Download Discrepancies between echocardiographic measurements of left

Clinical Science (1999) 97, 377–383 (Printed in Great Britain)
Discrepancies between echocardiographic
measurements of left ventricular mass in a
healthy adult population
Jenny A. DEAGUE*†, Catherine M. WILSON†, Leeanne E. GRIGG†
and Stephen B. HARRAP*
*Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia, and †Department of Cardiology, The
Royal Melbourne Hospital, Parkville, Victoria 3052, Australia
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Increased left ventricular (LV) mass is associated with increased cardiovascular morbidity and
mortality. LV mass is commonly estimated from echocardiography according to the Penn or ASE
(American Society of Echocardiography) conventions. No formal statistical test of agreement
between these methods has been published. Therefore we compared M-mode echocardiographic
LV mass estimates by the Penn and ASE methods in a normal adult population. M-mode
echocardiographic tracings were obtained in 169 healthy volunteers and used to calculate LV
mass using the Penn and ASE methods. Median values of the estimates were similar [Penn, 126 g
(interquartile range 96–170 g) ; ASE, 129 g (105–164 g) ; P l 0.08] and were highly intercorrelated
(r l 0.98, P 0.0001). However, the Bland–Altman analysis of agreement revealed significant
inconsistencies between Penn and ASE LV mass values. The difference between Penn and ASE
values was correlated significantly with heart size (P 0.0001), such that, for small hearts, the
Penn LV mass was lower than the ASE LV mass ; in contrast, for large hearts, Penn estimates were
greater than ASE values. In the upper 5 % of the LV mass distribution, the median value for the
Penn LV mass index was 132.4 g/m2, compared with 116.5 g/m2 for ASE values (2P l 0.017). Thus
the two most common methods of echocardiographic estimation of LV mass differ significantly
at the upper and lower ends of the heart size distribution. These results have important
implications for both cardiac research and clinical evaluation.
INTRODUCTION
Left ventricular (LV) hypertrophy is the single most
important cardiovascular risk factor [1–7] after age. This
is explained in part by the association of LV hypertrophy
with high blood pressure, ischaemic heart disease and
obesity. However, LV hypertrophy also appears to exert
an independent contribution to cardiovascular risk. The
association between LV mass and cardiovascular morbidity and mortality shows no threshold, being evident
across the full range of heart sizes [7]. Furthermore,
regression of LV hypertrophy as a result of antihypertensive medication has been associated with a
reduction in cardiovascular events [8–10]. Estimation of
LV mass in epidemiological studies, the diagnostic
classification of LV hypertrophy and studies of the
effects of therapeutic intervention depend on reliable and
comparable measurement techniques.
The measurement of LV dimensions in research and
clinical practice is most commonly carried out using Mmode echocardiography, which is widely available, noninvasive and free of radiation. M-mode methods are used
to record echocardiographic images of LV dimensions at
the mitral–chordal junction. Three principal dimensions
are measured : the LV internal diameter (LVID), the
interventricular septum (IVS) and the posterior wall
Key words : echocardiography, hypertrophy, left ventricle, M-mode, population.
Abbreviations : ASE, American Society of Echocardiography ; IQR, interquartile range ; IVS, interventricular septum ; LV, left
venticular ; LVID, LV internal diameter ; PW, posterior wall.
Correspondence : Professor Stephen B. Harrap.
# 1999 The Biochemical Society and the Medical Research Society
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(PW). Two measurement protocols are in common use.
The American Society of Echocardiography (ASE) recommends that dimensions are measured from the
leading edge to the leading edge of echocardiographic
borders. This results in the inclusion of endocardial
echoes from the IVS and PW, and the exclusion of
endocardial echoes from the LVID. Subsequently, the
Penn convention proposed measurements that exclude
endocardial echoes from IVS and PW dimensions, but
include endocardial echoes in measurement of the LVID.
Therefore, for any given recording, the Penn convention
gives larger cavity dimensions and smaller wall thicknesses than the ASE convention.
Measurements of LVID, PW and IVS are used in
formulae to estimate LV mass [11–17]. These formulae
are based on the assumption that the left ventricle
approximates a prolate ellipse. LV linear dimensions are
cubed to provide volume terms. However, the way in
which Cubic terms are derived and handled vary according to different formulae. Three basic formulae have
been described, two of which use measurements made
according to the ASE convention and one which uses
measurements according to the Penn convention. An
early Cubic formula based on geometric predictions and
using measurements made according to the ASE convention was described by Rackley et al. [16] :
1.0996o[(2LVIDjIVSjPW)
i0.5(IVSjLVIDjPW)#]k(LVID)$q.
Subsequently, the arithmetic nature of the formula was
simplified, and this version was recommended by the
ASE :
1.04[(IVSjLVIDjPW)$k(LVID)$].
Later, using the Penn convention to measure dimensions,
Devereux and co-workers [11,12] derived the Penn
formula :
1.04[(IVSjLVIDjPW)$k(LVID)$]k13.6,
by regression analysis using post-mortem LV weights. A
further regression analysis against autopsy specimens
[12] found that the original ASE formula overestimated
autopsy LV weight, and a mathematical modification was
suggested :
0.832[(IVSjLVIDjPW)$k(LVID)$]j0.6.
This modified ASE formula and the Penn formula are
both in common use to assess LV mass by M-mode
echocardiography.
Throughout this development, the agreement between
different methods has been assessed simply by linear
regression analysis and correlation coefficients. Close
linear correlation has led to general acceptance that the
Penn and ASE methods are more or less equivalent and
can be used interchangeably [18–20]. However, such
correlation analyses may obscure important differences
# 1999 The Biochemical Society and the Medical Research Society
between the estimates [21]. For this reason, Bland and
Altman [21] recommended a method in which the
differences between two measurements are compared
with their average values. Such analyses provide information about agreement between methods that is not
available from simple correlational analyses.
The aim of the present study was to compare the
estimates of LV mass derived according to the Penn, the
ASE and the original Cubic formulae over a broad
physiological range in a sample of the normal adult
population.
METHODS
Subjects
Subjects were drawn from the Victorian Family Heart
Study, which is a population-based study of the familial
patterns of cardiovascular risk factors. The total sample
comprises 3000 volunteers from 828 families. Each family
is composed of a minimum of a mother and father and
one natural child. At the time of original recruitment,
parents were aged between 40 and 70 years and offspring
were between 18 and 30 years of age. We invited a
random selection of families from the Victorian Family
Heart Study to participate in this study of echocardiography and LV mass. Altogether, 180 volunteers
agreed to participate in the study, and informed consent
was obtained from all participants. These experiments
were approved by the Ethics Committee of the Royal
Melbourne Hospital.
Echocardiography
The M-mode echocardiographic study of the left ventricle was performed under cross-sectional control with a
Hewlett-Packard 2500 or 1000 Echocardiography machine. Both Penn and ASE measurements of the LV
dimensions were taken from M-mode strip chart recordings. The mean value of at least three measurements
was determined for each LV dimension.
LV mass was determined using three formulae : (a) the
Penn formula o1.04[(IVSjLVIDjPW)$k(LVID)$]k
13.6q, using Penn convention measurements, (b) the ASE
formula o0.832[(IVSjLVIDjPW)$k(LVID)$]j0.6q,
using ASE convention measurements, and (c) the
original Cubic formula (1.0996o[(2LVIDjIVSjPW)i
0.5(IVSjLVIDjPW)#]k(LVID)$q), using ASE convention measurements. A combined estimate of LV mass
was calculated as the mean of the three individual
estimates of LV mass.
M-mode recordings and linear-dimension measurements were made by two of us (J. A. D. and C. M. W.).
Measurements of the intra- and inter-observer errors (average difference divided by the average of the measurements), based on ten subjects, were 0.15 % and 1.3 %
respectively for ASE measurements and 0.5 % and 2.5 %
Echo measurements of left ventricular mass
respectively for Penn measurements. Eleven of the 180
subjects were excluded because of technical difficulties
with M-mode echocardiographic measurements. Data
from the remaining 169 individuals were included and are
presented in these analyses.
Table 2 Univariate correlation matrix between estimates of
LV mass by the three different methods
These analyses were based on regression analyses using logarithmically transformed
values ; * P 0.0001.
Correlation coefficient
Statistical analyses
Summary data are expressed as the median and interquartile range (IQR), unless specified otherwise. For
entry in parametric analyses, logarithmic transformation
of LV mass values was used to normalize data distributions. Comparisons between groups were made
using non-parametric and parametric analysis of variance.
The linear association between variables was assessed
using non-parametric and parametric regression analyses.
The method of Bland and Altman [21] was used to
assess agreement between different methods of LV mass
estimation. Statistical significance was accepted when
P 0.05.
RESULTS
The basic characteristics of the 169 participants are shown
in Table 1. The combined estimates of LV masses showed
a unimodal distribution, with a skew to the upper values
(Figure 1), as reported previously in normal adult
populations [2,7]. The Penn, ASE and Cubic LV mass
Table 1
Basic characteristics of subjects
Descriptive statistics are given as median (IQR).
n
Females
Age (years)
Weight (kg)
Height (cm)
Body surface area
(kg/m2)
Parents
Offspring
96
52
57 (53–60)
75.5 (66–87)
167.5 (161–174.5)
1.87 (1.72–1.98)
73
41
29 (23–32)
69.5 (59.5–80)
169 (163–177.5)
1.77 (1.63–1.99)
Figure 1 Frequency histogram of combined LV mass (g) for
the subjects in this study
See the text for a definition of combined LV mass.
Penn
ASE
Cubic
Table 3
Penn
ASE
Cubic
1.000
–
–
0.980*
1.000
–
0.988*
0.999*
1.000
Pairwise differences between estimates of LV mass
The values represent the medians of the differences between estimates of LV mass
(column minus row). The values in parentheses represent the IQRs for these
differences.
Correlation coefficient
Penn
ASE
Cubic
Penn
ASE
Cubic
0
–
–
1.9 (12.3)
0
–
6.4 (10.9)
4.2 (2.2)
0
estimations were normalized by logarithmic transformation (results not shown).
Calculation of LV mass by each of the three formulae
resulted in median values that were reasonably close :
Penn, 126 g (IQR 96–170 g) ; ASE, 129 g (IQR
105–164 g) ; Cubic, 134 g (IQR 108–169 g). The nonparametric Friedman analysis of variance for related
samples suggested that these differences were significant
(χ# l 141.1, P 0.0001). The Wilcoxon rank test showed
a significant difference between Cubic values and both
ASE and Penn values. However, the difference between
ASE and Penn values was not significant statistically
(P l 0.08). Nevertheless, a strong linear correlation was
demonstrated between the three calculated estimates
of LV mass, as shown by the matrix with univariate
correlation coefficients in Table 2.
Despite the high degree of correlation, the differences
between individual estimates using the different formulae
varied widely (Table 3). These comparisons showed that
the median of differences between LV mass estimated by
the Penn and ASE methods was small (1.9 g). However,
individual estimates of LV mass by the Penn method
ranged from 54.2 g greater than to 29.0 g less than the
corresponding ASE estimates.
The magnitude and direction of these differences
between LV mass estimates calculated using the different
formulae appear to depend on the size of the heart. This
was demonstrable on the Bland–Altman plots. For each
subject, we plotted the individual combined LV mass
against differences in LV mass derived using the two LV
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Figure 2 Bland–Altman plots of the differences in LV mass
estimates as a function of combined LV mass
Differences in LV mass are shown as measured by the Penn and ASE methods (top
panel), the ASE and Cubic methods (middle panel) and the Penn and Cubic methods
(bottom panel).
mass formulae. Figure 2 (top panel) shows the differences
between the Penn and ASE estimates of LV mass. This
plot reveals a significant positive correlation (P
0.0001). Therefore, for smaller LV mass, Penn estimates
were lower than ASE estimates, whereas for larger LV
mass, Penn estimates were greater than ASE estimates
(Figure 2, upper panel). When we examined subjects in
the upper 5 % of the distribution for combined LV mass,
we found that the median LV mass estimate by the ASE
method was 241.5 g, compared with 268.1 g calculated by
the Penn method. This difference was statistically sig# 1999 The Biochemical Society and the Medical Research Society
nificant (Wilcoxon rank test ; 2P l 0.017). The same
conclusions were true when the data were expressed as
LV mass index, the values of which were 116.5 g\m# for
ASE estimates and 132.4 g\m# for Penn measurements
(2P l 0.017).
When compared with LV mass derived by the Cubic
formula, the Penn and ASE estimates showed distinctly
different relationships. Figure 2 (middle panel) shows
that the differences between Cubic and ASE estimates
were small, and were distributed evenly across the range
of combined LV size. In contrast, Figure 2 (bottom
panel) shows that the differences between Cubic and
Penn estimates varied substantially, and depended on LV
size. Penn estimates were less than Cubic estimates for
small hearts, and greater than Cubic estimates for large
hearts.
Two factors vary between these formulae : the arithmetic construction and the techniques for measuring
dimensions. The similarity between the Cubic and ASE
estimates, despite different mathematical constructions,
may reflect an overriding importance of using the same
dimensional measurements.
To understand further the differences between LV
mass estimates derived by the ASE and Penn methods,
we examined the effect of standardizing dimensional
measurements by entering into the Penn formula values
for LVID, PW and IVS measured according to the ASE
convention. This gave estimates of LV mass we refer to as
PennASE. By comparing Penn and PennASE values, we
studied the effects of different dimensional measurements
in the same arithmetic formula. In this instance the
median difference was large (20.1 g), with a wide IQR
(63.4 g to k9.5 g). The Bland–Altman plot (Figure 3,
upper panel) showed that the differences were significantly, but not closely, related to LV size, such that
the difference between Penn and PennASE became larger
as heart size increased.
The comparison of PennASE with ASE estimates
examined the effect of entering the same dimensional
measurements in two different arithmetic formulae. By
inspection of the mathematical construction of the Penn
and ASE formulae, it is clear that when LVID, IVS and
PW are the same (as they are in ASE and PennASE), the
formulae reduce to linear equations that differ only by
slope (1.04 for Penn ; 0.832 for ASE) and intercept (k13.6
for Penn ; 0.6 for ASE). Therefore the magnitude and
variation of differences between PennASE and ASE
estimates are dependent on simple mathematical considerations. As expected, the differences between these
estimates were highly correlated over the range of LV
mass (Figure 3, lower panel).
The discrepancy between the Penn and ASE estimates
is likely to be explained by the differences in both
arithmetic structure and dimensional measurements. The
greater slope of the Penn formula produces values of LV
mass greater than those obtained with the ASE formula,
Echo measurements of left ventricular mass
lines of different slopes with a common point at approximately the mid-population value.
DISCUSSION
Figure 3 Bland–Altman plots of the differences in LV mass
estimates measured by the Penn and PennASE methods (upper
panel) and the ASE and PennASE methods (lower panel), as a
function of combined LV mass
Figure 4 Scatter diagram of individual values of LV mass
estimated by the Penn ($) and ASE () methods plotted
against combined LV mass
and these differences increase with heart size (see Figure
3, lower panel). In addition, the use of Penn convention
measurements results in smaller LV mass estimates than
when using ASE convention measurements (see Figure 3,
upper panel). The combined result of these effects is
depicted in Figure 4, which shows the plots of Penn and
ASE estimates of LV mass against combined LV mass, i.e.
Echocardiographic measurement of LV mass is an important clinical and research technique. M-mode echocardiography is widely available, non-invasive and free of
radiation. In comparison with magnetic resonance
imaging (MRI), two-dimensional echocardiography and
three-dimensional echocardiography, both the Penn and
corrected ASE formulae have been anatomically validated
using autopsy weight as a ‘ gold standard ’ [11,12]. In
addition, both methods have demonstrated acceptable
intra-observer and inter-observer variability [22]. Internationally, the ASE and Penn methods are both in
common use, and there is no consensus on their relative
merits or advantages. The choice in a particular laboratory is often arbitrary.
It has been assumed that, because the average values of
LV mass obtained by the Penn and ASE methods are
similar and because individual values are highly intercorrelated, there is little difference between the estimates
of LV mass obtained using the two methods. Some
studies have incorporated both Penn and ASE data
[18,19] and have used them interchangably [18]. Indeed,
we were able to confirm high degrees of linear correlation
between Penn and ASE estimates of LV mass. However,
we found that this obscured substantial differences
between estimates at the lower and upper ends of the
population distribution of LV mass. For small hearts,
Penn estimates were less than ASE estimates, while for
large hearts Penn estimates were greater than ASE
estimates.
Our findings are relevant, therefore, to LV hypertrophy. Although definitions vary, LV hypertrophy is often
categorized as the upper 5 % of the distribution of LV
mass. When we examined this group, we found a
significant difference of 27 g (approx. 10 %) in the
estimates of LV mass by the Penn and ASE methods, and
a significant difference of 16 g\m# (approx. 13 %) in
values of LV mass index obtained using the two methods.
Vasan et al. [7], in an analysis of the Framingham data,
showed that even within the upper 5 % of LV mass there
is a correlation between cardiovascular risk and increasing LV mass. Therefore, as cardiovascular risk
increases, so does the discrepancy between Penn and ASE
estimates of LV mass.
These differences have important implications for the
comparison of studies of LV hypertrophy that are based
on different LV mass measurement criteria. Definition of
a threshold value for LV hypertrophy is arbitrary, since
LV mass is a continuous variable. There is no clear
consensus concerning LV hypertrophy cut-offs, and
various proposals have been based on the meanj2S.D. of
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the population distribution for LV mass index [2,7,18].
Data from the Framingham Study using the Penn criteria
defined LV hypertrophy as an LV mass index of greater
than 131 g\m# for men and 100 g\m# for women [23].
In the ASE technique used by De Simone and coworkers [19,20], LV hypertrophy was defined as an LV
mass index of greater than 117 g\m# for men and
104 g\m# for women. The discrepancies in LV mass
thresholds have been accepted largely without critical
evaluation. Our findings suggest that part of this difference, particularly in males, is due to the divergence of
estimates of LV mass at the upper end of the spectrum,
rather than fundamental differences in the populations
that were used to define these diagnostic thresholds.
Unless diagnostic criteria are clearly defined in relation
to a particular method of estimating LV mass, there is
considerable potential for mis-labelling in relation to LV
hypertrophy. Individual or group data derived by one
method of estimating LV mass cannot be applied directly
to studies in which other methods are used. This is
relevant to LV hypertrophy diagnosis and therapy in
relation to hypertension, valvular heart disease, ischaemic
heart disease and obesity. However, our findings have
equal importance at the other end of the population
spectrum, and epidemiological comparisons should also
take into account the methods used to estimate LV mass.
Our findings raise further questions : how are these
differences explained, and is one method more accurate
than the other ? Our data provide no information on the
accuracy of the various methods. However, our study
offers some insight into an explanation for the discrepancy between estimates of LV mass by echocardiography. It has been suggested [15] that the simplification of the original Cubic formula was incorrect.
However, we found that the values of LV mass derived
by the Cubic and ASE formulae were very close across
the range, despite differences in the mathematical structure of the two formulae. As both the Cubic and ASE
formulae use the same measurements of cavity and wall
dimensions, this observation suggests that physical dimensions, rather than arithmetic, are important. This view is
supported by our observation that when different dimensional measurements were incorporated into the
same arithmetic formula, larger discrepancies arose, as we
observed in the Penn–PennASE comparison. The justification for particular M-mode echocardiographic
methods has been based on linear correlations with LV
weight measured at autopsy. To our knowledge, no
Bland–Altman test of agreement between Penn or ASE
estimates and the anatomical LV mass has been published.
It seems that the differences between the Penn and
ASE conventions have arisen as a result of empirical
attempts to derive equations based on arbitrary measurement techniques that provide good correlation coefficients when compared with anatomical assessment of
LV mass. The problem is that simple correlation is an
# 1999 The Biochemical Society and the Medical Research Society
imperfect assessment of agreement. The discrepancy
between Penn and ASE estimates at low and high values
of LV mass has obvious implications for clinical and
research cardiology. It also seems necessary to use the
Bland–Altman method to test agreement between all
indirect methods of assessing LV mass and anatomical
measurements. Until such data become available, it would
seem sensible for individual echocardiography laboratories to use either the Penn or the ASE method and to
determine the distribution of LV mass in a representative
sample of their own population in order to determine
relevant definitions of clinically important diagnoses,
such as LV hypertrophy. In addition, multicentre studies
need to standardize their use of formula, so as to avoid
bias and confounding of analyses of LV mass.
ACKNOWLEDGMENTS
This work was supported by the Victorian Health
Promotion Foundation and the National Health and
Medical Research Council of Australia. We thank Ms.
Margaret Stebbing, Dr. John Hopper (Australian
NHRMC Twin Registry), Dr. Graham Giles (Collaborative Cohort Study, Health 2000), and the general
practitioners and research nurses for their contributions
to subject recruitment.
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Received 19 February 1999/4 May 1999; accepted 27 May 1999
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