Abstract
目的
早期发现无症状的舒张功能障碍对于防止高血压患者发生心力衰竭至关重要，目前的研究表明左房应变(left atrial strain，LAS)有助于左室舒张功能的评价，但关于高血压患者LAS与舒张功能的相关性研究相对较少。本研究应用二维斑点追踪技术评价高血压患者LAS的变化，并探讨LAS与高血压患者左室舒张功能的关系。
方法
选取2021年7月至2022年1月于中南大学湘雅三医院心内科门诊就诊的高血压患者82例(高血压组)及健康对照者59例(对照组)，根据2016年美国超声心动图学会舒张功能指南中推荐的评价左室舒张功能障碍的指标[二尖瓣环室间隔的血流速度(e´间)<7 cm/s，侧壁的血流速度(e´侧)<10 cm/s，二尖瓣血流E峰血流速度(E)/e´>14，左房容积指数> 34 mL/m2，三尖瓣反流速度>2.8 m/s]个数，将高血压患者分成3组，分别为Ⅰ组(0个指标，n=36)、Ⅱ组(1个指标，n=39)、Ⅲ组(2个指标，n=7)。采用二维斑点追踪技术测量左房储器应变(left atrial reservoir strain，LASr)、左房导管应变(left atrial conduit strain，LAScd)及左房收缩应变(left atrial contraction strain，LASct)，并分析LAS与高血压患者左室舒张功能的相关性。
结果
高血压组LASr、LAScd、LASr/(E/e´间)低于对照组，E/LASr高于对照组(均P<0.05)，2组左心室容积指数无明显差异(P>0.05)。与Ⅰ组比较，Ⅱ组和Ⅲ组LASr、LAScd、LASr/(E/e´间)降低，Ⅲ组E/LASr升高(均P<0.05)。与Ⅱ组比较，Ⅲ组LASr/(E/e´间)下降(P<0.05)。LASr与e´间、e´侧、E及E/二尖瓣血流A峰血流速度(A)呈正相关，与E/e´间呈负相关。
结论
高血压早期患者的左房功能变化早于左房结构改变，LAS及其与常规舒张功能超声指标[LASr/(E/e´间)]结合在评估高血压患者左室舒张功能方面具有潜在的应用价值。
Keywords: 左房应变, 高血压, 左室舒张功能, 斑点追踪成像
Abstract
Objective
Early detection of asymptomatic diastolic dysfunction is essential to prevent the development of heart failure in hypertensive patients. Current studies suggest that left atrial strain contributes to the evaluation of left ventricular diastolic function, but there are fewer studies on the correlation between left atrial strain and diastolic function in hypertensive patients. In this study, we applied a two-dimensional speckle tracking technique to evaluate the changes in left atrial strain in hypertensive patients, and to investigate the relationship between left atrial strain and left ventricular diastolic function.
Methods
A total of 82 hypertensive patients who were visited the Department of Cardiology at the Third Xiangya Hospital of Central South University from July 2021 to January 2022, were enrolled for this study, and 59 healthy subjects served as a control group. According to the number of left ventricular diastolic function indexes recommended by the 2016 American Society of Echocardiography Diastolic Function Guidelines (mitral annular e´ velocity: Septal e´<7 cm/s, lateral e´<10 cm/s, E/e´ ratio>14, left atrial volume index>34 mL/m2, peak tricuspid regurgitation velocity>2.8 m/s), the hypertensive patients were divided into 3 groups: Group Ⅰ (0 index, n=36 ), Group Ⅱ (1 index, n=39), and Group Ⅲ (2 indexes, n=7). Two-dimensional speckle tracking technique was used to measure left atrial reservoir strain (LASr), conduit strain, and contraction strain, and to analyze the correlation between left atrial strain and left ventricular diastolic function in hypertensive patients.
Results
The LASr, left atrial conduit strain (LAScd), and LASr/(E/septal e´) of the hypertension group were lower than those of the control group, and E/LASr was higher than that of the control group. There was no significant difference in left atrium volume index between the 2 groups (P>0.05). Compared with Group Ⅰ, LASr, LAScd, and LASr/(E/septal e´) were decreased in Group Ⅱ and Group Ⅲ, LASr/(E/septal e´) was also decreased in Group Ⅲ compared with Group Ⅱ (all P<0.05). Compared with Group Ⅰ, E/LASr was increased in Group Ⅲ. LASr was positively correlated with septal e´, lateral e´, E, and E/A, and negatively correlated with E/septal e´.
Conclusion
The changes of left atrial function in patients with early hypertension are earlier than those of left atrial structure. Left atrial strain and its combination with conventional ultrasonographic indices [LASr/(E/septal e´)] of diastolic function are potentially useful in assessing left ventricular diastolic function in hypertensive patients.
Keywords: left atrial strain, hypertension, left ventricular diastolic function, speckle tracking imaging
高血压是射血分数保留型心力衰竭的危险因素之一，射血分数保留型心力衰竭的主要发病机制是左室舒张功能障碍。准确评估左室舒张功能有利于疾病的早期诊断和有效干预，对患者的治疗、预后及管理十分重要。根据2016年美国超声心动图学会对舒张功能评价的建议[1]，目前仍然有部分患者不能通过常规超声心动图参数确定其舒张功能状态[2]。斑点追踪超声心动图已被广泛用于心室功能的评价，但对心房功能的评价相对较少。本研究通过二维应变成像评价高血压患者左房应变变化，旨在探讨左房应变与左室舒张功能之间的关系。
1. 对象与方法
1.1. 对象
本研究为回顾性研究。选取2021年7月至2022年1月于中南大学湘雅三医院心内科门诊就诊的高血压(1或2级)患者82例作为高血压组，另选59例无高血压病史的健康体检者作为对照组。排除条件：冠心病、结构性心脏病、先天性心脏病、原发性心肌病、心力衰竭、既往心脏手术、肾功能衰竭、肿瘤。2016年美国超声心动图学会[1]推荐的评价左室舒张功能障碍的超声指标为：二尖瓣环室间隔的血流速度(e´间)<7 cm/s，侧壁的血流速度(e´侧)< 10 cm/s，二尖瓣血流E峰血流速度(E)/e´>14，左心房容积指数(left atrium volume index，LAVI)>34 mL/m2，三尖瓣反流速度(tricuspid valve regurgitation velocity，VTVR)>2.8 m/s。本研究根据上述指标数目将高血压患者分成3组，分别为Ⅰ组(0个指标，n=36)、Ⅱ组(1个指标，n=39)、Ⅲ组(2个指标，n=7)。
1.2. 方法
1.2.1. 常规经胸超声心动图
采用美国GE公司VividTM E95超声诊断仪，配M5S-D探头，同步连接心电图，测量左室舒张末期内径(left ventricular end-diastolic diameter，LVEDd)、室间隔(interventricular septum，IVS)、左室后壁(left ventricular posterior wall，LVPW)、左房前后经(left atrial diameter，LAD)、左室射血分数(left ventricular ejection fraction，LVEF)、二尖瓣E峰血流速度(E)、二尖瓣A峰血流速度(A)、e´间及e´侧等常规参数。左心室质量(left ventricular mass，LVM)=0.8×1.04[(LVEDd+LVPW+IVS)3-LVEDd3]+0.6，左心室质量指数(left ventricular mass index，LVMI)=左心室质量/体表面积。采用双平面面积长度法测量左心房容积，LAVI=左心房容积/体表面积。选取聚焦左房的心尖四腔心及心尖两腔心，优化图像质量，记录3个连续的心脏周期用于离线分析。
1.2.2. 二维斑点追踪超声心动图
将心尖四腔心及两腔心的超声心动图导入EchoPAC软件，追踪左房心内膜边界。零应变的参考点设置在左室舒张末期，左房纵向应变为各节段的平均左房应变，2个峰值分别对应于左房储器应变[(left atrial reservoir strain，LASr)，第1个峰值]和左房收缩应变[(left atrial contraction strain，LASct)，第2个峰值]，左房导管应变(left atrial conduit strain，LAScd)为LASr和LASct的差值(图1)。
图1.
左房应变
Figure 1 Left atrial strain LASr: Left atrial reservoir strain; LAScd: Left atrial conduit strain; LASct: Left atrial contraction strain.
1.3. 统计学处理
采用SPSS 26.0统计学软件分析数据，计量资料采用均数±标准差( ±s)表示，2组比较采用两独立样本t检验，多组比较采用单因素方差分析，两变量间的相关分析采用Pearson线性相关分析，以P<0.05为差异有统计学意义。
2. 结 果
2.1. 一般资料及常规超声心动图参数比较
2组年龄、性别、LVEDd、LVEF、E、LAVI差异均无统计学意义(均P>0.05)，体重指数、IVS、LVPW、LVMI、E/A、e´间、e´侧、E/e´差异均有统计学意义(均P<0.05，表1)。
表1.
2组一般资料及超声心动图指标比较
Table 1 Comparison of baseline characteristics and echocardiographic variables between the 2 groups
| 组别 | n | 女/男 | 年龄/岁 | BMI/(kg·m-2) | LVEDd/mm | IVS/mm | LVPW/mm |
|---|---|---|---|---|---|---|---|
| P | 0.221 | 0.060 | <0.001 | 0.474 | <0.001 | <0.001 | |
| 对照组 | 58 | 33/25 | 39±12 | 22.3±2.35 | 44.2±3.5 | 9.1±1.0 | 9.2±1.0 |
| 高血压组 | 82 | 38/44 | 42±11 | 24.8±3.46 | 44.9±6.1 | 10.2±1.0 | 10.3±1.0 |
| 组别 | LVEF/% | E/(cm·s-1) | E/A | e´间/(cm·s-1) | e´侧/(cm·s-1) | E/e´ | LVMI/(g·m-2) |
|---|---|---|---|---|---|---|---|
| 对照组 | 68±5 | 80±16 | 1.2±0.5 | 10.3±2.9 | 15.9±14.6 | 6.8±1.8 | 135±28 |
| 高血压组 | 68±6 | 76±15 | 0.9±0.3 | 7.9±2.6 | 10.9±3.2 | 8.5±2.1 | 166±40 |
| P | 0.955 | 0.080 | 0.001 | <0.001 | 0.003 | <0.001 | <0.001 |
| 组别 | LAVI/(mL·m-2) | LASr/% | LASct/% | LAScd/% | LASr/(E/e´间) | E/LASr |
|---|---|---|---|---|---|---|
| 对照组 | 23.8±5.4 | 33.4±8.4 | 15.1±3.9 | 18.7±6.7 | 4.4±1.6 | 2.5±0.6 |
| 高血压组 | 25.8±7.5 | 28.5±7.1 | 14.4±3.5 | 14.1±5.2 | 3.1±1.2 | 2.8±0.7 |
| P | 0.180 | <0.001 | 0.363 | <0.001 | <0.001 | 0.015 |
计量资料采用均数±标准差( ±s)表示。BMI：体重指数；LVEDd：左室舒张末期内径；IVS：室间隔；LVPW：左室后壁；LVEF：左室射血分数；E：二尖瓣血流E峰血流速度；A：二尖瓣血流A峰血流速度；e´间：二尖瓣环室间隔血流速度；e´侧：二尖瓣环侧壁血流速度；LVMI：左心室质量指数；LAVI：左心房容积指数；LASr：左房储器应变；LASct：左房收缩应变；LAScd：左房导管应变。
2.2. 左房应变及其组合参数比较
高血压组LASr、LAScd、LASr/(E/e´间)低于对照组，E/LASr高于对照组，差异均有统计学意义(均P<0.05)，2组LASct差异无统计学意义(P>0.05，表1)。
与Ⅰ组比较，Ⅱ组和Ⅲ组LASr、LAScd、LASr/(E/e´间)均下降，Ⅲ组E/LASr升高，差异均有统计学意义(均P<0.05)。与Ⅱ组比较，Ⅲ组LASr/(E/e´间)也下降，差异有统计学意义(P<0.05)。3组LASct差异无统计学意义(P>0.05，表2)。
表2.
3组高血压患者左房应变及其组合参数比较
Table 2 Comparison of left atrial strain values of the patients with arterial hypertension among the 3 hypertensive groups
| 组别 | n | LASr/% | LASct/% | LAScd/% | LASr/(E/e´间) | E/LASr |
|---|---|---|---|---|---|---|
| Ⅰ组 | 36 | 30.5±6.5 | 14.7±3.5 | 15.8±4.8 | 3.7±1.0 | 2.7±0.6 |
| Ⅱ组 | 39 | 26.9±7.5* | 14.3±3.8 | 12.6±5.2* | 2.6±1.3* | 2.9±0.9 |
| Ⅲ组 | 7 | 23.5±6.7* | 13.0±2.3 | 10.5±5.6* | 2.0±0.6*† | 3.3±0.7* |
与Ⅰ组比较，*P<0.05；与Ⅱ组比较，†P<0.05。LASr：左房储器应变；LASct：左房收缩应变；LAScd：左房导管应变；E：二尖瓣血流E峰血流速度；e´间：二尖瓣环室间隔血流速度。
2.3. LASr与常规舒张功能指标的相关性
LASr与e´间、e´侧、E及E/A呈正相关(分别r=0.488、r=0.261、r=0.432、r=0.208，均P<0.05)，与E/e´间呈负相关(r=-0.243，P<0.001；图2)，与LAVI无明显相关(P=0.27)。
图2.
LASr与E/e´ 间的相关性
Figure 2 Correlation between LASr and E/septal e´
LASr: Left atrial reservoir strain.
3. 讨 论
高血压是左室舒张功能障碍的常见诱因，高血压患者早期左房和左室发生轻微的功能障碍不易通过传统的超声心动图参数判定。二维斑点追踪技术通过追踪斑点的运动，得到斑点的位移，通过对空间微分获得局部应变，具有与角度无关、受伪像影响小等优点[3]。本研究通过二维斑点追踪技术获得左房应变以评估心动周期中左房各时相的功能。
左房在左室充盈过程中发挥3种功能，分别为左室等容收缩至等容舒张末期的储器功能、左室快速充盈期至缓慢充盈期的管道功能及左室舒张末期的泵功能[4-5]。本研究结果显示高血压患者3种左房应变与对照组比较均降低，与既往研究[6-7]结果一致。这主要是由于高血压患者左室充盈压升高，二尖瓣开放时左房与左室直接相通，左室舒张压传递至左房，导致左房压力升高，左房壁张力增加，从而使左房充盈减少，功能降低[8]。另外，本研究中高血压组左房容积指数较对照组无明显差异，表明在高血压早期患者中，左房心肌的功能变化早于左房结构的变化，与既往研究[9-11]结果相符，提示左房应变可作为高血压性心脏病非常敏感的评价指标。
本研究入选的高血压患者只有1个或2个舒张功能评价的超声指标，无法根据2016年美国超声心动图学会的建议对左室舒张功能障碍进行准确的超声诊断；但本研究结果显示高血压患者LASr和LAScd随着左室舒张功能障碍指标数目增加而持续降低，LAScd的变化虽呈现下降趋势，但差异无统计学意义。这与Jarasunas等[12]的研究结果一致，Jarasunas等[12]的研究显示在左室舒张功能障碍早期，LASr和LAScd均降低，而LASct不同，轻度左室舒张功能障碍，LASct不变甚至可以增加，仅在舒张功能明显障碍时才会下降。提示LASr和LAScd评价舒张功能较LASct更为灵敏。这可以解释为LASr和LAScd受左室纵向收缩和左房心肌顺应性的影响，而LASct则受左房心肌收缩及左室充盈压的影响[13]。
本研究显示LASr与常规舒张功能评价指标(e´间、e´侧、E、E/A及E/e´间)均具有相关性。笔者尝试探索LASr结合常规舒张功能评价指标[如LASr/(E/e´间)及E/LASr]在高血压患者左室舒张功能评价中的潜在作用，结果显示高血压组LASr/(E/e´间)与E/LASr较对照组均有显著改变，且LASr/(E/e´间)随着舒张功能指标数目增加而降低，E/LASr在舒张功能指标数更多时才发生变化。既往研究[14-16]分别分析了E/LASr和LASr/(E/e´间)对左室充盈压的诊断性能，结果提示两者均明显优于E/e´、E/A、LAVI等常规舒张参数，并且与再住院率显著相关，但未对两者进行比较。本研究结果提示在高血压患者中LASr/(E/e´间)较E/LASr对舒张功能变化更为敏感，因此，我们认为LASr/(E/e´间)综合了左房功能和左室充盈压变化，可能是评估高血压患者舒张功能的有用参数。
本研究存在一定的局限性：1)为单中心研究，样本量偏少，结果可能存在一定偏倚；2)采用的是二维斑点追踪成像技术以及左室应变的软件，并脱机对左房功能进行计算，此技术及其软件均未在日常实践中常规进行。未来，可进一步探索左房应变的临床应用价值和左室舒张功能的评价指标。
基金资助
湖南省自然科学基金(2021JJ31014)。
This work was supported by the Natural Science Foundation of Hunan Province, China (2021JJ31014).
利益冲突声明
作者声称无任何利益冲突。
作者贡献
蔡金 研究构思、数据统计分析及论文撰写；梁中书 论文修改；冯文畅、龙辉 数据收集。所有作者阅读并同意最终的文本。
原文网址
http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/202306846.pdf
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