Stress Echocardiographic Myocardial Work in Healthy Adults and Heart Failure with Preserved Ejection Fraction Patients and Doubt about Early Systolic Lengthening

Stress Echocardiographic Myocardial Work in Healthy Adults and Heart Failure with Preserved Ejection Fraction Patients and Doubt about Early Systolic Lengthening | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Stress Echocardiographic Myocardial Work in Healthy Adults and Heart Failure with Preserved Ejection Fraction Patients and Doubt about Early Systolic Lengthening Liwei Huang, Luwei Ye, Hongmei Zhang, Qingfeng Zhang, Geqi Ding, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3906031/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The aims of this study were ( 1 ) to characterize myocardial work (MW) changes from rest to after exercise in healthy adults and heart failure patients with preserved ejection fraction (HFpEF), and ( 2 ) to explore the factors influencing the decrease in global work efficiency (GWE) after exercise in healthy adults. Methods This study enrolled 167 healthy adults and 38 HFpEF patients. All subjects underwent echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. Results GWE decreased after exercise in healthy adults. It was higher in women after exercise (women: 93% vs. men: 91%, p < 0.05). GWE was significantly lower after exercise in HFpEF patients (HFpEF: 85% vs. healthy: 92%, p < 0.05). The peak positive strain (PPS) was independently associated with global wasted work (GWW) both in healthy adults and HFpEF patients (healthy adults: r = 0.77, p < 0.001 at rest; r = 0.72, p < 0.001 after exercise; HFpEF: r = 0.74, p < 0.001 at rest; and r = 0.62, p < 0.001 after exercise). Conclusions MW parameters were less affected by sex in healthy individuals. MW parameters were lower in HFpEF than healthy adults both at rest and after exercise. GWE decreased in healthy adults after exercise because of increased GWW, and PPS was independently associated with GWW both at rest and under load, suggesting that early systolic lengthening (ESL) may be beneficial for subsequent contraction of the myocardium. Health sciences/Cardiology Health sciences/Medical research heart failure with preserved ejection fraction early systolic lengthening myocardial work exercise echocardiography peak positive strain Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The assessment of myocardial function plays an important role in routine clinical practice. The analysis of myocardial strain adds information on cardiac performance over that gained from traditional parameters of left ventricular (LV) systolic function 1 . However, strain does not reflect myocardial work (MW) or oxygen consumption, as this parameter is not adjusted for loading conditions. MW has been suggested as an alternative tool for studying LV myocardial systolic function, because it incorporates both deformation and load into the analysis. MW was initially calculated using invasive pressure measurements, which limited its widespread use in clinical practice. 2,3 Russell et al 4 proposed a method for the non-invasive estimation of regional and global MW from pressure–strain loop (PSL) analysis. Some studies have used this technique to analyse the reference ranges of MW in healthy adults. 5,6 The technique has also been used to analyse left ventricular systolic function in patients with coronary artery disease and cardiac amyloidosis, with reasonable results 7–9 . However, studies of MW parameters and their differences between sexes during treadmill exercise stress echocardiography in healthy individuals are rare. Borrie A’s study revealed that global work efficiency (GWE) decreased after exercise in healthy individuals, but their sample was small, and they did not study sex differences. 10 There are no studies on the factors influencing the decrease in GWE after exercise. Heart failure with preserved ejection fraction (HFpEF) is a growing health problem. 11 The role of systolic dysfunction despite preserved LV ejection fraction has not been well characterized, and no studies about MW reserve during exercise have been done in HFpEF patients. The aims of this study was to characterize the changes in MW associated with rest and load conditions in healthy adults and HFpEF patients and to explore the factors related to the decrease in GWE after exercise. METHODS Study Population Healthy adult group With a cross-sectional study design, we prospectively enrolled 192 healthy volunteers from May 2018 to December 2023. The healthy participants had blood pressure values within the healthy reference ranges, had healthy resting and stress electrocardiographic results, had negative coronary CT or angiography results, were not taking any medications, were non-smokers, and had no history of hypertension, diabetes, or cardiac diseases. According to these criteria, 25 subjects were excluded for having electrocardiographic abnormalities (5 subjects), metabolic syndrome (4 subjects) or poor acoustic windows (16 subjects). HFpEF group We enrolled 60 consecutive patients with left ventricular ejection fraction ≥ 50%, determined by an intermediate risk of 2–4 points on the HFA-PEFF scale during the noninvasive work-up. 12 The recruitment period ran from May 2018 to December 2023. The exclusion criteria were as follows: unstable angina or acute myocardial infarction; more than mild aortic valve disease; prosthetic heart valve or prosthetic ring; severe mitral annular calcification; severe (> 3+) mitral regurgitation; significant (> 50% stenosis) coronary artery disease according to coronary angiography; uncontrolled hypertension; severe chronic obstructive pulmonary disease; any contraindication to physical activity (e.g., gonarthrosis or symptomatic peripheral artery disease); inability to exercise; and poor acoustic window. According to these criteria, 22 patients were excluded for significant valvular heart disease (5 patients), severe chronic obstructive pulmonary disease (5 patients), contraindication for physical activity (3 patients), unstable angina (3 patients), or a poor acoustic window (6 patients). All subjects underwent clinical examinations, resting 12-lead electrocardiography, and comprehensive transthoracic echocardiography at rest and immediately after maximal treadmill stress testing. The clinical examination included measurements of height, weight, body mass index (BMI) and resting blood pressure. Body surface area (BSA) was calculated according to the DuBois formula. 13 The healthy adults were divided into male and female subgroups. Every subject was > 18 years of age and was included after providing informed written consent according to the principles of the Declaration of Helsinki. The study was conducted after approval from the local scientific ethics committee. Echocardiographic Data Acquisition All subjects underwent standard transthoracic echocardiography using a commercially available Vivid E95 ultrasound system equipped with an M5S 3.5-MHz transducer (GE Vivid E95, Vingmed Ultrasound, Horten, Norway) at rest and immediately after exercise in the left lateral decubitus position. Electrocardiogram-triggered echocardiographic data were acquired and digitally stored in a cine-loop format for offline analysis with EchoPAC (EchoPAC 203, General Electric Vingmed Ultrasound). At rest, all subjects underwent a comprehensive two-dimensional echocardiographic assessment in accordance with current guidelines. 14 LV end-diastolic (LVEDV) and end-systolic volumes (LVESV) were measured in the apical two- and four-chamber views. LVEF was calculated using the Simpson biplane method. 15 LVEDV and LVESV were indexed to BSA (presented as the LVEDVI and LVESVI, respectively). The magnitude of LV global longitudinal strain (GLS) was obtained using automated function imaging (AFI) in standard two-dimensional cine loops with a frame rate > 70 frames/sec. 16 The regional speckle area of interest was adjusted manually for optimal tracking results. GLS was calculated at the time of systole when the value peaked using a 17-myocardial segment model. 17 The principles for estimating LV pressure and work have been described. 4 In this method, a previously generated empiric reference curve for LV pressure was utilized. The reference curve was individualized by scaling the amplitude using measured systolic cuff pressure and warping it in time by aligning the valvular aorta and opening and closing the mitral valve, as assessed by echocardiography. The constructive and wasted work was measured at the segmental and global levels based on this pressure–strain curve. Constructive work (CW) included the sum of work performed during shortening in systole and the negative work performed during lengthening in the isovolumetric relaxation phase. The myocardial work index (WI) meant the total work within the area of the LV pressure–strain loop calculated from mitral valve closure to mitral valve opening. Wasted work (WW) comprised negative systolic work due to systolic lengthening and the work of shortening in the isovolumic relaxation phase. Myocardial work efficiency (WE) was calculated as the ratio of CW/(CW + WW). The LV global constructive work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were calculated as the average of the myocardial work index, constructive work, wasted work and work efficiency of all segmental values. All the MW parameters were analysed both at rest and after exercise. All echocardiographic parameters were averaged over three consecutive cardiac cycles. From the longitudinal speckle-tracking curve, we obtained the peak positive strain (PPS) during the early systole phase. 18 If no early systolic lengthening (ESL) occurred in the early systole phase, PPS was set to zero. If ESL occurred, the maximum value of positive strain during the ESL duration was PPS (Fig. 1 ). The MW reserve was calculated as the difference in GWI, GCW, GWW, and GWE between the resting and postexercise values (presented as ΔGWI, ΔGCW, ΔGWW and ΔGWE, respectively). Exercise Protocol All subjects performed a symptom-limited treadmill (TMX-425, Full Vision, Inc., Kansas) exercise test using standard Bruce protocols. 19 They were encouraged to exercise until exhaustion. A baseline 12-lead electrocardiogram (ECG) and blood pressure were acquired and repeated at 2-min intervals during the exercise examination, at peak exertion, and after exercise. The maximum exercise capacity of metabolic equivalents (METs) was recorded, where 1 MET = 3.5 mL/kg/min oxygen consumption was estimated based on the protocol, speed, and grade achieved. 20 Exercise duration and the ratio of peak HR to target HR (according to the 220 − age formula) were also automatically recorded. Statistical Analysis All statistical analyses were performed using SPSS version 23.0 (SPSS, Armonk, NY). The parameters with a normal distribution were tested by Student’s T test, and those with a nonnormal distribution were tested by a nonparametric test. Normally distributed data are presented as mean ± SD. Skewed data are presented as median (interquartile range [IQR]). Histograms and Q‒Q plots were used to check continuous values for normality. Continuous variables were compared between groups using the unpaired Student’s t test. The 95% confidence intervals were calculated as ± 1.96 SDs from the mean. P < 0.05 was considered statistically significant. Correlations between two parameters were calculated as Pearson’s correlation coefficient. Stepwise multiple regression analyses were used to determine the independent factors correlated with GWWrest and GWWpost-ex. Intra- and Interobserver Variability GWI analyses at baseline and immediately after exercise were repeated in 10 randomly selected patients at least 4 weeks after the initial analysis by the original investigator and by a second investigator who were both blinded to the original measurements to assess intraobserver and interobserver variability. The intraclass correlation coefficient (ICC) was calculated. RESULTS Patient Characteristics and Conventional Echocardiographic Parameters Resting and treadmill exercise stress echocardiography (SE) were performed in 167 healthy adults (55% women; aged 46.9 ± 12.8 years; age range, 22–75 years) and 38 HFpEF patients (54% women; aged 51.5 ± 12.9 years; age range, 30–77 years). The clinical characteristics of the healthy and HFpEF patients are displayed in Table 1 and Table 2 . Men had higher BSA and higher systolic blood pressure (SBP) than women ( p < 0.05). HFpEF patients had higher SBP than healthy patients ( p < 0.05). There was no significant difference in EF at rest between the sexes, but EF was significantly higher in men after exercise ( p < 0.05; Table 1 ). There was no significant difference in EF at rest between the HFpEF patients and healthy controls, while EF was significantly lower in the HFpEF group after exercise ( p < 0.05; Table 2 ). Table 1 Characteristics of population and conventional echocardiographic parameters in normal Parameters Total/167 Male/76 Female/91 P -value Age (years) 46.9 ± 12.8 46.5 ± 13.3 47.8 ± 12.6 0.560 Height (cm) 163.5 ± 9.4 169.3 ± 7.8 158.8 ± 4.5 < 0.001 Weight (kg) 62.4 ± 12.0 68.7 ± 12.0 55.2 ± 8.1 < 0.001 Body surface area (m 2 ) 1.71 ± 0.2 1.9 ± 0.2 1.6 ± 0.2 < 0.001 Body mass index (kg/m 2 ) 22.9 ± 3.1 23.5 ± 3.1 21.7 ± 2.4 < 0.001 Rest HR (bpm) 91 ± 15 92 ± 15 91 ± 15 0.620 SBP (mmHg) 127 ± 18 128 ± 16 118 ± 15 < 0.001 DBP (mmHg) 73 ± 11 81 ± 10 72 ± 10 0.004 EDVI (mL/m 2 ) 41.4 ± 8.6 42.5 ± 8.4 38.5 ± 7.4 0.004 ESVI (mL/m 2 ) 13.3 ± 3.3 14.8 ± 3.9 12.8 ± 3.5 0.003 EF (mL/m 2 ) 0.65 ± 0.07 0.64 ± 0.06 0.66 ± 0.06 0.319 Peak exercise period HR (bpm) 160 ± 16 167 ± 16 159 ± 16 0.067 SBP (mmHg) 170 ± 20 177 ± 23 160 ± 19 < 0.001 DBP (mmHg) 75 ± 12 75 ± 12 74 ± 13 0.905 EDVI (mL/m 2 ) 34.8 ± 7.8 34.3 ± 9.1 36.6 ± 8.3 0.093 ESVI (mL/m 2 ) 6.5 ± 2.5 6.2 ± 2.9 7.3 ± 3.1 0.009 EF (mL/m 2 ) 0.82 ± 0.04 0.83 ± 0.03 0.81 ± 0.06 0.004 Exercise time (min) 8.9 ± 1.9 9.0 ± 1.8 8.4 ± 1.8 0.030 METs 9.8 ± 1.6 9.9 ± 1.7 9.3 ± 1.7 0.029 HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; EDVI, end diastolic volume index; ESVI, end systolic volume index; EF, ejection fraction; METs, metabolic equivalents. Table 2 Characteristics of population and conventional echocardiographic parameters in normal compared with HFpEF Parameters Normal/167 HFpEF/38 P -value Age (years) 46.9 ± 12.8 51.5 ± 12.9 0.037 Height (cm) 163.5 ± 9.4 162.7 ± 10.1 0.623 Weight (kg) 62.4 ± 12.0 64.7 ± 13.1 0.045 Body surface area (m 2 ) 1.71 ± 0.2 1.72 ± 0.21 0.913 Body mass index (kg/m 2 ) 22.9 ± 3.1 24.15 ± 4.2 0.021 Rest HR (bpm) 91 ± 15 87 ± 12 0.833 SBP (mmHg) 127 ± 18 135 ± 21 0.025 DBP (mmHg) 73 ± 11 86 ± 13 0.020 EDVI (mL/m 2 ) 41.4 ± 8.6 51.2 ± 9.8 < 0.001 ESVI (mL/m 2 ) 13.3 ± 3.3 17.5 ± 5.4 0.015 EF (mL/m 2 ) 0.65 ± 0.07 0.65 ± 0.05 0.897 Peak exercise period HR (bpm) 160 ± 16 133 ± 15 0.002 SBP (mmHg) 170 ± 20 187 ± 29 < 0.001 DBP (mmHg) 75 ± 12 75 ± 12 0.987 EDVI (mL/m 2 ) 34.8 ± 7.8 46.3 ± 9.7 < 0.001 ESVI (mL/m 2 ) 6.5 ± 2.5 13.5 ± 5.6 < 0.001 EF (mL/m 2 ) 0.82 ± 0.04 0.73 ± 0.07 0.006 Exercise time (min) 8.9 ± 1.9 6.5 ± 2.6 0.023 METs 9.8 ± 1.6 6.7 ± 1.3 < 0.001 HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; METs, metabolic equivalents; EDVI, end diastolic volume index; ESVI, end systolic volume index; EF, ejection fraction. Myocardial Work Parameters GWI, GCW and GWW increased but GWE decreased in the healthy group (Table 3 ). There was no significant difference in any of the global MW parameters between the sexes at rest. GWE was significantly higher in women after exercise ( p < 0.05; Table 3 ). There were no significant differences in MW reserve between the sexes (Table 3 ). Table 3 MW parameters at rest and post-exercise in normal adults of different sexes Parameters Total/167 Male/76 Female/91 P -value Rest GWI (mmHg%) 1930 ± 421 1928 ± 382 1975 ± 391 0.432 GCW (mmHg%) 2298 ± 410 2289 ± 408 2326 ± 408 0.496 GWW (mmHg%) 69(40–100) 63 (43–100) 78(48–104) 0.498 GWE (%) 95 ± 2 95 ± 3 95 ± 2 0.877 Peak exercise period GWI (mmHg%) 2720 ± 369 2624 ± 389 2753 ± 401 0.348 GCW (mmHg%) 3520 ± 680 3522 ± 831 3519 ± 636 0.976 GWW (mmHg%) 210 (120–339) 220 (155–392) 203 (116–310) 0.085 GWE (%) 92 ± 5 91 ± 5 93 ± 5 0.031 △GLS(%) 4.5 ± 2.3 4.5 ± 2.2 4.0 ± 2.1 0.045 △GWI(mmHg%) 798 ± 319 815 ± 747 785 ± 697 0.817 △GCW(mmHg%) 1125 ± 380 1059 ± 391 1147 ± 375 0.624 △GWW(mmHg%) 150 (68–284) 173 (82–324) 132 (47–228) 0.414 △GWE(%) -2.9(-4.9 to 1.0) -4 (-7.5 to -1.0) -2.0(-5.0 to -0.24) 0.224 GLS, global longitudinal strain; GWI, global constructive work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency; △, change from rest to peak. GWE decreased in the HFpEF group after exercise (Table 4 , Fig. 2 ). GWE was significantly lower in HFpEF patients than in healthy individuals both at rest and after exercise ( p < 0.05; Table 4 , Fig. 2 ). MW reserve decreased significantly in HFpEF patients compared with healthy controls ( p < 0.05, Table 4 ). PPS increased in both the healthy and HFpEF groups after exercise (Table 4 ). Table 4 MW parameters at rest and post-exercise in normal adults compared with HFpEF Parameters Normal/167 HFpEF/38 P -value Rest GWI (mmHg%) 1930 ± 421 1660 ± 305 0.026 GCW (mmHg%) 2298 ± 410 2055 ± 403 0.030 GWW (mmHg%) 69(40–100) 199 ± 87 < 0.001 GWE (%) 95 ± 2 90 ± 3 0.040 GLS (%) 20.1 ± 3.2 16.7 ± 3.5 0.020 PPS (%) 0.60 ± 0.37 1.45 ± 0.97 0.031 Peak exercise period GWI (mmHg%) 2720 ± 369 2330 ± 378 0.041 GCW (mmHg%) 3520 ± 680 3098 ± 650 0.038 GWW (mmHg%) 210 (120–339) 359 ± 89 0.013 GWE (%) 92 ± 5 85 ± 3 0.019 GLS (%) 24.1 ± 3.9 17.9 ± 4.5 0.009 PPS (%) 1.55 ± 0.80 2.73 ± 1.23 0.023 △GLS (mmHg%) 4.5 ± 2.3 0.8 ± 0.3 < 0.001 △GWI (mmHg%) 798 ± 319 655 ± 320 0.029 △GCW (mmHg%) 1125 ± 380 988 ± 290 0.040 △GWW (mmHg%) 150 (68–284) 170 ± 39 0.039 △GWE(%) -2.9 (-4.9 to 1.0) -5 (-7.7 to 1.1) 0.023 GLS, global longitudinal strain; GWI, global constructive work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency;△, change from rest to peak; PPS, peak positive strain. Intra- and Interobserver Variability The ICCs for intraobserver variability were 0.92 for GWI at rest and 0.89 for GWI after exercise. The ICCs for interobserver variability were 0.91 for GWI at rest and 0.87 for GWI after exercise (Table 5 ). Table 5 Inter- and intra-observer variability of GWI Intra-observer Inter-observer Variable ICC Bias 95%LOA p ICC Bias 95%LOA p GWIrest 0.92 -0.02 ± 1.57 -3.12 to 3.07 < 0.01 0.91 0.13 ± 1.64 -3.10 to 3.38 < 0.01 GWIpost-ex 0.89 -0.14 ± 0.70 -1.51 to 1.23 < 0.01 0.87 0.01 ± 0.69 -1.33 to 1.36 < 0.01 GWI, global constructive work index; ICC, interclass correlation coefficient; LOA, limits of agreement; post-ex, immediately after exercise. The Relationship Between PPS and GWW in Healthy Adults Stepwise multiple regression analysis demonstrated that PPSrest (r = 0.77, p < 0.001) and PPSpost-ex (r = 0.72, p < 0.001) were independently associated with GWWrest and GWWpost-ex in healthy individuals. PPSrest (r = 0.74, p < 0.001) and PPSpost-ex (r = 0.62, p < 0.001) were also independently associated with GWWrest and GWWpost-ex in HFpEF patients (Fig. 3 ). DISCUSSION The main findings of the present study can be summarized as follows: ( 1 ) there were no significant differences in most of the MW parameters between males and females, which indicates that MW is a stable parameter for evaluating LV function regardless of sex; ( 2 ) the decrease in MW parameters in HFpEF patients could provide incremental information on myocardial function in HFpEF patients; ( 3 ) GWE decreased after exercise in healthy adults, and PPS was independently associated with GWW both at rest and during load, suggesting that ESL may be beneficial for subsequent contraction of the myocardium. Changes in Healthy Adults Yingchoncharoen T et al 21 showed that systolic blood pressure was an important determinant of myocardial strain. Conditions of increased afterload have a negative impact on strain. MW is emerging as an alternative tool for studying LV systolic function because it incorporates both deformation and load into its values. Russell et al 4 demonstrated that PSLs could predict LV performance in a noninvasive manner, deriving LV pressure curves from noninvasively acquired brachial artery cuff pressure. However, there are few reports on the use of MW combined with treadmill exercise stress echocardiography in healthy individuals, and its application remains to be explored. Galli et al 5 studied 115 healthy (mean age 36.3 years, 67% male) adults and reported that GWI and GCW were significantly higher in women at rest ( p < 0.05); however, there was no significant difference in GWE between the sexes. Manganaro et al 6 studied 226 healthy adults [mean age (45 ± 13) years, 38% male]. They found that only the GWE of men at rest was significantly lower than that of women. In our study, only the GWE of men was significantly lower than that of women after exercise, and other global MW parameters showed no significant difference either at rest or load. Previous studies and the present study have shown that global MW parameters are consistent between sexes at rest, while this study further shows that these parameters are consistent after exercise. The differences in cardiac chamber and great arterial dimensions between the sexes are largely attributable to variations in body size. 22 In the present study, many of the parameters were significantly higher in men than in women, which suggests that it is important to take into account the impacts of sex. ΔGLS is significantly higher in men, but it is similar between the sexes after adjustment for BSA. 23 In this study, MW reserve was not significantly different, although ΔGLS was higher in men. This demonstrated that the MW reserve was more stable than ΔGLS, which is less affected by sex. MW Changes in HFpEF Patients D'Andrea A et al 24 reported that the global MW parameters of HFpEF patients were significantly lower than those of healthy individuals at rest or at load, consistent with our results. Our study also found that the MW reserve parameters of HFpEF patients were significantly lower than those of healthy adults. Previous studies and the present study have shown that LV myocardial function is impaired in HFpEF patients. MW analysis could provide incremental information in the setting of HFpEF patients. The Relationship Between GWE and ESL in Healthy Adults When the left ventricle pressure rises during early systole, myocardial fibres with reduced contractility tend to stretch instead of shorten. This interval is known as the duration of ESL. It has been hypothesized that ESL occurs because of heterogeneity in the contractility profile of myocardial segments, thus representing an early marker of myocardial dysfunction. 25 ESL may be useful in the diagnosis of significant coronary artery disease and may be correlated with the final infarct size after myocardial infarction. 26,27 Prinzen FW et al 28 reported that early activated regions start to shorten before the aortic valve opens, thereby stretching later activated regions in patients with left bundle branch block. This early systolic stretching forces the late-activated regions to contract more forcefully due to the local Frank–Starling effect. At the same time, some studies have found that ESL is also present in some healthy adults without heart disease. 25,26 Our study found that ESL occurs in healthy adults both at rest and during load. The longitudinal speckle-tracking curve reveals that the contractile strain direction is negative and the stretched strain direction is positive. The myocardial strain during ESL is positive, and the maximum value of positive strain during this duration is PPS. According to Russell's theory, MW is calculated from strain and pressure, and the work done by myocardial stretching during the systole phase is WW. Therefore, the myocardial work during ESL is calculated as WW. 4 Our study also found that PPS increased after exercise in healthy adults. As a result, previous studies and our study have found an increase in GWW and a decrease in GWE after loading in healthy adults, but how can this occur, and why could this happen? 7 We further found that PPS was independently associated with GWW both at rest and under load. Therefore, we suggest that myocardial work during ESL should not be calculated as WW. In contrast, ESL is beneficial for myocardial work in healthy adults. During the early systole phase, the myocardium stretches first and then contracts, probably to make the myocardium contract more powerfully. However, there has been little research on this problem, so further exploration in larger samples is needed. Limitations This study reflects a single-centre experience with a moderate sample size. We will expand the sample in the future to investigate the differences in MW parameters between different age groups. Second, the image quality dependency inherent to the technique of speckle tracking echocardiography was amplified after exercise. Concurrently, faster heart rate reduces the temporal resolution and strain accuracy, though none of the subjects were excluded because of inadequate imaging. Third, in future studies, the presence of symptoms in HFpEF patients, cardiovascular risk factors, and increased BNP and MW reserve parameters should be combined to study these patients in more depth. CONCLUSION MW parameters were little affected by sex in healthy adults. The decrease in MW parameters in HFpEF patients could provide helpful information on myocardial function in this disease setting. GWE decreased in healthy adults after exercise because of increased GWW, and PPS was independently associated with GWW both at rest and under load, suggesting that ESL may be beneficial for the later contraction of the myocardium and that myocardial work during ESL duration should not be calculated as WW. Declarations Acknowledgments This work was supported by a research grant from the Science and Technology Department of Sichuan Province Project (grant number: 23NSFSC0118). Author contributions LH: Writing-Original Draft, Formal analysis. LY: Writing-Review&Editing. HZ, QZ, GD: participants collection.CL, YD:Writing-Review&Editing.LY: Supervison; Validation. YW: Supervison; Funding acquisition; Writing-Review&Editing, Formal analysis. All authors reviewed the manuscript. 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Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation. Echocardiography. 2021;38(10):1711-1721. doi:10.1111/echo.15194. Clemmensen TS, Eiskjær H, Mikkelsen F, et al. Left Ventricular Pressure-Strain-Derived Myocardial Work at Rest and during Exercise in Patients with Cardiac Amyloidosis. J Am Soc Echocardiogr. 2020;33(5):573-582. doi:10.1016/j.echo.2019.11.018. Borrie A, Goggin C, Ershad S, et al. Noninvasive Myocardial Work Index: Characterizing the Normal and Ischemic Response to Exercise. J Am Soc Echocardiogr. 2020 Oct;33(10):1191-1200. doi: 10.1016/j.echo.2020.05.003. Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(1):18-28. doi:10.1093/eurjhf/hfq121. Pieske B, Tschöpe C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) Eur Heart J. 2019;40(40):3297-3317. doi:10.1093/eurheartj/ehz641. Daros CB, Ciampi Q, Cortigiani L, et al. Coronary Flow, Left Ventricular Contractile and Heart Rate Reserve in Non-Ischemic Heart Failure. J Clin Med. 2021;10:15. doi:10.3390/jcm 10153405. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14. doi:10.1016/j.echo.2014.10.003. Pugliese NR, DE Biase N, Balletti A, et al. Characterization of hemodynamic and metabolic abnormalities in the heart failure spectrum: the role of combined cardiopulmonary and exercise echocardiography stress test. Minerva Cardiol Angiol. 2022;70(3):370-384. doi:10.23736/S2724-5683.21.05743-4. Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr. 2004;17(6):630-633. doi:10.1016/j.echo.2004.02.011. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105(4):539-542. doi:10.1161/hc0402.102975. Brainin P, Biering-Sørensen T, Jensen MT, et al. Prognostic Value of Early Systolic Lengthening by Strain Imaging in Type 2 Diabetes. J Am Soc Echocardiogr. 2021;34(2):127-135. doi:10.1016/j.echo.2020.09.008. Pellikka PA, Arruda-Olson A, Chaudhry FA, et al. Guidelines for Performance, Interpretation, and Application of Stress Echocardiography in Ischemic Heart Disease: From the American Society of Echocardiography. J Am Soc Echocardiogr. 2020;33(1):1-41.e8. doi:10.1016/j.echo.2019.07.001. Mahfouz RA, El Zayat A, Yousry A. Left ventricular restrictive filling pattern and the presence of contractile reserve in patients with low-flow/low-gradient severe aortic stenosis. Echocardiography. 2015;32(1):65–70. doi:10.1111/echo.12586. Yingchoncharoen T, Agarwal S, Popović ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr. 2013;26(2):185-191. doi:10.1016/j.echo.2012.10.008. Yao GH, Deng Y, Liu Y, et al. Echocardiographic measurements in normal chinese adults focusing on cardiac chambers and great arteries: a prospective, nationwide, and multicenter study. J Am Soc Echocardiogr. 2015;28(5):570-579. doi:10.1016/j.echo.2015.01.02. Wang Y, Li W, Zhang H, et al. Echocardiographic Normal Reference of Left Ventricular Contractile Reserve During Treadmill Exercise Stress Echocardiography in Healthy Chinese Adults - New Non-Sex-Specific Parameter for Left Ventricular Contractile Reserve Evaluation. Int J Gen Med. 2021;14:7089-7098. Published 2021 Oct 23. doi:10.2147/IJGM.S334400. D'Andrea A, Ilardi F, D'Ascenzi F, et al. Impaired myocardial work efficiency in heart failure with preserved ejection fraction. Eur Heart J Cardiovasc Imaging. 2021;22(11):1312-1320. doi:10.1093/ehjci/jeab153. Smedsrud MK, Sarvari S, Haugaa KH, et al. Duration of myocardial early systolic lengthening predicts the presence of significant coronary artery disease. J Am Coll Cardiol. 2012;60(12):1086-1093. doi:10.1016/j.jacc.2012.06.022. Brainin P, Biering-Sørensen SR, Møgelvang R, Jensen JS, Biering-Sørensen T. Duration of early systolic lengthening: prognostic potential in the general population. Eur Heart J Cardiovasc Imaging. 2020;21(11):1283-1290. doi:10.1093/ehjci/jez262. Minamisawa M, Koyama J, Kozuka A, et al. Duration of myocardial early systolic lengthening for diagnosis of coronary artery disease. Open Heart. 2018;5(2):e000896. Published 2018 Dec 4. doi:10.1136/openhrt-2018-000896. Prinzen FW, Lumens J. Investigating myocardial work as a CRT response predictor is not a waste of work. Eur Heart J. 2020;41(39):3824-3826. doi:10.1093/eurheartj/ehaa677. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3906031","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":271079416,"identity":"e265d960-ee9f-40e7-ad2a-aa0363e07eeb","order_by":0,"name":"Liwei Huang","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Liwei","middleName":"","lastName":"Huang","suffix":""},{"id":271079417,"identity":"d1861a29-261b-4271-94bf-7de4e193a6dc","order_by":1,"name":"Luwei Ye","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Luwei","middleName":"","lastName":"Ye","suffix":""},{"id":271079418,"identity":"48012879-df90-4c1a-aebb-b4b30232476c","order_by":2,"name":"Hongmei Zhang","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongmei","middleName":"","lastName":"Zhang","suffix":""},{"id":271079419,"identity":"58152d38-e6af-4dd9-83c4-e59428fd09e3","order_by":3,"name":"Qingfeng Zhang","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qingfeng","middleName":"","lastName":"Zhang","suffix":""},{"id":271079420,"identity":"4c9d426e-5f69-45c6-9dd3-8f24c7a82953","order_by":4,"name":"Geqi Ding","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Geqi","middleName":"","lastName":"Ding","suffix":""},{"id":271079421,"identity":"61a492e1-54b0-4f6b-aed7-b59c1c5b4ddf","order_by":5,"name":"Chunmei Li","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chunmei","middleName":"","lastName":"Li","suffix":""},{"id":271079422,"identity":"eae41a3f-d9ba-4a8b-946b-fe55476214be","order_by":6,"name":"Yan Deng","email":"","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's 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Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYNACgwOMfeyNjQ8+kKSljedws+EMEqwBapFIb5PmIMr842cPv+YpuCPbJvmwQZqBwU5Ot4GQljN5adY8Bs+M26QTG4wLGJKNzQ4Q0GJ2IMfMmMfgcCJIS/IMhgOJ2whqOf8GqkXyYMNhHqK03MgxfgzWIsHY2EyUFvsbb8wY5xgcNm7jSWxmnGFAhF8k+3OMP7z5c1i2n/348x8fKuzkCGoBAjYpHjjbgLByEGD++IM4haNgFIyCUTBSAQCiTEfvSxftYgAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Cardiovascular Ultrasound and Non-invasive Cardiology, Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yi","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-01-28 14:32:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3906031/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3906031/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50749868,"identity":"5f41aae5-a24b-4aba-aa9e-cebd246692c4","added_by":"auto","created_at":"2024-02-06 17:27:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":185497,"visible":true,"origin":"","legend":"\u003cp\u003eExample of normal adults with decreased GWE and increased PPS after exercise. A bull’s-eye plot of myocardial work shows GWE is 98% at rest (A) and 95% after exercise (C). Time-strain curve during one cardiac cycle (white dotted line) shows PPS during early systole phase at rest is 0% (B) and 1.09% after exercise (D).\u003c/p\u003e\n\u003cp\u003eGWI, global constructive work index; GWE, global work efficiency; GLS, global longitudinal strain; HR, heart rate; BP, blood pressure; PPS, peak positive strain; post-ex, immediately after exercise.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3906031/v1/ecc419777e62b59080122a6e.png"},{"id":50749866,"identity":"e59deb34-2b57-41fd-9919-34d6b1a46d87","added_by":"auto","created_at":"2024-02-06 17:27:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":74693,"visible":true,"origin":"","legend":"\u003cp\u003eMW parameters in normal adults compared with HFpEF patients. GWI, GCW and GWE are significantly reduced in HFpEF than normal.\u003c/p\u003e\n\u003cp\u003eGWI, global constructive work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3906031/v1/55482781cddb6adc6d19dfd0.png"},{"id":50749867,"identity":"94a6f0a6-7603-49f2-b2a4-818e4c7ab7df","added_by":"auto","created_at":"2024-02-06 17:27:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94015,"visible":true,"origin":"","legend":"\u003cp\u003eThe relationship between PPS and GWW in healthy adults. PPS was independently associated with GWW (A:rest, B:load) and HFpEF patients (C:rest, D:load).\u003c/p\u003e\n\u003cp\u003ePPS, peak positive strain; GWW, global wasted work; post-ex, immediately after exercise.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3906031/v1/b2d6d1a8df0aac250b69bc69.png"},{"id":52661234,"identity":"50dd86da-07f5-4841-a3d1-1c901a0c2825","added_by":"auto","created_at":"2024-03-14 07:59:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":717806,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3906031/v1/66d0dcd2-a4db-47d7-8390-d812e66f2c28.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Stress Echocardiographic Myocardial Work in Healthy Adults and Heart Failure with Preserved Ejection Fraction Patients and Doubt about Early Systolic Lengthening","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe assessment of myocardial function plays an important role in routine clinical practice. The analysis of myocardial strain adds information on cardiac performance over that gained from traditional parameters of left ventricular (LV) systolic function\u003csup\u003e1\u003c/sup\u003e. However, strain does not reflect myocardial work (MW) or oxygen consumption, as this parameter is not adjusted for loading conditions. MW has been suggested as an alternative tool for studying LV myocardial systolic function, because it incorporates both deformation and load into the analysis. MW was initially calculated using invasive pressure measurements, which limited its widespread use in clinical practice.\u003csup\u003e2,3\u003c/sup\u003e Russell et al\u003csup\u003e4\u003c/sup\u003e proposed a method for the non-invasive estimation of regional and global MW from pressure\u0026ndash;strain loop (PSL) analysis. Some studies have used this technique to analyse the reference ranges of MW in healthy adults.\u003csup\u003e5,6\u003c/sup\u003e The technique has also been used to analyse left ventricular systolic function in patients with coronary artery disease and cardiac amyloidosis, with reasonable results\u003csup\u003e7\u0026ndash;9\u003c/sup\u003e. However, studies of MW parameters and their differences between sexes during treadmill exercise stress echocardiography in healthy individuals are rare. Borrie A\u0026rsquo;s study revealed that global work efficiency (GWE) decreased after exercise in healthy individuals, but their sample was small, and they did not study sex differences.\u003csup\u003e10\u003c/sup\u003e There are no studies on the factors influencing the decrease in GWE after exercise. Heart failure with preserved ejection fraction (HFpEF) is a growing health problem.\u003csup\u003e11\u003c/sup\u003e The role of systolic dysfunction despite preserved LV ejection fraction has not been well characterized, and no studies about MW reserve during exercise have been done in HFpEF patients. The aims of this study was to characterize the changes in MW associated with rest and load conditions in healthy adults and HFpEF patients and to explore the factors related to the decrease in GWE after exercise.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003eHealthy adult group\u003c/h2\u003e \u003cp\u003eWith a cross-sectional study design, we prospectively enrolled 192 healthy volunteers from May 2018 to December 2023. The healthy participants had blood pressure values within the healthy reference ranges, had healthy resting and stress electrocardiographic results, had negative coronary CT or angiography results, were not taking any medications, were non-smokers, and had no history of hypertension, diabetes, or cardiac diseases. According to these criteria, 25 subjects were excluded for having electrocardiographic abnormalities (5 subjects), metabolic syndrome (4 subjects) or poor acoustic windows (16 subjects).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eHFpEF group\u003c/h2\u003e \u003cp\u003eWe enrolled 60 consecutive patients with left ventricular ejection fraction\u0026thinsp;\u0026ge;\u0026thinsp;50%, determined by an intermediate risk of 2\u0026ndash;4 points on the HFA-PEFF scale during the noninvasive work-up. \u003csup\u003e12\u003c/sup\u003e The recruitment period ran from May 2018 to December 2023. The exclusion criteria were as follows: unstable angina or acute myocardial infarction; more than mild aortic valve disease; prosthetic heart valve or prosthetic ring; severe mitral annular calcification; severe (\u0026gt;\u0026thinsp;3+) mitral regurgitation; significant (\u0026gt;\u0026thinsp;50% stenosis) coronary artery disease according to coronary angiography; uncontrolled hypertension; severe chronic obstructive pulmonary disease; any contraindication to physical activity (e.g., gonarthrosis or symptomatic peripheral artery disease); inability to exercise; and poor acoustic window. According to these criteria, 22 patients were excluded for significant valvular heart disease (5 patients), severe chronic obstructive pulmonary disease (5 patients), contraindication for physical activity (3 patients), unstable angina (3 patients), or a poor acoustic window (6 patients).\u003c/p\u003e \u003cp\u003eAll subjects underwent clinical examinations, resting 12-lead electrocardiography, and comprehensive transthoracic echocardiography at rest and immediately after maximal treadmill stress testing. The clinical examination included measurements of height, weight, body mass index (BMI) and resting blood pressure. Body surface area (BSA) was calculated according to the DuBois formula.\u003csup\u003e13\u003c/sup\u003e The healthy adults were divided into male and female subgroups. Every subject was \u0026gt;\u0026thinsp;18 years of age and was included after providing informed written consent according to the principles of the Declaration of Helsinki. The study was conducted after approval from the local scientific ethics committee.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiographic Data Acquisition\u003c/h2\u003e \u003cp\u003eAll subjects underwent standard transthoracic echocardiography using a commercially available Vivid E95 ultrasound system equipped with an M5S 3.5-MHz transducer (GE Vivid E95, Vingmed Ultrasound, Horten, Norway) at rest and immediately after exercise in the left lateral decubitus position. Electrocardiogram-triggered echocardiographic data were acquired and digitally stored in a cine-loop format for offline analysis with EchoPAC (EchoPAC 203, General Electric Vingmed Ultrasound). At rest, all subjects underwent a comprehensive two-dimensional echocardiographic assessment in accordance with current guidelines.\u003csup\u003e14\u003c/sup\u003e LV end-diastolic (LVEDV) and end-systolic volumes (LVESV) were measured in the apical two- and four-chamber views. LVEF was calculated using the Simpson biplane method.\u003csup\u003e15\u003c/sup\u003e LVEDV and LVESV were indexed to BSA (presented as the LVEDVI and LVESVI, respectively).\u003c/p\u003e \u003cp\u003eThe magnitude of LV global longitudinal strain (GLS) was obtained using automated function imaging (AFI) in standard two-dimensional cine loops with a frame rate\u0026thinsp;\u0026gt;\u0026thinsp;70 frames/sec.\u003csup\u003e16\u003c/sup\u003e The regional speckle area of interest was adjusted manually for optimal tracking results. GLS was calculated at the time of systole when the value peaked using a 17-myocardial segment model.\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe principles for estimating LV pressure and work have been described.\u003csup\u003e4\u003c/sup\u003e In this method, a previously generated empiric reference curve for LV pressure was utilized. The reference curve was individualized by scaling the amplitude using measured systolic cuff pressure and warping it in time by aligning the valvular aorta and opening and closing the mitral valve, as assessed by echocardiography. The constructive and wasted work was measured at the segmental and global levels based on this pressure\u0026ndash;strain curve. Constructive work (CW) included the sum of work performed during shortening in systole and the negative work performed during lengthening in the isovolumetric relaxation phase. The myocardial work index (WI) meant the total work within the area of the LV pressure\u0026ndash;strain loop calculated from mitral valve closure to mitral valve opening. Wasted work (WW) comprised negative systolic work due to systolic lengthening and the work of shortening in the isovolumic relaxation phase. Myocardial work efficiency (WE) was calculated as the ratio of CW/(CW\u0026thinsp;+\u0026thinsp;WW). The LV global constructive work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were calculated as the average of the myocardial work index, constructive work, wasted work and work efficiency of all segmental values.\u003c/p\u003e \u003cp\u003eAll the MW parameters were analysed both at rest and after exercise. All echocardiographic parameters were averaged over three consecutive cardiac cycles. From the longitudinal speckle-tracking curve, we obtained the peak positive strain (PPS) during the early systole phase.\u003csup\u003e18\u003c/sup\u003e If no early systolic lengthening (ESL) occurred in the early systole phase, PPS was set to zero. If ESL occurred, the maximum value of positive strain during the ESL duration was PPS (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The MW reserve was calculated as the difference in GWI, GCW, GWW, and GWE between the resting and postexercise values (presented as ΔGWI, ΔGCW, ΔGWW and ΔGWE, respectively).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eExercise Protocol\u003c/h2\u003e \u003cp\u003eAll subjects performed a symptom-limited treadmill (TMX-425, Full Vision, Inc., Kansas) exercise test using standard Bruce protocols.\u003csup\u003e19\u003c/sup\u003e They were encouraged to exercise until exhaustion. A baseline 12-lead electrocardiogram (ECG) and blood pressure were acquired and repeated at 2-min intervals during the exercise examination, at peak exertion, and after exercise. The maximum exercise capacity of metabolic equivalents (METs) was recorded, where 1 MET\u0026thinsp;=\u0026thinsp;3.5 mL/kg/min oxygen consumption was estimated based on the protocol, speed, and grade achieved.\u003csup\u003e20\u003c/sup\u003e Exercise duration and the ratio of peak HR to target HR (according to the 220\u0026thinsp;\u0026minus;\u0026thinsp;age formula) were also automatically recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS version 23.0 (SPSS, Armonk, NY). The parameters with a normal distribution were tested by Student\u0026rsquo;s T test, and those with a nonnormal distribution were tested by a nonparametric test. Normally distributed data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Skewed data are presented as median (interquartile range [IQR]). Histograms and Q‒Q plots were used to check continuous values for normality. Continuous variables were compared between groups using the unpaired Student\u0026rsquo;s t test. The 95% confidence intervals were calculated as \u0026plusmn;\u0026thinsp;1.96 SDs from the mean. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Correlations between two parameters were calculated as Pearson\u0026rsquo;s correlation coefficient. Stepwise multiple regression analyses were used to determine the independent factors correlated with GWWrest and GWWpost-ex.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eIntra- and Interobserver Variability\u003c/h2\u003e \u003cp\u003eGWI analyses at baseline and immediately after exercise were repeated in 10 randomly selected patients at least 4 weeks after the initial analysis by the original investigator and by a second investigator who were both blinded to the original measurements to assess intraobserver and interobserver variability. The intraclass correlation coefficient (ICC) was calculated.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics and Conventional Echocardiographic Parameters\u003c/h2\u003e \u003cp\u003eResting and treadmill exercise stress echocardiography (SE) were performed in 167 healthy adults (55% women; aged 46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8 years; age range, 22\u0026ndash;75 years) and 38 HFpEF patients (54% women; aged 51.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9 years; age range, 30\u0026ndash;77 years). The clinical characteristics of the healthy and HFpEF patients are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Men had higher BSA and higher systolic blood pressure (SBP) than women (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). HFpEF patients had higher SBP than healthy patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There was no significant difference in EF at rest between the sexes, but EF was significantly higher in men after exercise (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There was no significant difference in EF at rest between the HFpEF patients and healthy controls, while EF was significantly lower in the HFpEF group after exercise (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of population and conventional echocardiographic parameters in normal\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal/167\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale/76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale/91\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e46.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e47.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e163.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e169.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e158.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e68.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody surface area (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e21.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRest\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e91\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e92\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e91\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e127\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e128\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e118\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e73\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeak exercise period\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e160\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e167\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e159\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e170\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e177\u0026thinsp;\u0026plusmn;\u0026thinsp;23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e160\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e34.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExercise time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eHR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; EDVI, end diastolic volume index; ESVI, end systolic volume index; EF, ejection fraction; METs, metabolic equivalents.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of population and conventional echocardiographic parameters in normal compared with HFpEF\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal/167\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHFpEF/38\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e51.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e163.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e162.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.623\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e64.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody surface area (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e24.15\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRest\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e91\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e87\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e127\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e135\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e73\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e86\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeak exercise period\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e160\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e133\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e170\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e187\u0026thinsp;\u0026plusmn;\u0026thinsp;29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e46.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESVI (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF (mL/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExercise time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eHR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; METs, metabolic equivalents; EDVI, end diastolic volume index; ESVI, end systolic volume index; EF, ejection fraction.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eMyocardial Work Parameters\u003c/h2\u003e \u003cp\u003eGWI, GCW and GWW increased but GWE decreased in the healthy group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There was no significant difference in any of the global MW parameters between the sexes at rest. GWE was significantly higher in women after exercise (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There were no significant differences in MW reserve between the sexes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMW parameters at rest and post-exercise in normal adults of different sexes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal/167\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale/76\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale/91\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRest\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWI (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1930\u0026thinsp;\u0026plusmn;\u0026thinsp;421\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1928\u0026thinsp;\u0026plusmn;\u0026thinsp;382\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1975\u0026thinsp;\u0026plusmn;\u0026thinsp;391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2298\u0026thinsp;\u0026plusmn;\u0026thinsp;410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2289\u0026thinsp;\u0026plusmn;\u0026thinsp;408\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2326\u0026thinsp;\u0026plusmn;\u0026thinsp;408\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69(40\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (43\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78(48\u0026ndash;104)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.498\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWE (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.877\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeak exercise period\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWI (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2720\u0026thinsp;\u0026plusmn;\u0026thinsp;369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2624\u0026thinsp;\u0026plusmn;\u0026thinsp;389\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2753\u0026thinsp;\u0026plusmn;\u0026thinsp;401\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.348\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3520\u0026thinsp;\u0026plusmn;\u0026thinsp;680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3522\u0026thinsp;\u0026plusmn;\u0026thinsp;831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3519\u0026thinsp;\u0026plusmn;\u0026thinsp;636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (120\u0026ndash;339)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220 (155\u0026ndash;392)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e203 (116\u0026ndash;310)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWE (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GLS(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWI(mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e798\u0026thinsp;\u0026plusmn;\u0026thinsp;319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e815\u0026thinsp;\u0026plusmn;\u0026thinsp;747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e785\u0026thinsp;\u0026plusmn;\u0026thinsp;697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.817\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GCW(mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1125\u0026thinsp;\u0026plusmn;\u0026thinsp;380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1059\u0026thinsp;\u0026plusmn;\u0026thinsp;391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1147\u0026thinsp;\u0026plusmn;\u0026thinsp;375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.624\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWW(mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (68\u0026ndash;284)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e173 (82\u0026ndash;324)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132 (47\u0026ndash;228)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.414\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWE(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.9(-4.9 to 1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4 (-7.5 to -1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.0(-5.0 to -0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGLS, global longitudinal strain; GWI, global constructive work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency; △, change from rest to peak.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGWE decreased in the HFpEF group after exercise (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). GWE was significantly lower in HFpEF patients than in healthy individuals both at rest and after exercise (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). MW reserve decreased significantly in HFpEF patients compared with healthy controls (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). PPS increased in both the healthy and HFpEF groups after exercise (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMW parameters at rest and post-exercise in normal adults compared with HFpEF\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal/167\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHFpEF/38\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRest\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWI (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1930\u0026thinsp;\u0026plusmn;\u0026thinsp;421\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1660\u0026thinsp;\u0026plusmn;\u0026thinsp;305\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2298\u0026thinsp;\u0026plusmn;\u0026thinsp;410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2055\u0026thinsp;\u0026plusmn;\u0026thinsp;403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69(40\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e199\u0026thinsp;\u0026plusmn;\u0026thinsp;87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWE (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePeak exercise period\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWI (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2720\u0026thinsp;\u0026plusmn;\u0026thinsp;369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2330\u0026thinsp;\u0026plusmn;\u0026thinsp;378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3520\u0026thinsp;\u0026plusmn;\u0026thinsp;680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3098\u0026thinsp;\u0026plusmn;\u0026thinsp;650\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (120\u0026ndash;339)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e359\u0026thinsp;\u0026plusmn;\u0026thinsp;89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWE (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPS (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GLS (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWI (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e798\u0026thinsp;\u0026plusmn;\u0026thinsp;319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e655\u0026thinsp;\u0026plusmn;\u0026thinsp;320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GCW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1125\u0026thinsp;\u0026plusmn;\u0026thinsp;380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e988\u0026thinsp;\u0026plusmn;\u0026thinsp;290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWW (mmHg%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (68\u0026ndash;284)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170\u0026thinsp;\u0026plusmn;\u0026thinsp;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e△GWE(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.9 (-4.9 to 1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-5 (-7.7 to 1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eGLS, global longitudinal strain; GWI, global constructive work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency;△, change from rest to peak; PPS, peak positive strain.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eIntra- and Interobserver Variability\u003c/h2\u003e \u003cp\u003eThe ICCs for intraobserver variability were 0.92 for GWI at rest and 0.89 for GWI after exercise. The ICCs for interobserver variability were 0.91 for GWI at rest and 0.87 for GWI after exercise (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInter- and intra-observer variability of GWI\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eIntra-observer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003eInter-observer\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBias\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%LOA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eICC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eBias\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95%LOA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWIrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.12 to 3.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-3.10 to 3.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGWIpost-ex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.51 to 1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-1.33 to 1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eGWI, global constructive work index; ICC, interclass correlation coefficient; LOA, limits of agreement; post-ex, immediately after exercise.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eThe Relationship Between PPS and GWW in Healthy Adults\u003c/h2\u003e \u003cp\u003eStepwise multiple regression analysis demonstrated that PPSrest (r\u0026thinsp;=\u0026thinsp;0.77, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and PPSpost-ex (r\u0026thinsp;=\u0026thinsp;0.72, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were independently associated with GWWrest and GWWpost-ex in healthy individuals. PPSrest (r\u0026thinsp;=\u0026thinsp;0.74, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and PPSpost-ex (r\u0026thinsp;=\u0026thinsp;0.62, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were also independently associated with GWWrest and GWWpost-ex in HFpEF patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe main findings of the present study can be summarized as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) there were no significant differences in most of the MW parameters between males and females, which indicates that MW is a stable parameter for evaluating LV function regardless of sex; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) the decrease in MW parameters in HFpEF patients could provide incremental information on myocardial function in HFpEF patients; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) GWE decreased after exercise in healthy adults, and PPS was independently associated with GWW both at rest and during load, suggesting that ESL may be beneficial for subsequent contraction of the myocardium.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eChanges in Healthy Adults\u003c/h2\u003e \u003cp\u003eYingchoncharoen T et al\u003csup\u003e21\u003c/sup\u003e showed that systolic blood pressure was an important determinant of myocardial strain. Conditions of increased afterload have a negative impact on strain. MW is emerging as an alternative tool for studying LV systolic function because it incorporates both deformation and load into its values. Russell et al\u003csup\u003e4\u003c/sup\u003e demonstrated that PSLs could predict LV performance in a noninvasive manner, deriving LV pressure curves from noninvasively acquired brachial artery cuff pressure. However, there are few reports on the use of MW combined with treadmill exercise stress echocardiography in healthy individuals, and its application remains to be explored. Galli et al\u003csup\u003e5\u003c/sup\u003e studied 115 healthy (mean age 36.3 years, 67% male) adults and reported that GWI and GCW were significantly higher in women at rest (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05); however, there was no significant difference in GWE between the sexes. Manganaro et al\u003csup\u003e6\u003c/sup\u003e studied 226 healthy adults [mean age (45\u0026thinsp;\u0026plusmn;\u0026thinsp;13) years, 38% male]. They found that only the GWE of men at rest was significantly lower than that of women. In our study, only the GWE of men was significantly lower than that of women after exercise, and other global MW parameters showed no significant difference either at rest or load. Previous studies and the present study have shown that global MW parameters are consistent between sexes at rest, while this study further shows that these parameters are consistent after exercise.\u003c/p\u003e \u003cp\u003eThe differences in cardiac chamber and great arterial dimensions between the sexes are largely attributable to variations in body size.\u003csup\u003e22\u003c/sup\u003e In the present study, many of the parameters were significantly higher in men than in women, which suggests that it is important to take into account the impacts of sex. ΔGLS is significantly higher in men, but it is similar between the sexes after adjustment for BSA.\u003csup\u003e23\u003c/sup\u003e In this study, MW reserve was not significantly different, although ΔGLS was higher in men. This demonstrated that the MW reserve was more stable than ΔGLS, which is less affected by sex.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMW Changes in HFpEF Patients\u003c/h2\u003e \u003cp\u003eD'Andrea A et al\u003csup\u003e24\u003c/sup\u003e reported that the global MW parameters of HFpEF patients were significantly lower than those of healthy individuals at rest or at load, consistent with our results. Our study also found that the MW reserve parameters of HFpEF patients were significantly lower than those of healthy adults. Previous studies and the present study have shown that LV myocardial function is impaired in HFpEF patients. MW analysis could provide incremental information in the setting of HFpEF patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eThe Relationship Between GWE and ESL in Healthy Adults\u003c/h2\u003e \u003cp\u003eWhen the left ventricle pressure rises during early systole, myocardial fibres with reduced contractility tend to stretch instead of shorten. This interval is known as the duration of ESL. It has been hypothesized that ESL occurs because of heterogeneity in the contractility profile of myocardial segments, thus representing an early marker of myocardial dysfunction.\u003csup\u003e25\u003c/sup\u003e ESL may be useful in the diagnosis of significant coronary artery disease and may be correlated with the final infarct size after myocardial infarction.\u003csup\u003e26,27\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePrinzen FW et al\u003csup\u003e28\u003c/sup\u003e reported that early activated regions start to shorten before the aortic valve opens, thereby stretching later activated regions in patients with left bundle branch block. This early systolic stretching forces the late-activated regions to contract more forcefully due to the local Frank\u0026ndash;Starling effect. At the same time, some studies have found that ESL is also present in some healthy adults without heart disease.\u003csup\u003e25,26\u003c/sup\u003e Our study found that ESL occurs in healthy adults both at rest and during load. The longitudinal speckle-tracking curve reveals that the contractile strain direction is negative and the stretched strain direction is positive. The myocardial strain during ESL is positive, and the maximum value of positive strain during this duration is PPS. According to Russell's theory, MW is calculated from strain and pressure, and the work done by myocardial stretching during the systole phase is WW. Therefore, the myocardial work during ESL is calculated as WW.\u003csup\u003e4\u003c/sup\u003e Our study also found that PPS increased after exercise in healthy adults. As a result, previous studies and our study have found an increase in GWW and a decrease in GWE after loading in healthy adults, but how can this occur, and why could this happen?\u003csup\u003e7\u003c/sup\u003e We further found that PPS was independently associated with GWW both at rest and under load. Therefore, we suggest that myocardial work during ESL should not be calculated as WW. In contrast, ESL is beneficial for myocardial work in healthy adults. During the early systole phase, the myocardium stretches first and then contracts, probably to make the myocardium contract more powerfully. However, there has been little research on this problem, so further exploration in larger samples is needed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study reflects a single-centre experience with a moderate sample size. We will expand the sample in the future to investigate the differences in MW parameters between different age groups. Second, the image quality dependency inherent to the technique of speckle tracking echocardiography was amplified after exercise. Concurrently, faster heart rate reduces the temporal resolution and strain accuracy, though none of the subjects were excluded because of inadequate imaging. Third, in future studies, the presence of symptoms in HFpEF patients, cardiovascular risk factors, and increased BNP and MW reserve parameters should be combined to study these patients in more depth.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eMW parameters were little affected by sex in healthy adults. The decrease in MW parameters in HFpEF patients could provide helpful information on myocardial function in this disease setting. GWE decreased in healthy adults after exercise because of increased GWW, and PPS was independently associated with GWW both at rest and under load, suggesting that ESL may be beneficial for the later contraction of the myocardium and that myocardial work during ESL duration should not be calculated as WW.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by a research grant from the Science and Technology Department of Sichuan Province Project (grant number: 23NSFSC0118).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLH: Writing-Original Draft, Formal analysis. LY: Writing-Review\u0026amp;Editing. HZ, QZ, GD: participants collection.CL, YD:Writing-Review\u0026amp;Editing.LY: Supervison; Validation. \u0026nbsp;YW: Supervison; Funding acquisition; Writing-Review\u0026amp;Editing, Formal analysis. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eErsb\u0026oslash;ll M, Valeur N, Mogensen UM, et al. Prediction of all-cause mortality and heart failure admissions from global left ventricular longitudinal strain in patients with acute myocardial infarction and preserved left ventricular ejection fraction. J Am Coll Cardiol. 2013;61(23):2365-2373. doi:10.1016/j.jacc.2013.02.061.\u003c/li\u003e\n \u003cli\u003eTyberg JV, Forrester JS, Wyatt HL, Goldner SJ, Parmley WW, Swan HJ. An analysis of segmental ischemic dysfunction utilizing the pressure-length loop. Circulation.1974;49(4):748-754. doi:10.1161/01.cir.49.4.748.\u003c/li\u003e\n \u003cli\u003eDelhaas T, Arts T, Prinzen FW, Reneman RS. Regional fibre stress-fibre strain area as an estimate of regional blood flow and oxygen demand in the canine heart. J Physiol. 1994;477 ( Pt 3)(Pt 3):481-496. doi:10.1113/jphysiol.1994.sp020209.\u003c/li\u003e\n \u003cli\u003eRussell K, Eriksen M, Aaberge L, et al. A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work. Eur Heart J. 2012;33(6):724-733. doi:10.1093/eurheartj/ehs016.\u003c/li\u003e\n \u003cli\u003eGalli E, John-Matthwes B, Rousseau C, Schnell F, Leclercq C, Donal E. Echocardiographic reference ranges for myocardial work in healthy subjects: A preliminary study. Echocardiography.2019;36(10):1814-1824. doi:10.1111/echo.14494.\u003c/li\u003e\n \u003cli\u003eManganaro R, Marchetta S, Dulgheru R, et al. Echocardiographic reference ranges for normal non-invasive myocardial work indices: results from the EACVI NORRE study. Eur Heart J Cardiovasc Imaging. 2019;20(5):582-590. doi:10.1093/ehjci/jey188.\u003c/li\u003e\n \u003cli\u003eLin J, Wu W, Gao L, et al. Global Myocardial Work Combined with Treadmill Exercise Stress to Detect Significant Coronary Artery Disease. J Am Soc Echocardiogr. 2022;35(3):247-257. doi:10.1016/j.echo.2021.10.009.\u003c/li\u003e\n \u003cli\u003eEdwards NFA, Scalia GM, Putrino A, et al. Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation. Echocardiography. 2021;38(10):1711-1721. doi:10.1111/echo.15194.\u003c/li\u003e\n \u003cli\u003eClemmensen TS, Eiskj\u0026aelig;r H, Mikkelsen F, et al. Left Ventricular Pressure-Strain-Derived Myocardial Work at Rest and during Exercise in Patients with Cardiac Amyloidosis. J Am Soc Echocardiogr. 2020;33(5):573-582. doi:10.1016/j.echo.2019.11.018.\u003c/li\u003e\n \u003cli\u003eBorrie A, Goggin C, Ershad S, et al. Noninvasive Myocardial Work Index: Characterizing the Normal and Ischemic Response to Exercise. J Am Soc Echocardiogr. 2020 Oct;33(10):1191-1200. doi: 10.1016/j.echo.2020.05.003.\u003c/li\u003e\n \u003cli\u003eLam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(1):18-28. doi:10.1093/eurjhf/hfq121.\u003c/li\u003e\n \u003cli\u003ePieske B, Tsch\u0026ouml;pe C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) Eur Heart J. 2019;40(40):3297-3317. doi:10.1093/eurheartj/ehz641.\u003c/li\u003e\n \u003cli\u003eDaros CB, Ciampi Q, Cortigiani L, et al. Coronary Flow, Left Ventricular Contractile and Heart Rate Reserve in Non-Ischemic Heart Failure. J Clin Med. 2021;10:15. doi:10.3390/jcm 10153405.\u003c/li\u003e\n \u003cli\u003eLang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14. doi:10.1016/j.echo.2014.10.003.\u003c/li\u003e\n \u003cli\u003ePugliese NR, DE Biase N, Balletti A, et al. Characterization of hemodynamic and metabolic abnormalities in the heart failure spectrum: the role of combined cardiopulmonary and exercise echocardiography stress test. Minerva Cardiol Angiol. 2022;70(3):370-384. doi:10.23736/S2724-5683.21.05743-4.\u003c/li\u003e\n \u003cli\u003eReisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr. 2004;17(6):630-633. doi:10.1016/j.echo.2004.02.011.\u003c/li\u003e\n \u003cli\u003eCerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105(4):539-542. doi:10.1161/hc0402.102975.\u003c/li\u003e\n \u003cli\u003eBrainin P, Biering-S\u0026oslash;rensen T, Jensen MT, et al. Prognostic Value of Early Systolic Lengthening by Strain Imaging in Type 2 Diabetes. J Am Soc Echocardiogr. 2021;34(2):127-135. doi:10.1016/j.echo.2020.09.008.\u003c/li\u003e\n \u003cli\u003ePellikka PA, Arruda-Olson A, Chaudhry FA, et al. Guidelines for Performance, Interpretation, and Application of Stress Echocardiography in Ischemic Heart Disease: From the American Society of Echocardiography. J Am Soc Echocardiogr. 2020;33(1):1-41.e8. doi:10.1016/j.echo.2019.07.001.\u003c/li\u003e\n \u003cli\u003eMahfouz RA, El Zayat A, Yousry A. Left ventricular restrictive filling pattern and the presence of contractile reserve in patients with low-flow/low-gradient severe aortic stenosis. Echocardiography. 2015;32(1):65\u0026ndash;70. doi:10.1111/echo.12586.\u003c/li\u003e\n \u003cli\u003eYingchoncharoen T, Agarwal S, Popović ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr. 2013;26(2):185-191. doi:10.1016/j.echo.2012.10.008.\u003c/li\u003e\n \u003cli\u003eYao GH, Deng Y, Liu Y, et al. Echocardiographic measurements in normal chinese adults focusing on cardiac chambers and great arteries: a prospective, nationwide, and multicenter study. J Am Soc Echocardiogr. 2015;28(5):570-579. doi:10.1016/j.echo.2015.01.02.\u003c/li\u003e\n \u003cli\u003eWang Y, Li W, Zhang H, et al. Echocardiographic Normal Reference of Left Ventricular Contractile Reserve During Treadmill Exercise Stress Echocardiography in Healthy Chinese Adults - New Non-Sex-Specific Parameter for Left Ventricular Contractile Reserve Evaluation. Int J Gen Med. 2021;14:7089-7098. Published 2021 Oct 23. doi:10.2147/IJGM.S334400.\u003c/li\u003e\n \u003cli\u003eD\u0026apos;Andrea A, Ilardi F, D\u0026apos;Ascenzi F, et al. Impaired myocardial work efficiency in heart failure with preserved ejection fraction. Eur Heart J Cardiovasc Imaging. 2021;22(11):1312-1320. doi:10.1093/ehjci/jeab153.\u003c/li\u003e\n \u003cli\u003eSmedsrud MK, Sarvari S, Haugaa KH, et al. Duration of myocardial early systolic lengthening predicts the presence of significant coronary artery disease. J Am Coll Cardiol. 2012;60(12):1086-1093. doi:10.1016/j.jacc.2012.06.022.\u003c/li\u003e\n \u003cli\u003eBrainin P, Biering-S\u0026oslash;rensen SR, M\u0026oslash;gelvang R, Jensen JS, Biering-S\u0026oslash;rensen T. Duration of early systolic lengthening: prognostic potential in the general population. Eur Heart J Cardiovasc Imaging. 2020;21(11):1283-1290. doi:10.1093/ehjci/jez262.\u003c/li\u003e\n \u003cli\u003eMinamisawa M, Koyama J, Kozuka A, et al. Duration of myocardial early systolic lengthening for diagnosis of coronary artery disease. Open Heart. 2018;5(2):e000896. Published 2018 Dec 4. doi:10.1136/openhrt-2018-000896.\u003c/li\u003e\n \u003cli\u003ePrinzen FW, Lumens J. Investigating myocardial work as a CRT response predictor is not a waste of work. Eur Heart J. 2020;41(39):3824-3826. doi:10.1093/eurheartj/ehaa677.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"heart failure with preserved ejection fraction, early systolic lengthening, myocardial work, exercise echocardiography, peak positive strain","lastPublishedDoi":"10.21203/rs.3.rs-3906031/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3906031/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe aims of this study were (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) to characterize myocardial work (MW) changes from rest to after exercise in healthy adults and heart failure patients with preserved ejection fraction (HFpEF), and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) to explore the factors influencing the decrease in global work efficiency (GWE) after exercise in healthy adults.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study enrolled 167 healthy adults and 38 HFpEF patients. All subjects underwent echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eGWE decreased after exercise in healthy adults. It was higher in women after exercise (women: 93% vs. men: 91%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). GWE was significantly lower after exercise in HFpEF patients (HFpEF: 85% vs. healthy: 92%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The peak positive strain (PPS) was independently associated with global wasted work (GWW) both in healthy adults and HFpEF patients (healthy adults: r\u0026thinsp;=\u0026thinsp;0.77, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 at rest; r\u0026thinsp;=\u0026thinsp;0.72, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 after exercise; HFpEF: r\u0026thinsp;=\u0026thinsp;0.74, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 at rest; and r\u0026thinsp;=\u0026thinsp;0.62, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 after exercise).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMW parameters were less affected by sex in healthy individuals. MW parameters were lower in HFpEF than healthy adults both at rest and after exercise. GWE decreased in healthy adults after exercise because of increased GWW, and PPS was independently associated with GWW both at rest and under load, suggesting that early systolic lengthening (ESL) may be beneficial for subsequent contraction of the myocardium.\u003c/p\u003e","manuscriptTitle":"Stress Echocardiographic Myocardial Work in Healthy Adults and Heart Failure with Preserved Ejection Fraction Patients and Doubt about Early Systolic Lengthening","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:27:38","doi":"10.21203/rs.3.rs-3906031/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"611f5fbb-3d53-4822-b9f1-3a564591f000","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28566840,"name":"Health sciences/Cardiology"},{"id":28566841,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2024-03-14T07:50:54+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-06 17:27:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3906031","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3906031","identity":"rs-3906031","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}