【摘要】：背景心力衰竭是一種常見的臨床綜合征,也是各種心臟疾病的嚴重階段和最后戰(zhàn)場。2016年歐洲心臟病學會頒布的急、慢性心力衰竭診斷和治療指南,更新了對心力衰竭的分類。在射血分數減低的心力衰竭和射血分數保留的心力衰竭之間存在一個灰區(qū),此灰區(qū)內患者的左室射血分數在40-49%,指南將其定義為射血分數中間值的心力衰竭(heart failure with mid-range ejection fraction,HFmrEF),并明確了其診斷標準。將HFmrEF作為一個單獨的組別將有助于對這組患者病理生理特點、臨床特征和治療方法的深入研究。近年來,對心腔內血流的研究主要集中在血流向量成像(vector flow mapping,VFM)、超聲粒子圖像測速以及心肌磁共振成像等技術上。其中VFM技術結合了彩色多普勒成像和斑點追蹤兩大技術,通過連續(xù)方程的計算,可以得到任意點的速度向量,同時可定量計算心腔內血流粘滯摩擦產生的能量損耗(energyloss,EL)。然而,目前未見關于HFmrEF患者左室內能量損耗的明確報道。本研究結合二維、多普勒超聲心動圖、二維組織追蹤法(2D Tissue Tracking Analysis,2DTT),綜合評估HFmrEF患者心臟結構和功能的改變,運用VFM技術定量評估其左心室內血流能量損耗的特點。研究目的1.運用VFM技術評估HFmrEF患者左心室內血流能量損耗特點。2.探討HFmrEF患者EL與心臟結構、功能改變的相關性。材料與方法1.研究對象與分組連續(xù)選取就診于山東大學齊魯醫(yī)院且LVEF 40-49%的住院患者43例,根據2016年ESC急、慢性心力衰竭診斷和治療指南中HFmrEF診斷標準,選出HFmrEF患者28例;同時選取年齡、性別相匹配的健康志愿者23例。HFmrEF組內分組:按照舒張功能不全的診斷標準分為Ⅰ組(舒張功能不全,12例),Ⅱ組(非舒張功能不全,共16例)。2.臨床基本資料采集對所有研究對象,記錄性別、年齡,測量身高、體重,計算身體質量指數(BMI)、體表面積(BSA),記錄心率、血壓,對于HFmrEF組研究對象,同時記錄N端腦利鈉肽前體(NT-proBNP)值、空腹血糖值、甘油三酯、總膽固醇、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)的值。3.圖像與數據采集使用AlokaF75心臟彩超機,采圖的同時連接肢體導聯(lián),記錄同步心電圖。3.1二維超聲技術:采集胸骨旁左心室長軸圖像,定位于左室舒張末期,測量室間隔厚度(IVS)、左室內徑(LVEDd)、左室后壁厚度(LVPW),計算左室質量(LVM)、左室質量指數(LVMI);定位于左室收縮末期,測量左房內徑(LA)。采集標準心尖四腔心、二腔心動態(tài)圖像,分別定位于左室收縮末期和舒張末期測量左室收縮末容積(ESV)及左室舒張末容積(EDV),計算左室射血分數(LVEF)、心排血量(CO);定位于左室收縮末期,測量左房容積(LAV),計算左房容積指數(LAVI);測量左室長徑(L)、左室橫徑(S),并計算左室球形指數(SI)。3.2多普勒超聲心動圖:血流多普勒測量舒張早期及晚期二尖瓣跨瓣血流速度,分別記為E峰、A峰,計算E/A。組織多普勒測量二尖瓣環(huán)室間隔、側壁心肌舒張早期運動速度峰值,將其平均值記錄為e',計算E/e';測量二尖瓣環(huán)室間隔、側壁心肌收縮波,將其平均值記錄為Sm。3.3 2DTT技術:采集心尖四腔心左室動態(tài)圖像進行分析。記錄收縮期左室縱向長軸整體應變(GLS)。3.4 VFM技術:在VFM模式下,采集心尖三腔心動態(tài)圖像。圖像通過DAS-RS1工作站分析。結合心電圖、瓣膜開閉及時間一流量曲線確定等容舒張期(isovolumetric relaxation period,IVR)、快速充盈期(rapid filling period,RFP)、心房收縮期(atrial contraction period,ACP)、等容收縮期(isovolumetric contraction phase,IVC)、快速射血期(rapid ejection period,REP)5 個時相,并測得各時相左心室整體的血流能量損耗。4.統(tǒng)計學方法采用SPSS20.0軟件進行統(tǒng)計學分析及繪圖。所有計量資料均進行Kolmogorov-Smirnov正態(tài)性檢驗,不符合正態(tài)分布的經過自然對數轉換使之符合正態(tài)分布,正態(tài)分布的連續(xù)變量用均數±標準差表示。兩組間比較用獨立樣本T檢驗。分類變量比較采用X2檢驗。連續(xù)變量的相關性分析采用Pearson相關分析。估計解釋變量對因變量的影響程度用多元線性回歸分析。估測某指標對疾病的診斷價值做ROC曲線并計算曲線下面積。P0.05認為有統(tǒng)計學意義。結果本研究共收集了 LVEF40-49%的住院患者43例,從中篩選出HFmrEF患者28例。HFmrEF患者的男性比例64%,平均年齡61歲;均為冠心病患者,其中單純冠心病8例,合并高血壓11例,合并糖尿病3例,同時合并高血壓和糖尿病6例。1.LVEF40-49%人群與正常人比較(1)兩組間年齡、性別、心率、收縮壓、舒張壓均無統(tǒng)計學差異(P0.05);LVEF40-49%人群的BMI大于正常人,差異有統(tǒng)計學意義(P0.05)。(2)二維超聲參數比較:LVEF40-49%人群較正常人的EDV、ESV增大,SI減小,LA、LAV、LAVI增大,IVS增厚,LVEDd擴大,LVPW增厚,LVM、LVMI增加,LVEF減低,差異均有統(tǒng)計學意義(P0.05)。(3)血流多普勒超聲參數比較:兩組間E峰、A峰、E/A均無統(tǒng)計學差異(P0.05)。(4)組織多普勒超聲參數比較:LVEF40-49%人群較正常人的e'減低,E/e'增大,Sm減低,差異均有統(tǒng)計學意義(P0.05)。(5)2DTT參數比較:LVEF40-49%人群的GLS較正常人減小,差異有統(tǒng)計學意義(P0.05),GLS達峰時間無統(tǒng)計學差異(P0.05)。(6)VFM參數比較:LVEF40-49%人群的各期左室整體能量損耗均較正常人減小,其中等容舒張期、快速充盈期、等容收縮期、快速射血期差異有統(tǒng)計學意義(P0.05);心房收縮期無統(tǒng)計學意義(P0.05)。2.HFmrEF患者與正常人比較(1)兩組間年齡、性別、心率、收縮壓、舒張壓均無統(tǒng)計學差異(P0.05),HFmrEF組的BMI大于正常人,差異有統(tǒng)計學意義(P0.05)。(2)二維超聲參數比較:HFmrEF組較正常人的EDV、ESV增大,SI減小,LA、LAV、LAVI 增大,IVS 增厚,LVEDd 擴大,LVPW 增厚,LVM、LVMI增加,LVEF減低,差異均有統(tǒng)計學意義(P0.05)。(3)血流多普勒超聲參數比較:兩組間E峰、A峰、E/A均無統(tǒng)計學差異(P0.05)。(4)組織多普勒超聲參數比較:HFmrEF組較正常人的e'減低,E/e'增大,Sm減低,差異均有統(tǒng)計學意義(P0.05)。(5)2DTT參數比較:HFmrEF組的GLS較正常人減小,差異有統(tǒng)計學意義(P0.05),GLS達峰時間較正常人延長,差異有統(tǒng)計學意義(P0.05)。(6)VFM參數比較:HFmrEF組的各期左心室整體能量損耗均較正常人減小,其中快速充盈期、等容收縮期、快速射血期差異有統(tǒng)計學意義(P0.05);等容舒張期、心房收縮期差異無統(tǒng)計學意義(P0.05)。3.HFmrEF組內比較——按照舒張功能分級分為Ⅰ組(舒張功能不全,12例),Ⅱ組(非舒張功能不全,16例)(1)兩組間性別、年齡、BMI、心率、收縮壓、舒張壓均無統(tǒng)計學差異(P0.05),血清學指標中NT-proBNP、甘油三酯、總膽固醇、HDL-C、LDL-C均無統(tǒng)計學差異(P0.05),Ⅱ組較Ⅰ組的血糖升高(P0.05)。(2)二維超聲參數比較:Ⅰ組較Ⅱ組的EDV、ESV增大,Ⅰ組較Ⅱ組的LAV、LAVI增大,LVEDd擴大,差異均有統(tǒng)計學意義(P0.05)。(3)血流多普勒超聲參數比較:Ⅰ組較Ⅱ組E峰增高增大,差異有統(tǒng)計學意義(P0.05)。(4)組織多普勒超聲參數比較:Ⅰ組較Ⅱ組E/e'增大,差異有統(tǒng)計學意義(P0.05)。(5)2DTT參數比較:Ⅰ組較Ⅱ組的GLS減小,GLS達峰時間延長,但均無統(tǒng)計學差異(P＞0.05)。(6)VFM參數比較:Ⅰ組較Ⅱ組的等容舒張期、快速充盈期左室整體能量損耗增大,其中快速充盈期差異有統(tǒng)計學意義(P0.05);心房收縮期、等容收縮期、快速射血期能量損耗減小,但差異無統(tǒng)計學意義(P0.05)。4.HFmrEF組能置損耗與臨床資料及超聲資料的相關性分析(1)快速充盈期左室整體能量損耗與e'負相關(r=-0.453,P=0.016),與E/e'正相關(r=0.456,P=0.015),與 BMI 負相關(r=-0.444,P=0.018),與 LDL-C負相關相關(r=-0.476,P=0.016)。(2)心房收縮期左室整體能量損耗與GLS正相關(r=0.392,所有P=0.039)。(3)等容收縮期左室整體能量損耗與EDV負相關(r-0.468,P=0.012),與 ESV 負相關(r=-0.468,P=0.012),與 GLS 正相關(r=0.509,P=0.006),與 BMI 負相關(r=-0.382,P=0.045)。(4)快速射血期左室整體能量損耗與EDV負相關(r-0.419,P=0.026),與 ESV 負相關(r=-0.472,P=0.011),與 e'負相關(r=-0.392,P=0.039),與BMI 負相關(r=-0.524,P=0.004)。5.HFmrEF組能量損耗多元線性回歸分析(1)快速充盈期左室整體能量損耗與E/e'(β=0.423,P=0.019)、LDL-C(β=-0.418,P=0.020)獨立相關。(2)心房收縮期左室整體能量損耗與GLS(β=0.392,P=0.039)相關。(3)等容收縮期左室整體能量損耗與GLS(β=0.546,P=0.001)及BMI(β =-0.428,P=0.009)獨立相關。(4)快速射血期左室整體能量損耗與BMI(β=-0.524,P=0.004)相關。6.能量損耗診斷HFmrEF效力的ROC分析為評估左室快速充盈期、等容收縮期、快速射血期三個時期能量損耗聯(lián)合診斷HFmrEF的價值高低,將三個時期的能量損耗聯(lián)合進行模型擬合后得到聯(lián)合預測概率(模型已排除等容收縮期能量損耗),用該概率做ROC曲線并計算AUC。AUC=0.817,可知快速充盈期與快速射血期能量損耗聯(lián)合診斷HFmrEF效果較好。結論1.HFmrEF患者的收縮功能和舒張功能均下降。2.HFmrEF患者的左心室內能量損耗在快速充盈期、等容收縮期、快速射血期均明顯低于對照組。當伴有舒張功能不全時,快速充盈期能量損耗增大。3.快速充盈期左心室內EL與心臟舒張功能相關,而心房收縮期和等容收縮期左心室EL與心臟收縮功能相關。
[Abstract]:Background Heart failure is a common clinical syndrome and a serious stage and final battlefield of various heart diseases. In 2016, the European Society of Cardiology issued guidelines for the diagnosis and treatment of acute and chronic heart failure, which update the classification of heart failure. There is a grey area between which the left ventricular ejection fraction is 40-49%. The guideline defines it as heart failure with mid-range ejection fraction (HFmrEF) and defines its diagnostic criteria. In recent years, the study of intracardiac blood flow mainly focuses on the techniques of vector flow mapping (VFM), ultrasonic particle image velocimetry and myocardial magnetic resonance imaging (MRI). The velocity vector at any point can be obtained, and the energy loss (EL) produced by viscous friction of intracardiac blood flow can be quantitatively calculated. However, there is no definite report on the energy loss in left ventricle in patients with HFmrEF. This study combines two-dimensional, Doppler echocardiography, two-dimensional Tissue Tracking Analysis (2D Tissue Tracking Analysis, 2D Tissue Tracking Analysis). Objective 1. To evaluate the characteristics of left ventricular blood flow energy loss in patients with HFmrEF by VFM. 2. To investigate the correlation between EL and cardiac structure and function in patients with HFmrEF. Materials and Methods 1. Subjects and groupings: 43 inpatients with LVEF of 40-49% in Qilu Hospital of Shandong University were selected consecutively. According to the diagnostic criteria of HFmrEF in ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure in 2016, 28 patients with HFmrEF were selected, and 23 healthy volunteers matched in age and sex were selected. The diagnostic criteria were divided into group I (diastolic dysfunction, 12 cases) and group II (non-diastolic dysfunction, 16 cases). NT-proBNP, fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) values.3. Image and data acquisition using the Aloka F75 cardiac color Doppler machine, drawing at the same time connecting limb leads, recording synchronous electrocardiogram. Left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular mass index (LVM), left atrial diameter (LA) and septal thickness (IVS), left ventricular diastolic diameter (LVEDd), left ventricular posterior wall thickness (LVPW) were measured, and left ventricular mass index (LVM) was calculated. Left ventricular end systolic volume (ESV), left ventricular end diastolic volume (EDV), left ventricular ejection fraction (LVEF), cardiac output (CO), left atrial volume (LAV), left atrial volume index (LAVI), left ventricular length (L), left ventricular transverse diameter (S), and left ventricular spherical index (SI) were measured by Doppler echocardiography. Echocardiogram: Mitral annular septum was measured by Doppler flow imaging, and early diastolic and late diastolic velocities were recorded as E and A peaks respectively. Mitral annular septum and early diastolic velocities of lateral wall myocardium were measured by E/A tissue Doppler flow imaging. Value recording was Sm.3.32 DTT: Acquisition of apical four-chamber left ventricular dynamic images for analysis. Recording systolic left ventricular longitudinal long-axis global strain (GLS). 3.4 VFM technique: Acquisition of apical three-chamber echocardiogram in VFM mode. Image analysis was performed by DAS-RS1 workstation. Isovolemic relaxation was determined by combining electrocardiogram, valvular opening and closing and time-flow curve. Isometric relaxation period (IVR), rapid filling period (RFP), atrial contraction period (ACP), isovolumetric contraction phase (IVC), rapid ejection period (REP) were measured in 5 phases, and the total energy loss of left ventricle in each phase was measured.4. Statistical methods were analyzed and plotted by SPSS20.0 software. All measurement data were tested by Kolmogorov-Smirnov normality test. The non-conforming normal distribution was transformed into normal distribution by natural logarithm, and the continuous variables of normal distribution were expressed by mean-standard deviation. Variables were compared by X2 test. Correlation analysis of continuous variables was performed by Pearson correlation analysis. Multivariate linear regression analysis was used to estimate the influence of explanatory variables on dependent variables. Among 43 hospitalized patients, 28 were selected for HFmrEF. The male proportion of HFmrEF patients was 64%, with an average age of 61 years. All patients were coronary heart disease, including 8 cases of simple coronary heart disease, 11 cases of hypertension, 3 cases of diabetes, 6 cases of hypertension and diabetes mellitus. 1. LVEF40-49% of the population were compared with normal people (1) age, sex, heart rate between the two groups. There was no significant difference in systolic and diastolic blood pressure (P 0.05); BMI of LVEF40-49% of the population was higher than that of the normal population, and the difference was statistically significant (P 0.05). (2) Two-dimensional ultrasound parameters comparison: LVEF40-49% of the population than normal people EDV, ESV increased, SI decreased, LA, LAV, LAVI increased, IVS thickened, LVEDd enlarged, LVPW thickened, LVM, LVMI increased, LVEF decreased, the difference was statistically significant. Significance (P 0.05). (3) Blood flow Doppler ultrasound parameters comparison: between the two groups E peak, A peak, E/A were no significant difference (P 0.05). (4) Tissue Doppler ultrasound parameters comparison: LVEF40-49% of the population than the normal people's e'decreased, E/e'increased, Sm decreased, the difference was statistically significant (P 0.05). (5) 2DTT parameters comparison: LVEF40-49% of the population's GLS decreased, worse than the normal people. There was no significant difference in peak time of GLS (P 0.05). (6) VFM parameters: LVEF 40-49% of the population at all stages of the overall energy loss of the left ventricle were less than normal people, including isovolumic diastolic, rapid filling, isovolumic systolic, rapid ejection period were statistically significant (P 0.05); atrial systolic period was not statistically significant (P 0.0). The BMI of HFmrEF group was higher than that of normal group (P 0.05). (2) Two-dimensional ultrasound parameters comparison: HFmrEF group EDV, ESV increased, SI decreased, LAV, LAVI increased, IVS thickened, LVEDd enlarged, LV enlarged, LV enlarged. PW thickening, LVM, LVMI increased, LVEF decreased, the difference was statistically significant (P 0.05). (3) Blood flow Doppler ultrasound parameters comparison: between the two groups E peak, A peak, E/A were not statistically significant (P 0.05). (4) Tissue Doppler ultrasound parameters comparison: HFmrEF group compared with normal people e'decreased, E/e'increased, Sm decreased, the difference was statistically significant (P 0.05). (5) 2DTT parameters. The peak time of GLS in HFmrEF group was longer than that in normal group, and the difference was statistically significant (P 0.05). (6) Compared with VFM parameters, the total energy loss of left ventricle in HFmrEF group was lower than that in normal group, including rapid filling period, isovolumic systole period and rapid ejection period. There was no significant difference in isovolumic diastolic period and atrial systolic period (P 0.05). There was no significant difference in NT-proBNP, triglyceride, total cholesterol, HDL-C, LDL-C (P 0.05). Blood glucose in group II was higher than that in group I (P 0.05). (2) Comparison of two-dimensional ultrasound parameters: EDV and ESV in group I were higher than those in group II, LAV and LAVI in group I were higher than those in group II, LVEDd were larger, the difference was statistically significant (P 0.05). (3) Comparison of Doppler ultrasound parameters in group I: EDV and ESV in group II were higher than those in group II. Compared with group II, the E peak increased significantly in group I (P > 0.05). (4) Compared with group II, the E/e'of group I increased significantly (P 0.05). (5) Compared with group II, the GLS of group I decreased and the peak time of GLS prolonged, but there was no significant difference between group I and group II (P > 0.05). In isovolumic diastolic phase, the total energy loss of left ventricle in rapid filling phase increased, and the difference was statistically significant in rapid filling phase (P 0.05); in atrial systolic phase, isovolumic systolic phase, rapid ejection phase energy loss decreased, but the difference was not statistically significant (P 0.05). 4. Correlation analysis of energy loss between HFmrEF group and clinical data and ultrasound data (1) rapid filling. Total left ventricular energy loss was negatively correlated with e's (r = - 0.453, P = 0.016), positively correlated with E/e's (r = 0.456, P = 0.015), negatively correlated with BMI (r = - 0.444, P = 0.018), and negatively correlated with LDL-C (r = - 0.476, P = 0.016). (2) Total left ventricular energy loss during atrial systole was positively correlated with GLS (r = 0.392, all P = 0.039). EDV was negatively correlated with EDV (r-0.468, P = 0.012), ESV was negatively correlated with ESV (r = - 0.468, P = 0.012), GLSwas positively correlated with GLS (r = 0.509, P = 0.006), BMI was negatively correlated with BMI (r = - 0.382, P = 0.382, P = 0.382, P = 0.045). (4) Leventventventventventricular energy loss in rapid ejectperiod was nenegatively correlwith EDV (r-0.419, P = 0.026), ESV was nenegatively correlwith ESV (r =-0.472, P = 0.472, P = 0.011, P = 0.011), P = 0.039), negative to BMI Multivariate linear regression analysis of energy loss in HFmrEF group (1) Global energy loss in left ventricle during rapid filling was independently correlated with E/e'(beta = 0.423, P = 0.019), and LDL-C (beta = - 0.418, P = 0.020). (2) Global energy loss in left ventricle during atrial systole was correlated with GLS (beta = 0.392, P = 0.039). (4) Left ventricular global energy loss during rapid ejection was correlated with BMI (beta = - 0.524, P = 0.004). 6. ROC analysis of energy loss in diagnosing HFmrEF efficacy was used to assess the value of combined diagnosis of HFmrEF in three periods: rapid filling, isovolumic systole and rapid ejection. The combined predictive probability (the model excludes isovolumic systolic energy wastage) was obtained after the model fitting. ROC curve was made and AUC.AUC=0.817 was calculated. It is concluded that the combination of rapid filling and rapid ejection energy wastage is effective in the diagnosis of HFmrEF. Conclusion 1. Systolic and diastolic functions of HFmrEF patients. The left ventricular energy loss in HFmrEF patients was significantly lower than that in the control group during rapid filling, isovolumic systolic and rapid ejection. It is related to cardiac systolic function.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.6

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