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Background: Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear., Methods and Results: We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP., Conclusions: Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

Background: Left ventricular (LV) circumferential strain has received less attention than longitudinal deformation, which has recently become part of routine clinical practice. Among other reasons, this is because of the lack of established normal values. Accordingly, the aim of this study was to establish normative values for LV circumferential strain and determine sex-, age-, and race-related differences in a large cohort of healthy adults., Methods: Complete two-dimensional transthoracic echocardiograms were obtained in 1,572 healthy subjects (51% men), enrolled in the World Alliance Societies of Echocardiography Normal Values Study. Subjects were divided into three age groups (<35, 35-55, and >55 years) and stratified by sex and by race. Vendor-independent semiautomated speckle-tracking software was used to determine LV regional circumferential strain and global circumferential strain (GCS) values. Limits of normal for each measurement were defined as 95% of the corresponding sex and age group falling between the 2.5th and 97.5th percentiles. Intergroup differences were analyzed using unpaired t tests., Results: Circumferential strain showed a gradient, with lower magnitude at the mitral valve level, increasing progressively toward the apex. Compared with men, women had statistically higher magnitudes of regional and global strain. Older age was associated with a stepwise increase in GCS despite an unaffected ejection fraction, a decrease in LV volume, and relatively stable global longitudinal strain in men, with a small gradual decrease in women. Asian subjects demonstrated significantly higher GCS magnitudes than whites of both sexes and blacks among women only. In contrast, no significant differences in GCS were found between white and black subjects of either sex. Importantly, despite statistical significance of these differences across sex, age, and race, circumferential strain values were similar in all groups, with variations of the order of magnitude of 1% to 2%. Notably, no differences in GCS were found among brands of imaging equipment., Conclusion: This study established normal values of LV regional circumferential strain and GCS and identified sex-, age-, and race-related differences when present., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Enlargement of the mitral valve (MV) has gained attention as a compensatory mechanism for functional mitral regurgitation (FMR). We aimed to determine if MV leaflet area is associated with MV coaptation-zone area and identify the clinical factors associated with MV leaflet size and coaptation-zone area in patients with normal left ventricle (LV) systolic function and size using real-time 3D echocardiography (RT3DE).We performed RT3DE in 135 patients with normal LV size and ejection fraction. MV leaflet and coaptation-zone areas were measured using custom 3D software. The clinical factors associated with MV leaflet and coaptation-zone areas were evaluated using univariate and multivariate linear regression analyses.There was a significant relationship between MV leaflet and coaptation-zone areas (r = 0.499, P < 0.001). MV leaflet area was strongly associated with body surface area (BSA) (r = 0.905, P < 0.001) rather than LV size and age. MV leaflet area/BSA was independently associated with male gender (P = 0.002), lower diastolic blood pressure (P = 0.042), and LV end-diastolic volume (LVEDV) index (P = 0.048); MV coaptation-zone area/BSA was independently associated with lower LVEDV index (P = 0.01).In patients with normal LV systolic function and size, MV leaflet size has a significant impact on competent MV coaptation. MV leaflet area might be intrinsically determined by body size rather than age and LV size, and the MV leaflet area/BSA is relatively constant. On the other hand, some clinical factors might also influence MV leaflet and coaptation-zone area.

Aims: Obesity carries significant risk for unfavorable ventricular remodeling and subsequent heart failure (HF) development, although the association between abdominal fat distribution and subclinical ventricular dysfunction is unclear. This study aimed to compare the subcutaneous and visceral abdominal adiposity with the risk of decreased ventricular strain., Methods: We included 340 participants without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination, and speckle-tracking echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVLS)., Results: Mean age was 56 ± 9 years, and 244 of the participants (72%) were male. The mean LVGLS and RVLS were -19.1 ± 3.0% and -25.0 ± 4.1%, respectively. Both VFA and SFA correlated with LVGLS ( r  = 0.46 and r  = 0.15, both p  < 0.01) and RVLS ( r  = 0.38 and r  = 0.12, both p  < 0.05), demonstrating a stronger correlation between VFA and ventricular strain. Multivariable analysis showed that VFA was significantly associated with LVGLS and RVLS, independent of traditional cardiovascular risk factors as well as pertinent laboratory and echocardiographic parameters (both p  < 0.05), whereas SFA was not. Serum adiponectin level was correlated with LVGLS ( r  = -0.34, p  < 0.001) and RVLS ( r  = -0.25, p  < 0.001), although it lost statistical significance following multivariable adjustment., Conclusion: In a sample of the general population, VFA, but not SFA, accumulation was significantly associated with decreased LV and RV strain, an association that may be involved in the increased risk of HF in obese individuals.

Background: The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates individuals from multiple countries and races with the aim of describing normative values that could be applied to the global community worldwide and to determine differences and similarities among people from different countries and races. The present report focuses specifically on two-dimensional (2D) left ventricular (LV) dimensions, volumes, and systolic function., Methods: The WASE Normal Values Study is a multicenter international, observational, prospective, cross-sectional study of healthy adult individuals. Participants recruited in each country were evenly distributed among six predetermined subgroups according to age and gender. Comprehensive 2D transthoracic echocardiograms were acquired and analyzed following strict protocols based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. Analysis was performed at the WASE 2D core laboratory and included 2D LV dimensions, LV volumes, and LV ejection fraction (LVEF) by the biplane Simpson method and global longitudinal strain (GLS)., Results: Two thousand eight subjects were enrolled in 15 countries. The median age was 45 years (interquartile range, 32-65 years), 42.8% were white, 41.8% were Asian, and 9.7% were black. LV dimensions and volumes were larger in male subjects, while LVEF and GLS were higher in female subjects. Global WASE normal ranges for LV dimensions were smaller than those in the guidelines, but the upper limits of normal for LV volumes and the lower limits of normal for LVEF were higher in the WASE study. Significant intercountry variation was identified for all LV parameters reflecting LV size (dimensions, mass, and volumes) even after indexing to body surface area, with LV end-diastolic and end-systolic volumes having the highest variation. The largest volumes were noted in Australia, while the smallest were measured in India for both genders. This finding suggests that in addition to gender and body surface area, specific country should be considered when evaluating LV volumes. Intercountry variation for LVEF and GLS was smaller but still statistically significant (P < .05 for all)., Conclusions: LV dimensions and volumes are larger in men, while LVEF and GLS are higher in women. Current guideline-recommended normal ranges for LV volumes and LVEF should be adjusted. Intercountry variability is significant for LV volumes, and therefore nationality should be considered for defining ranges of normality., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Although a cardioprotective effect of estrogen has been suggested by experimental studies, clinical data on the influence of estrogen on left ventricular (LV) diastolic function are sparse. The LV untwisting rate obtained by 2D speckle tracking echocardiography (2D-STE) is correlated with the time constant of LV pressure decay (tau), and this correlation is independent of left atrial pressure. Therefore, we used conventional Doppler echocardiography and 2D-STE to investigate changes in LV diastolic function during a single menstrual cycle in premenopausal women., Methods: Twenty healthy premenopausal woman (mean age, 28.1±2.7 years) were enrolled. Clinical and echocardiographic data were obtained during the follicular phase (F-phase) and luteal phase (L-phase) of a single menstrual cycle. We compared the clinical and echocardiographic data, and estrogen levels between the two phases., Results: There were no significant differences in LV diastolic parameters derived from Doppler echocardiography (E/A, p=0.295; E/e', p=0.449, DcT, p=0.178) or 2D-STE (peak untwisting rate, p=0.892; time-to-peak untwisting, p=0.951) between the two phases of the menstrual cycle. However, there was a significant decrease in estrogen levels between the F- and L-phases (177±119pg/ml vs. 35±12pg/ml, p<0.0001)., Conclusions: LV diastolic function in healthy premenopausal women did not significantly change during the menstrual cycle. Estrogen does not appear to have a significant acute effect on LV diastolic function in premenopausal woman., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Obesity has been found to be associated with future development of diastolic heart failure. Other evidence has indicated that the effect of obesity on left ventricular (LV) mass varies among ethnicities. However, there are few data on the relationship between body mass index (BMI) and LV diastolic dysfunction in the Japanese population., Methods and results: We performed echocardiography in 788 subjects without valvular disease or LV systolic dysfunction. They were divided into 3 groups by BMI: normal weight, overweight, and obese. We used multivariable linear regression analysis to assess the clinical variables associated with diastolic parameters, including BMI. We also assessed the risk of diastolic dysfunction associated with BMI using multivariable logistic models. Overweight and obese subjects had significantly worse LV diastolic function and greater LV mass than normal weight subjects. In the multivariable analysis, BMI was independently associated with diastolic parameters. Furthermore, after adjusting for clinical factors, the increased risks of diastolic dysfunction in overweight subjects (adjusted odds ratio: 2.02, 95% confidence interval 1.21-3.36) and obese subjects (4.85, 3.36-16.27) were greater than those previously observed in Western populations., Conclusions: The Japanese population might be more susceptible than Western subjects to the effect of BMI on LV diastolic function. Differences between ethnicities should be taken into consideration in strategies for the prevention of diastolic heart failure. (Circ J 2016; 80: 1951-1956).

Background: Left ventricular (LV) diastolic dysfunction is known as an early marker of myocardial alterations in patients with diabetes. Because microvascular disease has been regarded as an important cause of heart failure or diastolic dysfunction in diabetic patients, we tested the hypothesis that coronary flow reserve (CFR), which reflects coronary microvascular function, is associated with LV diastolic dysfunction in patients with type 2 diabetes., Methods: We studied asymptomatic patients with type 2 diabetes but without overt heart failure. Transthoracic Doppler echocardiography was performed that included pulsed tissue Doppler of the mitral annulus and CFR of the left anterior descending artery (induced by adenosine 0.14 mg/kg/min). The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/e') was used as a surrogate marker of diastolic function. We also evaluated renal function, lipid profile, parameters of glycemic control and other clinical characteristics to determine their association with E/e'. Patients with LV ejection fraction <50%, atrial fibrillation, valvular disease, regional wall motion abnormality, renal failure (serum creatinine >2.0 mg/dl) or type 1 diabetes were excluded. Patients with a CFR <2.0 were also excluded based on the suspicion of significant coronary artery stenosis., Results: We included 67 asymptomatic patients with type 2 diabetes and 14 non-diabetic controls in the final study population. In univariate analysis, age, presence of hypertension, LV mass index, estimated glomerular filtration rate and CFR were significantly associated with E/e'. Multivariate analysis indicated that both LV mass index and CFR were independently associated with E/e'. In contrast, there were no significant associations between parameters of glycemic control and E/e'., Conclusions: CFR was associated with LV filling pressure in patients with type 2 diabetes. This result suggests a possible link between coronary microvascular disease and LV diastolic function in these subjects.

Noninvasive detection of coronary artery stenosis usually requires a stress test in patients without left ventricular (LV) regional wall motion abnormalities (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may persist beyond recovery from transient ischemia. The aim of the present study was to determine whether segmental analysis of abnormal regional LV relaxation using the strain imaging diastolic index (SI-DI) at rest could predict coronary artery stenosis in the three major vessels in patients without LV dysfunction or RWMA. We performed 2D speckle tracking echocardiography and coronary angiography in 85 patients without RWMA with suspected coronary artery disease. Patients with LV dysfunction or acute coronary syndrome were excluded. Echocardiographic images of the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6 segments. In each segment, SI-DI derived from transverse strain imaging was determined. Forty-eight patients had significant coronary artery stenosis (≥ 70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal segment for detecting left anterior descending artery stenosis (sensitivity, 83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity, 90.3%), and 61.5% in the basal inferior segment for detecting right coronary artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of SI-DI at rest predicted coronary artery stenosis in the three major vessels in patients without RWMA. This noninvasive method may be useful for detecting coronary artery stenosis without a stress test.

Background: The recently developed real-time 3-dimensional echocardiography (RT3DE) is a promising imaging method to quantify cardiac chamber volumes and their functions in clinical practice. However, normal reference values of RT3DE parameters have not been fully investigated in a large, healthy Japanese population., Methods and Results: This study consisted of 410 healthy subjects aged from 20 to 69 years who had a RT3DE at one of the 23 collaborating institutions. All subjects had no history of cardiac disease and no risk factors. The mean values in men and women were as follows: 50 ± 12 ml/m(2) and 46 ± 9 ml/m(2) for left ventricular (LV) end-diastolic volume index, 19 ± 5 ml/m(2) and 17 ± 4 ml/m(2) for end-systolic volume index, 61 ± 4% and 63 ± 4% for ejection fraction, 64 ± 1 2 g/m(2) and 56 ± 11 g/m(2) for mass index, 23 ± 6 ml/m(2) and 24 ± 6 ml/m(2) for left atrial (LA) maximum volume index, 10 ± 3 ml/m(2) and 10 ± 3 ml/m(2) for minimum volume index, and 58 ± 6% and 58 ± 6% for percent volume change. LV sizes decreased with age, whereas LV mass index did not change. LA sizes slightly increased with age., Conclusions: This multicenter investigation determined normal reference values for LV and LA sizes, and their functional parameters on RT3DE in a large, healthy Japanese population. The results of the present study support the use of RT3DE for the diagnosis and management of cardiovascular disease.

Background: The purpose of the present study was to investigate gender differences in age-related changes of left ventricular (LV) and right ventricular (RV) geometries and functions throughout the entire adult age range using the Japanese Normal Values for Echocardiographic Measurements Project (JAMP) study database., Methods and Results: Seven hundred healthy volunteers (aged 20-79 years) underwent 2-dimensional and Doppler echocardiography. The subjects were stratified into 6 different age groups and then stratified by gender in each age group. LV diastolic function was assessed from pulsed wave Doppler measurements of mitral early (E) and late (A) inflow velocities and tissue Doppler measurements of mitral early (e') and late (a') annular velocities. LV volume decreased and LV mass increased with age to a similar extent in both men and women. Furthermore, for subjects <50 years, women had significantly greater E, E/A ratio and e' than men, but these parameters were similar between genders in subjects >50 years. In addition, there was a significant interaction between age and gender that affected the differences in E, e' and E/e' among the groups (P<0.03, P<0.01, and P<0.03, respectively; ANOVA). There were no gender differences in age-related changes in RV parameters., Conclusions: Gender differences were found in age-related changes in LV diastolic function in a healthy population. Gender differences should be considered for optimal diagnosis and management of cardiovascular disease.

Objective: Most studies of the pathogenesis of functional mitral regurgitation (MR) have focused on alterations in ventricular function and geometry. We used a novel 3D echocardiographic method to assess abnormalities in mitral annular (MA) geometry and motion in patients with ischemic MR (IMR) and compared these data to those obtained from normal subjects and from patients with MR caused by dilated cardiomyopathy (DMR)., Methods: Real time 3D echo was performed in 12 normal subjects, 25 with IMR, and 14 with DMR. Eight points along the saddle-shaped MA were identified using our software at systole and diastole. From these eight points, four annular diameters at each cardiac phase were determined. Annular motion was assessed by measuring local displacement (LD) of a given point between systole and diastole., Results: Annular motion was different between groups: IMR had smaller LD in posterior MA segments than did normals (2.6 +/- 1.1 vs 4.8 +/- 1.9 mm, P < 0.01), while DMR had globally reduced LD. In IMR systolic MA dilatation was striking in the anterior-posterior (diameter; IMR vs controls, 28.3 +/- 3.5 vs 22.5 +/- 2.2 mm, P< 0.05) and anterolateral-posteromedial (31.7 +/- 3.5 vs 25.1 +/- 2.2 mm, P < 0.05) directions; in IMR, systolic MA diameters in these two directions correlated with MR severity(P = 0.02). MA dilatation occurred globally in DMR., Conclusion: This novel 3D echo method demonstrated that MA motion and dilatation were asymmetric in IMR and symmetric in DMR. These differences in MA geometry and motion may aid in the development of distinct new therapies for IMR and DMR.

We used a novel 3-dimensional (3D) echocardiographic technique to evaluate the impact of a coronary sinus-based percutaneous transvenous mitral annuloplasty (PTMA) on dynamic changes in mitral annular geometry and motion during the cardiac cycle in 8 sheep with ischemic mitral regurgitation. Using real-time 3D echocardiographic data before and after PTMA, 10 points along the saddle-shaped annulus were identified. For every 3D volume/frame during a cardiac cycle, we assessed mitral annular area and excursion defined as the traveling distance of the annular center. The PTMA device reduced both minimum and maximal mitral annular area (9.5 +/- 0.9-7.0 +/- 0.6 and 12.8 +/- 1.3-9.8 +/- 1.5 cm(2), P < .001 for both, respectively) with reduction of mitral regurgitation jet area (5.1 +/- 2.3-1.2 +/- 0.8 cm(2), P < .001), whereas it did not significantly impair mitral annular excursion amplitude (8.3 +/- 1.1-7.0 +/- 1.9 mm, P = .13). This 3D echocardiographic method noninvasively enabled dynamic study of mitral annular geometry and motion with quantitative analysis of the impact of PTMA.

Objectives: Left ventricular function was assessed by two-dimensional echocardiography before and one year after coronary artery bypass grafting(CABG) in a series of patients with severe coronary artery disease with diabetes mellitus(DM) and without DM(non-DM)., Methods: Twenty-three patients with DM and 50 patients without DM, all with no previous myocardial infarction, underwent two-dimensional echocardiography before CABG and one year after CABG, in a non-matched study. For a matched study, 31 patients without DM who had almost the same left ventricular function as DM patients at the baseline were selected to and compare the rate of improvement in left ventricular function between the DM group and the "matched" non-DM group., Results: In the non-matched study, patient characteristics were not significantly different between the 2 groups except for the incidence of congestive heart failure within one year before CABG, which was significantly higher in the DM group. Fractional shortening was significantly lower in the DM group at the baseline(p < 0.05) and also one year after CABG(p < 0.0001). Significant improvement in fractional shortening was seen in the non-DM group(p < 0.001), but not in the DM group. The left ventricular end-diastolic diameter(LVDd) was significantly larger in the DM group at the baseline(p < 0.01), and was still significantly larger in the DM group at one year after CABG(p < 0.01). No improvement in LVDd was seen in the DM group. In the matched study, fractional shortening of the non-DM group also showed significant improvement after CABG(p < 0.001). Moreover, the rate of improvement in fractional shortening was higher in the non-DM group than in the DM group(p < 0.05). LVDd tended to be larger in the DM group(p = NS)., Conclusions: Left ventricular dysfunction and left ventricular impaired improvement were seen in the patients with DM, and CABG improved left ventricular function in the patients without DM with poor left ventricular function. These findings indicate that CABG therapy may be inadequate for improving left ventricular function in patients with DM and severe left ventricular dysfunction at the baseline.