Background
Aging and gender may affect left ventricular (LV) mechanics. The aim of this study was to determine the age and gender dependency of LV mechanical indices obtained from real-time three-dimensional echocardiography (RT3DE).
Methods
RT3DE was performed in 280 healthy subjects (age range, 1–88 years; 137 men). From full-volume data sets, LV endocardial and epicardial borders were semiautomatically traced using quantitative software. LV volumes and corresponding long-axis diameter were measured throughout the cardiac cycle. Sphericity index was defined as the ratio of LV volume and spherical volume, calculated as 4/3 × π × (long-axis diameter/2) 3 . LV mass was calculated as (LV epicardial volume − LV endocardial volume) × 1.05. The ratio of LV mass to LV volume was also calculated.
Results
The mean value of LV ejection fraction did not change with age. However, LV volumes, mass, sphericity index, and LV mass/volume ratio were altered by age: (1) sphericity index was highest in the first decade of age and then declined until the fifth decade, (2) LV mass/volume ratio significantly increased in older age, and (3) LV mass/volume ratio was significantly higher in aged women compared with age-matched men.
Conclusions
Age has heterogeneous effects on LV shape and LV mass/volume ratio, potentially due to the growing process of myocardial fibers and the surrounding architecture in the younger population, as well as the aging process, with an increase in vascular stiffness and a loss of myocytes in older populations. Higher LV mass/volume ratios in older women might be a contributor to the preferential development of diastolic heart failure in this population.
Because of rapid increase in the aged population, the assessment of age-related and gender-related changes in left ventricular (LV) geometry and function are of paramount importance in the understanding of LV mechanics. Previous studies have demonstrated that heart failure with normal ejection fraction (EF) is frequently more common in aged women compared with aged men. The age and gender dependency of LV remodeling has been also reported in LV pressure overload hypertrophy. Specifically, women had greater fractional shortening and achieved smaller end-systolic chamber sizes and smaller LV mass than men in severe senile aortic stenosis. Moreover, it is demonstrated that age-related increase in arterial stiffening is associated with elevated systolic ventricular stiffening, even without LV hypertrophy. In microscopic animal studies, LV myocytes increased in length and became irregular in shape with aging. However, the width of myocytes remained constant with advanced aging. Age-related decrease in the number of myocytes and increase in collagen content have been associated with elevated LV end-diastolic pressure and decreased dP/dt. Therefore, aging and gender may have different impacts on LV volumes, mass, and shape. However, the effects of age and gender on LV geometry in normal subjects have not been extensively studied.
Real-time three-dimensional echocardiography (RT3DE) has proven useful for assessing LV mechanics because of its high feasibility rate of data acquisition, its relatively low observer and test-retest variability, and the widely available and convenient semiautomated offline analysis. Previous studies have reported that determination of LV volume and mass on RT3DE is accurate compared with cardiac magnetic resonance. RT3DE has been also useful for the assessment of LV shape.
We hypothesized that age and gender may have different effects on LV geometry, which can be reliably assessed by RT3DE. Accordingly, we sought to determine the effects of age and gender on LV volumes, mass, and shape using transthoracic RT3DE in a relatively large number of healthy subjects of both genders over a wide range of ages.
Methods
Study Subjects
A total of 322 healthy subjects over a wide range of ages (1–88 years; 150 men) were enrolled. Eligibility criteria included (1) normal blood pressure without a history of hypertension, (2) absence of diabetes and/or cardiovascular disease, and (3) no cardiac medication use. Subjects were recruited from three university hospitals from the United States and Japan and were predominantly hospital employees or their relatives and/or volunteers recruited through advertisements. All subjects underwent physical examinations and two-dimensional echocardiography to exclude valvular disease and the presence of regional wall motion abnormalities. The study protocol was approved by the ethics committee of each hospital, and informed consent obtained from all subjects.
RT3DE
A Sonos 7500 or iE33 scanner (Philips Medical Systems, Andover, MA) equipped with a fully sampled matrix-array transducer (X4 or X3-1, respectively) was used. Studies were acquired by experienced cardiac sonographers with subjects in the left lateral decubitus position. Full-volume data sets were acquired from the apical transducer position during held end-expiration. To ensure the inclusion of the entire LV volume within the pyramidal scan volume, data sets were acquired using the wide-angle mode, whereby four wedge-shaped subvolumes (93° × 21°) were acquired during a single 5-second to 7-second breath hold.
Doppler Echocardiography
Pulsed-wave Doppler examination of mitral inflow obtained in the apical four-chamber view was performed in each subject. Doppler tissue imaging, used to measure septal mitral annular velocity, was obtained by placing the sample volume in the septal corner of the mitral annulus in the apical four-chamber view.
Image Analysis
LV Volume, EF, and Shape Indices
Data sets were analyzed offline using commercially available software (3DQ ADV, QLAB version 7.0; Phillips Medical Systems), as described previously. Briefly, five anatomic landmarks (four points for the mitral annulus and one for the LV apex) were manually initialized on the end-diastolic frame using nonforeshortened apical four-chamber and two-chamber views selected from the pyramidal data set. The three-dimensional endocardial surface was automatically reconstructed using a deformable shell model. Subsequently, the end-systolic frame was manually selected by identifying the frame with the smallest LV cavity cross-sectional area in both apical views. After a similar initialization, LV surface detection was repeated on this frame to calculate end-systolic volumes. Finally, the computer algorithm automatically tracked the endocardial border throughout all frames of the cardiac cycle. Dynamic “casts” of the LV endocardium and LV volume-versus-time curves were displayed, from which LV end-diastolic and end-systolic volumes, stroke volume, and LV EF were then computed. In addition, the corresponding long-axis diameter, measured from the mid mitral annulus to the LV apex, was calculated.
For the determination of LV shape, we measured the sphericity index, which was defined as the ratio between the measured LV volume divided by the spherical volume of the left ventricle, calculated as 4/3 × π × (long-axis diameter/2) at either end-diastole or end-systole. For the assessment of arterial stiffness, we calculated total systemic arterial compliance, which was defined as stroke volume index divided by pulse pressure.
LV Mass and LV Mass/Volume Ratio
End-diastolic epicardial contours were manually traced to calculate LV epicardial volume. LV mass was calculated as (LV epicardial volume − LV endocardial volume) multiplied by the specific mass of myocardial tissue (1.05 g/mL). LV mass/volume ratio was also calculated as LV mass divided by LV end-diastolic volume.
Doppler Echocardiographic Indices
From mitral inflow velocities, the E-wave and A-wave velocities, E-wave deceleration time, and E/A velocity ratio were measured. Peak diastolic annular velocity during early diastolic rapid filling (E′) was also measured to calculate the E/E′ ratio in all subjects. All Doppler measurements were averaged from three consecutive beats.
Intraobserver and Interobserver Variability
Intraobserver variability was determined by having one observer repeat the three-dimensional measurements of LV end-diastolic volume and LV mass in 30 randomly selected subjects 1 month after completing the initial measurements. Interobserver variability was determined by having a second observer repeat these measurements in these same subjects. Intraobserver and interobserver variability values were calculated as the absolute difference between the corresponding two measurements in terms of percentage of their mean.
Statistical Analysis
Data are expressed as mean ± SD or as median (interquartile range). Frequencies are expressed as percentages. All statistical analysis was carried out using commercially available statistical software (JMP version 7.0 or StatView version 5.0; SAS Institute Inc., Cary, NC). Differences in continuous variables among groups were calculated using one-way analysis of variance with post hoc Bonferroni correction. Categorical variables were compared using Fisher’s exact tests or χ 2 tests. Linear or polynomial regression analysis was used to study the relation between two parameters. Multivariate linear regression analysis was used to test for independent associations between LV mass/volume ratio and clinical and known echocardiographic parameters associated with diastolic function, including age, sex, total systemic arterial compliance, E/A velocity ratio, E-wave deceleration time, and E′. P values < .05 were considered significant.
Results
Of the 322 subjects screened, 42 (13%) were excluded from analysis because of elevated systolic blood pressure (>140 mm Hg; n = 23) at the time of physical examination or poor image quality ( n = 19). Thus, the final study group consisted of 280 subjects (mean age, 38 ± 24 years; age range, 1–88 years; 137 men).
LV Volume, EF, and Shape Indices
LV end-diastolic volumes, end-systolic volumes, and stroke volumes were age dependent. LV volumes and stroke volumes reached their peak value during the third or fourth decade, followed by a mild but significant reduction during the remaining decades ( Table 1 ). An identical tendency was noted when these values were corrected for body surface area. In contrast, the mean value of LV EF remained unchanged throughout all decades. As expected, gender differences were noted in LV volumes and stroke volumes, depicting larger values in men ( Table 2 ). However, LV EF was slightly but significantly higher in women compared with men.
| Variable | Age group (y) | P | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 1–9 ( n = 53) | 10–19 ( n = 34) | 20–29 ( n = 29) | 30–39 ( n = 32) | 40–49 ( n = 25) | 50–59 ( n = 32) | 60–69 ( n = 51) | >70 ( n = 24) | ||
| Men | 27 | 17 | 13 | 17 | 12 | 20 | 18 | 13 | |
| BSA (m 2 ) | 0.79 ± 0.22 | 1.42 ± 0.23 | 1.70 ± 0.18 | 1.86 ± 0.22 | 1.74 ± 0.20 | 1.70 ± 0.24 | 1.57 ± 0.16 | 1.56 ± 0.20 | <.0001 |
| HR (beats/min) | 91 ± 18 | 71 ± 15 | 66 ± 11 | 68 ± 9 | 66 ± 12 | 63 ± 9 | 64 ± 11 | 65 ± 11 | <.0001 |
| SBP (mm Hg) | 103 ± 10 | 116 ± 10 | 120 ± 11 | 120 ± 13 | 121 ± 12 | 127 ± 11 | 126 ± 10 | 130 ± 8 | <.0001 |
| LVEDV (mL) | 40.8 ± 14.0 | 80.3 ± 21.7 | 103.3 ± 22.0 | 106.9 ± 18.7 | 91.3 ± 15.8 | 89.8 ± 20.1 | 73.6 ± 15.0 | 73.3 ± 15.9 | <.0001 |
| LVEDVI (mL/m 2 ) | 51.3 ± 7.6 | 56.8 ± 12.3 | 60.5 ± 9.8 | 57.4 ± 8.0 | 52.5 ± 6.4 | 52.2 ± 7.4 | 46.9 ± 8.1 | 46.7 ± 7.7 | <.0001 |
| LVESV (mL) | 13.8 ± 5.0 | 28.3 ± 10.1 | 36.0 ± 10.8 | 37.8 ± 10.6 | 29.8 ± 9.2 | 30.4 ± 11.1 | 24.1 ± 7.2 | 26.1 ± 7.7 | <.0001 |
| LVESVI (mL/m 2 ) | 17.4 ± 3.7 | 19.8 ± 5.6 | 20.9 ± 5.1 | 20.1 ± 4.9 | 17.0 ± 4.4 | 17.3 ± 5.3 | 15.4 ± 4.3 | 16.5 ± 4.0 | <.0001 |
| SV (mL) | 27.0 ± 9.7 | 52.1 ± 13.1 | 67.3 ± 13.0 | 69.1 ± 9.9 | 61.5 ± 9.2 | 59.4 ± 10.7 | 49.5 ± 8.8 | 47.2 ± 9.1 | <.0001 |
| SVI (mL/m 2 ) | 33.8 ± 5.6 | 36.9 ± 8.1 | 39.6 ± 6.2 | 37.3 ± 4.6 | 35.5 ± 3.8 | 34.9 ± 3.3 | 31.6 ± 4.7 | 30.2 ± 4.8 | <.0001 |
| LV EF (%) | 66.0 ± 5.2 | 65.2 ± 5.2 | 65.6 ± 5.0 | 65.2 ± 4.9 | 68.2 ± 5.7 | 67.1 ± 5.9 | 67.7 ± 4.7 | 64.9 ± 4.9 | n.s. |
| LVLAD (cm) | 6.14 ± 0.85 | 8.09 ± 0.85 | 8.93 ± 0.65 | 9.10 ± 0.57 | 8.67 ± 0.60 | 8.49 ± 0.85 | 7.81 ± 0.59 | 7.81 ± 0.69 | <.0001 |
| LVSAD (cm) | 3.27 ± 0.44 | 4.05 ± 0.45 | 4.34 ± 0.37 | 4.41 ± 0.51 | 4.15 ± 0.31 | 4.25 ± 0.52 | 3.86 ± 0.41 | 3.82 ± 0.49 | <.0001 |
| SI (ED) | 0.33 ± 0.06 | 0.29 ± 0.06 | 0.28 ± 0.04 | 0.27 ± 0.03 | 0.27 ± 0.03 | 0.28 ± 0.05 | 0.29 ± 0.04 | 0.29 ± 0.04 | <.0001 |
| SI (ES) | 0.22 ± 0.05 | 0.19 ± 0.05 | 0.17 ± 0.04 | 0.17 ± 0.03 | 0.16 ± 0.04 | 0.17 ± 0.04 | 0.17 ± 0.05 | 0.17 ± 0.04 | <.0001 |
| LVM (g) | 43.5 ± 16.5 | 88.9 ± 20.3 | 110.5 ± 21.1 | 118.1 ± 22.9 | 101.2 ± 19.1 | 106.4 ± 23.3 | 96.7 ± 16.2 | 103.8 ± 19.3 | <.0001 |
| LVMI (g/m 2 ) | 54.1 ± 8.5 | 63.1 ± 11.6 | 64.7 ± 9.0 | 63.5 ± 8.6 | 58.1 ± 7.4 | 62.0 ± 9.5 | 61.6 ± 7.4 | 65.7 ± 10.2 | <.0001 |
| LV mass/volume ratio (g/mL) | 1.06 ± 0.14 | 1.12 ± 0.14 | 1.08 ± 0.08 | 1.10 ± 0.09 | 1.11 ± 0.07 | 1.19 ± 0.11 | 1.34 ± 0.19 | 1.45 ± 0.29 | <.0001 |
| Total systemic arterial compliance (mL/mm Hg/m 2 ) | 0.82 ± 0.22 | 0.72 ± 0.19 | 0.81 ± 0.22 | 0.86 ± 0.24 | 0.79 ± 0.10 | 0.72 ± 0.15 | 0.63 ± 0.15 | 0.58 ± 0.15 | <.0001 |
| E/A ratio | 2.0 ± 0.6 | 2.3 ± 0.6 | 2.3 ± 0.8 | 1.9 ± 0.5 | 1.5 ± 0.4 | 1.3 ± 0.4 | 1.0 ± 0.3 | 0.8 ± 0.3 | <.0001 |
| DT (msec) | 147 ± 31 | 167 ± 27 | 175 ± 30 | 187 ± 25 | 195 ± 37 | 192 ± 33 | 218 ± 49 | 227 ± 49 | <.0001 |
| E′ | 12.1 ± 1.6 | 12.4 ± 2.1 | 12.7 ± 1.6 | 11.6 ± 1.6 | 10.0 ± 2.1 | 8.2 ± 1.7 | 7.0 ± 1.5 | 6.0 ± 1.4 | <.0001 |
| E/E′ ratio | 9.3 ± 1.5 | 8.6 ± 1.8 | 7.4 ± 1.8 | 7.7 ± 1.4 | 8.3 ± 1.6 | 10.2 ± 2.6 | 10.3 ± 2.2 | 12.4 ± 5.0 | <.0001 |
| Variable | 1–19 y | 20–39 y | 40–59 y | >60 y | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Male ( n = 44) | Female ( n = 43) | P | Male ( n = 30) | Female ( n = 31) | P | Male ( n = 32) | Female ( n = 25) | P | Male ( n = 31) | Female ( n = 44) | P | |
| BSA (m 2 ) | 1.02 ± 0.39 | 1.05 ± 0.38 | .66 | 1.86 ± 0.18 | 1.70 ± 0.22 | <.01 | 1.83 ± 0.21 | 1.57 ± 0.13 | <.0001 | 1.70 ± 0.16 | 1.47 ± 0.12 | <.0001 |
| LVEDV (mL) | 58.6 ± 28.6 | 53.9 ± 23.1 | .40 | 113.1 ± 19.9 | 97.5 ± 17.7 | <.01 | 100.7 ± 15.2 | 77.4 ± 12.5 | <.0001 | 84.2 ± 12.4 | 66.0 ± 12.2 | <.0001 |
| LVEDVI (mL/m 2 ) | 56.2 ± 11.5 | 50.5 ± 7.3 | <.01 | 60.9 ± 10.1 | 56.8 ± 7.4 | .07 | 55.0 ± 6.5 | 49.1 ± 6.0 | <.01 | 49.7 ± 7.3 | 44.9 ± 7.9 | <.05 |
| LVESV (mL) | 20.7 ± 11.6 | 18.2 ± 8.5 | .24 | 42.4 ± 10.3 | 31.6 ± 8.1 | <.0001 | 35.3 ± 9.4 | 23.5 ± 7.0 | <.0001 | 29.7 ± 6.2 | 21.3 ± 6.1 | <.0001 |
| LVESVI (mL/m 2 ) | 19.6 ± 5.1 | 17.1 ± 3.8 | <.05 | 22.8 ± 5.2 | 18.2 ± 3.5 | <.001 | 19.1 ± 4.8 | 14.9 ± 4.0 | .001 | 17.5 ± 3.7 | 14.5 ± 4.1 | <.01 |
| SV (mL) | 37.9 ± 17.7 | 35.7 ± 15.4 | .55 | 70.8 ± 11.1 | 65.8 ± 11.4 | .09 | 65.4 ± 8.8 | 53.9 ± 7.5 | <.0001 | 54.5 ± 7.8 | 44.7 ± 7.4 | <.0001 |
| SVI (mL/m 2 ) | 36.6 ± 7.8 | 33.4 ± 5.2 | <.05 | 38.2 ± 5.9 | 38.6 ± 5.3 | .77 | 36.0 ± 3.3 | 34.2 ± 3.5 | .07 | 32.1 ± 4.4 | 30.5 ± 4.8 | .14 |
| LV EF (%) | 65.3 ± 5.3 | 66.2 ± 5.1 | .43 | 62.9 ± 4.1 | 67.8 ± 4.4 | <.0001 | 65.6 ± 5.6 | 70.0 ± 5.1 | <.01 | 64.8 ± 3.8 | 68.2 ± 5.2 | <.01 |
| SI (ED) | 0.32 ± 0.06 | 0.31 ± 0.06 | .31 | 0.26 ± 0.03 | 0.28 ± 0.04 | <.05 | 0.27 ± 0.04 | 0.28 ± 0.04 | .28 | 0.29 ± 0.04 | 0.30 ± 0.04 | .11 |
| SI (ES) | 0.21 ± 0.05 | 0.20 ± 0.06 | .28 | 0.17 ± 0.03 | 0.17 ± 0.04 | .75 | 0.16 ± 0.04 | 0.17 ± 0.04 | .92 | 0.17 ± 0.03 | 0.17 ± 0.05 | .91 |
| LVM (g) | 62.8 ± 30.2 | 59.7 ± 27.2 | .62 | 124.2 ± 21.2 | 105.1 ± 19.1 | <.001 | 116.5 ± 18.5 | 88.3 ± 13.1 | <.0001 | 108.1 ± 17.1 | 92.6 ± 14.7 | <.0001 |
| LVMI (g/m 2 ) | 59.9 ± 11.6 | 55.2 ± 9.2 | <.05 | 66.8 ± 9.5 | 61.4 ± 7.2 | <.05 | 63.8 ± 8.9 | 56.1 ± 6.6 | <.001 | 62.8 ± 7.3 | 63.0 ± 9.3 | .91 |
| LV mass/volume ratio (g/mL) | 1.07 ± 0.13 | 1.10 ± 0.15 | .41 | 1.10 ± 0.08 | 1.08 ± 0.09 | .32 | 1.16 ± 0.10 | 1.15 ± 0.11 | .63 | 1.30 ± 0.21 | 1.43 ± 0.23 | <.05 |
| Total systemic arterial compliance (mL/mm Hg/m 2 ) | 0.78 ± 0.19 | 0.78 ± 0.23 | .94 | 0.87 ± 0.27 | 0.78 ± 0.16 | .34 | 0.76 ± 0.15 | 0.73 ± 0.13 | .55 | 0.65 ± 0.18 | 0.59 ± 0.12 | .08 |
| E/A ratio | 2.1 ± 0.6 | 2.1 ± 0.6 | .90 | 2.0 ± 0.7 | 2.2 ± 0.7 | .60 | 1.3 ± 0.4 | 1.4 ± 0.4 | .42 | 1.0 ± 0.3 | 1.0 ± 0.3 | .84 |
| DT (msec) | 157 ± 32 | 155 ± 30 | .87 | 182 ± 28 | 178 ± 29 | .75 | 202 ± 38 | 186 ± 29 | .15 | 218 ± 50 | 222 ± 49 | .75 |
| E′ | 12.4 ± 2.1 | 12.0 ± 1.4 | .34 | 12.4 ± 1.7 | 12.1 ± 1.7 | .56 | 8.2 ± 1.5 | 9.4 ± 2.2 | .09 | 7.1 ± 1.6 | 6.6 ± 1.5 | .23 |
| E/E′ | 9.1 ± 1.7 | 8.9 ± 1.6 | .58 | 7.0 ± 1.4 | 8.0 ± 1.7 | .05 | 9.6 ± 2.3 | 9.5 ± 2.6 | .93 | 9.9 ± 2.2 | 11.3 ± 3.6 | .11 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
