肺动脉高压血流动力学和右心功能与预后的研究

发布时间：2018-01-19 15:11

本文关键词： 先天性心脏病肺动脉高压肺血管顺应性预后肺血管顺应性急性肺血管反应试验钙通道阻滞剂右室内不同步化运动肺动脉高压右心功能预后　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：第一部分:肺血管顺应性对成人先天性心脏病相关性肺动脉高压预后预测价值的研究(International Heart Journal.已接收)目的:探讨肺血管顺应性(pulmonary vascular compliance,Cp)在预测成人先天性心脏病相关性肺动脉高压患者预后方面的价值。方法:连续入选2007年1月-2012年12月在阜外医院经右心导管确诊的成人先天性心脏病相关性肺动脉高压患者,所有患者进行详细的临床评估,包括世界卫生组织(world health organization,WHO)肺动脉高压功能分级、六分钟步行距离、超声心动图检查和血流动力学检查,收集肝功、肾功、血浆利钠肽、血气分析等血液化验结果。肺血管顺应性定义为右心每搏输出量/(肺动脉收缩压-舒张压)。所有患者每隔3-6个月进行电话或门诊随访,主要随访结局事件为全因死亡。结果:研究共纳入了 175例成人先天性心脏病相关性肺动脉高压患者,并根据临床分类分为3个组,包括Eisenmenger综合征112例,小缺损先天性心脏病合并肺动脉高压20例,左向右分流先天性心脏病矫正术后肺动脉高压43例。在各个组中肺血管顺应性与肺血管阻力均呈反比例关系。肺血管顺应性低的患者表现出更差的运动耐力、肝功能、右心功能、血氧分压和血流动力学状态。所有患者平均随访时间为67±26个月,随访过程中有23人死亡。单因素Cox回归分析提示与生存相关的危险因素为心率((HR=1.038,p=0.028)、肺血管顺应性(HR=1.359,p0.001)、肺血管阻力(HR=0.972,p=0.001)、肺循环血流量(HR=1.092,p=0.001)和六分钟步行距离(HR=1.003,p=0.037)。双变量Cox回归分析提示肺血管顺应性是患者预后的独立预测因素。受试者工作曲线(receiver operator characteristic curve,ROC)曲线获得肺血管顺应性预测预后的最佳临界值为1.04ml/mmHg;Kaplan-Meier曲线显示肺血管顺应性小于1.04ml/mmHg的患者的生存率要明显低于肺血管顺应性大于或等于1.04ml/mmHg 的患者。结论:肺血管顺应性可以反映成人先天性心脏病相关性肺动脉高压患者的病情严重程度,是患者预后的独立预测因素。第二部分:肺血管顺应性预测特发性肺动脉高压患者钙通道阻滞剂治疗长期获益的研究(Lung.2016;194(4):613-618)目的:探讨肺血管顺应性(pulmonary vascular compliance,Cp)预测特发性肺动脉高压(idiopathic pulmonary arterial hypertension,IP AH)患者能否长期获益于钙通道阻滞剂(calcium channel blockers,CCB)治疗方面的价值。方法:研究入选2009年1月-2014年12月在阜外医院肺血管病中心初诊为特发性肺动脉高压的患者,通过吸入伊洛前列素进行急性肺血管反应试验,评估吸药前和吸药后的肺血管顺应性。肺血管顺应性定义为右心每搏输出量/(肺动脉收缩压-舒张压)。急性肺血管反应试验阳性患者给予CCB治疗,并对患者进行至少1年的随访,主要随访内容为患者症状、运动耐力、世界卫生组织(world health organization,WHO)肺动脉高压分级和用药情况。结果:研究共纳入特发性肺动脉高压患者308例,其中35例为急性肺血管反应试验阳性,占11.7%。肺血管顺应性与患者WHO肺动脉高压功能分级、六分钟步行距离、肺动脉平均压、肺血管阻力呈明显相关性(r=-0.363,p0.001;r = 0.333,p0.001;r =-0.514,p0.001;r=-0.739,p0.001)。与阴性患者相比,阳性患者吸药前的肺血管顺应性更高(1.5±0.6ml/mmHg vs.1.1±0.7ml/mmHg,p = 0.003),肺动脉平均压(49±10mmHg vs.62±17mmHg,p0.001)和肺血管阻力(11.7 ± 4.6 wood单位 vs.17.1 ±8.1wood单位,p0.001)更低。吸药后阳性患者肺血管顺应性提高79%±48%,而阴性患者提高19%±47%,差异有统计学意义(p0.001)。35例阳性患者中有24例长期获益于CCB治疗。长期获益的患者吸药后肺血管顺应性增加更为明显(93%± 72%vs.48%±49%,p=0.039)。多因素逻辑回归结果提示,吸入伊洛前列素后肺血管顺应性的增加程度与CCB治疗长期获益相关,是钙通道阻滞剂治疗长期获益有力的预测因素(OR=1.24,p=0.031)。结论:急性肺血管反应试验阳性的IPAH患者具有更高的肺血管顺应性,急性肺血管反应试验过程中吸入伊洛前列素后肺血管顺应性的增加程度可预测钙通道阻滞剂治疗的长期有效性,有助于筛选CCB治疗长期获益的患者。第三部分:右室内不同步化运动对肺动脉高压患者右心功能及预后的影响目的:探讨右心室内不同步化运动对肺动脉高压患者右心功能和预后的影响。方法:研究入选150例在阜外医院肺血管病中心诊断为肺动脉高压的患者,所有患者进行详细的临床评估,包括世界卫生组织(world health organization,WHO)肺动脉高压功能分级、六分钟步行距离、右心导管检查等。通过二维超声斑点追踪技术评估右室内不同步化运动,Qlab软件分析获取右心室室壁各节段的应变-时间曲线,并记录右室游离壁中间段、基底段和室间隔中间段、基底段4个节段的纵向应变达峰时间(心电图QRS波起点至应变峰值的时间),计算右室壁4个节段应变达峰时间的标准差(RV-SD4),以RV-SD418ms作为判断患者是否存在右室内不同步化运动的标准。三维超声心动图测量右心室舒张末容积、收缩末容积,计算右心室射血分数。所有患者自确诊之日起每隔6个月进行电话或门诊随访,主要随访结局事件为全因死亡。结果:RV-SD4与右室收缩末容积、右室舒张末容积、肺血管阻力呈正相关(r=0.566,p0.001;r=0.532,p0.001;r=0.372,p0.001);与三尖瓣环收缩期位移幅度、右室射血分数、右室面积变化分数和心指数呈负相关(r=-0.394,p0.001;r=-0.336,p0.001;r=-0.427,p0.001;r=-0.420,p0.001)。85例患者存在右室内不同步化运动(RV-SD418ms),占56.7%。与同步化运动组患者相比,右室内不同步化运动患者右室游离壁基底段和室间隔基底段出现收缩延迟,且患者的WHO肺动脉高压分级更差,右室舒张末容积(150.1±65.1cm3vs.112.2±39.3cm3,p0.001)和收缩末容积(112.1±55.5cm3 vs.75.9±30.9cm3,p0.001)增加,右室射血分数(25.5%±10.1%vs.33.3%±8.6%,p0.001)和右室面积变化分数(25.9%±6.2%vs.32.8%± 9.0%,p0.001)降低。血流动力学方面,右室内不同步化运动患者心指数明显降低(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 单位 vs.11.7±6.1 wood单位,p0.001)。多因素逻辑回归分析显示右室收缩末容积增加、右室面积变化分数和心指数降低是与右室内不同步化运动相关的影响因素。研究平均随访时间为42±16个月,随访期间29例患者死亡。ROC曲线获得RV-SD4预测预后的最佳临界值为38ms。多因素Cox回归分析提示RV-SD438ms是患者死亡的独立预测因素(HR=2.962,p=0.048)。结论:肺动脉高压患者右心功能减低与右室内存在不同步化运动有关,右室内不同步化运动是肺动脉高压患者死亡的独立预测因素。
[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.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R544.1

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