Detailed quantification of cardiac morphology
The use of centiles for critical determination of the size and growth of
fetal organs is well established. Traditionally, available studies have
examined absolute values of normal structures across gestation. However,
as the size of the fetus may vary markedly throughout gestation, the use
of z-scores (expressed as the number of SDs a measurement departs from
the population mean) has been advocated. There is a general consensus
that cardiac measurements are not routinely required during
echocardiographic assessment of the fetus. Calculation of z-scores
normalizes cardiac structures to body size7. In 2005,
Schneider and colleagues published formulae for regression equations and
nomograms allowing z -scores to be calculated for 17 cardiac
structures in normal fetuses in relation to noncardiac biometric
parameters (femur length, biparietal diameter and gestation
age)8. Recently, novel nomograms for cardiac
(bi-)ventricular widths and their corresponding ratios have been
published (increase in the RV/LV ratio with GA)9.
Krishnan et al. examined 13 cardiac dimensions and concluded that
predictive models based on GA provided the best fit for determining
normal measurements of fetal cardiac structures10. In
fact, these normative data differ from those of prior
reports11. In a recent commentary on potential causal
variables, Cantinotti and colleagues highlighted multiple methodological
and numerical limitations of the available studies including the sample
size, data size, measurement methods, normalization, and expression of
data12. Moreover, the resultant nomograms were not
tested on affected fetuses with CHD nor were correlations quantified to
determine the clinical significance of abnormal
measures13. A number of left- and right-sided lesions
may antenatally present with abnormal ventricular proportions and growth
exceeding normal values. Precise quantification of these
echocardiographic parameters may act as a proxy to estimate the need for
neonatal intervention and single-ventricle palliation in fetuses with
suspected obstructive cardiac lesions14. In this
regard, fetuses with left ventricular length z-scores that are 2–4
standard deviations below normal have an increased risk of developing a
hypoplastic left heart syndrome (HLHS) variant. The initial
echocardiographic examination at 18–22 weeks is unable to distinguish
cases of fetal cardiac asymmetry that are destined to develop into HLHS
variants from the eventually normal cases, underscoring the need for
serial exams in cases suspicious for LVOT
obstructions15. In addition to the recommended
biometric cardiac parameters recommended by national and international
guidelines, a number of measurements have been introduced into the
literature16,17. Gagnon et al. published the results
of 57 cardiac measurements and found nonlinear relationships with GA for
most parameters investigated18. Particularly,
identification of subtle changes in cardiac morphology (e.g., aortic
arch anomalies) might be challenging. The fetal left common
carotid-to-left subclavian artery distance (LCSA) and ascending aorta
(AAo)-descending aorta (DAo) and transverse aorta (Tao)-DAo angles are
novel measures that can differentiate between subjects with and without
aortic coarctation (CoA)19. However, for reliable
quantification of an abnormal aortic angulation in cases suspicious for
CoA, a true sagittal anatomic plane is warranted. Similarly, as stated
above, proper assessment of abnormal ventricular or vascular size is
directly related to the ability to generate exact diagnostic sections of
the fetal heart. In general, to preclude off-axis images of the
4-chamber view, alignment is needed to visualize the entire boarders of
each cardiac chamber within the fetal thorax. Departing (oblique)
cutting planes may consecutively result in abnormal values for cardiac
dimensions. In 4D echocardiography, a specific cardiac phase can by
identified and analyzed by observing the global contractility of the
myocardium and the response and integrity of the cardiac valves within
an entire heart cycle (frame-by-frame)20,21. This
volumetric approach constitutes a reliable and accurate method for
obtaining true fetal cardiac dimension measurements in second and third
trimester fetuses22,23. The same applies for objective
evaluation of fetal cardiac function to provide important information on
hemodynamic status, which will be discussed later.
A major limiting factor is that detailed offline analysis and navigation
within a volume data set is useful when performed by skilled examiners
with expertise in (volume) echocardiography. Recent data show that a
semiautomatic workflow-based approach using FINE could reliably
reconstruct standard diagnostic planes even in unexperienced
hands24. This technology now allows calculation of
quantitative cardiac biometry measurements (e.g., ventricular and atrial
size, diameter of outflow tracts, valvular hinges)21.