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Background: Although the assessment of right ventricular (RV) diastolic function is feasible, it has garnered far less momentum for use compared with its left ventricular counterpart. The scarcity of data defining normative RV diastolic function and the fact that implications of RV diastolic dysfunction in different disease states on outcomes are less well known both hinder integration into routine clinical assessment. The aim of this study was to establish normal values of RV diastolic parameters stratified by sex, age, and race using data from the World Alliance Societies of Echocardiography study. Methods: A subset of 888 normal subjects from the World Alliance Societies of Echocardiography database were analyzed, including measurements of tricuspid valve (TV) inflow E- and A-wave velocities, E-wave deceleration time, and TV annular tissue Doppler e′ and a′ velocities. Additionally, right atrial (RA) maximal volume and RA peak reservoir strain were measured. Patients were grouped by age ([removed]65 years) and stratified by sex and race. Differences were analyzed using unpaired t tests. Results: Compared with men, women had significantly higher TV e′ and E-wave and A-wave velocities, though differences were modest. Increasing age was associated with stepwise lower TV E wave, e′ velocity, and TV E/A ratio and higher a′ velocity and E/e′ ratio. RA peak reservoir strain was also lower, and RA end-systolic volume trended toward being smaller for older age groups. Asian subjects demonstrated significantly higher a′ velocities, lower E wave, the smallest RA end-systolic volumes, and the lowest RA peak strain values compared with white subjects of both sexes. Conclusions: This study provides normal values for parameters used in the assessment of RV diastolic function stratified by race, sex, and age. The results demonstrate significant differences in RV diastolic parameters between age groups, which manifest in both individual parameters and composite ratios of TV inflow and annular velocities. Although limited sex- and race-related differences were also noted, age appears to have the most significant impact on RV diastolic parameters. These findings may aid in refining current normative values.

Background: Although increased left ventricular (LV) mass is associated with adverse outcomes, measured values vary widely depending on the specific technique used. Moreover, the impact of sex, age, and race on LV mass remains controversial, further limiting the clinical use of this parameter. Accordingly, the authors studied LV mass using a variety of two-dimensional and three-dimensional echocardiographic techniques in a large population of normal subjects encompassing a wide range of ages. Methods: Transthoracic echocardiograms obtained from 1,854 healthy adult subjects (52% men) enrolled in the World Alliance Societies of Echocardiography (WASE) Normal Values Study, were divided into three age groups (young, 18-35 years; middle aged, 36-55 years; and old, >55 years). LV mass was obtained using five conventional techniques, including linear and two-dimensional methods, as well as direct three-dimensional measurement. All LV mass values were indexed to body surface area, and differences according to sex, age, and race were analyzed for each technique. Results: LV mass values differed significantly among the five techniques. Three-dimensional measurements were considerably smaller than those obtained using the other techniques and were closer to magnetic resonance imaging normal values reported in the literature. For all techniques, LV mass in men was significantly larger than in women, with and without body surface area indexing. These technique- and sex-related differences were larger than measurement variability. In women, age differences in LV mass were more pronounced and depicted significantly larger values in older age groups for all techniques, except three-dimensional echocardiography, which showed essentially no differences. LV mass was overall larger in black subjects than in white or Asian subjects. Conclusions: Significant differences in LV mass values exist across echocardiographic techniques, which are therefore not interchangeable. Sex-, race-, and age-related differences underscore the need for separate population specific normal values.

Background: Normal values for three-dimensional (3D) right ventricular (RV) size and function are not well established, as they originate from small studies that involved predominantly white North American and European populations, did not use RV-focused views, and relied on older 3D RV analysis software. The World Alliance Societies of Echocardiography study was designed to generate reference ranges for normal subjects around the world. The aim of this study was to assess the worldwide capability of 3D imaging of the right ventricle and report size and function measurements, including their dependency on age, sex, and ethnicity. Methods: Healthy subjects free of cardiac, pulmonary, and renal disease were prospectively enrolled at 19 centers in 15 countries, representing six continents. Three-dimensional wide-angle RV data sets were obtained and analyzed using dedicated RV software (TomTec) to measure end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, and ejection fraction (EF). Results were categorized by sex, age (18-40, 41-65, and >65years) and ethnicity. Results: Of the 2,007 subjects with attempted 3D RV acquisitions, 1,051 had adequate image quality for confident measurements. Upper and lower limits for body surface area-indexed EDV, ESV, and EF were 48 and 95 mL/m2, 19 and 43 mL/m2, and 44% and 58%, respectively, for men and 42 and 81 mL/m2, 16 and 36 mL/m2, and 46% and 61%, respectively, for women. Men had significantly larger EDVs, ESVs, and stroke volumes (even after body surface area indexing) and lower EFs than women (P&nbsp

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 (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.

Background Accurate measurements of the aortic annulus and root are important for guiding therapeutic decisions regarding the need for aortic surgery. Current echocardiographic guidelines for identification of aortic root dilatation are limited because current normative values were derived predominantly from white individuals in narrow age ranges, and based partially on M-mode measurements. Using data from the World Alliance Societies of Echocardiography study, the authors sought to establish normal ranges of aortic dimensions across sexes, races, and a wide range of ages. Methods Adult individuals free of heart, lung, and kidney disease were prospectively enrolled from 15 countries, with even distributions among sexes and age groups: young (18–40 years), middle aged (41–65 years) and old (>65 years). Transthoracic two-dimensional echocardiograms of 1,585 subjects (mean age, 47 ± 17 years; 50.4% men; mean body surface area [BSA], 1.77 ± 0.22 m2) were analyzed in a core laboratory following American Society of Echocardiography guidelines. Measurements, indexed separately by BSA and by height, included the aortic annulus, sinuses of Valsalva, and sinotubular junction. Differences among age, sex, and racial groups were evaluated using unpaired two-tailed Student's t tests. Results All aortic root dimensions were larger in men compared with women. After indexing to BSA, all measured dimensions were significantly larger in women, whereas men continued to show larger dimensions after indexing to height. Of note, the upper limits of normal for all aortic dimensions were lower across all age groups, compared with the guidelines. Aortic dimensions were larger in older age groups in both sexes, a trend that persisted regardless of BSA or height adjustment. Last, differences in aortic dimensions were also observed according to race: Asians had the smallest nonindexed aortic dimensions at all levels. Conclusions There are significant differences in aortic dimensions according to sex, age, and race. Thus, current guideline-recommended normal ranges may need to be adjusted to account for these differences.

Background: Echocardiography remains the most widely used modality to assess left ventricular (LV) chamber size and function. Currently this assessment is most frequently performed using two-dimensional (2D) echocardiography. However, three-dimensional (3D) echocardiography has been shown to be more accurate and reproducible than 2D echocardiography. Current normative reference values for 3D LV analysis are based predominantly on data from North America and Europe. The World Alliance Societies of Echocardiography study was designed to sample normal subjects from around the world to provide more universal global reference ranges. The aim of this study was to assess the worldwide feasibility of LV 3D echocardiography and report on size and functional measurements. Methods: A total of 2,262 healthy subjects were prospectively enrolled from 19 centers in 15 countries. Three-dimensional LV full-volume data sets were obtained and analyzed offline using vendor-neutral software. Measurements included LV end-diastolic and end-systolic volumes, LV ejection fraction (LVEF), global longitudinal strain (GLS), and global circumferential strain. Results were categorized by age (18-40, 41-65, and >65 years), sex, and race. Results: A total of 1,589 subjects (feasibility 70%) had adequate LV data sets for analysis. Mean normal values for indexed end-diastolic volume, end-systolic volume, and LVEF in men and women were 70 ± 15 and 65 ± 12 mL/m2, 28 ± 7 and 25 ± 6 mL/m2, and 60 ± 5% and 62 ± 5%, respectively. Men had larger LV volumes and lower LVEFs than women. GLS and global circumferential strain were higher in magnitude in women. In both sexes, LV volumes were lower and LVEF tended to be higher with increasing age, especially considering the differences between the youngest and oldest age groups. Although GLS was similar across age groups in men, in women, the youngest and middle-age cohorts revealed higher magnitudes of GLS compared with the oldest age group. Global circumferential strain was higher in magnitude at older age in both men and women. Finally, Asians had smaller chamber sizes and higher LVEFs and absolute strain values than both blacks and whites. Conclusions: Age, sex, and race should be considered when defining normal reference values for LV dimension and functional parameters obtained by 3D echocardiography.

Background: Recent advances in mitral valve (MV) percutaneous interventions have escalated the need for a more quantitative and comprehensive assessment of the MV, which can be best achieved using three-dimensional echocardiography. Understanding normal valve size, structure, and function is essential for differentiation of healthy from disease states. The aims of this study were to establish normative values for MV apparatus size and morphology and to determine how they vary across age, sex, and race groups using data from the World Alliance Societies of Echocardiography Normal Values Study. Methods: Three-dimensional volumetric data sets obtained on transthoracic echocardiography in 748 normal subjects (51% men) were analyzed using commercial MV analysis software (TomTec Imaging Systems) to determine annular and leaflet dimensions and areas. The subjects were divided into groups by sex (378 men and 370 women) and age (18 to 40 years [n = 266], 41 to 65 years [n = 249], and >65 years [n = 233]) to identify sex- and age-related differences. In addition, differences among black, white, and Asian populations were studied. Inter- and intraobserver variability was assessed in a subset of 30 subjects and expressed as mean absolute difference between pairs of repeated measurements. Results: Compared with women, men had larger annular size measurements, larger tenting size parameters, and larger leaflet length and area. Compared with the black and white populations, the Asian population showed significantly smaller mitral annular size. Although many of the age, sex, and race differences in MV parameters were statistically significant, they were comparable with or smaller than the corresponding measurement variability. Indexing to body surface area and height did not eliminate these differences consistently, suggesting that parameters may need to be indexed according to their dimensionality. Conclusions: This analysis of the World Alliance Societies of Echocardiography data provides normative values of mitral apparatus size and morphology. Although sex- and age-related differences were noted, they need to be interpreted with caution in view of the associated measurement variability.

Background: Echocardiographic assessment of right ventricular (RV) systolic function is an important component of clinical decision making. Although professional societies have worked to define normal ranges of RV size and function, their guidelines have not included the impacts of age, sex, and ethnicity on these parameters, as they have for the left ventricle. The World Alliance of Societies of Echocardiography study was designed to investigate the effects of age, sex, and ethnicity on all cardiac chambers. The aim of this study was to explore whether these differences exist for RV systolic parameters. Methods: Adequate two-dimensional RV-focused views for the measurement of systolic parameters, including fractional area change and global and free wall longitudinal strain, were available in 1,913 subjects (mean age, 47 ± 17 years; 51% men). Basal and mid-RV dimensions, length, tricuspid annular peak systolic excursion, tissue Doppler S′ velocity, and myocardial performance index were also measured. Subjects were grouped by age ([removed]65 years), with results also stratified by sex and ethnicity (Asian, black, or white) and analyzed using vendor-independent software. Differences among groups were evaluated using analysis of variance. Results: Women had smaller absolute and indexed RV areas and absolute RV dimensions and higher magnitudes of fractional area change, free wall strain, and global longitudinal strain compared to men. With respect to age, most of the statistically significant differences were noted between the [removed]65-year age groups, with RV areas and lengths smaller in older age groups and RV functional parameters (S′, fractional area change, tricuspid annular plane systolic excursion, global longitudinal strain, free wall strain, and myocardial performance index) showing minimal decreases or no changes with age. Although there were no meaningful differences in functional parameters among ethnic groups, RV size was smallest in Asians. Conclusions: These findings suggest that although two-dimensional RV parameters are age and sex dependent, association with race is less apparent, excepting that the Asian population appears to have smaller chamber sizes compared with whites and blacks.

Background Left atrial (LA) evaluation includes volumetric and functional parameters with an abundance of diagnostic and prognostic implications. Solid normal reference ranges are compulsory for accurate interpretation in individual patients, but previous studies have yielded mixed conclusions regarding the effects of age, sex, and/or race. The present report from the World Alliance Societies of Echocardiography study focuses on two-dimensional (2D) and three-dimensional (3D) measures of LA structure and function, with subgroup analysis by age, sex, and race. Methods Transthoracic 2D and 3D echocardiographic images were obtained in 1,765 healthy individuals (901 men, 864 women) evenly distributed among age subgroups: 18 to 40 years (n = 745), 41 to 65 years (n = 618), and >65 years (n = 402); the racial distribution was 38.4% white, 39.9% Asian, and 9.7% black. Images were analyzed using dedicated LA analysis software to measure LA volumes and phasic function from 3D volume and 2D strain curves. Results Three-dimensional maximum and minimum LA volumes adjusted for body surface area were nearly identical for men and women, but women demonstrated higher 3D total and passive emptying fractions (EFs). Two-dimensional reservoir strain was similar for both sexes. Age was associated with an incremental rise in LA volumes alongside characteristic shifts in functional indices. Total 2D EF and reservoir and conduit strain varied inversely with age, counteracted by higher booster strain, with a greater magnitude of effect in women. Active 3D EF was significantly higher, while total and passive EFs decreased with age. Interracial differences were noted in LA volumes, without substantial differences in functional indices. Conclusion Although similar normal values for LA volumes and strain can be applied to both sexes, meaningful differences in LA size occur with aging. Indices of function also shift with age, with a compensatory rise in booster function, which may serve to counteract observed lower total and passive EFs. Defining age-associated normal values may help differentiate age-associated “healthy” LA aging from pathologic processes.

Background Assessment of cardiac output (CO) and stroke volume (SV) is essential to understand cardiac function and hemodynamics. These parameters can be examined using three echocardiographic techniques (pulsed-wave Doppler, two-dimensional [2D], and three-dimensional [3D]). Whether these methods can be used interchangeably is unclear. The influence of age, sex, and ethnicity on CO and SV has also not been examined in depth. In this report from the World Alliance of Societies of Echocardiography Normal Values Study, the authors compare CO and SV in healthy adults according to age, sex, ethnicity, and measurement techniques. Methods A total of 1,450 adult subjects (53% men) free of heart, lung, and kidney disease were prospectively enrolled in 15 countries, with even distributions among age groups and sex. Subjects were divided into three age groups (young, 18–40 years; middle aged, 41–65 years; and old, >65 years) and three main racial groups (whites, blacks, and Asians). CO and SV were indexed (cardiac index [CI] and SV index [SVI], respectively) to body surface area and height and measured using three echocardiographic methods: Doppler, 2D, and 3D. Images were analyzed at two core laboratories (one each for 2D and 3D). Results CI and SVI were significantly lower by 2D compared with both Doppler and 3D methods in both sexes. SVI was significantly lower in women than men by all three methods, while CI differed only by 2D. SVI decreased with aging by all three techniques, whereas CI declined only with 2D and 3D. CO and SV were smallest in Asians and largest in whites, and the differences persisted after normalization for body surface area. Conclusions The present results provide normal reference values for CO and SV, which differ by age, sex, and race. Furthermore, CI and SVI measurements by the different echocardiographic techniques are not interchangeable. All these factors need to be taken into account when evaluating cardiac function and hemodynamics in individual patients.

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.