Quantitative Analysis of Left Ventricular Flow Dynamics in Hypertrophic Cardiomyopathy using vector flow mapping: Comparison with hypertensive LV hypertrophy | 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 Research Article Quantitative Analysis of Left Ventricular Flow Dynamics in Hypertrophic Cardiomyopathy using vector flow mapping: Comparison with hypertensive LV hypertrophy Wei Wang, Yueheng Wang, Hui Bai, Ze Gao, Wang Feng, Shanshan Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2072528/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 Hypertrophic cardiomyopathy (HCM) and secondary hypertensive LV hypertrophy (H-LVH) differ in pathophysiology. However, the differences and mechanisms of their blood flow fields have not been well studied. This study aimed to assess energy loss (EL), circulation, vortex area, vorticity and intraventricular velocity gradient between these two hypertrophy types. Methods Vector flow mapping (VFM) echocardiography was performed in 35 healthy participants, 25 HCM patients, and 24 H-LVH patients. Circulation, vortex area and vorticity during atrial filling (A-filling), isovolumic contraction (IVC) and ejection period were measured, as well as intraventricular velocity gradient during the E-filling period and average energy loss (EL-ave) during one cardiac cycle for each period. Measurements were averaged over three cardiac cycles. Results The “absent E-filling vortex ring” phenomenon was found in 8 HCM cases (32%), with significantly increased EL-ave during the A-filling period and relatively reduced diastolic intraventricular velocity gradient between the base and the apex (Vbp) compared with patients with normal E-filling vortex ring. EL-ave during the E-filling period was weaker in HCM than in the control and H-LVH groups. From A-filling to ejection, EL-ave was obviously increased in the HCM and H-LVH groups compared to the control group. Multivariable analyses revealed that EL-ave during the E-filling period in the HCM and H-LVH groups was affected by different heart structure-related factors and had a good diagnostic efficiency in differentiating HCM from H-LVH. Conclusion Differences in abnormal hemodynamics observed between HCM and H-LVH are reflected in both VFM-derived parameters, especially non-physiological vortices and early filling EL, which is closely related to special morphology. EL during E-filling as a novel parameter may be may be useful in differentiating HCM from hypertensive LVH. Vector flow mapping Energy loss Hypertrophic cardiomyopathy hypertensive LV hypertrophy Intracardiac vortex Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder that can be considered a sarcomeric disorder; its pathology is characterized by asymmetric or concentric myocardial hypertrophy associated with myocardial fiber disarray and fibrosis manifested as collagen hyperplasia, disarray of fibers and fascicles, and myocardial cell damage and necrosis[ 1 ], leading to global and regional systolic and diastolic deformations. The myocardium of patients with hypertensive LV hypertrophy (H-LVH) is under long-term volume and pressure load with cardiomyocyte hypertrophy and interstitial fibrosis, impeding the normal contractile and diastolic functions of cardiac myocytes[ 2 ]. H-LVH and HCM both involve increased left ventricular (LV) wall thickness. Meanwhile, LV ejection fraction is frequently normal and diastolic function is reduced. Speckle-tracking echocardiography and cardiac magnetic resonance (CMR) imaging are often useful to compare early LV structural and LV functional abnormalities in diseases involving ventricular wall thickening[ 3 , 4 ]. Studies have confirmed that early segmental relaxation abnormalities in HCM and H-LVH are different,[ 5 ] and compare with HCM cases, the correlation between left ventricular wall thickness and diastolic function is stronger in patients with hypertension[ 6 ]. Currently, there are no reports comparing intracardiac hemodynamics between these two hypertrophy types. However, a comprehensive analysis of cardiac structure and hemodynamics is very important for accurate, objective and thorough evaluation of cardiac function. Vector flow mapping (VFM) is a promising method that enables an efficient evaluation of blood flow and the condition of early damaged blood flow field[ 7 ]. We hypothesized that intraventricular flow dynamics parameters differ between primary and secondary LV hypertrophy types due to distinct histopathological mechanisms, although no difference in the degree of LV function impairment is detected by conventional echocardiogram. The purpose of this study was to apply VFM to test the above hypothesis, and to ascertain the value of an index derived from intracardiac flow analysis in evaluating and managing ventricular wall thickening diseases in the future. Materials And Methods Study population The present cross-sectional study included 25 individuals diagnosed with HCM, 24 diagnosed with H-LVH, and 35 age and sex-matched healthy controls. The patients were prospectively enrolled from May 2020 to October 2021 at the first visit if meeting the 2014 ESC guidelines on the diagnosis and management of HCM[ 8 ] with a preserved LVEF > 50%. All enrolled HCM patients had exercise echocardiography. Patients with LV outflow tract pressure gradient ≥ 30 mmHg at rest or after exercise echocardiography were excluded. Patients with hypertensive diagnosis confirmed in accordance with the 2017 United States guidelines[ 9 ] were included. H-LVH diagnosis criteria were increased LV mass index (LVMI) (> 115 g/m 2 in males and > 95 g/m 2 in females) and increased relative wall thickness (RWT) (≥ 0.42). Healthy adults (with unremarkable echocardiographic examination and no cardiac disease history) assessed at the physical examination center of our hospital were enrolled as the control group over the same period. All subjects provided signed informed consent, and the study protocol was approved by the Medical Ethics Committee of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Exclusion criteria were: 1) need for hemodialysis; 2) a more than moderate valvular regurgitation; 3) non-sinus rhythm; 4) congenital heart disease or a history of cardiovascular surgery. 2.2 Echocardiography Clinical data, including sex, age, body mass index (BMI) and body surface area (BSA), were collected. Transthoracic echocardiography was performed in all subjects with an Aloka Prosound F75 scanner (Hitachi Aloka Medical co, Ltd, Tokyo, Japan) equipped with a frequency of 2–4 mHz transducer (UST5415). Cardiac chamber size and function were measured according to current guidelines[ 10 ], including LV end-diastolic diameter (LVEDd), posterior wall (LVPW) thickness, maximal myocardial thickness, LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and left atrial diameter (LAD). Relative wall thickness (RWT) was calculated as 2×LVPW thickness/LVEDd. LV mass index (LVMI) was calculated according to the Devereux formula[ 11 ]. LV ejection fraction (LVEF) and left atrial volume (LAV) were measured by the biplane Simpson’s method and LAV, LVEDV and LVESV were normalized for BSA as (LAVI), (LVEDVI) and (LVESVI), respectively. Transmitral E and A peak velocities (E and A peaks, respectively) were measured. We measured septal and lateral early diastolic peak of mitral annular velocity (e′) whose average value was used in subsequent analysis. The ratio of E to average e′(E/e′) was determined. Image acquisition and principles of vector flow mapping Intracardiac flow images were acquired in the VFM mode in the apical three-chamber view. Scanning width, imaging depth, and spatial-temporal settings were optimized to obtain the highest frame rate and the entire cardiac structure in the color-scan area. The blood flow should be high enough, and secondary aliasing should be avoided. All images were acquired in three consecutive cardiac cycles and stored for subsequent offline analysis. Offline analysis was performed with a commercially available VFM analysis software (DAS-RS1, Hitachi, Tokyo, Japan). A vortex in the velocity field was then defined as a closed area where a streamline forms the outer border, and each vortex was characterized by circulation (10 − 3 cm 2 /s), and vortex area (cm 2 ) and vorticity (s − 1 ). The cardiac cycle was divided into 5 phases according to the time-flow curve and valve opening and closing, into isovolumetric contraction (IVC), ejection(Ej), isovolumetric relaxation (IVR), early filling (E-filling) and atrial filling (A-filling) phases (Fig. 1 ). Average energy loss (EL-ave) was calculated in each period; subsequently, circulation, area and vorticity of the intracardiac vortex were calculated in the A-filling, IVC and ejection phases. Then, three vertical sampling cursors were placed in the center of the inflow at the base, middle, and apex of the LV along its long axis to measure LV’s velocity gradient during the E-filling period in the velocity vector mapping mode. The velocities at the base (Vbase) and apex (Vapex) were calculated as velocity = flow rate/length of the velocity sampling cursor. Next, velocity difference in the E-filling period between base and apex was determined as diastolic intraventricular velocity gradient (Vbp) = Vbase – Vapex. Statistical analysis All statistical data were analyzed with the SPSS 24.0 (SPSS, Inc., Chicago, IL). Normality was evaluated by the Kolmogorov-Smirnov test. Continuous data were expressed as mean ± Standard Deviation (SD) or median and interquartile range. Group differences were examined by one-way repeated measures analysis of variance (ANOVA) followed Tukey’s post hoc test (LSD test where equal variances were assumed, and Dunnett’s C test where equal variances were not assumed). Proportions were compared by the chi-square test. Multivariable linear regression analysis was performed to identify independent determinants of EL during the E-filling and A-filling phases. Univariate linear regression was performed to assess the effect of LVEDVI on EL-ave during the E-filling period. Receiver operating characteristic curve (ROC) analysis was performed to assess the ability of an index derived from VFM to distinguish HCM. All analyses were two-tailed, and P < 0.05 was considered statistically significant. Results Clinical and echocardiographic characteristics The demographic and echocardiographic characteristics are summarized in Table 1 . There were no significant differences in baseline data among the three groups, except for higher BMI in the HCM and H-LVH groups (Control vs. HCM, P = 0.002; Control vs H-LVH, P = 0.008). Maximal myocardial thickness and LVMI increased in the following order: control, H-LVH and HCM (HCM vs. Control, P < 0.001; HCM vs. H-LVH, P < 0.001). LVEDVI (HCM vs. Control, P = 0.038; HCM vs. H-LVH, P < 0.001) and LVESVI (HCM vs. Control, P = 0.034; HCM vs. H-LVH, P < 0.001) were lower in the HCM group than in the other two groups. Although E velocity was similar among the three groups, A velocity values were higher in the HCM and LVH groups (Control vs. HCM, P = 0.006; Control vs H-LVH, P < 0.001), resulting in lower E/A values (Control vs. HCM, P = 0.001; Control vs H-LVH, P < 0.001). The decreased E/A and e' (Control vs. HCM, P < 0.001; Control vs H-LVH, P < 0.001), and elevated E/e' (Control vs. HCM, P < 0.001; Control vs H-LVH, P < 0.001), LAVI (Control vs. HCM, P ; Control vs H-LVH, P ) in the HCM and H-LVH groups indicated impaired diastolic function and elevated left atrial pressure. There was no significant differences in diastolic and systolic functions between the HCM and H-LVH groups. Table 1 Clinical and echocardiographic characteristics of the study subjects Parameters Control (n = 35) HCM (n = 25) H-LVH (n = 24) P value Age ( years) 46.2 ± 10.5 48.8 ± 12.6 50.6 ± 12.1 0.37 Female N (%) 17(48.6%) 5(20%) 8(33.3%) 0.072 Body surface area (m²) 1.76 ± 0.21 1.87 ± 0.17 a 1.82 ± 0.17 0.1 Body mass index (Kg/m²) 23.53 ± 3.16 26.44 ± 3.26 a 26.18 ± 3.14 a 0.001 Left atrial volume index (mL/m²) 23.74 ± 4.4 36.05 ± 13 a 38.19 ± 11.59 a < 0.001 Maximal myocardial thickness (mm) 8.12 ± 1.07 19.48 ± 4.32 a 12.29 ± 1.87 ab < 0.001 LVEDVI (mL/m²) 59.53 ± 8.47 53.11 ± 13.99 a 65.54 ± 12.84 b 0.002 LVESVI (mL/m²) 19.37 ± 4.37 16.65 ± 4.00 a 21.66 ± 6.07 b 0.002 LV ejection fraction (%) 66.93 ± 4.43 68.68 ± 4.30 67.69 ± 4.30 0.333 LV mass index (g/m²) 71.03 ± 12.79 185.62 ± 48.49 a 119.5 ± 36.45 ab < 0.001 E peak (cm/s) 69.27 ± 12.61 61.92 ± 16.80 69.25 ± 21.19 0.189 A peak (cm/s) 58.09 ± 15.26 71.28 ± 21.01 a 80.68 ± 17.32 a < 0.001 E/A ratio 1.29 ± 0.45 0.94 ± 0.38 a 0.89 ± 0.33 a < 0.001 e’ (cm/s) 9.81 ± 2.46 5.60 ± 0.82 a 6.08 ± 1.69 a < 0.001 E/e‘ratio 6.46 ± 1.81 9.20 ± 2.07 a 10.15 ± 2.63 a < 0.001 LV diastolic function, n(%) < 0.001 Grade I 4(11.4%) 16(64%) a 12(50%) a Grade II 0 9(36) a 11(45.8) a Grade III 0 0 1(4.2%) Inconclusive 31(88.6%) 0 0 Date given as mean ± Standard Deviation or number (total) LV Left ventricular, LVEDVI Left ventricular end-diastolic volume index, LVESVI Left ventricular end-systolic volume index, e’ Average value of septal and lateral early diastolic peak of mitral annular velocity, HCM Hypertrophic cardiomyopathy, H-LVH hypertensive left ventricular hypertrophy a P <0.05 vs normal control group, b P <0.05 vs HCM group Intracardiac vortex flow characteristics The characteristics of vortex and streamline in different phases and different groups were shown in Fig. 2 . In the normal control and H-LVH groups, two vortices with opposite directions and asymmetric shapes were formed in the anterior and posterior leaflets of the mitral valve during the E-filling and A-filling phases (shown in Fig. 2 B-C and 2 J-K). These streamlines rotated clockwise and flowed through the LVOT after forming a vortex during IVC (shown in Fig. 2 D and 2 L) period and continued into the ejection period, turning into the laminar flow to gradually disappear. The number of vortices in the H-LVH group increased, partially in the apical part of the LV (shown in Fig. 2 J-K). In the HCM group, the streamlines of 8 patients (32%) crossing the mitral valve did not form the normal vortex ring in the LV during the E-filling stage (shown in Fig. 2 F). This phenomenon was termed “absent E-filling vortex ring”, in which, EL-ave was increased during the A-filling period (shown in Fig. 3 a), while Vbp was relatively reduced (shown in Fig. 3 b) (all P < 0.05). LVEDVI showed a decreasing trend, but the difference was not statistically significant (shown in Fig. 3 c). VFM-derived parameters Table 2 shows VFM-derived parameters in the three groups. Though there were no differences in diastolic and systolic functions between the HCM and H-LVH group, the diastolic intraventricular velocity gradient between the base and the apex (Vbp) (HCM vs. Control, P = 0.001; HCM vs. H-LVH, P = 0.023) and vortex area during the atrial filling (A-filling) period (HCM vs. Control, P = 0.008; HCM vs. H-LVH, P < 0.001), isovolumetric contraction (IVC) period (HCM vs. Control, P = 0.014; HCM vs. H-LVH, P < 0.001) and ejection periods (HCM vs. Control, P = 0.046; HCM vs. H-LVH, P = 0.025) were reduced in the HCM group compared with the control and H-LVH groups. The average energy loss was weaker in HCM than in the control and H-LVH groups during the E-filling period (HCM vs. Control, P = 0.002; HCM vs. H-LVH, P = 0.001) and were increased in the HCM and H-LVH groups than the control group from the A-filling period (HCM vs. Control, P = 0.047; H-LVH vs. Control, P = 0.007) and IVC period (HCM vs. Control, P = 0.004; H-LVH vs. Control, P = 0.005) to the ejection period (HCM vs. Control, P < 0.001; H-LVH vs. Control, P = 0.005). The analysis of left ventricular EL between HCM, H-LVH and control participants was also illustrated in Fig. 4 . Moreover, from this line chart, we can also find that the evolvement of the average energy loss in different phases of HCM group are similar to those of H-LVH group, with the lowest EL-ave in IVR period and the two peaks vales of EL-ave observed in one cardiac cycle during E-filling and ejection phases. Although the EL-ave of HCM group is also the lowest in IVR period, it gradually increases from E-filling to ejection period, with the highest peak value of EL-ave only appearing in the ejection phase. Table 2 VFM-derived parameters of the participants Parameters Control (n = 35) HCM (n = 25) H-LVH (n = 24) P value Circulation (10 − 3 m²/s) Atrial filling period 13.2 ± 6.32 10.93 ± 5.80 13.30 ± 5.70 0.262 Isovolumic contraction period 15.01 ± 7.76 14.31 ± 7.12 21.7 ± 7.82 ab 0.001 Ejection period 9.61 ± 5.39 11.39 ± 6.26 10.96 ± 4.51 0.412 Vortex area (cm²) Atrial filling period 2.27 ± 1.05 1.55 ± 0.72 a 3.17 ± 1.60 ab < 0.001 Isovolumic contraction period 4.5278 ± 1.9479 3.2111 ± 1.796 a 5.9018 ± 2.238 ab < 0.001 Ejection period 2.9141 ± 1.7699 2.0808 ± 1.187 a 3.1063 ± 1.62 b 0.053 Patients without E-filling vortex ring 0 8(32%) a 0 b < 0.001 Mean vorticity (s − 1 ) Atrial filling period 6.35 ± 3.3 7.69 ± 4.55 6.03 ± 4.41 0.449 Isovolumic contraction period 3.45 ± 1.61 8.58 ± 1.92 4.26 ± 2.47 0.164 Ejection period 3.56 ± 1.09 9.20 ± 1.90 a 3.93 ± 1.41 0.093 EL-ave (10 − 3 J/m s) isovolumic relaxation 1.23 ± 0.86 2.01 ± 1.21 1.92 ± 1.65 0.12 Early filling period 7.09 ± 4.03 4.19 ± 1.91 a 9.3 ± 5.75 ab < 0.001 Atrial filling period 3.34 ± 1.88 4.93 ± 3.35 a 5.55 ± 2.64 a 0.017 Isovolumic contraction period 2.75 ± 1.42 5.69 ± 4.24 a 5.64 ± 2.38 a 0.003 Ejection period 3.49 ± 1.54 10.67 ± 5.93 a 9.05 ± 5.66 a < 0.001 Intraventricular velocity Vbase (cm/s) 5.24 ± 1.15 4.87 ± 1.10 5.32 ± 0.99 0.289 Vapex (cm/s) 2.68 ± 1.02 2.92 ± 1.56 2.66 ± 0.89 0.677 Vbp (cm/s) 2.55 ± 1.07 1.58 ± 1.14 a 2.28 ± 0.8 b 0.003 Date given as mean ± Standard Deviation EL-ave Average energy loss, Vbp Diastolic intraventricular velocity gradient between the base and the apex, Vbase Intraventricular velocities at the base, Vapex Intraventricular velocities at the apex b P <0.05 vs HCM group, a P <0.05 vs control group Stepwise multiple linear regression analysis The results of multiple linear regression for predicting the average EL were shown in Table 3 . In the control group, E-peak and LVEDVI were independent predictors of the EL-ave during E-filling period, whereas the LVEDVI, Vbp and E/A, LVMI, Vbp were respectively independent predictors of the EL-ave during E-filling in the patients with HCM and H-LVH and the correlation between LVEDVI and EL-ave in the E-filling period in the HCM group was closer (shown in Fig. 5 ). EL-ave values during the A-filling period in all groups were independently associated with A peak. Except for A peak, it was also especially affected by LVEDVI in the HCM group but not in the other two groups. Table 3 Multiple linear regression for predicting EL-ave in the three groups Control Variables EL-ave E-filling A-filling coefficient β std.error P Variable coefficient β std.error P E peak 0.205 0.039 < 0.01 A 0.168 0.025 < 0.01 LVEDVI 0.127 0.059 0.038 Adjusted R 2 = 0.491, p < 0.05 Adjusted R 2 = 0.641, p < 0.05 HCM Variables E-filling A-filling Coefficient β Std.error P Variables Coefficient β std.error P LVEDVI 0.085 0.02 < 0.01 A 0.122 0.03 < 0.01 Vbp 0.660 0.187 0.002 LVEDVI -0.113 0.046 0.021 Adjusted R 2 = 0.66, p < 0.05 Adjusted R 2 = 0.352, p < 0.05 H-LVH E-filling A-filling Variables Coefficient β std.error P Variables Coefficient β std.error P E/A 14.753 2.294 < 0.01 A 0.104 0.024 P < 0.01 LVMI 0.054 0.019 0.009 Vbp 1.578 0.725 0.042 Adjusted R 2 = 0.672, p < 0.05 Adjusted R 2 = 0.440, p < 0.05 VFM-derived parameters differentiating HCM from H-LVH According to one-way ANOVA, there were significant differences between the HCM and H-LVH groups in EL-ave during the E-filling period, vortex area during the A-filling period, IVC during the ejection period and Vbp (all P < 0.05). ROC curve analysis showed that EL-ave during the E-filling phase was more effective for differential diagnosis of HCM and H-LVH; the best cutoff value was 5.04 10 − 3 J/m s, yielding a sensitivity of 76% and specificity of 80% (Fig. 6 ). Discussion EL in the E-filling period in the HCM and H-LVH groups The ventricular remodeling processes associated with heart disease alter left ventricular (LV) hemodynamic parameters, including intraventricular vortex and energy loss. Intraventricular vortex can be described as fluid structures that have circular or swirling motions[ 12 ]. Meanwhile, energy loss (EL) is the frictional heat generated by viscosity blood. Although there was no difference in the degree of diastolic dysfunction between HCM and H-LVH cases evaluated by conventional parameters, the changes of left ventricular hemodynamics especially during the E-filling phase differed. During the E-filling phase, average EL was lower in the HCM group compared with the H-LVH group, which was associated with reduced LVEDVI and intraventricular velocity gradient from base to apex (Vbp) determined by multiple stepwise regression analysis. The diastolic intraventricular velocity gradient derived from VFM could be useful for estimating impaired LV relaxation and local flow dynamics in the ventricular chambers[ 13 , 14 ]. Normally, there was a progressive intraventricular pressure difference that extends from the LA to the LV apex driving early diastolic filling, which is generated by rapid myocardial relaxation and recoil of elastic elements compressed during ejection [ 15 ]. Then, a strong vortex pair behind mitral valve leaflets appear was initiated. In this study, for patients with HCM, impaired relaxation and reduced intraventricular volume diminishes the ability of the LV to function as a suction pump, resulting in decreased Vbp [ 14 ], and the associated ring vortex at the mitral valve tips was reduced in size. Then, the weaker filling inflow jet would lead to decreased EL in the HCM group. Although Vbp in the H-LVH group also tended to decrease, EL during the E-filling period was significantly increased in the H-LVH group. This is likely because different from the effect of LVEDVI on EL during the E-filling period in the HCM group, EL during the E-filling period is instead affected by LVMI in the H-LVH group. “Pathological” left ventricular hypertrophy (LVH) in HCM mainly has primary myocardial properties at the microscopic level, including myocyte disarray, interstitial fibrosis and replacement fibrosis, and “compensatory” LVH in hypertension is usually a compensatory mechanism in response to increased hemodynamic load, resulting in cardiomyocyte hypertrophy and extracellular matrix remodeling[ 6 ]. With increasing left ventricular weight, the oxygen demand increases, myocardial cell compensation increases, and microvascular dysfunction occurs, aggravating myocardial fibrosis and endothelial cell dysfunction[ 16 ]. The increased pressure load on the inner myocardium compared with the outer myocardium weakens longitudinal contraction. Previous studies have found that although left ventricular strain is reduced in both diseases, HCM patients have marked reductions in LS and CS, whereas H-LVH cases have less reduction in LS and unaffected CS[ 17 ]. Uncoordinated contraction of inner and outer myocardium would produce irregular blood flow, and heterogeneous flow field caused by the strong collision between high flow speed and wall shear flow inevitably increases blood energy consumption[ 18 ]. In addition, LV mass and LV hypertrophy in hypertension are strongly associated with impaired relaxation and increased LV filling pressure[ 19 ]. When left ventricular filling pressure is elevated, the flow of left atrial blood into the left ventricle is limited, and the impact of left ventricular inflow tract blood flow on the mitral valve is reduced[ 16 ], which impairs the formation of normal vortices, with increased number of vortices and ineffective vortices loaded in the LV apical part during E-filling even to the end of the atrial contraction period. Non-physiological vortex formation leads to increased blood flow dispersion and instability, causing inflow tract deflection and lateral force generation as well as higher energy consumption. From the above, we can infer that differences in abnormal diastolic hemodynamics observed between HCM and H-LVH are reflected by EL during the E-filling phase and are affected by different pathological cardiac configurations between HCM and H-LVH. Non-physiological vortices in HCM and H-LVH Vortex area in the HCM group was the smallest in each period, and in eight patients (32%) of the latter group, no well-formed E-filling vortex ring core was detected; LV interior volumes tended to decrease, although statistical significance was not reached. Previous studies have confirmed that LV shape and internal volume also play critical roles in vortex ring dynamics in the LV filling and ejection phases. Reduced LV volume could deprive the LV of its ability to enhance the formation of ring vortices at the mitral valve tips,[ 20 ] indicating the importance of LV morphology. Interestingly, we also found that Vbp was smaller and EL during the A-filling phase was increased in HCM patients without normal vortex formation. Under normal circumstances, blood flows towards the apex prior to the mitral valve opening, and the mitral annulus moves rapidly away after the valve opens; thus, the created intracardiac pressure gradient promotes vortex formation. Once generated, vortices as relatively longstanding inertial flow structures can create a virtual hydrodynamic channel extending from the mitral valve towards the apex of the heart, which facilitates filling by reducing convective losses and enhancing the function of the LV as a suction pump[ 21 ]. These findings suggest that intraventricular pressure gradient and the vortex promote each other. Once vortex generation is impaired, this mechanism could weaken or even disappear. This suggested that myocardial diastolic function appears to be more vulnerable in patients with HCM, in accordance with previous studies[ 4 , 22 ]. The study demonstrated that the vortex additionally contributes to diastolic function by “pulling” blood from the LA into the LV, particularly during the E-wave deceleration, diastasis and late filling phases, which helps 10–15% of its filling volume enter the LV at no metabolic or pressure cost [ 23 ]. In most cases, its disappearance is unlikely to result in decreased cardiac output, because the heart can compensate for the disappeared vortex without affecting cardiac output. However, without changing the mechanical properties of the myocardium, this can only be achieved by increasing atrial thrust and/or accelerating diastolic speed, even increasing atrial pressure. In other words, the heart could fill the LV without normal vortex, but at the cost of increasing metabolic demand and/or atrial pressure[ 24 ]. EL during the A-filling and ejection phases EL increased in the A-filling and ejection phases in both HCM and H-LVH groups, but vortex circulation values did not increase accordingly. Circulation is one of the main parameters reflecting vortex strength. EL increase is related to elevated vortex strength, which seems to be a normal physiological phenomenon or in a highly hemodynamic state. However, in the absence of vortex strength increase, elevated EL indicates a turbulence in the intraventricular region [ 7 ]. The generation of intraventricular turbulence during A-filling in HCM and H-LVH is related to left ventricular diastolic dysfunction manifested by significantly decreased mitral annulus velocity (e ') and elevated left ventricular filling pressure. Decreased left ventricular elastic recoil and relaxation force may cause left atrial contraction compensatory filling actively [ 25 ]. To maintain a certain filling pressure, blood flow into the left ventricle with the direction and speed change drastically, intraventricular flow velocity increases, coupled with elevated left ventricular stiffness, and the turbulence phenomenon aggravates such irregular blood flow and shear flow chamber wall; the intense collision inevitably increases the energy consumption of blood. In addition, increased EL-ave during the A-filling period of HCM is related to decreased LVEDVI. It may be caused by the confinement imposed by decreased LV volume on the filling vortex, which could inhibit the formation of vortex and affect its stability[ 26 ]. At this time, the vortex loses its original assisting effect and increases energy consumption. Fibrosis of the left ventricular wall in HCM and H-LVH may lead to impaired contractile deformation ability of the left ventricular myocardium[ 27 ]. Therefore, extra work and enhanced energy consumption are required to maintain normal ejection. This reflects the inefficient hemodynamic status of HCM and H-LVH. There were several limitations that should be pointed out. The main limitation is that the sample size of this study was limited, especially in the HCM group. As a result, LVEDVI in HCM patients with no well-formed E-filling vortex ring was decreased, but statistical significance was not reached. It is necessary to assess more patients with HCM to explore the anatomical factors of HCM patients of no well-formed E-peak vortex ring, e.g., abnormal papillary muscle position, thickening of ventricular wall position, etc. Secondly, in this investigation, we did not measure LV pressure by cardiac catheterization, and the examined patients only underwent the vector flow mapping test. Our data generated by vector flow mapping have not been compared with the invasive intraventricular pressure gradient. Future studies with larger patient cohorts are required to overcome these limitations and to validate our findings. Conclusions In conclusion, energy inefficiency differences in HCM and H-LVH are reflected by diastole non-physiological vortex and EL, suggesting that future studies need to explore the application of VFM-related parameters for closely monitoring disease progression, predicting adverse outcomes, and exploring new therapeutic options. Abbreviations A: Mitral late filling wave peak velocity; HCM: Hypertrophic cardiomyopathy; H-LVH: Hypertensive left ventricular hypertrophy; E: Mitral early filling wave peak velocity; e’: Average value of septal and lateral early diastolic peak of mitral annular velocity; LVEDVI: Left ventricular end-diastolic volume index; Vbp: Diastolic intraventricular velocity gradient between the base and the apex; Vbase: Intraventricular velocities at the base; Vapex: Intraventricular velocities at the apex; IVR: Isovolumetric relaxation; E-filling: Early filling; A-filling: atrial filling; IVC: Isovolumetric contraction; EL-ave: Average energy loss; LVMI: Left ventricular mass index; VFM: Vector flow mapping; LVESVI: Left ventricular end-systolic volume index; ROC: Receiver-operating characteristic. Declarations Acknowledgements Not applicable Authors’ contributions WW, YH W, HB designed the experiments and analyzed and interpreted the data. YH W subsidized and conceived of the study. WW, ZG, FW, SS L contributed to the acquisition of image and the collection of data. WW wrote the manuscript and HB, YH W was helpful in text revision. All authors read and approved the final manuscript. Funding This study was supported by the Science and technology project of Hebei Provincial Health Commission in China. Availability of data and materials The datasets generated and analyzed in this study are available from the corresponding author on request. Ethics approval and consent to participate This clinical study was approved by the Ethics Committee of the Second Hospital of Hebei Medical University and the ethics number is 2020-R567. Written informed consent were signed by all participants. All methods were performed in accordance with the relevant guidelines and regulations. Competing interests The authors declare that there is no conflict of interest. Consent for publication Not applicable Author details 1 Department of Cardiac Ultrasound, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang 050000, Hebei, China. 2 Department of physical examination center, Hebei Provincial People's Hospital, Shijiazhuang City, Hebei Province, China. References Santos Mateo JJ, Sabater Molina M, Gimeno Blanes JR. Hypertrophic cardiomyopathy. Med Clin (Barc). 2018;150(11):434–42. Verdecchia P, Angeli F, Achilli P, Castellani C, Broccatelli A, Gattobigio R, Cavallini C. Echocardiographic left ventricular hypertrophy in hypertension: marker for future events or mediator of events? Curr Opin Cardiol. 2007;22(4):329–34. Servatius H, Raab S, Asatryan B, Haeberlin A, Branca M, de Marchi S, Brugger N, Nozica N, Goulouti E, Elchinova E, et al: Differences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes' Hearts . J Clin Med 2022, 11(5). Popa-Fotea NM, Micheu MM, Oprescu N, Alexandrescu A, Greavu M, Onciul S, Onut R, Petre I, Scarlatescu A, Stoian M, et al: The Role of Left - Atrial Mechanics Assessed by Two - Dimensional Speckle - Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left - Ventricular Hypertrophy . Diagnostics (Basel, Switzerland) 2021, 11 (5). Voigt C, Münch J, Avanesov M, Suling A, Witzel K, Lund G, Patten M. Early segmental relaxation abnormalities in hypertrophic cardiomyopathy for differential diagnostic of patients with left ventricular hypertrophy. Clin Cardiol. 2017;40(11):1026–32. Chacko BR, Karur GR, Connelly KA, Yan RT, Kirpalani A, Wald R, Jimenez-Juan L, Jacob JR, Deva DP, Yan AT. Left ventricular structure and diastolic function by cardiac magnetic resonance imaging in hypertrophic cardiomyopathy. Indian Heart J. 2018;70(1):75–81. Goya S, Wada T, Shimada K, Hirao D, Tanaka R. The relationship between systolic vector flow mapping parameters and left ventricular cardiac function in healthy dogs. Heart Vessels. 2018;33(5):549–60. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733–79. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ ASPC / NMA / PCNA Guideline for the Prevention , Detection , Evaluation , and Management of High Blood Pressure in Adults : Executive Summary : A Report of the American College of Cardiology / American Heart Association Task Force on Clinical Practice Guidelines . Hypertension (Dallas, Tex: 1979) 2018, 71 (6):1269–1324. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of, Cardiovascular Imaging . European heart journal Cardiovascular Imaging 2016, 17(4):412. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450–8. Cao Y, Sun XY, Zhong M, Li L, Zhang M, Lin MJ, Zhang YK, Jiang GH, Zhang W, Shang YY. Evaluation of hemodynamics in patients with hypertrophic cardiomyopathy by vector flow mapping: Comparison with healthy subjects. Exp Ther Med. 2019;17(6):4379–88. Chen M, Jin JM, Zhang Y, Gao Y, Liu SL. Assessment of left ventricular diastolic dysfunction based on the intraventricular velocity difference by vector flow mapping. J ultrasound medicine: official J Am Inst Ultrasound Med. 2013;32(12):2063–71. Berlot B, Moya Mur JL, Jug B, Rodríguez Muñoz D, Megias A, Casas Rojo E, Fernández-Golfín C, Zamorano JL. Effect of diastolic dysfunction on intraventricular velocity behavior in early diastole by flow mapping. Int J Cardiovasc Imaging. 2019;35(9):1627–36. Stewart KC, Kumar R, Charonko JJ, Ohara T, Vlachos PP, Little WC. Evaluation of LV diastolic function from color M-mode echocardiography. JACC Cardiovasc imaging. 2011;4(1):37–46. Zuo X, Yuan M, Jia H, Zhang M, Zhang C, Zhi G. Vector Flow Mapping Application in Local Cardiac Function in Hypertension Assessment. Int J Gen Med. 2021;14:4793–801. Sun JP, Xu TY, Ni XD, Yang XS, Hu JL, Wang SC, Li Y, Bahler RC, Wang JG. Echocardiographic strain in hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy. Echocardiography. 2019;36(2):257–65. Wang W, Wang Y, Chen X, Yuan L, Bai H. Evaluation of left ventricular diastolic function based on flow energetic parameters in chronic kidney disease with diastolic dysfunction. Echocardiography. 2019;36(3):567–76. Dini FL, Galderisi M, Nistri S, Buralli S, Ballo P, Mele D, Badano LP, Faggiano P, de Gregorio C, Rosa GM, et al. Abnormal left ventricular longitudinal function assessed by echocardiographic and tissue Doppler imaging is a powerful predictor of diastolic dysfunction in hypertensive patients: the SPHERE study. Int J Cardiol. 2013;168(4):3351–8. Sarashina-Motoi M, Iwano H, Motoi K, Ishizaka S, Chiba Y, Tsujinaga S, Murayama M, Nakabachi M, Yokoyama S, Nishino H, et al. Functional significance of intra-left ventricular vortices on energy efficiency in normal, dilated, and hypertrophied hearts. J Clin ultrasound: JCU. 2021;49(4):358–67. Charonko JJ, Kumar R, Stewart K, Little WC, Vlachos PP. Vortices formed on the mitral valve tips aid normal left ventricular filling. Ann Biomed Eng. 2013;41(5):1049–61. Liu W, Sun D, Yang J: Diastolic Dysfunction of Hypertrophic Cardiomyopathy Genotype - Positive Subjects Without Hypertrophy Is Detected by Tissue Doppler Imaging : A Systematic Review and Meta - analysis . Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 2017, 36 (10):2093–2103. Martínez-Legazpi P, Bermejo J, Benito Y, Yotti R, Pérez Del Villar C, González-Mansilla A, Barrio A, Villacorta E, Sánchez PL, Fernández-Avilés F, et al. Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol. 2014;64(16):1711–21. Ji L, Hu W, Yong Y, Wu H, Zhou L, Xu D. Left ventricular energy loss and wall shear stress assessed by vector flow mapping in patients with hypertrophic cardiomyopathy. Int J Cardiovasc Imaging. 2018;34(9):1383–91. Alis D, Guler A, Asmakutlu O, Topel C, Sahin AA. The Association between the Extent of Late Gadolinium Enhancement and Diastolic Dysfunction in Hypertrophic Cardiomyopathy. Indian J Radiol Imaging. 2021;31(2):284–90. Samaee M, Nelsen NH, Gaddam MG, Santhanakrishnan A. Diastolic Vortex Alterations With Reducing Left Ventricular Volume: An In Vitro Study . Journal of biomechanical engineering 2020, 142(12). Tanaka H. Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain. J echocardiography. 2021;19(2):71–9. 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-2072528","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":138244570,"identity":"a3eaeeed-d96d-476f-ae99-c8b046052eea","order_by":0,"name":"Wei Wang","email":"","orcid":"","institution":"The Second Hospital of He bei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wang","suffix":""},{"id":138244571,"identity":"85a6955b-3a3f-4550-bc4a-5fb188fd0248","order_by":1,"name":"Yueheng Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtElEQVRIiWNgGAWjYFACHjCSY2AmVYsx6VoSG4jWYHAj95jEm4rD6fPbeQ9+YKixiSZCS16a5Jwzh3M3HOZLlmA4lpZL0DqzGzlm0rxtQC3MPAYSjA2HidXy73C6fDOP8Q8StDQcTmA4zGNGnC32Z94YW845lm64AajFIoEYv0i25xjeeFNjLS/ff8b4xocaG8JaGAQSWCQYGJohnASCykGA/wDzBwaGOqLUjoJRMApGwQgFABDLPffD5fT7AAAAAElFTkSuQmCC","orcid":"","institution":"The Second Hospital of He bei Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yueheng","middleName":"","lastName":"Wang","suffix":""},{"id":138244572,"identity":"8ff45b8a-859c-4289-940f-072e5854dbd8","order_by":2,"name":"Hui Bai","email":"","orcid":"","institution":"The Second Hospital of He bei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Bai","suffix":""},{"id":138244573,"identity":"c92dba53-49cf-4de0-993e-d0d18a4392aa","order_by":3,"name":"Ze Gao","email":"","orcid":"","institution":"Hebei Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ze","middleName":"","lastName":"Gao","suffix":""},{"id":138244574,"identity":"f2cb112d-3e34-4ede-9574-15eaa5d836c9","order_by":4,"name":"Wang Feng","email":"","orcid":"","institution":"The Second Hospital of He bei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Feng","suffix":""},{"id":138244575,"identity":"b4c57ea4-7e42-49e0-b76b-dc2ae6c454b7","order_by":5,"name":"Shanshan Liu","email":"","orcid":"","institution":"The Second Hospital of He bei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shanshan","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2022-09-16 11:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2072528/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2072528/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":26903044,"identity":"af0556bc-0b8b-4ed4-8996-7b1012e0f36c","added_by":"auto","created_at":"2022-09-23 20:20:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44383,"visible":true,"origin":"","legend":"\u003cp\u003eTime-flow curve representing the five phases of a cardiac cycle. IVC starts from the closure of the mitral valve to the opening of the aortic valve; Ej starts from the opening of the aortic valve to its closure; IVR starts from the closure of the aortic valve to the opening of the mitral valve; E-filling starts from the opening of the mitral valve to another opening of the mitral valve; A-filling starts from the second opening of the mitral valve to its closure\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/ac49c8f34e57114373df6e43.jpg"},{"id":26903089,"identity":"3870dbce-2036-4b98-a6cc-3ddcee2e9479","added_by":"auto","created_at":"2022-09-23 20:25:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1279730,"visible":true,"origin":"","legend":"\u003cp\u003eChanges of vortex and streamline during isovolumetric relaxation (A,E,I), early filling (B,F,J), atrial filling (C,G,K) and isovolumetric contraction (D,H,L) are shown, respectively, in the control (A-D), HCM (E-H) and H-LVH (I-L) groups. Vortices are marked by orange circles.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/3e7aaad3dc0f09858c1d9867.png"},{"id":26903042,"identity":"7766fa2a-5dcb-4fd0-b14d-270eeca3fe55","added_by":"auto","created_at":"2022-09-23 20:20:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33084,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of statistically significant ultrasound parameters between HCM group with absence/presence of vortex ring at the early filling stage. a Average EL values of atrial filling period in patients with/without E-filling vortex ring in the HCM groups; b Intraventricular velocity difference between the base and the apex in patients with/without E-filling vortex ring in the HCM group; c Left ventricular end-diastolic volume index values in patients with/without E-filling vortex ring in the HCM group.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/4baed13760f707e5e0c4f288.jpg"},{"id":26903045,"identity":"c953be57-9cff-4bd4-9d95-9efcc2824e5d","added_by":"auto","created_at":"2022-09-23 20:20:51","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26621,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of average energy loss in different phases and various groups. During the E-filling phase, average EL was lower in the HCM group than in the control and H-LVH groups; from the A-filling phase to the ejection period, average EL levels obviously increased in the HCM and H-LVH groups.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/8392d7a0c68147f60c9c52e7.jpg"},{"id":26903043,"identity":"f39e6893-5225-4698-bc60-4e540272b7c5","added_by":"auto","created_at":"2022-09-23 20:20:51","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":28250,"visible":true,"origin":"","legend":"\u003cp\u003eLinear regression analysis of EL during the E-filling period and left ventricular end-diastolic volume index in the three groups.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/b219bc2f5435f35f606e1413.jpg"},{"id":26903088,"identity":"8b220616-5427-492f-ab51-b32fd930a4fe","added_by":"auto","created_at":"2022-09-23 20:25:51","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":37564,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis for the prediction of HCM. EL-ave in the E-filling period had the largest area under the ROC curve.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/95ab22694afa9eb3cf81a990.jpg"},{"id":30698108,"identity":"ab11f6db-4a90-45f1-955e-3c04444e82bc","added_by":"auto","created_at":"2022-12-23 05:14:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2000405,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2072528/v1/dae0e7a0-b48b-45f1-a76f-e27180287330.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quantitative Analysis of Left Ventricular Flow Dynamics in Hypertrophic Cardiomyopathy using vector flow mapping: Comparison with hypertensive LV hypertrophy","fulltext":[{"header":"Background","content":"\u003cp\u003eHypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder that can be considered a sarcomeric disorder; its pathology is characterized by asymmetric or concentric myocardial hypertrophy associated with myocardial fiber disarray and fibrosis manifested as collagen hyperplasia, disarray of fibers and fascicles, and myocardial cell damage and necrosis[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], leading to global and regional systolic and diastolic deformations. The myocardium of patients with hypertensive LV hypertrophy (H-LVH) is under long-term volume and pressure load with cardiomyocyte hypertrophy and interstitial fibrosis, impeding the normal contractile and diastolic functions of cardiac myocytes[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. H-LVH and HCM both involve increased left ventricular (LV) wall thickness. Meanwhile, LV ejection fraction is frequently normal and diastolic function is reduced.\u003c/p\u003e \u003cp\u003eSpeckle-tracking echocardiography and cardiac magnetic resonance (CMR) imaging are often useful to compare early LV structural and LV functional abnormalities in diseases involving ventricular wall thickening[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Studies have confirmed that early segmental relaxation abnormalities in HCM and H-LVH are different,[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and compare with HCM cases, the correlation between left ventricular wall thickness and diastolic function is stronger in patients with hypertension[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Currently, there are no reports comparing intracardiac hemodynamics between these two hypertrophy types. However, a comprehensive analysis of cardiac structure and hemodynamics is very important for accurate, objective and thorough evaluation of cardiac function.\u003c/p\u003e \u003cp\u003eVector flow mapping (VFM) is a promising method that enables an efficient evaluation of blood flow and the condition of early damaged blood flow field[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. We hypothesized that intraventricular flow dynamics parameters differ between primary and secondary LV hypertrophy types due to distinct histopathological mechanisms, although no difference in the degree of LV function impairment is detected by conventional echocardiogram. The purpose of this study was to apply VFM to test the above hypothesis, and to ascertain the value of an index derived from intracardiac flow analysis in evaluating and managing ventricular wall thickening diseases in the future.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe present cross-sectional study included 25 individuals diagnosed with HCM, 24 diagnosed with H-LVH, and 35 age and sex-matched healthy controls. The patients were prospectively enrolled from May 2020 to October 2021 at the first visit if meeting the 2014 ESC guidelines on the diagnosis and management of HCM[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] with a preserved LVEF\u0026thinsp;\u0026gt;\u0026thinsp;50%. All enrolled HCM patients had exercise echocardiography. Patients with LV outflow tract pressure gradient\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg at rest or after exercise echocardiography were excluded. Patients with hypertensive diagnosis confirmed in accordance with the 2017 United States guidelines[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] were included. H-LVH diagnosis criteria were increased LV mass index (LVMI) (\u0026gt;\u0026thinsp;115 g/m\u003csup\u003e2\u003c/sup\u003e in males and \u0026gt;\u0026thinsp;95 g/m\u003csup\u003e2\u003c/sup\u003e in females) and increased relative wall thickness (RWT) (\u0026ge;\u0026thinsp;0.42). Healthy adults (with unremarkable echocardiographic examination and no cardiac disease history) assessed at the physical examination center of our hospital were enrolled as the control group over the same period.\u003c/p\u003e \u003cp\u003e All subjects provided signed informed consent, and the study protocol was approved by the Medical Ethics Committee of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Exclusion criteria were: 1) need for hemodialysis; 2) a more than moderate valvular regurgitation; 3) non-sinus rhythm; 4) congenital heart disease or a history of cardiovascular surgery.\u003c/p\u003e \u003cp\u003e2.2 Echocardiography\u003c/p\u003e \u003cp\u003eClinical data, including sex, age, body mass index (BMI) and body surface area (BSA), were collected. Transthoracic echocardiography was performed in all subjects with an Aloka Prosound F75 scanner (Hitachi Aloka Medical co, Ltd, Tokyo, Japan) equipped with a frequency of 2\u0026ndash;4 mHz transducer (UST5415). Cardiac chamber size and function were measured according to current guidelines[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], including LV end-diastolic diameter (LVEDd), posterior wall (LVPW) thickness, maximal myocardial thickness, LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and left atrial diameter (LAD). Relative wall thickness (RWT) was calculated as 2\u0026times;LVPW thickness/LVEDd. LV mass index (LVMI) was calculated according to the Devereux formula[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. LV ejection fraction (LVEF) and left atrial volume (LAV) were measured by the biplane Simpson\u0026rsquo;s method and LAV, LVEDV and LVESV were normalized for BSA as (LAVI), (LVEDVI) and (LVESVI), respectively.\u003c/p\u003e \u003cp\u003eTransmitral E and A peak velocities (E and A peaks, respectively) were measured. We measured septal and lateral early diastolic peak of mitral annular velocity (e\u0026prime;) whose average value was used in subsequent analysis. The ratio of E to average e\u0026prime;(E/e\u0026prime;) was determined.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eImage acquisition and principles of vector flow mapping\u003c/h2\u003e \u003cp\u003eIntracardiac flow images were acquired in the VFM mode in the apical three-chamber view. Scanning width, imaging depth, and spatial-temporal settings were optimized to obtain the highest frame rate and the entire cardiac structure in the color-scan area. The blood flow should be high enough, and secondary aliasing should be avoided. All images were acquired in three consecutive cardiac cycles and stored for subsequent offline analysis.\u003c/p\u003e \u003cp\u003eOffline analysis was performed with a commercially available VFM analysis software (DAS-RS1, Hitachi, Tokyo, Japan). A vortex in the velocity field was then defined as a closed area where a streamline forms the outer border, and each vortex was characterized by circulation (10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e cm\u003csup\u003e2\u003c/sup\u003e/s), and vortex area (cm\u003csup\u003e2\u003c/sup\u003e) and vorticity (s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e).\u003c/p\u003e \u003cp\u003eThe cardiac cycle was divided into 5 phases according to the time-flow curve and valve opening and closing, into isovolumetric contraction (IVC), ejection(Ej), isovolumetric relaxation (IVR), early filling (E-filling) and atrial filling (A-filling) phases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Average energy loss (EL-ave) was calculated in each period; subsequently, circulation, area and vorticity of the intracardiac vortex were calculated in the A-filling, IVC and ejection phases.\u003c/p\u003e \u003cp\u003eThen, three vertical sampling cursors were placed in the center of the inflow at the base, middle, and apex of the LV along its long axis to measure LV\u0026rsquo;s velocity gradient during the E-filling period in the velocity vector mapping mode. The velocities at the base (Vbase) and apex (Vapex) were calculated as velocity\u0026thinsp;=\u0026thinsp;flow rate/length of the velocity sampling cursor. Next, velocity difference in the E-filling period between base and apex was determined as diastolic intraventricular velocity gradient (Vbp)\u0026thinsp;=\u0026thinsp;Vbase \u0026ndash; Vapex.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical data were analyzed with the SPSS 24.0 (SPSS, Inc., Chicago, IL). Normality was evaluated by the Kolmogorov-Smirnov test. Continuous data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard Deviation (SD) or median and interquartile range. Group differences were examined by one-way repeated measures analysis of variance (ANOVA) followed Tukey\u0026rsquo;s post hoc test (LSD test where equal variances were assumed, and Dunnett\u0026rsquo;s C test where equal variances were not assumed). Proportions were compared by the chi-square test. Multivariable linear regression analysis was performed to identify independent determinants of EL during the E-filling and A-filling phases. Univariate linear regression was performed to assess the effect of LVEDVI on EL-ave during the E-filling period. Receiver operating characteristic curve (ROC) analysis was performed to assess the ability of an index derived from VFM to distinguish HCM. All analyses were two-tailed, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinical and echocardiographic characteristics\u003c/h2\u003e \u003cp\u003eThe demographic and echocardiographic characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no significant differences in baseline data among the three groups, except for higher BMI in the HCM and H-LVH groups (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). Maximal myocardial thickness and LVMI increased in the following order: control, H-LVH and HCM (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). LVEDVI (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LVESVI (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were lower in the HCM group than in the other two groups. Although E velocity was similar among the three groups, A velocity values were higher in the HCM and LVH groups (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), resulting in lower E/A values (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The decreased E/A and e' (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and elevated E/e' (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LAVI (Control vs. HCM, \u003cem\u003eP\u003c/em\u003e; Control vs H-LVH, \u003cem\u003eP\u003c/em\u003e) in the HCM and H-LVH groups indicated impaired diastolic function and elevated left atrial pressure. There was no significant differences in diastolic and systolic functions between the HCM and H-LVH groups.\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\u003eClinical and echocardiographic characteristics of the study subjects\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\u003eControl (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHCM (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eH-LVH (n\u0026thinsp;=\u0026thinsp;24)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody surface area (m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (Kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.44\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.18\u0026thinsp;\u0026plusmn;\u0026thinsp;3.14\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrial volume index (mL/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.74\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.05\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.19\u0026thinsp;\u0026plusmn;\u0026thinsp;11.59\u003csup\u003ea\u003c/sup\u003e\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\u003eMaximal myocardial thickness (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.48\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003csup\u003eab\u003c/sup\u003e\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\u003eLVEDVI (mL/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.53\u0026thinsp;\u0026plusmn;\u0026thinsp;8.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.11\u0026thinsp;\u0026plusmn;\u0026thinsp;13.99\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.54\u0026thinsp;\u0026plusmn;\u0026thinsp;12.84\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVESVI (mL/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.37\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.66\u0026thinsp;\u0026plusmn;\u0026thinsp;6.07\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLV ejection fraction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.93\u0026thinsp;\u0026plusmn;\u0026thinsp;4.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.68\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLV mass index (g/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.03\u0026thinsp;\u0026plusmn;\u0026thinsp;12.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185.62\u0026thinsp;\u0026plusmn;\u0026thinsp;48.49\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e119.5\u0026thinsp;\u0026plusmn;\u0026thinsp;36.45\u003csup\u003eab\u003c/sup\u003e\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\u003eE peak (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.27\u0026thinsp;\u0026plusmn;\u0026thinsp;12.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.92\u0026thinsp;\u0026plusmn;\u0026thinsp;16.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.25\u0026thinsp;\u0026plusmn;\u0026thinsp;21.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA peak (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.09\u0026thinsp;\u0026plusmn;\u0026thinsp;15.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.28\u0026thinsp;\u0026plusmn;\u0026thinsp;21.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.68\u0026thinsp;\u0026plusmn;\u0026thinsp;17.32\u003csup\u003ea\u003c/sup\u003e\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\u003eE/A ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003csup\u003ea\u003c/sup\u003e\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\u003ee\u0026rsquo; (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003csup\u003ea\u003c/sup\u003e\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\u003eE/e\u0026lsquo;ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63\u003csup\u003ea\u003c/sup\u003e\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\u003eLV diastolic function, n(%)\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=\"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\u003eGrade I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(11.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(64%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(50%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \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\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(36)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11(45.8)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \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\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.2%)\u003c/p\u003e \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\u003eInconclusive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(88.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDate given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard Deviation or number (total)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eLV Left ventricular, LVEDVI Left ventricular end-diastolic volume index, LVESVI Left ventricular end-systolic volume index, e\u0026rsquo; Average value of septal and lateral early diastolic peak of mitral annular velocity, HCM Hypertrophic cardiomyopathy, H-LVH hypertensive left ventricular hypertrophy\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs normal control group, \u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs HCM group\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eIntracardiac vortex flow characteristics\u003c/h2\u003e \u003cp\u003eThe characteristics of vortex and streamline in different phases and different groups were shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the normal control and H-LVH groups, two vortices with opposite directions and asymmetric shapes were formed in the anterior and posterior leaflets of the mitral valve during the E-filling and A-filling phases (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB-C and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ-K). These streamlines rotated clockwise and flowed through the LVOT after forming a vortex during IVC (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eL) period and continued into the ejection period, turning into the laminar flow to gradually disappear. The number of vortices in the H-LVH group increased, partially in the apical part of the LV (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eJ-K). In the HCM group, the streamlines of 8 patients (32%) crossing the mitral valve did not form the normal vortex ring in the LV during the E-filling stage (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF). This phenomenon was termed \u0026ldquo;absent E-filling vortex ring\u0026rdquo;, in which, EL-ave was increased during the A-filling period (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea), while Vbp was relatively reduced (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb) (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). LVEDVI showed a decreasing trend, but the difference was not statistically significant (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eVFM-derived parameters\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows VFM-derived parameters in the three groups. Though there were no differences in diastolic and systolic functions between the HCM and H-LVH group, the diastolic intraventricular velocity gradient between the base and the apex (Vbp) (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) and vortex area during the atrial filling (A-filling) period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), isovolumetric contraction (IVC) period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and ejection periods (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) were reduced in the HCM group compared with the control and H-LVH groups. The average energy loss was weaker in HCM than in the control and H-LVH groups during the E-filling period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002; HCM vs. H-LVH, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and were increased in the HCM and H-LVH groups than the control group from the A-filling period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047; H-LVH vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007) and IVC period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004; H-LVH vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) to the ejection period (HCM vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; H-LVH vs. Control, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). The analysis of left ventricular EL between HCM, H-LVH and control participants was also illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Moreover, from this line chart, we can also find that the evolvement of the average energy loss in different phases of HCM group are similar to those of H-LVH group, with the lowest EL-ave in IVR period and the two peaks vales of EL-ave observed in one cardiac cycle during E-filling and ejection phases. Although the EL-ave of HCM group is also the lowest in IVR period, it gradually increases from E-filling to ejection period, with the highest peak value of EL-ave only appearing in the ejection phase.\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\u003eVFM-derived parameters of the participants\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\u003eControl (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHCM (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eH-LVH (n\u0026thinsp;=\u0026thinsp;24)\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\u003eCirculation (10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e m\u0026sup2;/s)\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\u003eAtrial filling period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.93\u0026thinsp;\u0026plusmn;\u0026thinsp;5.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.30\u0026thinsp;\u0026plusmn;\u0026thinsp;5.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsovolumic contraction period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.01\u0026thinsp;\u0026plusmn;\u0026thinsp;7.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.31\u0026thinsp;\u0026plusmn;\u0026thinsp;7.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.82\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEjection period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.61\u0026thinsp;\u0026plusmn;\u0026thinsp;5.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.39\u0026thinsp;\u0026plusmn;\u0026thinsp;6.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.96\u0026thinsp;\u0026plusmn;\u0026thinsp;4.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVortex area (cm\u0026sup2;)\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\u003eAtrial filling period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.001\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsovolumic contraction period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5278\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9479\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2111\u0026thinsp;\u0026plusmn;\u0026thinsp;1.796\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9018\u0026thinsp;\u0026plusmn;\u0026thinsp;2.238\u003csup\u003eab\u003c/sup\u003e\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\u003eEjection period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9141\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0808\u0026thinsp;\u0026plusmn;\u0026thinsp;1.187\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1063\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.053\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients without E-filling vortex ring\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(32%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.001\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean vorticity (s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003eAtrial filling period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.03\u0026thinsp;\u0026plusmn;\u0026thinsp;4.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsovolumic contraction period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.164\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEjection period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\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\u003eEL-ave (10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003eJ/m s)\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\u003eisovolumic relaxation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly filling period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.09\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.75\u003csup\u003eab\u003c/sup\u003e\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\u003eAtrial filling period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsovolumic contraction period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.24\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.64\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003csup\u003ea\u003c/sup\u003e\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\u003eEjection period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.93\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.05\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003csup\u003ea\u003c/sup\u003e\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\u003eIntraventricular velocity\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\u003eVbase (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVapex (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVbp (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003csup\u003eb\u003c/sup\u003e\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 \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDate given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard Deviation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eEL-ave Average energy loss, Vbp Diastolic intraventricular velocity gradient between the base and the apex, Vbase Intraventricular velocities at the base, Vapex Intraventricular velocities at the apex\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs HCM group, \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs control group\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=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStepwise multiple linear regression analysis\u003c/h2\u003e \u003cp\u003eThe results of multiple linear regression for predicting the average EL were shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In the control group, E-peak and LVEDVI were independent predictors of the EL-ave during E-filling period, whereas the LVEDVI, Vbp and E/A, LVMI, Vbp were respectively independent predictors of the EL-ave during E-filling in the patients with HCM and H-LVH and the correlation between LVEDVI and EL-ave in the E-filling period in the HCM group was closer (shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). EL-ave values during the A-filling period in all groups were independently associated with A peak. Except for A peak, it was also especially affected by LVEDVI in the HCM group but not in the other two groups.\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\u003eMultiple linear regression for predicting EL-ave in the three groups\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\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c10\" namest=\"c4\"\u003e \u003cp\u003eEL-ave\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c10\" namest=\"c4\"\u003e \u003cp\u003eE-filling A-filling\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ecoefficient β\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003estd.error\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecoefficient β\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003estd.error\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE peak\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.039\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\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.025\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\u003eLVEDVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c9\" namest=\"c3\"\u003e \u003cp\u003eAdjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.491, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 Adjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.641, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHCM\u003c/p\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003eE-filling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eA-filling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCoefficient β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStd.error\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\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCoefficient β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003estd.error\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\u003eLVEDVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\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\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.03\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\u003eVbp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.660\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eLVEDVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c10\" namest=\"c3\"\u003e \u003cp\u003eAdjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.66, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 Adjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.352, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH-LVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003eE-filling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eA-filling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCoefficient β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003estd.error\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\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCoefficient β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003estd.error\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\u003eE/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e14.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.294\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\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVbp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.725\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c10\" namest=\"c3\"\u003e \u003cp\u003eAdjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.672, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 Adjusted R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.440, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eVFM-derived parameters differentiating HCM from H-LVH\u003c/h2\u003e \u003cp\u003eAccording to one-way ANOVA, there were significant differences between the HCM and H-LVH groups in EL-ave during the E-filling period, vortex area during the A-filling period, IVC during the ejection period and Vbp (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). ROC curve analysis showed that EL-ave during the E-filling phase was more effective for differential diagnosis of HCM and H-LVH; the best cutoff value was 5.04 10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003eJ/m s, yielding a sensitivity of 76% and specificity of 80% (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEL in the E-filling period in the HCM and H-LVH groups\u003c/h2\u003e \u003cp\u003eThe ventricular remodeling processes associated with heart disease alter left ventricular (LV) hemodynamic parameters, including intraventricular vortex and energy loss. Intraventricular vortex can be described as fluid structures that have circular or swirling motions[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Meanwhile, energy loss (EL) is the frictional heat generated by viscosity blood. Although there was no difference in the degree of diastolic dysfunction between HCM and H-LVH cases evaluated by conventional parameters, the changes of left ventricular hemodynamics especially during the E-filling phase differed. During the E-filling phase, average EL was lower in the HCM group compared with the H-LVH group, which was associated with reduced LVEDVI and intraventricular velocity gradient from base to apex (Vbp) determined by multiple stepwise regression analysis. The diastolic intraventricular velocity gradient derived from VFM could be useful for estimating impaired LV relaxation and local flow dynamics in the ventricular chambers[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Normally, there was a progressive intraventricular pressure difference that extends from the LA to the LV apex driving early diastolic filling, which is generated by rapid myocardial relaxation and recoil of elastic elements compressed during ejection [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Then, a strong vortex pair behind mitral valve leaflets appear was initiated. In this study, for patients with HCM, impaired relaxation and reduced intraventricular volume diminishes the ability of the LV to function as a suction pump, resulting in decreased Vbp [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and the associated ring vortex at the mitral valve tips was reduced in size. Then, the weaker filling inflow jet would lead to decreased EL in the HCM group.\u003c/p\u003e \u003cp\u003eAlthough Vbp in the H-LVH group also tended to decrease, EL during the E-filling period was significantly increased in the H-LVH group. This is likely because different from the effect of LVEDVI on EL during the E-filling period in the HCM group, EL during the E-filling period is instead affected by LVMI in the H-LVH group. \u0026ldquo;Pathological\u0026rdquo; left ventricular hypertrophy (LVH) in HCM mainly has primary myocardial properties at the microscopic level, including myocyte disarray, interstitial fibrosis and replacement fibrosis, and \u0026ldquo;compensatory\u0026rdquo; LVH in hypertension is usually a compensatory mechanism in response to increased hemodynamic load, resulting in cardiomyocyte hypertrophy and extracellular matrix remodeling[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. With increasing left ventricular weight, the oxygen demand increases, myocardial cell compensation increases, and microvascular dysfunction occurs, aggravating myocardial fibrosis and endothelial cell dysfunction[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The increased pressure load on the inner myocardium compared with the outer myocardium weakens longitudinal contraction. Previous studies have found that although left ventricular strain is reduced in both diseases, HCM patients have marked reductions in LS and CS, whereas H-LVH cases have less reduction in LS and unaffected CS[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Uncoordinated contraction of inner and outer myocardium would produce irregular blood flow, and heterogeneous flow field caused by the strong collision between high flow speed and wall shear flow inevitably increases blood energy consumption[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, LV mass and LV hypertrophy in hypertension are strongly associated with impaired relaxation and increased LV filling pressure[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. When left ventricular filling pressure is elevated, the flow of left atrial blood into the left ventricle is limited, and the impact of left ventricular inflow tract blood flow on the mitral valve is reduced[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], which impairs the formation of normal vortices, with increased number of vortices and ineffective vortices loaded in the LV apical part during E-filling even to the end of the atrial contraction period. Non-physiological vortex formation leads to increased blood flow dispersion and instability, causing inflow tract deflection and lateral force generation as well as higher energy consumption. From the above, we can infer that differences in abnormal diastolic hemodynamics observed between HCM and H-LVH are reflected by EL during the E-filling phase and are affected by different pathological cardiac configurations between HCM and H-LVH.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eNon-physiological vortices in HCM and H-LVH\u003c/h2\u003e \u003cp\u003eVortex area in the HCM group was the smallest in each period, and in eight patients (32%) of the latter group, no well-formed E-filling vortex ring core was detected; LV interior volumes tended to decrease, although statistical significance was not reached. Previous studies have confirmed that LV shape and internal volume also play critical roles in vortex ring dynamics in the LV filling and ejection phases. Reduced LV volume could deprive the LV of its ability to enhance the formation of ring vortices at the mitral valve tips,[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] indicating the importance of LV morphology. Interestingly, we also found that Vbp was smaller and EL during the A-filling phase was increased in HCM patients without normal vortex formation. Under normal circumstances, blood flows towards the apex prior to the mitral valve opening, and the mitral annulus moves rapidly away after the valve opens; thus, the created intracardiac pressure gradient promotes vortex formation. Once generated, vortices as relatively longstanding inertial flow structures can create a virtual hydrodynamic channel extending from the mitral valve towards the apex of the heart, which facilitates filling by reducing convective losses and enhancing the function of the LV as a suction pump[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These findings suggest that intraventricular pressure gradient and the vortex promote each other. Once vortex generation is impaired, this mechanism could weaken or even disappear. This suggested that myocardial diastolic function appears to be more vulnerable in patients with HCM, in accordance with previous studies[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe study demonstrated that the vortex additionally contributes to diastolic function by \u0026ldquo;pulling\u0026rdquo; blood from the LA into the LV, particularly during the E-wave deceleration, diastasis and late filling phases, which helps 10\u0026ndash;15% of its filling volume enter the LV at no metabolic or pressure cost [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In most cases, its disappearance is unlikely to result in decreased cardiac output, because the heart can compensate for the disappeared vortex without affecting cardiac output. However, without changing the mechanical properties of the myocardium, this can only be achieved by increasing atrial thrust and/or accelerating diastolic speed, even increasing atrial pressure. In other words, the heart could fill the LV without normal vortex, but at the cost of increasing metabolic demand and/or atrial pressure[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eEL during the A-filling and ejection phases\u003c/h2\u003e \u003cp\u003eEL increased in the A-filling and ejection phases in both HCM and H-LVH groups, but vortex circulation values did not increase accordingly. Circulation is one of the main parameters reflecting vortex strength. EL increase is related to elevated vortex strength, which seems to be a normal physiological phenomenon or in a highly hemodynamic state. However, in the absence of vortex strength increase, elevated EL indicates a turbulence in the intraventricular region [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The generation of intraventricular turbulence during A-filling in HCM and H-LVH is related to left ventricular diastolic dysfunction manifested by significantly decreased mitral annulus velocity (e ') and elevated left ventricular filling pressure. Decreased left ventricular elastic recoil and relaxation force may cause left atrial contraction compensatory filling actively [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. To maintain a certain filling pressure, blood flow into the left ventricle with the direction and speed change drastically, intraventricular flow velocity increases, coupled with elevated left ventricular stiffness, and the turbulence phenomenon aggravates such irregular blood flow and shear flow chamber wall; the intense collision inevitably increases the energy consumption of blood. In addition, increased EL-ave during the A-filling period of HCM is related to decreased LVEDVI. It may be caused by the confinement imposed by decreased LV volume on the filling vortex, which could inhibit the formation of vortex and affect its stability[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. At this time, the vortex loses its original assisting effect and increases energy consumption.\u003c/p\u003e \u003cp\u003eFibrosis of the left ventricular wall in HCM and H-LVH may lead to impaired contractile deformation ability of the left ventricular myocardium[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, extra work and enhanced energy consumption are required to maintain normal ejection. This reflects the inefficient hemodynamic status of HCM and H-LVH.\u003c/p\u003e \u003cp\u003eThere were several limitations that should be pointed out. The main limitation is that the sample size of this study was limited, especially in the HCM group. As a result, LVEDVI in HCM patients with no well-formed E-filling vortex ring was decreased, but statistical significance was not reached. It is necessary to assess more patients with HCM to explore the anatomical factors of HCM patients of no well-formed E-peak vortex ring, e.g., abnormal papillary muscle position, thickening of ventricular wall position, etc. Secondly, in this investigation, we did not measure LV pressure by cardiac catheterization, and the examined patients only underwent the vector flow mapping test. Our data generated by vector flow mapping have not been compared with the invasive intraventricular pressure gradient. Future studies with larger patient cohorts are required to overcome these limitations and to validate our findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, energy inefficiency differences in HCM and H-LVH are reflected by diastole non-physiological vortex and EL, suggesting that future studies need to explore the application of VFM-related parameters for closely monitoring disease progression, predicting adverse outcomes, and exploring new therapeutic options.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eA: Mitral late filling wave peak velocity; HCM: Hypertrophic cardiomyopathy; H-LVH: Hypertensive left ventricular hypertrophy; E: Mitral early filling wave peak velocity; e\u0026rsquo;: Average value of septal and lateral early diastolic peak of mitral annular velocity; LVEDVI: Left ventricular end-diastolic volume index; Vbp: Diastolic intraventricular velocity gradient between the base and the apex; Vbase: Intraventricular velocities at the base; Vapex: Intraventricular velocities at the apex; IVR: Isovolumetric relaxation; E-filling: Early filling; A-filling: atrial filling; IVC: Isovolumetric contraction; EL-ave: Average energy loss; LVMI: Left ventricular mass index; VFM: Vector flow mapping; LVESVI: Left ventricular end-systolic volume index; ROC: Receiver-operating characteristic.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWW, YH W, HB designed the experiments and analyzed and\u0026nbsp;interpreted the data. YH W subsidized and conceived of the study. WW, ZG, FW, SS L contributed to the acquisition of image and the collection of data. WW wrote the manuscript and HB, YH W was helpful in text revision.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the\u0026nbsp;Science and technology project of Hebei Provincial Health Commission\u0026nbsp;in China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed in this study are available from the\u0026nbsp;corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis clinical study was approved by the Ethics Committee of the Second\u0026nbsp;Hospital of Hebei Medical University and the ethics number is 2020-R567. Written informed consent were signed\u0026nbsp;by all participants. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Cardiac Ultrasound, Second Hospital of Hebei Medical\u0026nbsp;University, 215 Hepingxi Road, Shijiazhuang 050000, Hebei, China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of physical examination center, Hebei Provincial People\u0026apos;s Hospital, Shijiazhuang City, Hebei Province, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSantos Mateo JJ, Sabater Molina M, Gimeno Blanes JR. Hypertrophic cardiomyopathy. Med Clin (Barc). 2018;150(11):434\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerdecchia P, Angeli F, Achilli P, Castellani C, Broccatelli A, Gattobigio R, Cavallini C. Echocardiographic left ventricular hypertrophy in hypertension: marker for future events or mediator of events? Curr Opin Cardiol. 2007;22(4):329\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eServatius H, Raab S, Asatryan B, Haeberlin A, Branca M, de Marchi S, Brugger N, Nozica N, Goulouti E, Elchinova E, et al: \u003cb\u003eDifferences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes' Hearts\u003c/b\u003e. J Clin Med 2022, 11(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePopa-Fotea NM, Micheu MM, Oprescu N, Alexandrescu A, Greavu M, Onciul S, Onut R, Petre I, Scarlatescu A, Stoian M, et al: \u003cb\u003eThe Role of Left\u003c/b\u003e-\u003cb\u003eAtrial Mechanics Assessed by Two\u003c/b\u003e-\u003cb\u003eDimensional Speckle\u003c/b\u003e-\u003cb\u003eTracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left\u003c/b\u003e-\u003cb\u003eVentricular Hypertrophy\u003c/b\u003e. \u003cem\u003eDiagnostics (Basel, Switzerland)\u003c/em\u003e 2021, \u003cb\u003e11\u003c/b\u003e(5).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVoigt C, M\u0026uuml;nch J, Avanesov M, Suling A, Witzel K, Lund G, Patten M. Early segmental relaxation abnormalities in hypertrophic cardiomyopathy for differential diagnostic of patients with left ventricular hypertrophy. Clin Cardiol. 2017;40(11):1026\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChacko BR, Karur GR, Connelly KA, Yan RT, Kirpalani A, Wald R, Jimenez-Juan L, Jacob JR, Deva DP, Yan AT. Left ventricular structure and diastolic function by cardiac magnetic resonance imaging in hypertrophic cardiomyopathy. Indian Heart J. 2018;70(1):75\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoya S, Wada T, Shimada K, Hirao D, Tanaka R. The relationship between systolic vector flow mapping parameters and left ventricular cardiac function in healthy dogs. Heart Vessels. 2018;33(5):549\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/\u003cb\u003eASPC\u003c/b\u003e/\u003cb\u003eNMA\u003c/b\u003e/\u003cb\u003ePCNA Guideline for the Prevention\u003c/b\u003e, \u003cb\u003eDetection\u003c/b\u003e, \u003cb\u003eEvaluation\u003c/b\u003e, \u003cb\u003eand Management of High Blood Pressure in Adults\u003c/b\u003e: \u003cb\u003eExecutive Summary\u003c/b\u003e: \u003cb\u003eA Report of the American College of Cardiology\u003c/b\u003e/\u003cb\u003eAmerican Heart Association Task Force on Clinical Practice Guidelines\u003c/b\u003e. \u003cem\u003eHypertension (Dallas, Tex: 1979)\u003c/em\u003e 2018, \u003cb\u003e71\u003c/b\u003e(6):1269\u0026ndash;1324.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cb\u003eRecommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of, Cardiovascular Imaging\u003c/b\u003e. European heart journal Cardiovascular Imaging 2016, 17(4):412.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao Y, Sun XY, Zhong M, Li L, Zhang M, Lin MJ, Zhang YK, Jiang GH, Zhang W, Shang YY. Evaluation of hemodynamics in patients with hypertrophic cardiomyopathy by vector flow mapping: Comparison with healthy subjects. Exp Ther Med. 2019;17(6):4379\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen M, Jin JM, Zhang Y, Gao Y, Liu SL. Assessment of left ventricular diastolic dysfunction based on the intraventricular velocity difference by vector flow mapping. J ultrasound medicine: official J Am Inst Ultrasound Med. 2013;32(12):2063\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerlot B, Moya Mur JL, Jug B, Rodr\u0026iacute;guez Mu\u0026ntilde;oz D, Megias A, Casas Rojo E, Fern\u0026aacute;ndez-Golf\u0026iacute;n C, Zamorano JL. Effect of diastolic dysfunction on intraventricular velocity behavior in early diastole by flow mapping. Int J Cardiovasc Imaging. 2019;35(9):1627\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStewart KC, Kumar R, Charonko JJ, Ohara T, Vlachos PP, Little WC. Evaluation of LV diastolic function from color M-mode echocardiography. JACC Cardiovasc imaging. 2011;4(1):37\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZuo X, Yuan M, Jia H, Zhang M, Zhang C, Zhi G. Vector Flow Mapping Application in Local Cardiac Function in Hypertension Assessment. Int J Gen Med. 2021;14:4793\u0026ndash;801.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun JP, Xu TY, Ni XD, Yang XS, Hu JL, Wang SC, Li Y, Bahler RC, Wang JG. Echocardiographic strain in hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy. Echocardiography. 2019;36(2):257\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang W, Wang Y, Chen X, Yuan L, Bai H. Evaluation of left ventricular diastolic function based on flow energetic parameters in chronic kidney disease with diastolic dysfunction. Echocardiography. 2019;36(3):567\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDini FL, Galderisi M, Nistri S, Buralli S, Ballo P, Mele D, Badano LP, Faggiano P, de Gregorio C, Rosa GM, et al. Abnormal left ventricular longitudinal function assessed by echocardiographic and tissue Doppler imaging is a powerful predictor of diastolic dysfunction in hypertensive patients: the SPHERE study. Int J Cardiol. 2013;168(4):3351\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarashina-Motoi M, Iwano H, Motoi K, Ishizaka S, Chiba Y, Tsujinaga S, Murayama M, Nakabachi M, Yokoyama S, Nishino H, et al. Functional significance of intra-left ventricular vortices on energy efficiency in normal, dilated, and hypertrophied hearts. J Clin ultrasound: JCU. 2021;49(4):358\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCharonko JJ, Kumar R, Stewart K, Little WC, Vlachos PP. Vortices formed on the mitral valve tips aid normal left ventricular filling. Ann Biomed Eng. 2013;41(5):1049\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu W, Sun D, Yang J: \u003cb\u003eDiastolic Dysfunction of Hypertrophic Cardiomyopathy Genotype\u003c/b\u003e-\u003cb\u003ePositive Subjects Without Hypertrophy Is Detected by Tissue Doppler Imaging\u003c/b\u003e: \u003cb\u003eA Systematic Review and Meta\u003c/b\u003e-\u003cb\u003eanalysis\u003c/b\u003e. \u003cem\u003eJournal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine\u003c/em\u003e 2017, \u003cb\u003e36\u003c/b\u003e(10):2093\u0026ndash;2103.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMart\u0026iacute;nez-Legazpi P, Bermejo J, Benito Y, Yotti R, P\u0026eacute;rez Del Villar C, Gonz\u0026aacute;lez-Mansilla A, Barrio A, Villacorta E, S\u0026aacute;nchez PL, Fern\u0026aacute;ndez-Avil\u0026eacute;s F, et al. Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol. 2014;64(16):1711\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJi L, Hu W, Yong Y, Wu H, Zhou L, Xu D. Left ventricular energy loss and wall shear stress assessed by vector flow mapping in patients with hypertrophic cardiomyopathy. Int J Cardiovasc Imaging. 2018;34(9):1383\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlis D, Guler A, Asmakutlu O, Topel C, Sahin AA. The Association between the Extent of Late Gadolinium Enhancement and Diastolic Dysfunction in Hypertrophic Cardiomyopathy. Indian J Radiol Imaging. 2021;31(2):284\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamaee M, Nelsen NH, Gaddam MG, Santhanakrishnan A. \u003cb\u003eDiastolic Vortex Alterations With Reducing Left Ventricular Volume: An In Vitro Study\u003c/b\u003e. Journal of biomechanical engineering 2020, 142(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka H. Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain. J echocardiography. 2021;19(2):71\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Vector flow mapping, Energy loss, Hypertrophic cardiomyopathy, hypertensive LV hypertrophy, Intracardiac vortex","lastPublishedDoi":"10.21203/rs.3.rs-2072528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2072528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHypertrophic cardiomyopathy (HCM) and secondary hypertensive LV hypertrophy (H-LVH) differ in pathophysiology. However, the differences and mechanisms of their blood flow fields have not been well studied. This study aimed to assess energy loss (EL), circulation, vortex area, vorticity and intraventricular velocity gradient between these two hypertrophy types.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e Vector flow mapping (VFM) echocardiography was performed in 35 healthy participants, 25 HCM patients, and 24 H-LVH patients. Circulation, vortex area and vorticity during atrial filling (A-filling), isovolumic contraction (IVC) and ejection period were measured, as well as intraventricular velocity gradient during the E-filling period and average energy loss (EL-ave) during one cardiac cycle for each period. Measurements were averaged over three cardiac cycles.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe \u0026ldquo;absent E-filling vortex ring\u0026rdquo; phenomenon was found in 8 HCM cases (32%), with significantly increased EL-ave during the A-filling period and relatively reduced diastolic intraventricular velocity gradient between the base and the apex (Vbp) compared with patients with normal E-filling vortex ring. EL-ave during the E-filling period was weaker in HCM than in the control and H-LVH groups. From A-filling to ejection, EL-ave was obviously increased in the HCM and H-LVH groups compared to the control group. Multivariable analyses revealed that EL-ave during the E-filling period in the HCM and H-LVH groups was affected by different heart structure-related factors and had a good diagnostic efficiency in differentiating HCM from H-LVH.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDifferences in abnormal hemodynamics observed between HCM and H-LVH are reflected in both VFM-derived parameters, especially non-physiological vortices and early filling EL, which is closely related to special morphology. EL during E-filling as a novel parameter may be may be useful in differentiating HCM from hypertensive LVH.\u003c/p\u003e","manuscriptTitle":"Quantitative Analysis of Left Ventricular Flow Dynamics in Hypertrophic Cardiomyopathy using vector flow mapping: Comparison with hypertensive LV hypertrophy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-23 20:20:49","doi":"10.21203/rs.3.rs-2072528/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":"efd1794e-8e61-4779-b419-cba8b7c279cc","owner":[],"postedDate":"September 23rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-12-23T05:14:24+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-23 20:20:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2072528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2072528","identity":"rs-2072528","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.