Echocardiographic chamber quantification in a healthy Dutch population
Neth Heart J
Echocardiographic chamber quantification in a healthy Dutch population
R. W. J. van Grootel 0 1 2
M. E. Menting 0 1 2
J. McGhie 0 1 2
J. W. Roos-Hesselink 0 1 2
A. E. van den Bosch 0 1 2
0 Department of Radiology, Erasmus MC , Rotterdam , The Netherlands
1 Department of Cardiology, Erasmus MC , Rotterdam , The Netherlands
2 R. W. J. van Grootel
Aim For accurate interpretation of echocardiographic measurements normative data are required, which are provided by guidelines. For this article, the hypothesis was that these cannot be extrapolated to the Dutch population, since in Dutch clinical practice often higher values are found, which may not be pathological but physiological. Therefore this study aimed to 1) obtain and propose normative values for cardiac chamber quantification in a healthy Dutch population and 2) determine influences of baseline characteristics on these measurements. Methods Prospectively recruited healthy subjects, aged 20-72 years (at least 28 subjects per age decade, equally distributed for gender) underwent physical examination and 2D and 3D echocardiography. Both ventricles and atria were assessed and volumes were calculated. Results 147 subjects were included (age 44 ± 14 years, 50% female). Overall, feasibility was good for both linear and volumetric measurements. Linear and volumetric parameters were consistently higher than current guidelines recommend, while functional parameters were in line with the guidelines. This was more so in the older population. 3D volumes were higher than 2D volumes. Gender dependency was seen in all body surface area (BSA) corrected volumes and with increasing age, ejection fractions decreased. Conclusion This study provides 2D and 3D echocardiographic reference ranges for both ventricles and atria derived from a healthy Dutch population. BSA indexed volumes are gender-dependent, age did not influence ventricular volumes and a rise in blood pressure was independently associated with increased right ventricular volumes. The higher volumes found may be indicative for the Dutch population being the tallest in the world.
Echocardiography; 3D; Normal values; Chamber quantification
Echocardiography is indispensable in clinical practice. It is
the most widely used non-invasive imaging tool to assess
and quantify cardiac structural and functional parameters,
mainly because of its versatility: it is widely available,
relatively cost-effective and mobile. To interpret the performed
measurements, solid normative data are essential. The
recently revised guideline for cardiac chamber quantification
provides guidance for echocardiographic assessment [
For some measurements, age- and gender-specific values
In the literature, there are four studies that show an
influence of gender and age on left ventricular (LV) and right
ventricular (RV) volumes [
]. However, besides age and
gender, there are implications that ethnicity also influences
cardiac size and function [
measurements performed in healthy Dutch people, the tallest
people worldwide , often supersede the upper limits of
normal (ULN) given by current guidelines though most
indices are corrected with body surface area (BSA). This
implies that BSA correction does not fully equalise
differences originating from height. Also, a study comparing
Caucasians with Asian Indians showed smaller 3D LV
volumes in Asians but with a comparable ejection fraction
(EF). However, ethnic-specific normal values for the Dutch
population are not yet available.
Therefore, this study aims to provide 1) age-specific
reference values for echocardiographic chamber
measurements specifically in a Dutch population and 2) identify the
influence of age, gender, body mass index (BMI), BSA and
blood pressure on the echocardiographic measurements.
Healthy volunteers, aged 20–72 years, were enrolled in
2014–2015 for this prospective cross-sectional study and
were stratified into five groups: 20–29, 30–39, 40–49,
50–59 and 60–72 years (each 50% female). Details have
been published earlier [
]. Healthy subjects were examined
at the cardiology outpatient clinic of the Erasmus Medical
Centre, Rotterdam. Exclusion criteria were: (prior)
cardiovascular disease, systemic disease, or cardiac medication,
the finding of cardiac abnormalities during examination or
cardiovascular risk factors consisting of hypertension
(systolic and diastolic blood pressure >140/80 mm Hg), diabetes
mellitus and hypercholesterolaemia. Professional athletes,
morbidly obese subjects (BMI >40 kg/m2), pregnant women
and women with breast implants were excluded. This study
was carried out according to the principles of the
Declaration of Helsinki and approved by the local ethics committee.
Written informed consent was obtained from all patients.
The study consisted of a questionnaire on medical history
and health status, physical examination, venous blood
sampling, 12-lead electrocardiogram and an echocardiogram.
Echocardiographic image acquisition
Echocardiographic studies were carried out by one of two
experienced sonographers. Two-dimensional greyscale
harmonic images were obtained in the left lateral decubitus
position using an i33 or EPIQ7 ultrasound system (Philips
Medical Systems, Best, the Netherlands) equipped with
a transthoracic broadband X5-1 matrix transducer
(composed of 3,040 elements with 1–5 MHz). Dedicated views
were taken for assessment of both atria and ventricles. The
studies were stored in Digital Imaging and Communications
in Medicine (DICOM) format.
The current recommendations for chamber quantification
were used [
]. LV end-diastolic and -systolic diameters
were measured in the parasternal short axis view, together
with their respective volumes using the apical four- and
two-chamber views. Volumes were measured using the
method-of-disk summation technique.
The left atrial (LA) area was measured in dedicated atrial
four- and two-chamber views to avoid foreshortening.
Biplane volumes were measured using the method-of-disk
For the right ventricle, end-diastolic and -systolic areas
(EDA and ESA) were measured in order to calculate the
fractional area change:
e nd d i ast ol i car ea − e ndsyst ol i car ea
e nd d i ast ol i car ea
End-diastolic basal- and mid-cavity diameters were
measured in the modified apical four-chamber view. The
proximal and distal outflow tract diameters were measured in
the parasternal short-axis view (Fig. 1). Tricuspid annular
plane systolic excursion (TAPSE) was measured.
For the right atrium, the single plane volume was
measured in the apical four-chamber view using the
method-ofdisk summation technique and the area length method.
LV volumetric measurements were performed with TomTec
4D LV function suite (4D LV Analysis; TomTec Imaging
Systems, Unterschleissheim, Germany) using a
semi-automated endocardial border trace, after the apex and the
middle of the mitral valve annulus are determined by the
operator. The end systolic and diastolic frame are automatically
detected in order to start contour detection. Corrections to
the endocardial trace were manually applied by the
operator if needed. For the right ventricle, a similar routine was
used (TomTec 4D RV function; TomTec Imaging Systems,
Normal distribution was checked using Shapiro-Wilks tests
and histograms. Depending on data distribution,
continuous data are presented as mean ± standard deviation (SD)
or median with first-third quartile (Q1-Q3). Categorical
data are presented as frequencies and percentages. Student’s
t-test, the Mann-Whitney-U test, χ2-test or Fisher’s exact
test was used when appropriate. Correlations were
n = 73
EDV end-diastolic volume, EF ejection fraction, EDD end-diastolic diameter, ESD end-systolic diameter, EDA end-diastolic area,
ESA end-systolic area, FAC fractional area change, RVOT right ventricular outflow tract, PLAX parasternal long-axis, SAX short-axis,
TAPSE tricuspid annular plane systolic excursion
sured using the Pearson correlation test. For correlations
between echocardiographic parameters and age, linear
regression analysis was applied. Variables that reached
significance and did not show collinearity with other variables
were included in a multivariable model. When collinearity
did occur, the variable with the highest correlation
coefficient was included. A p 0.05 was considered statistically
significant. Statistical analysis was done using the
Statistical Package for Social Science version 21 (IBM DPDD
Statistics for Windows, Armonk, New York, USA).
Of the 155 subjects eligible, 147 were included (mean age
44.6 ± 13.7 years, 50% female) (Fig. 2). Tab. 1 shows
the characteristics of the study population. LV volume and
function assessment with 3D echocardiography was
feasible in 121 (82.3%) volunteers; RV volume and function
assessment with 3D echocardiography was feasible in 97
(66.0%) volunteers. Height, weight, BMI, BSA and
tolic and diastolic blood pressure were significantly lower
Echocardiographic chamber measurements in relation
Echocardiographic chamber measurements in relation
Tab. 2 presents an overview of echocardiographic
parameters per age decade. For 3D derived volumes, the averages
for the left ventricle were: end-diastolic volume (EDV) 78 ±
12 ml/m2 and end-systolic volume (ESV) 34 ± 6 ml/m2. For
the right ventricle, values were 58 ± 12 ml/m2 and 24 ±
6 ml/m2. LV and RV volumes were not age-dependent; this
was true for both 2D and 3D echocardiography. Age was
inversely correlated with LVEF (57 ± 4 ml/m2 in the youngest
group and 55 ± 3 ml.m2 in the oldest group (r: –0.229, p:
0.012)). RVEF was 58 ± 4 ml/m2 and was not correlated
with age. Importantly, volumetric measurements acquired
with 2D echocardiography all exceeded the ULN as
recommended in the guideline. This was also true for 3D LV
volumes, but not for the 3D RV volumes.
Tab. 3 shows echocardiographic chamber measurements per
gender. Fig. 3 shows 2D measurements for both ventricles
(error bars at 2SD), with bars depicting the ULN (solid
line) or lower limit (dotted line) of normal according to
the guidelines [
]. Most of the measured variables showed
gender-dependency. 2D and 3D LV and RV dimensions
and volumes were gender-dependent. 2D and 3D EF was
also gender-dependent with the exception of 3D RVEF.
After BSA indexation, males had higher ventricular volumes.
BSA indexation of LA volume negated gender differences,
but BSA indexed right atrial (RA) volumes remained bigger
in men than women. On average, LA maximum volume was
28.8 ± 7.2 ml/m2, with 25% of the study population having
LA dilatation (>34 ml/m2) according to the guideline. In
this study, the ULN was 43.2 ml/m2.
Fig. 4 shows age- and gender-specific volumes for both
the LV and RV 3D data and the ULN according to the
guideline are again depicted. EF for both ventricles was
significantly correlated with age, EDV and ESV did not
RV longitudinal diameter
Male LV 3D volumes
Male RV 3D volumes
BSA correlated strongest with echocardiographic
parameters compared with height, weight or BMI. Ventricular
volumes were not correlated with age, and LVEF and RVEF
showed a decrease with age. RV volumes showed a linear
increase with higher blood pressure and heart rate, also after
correcting for heart rate, QRS duration and gender.
Agreement between 2D and 3D for the LV measurements
was moderate: LV EDV: r: 0.643, p < 0.001, and LV ESV
r: 0.583, p < 0.001, respectively. For the RV correlations
between 2D volumes and 3D areas were weak: 3D EDV
vs 2D EDA r: 0.295, p: 0.004 and ESV r: 0.295, p: 0.005
This prospective study presents normative data for
echocardiographic chamber quantification, age- and
gender-specific, in a healthy Dutch population. Overall, linear and
volumetric parameters exceeded the ULN as stated in the
guideline, while functional parameters agreed with them.
BSA remains the best variable for indexation.
Feasibility of LV measurements in this study is in line with
previous studies [
4, 10, 11
]. Feasibility is important when
a technique is considered for clinical use and the
percentages in this study are good, especially since subjects with
a poor acoustic window were not excluded. The need for
implementation of 3D echocardiography for LV volume and
EF in clinical use is high. The lower feasibility for the right
ventricle was expected given its location in the thorax right
behind the sternum. Higher percentages have been reported
in the literature but poor acoustic windows were an
exclusion criterion whereas this was not the case for this study
Differences with guidelines
Comparing the results from this study to the ULN as stated
in the guideline[
], we found some discrepancies. For most
of the parameters, ULN of this study exceeded those of the
guideline. This was true for linear and volumetric
measurements, regardless of which ventricle or atrium the parameter
belonged to: both were larger, this is especially outspoken
in the elderly. For instance, when looking at 2D LV
volumes: the older the group, the larger the difference. The
higher linear and volumetric parameters found may be
indicative to the Dutch people being the tallest people in the
world, which stresses the importance of specific normative
echocardiographic data for the Dutch population.
Comparing our data with results from the NORRE trial, a European
multicentre study pertaining to primarily white individuals,
we found that our volumes and dimensions were generally
]. Mean BSA in their study was 1.8 ± 0.2 vs our
1.89 ± 0.19 m2. This was due to both a higher weight (65 ±
12 vs 75 ± 13 kg) and height (169.8 ± 9.6 vs 175 ± 9 cm),
meaning that these higher values are not due to leaner
Given that the Dutch population is the tallest worldwide
], the question arose whether BSA was the best
parameter for indexation. Univariate analysis in this study showed
that BSA correlated strongest when compared with height,
weight or BMI; it was indeed the best candidate for
indexation. Most parameters exceeded the guideline, with one
exception: 3D derived volumes of the right ventricle were
in line with the guideline and current literature [
Functional parameters concerning LV and RV systolic function
(EF, RV FAC and TAPSE) agreed with the proposed
values in the guideline, meaning that the current guideline is
applicable for the Dutch population.
Multiple studies reported on the negative relation
between age and echocardiographic LV volumes[
10, 11, 13
which is similar to what is seen in CMR studies [
In this study, LV volumes did not decrease with age while
LVEF did. For the RV, there was no positive linear
correlation in RVEF as is reported by Maffessanti et al. (r 0.240,
p < 0.01)  , but a negative correlation. This probably
reached significance because of the lower mean RVEF in the
oldest group. Between the age groups 20–29 to 50–59 years,
values remain practically the same. Indeed, the
correlation between age and RVEF became stronger when the
study population was divided into groups 55 years and
>55 years. Maffessanti et al. reported similar values, but
in their cohort the oldest group (age >70 years) reported
higher values for RVEF. Perhaps RVEF does not increase
until old age (>70 years), which might explain why our
results are different. Clearly, the influence of age needs
Correlations with blood pressure
Hypertension was a reason for exclusion, but it is worth
mentioning that some volunteers had a higher blood
pressure but when checked again by a general practitioner were
found to be normal. These volunteers were not excluded.
Analysis showed that higher blood pressure led to higher
RV volumes. This could imply that sufficient blood pressure
regulation could influence the right ventricle.
The reference values in this study could lead to some
changes in clinical decision-making. Though most
guidelines use functional parameters, there are situations where
volumes or linear dimensions are being used. For instance,
when diagnosing LV diastolic dysfunction, LA dilatation
plays an important role [
]. With that in mind, in patients
suspected of heart failure with mid-range EF, LA
enlargement is used to substantiate the diagnosis [
]. An enlarged
left atrium is also a strong prognosticator in, for instance,
in the recurrence of atrial fibrillation after surgery [
RV size is of particular importance for patients with adult
congenital heart disease. In patients with an atrial septal
defect, if the right ventricle is enlarged intervention is
warranted; this is also true for patients with ventricular septal
The impact is smaller regarding valvular disease; LV
linear dimensions are still used as opposed to volumes [
and values of LV linear dimensions in this study did agree
Considering the size and Dutch ethnicity of the study
population, conclusions drawn should be interpreted with
This study presents age- and gender-specific normative data
specifically for the native Dutch population, and reveals
that linear and volumetric parameters exceed the ULN
while functional parameters agree with the guideline. The
higher linear and volumetric parameters found may be
indicative to native Dutch people being the tallest people
worldwide. The authors suggest specific normative values
for echocardiographic assessment in the Dutch population.
Funding This study was supported by a grant from the Thorax
Conflict of interest R.W.J. van Grootel, M.E. Menting, J. McGhie,
J.W. Roos-Hesselink, and A.E. van den Bosch declare that they have
no competing interests.
Open Access This article is distributed under the terms of the
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creativecommons.org/licenses/by/4.0/), which permits unrestricted
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appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
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