European Journal of Echocardiography Advance Access originally published online on September 30, 2008
European Journal of Echocardiography 2009 10(1):44-45; doi:10.1093/ejechocard/jen242
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.
Normalization of echocardiographically derived paediatric cardiac dimensions to body surface area: time for a standardized approach
Juan Pablo Kaski and
Piers E.F. Daubeney*
Consultant Paediatric and Fetal Cardiologist, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
accepted after revision 1 June 2008; online publish-ahead-of-print 30 September 2008.
* Corresponding author. National Heart and Lung Institute, Imperial College, London. Tel: +44 20 7351 8430; fax: +44 20 7351 8547. Email address: p.daubeney{at}rbht.nhs.uk
The quantification of cardiac dimensions derived from echocardiography is important in paediatric cardiac practice. Evaluation of the size and growth of cardiac chambers, valves, and great vessels plays a key role in the management of congenital heart disease, from the initial decision-making in the neonatal period to the nature and timing of subsequent interventions. It may also be important in the assessment and risk stratification of children with ‘acquired’ heart disease such as hypertrophic cardiomyopathy or coronary artery involvement in Kawasaki disease. Body size and cardiac dimensions change dramatically during normal growth and development. Therefore, it is necessary to place in context the measured size of a given cardiac structure by correcting for body size, through the process of normalization. The paper by Neilan et al.1 in this issue of the Journal is a timely addition to the literature on normalization in paediatric populations, and raises a number of important issues.
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Requirements for normalization
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Various algebraic formulae to describe the relationship between
cardiac dimensions (
y) and body size (
x) have been suggested.
Initial studies assumed a linear relationship, expressed as
y =
mx or
y =
mx +
c (where
c is the value of
y-intercept).
2,3 However, such linear relationships have not been found in childhood.
More recent studies have used allometric models, in which a
non-linear relationship is assumed.
4–6 These relationships
can be expressed in the form of
y =
axb (where
a is the scaling
factor and
b the scaling exponent) or the natural logarithmic
form ln(
y) = ln(
a) + (
b) ln(
x). There is now good evidence,
supported by the study in this issue, that the latter models
most accurately represent the relationship between body size
and cardiac dimensions, without heteroscedasticity (non-constant
variance). Sluysman and Colan
6 suggested in 2005 that a scaling
exponent of 0.5 provides the best index for cardiac and vascular
diameters, a prediction that appears to hold true in other studies.
4 Interestingly, however, they found that a linear relationship
best predicted cardiac and vascular areas.
6
An issue that remains to be resolved is which is the most appropriate measure of body size to use in normalization equations? Several parameters have been suggested, including weight, height, body surface area4–10 (estimated from published formulae),11,12 body mass index,1 and, in the fetus, femur length or biparietal diameter.13 Most paediatric studies have found that body surface area correlates most closely with cardiac dimensions. Neilan et al.'s study has suggested that correcting for weight provides the most accurate correlation with left atrial size,1 but it remains to be seen whether this holds true for other cardiac dimensions.
Normalization allows clinicians to quantify not only whether a given cardiac dimension falls within the normal range but also to monitor whether temporal changes are related to normal body growth or caused by pathological processes. When using normalized values, it would seem most appropriate that these are derived using the same modality and techniques. Therefore, for echocardiographic parameters, normal values derived from echocardiographic studies should be used, as these differ, for example, from normal values derived from cardiac magnetic resonance studies. This is particularly important in congenital heart disease patients, as the normal values most commonly used by cardiac surgeons to assess the size of cardiac and vascular structures intra-operatively are derived from formalin-fixed heart specimens examined post-mortem.14 As virtually all cardiac structures shrink during formalin fixation, there is a significant discrepancy between these values and those derived in vivo using non-invasive imaging techniques.15 As a result, it has been suggested that in the current era, echocardiographically derived normal values should be used as the gold standard on which to base management decisions.4 Long-term follow-up studies based on such values are required to confirm whether this approach is appropriate.
|
How best to express normalized data?
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Cardiac dimensions have been expressed as a percentage of the
mean normal value, but this does not take into account normal
variation. Another commonly used method for expressing normal
values is the use of centile charts. Although these are useful
for determining where a given value lies within the population,
values that lie above or below the uppermost or lowermost centile
lines, respectively, cannot be quantified. This limitation is
overcome by the use of
z-scores (i.e. the number of standard
deviations a measurement departs from the normal mean). The
use of
z-scores enables a more precise assessment of cardiac
dimensions, which is particularly important in conditions associated
with very small chamber dimensions (e.g. hypoplastic left heart
syndrome, pulmonary atresia) or very large measurements (e.g.
wall thickness in hypertrophic cardiomyopathy). Furthermore,
in the research setting,
z-scores are easily manipulated mathematically
to allow statistical comparisons to be made between subgroups
of patients. Z-scores can be expressed as nomograms or used
to create computer spreadsheets that generate a
z-score when
the body size and cardiac dimension variables are entered,
16 providing a very simple means for comparing echocardiographic
measurements with normal values.
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Limitations of current normalization data
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In recent years, there have been a number of studies reporting
normal echocardiographic values in the paediatric population.
2–10 Although these studies provide useful normative data, they are
limited by a number of problems. First, most of the reported
studies, with the notable exception of Neilan
et al.'s in this
issue, are very small, with <200 patients in any individual
study, ranging in age between birth and 18 years. As a result,
many of the normal values are derived by extrapolation. Despite
this, the relation between the mean value for a cardiac dimension
and square root of the body surface area is remarkable constant
across studies.
6 However, variation in the spread of the data
in different studies can lead to differing standard deviations,
hence differences in the unit ‘size’ of the
z-score
and consequently widely varying
z-score values when utilized
in disease states.
15 Furthermore, different studies use different
techniques (e.g. M-mode vs. two-dimensional echocardiography)
and not all studies provide normal values for all cardiac chambers,
valves, and great vessels. Perhaps not surprisingly, there is
considerable discrepancy between these individual studies. As
a result, data from individual institutions may not be comparable.
For an individual lesion, these discrepancies make the scientific
evaluation of medical, interventional, and surgical management
options problematic.
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Time for a standardized approach
|
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It is beyond debate that echocardiographic parameters in the
paediatric population must be normalized to body size. In order
to obtain accurate and reproducible results, a robust set of
normal values, derived from a large number of individuals and
comprising standardized and complete measurements of all cardiac
structures, using M-mode and two-dimensional echocardiography,
must be obtained. The study published in this issue of the Journal
1 is a timely step in the right direction. What is needed now
is for the paediatric cardiology scientific community to adopt
a single study to allow
z-score computation using an agreed
body surface area formula (e.g. the Haycock formula
12 which
may be more accurate at smaller surface areas).
6 The benefits
of this approach are self-evident and would lead to better comparability
of outcome studies in congenital heart disease, many of which
are undermined by differences in
z-score methodology. Achieving
this would require a concerted and collaborative international
approach involving the leading national and international congenital
societies. Although not underestimating the challenge that this
would present, we recommend that such discussions be initiated
immediately to achieve the goal of a universal standard.
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References
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- Neilan TG, Pradhan AD, King M-E, Weyman AE. Derivation of a size-independent variable for scaling of cardiac dimensions in a normal pediatric population. Eur J Echocardiogr (2008) Published online on March 14; doi:10.1093/ejechocard/jen110.
- Henry WL, Ware J, Gardin JM, Hepner SI, McKay J, Weiner M. Echocardiographic measurements in normal subjects. Growth-related changes that occur between infancy and early adulthood. Circulation (1978) 57:278–85.[Abstract/Free Full Text]
- Roman MJ, Devereux RB, Kramer-Fox R, O'Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol (1989) 64:507–12.[CrossRef][Web of Science][Medline]
- Daubeney PE, Blackstone EH, Weintraub RG, Slavik Z, Scanlon J, Webber SA. Relationship of the dimension of cardiac structures to body size: an echocardiographic study in normal infants and children. Cardiol Young (1999) 9:402–10.[Web of Science][Medline]
- First T, Skovranek J, Marek J. Normal values of 2-dimensional echocardiographic parameters in children. Cesk Pediatr (1992) 47:260–4.[Medline]
- Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol (2005) 99:445–57.[Abstract/Free Full Text]
- Daniels SR, Kimball TR, Morrison JA, Khoury P, Meyer RA. Indexing left ventricular mass to account for differences in body size in children and adolescents without cardiovascular disease. Am J Cardiol (1995) 76:699–701.[CrossRef][Web of Science][Medline]
- Hanseus K, Bjorkhem G, Lundstrom NR. Dimensions of cardiac chambers and great vessels by cross-sectional echocardiography in infants and children. Pediatr Cardiol (1988) 9:7–15.[CrossRef][Web of Science][Medline]
- King DH, Smith EO, Huhta JC, Gutgesell HP. Mitral and tricuspid valve anular diameter in normal children determined by two-dimensional echocardiography. Am J Cardiol (1985) 55:787–9.[CrossRef][Web of Science][Medline]
- Pearlman JD, Triulzi MO, King ME, Abascal VM, Newell J, Weyman AE. Left atrial dimensions in growth and development: normal limits for two-dimensional echocardiography. J Am Coll Cardiol (1990) 16:1168–74.[Abstract]
- Du Bois D, Du Bois E. Clinical calorimetry. X. A formula to estimate approximate surface area if height and weight be known. Arch Intern Med (1916) 17:863–71.[Web of Science]
- Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr (1978) 93:62–6.[Web of Science][Medline]
- Schneider C, McCrindle BW, Carvalho JS, Hornberger LK, McCarthy KP, Daubeney PE. Development of Z-scores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol (2005) 26:599–605.[CrossRef][Web of Science][Medline]
- Rowlatt UF, Rimoldi HJA, Lev M. The quantitative anatomy of the normal child's heart. Pediatr Clin North Am (1963) 10:499–588.
- Daubeney PE, Delany DJ, Anderson RH, Sandor GG, Slavik Z, Keeton BR, et al. Pulmonary atresia with intact ventricular septum: range of morphology in a population-based study. J Am Coll Cardiol (2002) 39:1670–9.[Abstract/Free Full Text]
- Devore GR. The use of Z-scores in the analysis of fetal cardiac dimensions. Ultrasound Obstet Gynecol (2005) 26:596–8.[CrossRef][Web of Science][Medline]
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