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\title{A `holistic' sonographic view on congenital heart disease -- how
semiautomatic reconstruction eases unveiling abnormal cardiac anatomy
part II: left heart anomalies}



\author[1]{Jan Weichert}%
\author[2]{Alexander Weichert}%
\affil[1]{University Hospital of Schleswig-Holstein, Campus Luebeck}%
\affil[2]{Charité Universitätsmedizin Berlin Campus Charite Mitte}%


\vspace{-1em}



  
  \date{April 25, 2026}


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\selectlanguage{english}
\begin{abstract}
Volume ultrasound has been shown to provide valid complementary
information on fetal anatomy. Three-dimensional assessment of the fetal
cardiovascular system using spatial-temporal image correlation (STIC)
allows for detailed examination of a highly complex organ from the early
second trimester onwards. There is compelling evidence that this
technique harbors quite a number of diagnostic opportunities, but manual
navigation through STIC volume datasets is highly operator dependent. In
fact, STIC is not incorporated yet into daily practice. Application of
the novel fetal intelligent navigation echocardiography (FINE)
considerably simplifies fetal cardiac volumetric examinations. This
semiautomatic technique reportedly has both high sensitivity and
specificity for the detection of congenital heart defects (CHDs). Part I
reviewed current data regarding detection rates of CHDs and illustrated
the additional value of a semiautomatic approach in delineating cardiac
anatomy exemplified by congenital lesions of the right heart. In part II
of this pictorial essay, we focused on left heart anomalies and aimed to
tabulate recent findings on the quantification of normal and abnormal
cardiac anatomy.%
\end{abstract}%



\sloppy


Introduction

Thorough assessment of the cardiovascular anatomy with two-dimensional
ultrasonography requires the operator to scan these vascular structures
in multiple scanning planes to obtain a mental reconstruction of their
spatial relationships\textsuperscript{1}. The introduction of
four-dimensional echocardiography using STIC facilitated examination of
the fetal heart by navigating through the volume data set in an
unlimited number of cutting planes. Since then, STIC technology has been
widely used for cardiac evaluation in a diagnostic setting. A growing
body of scientific work has shown that application of STIC technology
potentially aids in improving congenital heart defects (CHD)
detection\textsuperscript{2,3}. However, more than a decade ago, studies
on the effectiveness of STIC echocardiography failed to confirm its
superior clinical value for CHD detection compared to conventional 2D
ultrasound both in experienced and less experienced
hands\textsuperscript{4,5}. As fetal echocardiography using STIC
requires extra time and effort and exhibits a strong operator
dependency, its usefulness, particularly in a screening setting, has
been doubted.

With the advancement of an intelligent navigation approach applied on
STIC volumes, 4D echocardiography has been considerably simplified. With
marking of the proposed anatomical structures, all nine diagnostic
planes for comprehensive cardiac evaluation are semiautomatically
reconstructed. One of the advantages of intelligent over manual
navigation in volumetric sonography is the short time required for
acquiring the volume, marking and displaying all the cardiac view, along
with the added benefit of `guided' orientation and identification of
anatomical structures\textsuperscript{6}.

In part II of this paper, we focused on the additional diagnostic value
of fetal intelligent navigation echocardiography (FINE) in the
evaluation of the altered anatomy in left-sided cardiac lesions
simultaneously displayed in axial and longitudinally planes. We will
further discuss recent advances in 4D echocardiography and give a
concise overview of future perspectives on this technique for evaluating
fetal anatomy.

\emph{}

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 size\textsuperscript{7}. In 2005,
Schneider and colleagues published formulae for regression equations and
nomograms allowing \emph{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)\textsuperscript{8}. Recently, novel nomograms for cardiac
(bi-)ventricular widths and their corresponding ratios have been
published (increase in the RV/LV ratio with GA)\textsuperscript{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 structures\textsuperscript{10}. In
fact, these normative data differ from those of prior
reports\textsuperscript{11}. 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
data\textsuperscript{12}. Moreover, the resultant nomograms were not
tested on affected fetuses with CHD nor were correlations quantified to
determine the clinical significance of abnormal
measures\textsuperscript{13}. 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 lesions\textsuperscript{14}. 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
obstructions\textsuperscript{15}. In addition to the recommended
biometric cardiac parameters recommended by national and international
guidelines, a number of measurements have been introduced into the
literature\textsuperscript{16,17}. Gagnon et al. published the results
of 57 cardiac measurements and found nonlinear relationships with GA for
most parameters investigated\textsuperscript{18}. 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)\textsuperscript{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)\textsuperscript{20,21}. This
volumetric approach constitutes a reliable and accurate method for
obtaining true fetal cardiac dimension measurements in second and third
trimester fetuses\textsuperscript{22,23}. 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
hands\textsuperscript{24}. This technology now allows calculation of
quantitative cardiac biometry measurements (e.g., ventricular and atrial
size, diameter of outflow tracts, valvular hinges)\textsuperscript{21}.

Physiology of the left heart

The left ventricle (LV) is a pressurized chamber with a definite
myofiber architecture. The normal left ventricle is cone shaped,
posterior to and `hugged' by the right ventricle (RV) and comprises an
inlet portion containing the mitral valve apparatus, an overlapping
outlet portion leading to the aortic valve, and a rather smooth apical
portion containing fine crisscross trabeculations\textsuperscript{25}.
Anatomically, the LV is narrower and longer than the RV. Regarding the
myoarchitecture, the LV wall contains three layers from the
subepicardium to the subendocardium with a counterdirectional helical
arrangement of muscle fibers that is energetically efficient and
important for equal redistribution of stresses and strain in the
heart\textsuperscript{26}. Furthermore, there is a gradual thinning of
the LV wall that is observed toward the apical segments. In contrast to
the RV, there are two papillary muscles that originate from the LV free
wall and are attached to the mitral valve chordae tendinae. During
contraction, the base and apex of the LV rotate in opposite directions.
The left and right ventricles are also subjected to the same filling
pressure, and their combined ventricular output perfuses the fetal
system. The LV primarily perfuses the coronary and cerebral circulations
through the ascending aorta, and the RV perfuses the lower body and
placental circulation through the ductus arteriosus and descending
aorta. Postnatally, after programmed closure of the fetal shunts, the LV
pumps blood at higher pressures than other cardiac cavities as it faces
a much higher workload and mechanical afterload.~Recent findings from
the study by Junno et al. suggest that the fetal left ventricle seems to
be more sensitive to progressively worsening hypoxemia and acidemia than
the right ventricle\textsuperscript{27}. As stated by Sengupta and
colleagues, understanding the cardiac structure--function relationship
of both the left and right heart is essential and constitutes the basis
of a comprehensive and structured assessment of cardiac
anatomy\textsuperscript{26}. The advent of high temporal resolution
imaging methods, volumetric approaches and the recently introduced novel
semiautomatic algorithms for standardized reconstruction of cardiac
geometry might contribute to an improvement of prenatal detection rates
for more than just left-sided lesions. The potential of these
volume-based technologies to provide profound insights into global
anatomic changes of left heart anomalies will be discussed below.

Coarctation of the aorta

Coarctation of the aorta (CoA) is estimated to account for 4--6\% of
CHDs in newborns, with a reported prevalence of approximately 4 per 10
000 live births\textsuperscript{28}. Congenital coarctation of the aorta
increases impedance to the left ventricular outflow, but this condition
is usually well tolerated by the fetus because the foramen ovale and
ductus arteriosus equalize intracardiac and great arteries pressures and
shunts. Nevertheless, it potentially harbors life-threatening risks if
coarctation is not suspected and the arterial duct closes spontaneously
in postnatal life. This lesion was first described by Morgagni in 1761
and further delineated by Meckel in 1827 with a report on a sudden death
of a 35-year-old peasant who showed a ruptured right atrium beside an
exceedingly thinned aortic lumen with the diameter of a blade of a straw
right beneath the ligamentum aortae during
autopsy\textsuperscript{29-31}. Coarctation of the aorta shows a
considerable variability in its anatomic, physiologic and clinical
characteristics, and chromosomal and extracardiac anomalies are commonly
described. Morphologically, CoA encompasses a marked narrowing of the
ascending aorta and the aortic arch, typically affecting the isthmic
region (between the left subclavian artery and the ductus arteriosus).
Although often found to be a discrete anatomic anomaly, coarctation may
also consist of a long-segment stenosis associated with tubular
hypoplasia of the entire transverse aortic arch (as shown in fig. 1).
The embryologic origin is still not well understood, but CoA is
suggested to most likely result from a manifestation of an abnormality
in the development of the left fourth and sixth aortic arches during
embryogenesis. There are two pathophysiological concepts - according to
a hemodynamic theory, intracardiac lesions, which diminish the volume of
the left ventricular outflow, promote the development of coarctation in
the fetus by reducing flow through the aortic isthmus. In contrast, the
ductus tissue theory assumes that migration of smooth muscle cells into
the aorta leads to subsequent aortic constriction postnatally. The
latter concept is largely based on histological findings of differential
elastic fiber formation between the aorta and ductal
tissue\textsuperscript{32}. Bahado-Singh et al. published on fetal
epigenomic dysregulation of genes involved in both heart development and
postnatal cardiovascular diseases potentially associated with the
pathogenesis of CoA\textsuperscript{33}.

Grayscale ultrasound reveals different degrees of ventricular
disproportions and a larger pulmonary artery than the aorta suspicious
for CoA\textsuperscript{34,35}. Figure 1 clearly depicts these anatomic
changes -- an RV-LV discrepancy seen in the 4CV/5CV views and different
diameters of the pulmonary artery compared to the cross-section of the
aorta displayed in the short-axis view of the great vessels/RVOT.
However, most strikingly, the three vessels and trachea view (3VT) shows
a hypoplastic transverse aortic arch, confirming the small ascending
aorta seen in the 5CV/LVOT views. Hornberger et al. described the ratio
of right-to-left ventricular width to be 1.19 in normal fetuses and
greater than 1.69 in those with CoA\textsuperscript{36}. However, an
increased right-to-left ventricular ratio might also be found in other
cardiac conditions such as HLH, DORV, APVS, CDH or Ebstein's anomaly.
The volumetric approach described herein allows for detailed
reconstruction of additional planes in order to rule out these
differential diagnoses. Color Doppler interrogation may provide
additional information in all diagnostic planes, as described by Yeo and
Romero\textsuperscript{37}.

There is a general consensus that a normal appearance of the sagittal
section of the aortic arch on fetal echocardiography constitutes the
major exclusion criterion for CoA. In the case of coarctation, this view
might depict a posterior shelf or ridge in the aortic wall in addition
to a markedly narrowed aorta (as seen in figure 1). Arya et al. proposed
novel fetal echocardiographic morphometric measures for objective
antenatal assessment of the aortic arch and its branches and found
significant differences in the LCSA, AAo-DAo angle, and Tao-DAo angle
between normal fetuses and those with CoA\textsuperscript{19}. Similar
findings were published by other groups of researchers who found that a
smaller mitral valve diameter, MV to TV ratio, IDD, and isthmus-ductal
angle (IDA), carotid-subclavian artery index (CS) or distal arch index
(DAI) were associated with the development of CoA after
birth\textsuperscript{38-40}. In contrast to HLH, the apex is still
formed by the LV, and the myocardial contractility seems to be normal in
CoA. However, DeVore et al. described the 4CV view to be more spherical
in shape, increased in area and width, and decreased in length during
speckle tracking analysis\textsuperscript{41}. A recent metaanalysis
stated that adoption of multiparametric diagnostic models integrating
different ultrasound signs may assist examiners in identifying fetuses
with CoA. Interestingly, a persistent left superior vena cava, a
ventricular septal defect, and a bicuspid aortic valve were not
associated with an increased risk for this anomaly\textsuperscript{42}.
Acknowledging that these parameters might be helpful in the prenatal
diagnosis of coarctation, one has to admit that precise and reproducible
assessment is strongly operator dependent and inevitably needs different
cardiac planes for an exact calculation of the aforementioned objective
measures. This might partly explain the considerably high number of both
false-positive and false-negative diagnoses and why CoA remains the most
commonly missed ductal-dependent lesion to date.

From a functional perspective, recent data on cardiovascular adaptation
during neonatal life suggest that, despite biventricular remodeling and
cardiac output redistribution, fetuses with CoA have no significant
myocardial dysfunction\textsuperscript{43}. Regarding the postnatal
prognosis of CoA, the variables associated with intervention comprised
smaller AAo and transverse arch size, earlier gestational age at
diagnosis, and the additional finding of a higher peak AAo
Doppler\textsuperscript{44}. Confirmed cases of CoA must be followed
closely over the lifetimes of affected newborns for complications such
as recoarctation, aortic aneurysm, persistent hypertension, and changes
in any associated cardiac defects\textsuperscript{45}.

Aortic stenosis

The earliest description of a stenotic aorta as the leading cause of
death of a young man has been attributed to Lazarus Rivi\selectlanguage{ngerman}ére in 1659, who
found an enlarged LV and round masses occluding the aortic orificium
during necropsy\textsuperscript{46}. A prenatal diagnosis of aortic
stenosis is relatively rare, occurring in less than 10\% of newborns
requiring prostaglandin therapy and postnatal
intervention\textsuperscript{47}. The frequency has been estimated to be
0.2 to 0.5 in 1.000 live births, with a clear male predominance (4:1).

Aortic stenosis (AS) markedly varies in its clinical severity and
anatomical complexity, underscoring the need for a thorough cardiac
survey during targeted ultrasound to estimate whether a bi- or
univentricular circulation should be pursued\textsuperscript{47}.
Unfortunately, a large proportion of fetuses might present with rather
normal LV dimensions (e.g., a normal four-chamber view) in the
midtrimester, often precluding a prenatal diagnosis at an earlier
gestational age. According to the affected segment, obstructions of the
left ventricular outflow tract can occur at three anatomic levels:
valvular and (less frequently in fetal life) supravalvular or
subvalvular. In AS, the gross valvular dysmorphology encompasses a
diminished commissural separation leading to an increased rigidity of
the valve tissue. Morphologically, there is fibrous continuity between
the leaflets of the aortic and mitral valves\textsuperscript{48}. Owing
to this spatial proximity, AS is frequently accompanied by mitral valve
disease that worsens ventricular dysfunction. In general, fetal cardiac
adaptive changes to an increased hemodynamically significant pressure
load to the developing myocardium are characterized by myocyte
hyperplasia, LV dilation, endocardial fibroelastosis, myocardial
fibrosis, and early systolic and diastolic
dysfunction\textsuperscript{49}.

In moderate and less severe AS, fetal cross-sectional echocardiography
reveals impaired mobility of cusp tissue, an alteration in the phasic
movement of the aortic valve with reduced lateral and increased superior
excursions of valve echoes, and an increase in the internal aortic root
dimension beyond the level of the valve annulus\textsuperscript{50}.
However, proper imaging of the valve remains challenging as a number of
different planes are needed to display the valve (long axis view; axial
view of the valve annulus). The LV in these cases may appear normal or
only mildly hypertrophied, and an increased blood flow during color
Doppler interrogation can confirm the diagnosis of aortic stenosis. In
contrast, in critical AS, the left ventricle is markedly dilated and
hypocontractile with a typical echogenic inner appearance (endocardial
fibroelastosis). Color Doppler mapping fails to demonstrate forward flow
across the valve due to deteriorated ventricular dysfunction.

The case depicted in figure 2 shows the anatomic sequelae related to
valvular aortic stenosis. Most obvious is the enlarged LV with bulging
of the IVS to the right in the 4CV, 5CV and LVOT views caused by an
increase in pressure, as discussed above. The mitral valve leaflets are
also thickened. It has been shown that congenital valvular AS is
frequently a progressive disorder. Axt-Fiedner et al. reported on a case
of AS diagnosed in the first trimester with a normal four-chamber view
but increased blood flow velocity across the aortic valve. This fetus
showed subsequent progression to hypoplastic left heart
syndrome\textsuperscript{51}. In a recent large retrospective
multicenter study, the natural history of AS has been further
elucidated. Based on z-scores of the aortic and mitral valve and LV
dimensions, the risk of emerging HLH has been assessed to estimate the
proportion of ideal fetal candidates for fetal
valvuloplasty\textsuperscript{52}. The authors demonstrated
significantly smaller aortic and mitral valve diameters and reduced
growth velocities of the mitral valve in fetuses who ended up with a
univentricular circulation.

Aortic atresia

Aortic atresia is frequently associated with mitral atresia in the
context of a hypoplastic left heart and will be discussed below.
Isolated aortic atresia constitutes a rare cardiovascular anomaly. This
cardiac condition can occur with a ventricular septal defect and a
normal left ventricular size, but this occurrence is very rare and is
almost ever accompanied by a perforate mitral valve\textsuperscript{53}.
Additional (severe) mitral regurgitation has been shown to carry a
rather poor prognosis\textsuperscript{54}. Aortic atresia uncommonly can
complicate AV septal defects, univentricular hearts or transposition of
the great arteries\textsuperscript{55}.

Hypoplastic left heart

This term describes an anomaly characterized by a variable degree of an
underdeveloped, non-apex-forming left ventricle and stenosis/atresia of
the mitral and aortic valves, consequently failing to support systemic
circulation. This congenital cardiac lesion results in a univentricular
circulatory system dependent on right ventricle performance and an open
ductus arteriosus for perfusion. It is among the most common heart
defects, with an estimated incidence of 0.16 to 0.36 per 1000 live
births, accounting for 4.8\% to 9\% of CHDs\textsuperscript{56}. The
first description dates back to 1851 when von Bardeleben in 1851
described a severely ill newborn who died 27 weeks after birth from
progressive heart failure. Postmortem examination revealed extremely
diminished left heart structures and an atretic (obliterated) ascending
aorta\textsuperscript{57,58}. Interestingly, from a semantic
perspective, HLH syndrome has been discussed to be a misnomer as it
constitutes a heterogeneous, i.e., causally nonspecific, developmental
field defect\textsuperscript{59}. The most commonly held view regarding
the development of HLH is postulated to be altered biomechanical stimuli
(e.g., decreased ventricular filling resulting in reduced myocardial
strains) during a critical period of ventricular development with
advancing gestation\textsuperscript{60}. Nonetheless, it has been
hypothesized that the left ventricular hypoplasia might be caused by a
primary defect in ventricular development. A recent study on postmortem
HLH specimens suggested that the lesions seen represent acquired disease
occurring following closure of the embryonic interventricular
communication rather than sequelae of abnormal
embryogenesis\textsuperscript{61}. Morphologically, classic HLH
comprises hearts with mitral and aortic valve atresia with an intact
ventricular septum. On the other hand, there are variants of HLH
characterized by different degrees of left heart obstruction with mitral
atresia, a ventricular septal defect and a patent aortic valve or those
with aortic valve atresia\textsuperscript{56,62}. Recently, Crucean and
colleagues described three distinct subgroups relying on the
morphological appearance: (I) a slit-like LV (24\%); (II) a miniaturized
LV (6\%); and (III) a thickened LV with endocardial fibroelastosis (EFE;
70\%). Interestingly, only the slit-like ventricle grouping was found to
map to the current nomenclature: the combination of mitral atresia with
aortic atresia. Cases of a miniaturized LV all had normally formed,
although small, aortic and mitral valves, and the last and predominating
group was found to have a range of aortic valve malformations associated
with thickened left ventricular walls despite being described as either
atresia or stenosis\textsuperscript{62,63}.

In a typical hypoplastic left heart condition, prenatal ultrasound shows
a normally located right ventricle with a small hypocontractile LV often
associated with hypoplasia of the ascending aorta. In contrast to CoA,
the apex is formed by the RV, and there is markedly diminished LV
function in order to support systemic circulation in HLH (see figure 4).
As stated above, the shape and size of the LV can considerably vary
(e.g., small, round, slit-like, dilated or even normal). In almost all
cases, the aortic valve is atretic, but a common feature of HLH is an
obstruction of both the LV inflow and outflow tracts in specific
combinations of mitral valve (MV) atresia/aortic atresia (MA/AA), MV
stenosis/aortic stenosis or MV stenosis/aortic atresia. The latter
conditions account for nearly half of all HLH cases\textsuperscript{61}.
The left ventricular outflow is scarcely demonstrated in the 5CV/LVOT
views during echocardiographic examination, as exemplified in figures 3
\& 4. These figures further demonstrate a marked size discrepancy of the
left atrium being smaller than the right atrium, with the flap of the
foramen ovale excursing toward the RA as a consequence of the obstructed
inflow. Notably, HLH may be accompanied by different degrees of foramen
ovale restriction (up to 22\%), potentially leading to chronic left
atrial hypertension, which is transmitted onto pulmonary venous
structures, resulting in pulmonary hypertension and remodeling. Jadcak
et al. stated that an early appearance and a longer presence of FO
obstruction rather than the extent of obstruction are associated with an
increase in short-term mortality \textsuperscript{64}. Therefore, an
additional thorough assessment of pulmonary venous (PV) Doppler (PVD)
with a forward/reverse velocity-time integral (VTI) ratio of
\textless{}3 has been found to be the strongest predictor of postnatal
hemodynamic stability and the need for fetal
intervention\textsuperscript{65}. Despite a trend toward improved
preoperative morbidity in neonates with a prenatal diagnosis of HLH, a
recent systematic review revealed no significant impact on preoperative
or postoperative Stage I mortality\textsuperscript{66}. According to
recent data from Richard et al., frequent serial fetal echocardiograms
may not necessarily be needed to predict the need for an unexpected,
emergent procedure\textsuperscript{67}. However, this inevitably
underscores the need for an exact delineation of the phenotypic features
of the disease since hypoplasia of the left ventricle can be found in a
number of other cardiac lesions (including an unbalanced AV canal, a
double outlet right ventricle or a common arterial trunk). Moreover,
borderline cases of HLH might be left undetected in many early to
midgestation fetal exams and often tend to progress to HLH until birth.

Double-inlet left ventricle

Double-inlet left ventricle (DILV) is a rare cardiac anomaly in which
both the tricuspid and mitral valves enter the LV (double-inlet
univentricular connection). This lesion is estimated to occur in
approximately 0.05 to 0.1 per 1,000 live births\textsuperscript{68}. In
a recent retrospective report on 155 patients with a prenatal diagnosis
of functionally univentricular hearts, the frequency of DILV in a
subgroup of fetuses with dominant LV was 46.1\%\textsuperscript{69}. The
term DILV was introduced by de la Cruz and Miller in 1968, but the
earliest description is attributed to Andrew F. Holmes, who reported on
a 21-year-old young man who died from severe cardiac
distress\textsuperscript{70,71}. His pathological findings of a cor
triloculare biatriatum were reinspected and republished by M. Abbott in
1901\textsuperscript{72,73}.

According to its definition, a double-inlet ventricle exists when the
greater part of both atrioventricular (AV) junctions is supported by a
single ventricular chamber. Embryologically, a defect in the
left-to-right expansion of the atrioventricular canal results in the
connection of both atria to the primitive ventricle. Notably, solitary
ventricles in which a second ventricular chamber is not distinguishable
are exceedingly rare; more commonly, a rudimentary incomplete chamber
adjacent to the dominant ventricle is found\textsuperscript{74}. The
commitment of both AV valves to the same ventricular chamber limits the
characterization and localization of the AV valves as mitral or
tricuspid valves\textsuperscript{75}. In the vast majority of cases,
there is ventriculoarterial discordance with a left anteriorly located
ascending aorta from the RV and pulmonary trunk arising right
posteriorly from the dominant LV (74\%)\textsuperscript{76}. Concordant
ventriculoarterial connections with the aorta arising off the dominant
morphologic left ventricle, whereas cases in which the pulmonary artery
arises off the anterior hypoplastic right outlet chamber are
considerably rare (15\%; referred to as Holmes'
heart)\textsuperscript{77}. According to van Praagh et al., the exact
characterization of the morphology of the ventricular myocardium
constitutes the most important aspect for proper identification of the
underlying anatomic variant\textsuperscript{73}. Semilunar valve
stenosis or atresia (40\%) and aortic arch abnormalities, such as
coarctation and interrupted arch (12\%) and AV valve abnormalities
(39\%)\textsuperscript{76,78}, may be associated with a single LV.

Grayscale echocardiography usually shows an abnormal 4CV view with both
atria being connected to a dominant left ventricle. The small
underdeveloped right ventricle is occasionally seen in this cutting
plane. A detailed assessment reveals smooth ventricular myocardium with
fine mesh-like trabeculations corresponding to left ventricular
morphology. As aforementioned, in most cases, the rudimentary outlet
chamber is situated left anteriorly, and more cranial diagnostic planes
are needed for proper visualization. In figure 5a, an enlarged LV and a
smaller right-sided chamber with a rather coarse apical trabecular
component are shown. The cardiac axis is normal (28.7°). The RV
communicates with the dominant LV via a nonstenotic VSD (which is the
embryologic remnant of the bulboventricular foramen), as displayed in
the 4CV/5CV views. Both outlet vessels are normally arranged without
hemodynamically significant flow obstruction, which is in line with the
findings of a recent study on the relationship of the inflow and outflow
tracts, which demonstrated no pulmonary stenosis in relation to the
aorta in 72\% of cases of DILV\textsuperscript{79}. However, the 3VT
view in the present case shows a slightly smaller main pulmonary artery.
Figure 5b shows the more common anatomical arrangement of DILV with an
apparent ventriculoarterial discordance. In contrast to panel a, the RV
is barely seen, and the LV is the dominant chamber (fine trabeculation).
The ascending aorta is anteriorly displaced and arises from the
rudimentary RV (displayed in the LVOT and aortic arch views); the
pulmonary artery shows severe stenosis. In fact, DILV is well
tolerated\emph{in utero} without important fetal consequences. The
clinical presentation and postnatal management are mainly driven by the
presence of associated lesions and the arrangement of great arteries. It
generally involves staging toward the ultimate goal of Fontan
palliation\textsuperscript{80}.

Summary

The information gained is dependent on the

examiners image optimization and scanning skills, the examiners
knowledge of cardiac anatomy and anomalies,

and the spatial imagination of the interpreting physician.

In a recent nationwide, population-based study, increased accuracy and
prenatal detection rates of major CHDs have led to an increase in
terminated pregnancies and subsequently decreased live-birth incidence
of fetuses with major CHDs\textsuperscript{81,82}. These findings have
been confirmed by other groups\textsuperscript{83,84}, emphasizing that
vigilant care should be placed on cardiac evaluation when termination is
considered due to a cardiac anomaly. The question of if prenatal
diagnosis effectively improves population health has been addressed by a
number of publications to date. Antenatal detection of a treatable
critical congenital heart disease was associated with lower morbidity
and mortality\textsuperscript{85}. In this regard, as data from the
EPICARD study imply, postnatal survival may no longer be the most
relevant outcome criterion for evaluating the impact of a prenatal
diagnosis of a CHD. Indeed, as recent studies have shown, prenatal
diagnosis can improve the neurodevelopmental outcomes of newborns with
CHDs (e.g., TGA)\textsuperscript{86,87}. Thakur and colleagues
demonstrated that a prenatal diagnosis of a critical CHD in their study
was associated with a significantly shorter time interval from birth to
neonatal admission and the absence of life-threatening or fatal
preoperative cardiac events\textsuperscript{88}. Even in aneuploidy
syndromes, timely prenatal diagnosis of CHDs and appropriate follow-up
into adulthood have been shown to improve outcomes in these complex and
multisystem conditions\textsuperscript{89}.

However, acknowledging that antenatal identification of a number of
severe cardiac anomalies is good and merely straightforward, the
detection rates of CHDs in general have remained low. The most commonly
missed severe CHDs are conotruncal lesions, such as transposition of the
great arteries, tetralogy of Fallot, double outlet right ventricle or
truncus arteriosus, since the four-chamber view may be falsely
reassuring in the majority of these cases\textsuperscript{90}. The
addition of more standard views has been shown to increase the detection
rate of CHDs, as this increase may yield valuable information on most
left and right-sided cardiac lesions and is cost effective according to
recent data\textsuperscript{91,92}.

According to the results from a very recent national survey of
physicians, the main barriers preventing effective cardiac screening
were knowledge of CHD screening guidelines and minimal volumes of
cardiac scans\textsuperscript{93}. Detailed characterization of fetal
cardiac function in normal and abnormal fetal hearts is feasible and
well described using conventional 2D ultrasound. Functional assessment
of the fetal heart applying volume data sets has been shown to provide
reliable information on cardiac integrity irrespective of the fetal
position \emph{in utero} . Volume measurement using 4DUS allows for
virtual organ computer-aided analysis (VOCAL) to estimate the
ventricular volume and calculate the total systolic volume, ejection
fraction, and cardiac output\textsuperscript{94,95};
SonoAVC\textsuperscript{96} or M-STIC can be used to calculate the AV
valve annular plane systolic excursion
(MAPSE/TAPSE)\textsuperscript{97}. These imaging modalities are
applicable for different (patho)physiological fetal conditions (e.g.,
normal fetuses, fetuses with cardiac anomalies, growth restricted
fetuses or diabetic pregnancies)\textsuperscript{98-101}. However, as
aforementioned, the continuing challenge is primarily the capability of
morphologic assessment rather than the description of functional and
quantitative changes in cases suspicious for congenital heart disease.

There is a general consensus that high-quality STIC volume data sets are
informative and potentially able to effectively address this issue. The
introduction of electronic spatiotemporal image correlation (eSTIC)
reportedly improved four-dimensional fetal echocardiography in terms of
acquisition time and image quality\textsuperscript{102}. Depiction of
multiple parallel cut sections from the same image planes, as
exemplified by tomographic ultrasound imaging (TUI), might be of help in
illustrating spacious derangement in certain cases suspicious for
CHDs\textsuperscript{103}, but it fails to display differently
orientated diagnostic planes, as shown by fetal echocardiography
guidelines. The method reviewed herein automatically reconstructs all
nine standard fetal echocardiography views required to diagnose most
cardiac abnormalities, as illustrated above. Recently introduced novel
and advanced features of FINE including very rapid static volume
acquisition (i.e., 1 second), characterized by a high frame rate or the
ability to precisely manipulate a single cardiac plane (volume) along
the x, y, or z plane or perform parallel shifts by applying monoplanar
navigation have been shown to ease cardiac
volumetry\textsuperscript{21}.

Taken together, combining the details of (ab)normal cardiac morphology
using standardized approaches (FINE technology) with functional
parameters to quantify subtle changes (cardiac remodeling) retrieved
from a single STIC volume will prospectively contribute to improved
prenatal detection and surveillance of fetuses with CHDs and other
stressing conditions \emph{in utero} . This underscores the
indispensable need for adequate training of operators to effectively and
reproducibly deploy the benefits of cardiac volumetry.

\emph{}

Figures

Fig. 1: Coarctation of the aorta at 24 completed weeks with STIC volume
reconstruction and automatic labeling using the FINE method. In the
3-vessel-trachea view, the size of the transverse aorta is clearly
reduced. The 4-chamber view is abnormal with ventricular asymmetry
(LV\textless{}RV), and the size of the foramen ovale is normal. In both
the 5-chamber view (5CV) and left ventricular outflow tract (LVOT) view,
there is a smaller ascending aorta corresponding to an aortic
coarctation. Additionally, a perimembraneous outlet VSD is seen. The
RVOT view shows a normal main pulmonary artery and bifurcation. There is
a regularly filled stomach in the abdominal plane. The ductal arch view
is normal. In contrast, the aortic arch is thinned, which confirms the
finding of an obstructed LVOT. The RA appears to be enlarged. The vena
cava view denotes similar findings.

A - transverse aortic arch; Ao - aorta; Desc - descending; IVC -
inferior vena cava; LA - left atrium; LV - left ventricle; P - pulmonary
artery; PA - pulmonary artery; RA - right atrium; RV - right ventricle;
RVOT - right ventricular outflow tract; S - superior vena cava; SVC -
superior vena cava; Trans - transverse.

Fig. 2: Aortic stenosis at 27 gestational weeks. The 3VT view is rather
normal. In contrast, the LV is considerably larger than the RV, and the
interventricular septum is bulging toward the right side. The cardiac
axis is within the normal range. Both atria are normal in size and
shape. The ascending aorta shows a thickened, nondisappearing valve
during systole, and the mitral valve leaflets also appear thickened. The
ductal arch, aortic arch and bicaval views are normal.

Fig. 3: Aortic atresia seen at 23 weeks causing a hypoplastic left heart
with functional univentricular circulation. The left-sided cardiac
structures are markedly smaller than those on the right side. The
transverse aorta can barely be seen in the 3VT plane; accordingly, the
ascending aorta in the 5CV and LVOT planes is extremely small. The
residual LV has a slit-like appearance, and both atria and the tricuspid
valve are normal in size. There is a miniaturized mitral valve. The
RVOT, ductal arch and bicaval views are normal. The aortic arch is
hypoplastic.

Fig. 4: Fetus with a hypoplastic left heart at 23 weeks. The
characterizing anatomic features are clearly depicted after
semiautomatic reconstruction using FINE. There is a size discrepancy in
both great vessels on the 3-vessel-trachea view (PA\textgreater{}Ao).
The 4CV view is abnormal with a ventricular asymmetry (LV\textless{}RV),
the LV is round and hypocontractile with endocardial fibroelastosis, and
the foramen ovale is patent and nonrestrictive. Both the mitral valve
and the ascending aorta are small (5CV, LVOT). The RVOT views shows
normal main and branch pulmonary arteries. The ductal arch view is
normal, while the aortic arch is thinned, which confirms the finding of
an obstructed LVOT. The RA appears to be enlarged. The vena cava view
denotes similar findings.

Fig. 5: Two cases of a double-inlet left ventricle (DILV) at 26 and 22
completed gestational weeks. FINE application shows normally related
great vessels in panel a (3VT, LVOT, RVOT and arch views). Both AV
valves are connected to the anatomical LV, and the RV is small but
normally situated to the right of the dominant ventricle. The ascending
aorta in the LVOT and 5CV planes is normal in size. The RVOT view shows
the small RV giving rise to the main pulmonary artery. The longitudinal
ductal and aortic arch and bicaval views are normal. The rather rare
variant corresponds to so-called Holmes' heart. Panel b depicts the more
common type of DILV with ventriculoarterial discordance and an extremely
small RV giving rise to the anteriorly dislocated ascending aorta (LVOT,
aortic arch view). The main pulmonary artery is severely stenotic (3VT,
ductal arch view). The bicaval arrangement appears to be normal.

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