心脏瓣膜病是结构性心脏病最重要的组成部分，同时也是导致心力衰竭的重要病因。在全球范围内，尽管随着瓣膜治疗技术的进步和预防项目的成功开展，瓣膜手术的成功率逐渐提高。然而随着全球人口老龄化程度的加剧和人均寿命的增长，心脏瓣膜病的疾病负担仍呈指数级增加。中国目前也面临巨大挑战。《中国心血管病报告2021》指出：我国预计现有心脏瓣膜病患者2500万人，给个人和社会带来了巨大经济和疾病负担。

自我国21实际进入老龄化社会以来，老龄化速度逐渐加快、程度不断加深。目前全通通用的老年定义是65岁及以上人口。老龄是心脏瓣膜病及瓣膜外科手术的共同危险因素，因此随着人口结构的变化，我国将会面临更严峻的心脏瓣膜疾病负担及更复杂的瓣膜病因变化。并且老年瓣膜性心脏病人群合并心力衰竭的比例更高。然而，目前对于中国地区的老年瓣膜外科现状缺少总结，暂没有针对该人群的大型临床研究。

中国心血管外科注册登记研究（Chinese Cardiac Surgery Registry，CCSR）数据库是一项由阜外医院牵头开展的全国多中心观察性研究。本研究基于这一全国多中心注册登记数据库描述了当前我国合并心力衰竭的老年心脏瓣膜病外科的治疗现状。并且通过建立一个针对我国老年瓣膜病患者的风险预测模型，对老年瓣膜病外科围术期危险因素进行深入探讨，从而为进一步的老年瓣膜外科医疗质量改进工作提供参考依据。

主要研究结果如下：

第一部分 中国老年瓣膜病合并心衰患者的临床特征与外科治疗现状

目的：

依托中国心血管外科注册登记研究（Chinese Cardiac Surgery Registry，CCSR）数据库，分析中国合并心力衰竭的老年(定义为年龄≥65岁)心脏瓣膜病(valvular heart disease, VHD)患者的人群特征以及外科治疗现状。

方法：

基于CCSR数据库，回顾性收集2012年1月至2020年12月期间中国北部、东部、中部、南部、东北部、西南部、西北部7个地区接受心脏瓣膜手术且诊断为心衰且左心室射血分数<50%的老年VHD患者的人口统计学信息、临床特征和治疗情况。以院内死亡作为结局判断指标。使用广义线性分层模型计算各地区风险因素标化院内死亡率 (RSMR)。

结果：

自2012年1月至2020年12月,CCSR数据库纳入了109家年心血管外科手术量超过100例的心脏中心，共完成老年瓣膜病合并心衰外科手术患者2 521例，其中东部、北部、中部、西南部、西北部、东北部、南部7个地区分别为927例（36.8%）、554例（22.0%）、300例（11.9%）、300例（11.9%）、178例（7.1%）、156例（6.2%）、106例（4.2%），中位年龄为68.7（66.7, 72.2)岁，34.7%的患者为女性。风湿性心脏病占37.2%，退行性VHD占34.2%。其中主动脉瓣手术1 597例（63.3%），二尖瓣手术1 505例(59.7%)，主动脉瓣手术联合二尖瓣手术609例(24.1%)。823例(32.6%)患者同期接受冠状动脉旁路移植术（CABG）。总体院内观察死亡率为6.98%，总体院内主要并发症率为14.0%。西南地区院内观察死亡率最低仅为2.33%，西北地区最高为11.01%。对危险因素进行标化后，西北地区RSMR最高，为10.95%（95%CI:10.89%~11.01%），西南地区RSMR最低，为3.34%（95%CI：3.31%~3.38%），华北地区次之，RSMR为5.40%（95%CI：5.36%~5.64%）。

结论：

基于CCSR这一全国多中心注册登记研究数据库，本研究首次较为全面地展现了我国目前合并心衰的心脏瓣膜病老年患者的外科治疗现状及临床特征。中国合并心衰的老年VHD外科人群中，风湿性病变仍是最常见的病因，退行性病变所占比例增加。与欧美等发达国家相比，中国当前老年瓣膜心衰外科救治数量较少。并且在围术期死亡方面地区差异显著。

第二部分 老年心脏瓣膜病外科患者围术期死亡风险预测模型的建立和验证

目的：

建立并验证一个老年心脏瓣膜病患者外科术后院内全因死亡的风险预测模型。

方法：

回顾性收集2019年1月至2020年12月中国心血管外科注册登记研究（Chinese Cardiac Surgery Registry，CCSR）中接受心脏瓣膜外科手术的3367例老年患者（定义为年龄≥65岁），将在2019年1月到2020年4月接受瓣膜手术的患者人群作为模型建模队列（n=2484），2020年5月到2020年12月接受瓣膜手术的患者人群作为模型验证队列(n=883)。采用单因素分析和多因素Logistic回归建立一个预测老年心脏瓣膜外科手术院内死亡风险的列线图模型，分别应用受试者工作特征曲线下面积、Hosmer-Lemeshow校准曲线及Brier评分评价新模型在建模及验证队列中的区分度和校准度，并将新模型的结果与EuroSCORE II进行比较。

结果：

本研究中接受心脏瓣膜外科手术治疗的老年女性患者1476例（43.8%），男性1891例（56.2%），中位年龄为68.9（66.7,72.1）岁，总体院内死亡率为4.6%(156/3367)。最终纳入列线图预测模型的危险因素包括年龄>70岁、肾小球滤过率<50ml/min/1.73m²、术前左心室射血分数<40%、吸烟史、充血性心力衰竭史、NYHA IV、周围血管病、三尖瓣重度关闭不全、二次手术、非择期手术、合并冠状动脉旁路移植术。新的列线图模型在训练集和验证集中的Brier评分分别为0.042、0.041。EuroSCORE II在训练集和验证集中的Brier评分分别为0.045、0.043，列线图模型在训练集和验证集的曲线下面积（AUC）分别为0.751、0.713，均显著高于EuroSCORE II在训练集和验证集的AUC（分别为0.604、0.617）。

结论：

年龄、三尖瓣重度关闭不全等11个因素为老年心脏瓣膜外科术后院内死亡的独立危险因素，新的列线图预测模型可以准确地预测老年患者瓣膜术后的院内死亡率。

Valvular heart disease (VHD) is one of the most important components of structural heart disease and a major cause of heart failure. Worldwide, the mortality rate of valve surgery is improving with advances in valve therapy techniques and successful prevention programs. However, as the global population ages and life expectancy increases, the disease burden of valvular heart disease is increasing exponentially. China also faces huge challenges. According to the China Cardiovascular Disease Report 2021, there are an estimated 25 million patients with valvular heart disease in China, which brings a huge economic burden to society and individuals.

In China, the speed of population aging has been accelerating and the degree has been deepening since the 21st century. The current general definition of senior-aged people is people aged 65 years and older. Aging is a risk factor for both valvular heart disease and valve surgery. Therefore, with the transition of demographic, China will meet the challenges of a more severe burden of valvular heart disease. In addition, the proportion of senior-aged patients with valvular heart disease complicated with heart failure is higher. However, there is a lack of large clinical studies for senior-aged patients with VHD.

The Chinese Cardiac Surgery Registry (CCSR) database is a national multicenter observational study led by Fuwai Hospital. Based on CCSR, we present the current status of surgical treatment of valvular heart disease in senior-aged patients in China. Besides, in this study, we will have an in-depth discussion of some representative aspects, such as baseline characteristics, perioperative treatment, and etiology, to provide a reference for further improvement of the medical quality in valve surgery.

The main results are as follows:

Part 1: Analysis of surgical quality and perioperative risk factors in senior-aged patients with valvular heart disease in China

Objectives: To analysis the clinical characteristic and surgical treatment status of senior-aged patients with valvular heart disease (VHD) and heart failure in China.

Methods: We established the the Chinese Cardiac Surgery Registry (CCSR) database to obtain the demographic, clinical characteristics and treatment patterns of senior-aged patients with heart failure undergoing valve surgery in China. Data were obtained at 7 different regions (North East, North, East, Central, South, South West, and North West) from January 2012 to December 2020. In-hospital mortality were regarded as outcome indexes. We estimated region-level risk standardized in-hospital mortality rates (RSMR) by using hierarchical generalized linear models.

Results: From January 2012 to December 2020, data on 2 521 senior-aged patients with VHD with heart failure from 7 regions were registered from 109 participating centers with the adult cardiac surgery volume more than 100 operations per year. Among cases, rheumatic heart disease (RHD) accounted for 37.2%, and degenerative VHD accounted for 34.2%. The number of aortic valve surgeries was 1 597 (63.3%), which was slightly higher than that of mitral valve surgeries (n=1 505, 59.7%). The number of concurrent aortic and mitral valve surgeries was 609 (24.1%). A total of 823 surgical VHD patients (32.6%) also underwent coronary artery bypass grafting (CABG). The overall observed in-hospital mortality rate was 6.98%. The lowest and highest observed in-hospital mortality rates were in the southwest region (2.33%) and the northwest region (10.11%), respectively. The lowest RSMR (3.34%)（95% CI：3.31%~3.38%） was in the southwest region, followed by 5.40% （95% CI：5.36%~5.64%）in the north region and the highest RSMR (10.95%)（95% CI:10.89%~11.01%）was in the northwest region. 

Conclusions: Based on the CCSR database, a national multi-center database, this study comprehensively presents the current status and clinical characteristics of surgical treatment in elderly patients with valvular heart disease complicated with heart failure in China for the first time. In the senior-aged patients with heart failure who underwent valve surgery in China, RHD was still the major cause of the VHD, with a significant increase in degenerative heart disease. The number of valve surgery in this special population is small and there are marked regional variation in the perioperative mortality of valve surgery.

Part 2：An In-Hospital Mortality Risk Model for senior-aged Patients Undergoing Cardiac Valvular Surgery Based on Logistic Regression

Background：We aimed to develop and validate a prediction model for in-hospital mortality in senior-aged patients with valvular heart diseases (VHD).

Methods: Between January 2019 and December 2020, all consecutive senior-aged patients undergoing valvular surgery in the Chinese Cardiac Surgery Registry (CCSR) database were included. Finally, 3,367 patients were identified for analysis. As a training group for model derivation, we used patients who had surgery between January 2019 and April 2020 (2,484 in total). To validate the model, patients who underwent surgery between May 2020 and December 2020 (a total of 883 patients) were included as a testing group. In training group, we constructed a nomogram prediction model to predict in-hospital mortality in senior-aged patients undergoing cardiac valvular surgery by using univariable analysis and multivariable logistic regression. Then we validated the nomogram model in the testing group. Brier score and calibration curves using bootstrapping with 1000 re-samples were used to evaluate the calibration. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination. The results were also compared to EuroSCORE II.

Results: A total of 3367 patients were included in this study, with a median age of 68.9 years, and 43.8% were women. Overall, the in-hospital mortality was 4.6%. The final nomogram model included eleven risk factors: ag＞70 years; smoking history; peripheral vascular disease; left ventricular ejection fraction (LVEF)<40%; congestive heart failure; New York Heart Association Class (NYHA) IV; severe tricuspid valve regurgitation; re-operation; combined coronary artery bypass grafting (CABG); estimated glomerular filtration rate (eGFR)< 50ml/min/1.73m2; non-elective surgery. Brier scores in the training and testing groups of the nomogram model were 0.042 and 0.041, respectively. Brier scores in the training and testing groups of EuroSCORE II were 0.045 and 0.043, respectively. The area under the curve (AUC) values of the nomogram model in the training and testing groups were 0.751 and 0.713, respectively, which was significantly higher than EuroSCORE II in both the training (AUC = 0.604, p < 0.05) and testing (AUC = 0.617, p < 0.05) groups.

Conclusion: The new nomogram model could accurately predict in-hospital mortality rates in senior-aged patients undergoing cardiac valvular surgery.