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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/m 2 , 19 and 43 mL/m 2 , and 44% and 58%, respectively, for men and 42 and 81 mL/m 2 , 16 and 36 mL/m 2 , 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., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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.)

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., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Transthoracic echocardiography is the leading cardiac imaging modality for patients admitted with COVID-19, a condition of high short-term mortality. The aim of this study was to test the hypothesis that artificial intelligence (AI)-based analysis of echocardiographic images could predict mortality more accurately than conventional analysis by a human expert., Methods: Patients admitted to 13 hospitals for acute COVID-19 who underwent transthoracic echocardiography were included. Left ventricular ejection fraction (LVEF) and left ventricular longitudinal strain (LVLS) were obtained manually by multiple expert readers and by automated AI software. The ability of the manual and AI analyses to predict all-cause mortality was compared., Results: In total, 870 patients were enrolled. The mortality rate was 27.4% after a mean follow-up period of 230 ± 115 days. AI analysis had lower variability than manual analysis for both LVEF (P = .003) and LVLS (P = .005). AI-derived LVEF and LVLS were predictors of mortality in univariable and multivariable regression analysis (odds ratio, 0.974 [95% CI, 0.956-0.991; P = .003] for LVEF; odds ratio, 1.060 [95% CI, 1.019-1.105; P = .004] for LVLS), but LVEF and LVLS obtained by manual analysis were not. Direct comparison of the predictive value of AI versus manual measurements of LVEF and LVLS showed that AI was significantly better (P = .005 and P = .003, respectively). In addition, AI-derived LVEF and LVLS had more significant and stronger correlations to other objective biomarkers of acute disease than manual reads., Conclusions: AI-based analysis of LVEF and LVLS had similar feasibility as manual analysis, minimized variability, and consequently increased the statistical power to predict mortality. AI-based, but not manual, analyses were a significant predictor of in-hospital and follow-up mortality., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial scar correlates with clinical outcomes. Traditionally, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to detect and quantify scar. In this prospective study using LGE CMR as reference, the authors hypothesized that nonlinear ultrasound imaging, namely, power modulation, can detect and quantify myocardial scar in selected patients with previous myocardial infarction. In addition, given the different histopathology between ischemic and nonischemic scar, a further aim was to test the diagnostic performance of this echocardiographic technique in unselected consecutive individuals with ischemic and nonischemic LGE or no LGE on CMR., Methods: Seventy-one patients with previous myocardial infarction underwent power modulation echocardiography following CMR imaging (group A). Subsequently, 101 consecutive patients with or without LGE on CMR, including individuals with nonischemic LGE, were scanned using power modulation echocardiography (group B)., Results: In group A, echocardiography detected myocardial scar in all 71 patients, with good scar volume agreement with CMR (bias = -1.9 cm 3 ; limits of agreement [LOA], -8.0 to 4.2 cm 3 ). On a per-segment basis, sensitivity was 82%, specificity 97%, and accuracy 92%. Sensitivity was higher in the inferior and posterior segments and lower in the anterior and lateral walls. In group B, on a per-subject basis, the sensitivity of echocardiography was 62% (91% for ischemic and 30% for nonischemic LGE), with specificity and accuracy of 89% and 72%, respectively. The bias for scar volume between modalities was 5.9 cm 3 , with LOA of 34.6 to 22.9 cm 3 (bias = -1.9 cm 3 [LOA, -11.4 to 7.6 cm 3 ] for ischemic LGE, and bias = 18.9 cm 3 [LOA, -67.4 to 29.7.6 cm 3 ] for nonischemic LGE)., Conclusions: Power modulation echocardiography can detect myocardial scar in both selected and unselected individuals with previous myocardial infarction and has good agreement for scar volume quantification with CMR. In an unselected cohort with nonischemic LGE, sensitivity is low., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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/m 2 , 28 ± 7 and 25 ± 6 mL/m 2 , 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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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 m 2 ) 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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 infection is known to cause a wide array of clinical chronic sequelae, but little is known regarding the long-term cardiac complications. We aim to report echocardiographic follow-up findings and describe the changes in left (LV) and right ventricular (RV) function that occur following acute infection., Methods: Patients enrolled in the World Alliance Societies of Echocardiography-COVID study with acute COVID-19 infection were asked to return for a follow-up transthoracic echocardiogram. Overall, 198 returned at a mean of 129 days of follow-up, of which 153 had paired baseline and follow-up images that were analyzable, including LV volumes, ejection fraction (LVEF), and longitudinal strain (LVLS). Right-sided echocardiographic parameters included RV global longitudinal strain, RV free wall strain, and RV basal diameter. Paired echocardiographic parameters at baseline and follow-up were compared for the entire cohort and for subgroups based on the baseline LV and RV function., Results: For the entire cohort, echocardiographic markers of LV and RV function at follow-up were not significantly different from baseline (all P > .05). Patients with hyperdynamic LVEF at baseline (>70%), had a significant reduction of LVEF at follow-up (74.3% ± 3.1% vs 64.4% ± 8.1%, P < .001), while patients with reduced LVEF at baseline (<50%) had a significant increase (42.5% ± 5.9% vs 49.3% ± 13.4%, P = .02), and those with normal LVEF had no change. Patients with normal LVLS (<-18%) at baseline had a significant reduction of LVLS at follow-up (-21.6% ± 2.6% vs -20.3% ± 4.0%, P = .006), while patients with impaired LVLS at baseline had a significant improvement at follow-up (-14.5% ± 2.9% vs -16.7% ± 5.2%, P < .001). Patients with abnormal RV global longitudinal strain (>-20%) at baseline had significant improvement at follow-up (-15.2% ± 3.4% vs -17.4% ± 4.9%, P = .004). Patients with abnormal RV basal diameter (>4.5 cm) at baseline had significant improvement at follow-up (4.9 ± 0.7 cm vs 4.6 ± 0.6 cm, P = .019)., Conclusions: Overall, there were no significant changes over time in the LV and RV function of patients recovering from COVID-19 infection. However, differences were observed according to baseline LV and RV function, which may reflect recovery from the acute myocardial injury occurring in the acutely ill. Left ventricular and RV function tends to improve in those with impaired baseline function, while it tends to decrease in those with hyperdynamic LV or normal RV function., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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 (<40, 41-65, and >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 <40- and >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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial scar appears brighter compared with normal myocardium on echocardiography because of differences in tissue characteristics. The aim of this study was to test how different ultrasound pulse characteristics affect the brightness contrast (i.e., contrast ratio [CR]) between tissues of different acoustic properties, as well as the accuracy of assessing tissue volume., Methods: An experimental in vitro "scar" model was created using overheated and raw pieces of commercially available bovine muscle. Two-dimensional and three-dimensional ultrasound scanning of the model was performed using combinations of ultrasound pulse characteristics: ultrasound frequency, harmonics, pulse amplitude, steady pulse (SP) emission, power modulation (PM), and pulse inversion modalities., Results: On both two-dimensional and three-dimensional imaging, the CR between the "scar" and its adjacent tissue was higher when PM was used. PM, as well as SP ultrasound imaging, provided good "scar" volume quantification. When tested on 10 "scars" of different size and shape, PM resulted in lower bias (-9.7 vs 54.2 mm 3 ) and narrower limits of agreement (-168.6 to 149.2 mm 3 vs -296.0 to 404.4 mm 3 , P = .03). The interobserver variability for "scar" volume was better with PM (intraclass correlation coefficient = 0.901 vs 0.815). Two-dimensional and three-dimensional echocardiography with PM and SP was performed on 15 individuals with myocardial scar secondary to infarction. The CR was higher on PM imaging. Using cardiac magnetic resonance as a reference, quantification of myocardial scar volume showed better agreement when PM was used (bias, -645 mm 3 ; limits of agreement, -3,158 to 1,868 mm 3 ) as opposed to SP (bias, -1,138 mm 3 ; limits of agreement, -5,510 to 3,233 mm 3 )., Conclusions: The PM modality increased the CR between tissues with different acoustic properties in an experimental in vitro "scar" model while allowing accurate quantification of "scar" volume. By applying the in vitro findings to humans, PM resulted in higher CR between scarred and healthy myocardium, providing better scar volume quantification than SP compared with cardiac magnetic resonance., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The novel severe acute respiratory syndrome coronavirus-2 virus, which has led to the global coronavirus disease-2019 (COVID-19) pandemic is known to adversely affect the cardiovascular system through multiple mechanisms. In this international, multicenter study conducted by the World Alliance Societies of Echocardiography, we aim to determine the clinical and echocardiographic phenotype of acute cardiac disease in COVID-19 patients, to explore phenotypic differences in different geographic regions across the world, and to identify parameters associated with in-hospital mortality., Methods: We studied 870 patients with acute COVID-19 infection from 13 medical centers in four world regions (Asia, Europe, United States, Latin America) who had undergone transthoracic echocardiograms. Clinical and laboratory data were collected, including patient outcomes. Anonymized echocardiograms were analyzed with automated, machine learning-derived algorithms to calculate left ventricular (LV) volumes, ejection fraction, and LV longitudinal strain (LS). Right-sided echocardiographic parameters that were measured included right ventricular (RV) LS, RV free-wall strain (FWS), and RV basal diameter. Multivariate regression analysis was performed to identify clinical and echocardiographic parameters associated with in-hospital mortality., Results: Significant regional differences were noted in terms of patient comorbidities, severity of illness, clinical biomarkers, and LV and RV echocardiographic metrics. Overall in-hospital mortality was 21.6%. Parameters associated with mortality in a multivariate analysis were age (odds ratio [OR] = 1.12 [1.05, 1.22], P = .003), previous lung disease (OR = 7.32 [1.56, 42.2], P = .015), LVLS (OR = 1.18 [1.05, 1.36], P = .012), lactic dehydrogenase (OR = 6.17 [1.74, 28.7], P = .009), and RVFWS (OR = 1.14 [1.04, 1.26], P = .007)., Conclusions: Left ventricular dysfunction is noted in approximately 20% and RV dysfunction in approximately 30% of patients with acute COVID-19 illness and portend a poor prognosis. Age at presentation, previous lung disease, lactic dehydrogenase, LVLS, and RVFWS were independently associated with in-hospital mortality. Regional differences in cardiac phenotype highlight the significant differences in patient acuity as well as echocardiographic utilization in different parts of the world., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The World Alliance Societies of Echocardiography study is a multicenter, international, prospective, cross-sectional study whose aims were to evaluate healthy adult individuals to establish age- and sex-normative values of echocardiographic parameters and to determine whether differences exist among people from different countries and of different ethnicities. The present report focuses on two-dimensional (2D) and three-dimensional (3D) right atrial (RA) size and function., Methods: Transthoracic 2D and 3D echocardiographic images were obtained in 2,008 healthy adult individuals evenly distributed among subgroups according to sex (1,033 men, 975 women) and age 18 to 40 years (n = 854), 41 to 65 years (n = 653), and >65 years (n = 501). For ethnicity, 34.9% were white, 41.6% Asian, and 9.7% black. Images were analyzed in a core laboratory according to current American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. RA measurements included 2D dimensions, 2D and 3D RA volumes (RAVs) indexed to body surface area (BSA), emptying fraction (EmF), and global longitudinal strain, including total/reservoir, passive/conduit, and active/contractile phases. Differences among age and sex categories and among countries were also examined., Results: RAVs were larger in men (even after BSA indexing), while 3D total EmF and global longitudinal strain magnitudes were higher in women. For both sexes, there were no significant age-related differences in 2D RAV measurements, but 3D RAV values differed minimally with age, remaining significant after BSA indexing. RA total EmF and reservoir strain and passive EmF and conduit strain magnitude were lower in older groups for both sexes. Interestingly, whereas RA active EmF increased with age, contractile strain magnitude decreased. Considerable geographic variations were identified: Asians of both sexes had significantly lower BSA than non-Asians, and their 2D and 3D end-systolic RAVs were significantly smaller even after BSA indexing. Of note, 2D end-systolic RAVs in this group were considerably lower than normal values provided in the current guidelines., Conclusions: There is significant sex, age, and geographic variability in normal RA size and function parameters. Current guideline-recommended normal ranges for RA size and function parameters should be adjusted geographically on the basis of the results of this study., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF)., Methods: This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy., Results: The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P < .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, β-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S' > 5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02)., Conclusions: A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to describe echocardiographic normal values in adults and to compare races and nationalities using a uniform acquisition and measurement protocol. This report focuses on left ventricular (LV) diastolic function., Methods: WASE is an international, cross-sectional study. Participants were enrolled with equal distribution according to age and gender. Echocardiograms were analyzed in a core laboratory based on the latest American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Left ventricular diastolic function was assessed by E, E/A, e' velocities, E/e', left atrial volume index (LAVI), and tricuspid regurgitation velocity. Determination of LV diastolic function was made using the algorithm proposed by the guidelines., Results: A total of 2,008 subjects from 15 countries were enrolled. The majority were of white or Asian race (42.8%, 41.8%, respectively). E and E/e' were higher in female patients, while LAVI was similar in both genders. Consistent increase in E/e' and decrease in E/A, E, and e' were found as age increased. The upper limit of normal for LAVI was higher in WASE compared with the guidelines. The lower limits of normal for e' were smaller in elder groups than those in the guidelines, while the upper limits of normal for E/e' were below the guideline values. These findings suggest that the cutoff value for LAVI should be shifted upward and age-specific cutoff values for e' should be considered. In WASE, <93.6% of patients were classified as normal LV diastolic function using the guidelines' algorithm, and the proportion increased to 97.4% when applying the revised cutoff values for LAVI obtained in our study., Conclusions: Guideline-recommended normal values for e' velocities and LAVI should be reconsidered. The algorithm for the determination of LV diastolic function proposed by the guidelines is useful, but adjustments to LAVI could further improve it., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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: Three-dimensional (3D) echocardiography is fundamental for left ventricular (LV) assessment. The aim of this study was to determine discrepancies in 3D LV endocardial tracings and suggest tracing guidance., Methods: Forty-five 3D LV echocardiographic data sets were traced by three experienced operators, from different centers, according to predefined guidelines. The 3D meshes were compared with one another, and the endocardial areas of discrepancies were identified. A discussion and retracing protocol was used to reduce discrepancies. For each data set, an average 3D mesh was produced (reference mesh). Subsequently, four novice operators, divided into two groups, traced 20 of the data sets. Two operators followed the tracing protocol and two did not., Results: The intraclass correlation coefficients among the three experienced operators for end-diastolic volume, end-systolic volume, and ejection fraction were 0.952, 0.955, and 0.932. The absolute distances between tracings were 1.11 ± 0.45 mm. The highest tracing discrepancies were at the apical cap and anterior and anterolateral walls in end-diastole and end-systole and also at the basal anteroseptum in end-systole. Agreement with the reference meshes was better for the novice operators who followed the guidance (10.9 ± 17.3 mL, 10.2 ± 14.7 mL, and -2.2 ± 4.1% for end-diastolic volume, end-systolic volume, and ejection fraction) compared with those who did not (16.3 ± 16.4 mL, 17.0 ± 16.0 mL, and -4.2 ± 4.1%, respectively)., Conclusions: Comparing 3D LV tracings, the endocardial areas that are the most difficult to delineate were identified. The suggested protocol for LV tracing resulted in very good agreement among operators. The reference 3D meshes are available for online testing and ranking of LV tracing algorithms., (Copyright © 2017 American Society of Echocardiography. All rights reserved.)

Background: The use of transcatheter aortic valve replacement (TAVR) is increasing worldwide. We present our 6-year experience using three-dimensional (3D) transesophageal echocardiography (TEE) and investigate whether different sizing methods of the aortic annulus lead to different prosthesis size that may impact outcome., Methods: We investigated 262 patients who underwent TAVR and had 3D TEE data sets of the aortic annulus. We have used the area-derived diameter (D area  = 2(area/π)) and the circumference-derived diameter (D circ  = Circumference/π) to size the prosthesis in separate populations in different time periods., Results: The D circ method is correlated with lower incidence of paravalvular aortic regurgitation (PVAR; odds ratio = 0.44, 95% confidence interval, 0.23-0.85; P = .015). Other factors associated with PVAR were the cover index, area-mismatch index, and circumference-mismatch index. Retrospectively, for the purposes of the study, we used the Edwards-Sapien 3 Valve 3D sizing guide in all patients, to predict the hypothetical valve size with each method. In the whole population, the calculated D circ was higher in all cases (D circ  = 23.4 ± 2.3 mm vs D area  = 22.9 ± 2.3 mm; P < .001). The two methods had good agreement in predicting the valve size (kappa = 0.600). In total, 192 (73.3%) patients were assigned for the same prosthesis size, whereas 70 (26.7%) would be eligible for a different size, of which 44 (16.7%) would definitely have had a different valve implanted., Conclusion: Using the aortic annulus area or circumference to calculate the annular diameter provides different values. Comparing the two methods, a different prosthesis size could have been implanted in 26.7% of patients. In our series the use of circumference-derived diameter resulted in lower incidence of PVAR. The findings of this study may be independent of the imaging modality and may therefore also apply to computed tomography-based aortic annulus measurements, but this needs to be further investigated., (Copyright © 2017 American Society of Echocardiography. All rights reserved.)

In an era of catheter-based structural heart disease and left-side electrophysiologic interventions, transseptal puncture (TSP) is probably the most common transcatheter procedure. Experienced interventional cardiologists and electrophysiologists may safely perform TSP using fluoroscopic guidance alone. However, at present TSP is usually the first step in complex percutaneous catheter-based structural heart disease procedures and necessitate a precise site-specific TSP. Thus, in these procedures most interventional cardiologists perform TSP under fluoroscopic and two- or three-dimensional transesophageal echocardiographic guidance. The EchoNavigator system may provide a solution by fusing fluoroscopic and transesophageal echocardiographic images. In this review, the authors describe advantages and limitations of this new imaging system in guiding TSP and suggest specific echocardiographic-fluoroscopic fusion imaging perspectives that may facilitate TSP, making it potentially easier and safer., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous valve-in-valve therapy has become an important treatment option for failing bioprosthetic heart valves. Accurate assessment of valve internal diameter (ID) is essential for effective and safe treatment. These data may not be available in an individual patient, or the manufacturer-supplied dimensions may be incorrect because they do not allow for the space occupied by valve leaflet material., Methods: In total, 2,332 two-dimensional and three-dimensional transesophageal echocardiographic in vitro measurements were performed using both Philips iE33 and GE Vivid E9 systems with a range of system settings on 53 bioprosthetic valves in all available sizes. Two-dimensional echocardiographic ID measurements were made in two orthogonal planes at the level of the sewing ring, and similar three-dimensional measurements were generated from multiplane reconstructions. They were compared with both manufacturer-supplied valve ID (MID) and the true ID (TID) measured with Hegar dilators., Results: Both the iE33 and the Vivid 9 provided comparable valve ID measurements. TID was statistically significantly smaller than MID (P < .001). All echocardiographic measurements were closer to TID than to MID. Two-dimensional measurements were closest to TID because of higher spatial resolution., Conclusions: Transesophageal echocardiographic valve ID measurements compare well with TID, which is overestimated by MID. These findings have potentially important implications for valve-in-valve procedures because an inaccurate measurement of TID might lead to the wrong choice of implanted valve., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Successful transcatheter aortic valve implantation (TAVI) mandates comprehensive, accurate multimodality imaging. Echocardiography is involved at all key stages and, with the advent of real-time three-dimensional (3D) transesophageal echocardiography, is uniquely placed to enable periprocedural monitoring. The investigators describe a comprehensive two-dimensional (2D) and 3D echocardiographic protocol, and the additional benefits of 3D TEE, within a high-volume TAVI program., Methods: TAVI was performed with 2D and 3D transesophageal echocardiographic and fluoroscopic guidance in consecutive high-risk patients with symptomatic severe aortic stenosis. The role of TEE, including the additive value of 3D TEE, was examined, and procedural and echocardiographic outcomes were evaluated. A 3D sizing transcatheter heart valve (THV) strategy was used, except as mandated by study protocol., Results: Procedural success was achieved in 99% of 256 patients (mean age, 82.9 ± 7.1 years, mean logistic European System for Cardiac Operative Risk Evaluation score, 21.6 ± 11.2%; mean aortic valve area, 0.63 ± 0.19 cm(2)), with no procedural deaths. Acceptable 2D and 3D transesophageal echocardiographic images were achieved in all patients. Aortic valve annular dimensions by 2D transthoracic echocardiography, 2D TEE, and 3D TEE were 21.6 ± 1.9 mm, 22.5 ± 2.2 mm (P < .001), and 23.0 ± 2.0 mm (P = .004 vs 2D TEE), respectively. The 2D THV sizing strategy would have changed THV selection in 23% of patients, downsizing in most. Three-dimensional TEE provided superior spatial visualization and anatomic orientation and optimized procedural performance. Postprocedural mild, moderate, and severe paravalvular aortic regurgitation was observed in 24%, 3%, and 0% of patients, respectively, with no or trace transvalvular aortic regurgitation in 95%. A second valve was successfully deployed in five patients, and TEE detected five other periprocedural complications., Conclusions: A systematic, comprehensive echocardiographic protocol, incorporating the additional benefits of 3D TEE, has a vital role within a TAVI program and, combined with a 3D THV sizing strategy, contributes to excellent outcomes., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing trans-catheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease., (Copyright © 2011 European Society of Cardiology and The Author. Published by Mosby, Inc. All rights reserved.)

Automated border-detection techniques such as acoustic quantification have proven accurate and useful for quantifying left ventricular (LV) function. We acquired LV acoustic quantification waveforms from the parasternal short-axis window in 140 healthy patients in the age range of 16 to 78 years. Signal-averaged waveforms were analyzed for parameters of systolic and diastolic performance. The average fractional area change was 54 +/- 12%, and there were no significant changes in LV systolic function in the age range studied. There were significant changes in diastolic parameters with aging. The percentage of contribution to total LV filling occurring during atrial filling nearly tripled during the 6 decades studied, from 13% in the youngest cohort to 36% in the eighth decade of life. This study provides normal reference values for systolic and diastolic parameters of LV function determined from signal-averaged acoustic quantification waveforms acquired from the parasternal short-axis view in adult and adolescent patients over a wide age range.