Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis

Abstract

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).

Keywords: Cardiac function; Children; Global longitudinal strain; Right ventricle; Speckle-tracking echocardiography.

Figure 1

Right ventricle “Global” longitudinal strain methods of data analysis: Full RV myocardium method vs. Right Ventricle Free Wall (RVFW) only method. A): Full RV myocardium: A region of interest is placed around the entire RV myocardium including the RV free wall and the septal wall. The segmental strain is graphically presented by six different color-code curves and the global longitudinal strain by the white dotted curve. The peak of the average curve of the six segments (the dotted curve) was considered as peak global longitudinal strain (pGLS). B) RVFW only : A region of interest is placed around the RVFW only. The basal (yellow), mid (blue), and apical (green) segments of the RV free wall are depicted, as well as the global strain (white dots) of the RV free wall. The peak of the average curve of the 3 segments (the dotted curve) was considered as peak global longitudinal strain (RV pGLS).

Figure 2

Process of inclusion of studies in the meta-analysis

Figure 3

Normal value of RV pGLS by (A) method of generating RV “global” longitudinal strain and (B) age distribution. The forest plot lists the names of the included studies in chronological order, the mean and confidence intervals with the upper (95%) and lower (5%) limits. Each study is represented by a square that reflects the mean at the point estimate of effect and is proportional to the study's weight in the meta-analysis. A horizontal line extending from either side of the square reflects the 95% confidence interval. The overall meta-analysis measure of effect is plotted as a diamond with the lateral points of the diamond indicating confidence intervals for this mean estimate.

Figure 3

Normal value of RV pGLS by (A) method of generating RV “global” longitudinal strain and (B) age distribution. The forest plot lists the names of the included studies in chronological order, the mean and confidence intervals with the upper (95%) and lower (5%) limits. Each study is represented by a square that reflects the mean at the point estimate of effect and is proportional to the study's weight in the meta-analysis. A horizontal line extending from either side of the square reflects the 95% confidence interval. The overall meta-analysis measure of effect is plotted as a diamond with the lateral points of the diamond indicating confidence intervals for this mean estimate.

Figure 4

Normal values of RV global longitudinal systolic strain rate (RV pGLSRs). The forest plot lists the names of the included studies in chronological order, the mean and confidence intervals with the upper (95%) and lower (5%) limits. Each study is represented by a square that reflects the mean at the point estimate of effect and is proportional to the study's weight in the meta-analysis. A horizontal line extending from either side of the square reflects the 95% confidence interval. The overall meta-analysis measure of effect is plotted as a diamond with the lateral points of the diamond indicating confidence intervals for this mean estimate.

Figure 5

Normal values of RV Segmental longitudinal strain; a)Apex (RV SLSA); b) mid-ventricular (RV SLSM) c) base (RV SLSB). A significant base-to-apex gradient exists for right ventricle segmental longitudinal strain (P < 0.05).

Figure 6

Publication bias. Funnel plot for studies of right ventricle peak global longitudinal strain (RV pGLS). The standard error of the effect estimate is plotted on the vertical axis. The mean of the RV pGLS is plotted on the horizontal axis. Visual inspection shows symmetry in the distribution of the studies that suggests the absence of publication bias (P=0.59 from the Egger test for statistical funnel plot symmetry).