascular resistance was inversely proportional relationship. Pulmonary vascular compliance in patients with low show endurance, worse liver function of right heart function, blood oxygen pressure and hemodynamics. All patients were followed up for an average of 67 + 26 months, there were 23 deaths during follow-up. The single factor Cox regression analysis indicated that the risk factors associated with survival for heart rate ((HR=1.038, p= 0.028), pulmonary vascular resistance (HR=1.359, p0.001), pulmonary vascular resistance (HR=0.972, p=0.001), pulmonary blood flow (HR=1.092, p=0.001) and six minutes walking distance (HR=1.003, p=0.037). The bivariate Cox regression analysis showed that pulmonary vascular compliance is an independent predictor of the prognosis of the patients. The subjects of work curve (receiver operator characteristic curve, ROC) curve of pulmonary vascular optimal threshold prediction prognosis for 1.04ml/mmHg; Kaplan-Meier curve showed that the pulmonary vascular resistance is less than the survival rate of 1.04ml/mmHg patients is significantly lower than that of pulmonary vascular resistance is greater than or equal to 1.04ml/mmHg patients. Conclusion: pulmonary vascular compliance can reflect patients of pulmonary artery correlation of adult congenital heart disease hypertension severity were the independent predictors of prognosis. The second part: the prediction of pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension Study on long-term calcium channel blocker (Lung.2016; 194 (4): 613-618) objective: To investigate the pulmonary vascular compliance (pulmonary vascular, compliance, Cp) prediction of idiopathic pulmonary arterial hypertension (idiopathic pulmonary arterial hypertension, IP AH) in patients with long-term benefit from calcium channel blockers (calcium channel, blockers, CCB) treatment the value. Methods: the study selected in January 2009 December -2014 at the center of Fuwai Hospital pulmonary vascular disease diagnosed as idiopathic pulmonary arterial hypertension patients by inhaled iloprost for acute pulmonary vasoreactivity testing, evaluation of pulmonary vascular drugs before and after inhalation of drug compliance. Pulmonary vascular compliance is defined as the right heart the stroke volume / (pulmonary artery systolic pressure and diastolic blood pressure). Patients with positive acute pulmonary vasoreactivity testing treated with CCB, and at least 1 years of follow-up, the main content of follow-up for patients symptoms, Exercise endurance, WHO (World Health Organization, WHO) of pulmonary arterial hypertension grading and medication. Results: there were 308 cases of idiopathic pulmonary arterial hypertension patients, including 35 cases of acute pulmonary vasoreactivity test positive, accounting for 11.7%. of pulmonary vascular resistance and pulmonary hypertension in patients with WHO functional class, six minutes walk the distance, mean pulmonary artery pressure, pulmonary vascular resistance was significantly correlated (r=-0.363, p0.001; r = 0.333, p0.001; R p0.001; =-0.514, r=-0.739, p0.001). Compared with the negative patients, patients with positive drugs before the pulmonary vascular compliance is higher (1.5 + 0.6ml/mmHg vs.1.1 + 0.7ml/mmHg, P = 0.003), mean pulmonary artery pressure (49 + 10mmHg vs.62 + 17mmHg, p0.001) and pulmonary vascular resistance (11.7 + 4.6 wood vs.17.1 + 8.1wood, p0.001). Lower compliance increased by 79% + 48% positive patients with pulmonary vascular drugs, while negative patients increased by 19% - 47%, The difference was statistically significant (p0.001).35 positive patients, 24 cases of long-term benefit from CCB treatment. The long-term benefit patients after inhalation of pulmonary vascular resistance was significantly increased (93% + 72%vs.48% + 49%, p=0.039). Multivariate logistic regression results suggest that inhaled iloprost after pulmonary vascular resistance increased the degree of benefit associated with the long-term CCB treatment, is a calcium channel blocker to treat long-term predictors of strong (OR=1.24, p=0.031). Conclusion: acute pulmonary vasoreactivity testing positive IPAH patients with higher pulmonary vascular compliance, long-term effectiveness of iloprost for pulmonary vascular adaptation increases the degree of predictability of calcium blocker therapy channel inhalation acute pulmonary vasoreactivity test process, contribute to the screening of CCB treatment of long-term benefit patients. The third part: the right movement of different indoor step right pulmonary hypertension in patients with heart function and prognosis Objective: To investigate the effects of different indoor step effect of right heart movement on cardiac function and prognosis of pulmonary arterial hypertension in patients with right. Methods: the study selected 150 cases of pulmonary vascular disease in Fuwai Hospital diagnosed as pulmonary hypertension patients, all patients underwent a detailed clinical evaluation, including WHO (World Health Organization, WHO) pulmonary function high grade, six minutes walking distance, right heart catheterization. Tracking assessment of right indoor different step motion by two-dimensional ultrasound speckle analysis, strain acquisition of right ventricular wall segmental time curves of Qlab software, and record the right ventricular free wall of the middle section, the middle section of basal segment and septal basal segment, longitudinal strain the 4 section of the peak time (ECG QRS wave starting point to the peak strain time), calculation of right ventricular wall in 4 segments of time to peak strain and standard deviation (RV-SD4), using RV-SD418ms as a judge If the patient is right off the different indoor step movement. The standard three-dimensional echocardiography measurement of right ventricular end diastolic volume and end systolic volume, right ventricular ejection fraction calculation. All patients by telephone or outpatient follow-up every 6 months from the date of diagnosis, the main outcome was all-cause mortality follow-up. Results: RV-SD4 and right ventricular end systolic volume, right ventricular end diastolic volume, pulmonary vascular resistance was positively correlated (r=0.566, p0.001; r=0.532, p0.001; r=0.372, p0.001); and three tricuspid annular systolic displacement amplitude, right ventricular ejection fraction, the area change of right ventricular and cardiac index were negatively correlated (r=-0.394. P0.001; r=-0.336, p0.001; r=-0.427, p0.001; r=-0.420, p0.001).85 patients have different right indoor movement step (RV-SD418ms), accounting for 56.7%. and synchronization of the exercise group were compared, different step right indoor exercise in patients with right ventricular free wall basal segment and septal basal segment Contraction delay, and the classification of WHO patients with pulmonary hypertension worse, right ventricular end diastolic volume (150.1 + 65.1cm3vs.112.2 + 39.3cm3, p0.001) and end systolic volume (112.1 + 55.5cm3 vs.75.9 + 30.9cm3, p0.001), right ventricular ejection fraction (25.5% + 10.1%vs.33.3% + 8.6%, p0.001) and right ventricular area change scores (25.9% + 6.2%vs.32.8% + 9%, p0.001) decreased. Hemodynamics, cardiac index of different step right indoor exercise in patients with significantly lower (2.5 + 0.7 L/min.m2 vs.3.3 + 1.6L/min.m2, p0.001), and pulmonary vascular resistance increased (16.3 + 8.0wood vs.11.7 + 6.1 wood units, p0.001). Multivariate logistic regression analysis right ventricular end systolic volume increased, the right ventricular fractional area change and cardiac index is reduced and the right effect of different indoor step movement related factors. The average follow-up was 42 + 16 months follow-up period, 29 patients died of.ROC curve To obtain the optimal critical value of RV-SD4 in predicting the prognosis for multivariate 38ms. regression analysis showed that RV-SD438ms Cox was an independent predictor of death in patients with (HR=2.962, p=0.048). Conclusion: the right pulmonary hypertension in patients with cardiac dysfunction and right ventricle are different step movement, right indoor different step motion is independent prognostic factor in patients with pulmonary arterial hypertension death.

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R544.1

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