title: 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).
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri. Electronic address: levy_p@kids.wustl.edu.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Levy
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Aura A
authors.initials: AA
authors.lastname: Sanchez Mejia
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Aliza
authors.initials: A
authors.lastname: Machefsky
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Susan
authors.initials: S
authors.lastname: Fowler
authors.affiliation: Department of Radiology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Holland
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gautam K
authors.initials: GK
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003971:Diastole / Q000502:physiology; D004452:Echocardiography / Q000592:standards* / Q000706:statistics & numerical data*; D055119:Elastic Modulus / Q000502:physiology; D054459:Elasticity Imaging Techniques / Q000592:standards* / Q000706:statistics & numerical data*; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013599:Systole / Q000502:physiology; D016278:Ventricular Function, Right / Q000502:physiology*; D055815:Young Adult
keywords: Cardiac function; Children; Global longitudinal strain; Right ventricle; Speckle-tracking echocardiography