【作者】 曹翔；

【导师】 邹良建；

【作者基本信息】 第二军医大学 ， 外科学， 2011， 博士

【摘要】 【目的】本课题利用我国心脏瓣膜外科治疗数据库,对长海医院20年间成人主动脉瓣置换病例资料进行回顾性分析,对EuroSCORE和STS-PROM模型预测成人主动脉瓣置换死亡风险的应用进行评价,并分析影响成年患者单纯主动脉瓣置换早期预后的危险因素。【方法】(一)成人主动脉瓣置换927例回顾性分析:1、选择长海医院1990年至2009年间首次行主动脉瓣置换、年龄≥18岁患者作为研究对象,包括同期行冠脉动脉搭桥(CABG)手术、同期大血管手术、同期先心矫治手术的患者,并排除同期其它瓣膜置换、主动脉夹层动脉瘤累及主动脉瓣而手术患者。研究对象还包括因主动脉瓣原发疾病引起二、三尖瓣继发性关闭不全而行成形手术的患者。2、以研究对象的在院死亡作为终点考察事件。(二)EuroSCORE和STS-PROM模型对成人主动脉瓣置换死亡风险预测的评价:1、按照EuroSCORE和STS-PROM模型定义要求,回顾性收集1999年至2008行主动脉瓣置换术521例患者的临床资料,其中包括同期行冠脉动脉搭桥(CABG)手术患者,排除同期其它瓣膜置换、大血管外科、先天性心脏病矫治及房颤外科手术治疗患者。以患者在院死亡作为终点考察事件。2、利用网页分别在线计算EuroSCORE和STS-PROM预测的在院死亡率,并根据additive EuroSCORE评分结果把患者分为低、中、高三个风险组。3、通过实际、预测死亡率间的比较以及模型符合度、鉴别度的验证来评价各风险模型对患者在院死亡率的预测能力。(三)成人主动脉瓣置换术后在院死亡危险因素分析:1、选择1995年至2009年行单纯主动脉瓣置换或主动脉瓣置换合并冠脉搭桥手术的成年患者作为研究对象,排除联合瓣膜置换、术中同时二尖瓣和/或三尖瓣成形术、同期先天性心脏病矫治术和同期大血管手术患者。以患者在院死亡作为终点考察事件。2、选取患者临床资料中可能与术后死亡有关的临床变量进行单因素的统计分析。3、对单变量检验中有统计学差异的变量及被认为具有生物学重要意义的变量进行多元Logistic回归分析。【结果】(一)成人主动脉瓣置换927例回顾性分析:1、共有927例主动脉瓣手术患者纳入研究,约92%患者伴有不同程度的临床症状。20年间,主动脉瓣手术量和手术患者的平均年龄在不断增加,而病程时间不断缩短。先天性、退行性和风湿性是我国成人单纯主动脉瓣置换术患者的主要病因。风湿性病变和感染性心内膜炎比例逐渐下降,退行性和先天性比例不断上升。风湿性主动脉瓣病变患者年龄低于退行性、先天性和感染性的年龄(P<0.001)。各病因组中,男性数量均多于女性(2～2.4:1)。单纯主动脉瓣关闭不全(AR)患者人数比单纯主动脉瓣狭窄(AS)和主动脉瓣狭窄合并关闭不全(AS+AR)多。单纯AR组的年龄要显著低于单纯AS组和AS+AR组(P<0.001),而AS组和AS+AR组年龄间并无统计学差异。2、自1990年至2009年,主动脉瓣置换合并其他手术的比例不断上升。对于单纯主动脉瓣手术,体外循环时间和主动脉阻断时间较前明显缩短(P<0.05)。主动脉机械瓣的使用占91.3%,生物瓣占7.2%。绝大多数的机械瓣为进口瓣膜(85.6%),国产机械瓣仅占9%。主动脉瓣部位最常使用的是Carbomedics瓣(54%)。男性患者多选择23和25号主动脉瓣,女性多选择21、23和25号。3、近十年间,患者术后呼吸机辅助时间(P<0.05)、术后ICU停留时间(P<0.001)及术后住院时间(P<0.001)均比前十年明显缩短。927例患者中,术后发生在院死亡44例(4.7%)。死亡率在男女性别间无差异。近15年内的患者手术死亡率显著下降,尤其最近5年的死亡率明显低于1990年～1994年(P<0.05)。60岁以上患者的死亡率明显高于年轻(≤60岁)患者(8.8% vs. 3.8%,P<0.01)。(二)EuroSCORE和STS-PROM模型对成人主动脉瓣置换死亡风险预测的评价:1、全部521例患者中,术后发生在院死亡21例,实际在院死亡率为4%。additive EuroSCORE、logistic EuroSCORE和STS-PROM预测的在院死亡率分别为3.36%、2.82%和1.25%,实际观察值/预测值(O/E)分别为1.2、1.43和3.23。STS-PROM明显低估实际在院死亡率(P<0.0001),logistic EuroSCORE评分有低估实际在院死亡率的趋势,而additive EuroSCORE评分较接近实际总体死亡率。2、根据additive EuroSCORE评分结果将患者分为低、中、高三个风险组,其中低风险组患者193例、中风险组患者275例及高风险组患者53例,各风险组患者的实际在院死亡率分别为0.5%、4.7%和13.2%。STS-PROM对中、高风险组患者的预测明显低于实际在院死亡率(P<0.01),logistic EuroSCORE明显低估中风险组患者实际在院死亡率(P<0.05)。尽管差异未达到统计学意义,但additive EuroSCORE和logisticEuroSCORE都有低估了高风险组患者实际在院死亡率的趋势,实际观察值/预测值(O/E)分别为1.84和1.46。3、additive EuroSCORE、logistic EuroSCORE和STS-PROM对全组患者评分的ROC曲线下面积分别为0.727、0.753和0.753。而additive EuroSCORE和logistic EuroSCORE在高、中、低各组以及STS-PROM在中、高风险组中评分的ROC曲线下面积都低于0.7。(三)成人主动脉瓣置换术后在院死亡危险因素分析:1、693例主动脉瓣置换成年患者中,术后发生在院死亡30例,死亡率4.3%。主要的死亡原因是低心排综合症和严重心律失常,两者占死亡总数的53.3%。死亡率在男女性别上无差异。2、单因素分析结果显示与患者术后死亡有关的临床变量有:年龄、病程时间、糖尿病、慢性阻塞性肺部疾病、肌酐、心房纤颤、左室射血分数、短轴缩短率、室间隔厚度、左室后壁厚度、相对室壁厚度、左房容积、右房容积、主动脉瓣狭窄、主动脉瓣关闭不全、冠脉造影异常、NYHA心功能分级、术前心肌梗死、同期冠状动脉旁路移植术、体外循环时间、主动脉阻断时间和辅助循环时间。3、多元Logistic回归分析发现房颤、左室后壁厚度和同期冠状动脉旁路移植术是成人主动脉瓣置换术后死亡的独立危险因素。【结论】1、20年来,体外循环和外科技术在不断进步,接受外科手术治疗的主动脉瓣疾病患者人数也不断增加。成人主动脉瓣置换患者的术后在院死亡率较前明显下降。2、无论是STS-PROM还是EuroSCORE对本组主动脉瓣置换患者手术死亡风险的预测均较差,不能被直接用作筛选主动脉瓣置换术高危患者的工具。在选择患者手术时,仍需依靠临床判断,而现有的手术风险模型仅可作为参考。有必要建立适合我国瓣膜患者特征的手术风险预测模型。3、通过对相关临床危险因素的分析,确定了部分影响主动脉瓣术后在院死亡的独立预后因素。它们可用于术前评估风险、高危手术患者识别和指导日常临床工作。更多还原

【Abstract】 【Objective】Over the 20-year study period, we analyzed a consecutive series of aortic valve replacement in adults (1) to determine implications for patients referred for AVR (2) to analyze the predictive value of the European system for cardiac operative risk evaluation score (EuroSCORE) and the Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) in adults undergoing aortic valve replacement (AVR) (3) and, to determine predictors of in-hospital mortality after aortic valve replacement.【Methods】1、Aortic valve replacement in adults: a retrospective study of 927 cases.(1) The study population consisted of patients 18 years old or older who underwent primary aortic valve procedure at Changhai hospital between 1999 and 2008. Patients were excluded if they underwent combined valve replacement or aortic valve replacement for aortic dissection. Patients with an additional surgical procedure, including concomitant coronary artery bypass grafting, correction of congenital heart disease, thoracic aortic surgery and valvuloplasty for mitral or tricuspid regurgitation caused by aortic valve disease, were also included.(2) The clinical outcome considered was in-hospital mortality, defined as the patient’s status at discharge after the operation.2、Validation of the EuroSCORE and the STS-PROM in adult patients undergoing aortic valve replacement.(1) We carried out a retrospective statistical analysis on adult patients undergoing AVR between 1999 and 2008 according to the definitions of the EuroSCORE or STS-PROM. Patients with concomitant coronary artery bypass grafting were also included. Excluded from this study were patients having surgery for congenital heart defects, aneurysm of thoracic aorta and atrial fibrillation. Operative mortality was defined as death before discharge from the hospital (in-hospital mortality).(2) The mortality risk calculation of EuroSCORE and STS-PROM for aortic valve procedures was performed by the online available EuroSCORE or STS score calculator. Based on the additive EuroSCORE risk calculation, patients were divided into low-risk, medium-risk and high-risk groups.(3) The valuation of three different algorithms depended on the assessment of two features: calibration and discrimination. A comparison of observed and predicted mortality rates was also performed.3、Multivariable prediction of in-hospital mortality associated with aortic valve replacement in the adult.(1) Data was collected on adult patients undergoing aortic valve replacement or aortic valve replacement plus coronary artery bypass surgery between 1995 and 2009 from registry of our institute. Excluded from this study were patients having combined valve replacement, patients with mitral or tricuspid valvoplasty, patients with surgical correction of congenital heart disease, and patients undergoing surgery of the thoracic aorta. The end point wasin-hospital mortality. (2) The univariate association between risk factors and in-hospital mortality was assessed with a univariate analysis.(3) All variables significant in the univariate analysis were subsequently entered into a multivariable logistic regression analysis.【Results】1、Aortic valve replacement in adults: a retrospective study of 927 cases.(1) During the 20-year study period, a total of 927 patients were identified as having aortic valve replacement, 92% of which resenting with a variety of different symptoms. Both the number of AVRs and the age of patients increased,while course of the disease became shorter. The major cause of the aortic valve disease included congenital valve, degenerative and rheumatic change. There was a shift in the causes of aortic valve disease. Patients with aortic regurgitation (AR) were younger compare to other groups (P<0.001). There was no age difference between AS and AS+AR group.(2) The proportion of AVR combined with other procedure increased between 2000 and 2009. For isolated aortic valve surgery, the CPB time and aortic clamping time were significantly shorter than those of before (P <0.05). Aortic valve replacement using mechanical valve accounted for 91.3% of aortic valve surgical procedure. For the aortic position, the most commonly used valve were Carbomedics series (54%). Among the various sizes of aortic valve prostheses, the most commonly used valves were 23mm and 25mm size for males and 21mm, 23mm and 25mm size for females. (3) During the Last Decade, duration of postoperative ventilation (P <0.05), time in the intensive care unit (ICU) (P <0.001) and length of postoperative hospital stay (P <0.001) reduced significantly compare with those of the first decade. The overall in-hospital mortality was 4.7% (44 of 927 patients). No gender difference was found in operative mortality. The mortality have greatly decreased in the past 15 years,and in-hospital mortality of the last 5 years (2005-2009) was lower than that of the first 5 years (1990-1994)(P<0.05). The mortality in patients over 60 years was higher than that in younger (≤60 years) patients (8.8% vs. 3.8%, P <0.01).2、Validation of the EuroSCORE and the STS-PROM in adult patients undergoing aortic valve replacement:(1) A total of 521 patients were identified as having undergone aortic valve replacement. In-hospital mortality was 4% overall. The expected mortality for the additive, logistic EuroSCORE and the STS-PROM was 3.36%, 2.82% and 1.25%, respectively. The observed to expected ratio was 1.2 for additive EuroSCORE,1.43 for logistic EuroSCORE and 3.23 for STS-PROM. The STS-PROM underpredicted observed mortality significantly (P<0.0001). The logistic EuroSCORE showed a tendency to underpredict observed mortality. However, additive EuroSCORE was close to actual mortality.(2) There were 193, 275 and 53 patients classified as low-, medium- and high-risk group according to the additive EuroSCORE score, and the observed mortality was 0.5%, 4.7% and 13.2%, respectively. The STS-PROM underpredicted observed mortality in medium- and high-risk group, significantly (P<0.01). The logistic EuroSCORE underpredicted observed mortality in the medium-risk subgroup, significantly (P<0.05). EuroSCORE show a tendency to underpredict observed mortality in the high-risk subgroup with the observed to expected radio of 1.84 for additive EuroSCORE and 1.46 for logistic EuroSCORE.(3) The discriminative power of models for the entire cohort with the area under the ROC curve of 0.727 for additive EuroSCORE,0.753 for logistic EuroSCORE and 0.753 for STS-PROM. The EuroSCORE in three subgroups showed poor discrimination in predicting mortality as well as the STS-PROM did in the medium- and high-risk subgroups.3、Multivariable prediction of in-hospital mortality associated with aortic valve replacement in the adult:(1) A total of 693 patients were identified as having undergone aortic valve replacement. In-hospital mortality was 4% overall. The leading causes of death were low cardiac output syndrome and severe arrhythmia, which accounted for 53.3% of deaths. No gender difference was found in operative mortality.(2) Candidate predictors significant in the univariate analysis were age, time-course of disease, diabetes, chronic obstructive pulmonary disease, creatinine,atrial fibrillation, left ventricular ejection fraction, shortening fraction, interventricular septal thickness, left ventricular posterior wall thickness, relative wall thickness, left atrial volume, right atrial volume, aortic stenosis, aortic insufficiency, abnormal coronary angiography, NYHA functional class, preoperative myocardial infarction, concomitant CABG surgery, cardiopulmonary bypass (CPB) time, cross-clamp time and assisted CPB time.(3) Atrial fibrillation, left ventricular posterior wall thickness and concomitant CABG surgery were confirmed to be independent predictors of in-hospital mortality.【Conclusions】1、During the 20-year study period, with improved surgical techniques , better intensive care treatment and different protocols of myocardial protection, more and more patients referred for aortic valve replacement. The in-hospital mortality decreased to a level lower than that of before.2、Both the EuroSCORE and the STS-PROM give an imprecise prediction for individual operative risk in patients undergoing aortic valve replacement in our study. These algorithms seem unsuitable to identify a high-risk patient population undergoing isolated AVR. It is necessary to construct a risk stratification model for valve surgery according to the profiles of Chinese patients.3、By multivariable logistic regression analysis, some associated Risk Factors for AVR were confirmed to be independent predictors of in-hospital mortality, which could be used to identify patients at high risk of postoperative morbidity and mortality.更多还原