Three-Dimensional Echocardiography Derived Nomograms for Left Ventricular Volumes in Healthy Caucasian Italian Children

Abstract

Three-dimensional echocardiography (3DE) is increasingly used for the evaluation of children with congenital heart disease (CHD).1Zhang L. Gao J. Xie M. Yin P. Liu W. Li Y. et al.Left ventricular three-dimensional global systolic strain by real-time three-dimensional speckle-tracking in children: feasibility, reproducibility, maturational changes, and normal ranges.J Am Soc Echocardiogr. 2013; 26: 853-859Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Indications for 3DE include not only characterization of complex defects but also measurements of chamber volumes and valvular and vascular dimensions.1Zhang L. Gao J. Xie M. Yin P. Liu W. Li Y. et al.Left ventricular three-dimensional global systolic strain by real-time three-dimensional speckle-tracking in children: feasibility, reproducibility, maturational changes, and normal ranges.J Am Soc Echocardiogr. 2013; 26: 853-859Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Ventricular volumes by 3DE have superior agreement with magnetic resonance imaging (MRI) and computed tomography (CT), as compared with those obtained by 2D echocardiography (2DE).1Zhang L. Gao J. Xie M. Yin P. Liu W. Li Y. et al.Left ventricular three-dimensional global systolic strain by real-time three-dimensional speckle-tracking in children: feasibility, reproducibility, maturational changes, and normal ranges.J Am Soc Echocardiogr. 2013; 26: 853-859Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 2Friedberg M.K. Su X. Tworetzky W. Soriano B.D. Powell A.J. Marx G.R. Validation of 3D echocardiographic assessment of left ventricular volumes, mass, and ejection fraction in neonates and infants with congenital heart disease: a comparison study with cardiac MRI.Circ Cardiovasc Imaging. 2010; 3: 735-742Crossref PubMed Scopus (75) Google Scholar, 3Wood P.W. Choy J.B. Nanda N.C. Becher H. Left ventricular ejection fraction and volumes: it depends on the imaging method.Echocardiography. 2014; 31: 87-100Crossref PubMed Scopus (159) Google Scholar, 4Jenkins C. Moir S. Chan J. Rakhit D. Haluska B. Marwick T.H. Left ventricular volume measurement with echocardiography: a comparison of left ventricular opacification, three-dimensional echocardiography, or both with magnetic resonance imaging.Eur Heart J. 2009; 30: 98-106Crossref PubMed Scopus (191) Google Scholar, 5Alghamdi M.H. Grosse-Wortmann L. Ahmad N. Mertens L. Friedberg M.K. Can simple echocardiographic measures reduce the number of cardiac magnetic resonance imaging studies to diagnose right ventricular enlargement in congenital heart disease?.J Am Soc Echocardiogr. 2012; 25: 518-523Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar A recent investigation by Wood et al.3Wood P.W. Choy J.B. Nanda N.C. Becher H. Left ventricular ejection fraction and volumes: it depends on the imaging method.Echocardiography. 2014; 31: 87-100Crossref PubMed Scopus (159) Google Scholar showed that left ventricular (LV) volumes in adults measured using different echocardiographic methods (2DE, 3DE, and contrast) were smaller compared with those obtained by MRI. However, LV volumes by 3DE were closer to the reference standard MRI3Wood P.W. Choy J.B. Nanda N.C. Becher H. Left ventricular ejection fraction and volumes: it depends on the imaging method.Echocardiography. 2014; 31: 87-100Crossref PubMed Scopus (159) Google Scholar, 4Jenkins C. Moir S. Chan J. Rakhit D. Haluska B. Marwick T.H. Left ventricular volume measurement with echocardiography: a comparison of left ventricular opacification, three-dimensional echocardiography, or both with magnetic resonance imaging.Eur Heart J. 2009; 30: 98-106Crossref PubMed Scopus (191) Google Scholar and comparable to MRI when contrast enhancement was used, indicating that the use of 3DE allows for more accurate estimation of LV volumes. Recent publications have established 3DE norms for the LV in adults.6Chahal N.S. Lim T.K. Jain P. Chambers J.C. Kooner J.S. Senior R. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction.JACC Cardiovasc Imaging. 2012; 5: 1191-1197Crossref PubMed Scopus (70) Google Scholar, 7Bernard A. Addetia K. Dulgheru R. Caballero L. Sugimoto T. Akhaladze N. et al.3D echocardiographic reference ranges for normal left ventricular volumes and strain: results from the EACVI NORRE study.Eur Heart J Cardiovasc Imaging. 2017; 18: 475-483Crossref PubMed Scopus (59) Google Scholar, 8Muraru D. Cucchini U. Mihăilă S. Miglioranza M.H. Aruta P. Cavalli G. et al.Left ventricular myocardial strain by three-dimensional speckle-tracking echocardiography in healthy subjects: reference values and analysis of their physiologic and technical determinants.J Am Soc Echocardiogr. 2014; 27: 858-871.e1Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 9Fukuda S. Watanabe H. Daimon M. Abe Y. Hirashiki A. Hirata K. et al.Normal values of real-time 3-dimensional echocardiographic parameters in a healthy Japanese population: the JAMP-3D Study.Circ J. 2012; 76: 1177-1181Crossref PubMed Scopus (63) Google Scholar, 10Buccheri S. Costanzo L. Tamburino C. Monte I. Reference values for real time three-dimensional echocardiography-derived left ventricular volumes and ejection fraction: review and meta-analysis of currently available studies.Echocardiography. 2015; 32: 1841-1850Crossref PubMed Scopus (20) Google Scholar with large (>900 subjects)6Chahal N.S. Lim T.K. Jain P. Chambers J.C. Kooner J.S. Senior R. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction.JACC Cardiovasc Imaging. 2012; 5: 1191-1197Crossref PubMed Scopus (70) Google Scholar or relatively large (>400 subjects) sample sizes.7Bernard A. Addetia K. Dulgheru R. Caballero L. Sugimoto T. Akhaladze N. et al.3D echocardiographic reference ranges for normal left ventricular volumes and strain: results from the EACVI NORRE study.Eur Heart J Cardiovasc Imaging. 2017; 18: 475-483Crossref PubMed Scopus (59) Google Scholar, 9Fukuda S. Watanabe H. Daimon M. Abe Y. Hirashiki A. Hirata K. et al.Normal values of real-time 3-dimensional echocardiographic parameters in a healthy Japanese population: the JAMP-3D Study.Circ J. 2012; 76: 1177-1181Crossref PubMed Scopus (63) Google Scholar In the pediatric setting, 3DE norms for LV volumes have been calculated in limited sample sizes.1Zhang L. Gao J. Xie M. Yin P. Liu W. Li Y. et al.Left ventricular three-dimensional global systolic strain by real-time three-dimensional speckle-tracking in children: feasibility, reproducibility, maturational changes, and normal ranges.J Am Soc Echocardiogr. 2013; 26: 853-859Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 6Chahal N.S. Lim T.K. Jain P. Chambers J.C. Kooner J.S. Senior R. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction.JACC Cardiovasc Imaging. 2012; 5: 1191-1197Crossref PubMed Scopus (70) Google Scholar, 11Hascoët S. Brierre G. Caudron G. Cardin C. Bongard V. Acar P. Assessment of left ventricular volumes and function by real time three-dimensional echocardiography in a pediatric population: a TomTec versus QLAB comparison.Echocardiography. 2010; 27: 1263-1273Crossref PubMed Scopus (34) Google Scholar, 12Laser K.T. Houben B.A. Körperich H. Haas N.A. Kelter-Klöpping A. Barth P. et al.Calculation of pediatric left ventricular mass: validation and reference values using real-time three-dimensional echocardiography.J Am Soc Echocardiogr. 2015; 28: 275-283Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar We sought to investigate pediatric nomograms for LV volumes by 3DE in a large cohort of healthy children. Healthy Caucasian children evaluated from April 2017 to December 2018 for CHD screening in the outpatient pediatric cardiology department at a single institution were prospectively recruited. The population included 400 healthy children previously reported in recent publications of other measurements.14Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar All subjects with clinical, electrocardiographic, or echocardiographic evidence of CHD or acquired heart disease were excluded. Other exclusion criteria consisted of patients with known or suspected neuromuscular disease, genetic syndromes, or chromosomal abnormalities; body mass index ≥95th percentile for children ≥2 years old13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar or weight-for-length Z-score ≥214Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar; pulmonary hypertension14Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar; systemic hypertension (for children > 4 year of age); connective tissue disorder; or family history of genetic cardiac disease.14Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Approval for this study was obtained from the Local Ethics Committee. Parents or legal guardians of all enrolled children were informed, and they accepted to participate by signing consent. All patients underwent 3D examination with full-volume data sets obtained from R-wave triggered two- to four-beat acquisitions (iE33 system, phased array 7 and 5 Mhz transducers; Philips, Bothell). Breath holding was done if the child was able; if the child was unable to hold his or her breath, multiple data sets were acquired, and only those with good quality and without respiratory (“stitch”) artifacts were selected. Images were digitally stored for subsequent off-line analysis on Q Lab 9 (Philips). Three-dimensional end-diastolic and end-systolic LV volumes were measured, with ventricular trabeculae and papillary muscles included in the LV cavity, and end systole was defined as the frame before mitral valve opening. Tracing consisted of setting five points—septal, lateral, anterior and inferior mitral annulus and the apex, followed by semiautomated computation with manual correction of the endocardial contour. Two independent experienced pediatric cardiologists (M.C., E.F.) acquired the images and performed all measurements. Measurements were repeated three times on the same selected 3D data set and the mean was calculated. Rates of intraobserver and interobserver variability of echocardiographic indices were calculated from 20 randomly selected patients. The sample size was calculated on the basis of previous observations.14Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar To examine the relationship between parameters of body size, heart rate, age, and each of the echocardiographic variables, multiple models using linear, logarithmic, exponential, and square root equations were tested. Among the models that satisfied the assumption of homoskedasticity, the model with the highest R2 value was considered to provide the best fit. The presence or absence of heterosKedasticity was tested by the White test and the Breusch-Pagan test as described elsewhere.14Cantinotti M. Scalese M. Giordano R. Franchi E. Assanta N. Marotta M. et al.Normative data for left and right ventricular systolic strain in healthy Caucasian Italian children by two-dimensional speckle-tracking echocardiography.J Am Soc Echocardiogr. 2018; 31: 712-720.e6Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar To test the normality of residuals, the Shapiro-Wilk and Lilliefors (Kolmogorov-Smirnov) tests were used. The Haycock formula was used to calculate body surface area (BSA). Outliers were identified visually and by using the leverage values and the studentized error residuals; those observations were omitted from the final analysis if they significantly deviated from the models. The effects of gender were also evaluated as covariates in these models. Among 878 subjects enrolled, the final study population comprised 800 subjects (age 1 day to 18 years; mean age 89.5 months; median 86.6 months; interquartile range 48.1-135.4 months; 48.3% female). Demographic data are provided in Table 1. The feasibility for obtaining full-volume images of good quality was 91.1%. Feasibility was significantly lower at lower ages (P < .001; Table 1 and Supplemental Table 1, available at www.onlinejase.com). The measurements were first modeled with heart rate, age, weight, height, and BSA. The best-fit models for each measurement was the power (ln[y] = a + b * ln[x]) model because it satisfied the assumption of homoskedasticity and normality of residuals and showed the highest R2 score (Supplemental Table 2, available at www.onlinejase.com). The predicted values and Z-score boundaries for all measurements are presented in Table 2. Z-score charts are presented in Figure 1. The interobserver and intraobserver coefficients of variation showed acceptable reproducibility. The intraobserver difference was 1.2% for LV end-diastolic volume (LVEDV; interclass coefficient [ICC], 0.998; 95% CI, 0.995-0.999) and 2.5% for LV end-systolic volume (LVESV; ICC, 0.992; 95% CI, 0.982-0.997); interobserver difference was 0.7% for LVEDV (ICC, 0.999; 95% CI, 0.998-1.000) and 1.5% for LVESV (ICC, 0.997; 95% CI, 0.993-0.999; Supplemental Table 3, available at www.onlinejase.com). To evaluate the influence of gender a multiple linear regression model was used including gender as a covariate along with BSA. We found a slight but significant effect of gender in the models, but R2 did not significantly improve with addition of gender (Supplemental Table 4, available at www.onlinejase.com).Table 1Distribution of BSA calculated with the Haycock formulaBSAn%Feasibility, %[0.15-0.25]141.870.0[0.25-0.3]131.668.4[0.3-0.35]212.680.7[0.35-0.4]303.883.3[0.4-0.45]283.582.3[0.45-0.5]182.381.8[0.5-0.6]344.391[0.6-0.7]698.695[0.7-0.8]8010.094.1[0.8-0.9]8610.895.5[0.9-1.0]637.992.6[1.0-1.1]546.891.5[1.1-1.2]465.892[1.2-1.3]374.692.5[1.3-1.4]455.693.7[1.4-1.5]415.193.1[1.5-1.6]394.990.6[1.6-2.1]8210.396.4Total80010091.1 Open table in a new tab Table 2Predicted values (mean ± 2 SD) of measured echocardiography variables expressed by BSA using the Haycock formulaBSA, m20.150.200.250.300.350.400.500.600.700.800.901.03D LVEDV, mL4.50 (2.49, 8.11)6.54 (3.63, 11.81)8.76 (4.85, 15.80)11.11 (6.16, 20.04)13.59 (7.53, 24.51)16.17 (8.96, 29.17)21.64 (11.99, 39.03)27.45 (15.22, 49.52)33.57 (18.61, 60.55)39.96 (22.15, 72.08)46.60 (25.83, 84.06)53.46 (29.64, 96.45)3D LVESV, mL1.47 (0.81, 2.67)2.18 (1.20, 3.94)2.94 (1.63, 5.33)3.77 (2.08, 6.83)4.64 (2.56, 8.41)5.56 (3.07, 10.08)7.53 (4.16, 13.64)9.64 (5.32, 17.46)11.88 (6.56, 21.51)14.23 (7.86, 25.78)16.70 (9.22, 30.24)19.26 (10.63, 34.88)BSA, m21.11.21.31.41.51.61.71.81.92.02.13D LVEDV, mL60.54 (33.56, 109.2)67.82 (37.60, 122.36)75.29 (41.74, 135.83)82.94 (45.97, 149.62)90.75 (50.31, 163.72)98.73 (54.73, 178.10)106.85 (59.23, 192.76)115.13 (63.82, 207.69)123.55 (68.49, 222.88)132.10 (73.23, 238.31)140.78 (78.04, 253.97)3D LVESV, mL21.91 (12.10, 39.69)24.66 (13.61, 44.66)27.48 (15.17, 49.77)30.38 (16.78, 55.03)33.36 (18.42, 60.43)36.41 (20.10, 65.95)39.53 (21.82, 71.59)42.71 (23.58, 77.36)45.96 (25.37, 83.24)49.27 (27.20, 89.23)52.63 (29.06, 95.33)The values in parentheses are (–2 SD, +2 SD). Open table in a new tab The values in parentheses are (–2 SD, +2 SD). Normal values for LV volumes and ejection fraction derived by 3DE in a large cohort of healthy children are presented. This is the largest reported series on normal 3DE pediatric LV volumes. Early work in this field had sample size limitations.1Zhang L. Gao J. Xie M. Yin P. Liu W. Li Y. et al.Left ventricular three-dimensional global systolic strain by real-time three-dimensional speckle-tracking in children: feasibility, reproducibility, maturational changes, and normal ranges.J Am Soc Echocardiogr. 2013; 26: 853-859Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 11Hascoët S. Brierre G. Caudron G. Cardin C. Bongard V. Acar P. Assessment of left ventricular volumes and function by real time three-dimensional echocardiography in a pediatric population: a TomTec versus QLAB comparison.Echocardiography. 2010; 27: 1263-1273Crossref PubMed Scopus (34) Google Scholar A more recent study13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar included 370 children (1 day to 219 months) using a rigorous methodology, but it was still limited by a relatively small sample size and unclear racial composition. The multicenter design of that study with acquisitions performed at three different centers by five different operators might also have introduced a bias partly attenuated using a core lab for analysis. Moreover, the authors computed percentiles instead of Z-scores. The Z-score, a widely accepted tool in pediatric echocardiography, is a standard bearer value that indicates by how many SDs a value is above or below the mean in a normally distributed population. The Z-score would allow clinicians to appreciate the “magnitude of abnormality” and its progression over time, and reporting 3DE Z-scores for the LV is a strength of the present study. The present study also provides a comparison of 2DE- and 3DE-derived LV parameters.11Hascoët S. Brierre G. Caudron G. Cardin C. Bongard V. Acar P. Assessment of left ventricular volumes and function by real time three-dimensional echocardiography in a pediatric population: a TomTec versus QLAB comparison.Echocardiography. 2010; 27: 1263-1273Crossref PubMed Scopus (34) Google Scholar, 13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In line with publications in adults3Wood P.W. Choy J.B. Nanda N.C. Becher H. Left ventricular ejection fraction and volumes: it depends on the imaging method.Echocardiography. 2014; 31: 87-100Crossref PubMed Scopus (159) Google Scholar we found 2DE to systematically underestimate LV volumes compared with 3DE; however, the differences were significant only for LV end-diastolic volumes (P < .001; Supplemental Table 5, available at www.onlinejase.com). The present report has limitations. Since Caucasians constitute the main population in our region, the study was limited to this ethnic group. However, this eliminated the bias of differing racial compositions and would potentially allow future comparisons. Studies in adults suggest significant differences in ventricular volumes among different races. For example, indexed 3DE LV volumes were significantly smaller in Indian Asians compared with European whites.6Chahal N.S. Lim T.K. Jain P. Chambers J.C. Kooner J.S. Senior R. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction.JACC Cardiovasc Imaging. 2012; 5: 1191-1197Crossref PubMed Scopus (70) Google Scholar A complete set of measurements was not available for the subjects studied. We provide data only for vendor-dependent software (QLab 9, Philips). A previous study showed LV volumes to be greater with QLAb compared with independent software Tomtec 30 (TomTec, Unterschleissheim, Germany), with a bias of 0.8% for end-systolic volumes and 2.2% for diastolic volumes.13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar However, when only good-quality examinations were evaluated, differences significantly decreased, especially for end-systolic volumes. The study also lacks comparisons with MRI. Krell et al.13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar compared 3DE LV volumes obtained from different software (Qlab, TomTec 30 and TomTec 75) against MRI in a small cohort of healthy subjects. As expected, 3DE underestimated volumes, especially for end-diastolic volumes.13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar The smallest difference was noted between QLab and MRI, followed by TomTec 30 and MRI, while greater differences were noted between TomTec 75 and MRI.13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Bias among volumes estimated by MRI and 3DE (QLab) were statistically insignificant for end-systolic volume and end-diastolic volume.13Krell K. Laser K.T. Dalla-Pozza R. Winkler C. Hildebrandt U. Kececioglu D. et al.Real-time three-dimensional echocardiography of the left ventricle—pediatric percentiles and head-to-head comparison of different contour-finding algorithms: a multicenter study.J Am Soc Echocardiogr. 2018; 31: 702-711Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In conclusion, we present 3DE-derived Z-scores for the LV in a large cohort of healthy children. Our data could serve as a pediatric reference for the LV for studies in children with CHD. Further studies are required to reinforce these data. More work is also needed to evaluate other chambers, examine the influence of various confounders including race and ethnic groups, and inspect the differences between vendor-specific and vendor-independent software. Supplemental Table 1Demographic characteristicsMeanSDMedianPercentile 25Percentile 75MinimumMaximumAge, mo89.555.986.648.1135.40.03217.5BSA, m20.990.430.930.681.320.182.15Weight, kg29.318.324.516.042.02.693.0Height, cm121.433.1123.0101.0149.043.0185.0Heart rate, bpm9224887710346151 Open table in a new tab Supplemental Table 2Coefficients for regression equations showing the relationships among echocardiographic measurements and BSA, the standard error of the estimate, and the determination coefficientMeasurementInterceptBSEE (√MSE)R2SWKSBPW3D LVEDV, mL3.9791.3050.2950.8340.0010.0540.7840.0143D LVESV, mL2.9581.3550.2970.8420.0050.0560.1150.0193D EF, %4.160–0.0150.0560.0190.0010.0010.9020.975BP, Breusch-Pagan test; EF, ejection fraction; KS, Kolmogorov-Smirnov test; MSE, mean square error; R2, coefficient of determination; SEE, standard error of the estimate; SW, Shapiro-Wilk test; W, White test.Normality test: Shapiro-Wilk and Lilliefors (Kolmogorov-Smirnov). Heteroskedasticity test (White test and Breusch-Pagan test). BSA by the Haycock formula (ln[y] = a + b * ln[x]); Z-value = (ln[Measurement] – (Intercept + B * ln[BSA]))/√MSE. Open table in a new tab Supplemental Table 3Inter- and intraobserver analysisMeasurementsICCintraobserverP valueinterobserverICCinterobserverP valueinterobserverCVintraobserver, %CVinterobserver, %3D LVEDV, mL0.999 (0.998-1.000)<.0010.998 (0.995-0.999)<.0010.71.23D LVESV, mL0.997 (0.993-0.999)<.0010.992 (0.982-0.997)<.0011.52.53D EF, %0.950 (0.888-0.978)<.0010.815 (0.619-0.916)<.0010.61.2CV, Coefficient of variation; EF, ejection fraction. Open table in a new tab Supplemental Table 4Coefficients for regression equations showing the relationship of echocardiographic measurements to Haycock BSA and genderDependent variableGenderP valueR23D LVEDV, mL0.061.0020.8363D LVESV, mL0.064.0020.8443D EF, %0.001.9060.018EF, Ejection fraction.Same equations as in Supplemental Table 2, with gender as an independent variable as well. R2 does not improve with respect to the model of Supplemental Table 2. Open table in a new tab Supplemental Table 5Comparison of LV volumes calculated by 2DE and 3DEMeasurements, mL3DE2DEP valuenLVEDV53.57 ± 32.7050.75 ± 30.79<.001526LVESV19.40 ± 12.2719.23 ± 12.20.897510Data are expressed as mean ± SD. Open table in a new tab BP, Breusch-Pagan test; EF, ejection fraction; KS, Kolmogorov-Smirnov test; MSE, mean square error; R2, coefficient of determination; SEE, standard error of the estimate; SW, Shapiro-Wilk test; W, White test. Normality test: Shapiro-Wilk and Lilliefors (Kolmogorov-Smirnov). Heteroskedasticity test (White test and Breusch-Pagan test). BSA by the Haycock formula (ln[y] = a + b * ln[x]); Z-value = (ln[Measurement] – (Intercept + B * ln[BSA]))/√MSE. CV, Coefficient of variation; EF, ejection fraction. EF, Ejection fraction. Same equations as in Supplemental Table 2, with gender as an independent variable as well. R2 does not improve with respect to the model of Supplemental Table 2. Data are expressed as mean ± SD.