Diagnostic And Prognostic Value Of Left Ventricular Deformation Measurements Derived From Real-Time 3D-STE Combined With Red Cell Distribution Width In HFpEF

AIMSIt is difficult in diagnosis and prognosis prediction for HFpEF.Although some researchers have paid attention to the application value of red cell distribution width（RDW）or left ventricular strain parameters in HFpEF,few researchers have studied the relationship between RDW and left ventricular myocardial deformation and the comprehensive value of their combined application in HFpEF diagnosis and prognosis.In this study,we try to discuss the relationship between RDW and left ventricular strain parameters based on real-time three-dimensional speckle tracking echocardiography（3D-STE）in HFpEF,and assess the value of left ventricular deformation parameter combined with RDW in the prediction of HFpEF.In addition,this study will further explore the role of RDW and left ventricular deformation parameters in determining the prognosis of HFpEF,so as to determine whether the combined application of the two has incremental value in determining the prognosis of HFpEF.METHODS169 patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 2017 to November 2018 with symptoms or signs of chronic heart failure and left ventricular ejection fraction（LVEF）≥50%were recruited in the study.And they were divided into three subgroups:SubgroupⅠ:patients with no substantial cardiac dysfunction and configuration change.LVEF≥50%,left atrial volume index（LAVI）≤34mL/m²,NT-proBNP<400ng/L:n=55;SubgroupⅡ:patients with suspected HFpEF,LVEF≥50%,LAVI>34mL/m² or NT-proBNP≥400ng/L:n=52;SubgroupⅢ:patients with definite HFpEF,LVEF≥50%,LAVI>34mL/m²,NT-proBNP≥400ng/L:n=62。50 healthy volunteers were included in the control group,with no history of cardiovascular or systemic diseases,and the results of physical examination,electrocardiogram,echocardiography and chest X-ray examination were all normal.GE Vivid E9（GE Healthcare,Inc.USA）ultrasound and 4V volume probe were used for echocardiography.The left atrial diameter（LAD）,interventricular septum thickness（IVST）,left ventricular end diastolic diameter（LVEDD）,left ventricular posterior wall thickness were（LVPWT）,early diastolic and late mitral annulus peak velocity e’and a’,early diastolic and late mitral flow peak velocity E and A（and calculate E/A and E/e’）and tricuspid regurgitation peak velocity(V_TR)were measured by routine echocardiography.Left atrial volume at the end of systole was measured according to the"two-plane Simpson method"and indexed by body surface area（BSA）to obtain LAVI.Full-volume dynamic images of 3 consecutive cardiac cycles were obtained at the apex.Real-time 3D-STE analysis was conducted in automatic left ventricular quantification（LVQ）module.The software automatically calculated the measurements including left ventricular global longitudinal strain（GLS）,global radial strain（GRS）,global circumferential strain（GCS）,global area strain（GAS）,left ventricular end-diastolic volume,left ventricular mass and LVEF.Left ventricular end diastolic volume index（LVEDVI）and Left ventricular mass index（LVMI）were calculated by using BSA to index.Venous blood samples were collected for laboratory examination on the same day as the echocardiography study.The RDW has a reference range of 11.5-14.5%.62 definite HFpEF patients were followed up in cardiovascular medicine department or other internal medicine outpatient department of the Second Affiliated Hospital of Anhui Medical University after discharge.Meanwhile,combined with regular telephone and WeChat follow-up,the obtained information was summarized and recorded in detail.The end point of the study was major adverse cardiac events（MACE）,which was death caused by various causes or hospitalization for heart failure,whichever occurred first.Spearman correlation analysis was used to analyze the correlation between RDW and clinical and echocardiographic parameters.To determine the factors related to HFpEF,univariate Logistic regression analysis was conducted with clinical,echocardiographic parameters and RDW as independent variables and HFpEF as dependent variable.Then,multivariate Logistic regression analysis was carried out for variables with statistical significance（P<0.10）in univariate analysis.Receiver operator characteristic（ROC）curves are drawn to determine the diagnostic value of the left ventricular strain parameters and RDW for HFpEF.The ROC curve for predicting the prognosis of HFpEF was drawn by left ventricular myocardial strain number.The predictive value of conventional clinical and echocardiographic parameters on the prognosis of HFpEF was analyzed by univariate Logistic regression.The variables with statistical significance in univariate Logistic regression（P<0.01）and left ventricular strain parameters and RDW were stepped to enter multivariate Logistic regression analysis.Cox regression was used to analyze which was related to the prognosis of HFpEF patients in left ventricular strain parameters and RDW.RESULTSOf the 169 enrolled cases,55 were clinically excluded from HFpEF,52 were suspected of HFpEF,and 62 were confirmed as HFpEF.The patients in SubgroupⅢwere older,with larger body surface area and poorer renal function.The levels of NT-proBNP and RDW were higher than those in the other two subgroups.There were also significant differences in these parameters between the patient group and the control group（P<0.01）.The diameter,volume of the left ventricle and left atrium,IVST and LVMI were significantly increased in the patient group.E’was lower,E/e and V_TRR were higher in patient group,reflecting higher left ventricular filling pressure.In SubgroupⅢ,left heart was bigger,the left ventricular wall was thicker,and left ventricular filling pressure was higher than the other two subgroups.Strain values in the patient group were significantly lower than the control group,strain parameters in SubgroupⅢwere also significantly lower than the other two groups.In univariate Logistic regression analysis,HFpEF was correlated with age,New York Heart Association（NYHA）grade,history of hypertension,RDW,LVEDD,LVEDVI,IVST,LVMI,diastolic dysfunction parameters and real-time 3D-STE parameters.All these indicators were combined with gender for multivariate regression analysis.The predictive ability for HFpEF of age,gender,NYHA grading,history of hypertension,LVEDVI,IVST,LVMI and diastolic function parameters（Model 1）was significantly improved after adding strain parameters（Model 2）（P<0.01）,and further improved after adding RDW（Model 3）（P<0.01）.RDW is correlated with HFpEF,independent of age,gender,NYHA grading,hypertension history,LVEDVI,IVST,diastolic function parameters and strain parameters.The predictive accuracy for HFpEF of Model 1,Model 2 and Model 3 is 65.7%,86.4%and 88.8%,respectively.ROC curves of E/E’,GLS,GCS,GRS and RDW predicted HFpEF were plotted.Area under curve（AUC）of GLS is the largest（AUC=0.869,P<0.001）.A median follow-up of 220.5（195-244）days was conducted in 62 patients with definite HFpEF.2 patients were lost.2 patients died and 16 patients were re-admitted due to heart failure.The ROC curve of left ventricular strain parameter prediction for MACE occurrence of HFpEF was drawn,showing that the AUC predicted by GLS for MACE was 0.751（95%CI:0.620-0.883）（P=0.002）,which was better than GAS（95%CI:0.566-0.867）（P=0.008）.GRS and GCS had no significant statistical significance in predicting the AUC of MACE（P>0.05）.In the univariate Logistic regression analysis of conventional clinical and echocardiographic parameters predicting MACE occurrence of HFpEF,LAVI,NT-proBNP and E/e’were correlated with the occurrence of MACE（P<0.10）.Multivariate Logistic regression analysis（Model a）was conducted with the three variables together with age and gender,and its ability to predict MACE occurrence was significantly improved after the addition of left ventricular strain parameter（Model b）（P<0.01）,and further improved after the addition of RDW（Model c）（P=0.02）.The prediction accuracy of Models a,b and c is 70.0%,75.0%and 81.7%respectively.It indicates that the addition of left ventricular strain parameters and RDW on the basis of conventional parameters has incremental value for the prediction of MACE.Cox regression model was used to explore the effects of conventional parameters,left ventricular strain parameters and RDW on the incidence of MACE in HFpEF patients,and the survival curve was plotted.After the addition of left ventricular strain parameters（GLS,GRS,GCS,GAS）and RDW,the logarithmic likelihood of-2 andχ2of COX model decreased gradually,and the P-value decreased from 0.231 to 0.056 and0.022,indicating that the correlation between conventional parameters and MACE was enhanced after the addition of left ventricular strain parameters and RDW.According to conditional regression,NT-proBNP,GAS and RDW finally entered the equation,which were all related factors of MACE occurrence,RR（Exp（beta）95%CI）>1,not crossing1（P<0.05）.Conclusions（1）In patients with suspected heart failure with symptoms or signs of heart failure,RDW was independently correlated with NT-proBNP and real-time 3D-STE left ventricular strain parameters.（2）GLS,GRS,GCS,GAS,RDW and E/e’have potential diagnostic value for HFPEF,among which GLS and GAS have the strongest diagnostic ability.（3）On the basis of clinical and ultrasonographic parameters,combined with left ventricular strain parameters and RDW,the diagnostic accuracy of HFpEF is gradually improved,which indicates that left ventricular strain parameters and RDW have incremental value in the diagnosis of HFpEF.（4）In real-time 3D-STE left ventricular strain parameters,GLS is better than GAS in predicting the occurrence of MACE in HFpEF patients.（5）Adding left ventricular strain parameters and RDW to conventional clinical and echocardiographic parameters also has incremental value in predicting the occurrence of MACE in HFpEF patients.（6）The correlation between conventional clinical and echocardiographic parameters and MACE occurrence was enhanced after left ventricular strain parameters and RDW were added,NT-proBNP,GAS and RDW were the related factors of MACE occurrence.（7）The left ventricular strain parameters derived from real-time 3D-STE showed great reproducibility in both intra-observer and inter-observer.