Reference value studies for myocardial deformation parameters in children are relatively few, especially in the preschool-aged children. In this single-center study, we aimed to determine normal range values for LV systolic function among healthy Egyptian preschool pediatric population using 2D and 3D STE. It is one of the largest reports to date of 2D and 3D STE in preschool-age children with structurally normal hearts and no cardiovascular disease.
Normal range and age correlation in left ventricle two-dimensional strain
In our study, 2D STE GLS strain ranged from -18.1% to -30.7% with a mean of –22.1345 ± 2.166%, GCS was from -16.7% to -23.4% with a mean of -19.02 ± 1.23%.,while GRS ranged from 37.4% to 52.6% with a mean of 42.25 ± 2.35%.
From the previous reports that studied all strain measurements and correlated with our values with slight differences, the study conducted by Liselotte M. Klitsie et al. included 37 children in the study group below 1 year of age. The mean strain values were -20.6 ± 3.1% for GLS , -21.7 ± 4.7 for GCS, and 40.5 ± 13.5 for GRS in the study group of 1–4 years. Their mean strain values were 23.6 ± 1.5% for GLS, -22.1 ± 3.6% for GCS, and 49.8 ± 13.7% for GRS. All data were collected and analyzed using GE VIVID 7 echo system with EchoPAC 11.1.8 [9].
Several previous studies did not include radial strain and were conducted by different echo vendor machines as the following studies that used the Philips echo machine. Adi Adar et al. conducted a study with subjects from 1 to 5 years where the GLS mean was -25.22 ± 2.43% and GCS mean was -23.89 ± 3.72%. All data were collected and analyzed using Philips EPIQ system [10]. Massimiliano Cantinotti et al. conducted a study with age-group below 2 years where the GLS mean was -26 ± 2.3% and GCS mean was -24.6 ± 4.2%. Also, in his study with age-group from 2 to 5yrs, the mean GLS was -25 ± 2.2% and GCS mean was -23.3 ± 4.3%. Imaging and analysis were done using Philips iE33 system [11]. Also, Laurens P. Koopman et al. conducted a study in the age-group from 1 to 6 years, where the GLS mean was -22.3 ± 2.2%, while the GCS mean was -23.8 ± 2.6%. All data were collected and analyzed using Philips iE33 medical system of echocardiography [2].
While other studies had differences as regard measurements, especially the GCS, Shaimaa et al. conducted a study with an older age-group ranging from 6 to 9 years. Data were collected using GE VIVID E9 echocardiography system. They found that GLS mean in the whole study population was -22.5 ± 2.56%, while GCS mean value was -33.9 ± 8.59% and GRS mean value was 56.5 ± 9.52% [12].
On categorizing our study population into age-groups and correlating the data with age-groups, we found that circumferential systolic strain of the left ventricle is independent of age, while longitudinal strain of the left ventricle decreases with increasing age. And also, there was a correlation of radial strain with age. There was a strong positive significant correlation between age and 2D values of strain with r value in GLS of 0.913 and P value of 0.001. The GCS showed a weakly positive nonsignificant correlation, r value was 0.074 and P value was 0.475, while GRS showed a strongly negative significant correlation, with r value of -0.86 and P value of 0.001.
Several studies have reported reduced longitudinal strain with increasing age, in agreement with our results. Yet other previous studies have reported that GLS is not age dependent. These discrepant results might partly be related to the different modalities, the software used for analysis, and the size of the study populations [4].
We found that circumferential systolic strain of the left ventricle is independent of age, while longitudinal strain of the left ventricle decreases with increasing age. And also, there was a correlation with radial strain with age. There was a strong positive significant correlation between age and 2D values of strain with r value in GLS of 0.913 and P value of 0.001. The GCS showed a weakly positive nonsignificant correlation, r value was 0.074, and P value was 0.475, while GRS showed a strongly negative significant correlation, with r value of -0.86 and P value of 0.001.
In Adi Adar et al. study, data were correlated with age and they found GLS has a weak positive significant correlation with age with r value of 0.34 and P value less than 0.001. But GCS was found to have a nonsignificant correlation with age with P value 0.07 which was similar to our study [10]. Also, Laurens P. Koopman et al. study data were correlated with age and they stated a weakly positive but significant correlation between GLS and age with r value of 0.33 and P value of 0.001, while GCS correlation with age was weak and nonsignificant with r value 0.03 and P value 0.79 [2]. It was in agreement too with our study with differences regarding GLS which showed a strong positive correlation which can be explained by our larger study group number and different vendor machine used. Also, as regard to correlation with age Massimiliano Cantinotti et al., in their study that included 239 healthy children up to 5 years of age, stated that there was a weak correlation between strain values and age with r value less than 0.01 and did not include radial strain, yet this study was done using the Philips iE3 [11], while other studies despite using the GE vivid echo vendor machine as Liselotte M. Klitsie et al. regarding correlation with age stated that all data were nonsignificant which can be explained by a small number of subject group and different ethnicity [9].
Normal range and age correlation in left ventricle three-dimensional strain
Three-dimensional STE is a new technology used to assess LV global and regional function. 3D STE supposed to be more precise than 2D STE, because the speckles are within the pyramidal volume scan. So, 3D STE should remove the confounding effects of through-plane myocardial motion, which may affect the preciseness of LV strain measurements using 2D STE. Yet, the low temporal and spatial resolution of 3DE could adversely affect the preciseness of 3D STE measurements in patients with sets at the low frame rate range [4].
The quality of the image remains an important factor in the ability to acquire accurate stress and strain data by both 2D and 3D methods. However, the low frame rates that inevitably come with 3D imaging cannot be overcome yet. Another potential source of error is the failure to acquire the entirety of the LV apex when the 3D dataset is obtained from the apical four-chamber window [13].
Three-dimensional LV speckle studies were done on young age-group as our study is very scarce. Also, in our study young age-group below 2 years were excluded which were 20 subjects due to inadequate image quality. So, we finally included only 180 children aged 2–6yrs that underwent 3D STE.
Regarding the 3D STE data of our study, GLS ranged from -17% to −30% with a mean of -20.73 ± 2.03%. GCS ranged from -10% to -21% with a mean of 13.90 ± 2.05%, while GRS ranged from 41 to 61% with a mean of 47.51 ± 4.82%.
From the previous reports that studied all strain measurements, Zhou Lin et al. study included 51 children with a mean age 11.3 ± 2.1 years; their 3D GLS was 19.84 ± 2.73%, GCS was -19 ± 3.38% and GRS was 53.73 ± 11.17%. GE vivid E 95 was used to collect and analyze the data [14]. Also, Kyoko et al. concluded a study that included 15 subjects below 3 years of age with mean age 2 ± 1 year, with their GLS mean of -22.7 ± 2.6%, GCS mean of -29.3 ± 3% and GRS mean of 88.6 ± 6.1%, and another group of age ranged from 4 to 9 years with a mean age of 7 ± 2 years, their GLS mean of -21.9 ± 2.1%, GCS mean of -29.4 ± 4.3% and GRS mean of 92.7 ± 20.8%. All the data and analysis were done using Philips IE33 system [4]. While Perixu Zhang et al.’s study included 195 children with a mean age of 9.56 ± 1.21, their 3D strain values were GLS -19.54 ± 2.15%, GCS -23.14 ± 3.48%, and GRS 58.14 ± 11.59%. Toshiba echo system was used to collect and analyze the data [15]. All studies were in agreement with our results as regard to GLS, yet differences in GRS and GCS were evident which may be attributed to different vendor machines used as previous studies reported findings of lower circumferential strain values using the General Electric platform compared to the Philips platform and highlights the need for vendor-dependent normal values for circumferential strain until standardization initiatives have been deployed for this particular deformation parameter [2]. Also, there may be ethnicity difference and study group ages, BSA, and study population number discrepancies.
LV architecture can be reflected by the difference in the movement of the longitudinal versus the circumferential fibers, where both fibers are not interspersed but, on the contrary, are thought to be distinct regionally. That is, the fibers of the mid-wall are predominantly circumferential, whereas those of both the sub-endocardium and sub-epicardium are mostly longitudinal. Before reports of maturational changes of strain have been conflicting, with some reports showing no association and others describing relations of varying strength. These differences may be related to vendor-based differences in measurement or analysis, or to the specific age range in each age-group [10].
Stratifying this deformation parameter for age is needed. The short duration of each cardiac cycle may reflect the high strain rate values in comparison with older children. Strain values are usually comparable in different age-groups, so when the cardiac cycle is short, the deformation rate should be higher. Since heart rate and age show a very strong collinearity, this hypothesis is difficult to prove [2].
In our study, 3D GLS values had a strongly positive significant correlation with age with r value of 0.766 and P value of 0.001, while GCS showed a weakly positive nonsignificant correlation with r value of 0.055 and P value of 0.955 and GRS showed a strongly negative significant correlation with r value of -0.653 and P value of 0.001.
From the previous studies that correlated all 3D strain measurements with age, Li Zhang et al. study included 106 children aged from 1 to 5 years that concluded with regard to correlation with age; a weak nonsignificant correlation between strain values and age with r values of GLS was 0.049, GCS 0.013 and GRS 0.012, and P values for all of them were more than 0.05. Yet all data were collected and analyzed using Philips iE33 echo system with an older software version used [16]. On the other hand, recently Joseph D. Kuebler et al. concluded a study that included 35 healthy children from 1- to 5 years and concluded with regard to correlation with age; there was a weak but significant correlation between GLS and age with r value 0.22 and P value 0.001. But GCS had a weak nonsignificant correlation with age with r value 0.09 and P value 0.15 which agreed with our study results. GRS was not included. All data were collected and analyzed using Philips IE33 system [13].
Correlation between two-dimensional and three-dimensional left ventricle speckle strain values
In our study, correlation analysis of 2D and 3D values of strain showed that GLS had a strongly positive significant correlation with r value 0.702 and P value 0.001, while GCS showed a weakly positive nonsignificant correlation with r value 0.105 and P value 0.161 and GRS showed a strongly positive significant correlation with r value 0.6 and P value 0.001.
On the other hand, Sowmya et al. made a comparison between results of 2D and 3D STE with 17 subjects involved with a mean age of 13.9 years using Siemens medical system for data collection and analysis and they found that there was a positive strong significant correlation regarding GLS with r value 0.68 and P value 0.001. GCS showed a strong positive correlation with r value 0.62 and P value 0.004. GRS strain showed a weak nonsignificant correlation. All data were collected and analyzed using Siemens echo system [17]. In comparison with our study with Sowmya et al., there was concordance with our study with GLS, but GCS and GRS showed discordance with our study that may be attributed to different echo system used, different age-group, and different ethnicity.
Doaa Aly et al. recently conducted a study on 105 pediatric subjects with age from 1 to 18 years with normal cardiac structure correlating 2D and 3D GLS only, yet showed good agreement between both and correlation which was high with r value 0.7 and P value < 0.05; the analyses were performed using TOMTEC software. This shows that at least 3D GLS can be a promising good alternative to 2D GLS in assessing the LV function due to its less time consumption and less sophisticated analysis method [18].
Limitations
Image quality remains a significant factor in the ability to obtain accurate stress and strain parameters by both 2D and 3D methods. However, the lower frame rates that inevitably accompany 3D imaging cannot yet be overcome. All subjects involved in the study had conventional and 2D STE, but not all of them had a 3D examination due to poor echogenic windows and relatively small BSA in comparison with large probe size and low frame rate as detected by the software. This study was constructed during the COVID-19 era in a single-center study which led to limited number of patients. Although this reference value study included around 200 participants, estimation of the mean values would have been more robust if more participants were included. Especially in younger children where the number of participants was lower, the normal values should be interpreted with caution.