Background
Establishment of the range of normal values and associated variations of two-dimensional (2D) speckle-tracking echocardiography (STE)–derived right ventricular (RV) strain is a prerequisite for its routine clinical application in children. The objectives of this study were to perform a meta-analysis of normal ranges of RV longitudinal strain measurements derived by 2D STE in children and to identify confounders that may contribute to differences in reported measures.
Methods
A systematic review was conducted in PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov . Search hedges were created to cover the concepts of pediatrics, STE, and the right heart ventricle. Two investigators independently identified and included studies if they reported the 2D STE–derived RV strain measure RV peak global longitudinal strain, peak global longitudinal systolic strain rate, peak global longitudinal early diastolic strain rate, peak global longitudinal late diastolic strain rate, or segmental longitudinal strain at the apical, middle, and basal ventricular levels in healthy children. Quality and reporting of the studies were assessed. The weighted mean was estimated using random effects with 95% confidence intervals (CIs), heterogeneity was assessed using Cochran’s Q statistic and the inconsistency index ( I 2 ), and publication bias was evaluated using funnel plots and Egger’s test. Effects of demographic, clinical, equipment, and software variables were assessed in a metaregression.
Results
The search identified 226 children from 10 studies. The reported normal mean values of peak global longitudinal strain among the studies varied from −20.80% to −34.10% (mean, −29.03%; 95% CI, −31.52% to −26.54%), peak global longitudinal systolic strain rate varied from −1.30 to −2.40 sec −1 (mean, −1.88 sec −1 ; 95% CI, −2.10 to −1.59 sec −1 ), peak global longitudinal early diastolic strain rate ranged from 1.7 to 2.69 sec −1 (mean, 2.34 sec −1 ; 95% CI, 2.00 to 2.67 sec −1 ), and peak global longitudinal late diastolic strain rate ranged from 1.00 to 1.30 sec −1 (mean, 1.18 sec −1 ; 95% CI, 1.04 to 1.33 sec −1 ). A significant base-to-apex segmental strain gradient ( P < .05) was observed in the RV free wall. There was significant between-study heterogeneity and inconsistency ( I 2 > 88% and P < .01 for each strain measure), which was not explained by age, gender, body surface area, heart rate, frame rate, tissue-tracking methodology, equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias ( P = .59).
Conclusions
This study is the first to define normal values of 2D STE–derived RV strain in children on the basis of a meta-analysis. The normal mean value in children for RV global strain is −29.03% (95% CI, −31.52% to −26.54%). The normal mean value for RV global systolic strain rate is −1.88 sec −1 (95% CI, −2.10 to −1.59 sec −1 ). RV segmental strain has a stable base-to-apex gradient that highlights the dominance of deep longitudinal layers of the right ventricle that are aligned base to apex. Variations among different normal ranges did not appear to be dependent on differences in demographic, clinical, or equipment parameters in this meta-analysis. All of the eligible studies used equipment and software from one manufacturer (GE Healthcare).
Right ventricular (RV) function is an important prognostic determinant of cardiopulmonary pathologies in children. The RV myofiber architecture is composed of superficial oblique and dominant deep longitudinal layers, but the longitudinal shortening is the dominant deformation of the right ventricle that provides the major contribution to stroke volume during systole. Myocardial strain that describes this longitudinal deformation under an applied force provides a new sensitive measure of the RV function in children. Two-dimensional (2D) speckle-tracking echocardiography (STE) is an angle-independent method for myocardial strain measurement that has been used to estimate deformation measures and quantitatively characterize cardiac function in children.
The use of myocardial strain parameters derived from 2D STE to measure RV function in children requires knowledge of the range of normal values. Clinical applications of strain imaging to assess systolic and diastolic function in children with a variety of complex conditions (congenital heart disease, cystic fibrosis, sickle-cell anemia, and chronic lung disease) have recently reported measures of global and segmental longitudinal strain and strain rate. However, the mean values and associated variations of these strain values need to be firmly established before routine clinical adoption of RV strain measurements can be implemented in children.
There are several potential sources of variation among the reported values in studies that may influence the acquisition and generation of strain measures, specifically patient demographics (age, gender, race), clinical factors (heart rate [HR], blood pressure, weight, body surface area [BSA]), and equipment and image technique variables (ultrasound and vendor-customized software, probe size, tissue-tracking methodology, and frame rate). Similar to Yingchoncharoen et al ‘s. 2012 meta-analysis of the normal ranges of left ventricular strain in adults, we sought to define a range of normal RV strain measures using a compilation of all studies that reported values for cohorts of normal or control children. The objectives of our study were to perform a meta-analysis of normal ranges of RV longitudinal strain and strain rate measurements derived from 2D STE in children and to identify confounders that may contribute to differences and variability in reported measures.
Methods
Search Strategy and Protocol
S.F., our librarian trained in systematic reviews, created search hedges to cover the concepts of pediatrics or children, STE, and the right heart ventricle using terms harvested from standard term indices and on-topic articles ( Appendix 1 ; available at www.onlinejase.com ). To exclude animals, S.F. used the human filter for PubMed, recommended in the Cochrane Handbook for Systematic Reviews of Interventions , and then used that as a model to create similar filters for the other searched databases. The search strategy was conducted in PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov . Searches were completed by May 2013.
Study Selection and Eligibility Criteria
Studies were included if the articles reported using strain derived from 2D STE to measure RV function in healthy pediatric normal or control subjects. Studies that exclusively included children aged <21 years were considered eligible for the meta-analysis. The systematic review incorporated observational studies that used pediatric control groups with normal results on echocardiography (who were recruited for specific studies) or if the children were the primary objective.
Seven specific global and segmental strain and strain rate measurements were included in the meta-analysis. The global longitudinal strain measures included (1) peak global longitudinal strain (pGLS) within the systolic period, (2) peak global longitudinal systolic strain rate (pGLSRs), (3) peak global longitudinal early diastolic strain rate (pGLSRe), and (4) peak global longitudinal late diastolic strain rate (pGLSRa). The segmental longitudinal strain measures included segmental longitudinal strain at the (5) apex, (7) middle, and (7) basal ventricular levels of the RV free wall (RVFW). Studies were excluded from this analysis if they were abstracts only without full text or review articles. All echocardiographic strain measurements were generated from digitally stored images. Currently, there are two reported methods to generate RV “global” longitudinal strain measures from the apical four-chamber view ( Figure 1 ). In method 1 (full RV myocardium), global longitudinal myocardial deformation can be calculated on the basis of the entire traced contour of the right ventricle, which includes the RVFW and the septal wall. In method 2 (RVFW), the weighted average of the three regional values of the lateral RVFW only (basal, middle, and apical segments) provides the value of global longitudinal RV strain ( Figure 1 ). We stratified our meta-analysis by the “full RV myocardium” versus “RVFW only” methods of reporting “global” RV strain and strain rate to account for the different techniques used among studies.
