According to the latest ESC guidelines, we enrolled 168 consecutive patients with signs or symptoms of HF and LVEF≥50% at the Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. The recruitment period lasted from March 2021 to March 2022. Patients were further divided into two subgroups based on the median value of GWE.
The exclusion criteria were: congenital heart disease, severe mitral annular calcification, severe mitral regurgitation, severe aortic valve disease, prosthetic heart valve or prosthetic ring, severe chronic obstructive pulmonary disease, persistent atrial fibrillation, and poor acoustic window.
According to these criteria, 61 patients were excluded: congenital heart disease (1 patient), severe chronic obstructive pulmonary disease (9 patients), severe mitral annular calcification (4 patients), severe mitral regurgitation (4 patients), severe aortic stenosis (5 patients), severe aortic regurgitation (2 patients), prosthetic heart valve or prosthetic ring (6 patients), persistent atrial fibrillation (16 patients), and poor acoustic window (14 patients).
Thirty-two sex-matched asymptomatic subjects who were referred to our hospital for screening were included as the control group. Subjects were excluded if they had: (1) hypertension, (2) type 2 diabetes, (3) coronary artery disease, (4) congenital heart disease, (5) more than trivial valve regurgitation or valve stenosis of any degree, (6) any previous cardiac or vascular surgery or interventional procedure, (7) any kind of cardiac therapy.
This prospective study was approved by the ethics committee of Beijing chaoyang Hospital Affiliated to capital medical University (No: 2021-11-26-17)..
At the time of transthoracic echocardiography (TTE), data pertaining to the following demographic and clinical variables were collected: age, sex, systolic and diastolic blood pressure, heart rate, height, and weight. Medical history of hypertension, diabetes, coronary artery disease, and smoking were obtained simultaneously. Plasma B-type natriuretic peptide and serum creatinine levels were determined within 7 days of the TTE. The estimated glomerular filtration rate (eGFR) was measured using the modified MDRD Study equation for Chinese (the Chinese equation).
Two-dimensional and Doppler echocardiography were performed using standard equipment (Vivid E95, General Electric Medical Systems, Milwaukee, WI, USA). At least 3 consecutive cardiac cycles of standard echocardiographic views were acquired and stored digitally for subsequent analysis by trained physicians. LVEF, left atrial volume index (LAVi), and stoke volume (SV) were measured through tracing the apical four- and two-chamber views based on the modified biplane Simpson’s method. Left atrial enlargement was defined as LAVi≥34 mL/m2. Left ventricular dimensions variables, including left ventricular end-diastolic diameter (LVEDd), interventricular septum thickness at end diastole (IVSd), and posterior wall thickness at end diastole (PWTd), were measured according to the recommended criteria, and LV mass index (LVMi) and relative wall thickness (RWT) were calculated accordingly. Mitral inflow peak (E), peak (A), and issue Doppler mitral annular early diastolic velocity (e’) were measured for calculation of E/A and E/e’. All indices were measured in accordance with the latest chamber quantitation guidelines of the American Society of Echocardiography.
Speckle Tracking Imaging
Global longitudinal myocardial strain was assessed using a semiautomated 2D speckle tracking software (EchoPac 204, General Electric Medical Systems) in the apical four chamber (A4C) view, apical two chamber (A2C) view, and apical three chamber (A3C) view with typical temporal resolution of 60–90 frames/s. After manual tracing of the endocardial border and selecting the appropriate wall thickness, the software automatically identified six segments in each view and tracked the motion of acoustic markers. Segments that failed to track satisfactorily were readjusted manually, and, if this was ineffective, these were excluded from further analysis. Timing of the aortic and mitral valve opening and closure were obtained using single-gated pulsed-wave Doppler traces. GLS was derived as the average of the 17 segmental strain values and is described as an absolute value for simplicity.
Global myocardial work evaluation
Global myocardial work was calculated as recommended. In brief, GMW was measured using the combination of LV GLS and the subject’s brachial cuff blood pressure in place of left ventricular pressure. LV GLS was measured as above taking R-wave in ECG as the onset. After 5 to 10 minutes rest and choosing an appropriate cuff, blood pressure was measured in the supine position immediately before the echocardiographic study. All echocardiography and blood pressure data were stored and then analyzed offline. After strain measuring and valvular event timing setting, we could get a pressure strain loop (PSL). The software further calculated the following four parameters:
(a) Global work index (GWI, mmHg%): The area of the PSL which was calculated from the mitral valve closure to its opening.
(b) Global constructive work (GCW, mmHg%): The work that contributes to the LV ejection during systole, i.e., the sum work of myocardial shortening during systole and lengthening during isovolumic relaxation.
(c) Global waste work (GWW, mmHg%): The work that does not contribute to LV ejection, calculated as the sum of lengthening during systole and shortening in isovolumic relaxation.
(d) Global work efficiency (GWE, mmHg%): GCW divided by the sum of GCW and GWW.
Intra- and inter-observer variability
Twenty-five patients were randomly selected and independently remeasured by another two researchers. Intra-observer variability was assessed at two different time points more than 4 weeks apart, while inter-observer variability was assessed by comparing the measurements by two different researchers on the same patient data. The reproducibility and variability were analyzed using Bland-Altman plots and intraclass correlation coefﬁcient (ICC).
Normality of distribution of continuous variables was assessed using the Kolmogorov-Smirnov test. Continuous variables are reported as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables are expressed as frequency (percentage). Between-group differences with respect to continuous variables were assessed using the Mann-Whitney U test or Kruskal-Walli’s test. Between-group differences with respect to categorical variables were assessed using the Chi-squared test or Fisher exact test, and a covariance analysis was performed when necessary. Spearman’s rank correlation coefficient was used to assess the correlation between different variables, and then linear multivariate regression or logistic multivariate analysis was performed to evaluate the independent effect of covariates. Patients with HFpEF were further divided into two subgroups with different RWT according to the latest guidelines for cardiac chamber quantiﬁcation. P values < 0.05 were considered indicative of statistical signiﬁcance. All statistical analyses were performed using IBM SPSS Statistics version 25 (IBM, Armonk, New York), Graphpad Prism version 8.0 and Origin Pro 2021.