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ORIGINAL ARTICLE
A pediatric echocardiographic Z‑score nomogram for a developing
country: Indian pediatric echocardiography study – The Z‑score
Rajendra Kumar Gokhroo, Avinash Anantharaj, Devendra Bisht1, Kamal Kishor, Nishad Plakkal2, Rajeswari Aghoram3,
Nivedita Mondal2, Shashi K Pandey, Ramsagar Roy
Department of Cardiology, JLN Medical College and Associated Group of Hospitals, Ajmer, Rajasthan, 1Department of Cardiology, Ace Heart and Vascular
Institute, Shivalik Hospital Premises, Sector 69, Mohali, Punjab, 2Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education and
Research, Puducherry, 3Department of Medicine, Indira Gandhi Medical College and Research Institute, Puducherry, India
ABSTRACT
Background : Almost all presently available pediatric echocardiography Z-score nomograms are based
on Western data. They may not be a suitable reference standard for assessing the sizes
of cardiac structures of children from developing countries.
Objective : This study’s objective was to collect normative data of 21 commonly measured
cardiovascular structures using M-mode and two-dimensional echocardiography in
Indian children aged between 4 and 15 years and to derive Z-score nomograms for each.
Subjects and : The study was conducted at two centers in India - Ajmer, Rajasthan, and Mohali, Punjab.
Methods We studied a community-based sample involving healthy school going children. After
excluding children with cardiovascular abnormalities on the screening echocardiogram,
746 children were included in the final analysis. Echocardiographic assessment was
performed using a Philips iE33 system.
Results and : For each parameter measured, seven models were evaluated to assess the relationship of
Analysis that parameter with the body surface area and the one with the best fit was used to plot
the Z-score chart for that parameter. Z score charts were thus derived.
Conclusions : The Z-score nomograms derived by this study may be better alternatives to the Western
nomograms for use in India and other developing countries for preprocedural decision
making in the pediatric population. However, they will require validation in large-scale
studies before they can become clinically applicable.
Keywords : Developing country, echocardiography, pediatric, Z‑score
One of the methods to depict the deviation of a specified
INTRODUCTION
structure’s measured value from the population
Description of the sizes of cardiac chambers, valves, and mean is the Z‑score. It provides a way to record and
great vessels in terms of Z‑score is an important step in compare serial measurements in children undergoing
quantifying abnormal findings and planning pediatric sequential echocardiographic measurements over
cardiac interventions and cardiac surgeries. Currently time. By definition, Z = (x − µ)/σ, where x is the child’s
used nomograms are based on the Western studies and
This is an open access article distributed under the terms of the
may be inappropriate for use in developing countries.
Creative Commons Attribution-NonCommercial-ShareAlike 3.0
License, which allows others to remix, tweak, and build upon the
Access this article online work non-commercially, as long as the author is credited and the
Quick Response Code: new creations are licensed under the identical terms.
Website:
www.annalspc.com For reprints contact:
[email protected] How to cite this article: Gokhroo RK, Anantharaj A, Bisht D, Kishor K,
DOI: Plakkal N, Aghoram R, et al. A pediatric echocardiographic Z-score
10.4103/0974-2069.197053 nomogram for a developing country: Indian pediatric echocardiography
study – The Z-score. Ann Pediatr Card 2017;10:31-8.
Address for correspondence: Dr. Avinash Anantharaj, Department of Cardiology, JLN Medical College and Associated Group of Hospitals,
Ajmer ‑ 305 001, Rajasthan, India. E‑mail: [email protected]
© 2017 Annals of Pediatric Cardiology | Published by Wolters Kluwer - Medknow 31
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
measured value for the specified structure, µ is the
MATERIALS AND METHODS
mean of the population the child hails from, and σ is
their standard deviation. Studies providing Z‑scores The study was conducted at two centers in India with
for various cardiac structures are available, and it the objective of collecting normative data for the
is with the help of these references that current day measurements of the various cardiac structures using
practitioners of pediatric cardiology derive Z‑scores M‑mode and two‑dimensional (2D) echocardiography
for their patients. in normal children aged between 4 and 15 years and to
For the assessment of acquired and congenital heart calculate Z‑scores for each measured parameter. Seven
disease (CHD) in children, quantification of cardiac hundred and forty‑eight children were enrolled at
chambers, valves, and great vessels is of absolute Ajmer, Rajasthan, and thirty at Mohali, Punjab. Children
importance since major decisions regarding the need were recruited from three different schools of Ajmer.
for and timing of intervention is made on the basis of In the Mohali center, children accompanying patients
these values. The Z‑score for each measured parameter attending an adult cardiology facility were enrolled.
is assessed from nomograms or Z‑score charts, which Children with any chronic underlying disease or a CHD
are available on dedicated websites and as smartphone were excluded from the study. After obtaining written
applications. The routine practice world over is to use informed consent from the parents, the children were
one of these sources to get the individual patient’s evaluated clinically followed by echocardiographic
Z‑score for the measured parameter. Almost all of these screening. Echocardiographic evaluation was performed
nomograms are derived from studies done in developed using a Philips iE33 system (Philips Medical Systems,
countries. Thus, key decisions like necessity for and Bothell,WA, USA). The 2D and M‑mode measurements
timing of intervention in children with CHD hailing of 21 cardiovascular structures were obtained for
from developing countries are made based on Western each subject. Age‑appropriate transducers (4–12,
standards. Since biological parameters often vary 2–7, 2–5 MHz) were used. Echocardiograms were
between populations due to differences in ethnicity and obtained at the standard precordial positions. We
environmental influences, Western data may not serve followed the recommendations for standardizing
as a suitable reference standard for the developing measurements made from M‑mode and 2D quantification
countries. A detailed search on the available pediatric echocardiograms as described by Lopez et al.[3] The
echocardiographic Z‑score studies from countries in views utilized and the methods employed for measuring
Asia and the Middle East (our search included India, the 2D echocardiographic parameters are shown in
Bangladesh, Nepal, Myanmar, Bhutan, Pakistan, China, Table 1. Two operators (one in the Ajmer center and
Singapore, Taiwan, North and South Korea, Hong Kong, the other in Mohali) were involved in the acquisition
Japan, and Saudi Arabia) revealed only two published of echocardiographic measurements. Since only
studies, both of which had focused on coronary thirty subjects were evaluated at the Mohali center,
artery diameter z scores.[1,2] Therefore, the primary a formal inter/intra‑observer variability analysis
objective of our study was to derive echocardiographic was not performed. The measurements acquired by
nomograms .for the commonly measured cardiac fellows in training were reassessed by the senior
structures in healthy Indian children (early childhood consultant (offline), and when found nonsatisfactory,
to adolescence). repeat evaluation was done subsequently. The
Table 1: Methods and views employed in two‑dimensional echocardiographic measurements
Measured parameter View Description
Ao An Parasternal long axis Inter hinge point distance during systole
SoV Parasternal long axis Maximum dimension in systole
STJ Parasternal long axis Maximum dimension in systole
Asc aorta Parasternal long axis Maximum dimension in systole as it crosses in front of the right pulmonary artery
MVA Apical four chamber Inter hinge point distance during diastole
TVA Apical four chamber Inter hinge point distance during diastole
LA minor axis diameter Apical four chamber Point to point distance at end‑systole
LA major axis length Apical four chamber Point to point distance at end‑systole
RA minor axis diameter Apical four chamber Point to point distance at end‑systole
RA major axis length Apical four chamber Point to point distance at end‑systole
RV basal diameter Apical four chamber Maximum dimension in diastole; point to point distance
RV mid cavity diameter Apical four chamber Maximum dimension in diastole; point to point distance
RV long axis length Apical four chamber Point to point distance
Ao An: Aortic valve annulus, SoV: Sinuses of Valsalva, STJ: Sino tubular junction, Asc aorta: Ascending aorta, MVA: Mitral valve annulus,
TVA: Tricuspid valve annulus, LA minor: Left atrial dimension along the minor axis, LA major: Left atrial dimension along the major axis, RA minor: Right
atrial dimension along the minor axis, RA major: Right atrial dimension along the major axis, RV basal: Right ventricular dimension at the basal level,
RV mid: Right ventricular dimension at the mid cavity level, RV long: Right ventricular dimension along the long axis
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
data obtained were expressed in relation to body Wilk and Kolmogorov–Smirnov tests were employed for
surface area (BSA) calculated by Haycock’s formula assessment of normality of residuals. The regression
(BSA = weight0.5378 × height0.3964 × 0.024265).[4] equation which had the highest R2 (goodness‑of‑fit) was
selected. Thus, for each measured parameter, we came
Calculation of sample size
up with one best regression equation out of the seven.
For sample size calculation, we followed the method used Z‑score charts for all the studied parameters were then
by Cantinotti et al.[5] The population of interest was divided derived [Figures 2-11]. The parameters, the best fit
age‑wise into four sections (section 1, 4–6 years; section model for each, and the respective R2 values are shown
2, 73 months ‑ 8 years; section 3, 97 months ‑ 10 years; in Table 2. The regression equations are provided in
and section 4, 121 months ‑ 15 years). The standard Table 3. The analysis was done using Stata version 14.1
deviation of the population was assumed as 0.5 and for Windows;Stata Statistical Software Release 14. College
distribution of the variables as normal.[6,7] A minimum of Station Tx:StataCorp, LP.
100 subjects per age section would be needed to reach
a 95% confidence interval at a margin of error of 0.1. To calculate the Z‑score for a subject using these
All the 21 measurements might not be available in the regression equations in Table 3, the user has to substitute
echocardiographic examination of every subject. Giving the subject’s BSA and the measurement for the concerned
allowance for this fact, a higher number of subjects were parameter and the other values as provided in the table.
deemed necessary in each study section. We assumed The other way is to directly plot the measurement in the
that at least 70% examinations would be complete, Z‑score charts provided and directly arrive at the Z‑score.
containing all the 21 measurements. This meant we Due to space constraints, the Z‑score charts are provided
needed a minimum of 140 subjects per section to reach only for ten parameters. The authors would be happy to
the 95% confidence interval. Thus, we arrived at the final provide interested users with the Z‑score charts for the
sample size of ≥560 subjects. other parameters on request.
Seven hundred and forty‑eight children were evaluated
Table 2: Parameters assessed, the regression
at Ajmer, Rajasthan, and thirty at Mohali, Punjab. After
equation which provided the best fit model and
excluding children who had CHD in the screening
corresponding R2 values for each
echocardiogram and incomplete examinations, the final
Category Parameter assessed Model with best fit R2
number of subjects included in the analysis was 720 from
M mode IVSd y=a+b√x 0.188
Ajmer and 26 from Mohali [Figure 1]. M mode LVIDd y=a+bx 0.355
M mode LVPWD y=a+bx 0.218
Statistical analysis M mode IVSs y=a+bx 0.316
M mode LVIDs y=a+bx 0.114
To assess the relationship of a parameter with the
M mode LVPWS y=a+bx 0.323
BSA, regression equations were used. We chose seven M mode AoR y=a+bxln (x) 0.346
different models of regression namely;- (1) linear: y M mode AoVCS √y=a+b√x 0.203
= a + bx, logarithmic: (2) y = a + b ln[x], (3) ln[y] = a 2D echo Ao An √y=a+bx 0.288
2D echo SoV y=a+bx 0.372
+ bx), exponential: (4) ln[y] = a + b ln[x]) and square 2D echo STJ √y=a+bx 0.32
root: (5) y = a + b√x, (6) √y = a + bx, (7) √y = a + b√x, 2D echo Asc aorta y=a+bxln (x) 0.35
which were applied to each measured parameter. As 2D echo MVA y=a+bx 0.36
2D echo TVA y=a+bx 0.346
one of the assumptions of regression analysis is that 2D echo LA minor y=a+bx 0.244
the residuals should be normally distributed, Shapiro– 2D echo LA major y=a+bx 0.177
2D echo RA minor y=a+bxln (x) 0.263
2D echo RA major y=a+bx 0.338
2D echo RV basal y=a+bx 0.366
2D echo RV mid y=a+bxln (x) 0.254
2D echo RV long y=a+bx 0.288
IVSd: Interventricular septal thickness in diastole, LVIDd: Left
ventricular cavity internal dimension in diastole, LVPWD: Left ventricular
posterior wall thickness in diastole, IVSs: Interventricular septal
thickness in systole, LVIDs: Left ventricular cavity internal dimension
in systole, LVPWS: Left ventricular posterior wall thickness in systole,
AoR: Aortic root, AoVCS: Aortic valve cusp separation, Ao An: Aortic
valve annulus, SoV: Sinuses of Valsalva, STJ: Sino tubular junction,
Asc aorta: Ascending aorta, MVA: Mitral valve annulus, TVA: Tricuspid
valve annulus, LA minor: Left atrial dimension along the minor axis,
LA major: Left atrial dimension along the major axis, RA minor: Right
atrial dimension along the minor axis, RA major: Right atrial dimension
along the major axis, RV basal: Right ventricular dimension at the
basal level, RV mid: Right ventricular dimension at the mid cavity
level, RV long: Right ventricular dimension along the long axis,
Figure 1: Screening and recruitment of children at the two centers 2D: Two‑dimensional
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
Table 3: Coefficients for regression equations for the measured echocardiographic parameters
Parameter assessed Intercept B SEE (√MSE) Kolmogorov–Smirnov Shapiro–Wilk
Parameters with best fit with y=a+bx Z=(measurement − [intercept + B × BSA])/√MSE
LVIDd 22.450 12.807 3.660 0.040 0.992
LVPWD 4.990 2.242 0.917 0.087 0.972
IVSs 6.685 4.301 1.445 0.074 0.983
LVIDs 14.763 6.561 3.759 0.040 0.988
LVPWS 6.583 4.234 0.362 0.077 0.981
SoV 12.492 8.404 2.398 0.060 0.977
MVA 13.540 9.250 2.690 2.690 0.992
TVA 15.319 9.087 3.250 0.036 0.973
LA minor 16.023 9.621 3.610 0.066 0.979
LA major 21.464 12.063 5.410 0.038 0.038
RA major 17.659 12.716 3.831 0.069 0.986
RV basal 16.822 11.355 3.440 0.065 0.968
RV long 29.944 20.981 7.810 0.033 0.980
y=a + b X ln (x) Z=(measurement – [intercept + B × ln BSA])/√MSE
RA minor 17.290 9.791 3.560 0.049 0.981
RV mid 14.376 9.188 3.600 0.044 0.970
Asc Aorta 9.576 6.329 1.896 0.076 0.982
AoR 12.799 8.176 2.450 0.051 0.993
√y=a+bx Z=(√measurement – [intercept + B × BSA])/√MSE
STJ 9.917 6.967 2.225 0.067 0.934
Ao An 8.470 5.690 2.010 0.064 0.904
y=a+b√x Z=(measurement – [intercept + B × √BSA])/√MSE
IVSd 5.187 2.237 0.972 0.077 0.987
√y=a+b√x Z=(√measurement – [intercept + B × √BSA])/√MSE
AoVCS 10.703 5.197 2.388 0.093 0.793
Normality test: Shapiro–Wilk and Kolmogorov–Smirnov. B: Coefficient, IVSd: Interventricular septal thickness in diastole, LVIDd: Left ventricular cavity
internal dimension in diastole, LVPWD: Left ventricular posterior wall thickness in diastole, IVSs: Interventricular septal thickness in systole, LVIDs: Left
ventricular cavity internal dimension in systole, LVPWS: Left ventricular posterior wall thickness in systole, AoR: Aortic root, AoVCS: Aortic valve cusp
separation, Ao An: Aortic valve annulus, SoV: Sinuses of Valsalva, STJ: Sino tubular junction, Asc aorta: Ascending aorta, MVA: Mitral valve annulus,
TVA: Tricuspid valve annulus, LA minor: Left atrial dimension along the minor axis, LA major: Left atrial dimension along the major axis, RA minor: Right
atrial dimension along the minor axis, RA major: Right atrial dimension along the major axis, RV basal: Right ventricular dimension at the basal
level, RV mid: Right ventricular dimension at the mid cavity level, RV long: Right ventricular dimension along the long axis, BSA: Body surface area,
MSE: Mean square error, SEE: Standard error of estimate
RESULTS Table 4: Distribution of the body surface area in
the study subjects
The study included 746 healthy children, age ranging from BSA (m2) n (%)
4 to 15 years. Seventy‑one percent were boys and 29% were 0.57–0.8 175 (24.1)
girls. The BSA ranged from 0.57 cm2 to 1.88 cm2, median of 0.81–1 235 (32.36)
1.01–1.2 188 (25.9)
0.95 cm2, and interquartile range (IQR) of 0.8–1.12 cm2. The
1.21–1.88 128 (17.6)
weight ranged from 11 kg to 77 kg, median of 25 kg, and
BSA: Body surface area
IQR of 20–33 kg. The height ranged from 95 cm to 180 cm,
median of 131 cm, and IQR of 119–143 cm. The distribution
West. All pediatric centers in India and other developing
of BSA in the study subjects is shown in Table 4.
countries have depended on these Western data till
date for Z‑score calculations for their young patients.
DISCUSSION Although there is no direct proof that growth parameters
The World Health Organization growth charts[8] based on and dimensions of the heart vary between Western and
Western data[9‑12] were found to grossly underestimate Indian children, reasons exist to believe they do.[13]
growth in Indian children.[13] The current day under‑5 Therefore, separate Z‑scores charts based on indigenous
growth charts[14] were designed after elaborate studies in studies are needed in developing countries. There have
developing countries. On the same lines, utilizing Western been multiple studies for calculating Z‑scores of various
Z‑score standards for deriving Z‑score values in Indian cardiac structures.[15] The most recent publications in this
children or children from any other developing country area[5,16‑20] reveal that none of the latest Z‑score research
might lead to erroneous judgments and faulty decisions. has come from any developing country.
Almost all published data on Z‑scores of various heart Almost all these studies [5,16‑20] have been done on
structures have been based on studies conducted in the hospital‑based samples. Hospital‑based samples have
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
Figure 2: Z‑score chart plot obtained by plotting the interventricular Figure 3: Z‑score chart plot obtained by plotting the left ventricular
septal thickness in diastole (in millimeters [mm]) against the body cavity internal dimension in diastole (in millimeters [mm]) against
surface area (m2) the body surface area (m2)
Figure 5: Z‑score chart plot obtained by plotting mitral valve
Figure 4: Z‑score chart plot obtained by plotting the left ventricular
annulus measurement (two‑dimensional echo) in millimeters [mm])
cavity internal dimension in systole (in millimeters [mm]) against
against the body surface area (m2)
the body surface area (m2)
Figure 7: Z‑score chart plot obtained by plotting the left atrial‑major
Figure 6: Z‑score chart plot obtained by plotting tricuspid valve axis dimension (two‑dimensional echo) in millimeters [mm])
annulus measurement (two‑dimensional echo) in millimeters [mm]) against the body surface area (m2)
against the body surface area (m2)
with children hailing from less privileged sections of
their inherent disadvantages including selection bias.
the society. Majority of children from this school were
We studied healthy school going children. To the best undernourished. We did not exclude children based
of our knowledge, ours is the first study on such a on malnutrition, obesity, or stunting. Malnutrition has
large sample of children from the community. One of an impact on cardiac growth. Studies uniformly agree
the schools included in our study was run by a private that left ventricular (LV) mass decreases in severe
organization with the majority of children from an affluent malnutrition.[21] LV posterior wall and interventricular
background. The second was also a private institution septal thickness have been found to fall below the
with children from less affluent families. The third school 5th centile in proportion to the decrease in body size in
was a non-governmental organization funded institution majority of children with established kwashiorkor.[22]
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
Figure 9: Z‑score chart plot obtained by plotting the aortic annulus
Figure 8: Z‑score chart plot obtained by plotting the right ventricular measurements (two‑dimensional echo) in millimeters [mm])
cavity dimension measurement at the basal level (two‑dimensional against the body surface area (m2)
echo) in millimeters [mm]) against the body surface area (m2)
Figure 11: Z‑score chart plot obtained by plotting aortic
Figure 10: Z‑score chart plot obtained by plotting aortic measurements at the sinotubular junction (two‑dimensional echo)
measurements at the sinuses of Valsalva (two‑dimensional echo) in millimeters [mm]) against the body surface area (m2)
in millimeters [mm]) against the body surface area (m2)
Table 5: Comparison of the present study’s
However, what happens in lesser degrees of malnutrition
measurements with previously published
is unclear. We hypothesize that cardiac wall thickness
Western nomograms for a child with a body
and dimensions are maintained till a critical level of
surface area of 1 m2 (selected parameters)
nutritional imbalance is reached. Including children
Cardiac Mean±2SD
with lesser degrees of malnutrition who had lower BSA structure Our study Cantinotti Pettersen
but preserved cardiac dimensions may have resulted (mm) et al. (mm)[5] et al. (mm)[23]
in the low R2 values in our study. We compared the RA minor 27.72 31.50
measurements of selected cardiac structures from our (19.18–33.71) (25.53–38.86)
study with existing nomograms [Table 5].[5,23] RA major 30.01 34.06
(18.90–37.92) (27.83–41.68)
As seen in Table 5, the majority of parameters had RV basal 28.72 31.34
values, which were uniformly lower in comparison to the (21.36–35.32) (25–39.29)
RV long 49.77 51.11
Western standards. This reinstates our emphasis on the
(36.11–63.11) (42.01–62.18)
need for an indigenously developed Z‑score nomogram LA minor 26.04 30.02
for use in developing countries. (18.52–32.72) (24.83–36.31)
LVIDd 35.02 39.09
Strength and limitations of the study (27.82–42.04) (32.06–48.79)
LVIDs 21.62 24.96
This study has attempted to derive Z‑scores for various 2D (14.36–27.6) (18.92–31.80)
Echo and M‑mode parameters in Indian children. The study RA minor: Right atrial dimension along the minor axis, RA major: Right
subjects have been chosen from school going children. This atrial dimension along the major axis, RV basal: Right ventricular
community‑based sampling adds to the strength of the dimension at the basal level, RV mid: Right ventricular dimension at the
mid cavity level, RV long: Right ventricular dimension along the long axis,
study. Children included in the study represent multiple LVIDd: Left ventricular cavity internal dimension in diastole, LVIDs: Left
socioeconomic strata in our society. While this increases ventricular cavity internal dimension in systole, SD: Standard deviation
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Gokhroo, et al.: Indian pediatric echocardiography study – The Z score
the external validity of our findings, the effects of varying
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