Normal Values of Three-Dimensional Right Ventricular Size and Function Measurements: Results of the World Alliance Societies of Echocardiography Study.

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 >65 years) 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 < .05). EDV and ESV did not show any meaningful differences among age groups. Three-dimensional RV volumes were smallest in Asians. CONCLUSIONS: Reliability of 3D RV acquisition is low worldwide, underscoring the importance of future improvements in imaging techniques. Sex and race must be taken into consideration in the assessment of both RV volumes and EF.

Age-, Sex-, and Race-Based Normal Values for Left Ventricular Circumferential Strain from the World Alliance Societies of Echocardiography Study.

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.

Normal Values of Left Ventricular Mass by Two-Dimensional and Three-Dimensional Echocardiography: Results from the World Alliance Societies of Echocardiography Normal Values Study.

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.

Normative values of the aortic valve area and Doppler measurements using two-dimensional transthoracic echocardiography: results from the Multicentre World Alliance of Societies of Echocardiography Study.

AIMS: Aortic valve area (AVA) used for echocardiographic assessment of aortic stenosis (AS) has been traditionally interpreted independently of sex, age and race. As differences in normal values might impact clinical decision-making, we aimed to establish sex-, age- and race-specific normative values for AVA and Doppler parameters using data from the World Alliance Societies of Echocardiography (WASE) Study. METHODS AND RESULTS: Two-dimensional transthoracic echocardiographic studies were obtained from 1903 healthy adult subjects (48% women). Measurements of the left ventricular outflow tract (LVOT) diameter and Doppler parameters, including AV and LVOT velocity time integrals (VTIs), AV mean pressure gradient, peak velocity, were obtained according to ASE/EACVI guidelines. AVA was calculated using the continuity equation. Compared with men, women had smaller LVOT diameters and AVA values, and higher AV peak velocities and mean gradients (all P < 0.05). LVOT and AV VTI were significantly higher in women (P < 0.05), and both parameters increased with age in both sexes. AVA differences persisted after indexing to body surface area. According to the current diagnostic criteria, 13.5% of women would have been considered to have mild AS and 1.4% moderate AS. LVOT diameter and AVA were lower in older subjects, both men and women, and were lower in Asians, compared with whites and blacks. CONCLUSION: WASE data provide clinically relevant information about significant differences in normal AVA and Doppler parameters according to sex, age, and race. The implementation of this information into clinical practice should involve development of specific normative values for each ethnic group using standardized methodology.

Three-Dimensional Transthoracic Static and Dynamic Normative Values of the Mitral Valve Apparatus: Results from the Multicenter World Alliance Societies of Echocardiography Study.

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.

Normal Values of Aortic Root Size According to Age, Sex, and Race: Results of the World Alliance of Societies of Echocardiography Study.

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.

Sex-, Age-, and Race-Related Normal Values of Right Ventricular Diastolic Function Parameters: Data from the World Alliance Societies of Echocardiography Study.

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 (<40, 41-65, and >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.

Normal Values of Left Atrial Size and Function and the Impact of Age: Results of the World Alliance Societies of Echocardiography Study.

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.

Normal Values of Left Ventricular Size and Function on Three-Dimensional Echocardiography: Results of the World Alliance Societies of Echocardiography Study.

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.

Normal Values of Cardiac Output and Stroke Volume According to Measurement Technique, Age, Sex, and Ethnicity: Results of the World Alliance of Societies of Echocardiography Study.

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.

Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging.

OBJECTIVES: We tested a newly developed 4-dimensional (4D) right ventricular (RV) analysis method for computing RV volumes for both 3-dimensional (3D) ultrasound (US) and magnetic resonance (MR) images. BACKGROUND: Asymmetry and the anatomical complexity of the RV make accurate determination of RV shape and volume difficult. METHODS: Thirty patients, 14 with grossly normal cardiac anatomy and 16 with major congenital heart disease, were studied at the same visit with both 3D echocardiography (echo) and magnetic resonance imaging (MRI) for RV size and function. Ultrasound images were acquired on a Philips 7500 system (Philips Medical Systems, Andover, Massachusetts) with a matrix-array transducer (real-time 3D echo) with full volume sweeps from apical and subcostal views. Sagittal, 4-chamber, and coronal views were derived for contour detection (all 12 to 24 slices). The MR images were acquired with a 3-T MRI magnet with segmented cine-loop gradient echo sequences in short- and rotated long-axis views to cover the RV inflow, body, and outflow tract. The RV volumes were analyzed with the new software applicable to 3D echo MR images. RESULTS: New software aided delineation of the RV free wall, tricuspid valve, RV outflow tract, and apex on 3D echo volumes. Although there was a slightly higher variability measuring right ventricular ejection fraction (RVEF) and volumes obtained by US compared with MRI, both imaging methods showed closely correlated results. The RVEF was measured with 4% variability for US and 5% variability for MRI with a correlation coefficient of r = 0.91. The RV end-diastolic volume was measured at 70.97 +/- 15.0 ml with 3D US and at 70.06 +/- 14.8 ml with MRI (r = 0.99), end-systolic volume measured 39.8 +/- 10.4 ml with 3D US and 39.1 +/- 10.2 ml with MRI (r = 0.98). CONCLUSIONS: The new RV analysis software allowed validation of the accuracy of 4D echo RV volume data compared with MRI.