Introduction
Recent advances in imaging diagnostics have led to the introduction of new ultrasound imaging techniques such as 2-dimensional speckle tracking echocardiography (2D-STE). In the past, speckle tracking analysis during pregnancy was mainly used to measure fetal ventricular strain and strain rate [1-14]. However, the DeVore group, together with Tom Tec, has developed fetalHQ® software that integrates 2D-STE, which has expanded its use to also measure the size, shape, and contractility of both ventricles by utilising the 49 coordinates provided [15]. It is important to mention that, in the literature, there is a relative paucity of fetal heart nomograms for ventricular size, shape, and function variables that are based on longitudinal studies, and the fetalHQ® capability allows researchers to assess several important parameters, including the global longitudinal strain (GLS) [16], end-diastolic diameter (EDD), segmental fractional shortening (FS) [17], and global sphericity index (GSI) for each of the 24 segments of the right and left ventricles. This comprehensive analysis also provides valuable insights into overall heart function, such as stroke volume (SV), cardiac output (CO), ejection fraction (EF), or fractional area change (FAC) [18], as well as local abnormalities in geometry and contractility of individual segments. Data obtained from fetalHQ® showed excellent intra- and inter-observer reproducibility [19], and regression on independent variables allows the generation of centile tables and Z-scores for gestational age. This innovative approach has significantly advanced our understanding of the structural and functional relationships within these chambers of the heart, leading to a thorough assessment of cardiac contractility. As a result, it has introduced a more comprehensive methodology that has greatly enhanced the way we interpret and analyse cardiac function during pregnancy [20]. The objective of this paper is to review the current literature on 2D-STE and its application in assessing fetal ventricular function.
Cardiac output
The main function of the heart is to generate CO. This is achieved through the work of the ventricles and the appropriate volume of blood that fills them. In the field of prenatal cardiology, CO and SV are typically calculated by multiplying the velocity time integral (VTI) by the area of the aortic or pulmonary valves annulus, respectively, measured at the ventricular outflow tract. There have been numerous studies on the SV and CO [21-23], and reference values for these measurements are well established [24]. However, it is important to acknowledge certain limitations associated with this method. While the positioning of the pulsed-wave Doppler gate and the angle of insonation can influence the VTI measurement [25], the critical factor is the accurate measurement of the aortic annulus diameter [26, 27]. A small change in this measurement can significantly impact the SV calculated. FetalHQ® software assesses SV using Simpson’s single-plane rule of disk summations [28-30]. DeVore et al. compared left ventricle (LV) SV obtained with 2D-STE to previously studies that used pulsed-wave Doppler for assessing SV [30]. Serafin et al. conducted a comparison of 2 methods to measure SV in the same group of patients [26]. Their findings indicated that the SV values obtained using pulsed-wave Doppler were, on average, 88% higher than those calculated with fetalHQ® during the 2nd trimester. In the 3rd trimester, the difference was slightly lower, with pulsed-wave Doppler measurements being, on average, 76% higher than those from fetalHQ®. These results are visually illustrated in Figure 1, which presents the 5th, 50th, and 95th percentiles for the SV values obtained through both techniques.
Myocardial contractility
FetalHQ® software allows for the analysis of longitudinal and transverse displacement of the endocardium (Video 1). This approach develops a comprehensive assessment of both global and segmental contractility parameters. Measurements of ventricular contractility and LV function, obtained through 2D-STE are presented in Table 1. For the segmental assessment of contractility in each of the 24 segments of both ventricles, we utilise FS. This measure is independent of gestational age and fetal size. When looking at the basal segments, no notable differences in FS were found between the LV and the right ventricle (RV). However, the intermediate and apical segments exhibited significantly higher FS values in the LV compared to the RV (Figure 2) [17]. To better understand the contractility and intricate geometry of the right ventricle, it is crucial to investigate the orientation of the muscle fibres that compose the ventricular walls. Mekkaoui et al. studied the fibre orientation in the myocardium and discovered 2 opposing helical fibre tracts that extend from the base to the apex of the lateral wall of the LV, in addition to a nonhelical circumferential fibre tract [31]. In fetal hearts, the fibre orientation resembles adult hearts by approximately 19 weeks of gestation, with minimal resemblance at 10 weeks (Figure 3). Buckberg et al. explored the helical structure of the ventricles, supporting Torrent-Guasp’s theory that the heart comprises 2 continuous muscle bands: the basal loop, which contains transverse fibres encircling both ventricles, and the apical loop, which consists of right- and left-handed helices intersecting at a 60-degree angle, forming an apical vortex (Figure 4A) [32, 33]. These helices are essential for generating opposing contraction forces between the base and apex of each ventricle, enabling effective blood ejection and refilling. The specific orientation of myocardial fibres means that primarily the interventricular septum supports the function of the RV. Research indicates that the longitudinal shortening of the RV, from its base to apex, results from the contraction and coiling of the apical helix, with minimal contribution from the longitudinal and circumferential fibres of the ventricular free wall. This unique anatomical arrangement presents a limiting factor for the use of the segmental FS in the RV, as in the case for Simpson’s rule of disk summation calculated on its basis. Research on the RV indicates that its longitudinal shortening from base to apex primarily results from the coiling and contraction of the apical helix, with minimal contribution from the longitudinal and circumferential fibres of the lateral wall. Notably, studies conducted in both adults and animal models reveal that RV failure does not occur solely due to the dysfunction of the free wall; rather, it typically arises under conditions of RV overload. Interestingly, heart insufficiency develops when the interventricular septum experiences ischaemia [34-36]. Supporting this notion, Serafin et al. in a prenatal study confirmed the negligible role of the free wall in generating RV CO [37].
Motion vector analysis
FetalHQ® software offers real-time visualisation of speckle motion vectors. Through vector analysis, it reveals insights into muscle fibre orientation and contraction direction, enhancing our understanding of myocardial anatomy and physiology (Figure 4) [37-40], and it facilitates our understanding of complex pathophysiological mechanisms in the fetal heart. Figure 5 illustrates the right ventricular systolic dysfunction observed in a fetus with a RV free wall aneurysm. It depicts the physiological contraction of the opposing helices of the interventricular septum, the contraction of the circular fibres of the LV, and the displacement area of the RV affected by the aneurysm along the interventricular septum. Video 2 presents the same case, where motion vector analysis highlights the displacement of the stiff, akinetic RV along the interventricular septum, known as the “frozen ventricle sign”. Additionally, tricuspid valve stenosis is evident, characterised by a stiff, akinetic tricuspid valve alongside a properly functioning mitral valve [37].
Detection of congenital heart defects
Despite significant advancements in ultrasonography, detecting congenital heart defects (CHD) during the prenatal period continues to pose challenges [41]. A comprehensive qualitative and quantitative assessment of the heart is essential for identifying CHD. This includes not only detecting structural changes but also assessing abnormalities in the shape, contractility, strain rate, and size of the ventricles. The role of 2D-STE in detecting CHD has advanced from basic single measurements of longitudinal strain and strain rate to more complex assessments. Initial approaches focused on simple longitudinal strain measurements [3-7]. This has progressed to longitudinal multiparameter analyses [42, 43] and, more recently, to sophisticated multiparameter evaluations that assess both the size and contractility of the right and left ventricles. These advanced measurements, when through logistic regression analysis, enable a precise determination of the risk of specific pathologies.
Tetralogy of Fallot and D-transposition of the great arteries
In a study by DeVore et al., 44 fetuses diagnosed with tetralogy of Fallot (TOF) were evaluated using 2D-STE, focusing on the size and shape of the 4-chamber view (4CV). This approach served as a screening tool to identify fetuses at risk for this malformation. Logistic regression analysis revealed that specific end-diastolic measurements could predict tetralogy of Fallot with a sensitivity of 90.9% and a specificity of 98.5% [44]. DeVore et al. analysed 88 fetuses 44 with TOF and 44 with D-transposition of the great arteries (D-TGA) to assess whether specific measurements of the 4CV and ventricles could identify fetuses at risk for these congenital heart defects. Using logistic regression analysis, the study identified 8 end-diastolic measurements. The analysis demonstrated high sensitivity for detecting either condition: 94.3% overall, with a false-positive rate (FPR) of 5.7%. Specifically, the sensitivity for TOF was 95.5%, FPR 4.5%, and for D-TGA it was 93.2%, FPR 6.8% [45]. This approach allows for rapid assessment of congenital heart defects from just 8 simple measurements, enhancing the likelihood of identifying these malformations during routine fetal examinations. Supplement 1 provides a calculator to predict the probability of either condition based on these measurements.
Speckle tracking analysis was utilised also to assess the size, shape, and contractility of the RV and LV in fetuses with D-TGA. The study aimed to identify fetuses requiring emergent balloon atrial septostomy (BAS) postnatally. Differences in cardiac parameters were found between the 2 groups, with logistic regression successfully identifying 91% of neonates needing BAS, yielding an FPR of 12% [46]. A calculator (Supplement 2) is provided for predicting fetuses at high risk for requiring neonatal BAS based on these measurements.
Coarctation of the aorta
The study by DeVore et al. aimed to improve the prenatal detection of coarctation of the aorta (CoA) by analysing fetal size and cardiac measurements. Using a control group of 200 normal fetuses, z-scores were calculated for 108 fetuses (54 true CoA and 54 false-positive CoA). Logistic regression identified 28 variables that distinguished true CoA from false positives with a sensitivity of 96%, a FPR of 4%, and a false-negative rate of 4%. Key findings included that 80% of true CoA fetuses exhibited RV/LV area disproportion, and true CoA was more often associated with cardiac abnormalities compared to FP-CoA (93% vs. 61%, p < 0.001) [47]. The most common malformations included bicuspid aortic valve and aortic arch hypoplasia, both significantly more frequent in the true CoA group. DeVore et al. conducted another retrospective study analysing 108 fetuses identified by paediatric cardiologists as being at risk of CoA. The regression equation derived from the test group identified several key end-diastolic measurements: 4CV, GSI, RV area to heart area ratio (RV area/HA), LV base segmental sphericity index (SI), and RV base segmental SI. The test group consisted of 14 out of 27 (52%) fetuses with isolated CoA and 13 out of 27 (48%) fetuses with additional cardiac abnormalities. For the validation group, the breakdown was 10 out of 27 (37%) with isolated CoA and 17 out of 27 (63%) with additional cardiac anomalies. Using the logistic regression equation derived from the test group (a total of 54 fetuses: 27 with CoA and 27 without CoA), the validation group (also a total of 54 fetuses: 27 with CoA and 27 without CoA) showed promising results: sensitivity for detecting CoA was 98.15%, specificity was 98.15%, and the FPR was 1.85% [48]. When applying the logistic regression analysis specifically to the test group of fetuses with isolated CoA, 100% (14/14) were correctly identified. For the validation group, 9 out of 10 (90%) of the fetuses with isolated CoA were identified using the logistic regression equation. Those studies concluded that advanced analysis of ventricular measurements could enhance prenatal diagnosis of CoA. The findings were accompanied by a calculator designed for use with fetalHQ® software (Supplement 3), streamlining the computation of z-scores based on these variables.
Assessment of ventricular function
The assessment of heart function is essential for making informed clinical decisions regarding pharmacotherapeutic treatments, prenatal interventions, and timing of delivery, all of which significantly impact postnatal outcomes. FetalHQ® software enables the visualisation of subclinical changes [9, 49], which often precede commonly detected pathologies, such as ventricular remodeling. For instance, a decrease in GSI can occur before haemodynamic changes in the umbilical artery in fetuses with fetal growth restriction [50]. Murlewska et al. reported a decrease in GSI value in fetuses receiving digoxin therapy, highlighting the software’s applicability in monitoring evolving heart defects [51]. FetalHQ® provides a comprehensive analysis of contractility, offering both global and segmental assessments of fetal heart function. The values obtained are regressed against 7 independent variables and presented as percentiles and Z-scores, reinforcing its diagnostic utility. The “parallel” model of fetal circulation indicates that when one ventricle malfunctions, the other can partially compensate, leading to secondary adaptations. Consequently, simultaneous analysis of both ventricles is crucial, a feature that fetalHQ® effectively supports. This positions fetalHQ® as a valuable diagnostic tool for improving fetal outcomes through enhanced monitoring and early intervention.
The most striking example of an anatomical abnormality associated with cardiac dysfunction is hypoplastic left heart syndrome (HLHS). Figure 6 illustrates a 28-week fetus affected by HLHS, determined by mitral and aortic stenosis (MS-AS). Observations during systole and diastole reveal notable changes in the shape, size, and proportions of the LV and RV. Comprehensive analysis of end-diastolic diameter (EDD) and FS indicates significant LV contractility and shape abnormalities, with the LV becoming spherical. This morphological change is accompanied by marked reductions in key functional parameters such as EF, SV, end-diastolic volume (EDV), and CO. Video 3 (the same case) demonstrates LV akinesia and a paradoxical increase in LV longitudinal dimension during early systole, resulting in a positive GLS value. This case underscores the critical impact of structural defects on cardiac function in HLHS. Video 4 presents a 35-week fetus affected by critical aortic stenosis (CAS), revealing a comprehensive examination of LV and RV dimensions and their contractility. Notably, there is a reduction in all LV dimensions, including the EDD, while the RV EDD shows an increase. This imbalance is accompanied by impaired global and segmental contractility both the LV and RV. Despite the diminished FS and size of the LV, it retains a normal shape, as evidenced by the LV GSI across all 24 segments. The preserved shape and the absence of fibroelastosis features suggest a promising outlook for postnatal LV function. This detailed analysis underscores the complexities of ventricular function regarding their geometry and contractility, paving the way for further insights into the condition’s impact on postnatal outcomes. Serafin et al. described a case of RV free wall aneurysm leading to hypoplastic right heart syndrome, with ductus-dependent pulmonary circulation, noting effective digoxin treatment and successful postnatal surgery. Alongside traditional Doppler methods, they utilised fetalHQ® software to assess LV and RV function and monitor contractility disorders (Figure 5, Video 2 ) [37].
Blood speckle imaging
Colour Doppler estimates blood flow velocity using the autocorrelation technique. This involves transmitting an ensemble of pulses along a line and measuring phase shifts of echoes from the same depth, after filtering out stationary tissue signals. However, it only captures velocity along the ultrasound beam’s direction, missing perpendicular flow components and underestimating velocity due to beam-to-flow angle. The maximum measurable velocity is limited by the pulse repetition frequency (PRF) and decreases with increased depth due to the time required for pulses to return. Blood speckle imaging (BSI) is a new flow assessment, combining colour Doppler with speckle tracking. This method requires high frame rates and broad transmit beams with multiple parallel receivers. After eliminating tissue signals, blood speckles are tracked over time, producing a 2-dimensional velocity field without restrictions by the Nyquist limits, allowing for higher velocity estimates. While the tracking algorithm demands significant computation and results in a lower spatial resolution, it is less affected by the angle of flow, relying more on ultrasound signal strength. BSI introduces a 2-dimensional field of blood velocities in ultrasound imaging, enhancing visualisation beyond traditional colour Doppler methods. By making the colour Doppler partially transparent and showing moving particles that represent blood flow, akin to bubbles in water, users can better interpret flow dynamics. Particle colours are based on the original colour Doppler mapping, providing visual guidance. For detailed examination, moving particles can be displayed in a loop for a single frame, regardless of cine playback. With customisable settings, BSI improves flow analysis, enhancing temporal resolution and velocity estimation, presents new opportunities for diagnostics, and it has shown promise in paediatric cardiology [52, 53], offering an alternative to conventional methods. Notably, advancements in fetal cardiology have validated BSI’s effectiveness in examining haemodynamics in the fetal heart. This technique, utilised with specialised obstetric systems and probes, broadens its application beyond cardiac assessments to include fetal and maternal circulation analysis. During LV diastole, a significant phenomenon observed with BSI is the formation of intraventricular vortices (Figure 7, Video 5 ). These vortices result from the chiral geometry of the heart and the interaction of the filling jet with the LV walls and mitral valve, primarily serving to conserve kinetic energy of blood flow. This minimises shear effects on the LV walls and enhances flow efficiency during systole. Studies using BSI have examined the LV vortex characteristics in fetuses, particularly in those with coarctation of the aorta (CoA). Zhou et al. found that vortices were present in 93% of fetuses and that those with CoA had significantly larger and wider vortices compared to controls (p < 0.05). They identified positive correlations between vortex area and both LV sphericity index and isovolumetric relaxation time, while a negative correlation existed between vortex area and mitral valve size [54]. Xu et al. investigated 105 fetuses across 3 groups: normal, left-sided obstruction (LSOL), and right-sided obstruction (RSOL). They analysed blood flow patterns and vortex presence using BSI. Their results showed a higher frequency of vortex and turbulent flow in the LSOL and RSOL groups compared to controls (p < 0.01) [55].
In conclusion, BSI proves to be a more sensitive diagnostic method than traditional Doppler techniques, providing valuable insights into haemodynamic anomalies associated with various cardiac conditions, independent of insonation angle.
Conclusions
Incorporating 2D-STE, especially fetalHQ® software and BSI, into fetal cardiology centres enhances the precision of fetal cardiac assessments and improves evaluation of fetal heart function regardless of its structures. These advancements are important for making informed clinical decisions, ultimately leading to better prenatal care and outcomes for fetuses with cardiovascular anomalies. The dynamic capabilities offered by these tools mark a significant leap in the field of prenatal cardiology, reinforcing the importance of adopting these technologies in clinical practice.
Disclosures
Ethical considerations: none.
This research received no external funding.
The authors declare no conflict of interest.
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