Abstract
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 (WASE) Study, we sought to establish normal ranges of aortic dimensions across sexes, races and a wide range of ages.
Methods:
Adult individuals free from heart, lung and kidney disease were prospectively enrolled from 15 countries with even distribution among sexes and age groups: young (18–40), middle (41–65) and old (>65 years). Transthoracic 2D echocardiograms of 1,585 subjects (age 47±17 years, 50.4% male, body surface area (BSA) 1.77±0.22 m2) were analyzed in a core laboratory following ASE guidelines. Measurements, indexed separately by BSA and by height, included the aortic annulus, sinuses of Valsalva (SoV), and sinotubular junction (STJ). 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 males compared to females. After indexing to BSA, all measured dimensions were significantly larger in females, whereas males 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 to the guidelines. Aortic dimensions were larger in older age groups in both sexes, a trend that persisted regardless of BSA- or height adjustment. Lastly, differences in aortic dimensions were also observed according to race: Asians had the smallest non-indexed 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.
Keywords: aortic root dimensions, aorta, 2D echocardiography
Introduction
Transthoracic echocardiography is widely used to obtain measurements of the aortic annulus and proximal aortic segments. These measurements are used for, among other indications, screening for thoracic aortic aneurysms, identifying when a threshold diameter is reached for prophylactic interventions as in Marfan’s syndrome, bicuspid aortic valve and other genetic aortopathies, determining the etiology of aortic insufficiency, and pre-procedural planning for transcatheter aortic valve replacement procedures. Establishing normative values and reference ranges, which account for age, sex, ethnicity, body surface area (BSA) and height using current echocardiographic techniques is of great importance for the detection and classification of aortic diseases and for guiding therapeutic decisions.
The 2015 guidelines on chamber quantification jointly published by the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) 1 provide normal reference values for the aortic annulus and sinotubular junction (STJ). While used worldwide, several limitations of these guidelines are worth mentioning. First, these values were derived from relatively small samples of predominantly white American and European populations and therefore fail to represent individuals from other ethnicities. Second, the data for these recommendations were obtained from early studies, predominantly based on M-mode echocardiographic measurements 2. Utilizing these data within the current guidelines, now over two decades later, is problematic, as improvements in technology have led to the need for new recommendations based on 2-dimensional (2D) echocardiographic measurements. Importantly, the aortic size is known to be age, sex and body size dependent. Some groups have also suggested indexing by height to avoid the influence of obesity on BSA. Nevertheless, large series on subjects across a wide range of ages and ethnicities acquired to define normal ranges are lacking.
Against this background, the ASE in collaboration with its International Alliance Partners conducted the World Alliance of Societies of Echocardiography (WASE) Normal Values Study to establish and compare normal echocardiographic values across races, ethnicities, and countries worldwide. The specific aim of our current report of the WASE Study was to establish 2D echocardiographic normative values of aortic dimensions, and to investigate their age-, sex-, BSA-, height- and ethnicity dependencies.
Methods
Study Design and Population
The rationale and design of the WASE Study has been described in detail elsewhere 3. Briefly, this is a multicenter, international, observational, prospective, cross-sectional study of healthy adult individuals. The ASE invited representatives of all member societies of the ASE International Alliance Partners to participate in this study. Each participant center was tasked with enrolling 100 local healthy adult volunteers without a history or clinical evidence of heart, lung, or kidney disease.
Individuals recruited in each country were evenly distributed among six predetermined subgroups according to age (young, 18–40 years; middle-aged, 41–65 years; and older adults, >65 years) and sex, to allow adequate sample sizes for comparisons needed to address the above aims. BSA was calculated using the Dubois formula 4. For the purposes of the WASE study, the definitions of race and ethnicity were adapted from those proposed for the 2020 US census, the United States Food and Drug Administration, and the 2011 United Kingdom census.
From September 2016 to January 2019, 2262 individuals were screened at 19 centers in 15 countries, representing six continents. Collection of basic demographic information and acquisition of comprehensive transthoracic 2D and 3D echocardiograms were performed in a single visit for each subject. The study was approved by local institutional review boards (IRB) or ethics committees, and subjects provided consent as mandated by each of the enrolling centers.
Echocardiographic Image Acquisition and Analysis Protocol
A comprehensive transthoracic echocardiogram was acquired following a study-specific standardized protocol created by the WASE core laboratories (MedStar Health Research Institute and the University of Chicago) and on the basis of the recent ASE recommendations 1, 5. Images were acquired using the enrolling center’s ultrasound imaging system of preference, which had to be capable of acquiring 2D and 3D datasets. All 2D echocardiographic data analysis was performed by board-certified echocardiographers in both core laboratories using a vendor-neutral workstation (Image Arena; TomTec, Unterschleissheim, Germany), following ASE/EACVI guidelines 1. Inter- and intra-observer reproducibilities of aortic root dimensions were tested using repeated measurements of the SoV diameter by two independent observers (TM, HP) for 204 studies and was quantified using coefficients of variation, defined as absolute difference between the repeated measurements in percent of their mean.
Aortic annulus linear dimensions were measured from the parasternal long axis (PLAX) images in zoom mode in mid-systole, between the hinge points of the aortic valve leaflets from inner edge-to-inner edge (Figure 1). All aortic measurements (i.e. maximal diameter of the SoV and STJ) were made at end-diastole, perpendicular to the long axis of the aorta using the leading edge-to-leading edge convention 1. All 2D aortic annulus, SoV, and STJ linear measurements were separately indexed to BSA and to height.
Figure 1.
Example of 2D echocardiographic measurements of aortic dimensions at the level of the aortic annulus (A), sinuses of Valsalva (B) and sinotubular junction (C). All measurements were obtained in a zoomed parasternal long-axis view. The aortic annulus was measured at mid-systole using the inner edge to inner edge method. The sinuses of Valsalva and sinotubular junction were measured at end-diastole using leading edge to leading edge technique.
Statistical Analysis
All data were presented as mean ± standard deviation (SD). Group differences were evaluated using the unpaired two-tailed student’s t-tests. In cases of 3-group comparisons, 3-way ANOVA was first used to identify significant differences. Statistical significance was defined as p<0.05. The upper limits of normal for the annulus, SoV, and STJ dimensions were calculated as the 97.5th percentile of the corresponding sex and age group for each measurement technique. This is in accordance of the definition of “normal” as falling within 95% of the normal population, with the remaining 5% being distributed equally between the two tails of the distribution, irrespective of whether the distribution is Gaussian.
Results
A total of 1,585 subjects (50% male, mean age 47 ± 17 years) formed the final population of the 2D analysis of the peri-annular aortic dimensions after the exclusion of subjects who did not have complete datasets suitable for analysis. Basic demographic characteristics of the study population, including race and ethnicity, are listed in Table 1. Most individuals were white (n=540, 34.1%) or of Asian race (n=687, 43.3%), with a minority being black (n=182, 11.5%) or mixed race (n=176, 11.1%). Subjects from the different nationality groups were also evenly distributed among age and sex groups, with the exception of Italy, Japan, India and USA who had two enrollment centers per country. Subjects were evenly distributed in six sub-groups according to age and sex: 18–40 years (337 males, 336 females), 41–65 years (294 males, 271 females) and >65 years (168 males and 179 females).
Table 1.
Demographics of the overall included WASE population
| All subjects |
Men |
Women |
|
|---|---|---|---|
| (n = 1,585) | (n = 799) | (n = 786) | |
|
| |||
| Age, y | 47 ± 17 | 47 ± 17 | 47 ± 18 |
| Height, cm | 167 ± 10 | 173 ± 8 | 160 ± 7* |
| Weight, kg | 68 ± 14 | 75 ± 13 | 61 ± 11* |
| BSA, m2 | 1.77 ± 0.22 | 1.89 ± 0.19 | 1.65 ± 0.16* |
| Systolic BP, mm Hg | 120 ± 13 | 123 ± 12 | 118 ± 13* |
| Diastolic BP, mm Hg | 74 ± 9 | 75 ± 9 | 72 ± 9* |
| Race | |||
| White | 540 (34.1) | 278 (34.8) | 262 (33.3) |
| Black | 182 (11.5) | 96 (12.0) | 86 (10.9) |
| Asian | 687 (43.3) | 339 (42.4) | 348 (44.3) |
| Other | 176 (11.1) | 86 (10.8) | 90 (11.5) |
Data are expressed as mean ± SD or as number (percentage).
BP, Blood pressure.
P < .05, men versus women.
Measurement Reproducibility
Reproducibility of the aortic measurements was good, with coefficients of variation of 0.5±1.8% for intra- and 10.9±9.5% for inter-observer variability.
Sex Differences in Aortic Parameters
Table 2 shows the nonindexed, BSA-indexed and height-indexed normal ranges for aortic dimensions by sex. Aortic dimensions were significantly larger in males compared with females at all measured sites. After indexing to BSA, dimensions of the measured portions of the aorta were significantly larger in females compared to males at all levels. In contrast, after indexing to height, males continued to show larger aortic dimensions at all levels, reaching statistical significance at the SoV level. Of note, compared with guideline recommendations, mean aortic annulus, SoV, and STJ dimensions were several millimeters smaller in the WASE population for both sexes, both when not indexed and indexed by BSA.
Table 2.
Aortic measures according to sex
| All subjects |
Men |
Women |
|
|---|---|---|---|
| (n = 1,585) | (n = 799) | (n = 786) | |
|
| |||
| Aortic annular diameter, mm | 20.4 ± 2.3 | 21.2 ± 2.2 | 19.5 ± 2.1* |
| BSA-indexed annular diameter, mm/m2 | 11.6 ± 1.4 | 11.3 ± 1.3 | 11.9 ± 1.4* |
| Height-indexed annular diameter, mm/m | 12.2 ± 1.2 | 12.3 ± 1.2 | 12.2 ± 1.3 |
| Height2.13-indexed annular diameter, mm/m2.13 | 6.9 ± 0.9 | 6.6 ± 0.8 | 7.2 ± 0.9 |
| Aortic SoV diameter, mm | 30.8 ± 3.9 | 32.2 ± 3.7 | 29.3 ± 3.6* |
| BSA-indexed aortic SoV diameter, mm/m2 | 17.6 ± 2.6 | 17.2 ± 2.5 | 18.0 ± 2.6* |
| Height-indexed aortic SoV diameter, mm/m | 18.5 ± 2.3 | 18.6 ± 2.3 | 18.4 ± 2.3* |
| Height2.13-indexed aortic SoV diameter, mm/m2.13 | 10.4 ± 1.6 | 10.1 ± 1.5 | 10.8 ± 1.6 |
| Aortic STJ diameter, mm | 26.6 ± 3.7 | 27.7 ± 3.7 | 25.5 ± 3.3* |
| BSA-indexed aortic STJ diameter, mm/m2 | 15.2 ± 2.4 | 14.8 ± 2.3 | 15.6 ± 2.4* |
| Height-indexed aortic STJ diameter, mm/m | 16.0 ± 2.2 | 16.0 ± 2.2 | 15.9 ± 2.2 |
| Height2.13-indexed aortic STJ diameter, mm/m2.13 | 9.0 ± 1.5 | 8.7 ± 1.4 | 9.4 ± 1.5 |
Data are expressed as mean ± SD or as number (percentage).
P < .05, men versus women.
Age-Related Changes in Aortic Root Dimensions
The values of aortic measurements according to sex and age are summarized in Table 3. For both males and females, nonindexed aortic dimensions tended to increase with age with the exception of the aortic annulus dimension. These age-related differences persisted in both sexes irrespective of normalization by BSA or height.
Table 3.
Aortic measures according to age and sex
| Men |
Women |
|||||||
|---|---|---|---|---|---|---|---|---|
| 18–40 y |
41–65 y |
>65 y |
18–40 y |
41–65 y |
>65 y |
|||
| (n = 337) | (n = 294) | (n = 168) | P | (n = 336) | (n = 271) | (n = 179) | P | |
|
| ||||||||
| BSA, m2 | 1.91 ± 0.20 | 1.90 ± 0.19 | 1.84 ± 0.18 | * ,†,‡ | 1.64 ± 0.16 | 1.68 ± 0.15 | 1.63 ± 0.17 | * ,†,§ |
| Height, cm | 175 ± 8 | 172 ± 8 | 170 ± 8 | * ,†,‡,§ | 162 ± 7 | 161 ± 7 | 157 ± 7 | * ,†,‡,§ |
| Systolic BP, mm Hg | 121 ± 11 | 123 ± 12 | 126 ± 12 | * ,‡,§ | 113 ± 11 | 119 ± 12 | 126 ± 12 | * ,‡,§ |
| Diastolic BP, mm Hg | 74 ± 9 | 76 ± 9 | 74 ± 8 | * ,‡,§ | 71 ± 9 | 73 ± 9 | 75 ± 9 | * ,†,§ |
| Aortic annular diameter, mm | 21.5 ± 2.1 | 21.2 ± 2.2 | 20.7 ± 2.2 | * ,†,‡ | 19.5 ± 1.9 | 19.5 ± 2.2 | 19.4 ± 2.3 | |
| BSA-indexed annular diameter, mm/m2 | 11.3 ± 1.3 | 11.2 ± 1.4 | 11.3 ± 1.4 | 12.0 ± 1.4 | 11.7 ± 1.4 | 12.1 ± 1.6 | * ,†,‡,§ | |
| Height-indexed annular diameter, mm/m | 12.3 ± 1.1 | 12.3 ± 1.2 | 12.2 ± 1.2 | 12.1 ± 1.2 | 12.2 ± 1.3 | 12.3 ± 1.4 | ||
| Aortic SoV diameter, mm | 31.2 ± 3.4 | 32.8 ± 3.7 | 33.1 ± 4.0 | * ,†,§ | 28.1 ± 3.6 | 29.8 ± 3.2 | 31.1 ± 3.2 | * ,†,‡,§ |
| BSA-indexed aortic SoV diameter, mm/m2 | 16.5 ± 2.2 | 17.4 ± 2.4 | 18.2 ± 2.7 | * ,†,§ | 17.3 ± 2.4 | 17.9 ± 2.4 | 19.3 ± 2.8 | * ,†,§ |
| Height-indexed aortic SoV diameter, mm/m | 17.8 ± 2.0 | 19.0 ± 2.1 | 19.5 ± 2.4 | * ,†,§ | 17.4 ± 2.3 | 18.6 ± 2.0 | 19.7 ± 2.1 | * ,†,‡,§ |
| Aortic STJ diameter, mm | 26.7 ± 3.2 | 28.4 ± 3.6 | 28.6 ± 4.0 | * ,†,§ | 24.4 ± 3.3 | 26.0 ± 3.2 | 26.7 ± 3.0 | * ,†,§ |
| BSA-indexed aortic STJ diameter, mm/m2 | 14.1 ± 2.0 | 15.0 ± 2.2 | 15.7 ± 2.6 | * ,†,‡,§ | 15.0 ± 2.2 | 15.6 ± 2.2 | 16.6 ± 2.6 | * ,†,‡,§ |
| Height-indexed aortic STJ diameter, mm/m | 15.2 ± 1.9 | 16.5 ± 2.1 | 16.9 ± 2.4 | * ,†,§ | 15.2 ± 2.0 | 16.2 ± 2.0 | 17.0 ± 2.0 | * ,†,‡,§ |
Data are expressed as mean ± SD.
BP, Blood pressure.
P < .05 by three-way analysis of variance.
P < .05, 18 to 40 versus >65 years (t test).
p < .05, 41 to 65 versus >65 years (t test).
P < .05, 18 to 40 versus 41 to 65 years (t test).
Comparison among races
Differences were observed in the aortic sizes by race (Table 4). Asians had the smallest BSA, and blacks had the largest. Compared to whites and blacks, Asians had the largest BSA-indexed values for all 3 aortic diameters. These relationships largely persisted in all sex-specific subgroups (Table 5).
Table 4.
Aortic dimensions according to race
| Asian |
Black |
White |
||
|---|---|---|---|---|
| n | (n = 790) | (n = 181) | (n = 665) | P |
|
| ||||
| BSA, m2 | 1.68 ± 0.19 | 1.86 ± 0.22 | 1.84 ± 0.21 | * ,†,‡ |
| Height, cm | 163 ± 9 | 169 ± 9 | 171 ± 10 | * ,†,‡ |
| Systolic BP, mm Hg | 123.4 ± 12.0 | 121.5 ± 11.5 | 118.4 ± 12.9 | * ,‡ |
| Diastolic BP, mm Hg | 76.0 ± 8.5 | 72.7 ± 9.0 | 72.1 ± 8.6 | * ,†,‡ |
| Aortic annular diameter, mm | 20.1 ± 2.2 | 21.0 ± 2.2 | 20.4 ± 2.2 | * ,†,§ |
| BSA-indexed annular diameter, mm/m2 | 11.8 ± 1.3 | 11.6 ± 1.4 | 11.3 ± 1.4 | * ,†,§ |
| Height-indexed annular diameter, mm/m | 12.0 ± 1.1 | 12.2 ± 1.0 | 12.2 ± 1.1 | * ,† |
| Aortic SoV diameter, mm | 29.6 ± 3.8 | 31.3 ± 3.8 | 32.1 ± 3.7 | * ,†,‡,§ |
| BSA-indexed aortic SoV diameter, mm/m2 | 16.9 ± 2.3 | 17.6 ± 2.4 | 18.8 ± 2.8 | * ,†,‡,§ |
| Height-indexed aortic SoV diameter, mm/m | 17.7 ± 1.9 | 19.2 ± 1.9 | 20.3 ± 2.1 | * ,†,‡,§ |
| Aortic STJ diameter, mm | 25.5 ± 3.5 | 27.3 ± 3.6 | 27.6 ± 3.6 | * ,†,‡ |
| BSA-indexed aortic STJ diameter, mm/m2 | 14.6 ±2.1 | 15.3 ± 2.2 | 16.2 ± 2.6 | * ,†,‡,§ |
| Height-indexed aortic STJ diameter, mm/m | 15.2 ± 1.7 | 16.6 ± 1.8 | 17.5 ± 2.0 | * ,†,‡,§ |
Data are expressed as mean ± SD.
BP, Blood pressure.
P < .05 by three-way analysis of variance.
P < .05, Asian versus black (t test).
P < .05, Asian versus white (t test).
P < .05, black versus white (t test).
Table 5.
Aortic measures according to race and sex
| Men |
Women |
|||||||
|---|---|---|---|---|---|---|---|---|
| Asian |
Black |
White |
Asian |
Black |
White |
|||
| (n = 410) | (n = 95) | (n = 339) | P | (n = 380) | (n = 86) | (n = 326) | P | |
|
| ||||||||
| BSA, m2 | 1.78 ± 0.17 | 1.94 ± 0.22 | 1.98 ± 0.17 | * ,†,‡ | 1.56 ± 0.16 | 1.76 ± 0.17 | 1.70 ± 0.15 | * ,†,‡ |
| Height, cm | 169 ± 7 | 175 ± 8 | 177 ± 7 | * ,†,‡,§ | 156 ± 7 | 163 ± 6 | 164 ± 7 | * ,†,‡ |
| Systolic BP, mm Hg | 126 ± 11 | 123 ± 11 | 121 ± 12 | * ,‡ | 121 ± 11 | 120 ± 12 | 116 ± 13 | * ,‡,§ |
| Diastolic BP, mm Hg | 77 ± 8 | 74 ± 9 | 73 ± 8 | * ,†,‡ | 74 ± 7 | 72 ± 9 | 71 ± 9 | * ,†,§ |
| Aortic annulare diameter, mm | 20.9 ± 2.1 | 20.8 ± 2.1 | 19.5 ± 1.8 | * ,‡,§ | 18.9 ± 2.1 | 20.7 ± 1.9 | 19.3 ± 2.1 | |
| BSA-indexed annular diameter, mm/m2 | 11.8 ± 1.3 | 10.8 ± 1.2 | 11.4 ± 1.3 | 12.2 ± 1.5 | 11.8 ± 1.5 | 11.3 ± 1.3 | * ,†,§ | |
| Height-indexed annulus diameter, mm/m | 12.4 ± 1.2 | 11.9 ± 1.1 | 11.9 ± 1.0 | * ,†,§ | 12.1 ± 1.3 | 12.7 ± 1.2 | 11.8 ± 1.3 | * ,†,§ |
| Aortic SoV diameter, mm | 32.2 ± 3.6 | 30.5 ± 3.2 | 30.5 ± 3.1 | * ,†,‡ | 29.0 ± 2.9 | 29.8 ± 3.2 | 29.6 ± 3.6 | * ,†,‡,§ |
| BSA-indexed aortic SoV diameter, mm/m2 | 18.2 ± 2.5 | 15.8 ± 2.0 | 17.9 ± 2.4 | * ,†,‡,§ | 18.7 ± 2.9 | 17.1 ± 2.5 | 17.3 ± 2.7 | * ,†,‡,§ |
| Height-indexed aortic SoV diameter, mm/m | 19.1 ± 2.2 | 17.4 ± 1.7 | 18.7 ± 2.1 | * ,†,‡,§ | 18.6 ± 2.6 | 18.3 ± 2.1 | 18.1 ± 2.5 | * ,‡ |
| Aortic STJ diameter, mm | 27.6 ± 3.5 | 25.9 ± 3.1 | 26.6 ± 2.9 | * ,†,‡ | 25.0 ± 3.9 | 25.7 ± 3.1 | 25.8 ± 2.9 | * ,†,‡ |
| BSA-indexed aortic STJ diameter, mm/m2 | 15.6 ± 2.2 | 13.4 ± 1.9 | 15.7 ± 2.3 | * ,†,‡,§ | 16.2 ± 2.8 | 14.7 ± 2.2 | 15.1 ± 2.3 | * ,†,‡,§ |
| Height-indexed aortic STJ diameter, mm/m | 16.3 ± 2.1 | 14.8 ± 1.7 | 16.4 ± 2.0 | * ,†,§ | 16.1 ± 2.6 | 15.8 ± 2.0 | 15.8 ± 2.0 | |
Data are expressed as mean ± SD.
BP, Blood pressure.
P < .05 by three-way analysis of variance.
P < .05, Asian vs black (t test).
P < .05, Asian versus white (t test).
P < .05, black versus white (t test).
Nomograms
In order to facilitate a graphical approach to normal proximal aorta dimensions, dedicated nomograms have been constructed for SoV measurements, similar to those included in the current guidelines 1. Figure 2 shows SoV dimensions by age as indexed by BSA. Figure 3 shows SoV dimensions by age as indexed by height. Both figures include the equations for the upper limits of normal SoV dimensions as a function of BSA (Figure 2) and height (Figure 3) for each age group.
Figure 2.
Nomograms of aortic dimensions at the SoV level according to different calculated BSA, for three age groups. Dashed lines show existing guideline data 1; colored area represents the upper and lower limits of normal, with the equation for the former (ULN) shown below each plot.
Figure 3.
Nomograms of aortic dimensions at the SoV level according to different heights for three age groups. Colored area represents upper and lower limits of normal, with the equation for the former (ULN) shown below each plot.
Discussion
This WASE study of aortic dimensions provides normal values by transthoracic echocardiography from a large cohort of healthy subjects across the spectrum of sex, age and race. The main findings are summarized as follows: 1) aortic dimensions were larger in males compared with females, and remained so when adjusted for height but not when adjusted for BSA; 2) aortic dimensions generally are larger in older age; and 3) aortic dimensions vary according to ethnicity.
Echocardiography is a widely-used, first-line imaging modality for the quantification of aortic dimensions. Importantly, these measurements should be evaluated based on normative data. A recent call to establish subject-specific, rather than generic threshold values, has culminated in several publications of echocardiographic normative data (NORRE, JAMP, EMINCA, NORMAL) 6–9. Nevertheless, our understanding of the ethnic dependency of aortic dimensions remains fragmentary. In addition, advances in 2D echocardiography technology, allowing improved determination of the blood-tissue interface, further underscore the need for updated echocardiographic guidelines for aortic sizing.
Demographic associations of aortic dimensions
Non-indexed aortic dimensions were consistently larger in males with clear statistical significance at all measured levels. Consistent with results from the NORRE study 8, when aortic dimensions were indexed to BSA, females showed slightly larger indexed diameters that reached statistical significance at all aortic measurement levels. In contrast, when aortic dimensions were indexed to height, males tended to show larger values, only reaching statistical significance at the level of the SoV. Notably, compared with current guideline recommendations 1, aortic dimensions (both non-indexed and BSA-indexed) were slightly smaller in the global WASE population for both sexes.
The effects of age and sex were consistent with previous studies 6, 10 with the size of the aortic diameters larger in older age groups for both males and females, with the exception of the aortic annulus, which appeared to be similar among all ages. These age-related differences persisted in both sexes irrespective of BSA or height adjustments, consistent with prior reports 6, 8. Age-related dilation of the SoV has been reported in multiple autopsy series and multimodality clinical studies. Such an age-related difference in vessel dimensions is seen in other vascular territories 11, 12 and may be related to thinning and fracturing of the elastic laminae, presumably related to the effects of prolonged cyclical stress 13. It has been postulated that because aortic distensibility declines with age, the aorta diameter increases, so that the volume buffering capacity remains constant 12.
Differences were observed in the aortic dimensions by race, these persisted even after adjusting for BSA and in sex-specific subgroups. Asians had the largest BSA-indexed aortic dimensions, and showed values very similar to previous studies with predominantly Asian populations6–9, 14. These differences were relatively small, but could result in under- or over-diagnosis of aortic dilatation in some individuals, when using reference ranges derived from studies that did not account for racial diversity.
Nomograms
Echocardiographic nomograms have been used to present reference intervals against a dependent variable, such as BSA, in a visually appealing and clinically useful manner. These nomograms are tools used to estimate whether an aortic dimension falls within the normal range or how far it diverges from it. The currently proposed normal SoV ranges have been compared against three age-specific nomograms derived from a single report by Roman, et al. 2. While these were primarily recommended for the pediatric population, cardiac dimensions also change with age in the adult population, and can differ according to sex and body size, as shown in the present study and others 1, 9, 15, 16. Currently used adult nomograms are fraught with limitations including: small sample size, poorly defined ‘normal’ subjects, bias to BSA (which is closely related to obesity), and a steep change in results when the subject turns 40, owing to a change in the equation used 17. More recently, the NORRE dataset demonstrated that aortic dimensions are best correlated to height and not BSA 8, 18. Building upon this, our data, obtained in a more diverse population, showed a stronger association with age, when height indexing was used, providing additional support to the advantage of using height over BSA for normalization. While weight can fluctuate over the course of adulthood, height is largely genetically predetermined and remains fairly constant. Compared to BSA indexation, the aortic height index has also been introduced as a slightly superior tool for the estimation of adverse aortic outcomes 19. Accordingly, we constructed dedicated nomograms of the aortic dimensions at the SoV level according to different height, in addition to BSA, for three age groups. This is a change from the current practice and may have potential benefits in overweight individuals.
Limitations
While the WASE study was designed to be inclusive in order to represent multiple regions around the world, certain areas remained underrepresented. Specifically, the number of black subjects was considerably smaller than whites and Asians, since only two of the participating sites (Nigeria and Chicago) had access to black populations. However, we had to identify a balance between this inclusivity and feasibility with the available resources. Also, the number of subjects over 80 years old was small, limiting the generalizability of the reported results in this population. Additionally, larger regional studies should be considered to establish more specific normality ranges for countries and ethnicities, which were not included in this study.
Conclusion
Our results from the WASE Normal Values Study provide normal reference ranges for aortic dimensions, which differ according to sex, age, and race. Current guideline-recommended normal ranges may need to be adjusted to account for these differences.
Highlights:
Normal values of aortic root dimensions from 1,585 healthy adult subjects
Normal limit established for aortic annulus, sinuses of Valsalva and sinotubular junction
Normal values differ by age, sex and race
Disclosures:
Marcus Schreckenberg, Michael Blankenhagen, Markus Degel and Niklas Hitschrich are employees of TOMTEC Imaging Systems. No other direct conflicts of interest related to this study have been reported by any of the authors. All authors have been involved in the design of the WASE study, patient enrollment and/or data analysis and all have critically reviewed and approved the manuscript prior to submission. A full list of WASE investigators is provided at the end of the manuscript.
Abbreviations
- BSA
body surface area
- 2D
2-dimensional
- ASE
American Society of Echocardiography
- EACVI
European Association of Cardiovascular Imaging
- WASE
World Alliance of Societies of Echocardiography
- LVOT
Left ventricular outflow tract
- STJ
sinotubular junction
- SoV
sinuses of Valsalva
Footnotes
Additional WASE Investigators:
Argentina: Aldo D. Prado, Centro Privado de Cardiologia, Tucumán, Argentina; Eduardo Filipini, Universidad Nacional de la Plata, Buenos Aires, Argentina
Australia: Agatha Kwon and Samantha Hoschke-Edwards, Heart Care Partners, Queensland, Australia
Brazil: Tania Regina Afonso, Albert Einstein Hospital, Sao Paulo, Brazil
Canada: Babitha Thampinathan and Maala Sooriyakanthan, Toronto General Hospital, University of Toronto, Canada
China: Mei Zhang, Yingbin Wang and Yu Zhang, Qilu Hospital of Shandong University, Jinan, China; Tiangang Zhu and Zhilong Wang, Peking University People’s Hospital, Beijing, China; Lixue Yin and Shuang Li, Sichuan Provincial People’s Hospital, Sichuan, China.
India: R. Alagesan, Madras Medical College, Chennai, India; S. Balasubramanian, Madurai Medical College, Madurai, India; R.V.A. Ananth, Jeyalakshmi Heart Center, Madurai, India; Manish Bansal, Medanta Heart Institute, Medanta, Haryana, India
Iran: Azin Alizadehasl, Rajaie Cardiovascular Medical Center, IUMS, Tehran, Iran
Italy: Luigi Badano, University of Milano-Bicocca, and Istituto Auxologico Italiano, IRCCS, Milan, Italy; Eduardo Bossone, Davide Di Vece and Michele Bellino, University of Salerno, Salerno, Italy.
Japan: Tomoko Nakao, Takayuki Kawata, Megumi Hirokawa and Naoko Sawada MD, The University of Tokyo, Tokyo, Japan; Yousuke Nabeshima MD, University of Occupational and Environmental Health, Kitakyushu, Japan
Republic of Korea: Hye Rim Yun and Ji-won Hwang, Samsung Medical Center, Seoul, Republic of Korea
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