左心室射血分数保留的类风湿性关节炎患者心肌做功与疾病活动度的相关性--基于无创压力-应变环的回顾性研究
Correlation between myocardial work and disease activity in rheumatoid arthritis patients with preserved left ventricular ejection fraction:a retrospective study based on noninvasive pressure-strain loops

目的：应用左心室压力-应变环（LV-PSL）技术评估左心室射血分数保留的类风湿性关节炎（Rheumatoid arthritis，RA）患者左心室功能的变化，探讨其心肌做功能力与疾病活动度的相关性。
Objective:To evaluate left ventricular function in rheumatoid arthritis (RA) patients with preserved left ventricular ejection fraction (LVEF) by left ventricular pressure-strain loop (LV-PSL)and to explore the correlation between myocardial performance and disease activity.

方法：选取2021年1月至2023年9月在江苏大学附属武进医院就诊的左心室射血分数(LVEF)保留的RA患者62例，根据28关节病活动度评分(DAS28评分)分为低疾病活动度组 (25 例)、中疾病活动度组 (18例) 及高疾病活动度组 (19例)，以29名健康体检者为对照组。采用 LV-PSL观察并比较各组左心室整体纵向应变(GLS) 及心肌做功( MW) 参数，包括整体有用功(GCW)、整体无用功(GWW)、整体做功指数(GWI)及整体做功效率(GWE)。对心肌做功参数与GLS，LVEF，DAS28评分进行相关性分析。结果：病例组与对照组一般资料差异无统计学意义 (P>0.05)，实验室检查指标（RF、CRP、ESR、NEUT、LYM、PLT）差异有统计学意义 (P＜0.05)，常规超声检查结果（EF、IVSD、LVEDV、LVESV、HR）及GWW差异无统计学意义 (P>0.05)。高疾病活动度组 GWI、GCW 、GWE、GLS较对照组显著减低 (P<0.05)。病例组 GWI、GCW、GWE与LVEF及GLS绝对值呈正相关，GWW与LVEF呈负相关（P<0.05），与GLS无显著相关(P >0.05)。病例组GWI、GCW 、GWE随DAS28增高依次减低，GWE与DAS-28呈负相关（P<0.05），其他MW参数与DAS-28无显著相关(均P >0.05)。结论：RA患者疾病活动度与心肌做功受损有密切相关，PSL能早期发现早期发现射血分数保留的RA患者心肌功能异常，对于RA患者的管理具有重要的指导意义。 重试    错误原因

关键词：Rheumatoid arthritis, Left ventricular pressure-strain loop,myocardial work, speckle tracking echocardiography

RA是一种多系统受累的自身免疫性疾病，其关节外损害日益受到临床医生的关注。心脏是RA的常见靶器官之一，心包、血管、心肌、瓣膜都会受到影响。一项为期10年的匹配队列研究发现，RA 患者发生急性冠脉综合征（ACS）的可能性是对照组的1.43 倍[风险比 (HR) 1.43，95% CI 1.10-1.84]。根据欧洲心脏病学会的指南，RA被认为是心血管疾病（CVD）的重要危险因素，其心血管疾病风险高达一般人群的两倍。心血管死亡风险最高增加 50%。 重试    错误原因

RA患者中早期心脏损害非常普遍，但通常是亚临床的。因为它们的隐匿性或没有典型特征，RA早期心脏损害常常被忽视。当出现明显症状时，其心脏损害往往是严重且不可逆转的，严重者危及患者生命。因此，自身免疫性疾病中心脏损害的早期发现和治疗尤为重要。 重试    错误原因

左室射血分数（left ventricular ejection fraction, LVEF）仍是超声心动图用于评价心脏收缩功能的首选检查指标，但对于收缩功能的评估具有较大的局限性[¹]。近年来，心脏超声成像技术在心肌功能评估领域取得了显著进展。特别是非侵入式左室压力-应变环(pressure-strain loops,PSL) 技术在评估LVEF保留的患者中显示出其独特的价值。该技术在二维应变技术基础上加入无创测量的动脉压力，可有效抑制后负荷影响，为心肌做功（Myocardial Work, MW）提供了一个全新的评估维度。最新的研究表明，整体做功效率( global work efficiency，GWE)和整体做功指数（Global Work Index, GWI）等参数在评估心肌做功方面具有重要意义[]。Meucci等的研究表明，非侵入式左心室心肌工作是评估慢性主动脉瓣关闭不全和LVEF保留患者心肌表现的一个新参数，可以更好的帮助临床医师了解患者的心肌功能和能量学。
Left ventricular ejection fraction (LVEF) is still the first choice for echocardiography to evaluate cardiac systolic function, but it has great limitations in evaluating systolic function[¹]. In recent years,cardiac ultrasound imaging technology has made significant progress in the field of myocardial function assessment. In particular, noninvasiveleft ventricular pressure-strain loops (PSL)havedemonstrated their unique value in assessing LVEF preservation. This techniqueadds non-invasive arterial pressure measurement to the two-dimensional strain technique, which can effectively suppress the afterload effectandprovide a new evaluation dimension for myocardial work (MW). The latest research showsthatparameters such as global work efficiency (GWE)andglobal work index(GWI) are of great significance in evaluating myocardial work[].Meucci et al.showed that noninvasive left ventricular myocardial work is a new parameter to assess myocardial performance in patients with chronic aortic insufficiency and LVEF preservation, andcanbetterhelp clinicians understandmyocardial function and energetics in patients.

本研究旨在使用先进的无创LV-PSL技术来评估左心室射血分数保留RA患者的心肌做功，通过分析患者心肌做功与疾病活动度之间的关系，希望为这一特殊患者群体提供更个体化、精准的心脏评估，早期识别RA患者心功能异常，为RA患者的心脏功能管理提供新的见解和决策支持。
The aim of this study is toassess myocardial work in RA patients with preserved left ventricular ejection fraction using advanced noninvasive LV-PSL technology.By analyzingthe relationship between myocardial work and disease activity,wehope to provide more individualized and accurate cardiac assessment for this special patient group,identifycardiac dysfunction in RA patients early,and provide new insights and decision supportforcardiac function management in RA patients.

资料与方法
Materials and Methods

1.1 研究对象
1.1Subjects

选取2021年1月至2023年9月在江苏大学附属武进医院就诊的左心室射血分数保留的RA患者62例。根据 28 关节疾病活动度评分 (diseaseactivity scores28,DAS28) 进行分组: 低疾病活动度组 (DAS28≤3 2分)，25例，男5例，女20例，年龄36~ 77岁[58(51,71.5) ] 岁；中疾病活动度组 (3 2分< DAS28≤5 1分)，18例，男6例，女12例年龄36~ 72岁[63(53,71)]；高疾病活动度 (DAS28> 5 1分)，19例，男3例，女16例，年龄46~ 80岁[62. 5(53.25,72.5)]。以29名健康体检者为对照组，男10例，女19例，年龄24~ 88岁[64(57,72)]。纳入标准:①窦性心律；②按2010年风湿病学会(ACR)联合欧洲抗风湿病联盟ULAR) RA 诊断标准，确诊为RA的患者；③常规超声未见明显室壁运动异常，且左心室射血分数(left ventricular ejection fraction，LVEF) ≥50％。排除标准:①心律失常;②既往高血压致左心室肥厚者,以及合并严重瓣膜病、心肌病、先天性心脏病、心力衰竭；③肾功能损害及患有其他结缔组织病者；④图像质量差者。依据 1999 年 WHO糖尿病诊断标准，空腹血糖≥7.0或口服葡萄糖耐量试验(oral glucose tolerance test，OGTT)餐后2小时血糖≥11.1mmol／L诊断为糖尿病。高血压的诊断参照 ISH2020国际高血压实践指南[]:即收缩压 ≥140 mmHg 和（或）舒张压 ≥90 mmHg。 参照 WHO 关于吸烟的标准化定义，患者每天吸卷烟 1支以上，连续或累6个月即定义为吸烟。本研究获医院伦理委员会批准。检查前受试者均签署知情同意书。 重试    错误原因

1.2 仪器与方法

1.2.1仪器

采用 GE Vivid E95 超声诊断仪、M5Sc-D 探头，频率 1．7~3．3 MHz 。

1,2,2图像采集

在超声检查前10 min测量平静状态下血压。 嘱受试者左侧卧，连接心电图，确保稳定的ECG曲线，参照美国心动图协会指南[]方法采集胸骨旁左心室长轴切面，观察左心室舒张末期内径 (left ventricular end－diastolic diameter，LVEDD)、室间隔舒张末期厚度(interventricular septum thickness at end－diastole,IVSD)、左心室后壁舒张末期厚度 (left ventricular posterior wall thickness at end－diastole,LVPWD)，二维双平面Simpson法获得舒张末期左心室容积(LVEDV),收缩末期左心室容积(LVESV),左心室射血分数(LVEF) ；嘱检查者屏住呼吸，分别采集心尖四腔心切面、 心尖两腔心切面、心尖长轴切面分别采集动态二维图像，至少连续采集 3个稳定、清晰的心动周期动态图像；心尖长轴切面清晰显示二尖瓣和主动脉瓣，获取主动脉瓣脉冲多普勒频谱图像，以定义收缩末期时相。储存以上动图和图像用于分析。采集图像时的帧频为40~80帧/s。
在超声检查前10 min测量平静状态下血压。Ask the subject to lie on the left side, connect ECG, ensure stable ECG curve,collect parasternal left ventricularlong-axis tangentplaneaccordingto AmericanAssociation of Cardiography guidelines[],observe left ventricular end-diastolic diameter(LVEDD),ventricularseptalthicknessatend-diastolic(IVSD), left ventricular posterior wall end-diastolic thickness (<span id=2929>left ventricular posterior wall thickness at end－diastole,LVPWD)，二维双平面Simpson法获得舒张末期左心室容积(LVEDV),收缩末期左心室容积(LVESV),左心室射血分数(LVEF) ；嘱检查者屏住呼吸，分别采集心尖四腔心切面、 心尖两腔心切面、心尖长轴切面分别采集动态二维图像，至少连续采集 3个稳定、清晰的心动周期动态图像；心尖长轴切面清晰显示二尖瓣和主动脉瓣，获取主动脉瓣脉冲多普勒频谱图像，以定义收缩末期时相。储存以上动图和图像用于分析。采集图像时的帧频为40~80帧/s。

1.2.3 图像分析

将血压值输入 EchoPAC工作 站，于主动脉瓣及二尖瓣频谱图像中标记瓣膜开闭时间，选择自动功能成像模式，之后分别在心尖三腔心、四腔心、两腔心切面动态图像上勾画心内膜轮廓，对系统自动描记的心内膜边界按照需要加以手动调整，使用17节段模型，软件根据所有节段的峰值收缩纵向应变的加权平均值计算获得左心室整体纵向应变 (global longitudinal strain,GLS)，生成纵向应变曲线及牛眼图，进行存储。如遇图像一个或者多个区域节段跟踪不理想，则将患者从研究中排除。然后打开Event Timing，根据频谱多普勒确定主动脉瓣和二尖瓣开放和关闭时间。输入患者超声心动图检查前即刻通过血压计测量的血压。选择“MyocardiacWork”，显示整体心肌做功牛眼图。获得左心室心肌整体MWI参数，其参数包括 ①整体有效功( global constructive work,GCW) ，收缩期心肌缩短或舒张期心肌延长所做正功，即有助于左心室射血的功；② 整体无效功 ( global wasted work,GWW) ，收缩期心肌延长或舒张期心肌缩短所做负功，即对抗左心室射血的功；③整体做功效率( global work efficiency，GWE)，GWE = GCW /(GCW + GWW) ；④整体做功指数( global work index,GWI)，是心肌17节段心肌做功指数加权平均数。（见图1）
Input the blood pressure value intoEchoPACworkstation,mark the valve opening and closing time in the main aortic valve and mitral valve spectral images,select the automatic functional imaging mode, then delineate the endocardial contour on the apical three-chamber heart, four-chamberheart andtwo-chamber heart dynamic images respectively, manually adjust the endocardial boundary of the system autographaccording to needs,use the 17-segment model, calculate the global longitudinal strain (GLS ) of the left ventricle according to the weighted average value of the peak systolic longitudinal strain of all segments, generate the longitudinal strain curve and bull's eye diagram, and store them. Patients were excluded from the study if one or more of the image segments were not tracked satisfactorily. Event Timing is then turned on to determine aortic and mitral valve opening and closing times based on spectral Doppler. Enter the patient's blood pressure measured by sphygmomanometer immediately prior to the echocardiogram. SelectMyocardiacWork to display the overall myocardial work bull chart.TheMWI parameters of left ventricular myocardiumwere obtained.The parameters included ① global effective work ( global constructive work (GCW)), the positive work done by systolic myocardial shortening or diastolic myocardial lengthening, that is, the work that contributes to left ventricular ejection;② overall ineffective work global wasted work (GWW), negative work done by myocardial prolongation in systole or myocardial shortening in diastole, i.e., work against left ventricular ejection Global work index (GWI) is the weighted average of myocardial work index of 17 segments.(See Figure 1)

1.5 统计学分析
1.5 statistical analysis

采用SPSS26.0（IBM, Armonk, NY）和MedCalc（MedCalc Software bvba, Ostend, Belgium）统计分析软件。计量资料分布类型采用K-S检验，符合正态性分布计量资料以 x±s 表示， 三组间比较采用方差分析，组间两两比较采用 LSD-t-检验，不符合正态分布计量资料以 M（QR）表示，多组比较采用Kruskal Wallis秩和检验，两两比较采用Bonferroni校正显著性水平。计数资料以例表示，采用χ2检验。以Spearman相关分析评价MW参数与DAS28、GLS、LVEF的相关性，r≥0.6为强相关，0.4≤r<0.6 为中等相关，r<0.4为弱相关。
SPSS26.0 (IBM, Armonk, NY) and MedCalc (MedCalc Software bvba, Ostend, Belgium) statistical analysis software were used. K-S test was used for the distribution type of measurement data, and the measurement data conforming to normal distribution were expressed by x±s. Analysis of variance was used for comparison among three groups. LSD-t-test was used for pairwise comparison among groups. Measurement data not conforming to normal distribution were expressed by M (QR). Kruskal Wallis rank sum test was used for multi-group comparison, and Bonferroni correction significance level was used for pairwise comparison. Counting data were expressed as examples and chi-square test was used. Spearman correlation analysis was used to evaluate the correlation betweenMW parametersandDAS28, GLS, LVEF. r≥0.6 was strong correlation, 0.4≤r<0.6 was moderate correlation, r<0.4 was weak correlation.

二、结果
II. Results

2.1各组间一般资料参数比较
2.1Comparisonof generaldataparametersamong groups

各病例组与对照组间年龄、性别、高血压史、糖尿病史、吸烟史、收缩压、舒张压、心率差异均无统计学意义（P>0.05）。（表1） 重试    错误原因

2.2各组间疾病活动度指标比较 重试    错误原因

各病例组与对照组比较，实验室检查指标（RF、CRP、ESR、NEUT、LYM、PLT）差异有统计学意义 (P＜0.05)。高疾病活动度组与低级疾病活动度组比较，ESR、NEUT、PLT有统计学差异(P＜0.05)，与中疾病活动度组比较LYM有统计学差异(P＜0.05)。三组不同活动度疾病组间比较，DAS-28均有统计学差异(P＜0.05)。（表2）
Therewere significant differences in laboratory parameters (RF, CRP, ESR,NEUT, LYM, PLT) between the two groups (P<0.05). Compared with low disease activity group, high disease activity group had significant difference inESR,NEUT, PLT(P<0.05), andcompared with middle disease activity group,LYM(P<0.05). DAS-28was significantly differentamong the three groups (P<0.05). (Table 2)

2.3 各组间常规超声心动图参数、应变参数和心肌做功参数比较
2.3Comparison ofconventional echocardiographic parameters,strain parameters and myocardial work parametersamong groups

各病例组与对照组常规超声心动图检查结果（EF、IVSD、LVEDV、LVESV、HR）差异无统计学意义 (P>0.05)。各病例组应变参数GLS的绝对值与对照组相比均明显减低差异有统计学意义[-19.8(-21.1,-18.7) , -20(-22,-18.86), -19.85(-20.82,-15.70) vs -22.2(-22.8,-20), (P<0.05)]。从对照组到低、中、高疾病活动度组，GWI、GCW 、GWE依次减低，且高疾病活动度组 GWI、GCW 、GWE较对照组显著减低，差异有统计学意义[1992.79±471.39 vs 2421.48±305.70, 2118.63±513.35 vs 2482.22±340.15, 89.5(87,92.75) vs 90(90,94), (P<0.05)]。各病例组间GWW依次增高，但差异无统计学意义 (P >0.05)。
Therewasno significant difference in EF, IVSD, LVEDV, LVESV and HR between the two groups (P% 3E0.05). Theabsolute values of GLS ineach case group were significantly lower than those in the control group[-19.8(-21.1,-18.7),-20(-22,-18.86),-19.85(-20.82,-15.70)vs-22.2(-22.8,-20),(P<0.05)]. GWI, GCW and GWE decreased in turn from control group to low, middle and high disease activity groups, andGWI, GCW and GWE decreased significantly in high disease activity group compared with control group.39 vs 2421.48±305.70, 2118.63±513.35 vs 2482.22±340.15, 89.5(87,92.75) vs 90(90,94), (P<0.05)]。各病例组间GWW依次增高，但差异无统计学意义 (P >0.05)。

2.4各心肌做功参数与GLS、EF、DAS28的相关性分析

采用Spearman相关分析方法，对研究组各心肌做功参数与GLS、EF、DAS28的相关性进行分析(表4)。结果显示病例组GWE、 GWI、GCW与GLS的绝对值呈中强正相关（r＝-0.501、-0746、-0.666，P均＜0.01），GWW与GLS无明显相关(P >0.05)；各心肌做功参数与LVEF 呈弱相关(P<0.05)；病例组GWE与DAS-28呈中等负相关（r=-0.402，P<0.05），其他MW参数与DAS-28均无显著相关(均P >0.05)。（详见表4、图2） 重试    错误原因

三 讨论 重试    错误原因

根据2021 年全球疾病负担研究发布的数据，在过去30年来，全球RA死亡率有所下降，从 1990 年到 2020 年下降了  23.8%（17.5-29.3），一项来自丹麦的全国范围内基于人群的匹配队列研究得到类似的结果。但RA患病率增长了 14.1%（12.7-15.4）。 In 2020, an estimated 17·6 million (95% uncertainty interval 15·8-20·3) people had rheumatoid arthritis worldwide.  预计到 2050 年病例数将继续增加，需要在全球范围内改善类风湿性关节炎的早期诊断和治疗，以减轻该疾病的未来负担。 重试    错误原因

目前RA患者发病机制尚不明确，但RA 患者死亡的首要原因是心血管事件[19]，其中动脉粥样硬化性疾病占很大部分原因。RA心血管事件风险增加是由传统风险因素和疾病相关风险因素之间复杂的相互作用所致，其中慢性炎症和持续的疾病活动是这种风险的关键决定因素。长期慢性炎症刺激及机体自身免疫反应介导的免疫系统功能紊乱所致的损伤和修复有关[ ]。无明显临床症状的冠状动脉粥样硬化普遍存在于RA患者中[]。有学者提出炎症有助于加速RA等自身免疫性疾病中血管重塑和动脉粥样硬化形成的过程。严格的炎症控制在降低心血管风险方面起着核心作用。另外RA 患者的临床治疗会使用类固醇及非甾体抗炎药，这些药物的不良反应可能会增加心血管风险。
At present, the pathogenesis of RA patients is not clear,butthe primary cause of death in RA patients is cardiovascular events [19], among which atherosclerotic diseases account for a large part of the causes. Theincreased risk of cardiovascular events in RAresultsfrom complex interactions between traditional and disease-related risk factors, withchronic inflammation and ongoing disease activity being key determinants of this risk. The damage and repair caused by the immune system dysfunction mediated by long-term chronic inflammation stimulation and autoimmune reaction of the body[]. Coronary atherosclerosis without obvious clinical symptoms is common in RA patients []. Some scholars suggest that inflammationhelps acceleratethe process of vascular remodeling and atherosclerosis formation in autoimmune diseases such as RA. Strict inflammation control plays a central role in reducing cardiovascular risk. In addition, RA patients are clinically treated with steroids and nonsteroidal anti-inflammatory drugs, and adverse reactions of these drugs may increase cardiovascular risk.

RA心脏损害的早期症状和体征隐匿，临床上可通过心肌酶谱、心电图等检查对心功能状态进行评估，但是心肌酶谱、心电图检查敏感性低，且对发病时间要求严格，致使其应用受限。经导管心内膜下心肌活检虽然可作为检验心肌损害的金标准，但是因其操作有创不能用于常规筛查。磁共振心脏显像和核素心室造影也能对心功能进行评价，但费用昂贵，使其在临床的推广中受到限制。因此，类风湿性关节炎早期心肌功能损害在临床中的诊断率较低。 我们的研究也提示了传统超声心动图参数对RA早期心脏损害的灵敏性不高，本研究结果显示各病例组与对照组比较，实验室检查指标（RF、CRP、ESR、NEUT、LYM、PLT）差异有统计学意义 (P＜0.05)。 说明活动期 RA 患者体内存在较严重的炎症反应。同时高疾病活动度组与低级疾病活动度组比较，ESR、NEUT、PLT有统计学差异(P＜0.05）。有研究表明RA患者机体长期免疫反应和慢性炎症使得心肌细胞凋亡过程加速，对心肌组织产生直接伤害。炎性细胞和免疫细胞在炎性反应中释放各类促纤维化因子使成纤维细胞活性增加引起的心肌间质纤维化[22][11]，进而促使动脉粥样硬化，导致心肌缺血、左心室收缩和舒张功能降低[12]。 然而，本研究所有受检者常规超声心动图参数均位于正常值范围内，且病例组与对照组常规超声心动图检查结果（EF、IVSD、LVEDV、LVESV、HR）差异无统计学意义 (P>0.01），说明上述常规超声心动图观测指标评估 RA 患者心脏功能损伤具有一定局限性。
The early symptoms and signs of RA heart damage are hidden, and the cardiac function can be evaluated by myocardial zymogram and electrocardiogram in clinic. However, the sensitivity of myocardial zymogram and electrocardiogram is low, and the time of onset is strictly required, which leads to their limited application. Transcatheter subendocardial myocardial biopsy may be the gold standard for detecting myocardial damage, but it is not routinely used for screening because of its invasive procedure. Magnetic resonance imaging and radionuclide ventriculography can also evaluate cardiac function, but their high cost limits their clinical application. Therefore, the diagnosis rate of early myocardial dysfunction in rheumatoid arthritis is low. Our study also suggested that the sensitivity of traditional echocardiographic parameters to early cardiac damage in RA was not high. The results ofthis studyshowedthat there were statistically significant differences inlaboratory parameters (RF, CRP, ESR,NEUT, LYM, PLT) between each case group and the control group (P<0.05). Itindicated that there was a serious inflammatory reaction in RA patients at active stage. At the same time, there were significant differences in ESR, NEUT and PLT between high disease activity group and low disease activity group(P<0.05). Studies have shown that RA patientswith long-term immune response and chronic inflammation of the body makes myocardial apoptosis accelerated, resulting in direct damage to myocardial tissue.Inflammatory cells and immune cells release various pro-fibrotic factors in the inflammatory responseto increase fibroblast activity and cause myocardial interstitial fibrosis [22][11], which in turn promotes atherosclerosis, resulting in myocardial ischemia and reduced left ventricular systolic and diastolic function [12]. however, all that routine echocardiographic parameter were within the normal range, andthere wasno significant difference in EF, IVSD, LVEDV, LVESV, HR between the case group and the control group (P>0.01),indicating that the above conventional echocardiographic observation index have certain limitations in evaluating cardiac function damage in RA patients.

PSL技术是通过结合超声心动图测得的心肌应变数据和非侵入性估计的左心室压力数据，以创建压力-应变环图。左室 PSL 在应变的基础上同时考虑心脏后负荷影响,克服了二维斑点追踪技术所得应变数据的负荷依赖性,可以更准确地评估患者的左室心肌功能受损情况。既往研究报道，超声心动图 PSL评估心肌做功的结果与心导管结果显著相关[²]。 Chan等[³]在三组不同心血管情况的患者应用PSL进行了心肌做功的评估。研究显示收缩压>160mmHg的高血压患者，与健康对照者相比，左室GWI、GCW显著增加，但整体纵向应变和LVEF正常且相对不变。PSL技术的开发为心肌功能提供一个更全面的评估工具，它不仅可以定量测量心脏的运动，还能评估心脏的做功效率，并且与心肌代谢有明显相关性[]。作为一种无创性检查，PSL技术在心脏病学领域得到了广泛的应用和发展。一项研究将甲状腺机能亢进的患者分为心动过速组（TH1组，n=31）和无心动过速组（TH2组，n=34），应用无创心肌做功评估其左室功能，结果表明甲状腺功能亢进可显著降低左心室的GWE，增加GWW，这种变化在心动过速患者中更为明显[]。另一项研究通过PSL技术评估2型糖尿病（T2DM）患者在有无高血压（HT）情况下的无症状左心室（LV）心肌收缩功能障碍。结果显示T2DM及有HT的T2DM患者的GWI、GCW、GWE/GWW均显著低于正常对照组（p < 0.05）；2型糖尿病及2型糖尿病合并高血压组左室前壁WI、CW、WE及CW/WW均明显低于正常对照组（p < 0.05）；ROC分析显示结合GWI、GCW、GWE和GCW/GWW的曲线下面积（AUC）明显高于各个指标的AUC（p < 0.05）。证明心肌做功可以无创且准确地评估有无HT的T2DM患者的无症状全球和局部LV心肌收缩功能障碍。PSL技术的出现，让我们更加深入的了解患者的心肌功能，是早期检测亚临床左室功能障碍的有前途的新工具。
The PSL technique combines echocardiographically measured myocardial strain data with noninvasively estimated left ventricular pressure data to create a pressure-strain loop. Left ventricular PSL can overcome the load-dependence of strain data obtained by two-dimensional speckle tracking technique by considering the effect of cardiac afterload on the basis of strain, and can more accurately evaluate the damage of left ventricular myocardial function. Previous studies have reported significant correlation between echocardiographic PSL assessment of myocardial work and cardiac catheterization results[²]. Chanet al.[³]assessed myocardial work using PSL in three groups of patients with different cardiovascular conditions. Compared with healthy controls, hypertensive patients with systolic blood pressure of >160mmHg had significantly increased left ventricular GWI and GCW, but normal global longitudinal strain and LVEF. The development of PSL technologyprovides a more comprehensive assessment tool for myocardial function, which can not onlyquantitativelymeasure cardiac motion, but also assess cardiac work efficiency,and has a significant correlation with myocardial metabolism [].作为一种无创性检查，PSL技术在心脏病学领域得到了广泛的应用和发展。一项研究将甲状腺机能亢进的患者分为心动过速组（TH1组，n=31）和无心动过速组（TH2组，n=34），应用无创心肌做功评估其左室功能，结果表明甲状腺功能亢进可显著降低左心室的GWE，增加GWW，这种变化在心动过速患者中更为明显[]。另一项研究通过PSL技术评估2型糖尿病（T2DM）患者在有无高血压（HT）情况下的无症状左心室（LV）心肌收缩功能障碍。结果显示T2DM及有HT的T2DM患者的GWI、GCW、GWE/GWW均显著低于正常对照组（p < 0.05）；2型糖尿病及2型糖尿病合并高血压组左室前壁WI、CW、WE及CW/WW均明显低于正常对照组（p < 0.05）；ROC分析显示结合GWI、GCW、GWE和GCW/GWW的曲线下面积（AUC）明显高于各个指标的AUC（p < 0.05）。证明心肌做功可以无创且准确地评估有无HT的T2DM患者的无症状全球和局部LV心肌收缩功能障碍。The advent of PSL technology allows us to gain a deeper understanding of patient myocardial function and is a promising new tool forearly detection of subclinicalleft ventriculardysfunction.

GLS被认为是评估心脏功能早期变化的敏感指标[ ]。Yasser Gazar等应用斑点追踪超声心动图（STE）应变技术评价无心血管疾病的类风湿关节炎（RA）患者的左室收缩功能。发现RA组的GLS降低[-16.80% vs.-22.35%，PP<0.001]。应用受试者工作特征曲线（ROC）确定GLS值的最佳截断值为-20，其敏感性为76.7%，特异性为80%，阳性预测值为92%，阴性预测值为63%，诊断准确率为83.9%。因此使用STE的GLS测量在检两射血分数保留的RA患者的左心室收缩功能受损方面是有价值的。Giovanni Cioffi等的研究发现低(GLS) 和低整体周向应变 (GCS) 是RA患者发生心血管事件的强有力的独立预测因素。 本研究中各病例组应变参数GLS的绝对值与对照组相比均明显减低差异有统计学意义(P<0.05)。这表明GLS 可敏感发现 RA 患者亚临床左心室功能改变。这可能与左室心肌的解剖结构有关。左室心肌由纵行心肌 、斜行心肌和环形心肌组成，心肌纵向应变主要受纵形心肌纤维影响，而纵行心肌位于心内膜下，通常在整个心肌病变过程中最先受累。本研究相关性分析显示GWI、GCW与GLS显著相关，与以往的研究一致[ ]。故PSL技术在辅助评估RA患者早期心肌功能方面具有可行性。然而本研究中疾病活动度组的GLS绝对值较低疾病活动度组有所增加，但差异无统计学意义。这可能与GLS的测量易受后负荷影响有关。因此虽然GLS在评估心肌功能早期损伤方面非常敏感，但后负荷的影响无法避免，结合最新的PSL技术，结果会更准确更全面。 重试    错误原因

我们的心肌做功研究显示，对照组，低疾病活动度组，中等疾病活动度组，高疾病活动度组，GWI、GCW 、GWE依次减低，且高疾病活动度组 GWI、GCW 、GWE较对照组显著减低。说明RA患者心肌做功能力随疾病活动度的增加而降低。相关性分析显示GWE与GLS和DAS-28均呈中度相关，表明RA疾病活动度与心肌功能受损有密切联系。近年来，越来越多的研究关注RA的疾病活动度与心肌损害的关系。早在2013年，Nowell M Fine等发现与健康患者相比，类风湿性关节炎患者的整体纵向左心室和右心室应变降低，且应变异常与类风湿性关节炎的严重程度相关。Małgorzata Biskup等发现持续性低疾病活动的RA与动脉粥样硬化和心脏功能障碍有关。一项为期 5 年的前瞻性研究发现与达到持续缓解的RA患者相比，持续中度或高度疾病活动性的患者亚临床动脉粥样硬化进展 (AP+)风险显著增加（OR 5.05，95% CI 1.53，16.64，p=0.008），Punchong Hanvivadhanakul的研究发现患有RA且无临床心血管疾病的患者左心室收缩功能下降，表现为GLS较低，且与疾病活动性（DAS28-CRP）显著相关，这些发现与我们的研究不谋而合。其背后的机制可能是 RA 患者炎症反应引起的免疫复合物不断沉积于血管壁，累及冠状动脉的细小分支，加速冠状动脉的微血管发生粥样硬化，使末梢循环的灌注量减少，最终导致冠状动脉管腔狭窄，引起主要由末梢血管供血的心内膜下心肌缺血[40]。而心内膜下纵行心肌纤维在左室长轴的运动中发挥着特别重要的作用，有研究表明，如果没有纵行心肌纤维参与心室收缩运动，由肌小节缩短产生的射血分数将会大幅降低[38]，且心内膜下的纵行心肌纤维的收缩更容易受到心肌缺血的影响[39]。另外，炎症和细胞毒性因子（包括抗脂抗体、抗环瓜氨酸抗体、凝血因子、组织纤溶酶原激活剂抗原等）还可以导致心肌纤维化和细胞凋亡。这些综合因素作用进一步加速心肌损伤[32]。随病情加重，心肌形变能力随之逐渐降低，进一步使得心肌做功能力下降。
Our myocardial work study showed that GWI, GCW and GWE decreased in turn in control group, low disease activity group, moderate disease activity group and high disease activity group, and GWI, GCW and GWE decreased significantly in high disease activity group compared with control group. It indicated that the myocardial work ability of RA patients decreased with the increase of disease activity. Correlation analysis showed that GWE was moderately correlated with both GLS and DAS-28, indicating that RA disease activity was closely related to myocardial dysfunction. In recent years, more and more studies have focused on the relationship between RA disease activity and myocardial damage. As early as 2013, Nowell M Fine et al. found that overall longitudinal left and right ventricular strain was reduced in RA patients compared to healthy patients, and that abnormal strain correlated with severity of RA. Małgorzata Biskup et al. found that RA with persistent low disease activity is associated with atherosclerosis and cardiac dysfunction. A 5-year prospective study found that patients with persistent moderate or high disease activity had a significantly increased risk of subclinical atherosclerotic progression (AP+) compared with RA patients who achieved sustained remission.(OR 5.05, 95% CI 1.53, 16.64, p=0.008) Punchong Hanvivadhanakul's findings of decreased left ventricular systolic function in patients with RA and no clinical cardiovascular disease, manifested by lower GLS and significantly associated with disease activity (DAS28-CRP), coincide with our findings. The mechanism behind this may be that immune complexes caused by inflammatory reactions in RA patients continue to deposit on the blood vessel wall, involving small branches of the coronary artery, accelerating atherosclerosis in the microvessels of the coronary artery, reducing the perfusion of the peripheral circulation, and ultimately leading to coronary artery lumen stenosis, causing subendocardial myocardial ischemia mainly supplied by peripheral blood vessels [40]. Subendocardial longitudinal myocardial fibers play a particularly important role in the movement of the long axis of the left ventricle. Studies have shown that if longitudinal myocardial fibers do not participate in ventricular contraction, the ejection fraction generated by sarcomere shortening will be greatly reduced [38], and the contraction of subendocardial longitudinal myocardial fibers is more susceptible to myocardial ischemia [39]. In addition, inflammatory and cytotoxic factors (including anti-lipid antibodies, anti-cyclic citrulline antibodies, coagulation factors, tissue plasminogen activator antigens, etc.) can also lead to myocardial fibrosis and apoptosis. These combined factors further accelerate myocardial damage [32]. With the aggravation of the disease, the myocardial deformation ability gradually decreased, which further reduced the myocardial work ability.

综上所述，尽管LVEF在正常范围内，PSL技术仍然能够识别出RA患者中潜在的心肌功能异常。这种细微的功能变化可能在传统的心脏功能评估方法中被忽视，但对于RA患者心血风险的早期评估、早期诊断，从而今早做出治疗规划具有重要的临床意义。本研究表明超声心动图PSL技术检测心肌做功参数可作为无创检查工具辅助早期诊断RA患者心肌功能。为早期发现RA患者心肌功能异常，指导制定治疗策略和预测患者预后提供了一种无创、便捷、经济、可靠的检测方法。
In conclusion,PSL techniques can identify potential myocardial dysfunction in RA patients despite LVEF within normal ranges. This subtle functional change may be overlooked in traditional cardiac function assessment methods, but it has important clinical significance forearly assessment,early diagnosisandtreatment planning of RA patients. This studysuggeststhat echocardiography PSL techniquecan be used as a noninvasive tool to assist in the early diagnosis ofmyocardial function in RA patients. It provides a noninvasive, convenient, economical and reliable method forearly detection of myocardial dysfunction in RA patients,guidance for treatmentstrategyandprediction of prognosis.

虽然本研究提供了心肌做功参数在评估RA患者左室心肌功能中的有效性的有力证据，但本研究病例组各亚组例数较少，且RA患者在入组前期治疗方式存在差异，这对研究结果也有可能造成一定影响。未来的研究需要进行多中心研究，在更大的患者群体中验证这些发现，并对心肌做功参数中每个参数的具体效力做进一步研究。同时进一步的研究应当集中于如何将这些心肌做功参数整合到现有的临床实践中，以及它们对治疗策略调整的影响。
Although this study provides strong evidence for the validity of myocardial performance parameters in assessingleft ventricular myocardial function in RA patients,the small number of patients in each subgroup of this study group andthe differences in treatment methods in RA patients beforeenrollment may also have some impact on the study results. Future studies will need tobe multicenter tovalidate these findings in larger patient populationsand tofurther investigate the specific efficacy of each of the cardiac work parameters. Furtherresearch should focus on how these myocardial performance parameters are integrated into existing clinical practice and their impact on therapeutic strategy adjustments.