Transversal cardiac diameter is increased in fetuses with dextro-transposition of the great arteries older than 28th weeks of gestation

Introduction

Fetal heart size (FHS) measurement is a fundamental and essential part of fetal echocardiographic examination [1], 2]. The fetal heart should be assessed during every fetal anatomical ultrasound. Nevertheless, as highlighted by prof. DeVore it would be preferable to directly measure the end-diastolic size of the heart in the four-chamber view rather than to assume that its size is increased or decreased based on the cardiothoracic area ratio [3]. According to recommendations in many guidelines, abnormal heart size values should indicate the need for a detailed fetal echocardiography [1], 4]. With the continued advancement of prenatal diagnosis, an increasing number of pregnancies complicated by fetal congenital heart defects (CHD) are being detected [5]. Cardiomegaly might be present in certain conditions, such as Ebstein anomaly and ventricular diverticulum (Table 1) [6], [7], [8]. Polish Society of Gynecologists and Obstetricians recommends the last fetal ultrasound between 28th to 32nd week of gestation. However, pregnancies may continue until the 40th week of gestation, and the longer pregnancy duration lacks ultrasound evaluation. The so-called “third trimester ultrasound” could be the last opportunity to detect a fetal heart defect. In clinical practice, the quality of late ultrasound and echocardiography depends significantly on maternal and fetal conditions, especially maternal weight, amniotic fluid volume, and fetal position. It also typically requires experience and favourable clinical skills. As presented by DeVore G. et al. fetal end-diastolic transversal width of the heart in four chamber view (4CV TW ED) might be a simple screening tool to evaluate fetuses who may have undetected dextro-transposition of the great arteries (d-TGA) [9]. Therefore, the aim of this study was to reevaluate the potential for late detection of d-TGA based on simple fetal heart measurement.

Materials and methods

This was a single-centre, retrospective study, based on a database of ultrasound and echocardiographic examination records, performed at a tertiary fetal cardiology center. Fetal ultrasound scans and fetal echocardiographic examinations were conducted by fetal medicine specialists using the Samsung HERA w10, GE Voluson E8, GE Voluson 10, and Phillips iU22.

Results

Control group

The age of the fetuses ranged from min. 18 to max. 37 weeks of gestation according to fetal biometry in singleton pregnancies. Of 3,553 records for estimation of 4CV TW ED nomograms 1,154 healthy fetuses met inclusion criteria and were included in the control group.

The regression equation for 4CV TW ED as a function of GA in weeks was:

4 CV TW ED = GA  in weeks × 0.7 + 8.2   mm   0.95   C . I .   r = 0.9108   p < 0.001 .

Linear regression demonstrated statistically significant correlation between 4CV TW ED and GA.

Z-score values of 4CV TW ED were calculated according to DeVore [10] and presented in Figures 1 and 2 and Table 2.

Figure 1:

Scatter graph of integrated normal 4CV TW ED of singleton healthy fetuses between 18th and 37th week of gestation.

Figure 2:

Normal values of 4CV TW ED of singleton healthy fetuses between 18th and 37th week of gestation using fractional polynomial regression analysis.

Table 2:

Normal 4CV TW ED during gestation presented as Z-scores.

GA, week	No. of fetuses	Mean	−2 Z-score	−1 Z-score	+1 Z-score	+2 Z-score
18	35	20	18	19	22	23
19	28	21	17	19	23	25
20	48	22	18	20	24	26
21	30	22	20	21	24	25
22	41	23	18	21	26	28
23	41	24	21	22	26	27
24	44	25	19	22	28	31
25	50	26	21	24	28	30
26	56	27	22	24	29	31
27	52	27	23	25	29	31
28	55	28	23	25	30	33
29	59	29	25	27	30	32
30	92	29	25	27	32	34
31	72	30	26	28	32	34
32	73	31	27	29	32	34
33	63	31	28	30	33	35
34	57	32	29	31	34	36
35	47	33	29	31	35	37
36	33	34	30	32	36	37
37	40	34	30	32	37	39

4CV TW ED in D-transposition of the great arteries fetuses-study group

There were 74 fetuses with d-TGA, without extracardiac malformations, between 18th and 40th weeks of gestation. These 74 fetuses had 152 fetal echocardiographic examinations (range 1–7). 63 cases had 128 echocardiographic examinations performed between 28th to 40th week of gestation. There were 18 cases of d-TGA had additionally small ventricular septal defect. There were 43 male and 20 female fetuses. In the study group 43 cases (68 %) presented 4CV TW ED measurement greater than +2 Z-score fitted to gestational age [Figure 3]. Mean gestational age at birth was 38 ± 1 week. There were 34 (54 %) cesarean sections, 28 (44 %) vaginal deliveries and 1 (1 %) forceps delivery. Mean birth weight was 3,257 ± 452 g. Median Apgar score for 1st and 5th minute was 9 and 9. Data for Rashkind procedure was available for 47 cases (75 %).

Figure 3:

4CV TW ED values of d-TGA cases on 0.95 CI scatter graph. 30 cases (68 %) of d-TGA cases presented increased 4CV TW ED measurement during pregnancy according to normal values presented in Table 1.

Baloon atrial septostomy

Of these 47 cases Rashkind procedure during first 24 h after birth was performed in 30 (63 %) cases. Of these 30 cases who had Rashkind procedure, 23 cases (76 %) had 4CV TW ED value greater than Z-score +2 fitted for GA during pregnancy and 7 (23 %) cases had normal 4CV TW ED (Figure 4). Of 17 cases who did not have Rashkind procedure, 9 (53 %) cases had 4CV TW ED value greated than Z-score +2 fitted for GA and 8 (47 %) cases had normal 4CV TW ED. Increased 4CV TW ED was more frequently seen in fetuses who needed Rashkind procedure after birth, but without statistical significance (p=0.09).

Figure 4:

4CV TW ED values of d-TGA cases with and without Rashkind on 0.95 CI scatter graph. 4CV TW ED is not predictive for Rashkind procedure.

Discussion

FHS assessment can be performed in several ways [11], [12], [13], [14]. The literature includes numerous articles on fetal heart measurements [Table 3] [11], 13], [15], [16], [17], [18]. Here, we present a continuation and development of previously published study [16]. Respondek et al. in 1992 described methods for assessing the FHS by calculating the ratio of the area of the four chambers to the chest area when viewed in the same plane. Additionally, She presented a method involving the measurement of the 4CV TW ED of the heart. In this second method, dimensions are measured in the longitudinal plane of the fetal trunk divided by the 4CV TW ED diameter of the chest just above the liver [16]. In her study, fetal echocardiograms were obtained from 99 women between the 22nd and 38th weeks of pregnancy. In our another study conducted in 2018, we analyzed fetal heart measurements including ratio of heart area to chest area (HA/CA) and 4CV TW ED, and their correlation with GA. Our study group consisted of 609 fetuses, and we concluded that the hearts’ transverse diameter correlates with GA, while HA/CA ratio remained relatively constant with slight increase as GA progressed [18]. 4CV TW ED was found to be a simple method for measuring FHS (Figure 4). As shown in our new nomograms, the 4CV TW ED correlates with GA (r=0.91). Our nomograms presented the Z-scores of 4CV TW ED between weeks 18 and 37 of gestation and can be used in clinical practice to confirm normal FHS. For further analysis, dimensions above Z-score +2 were considered increased. These nomograms may be useful in evaluating both normal and abnormal fetuses and in assessing the progression of heart defect.

Figure 5:

Four-chamber view of fetal heart. The same time 4CV TW ED (measurement D1), longitudinal fetal heart diameter, heart area and chest area measurements may be obtained.

CHD are the most common congenital defects. Depending on type of defect, study population, and geographic variations, the prevalence of CHD ranges from 3 to 12 per 1,000 pregnancies [19], 20]. Since the 1980s, echocardiographic examination has become the most important technique for the prenatal detection and diagnosis of CHD. Every fetus with CHD, particularly those with abnormal fetal heart structure, has its own unique haemodynamic physiology. In these cases, cardiac remodeling may depend on the type of defect and haemodynamic stability of the fetus. Known patterns of remodeling include changes in shape (response to pressure overload), myocardial hypertrophy (response to pressure overload), cavity dilation (improving contractility as response to volume overload) or hypoplasia. Cardiac remodeling in structure and shape is usually correlated with changes in heart function. This process can lead to heart dysfunction, which may then affect systolic and/or diastolic function [21], [22], [23]. Mild cardiomegaly defined as 4CV TW ED greater than Z-score +2 for GA, may indicate fetal heart remodeling as a compensatory response. In cases of d-TGA abnormal ventriculo-arterial connections results in pathological conditions for both the left and right ventricles, which normally pump blood to the correct parts of the fetus. This type of response, including myocardial hypertrophy, may increase fetal inotropic capability, and in some cases, protect the fetal cardiovascular system from increased intracardiac pressure and circulatory failure caused by abnormal fetal heart anatomy. However, future, more profound studies are needed.

In 1984, Jeanty and colleagues created nomograms of transverse and longitudinal diameters of the fetal heart, which were useful in diagnosis various congenital anomalies [15]. They developed nomograms for 12–40 weeks of gestation the mean value of 4CV TW ED increases by approximately 1–2 mm each week, which was also confirmed by our study. The highest value recorded in the range of 18–37 weeks was 45 mm located at the 95 percentile. In our research, the highest value was also observed at 37 weeks, which was 39 mm, located in Z-score +2. The lowest value in Jeanty and other studies was 10 mm, located in 5 percentile, examined in 18 weeks. In contrast, we observed 12 mm in 18 weeks, located under Z-score −2. These dissimilarities likely have no significant clinical value.

According to ISUOG guidelines, FHS measurement is recommended between 18 and 22 weeks of pregnancy. However, as we have demonstrated, examining the fetal heart in the third trimester of pregnancy, particularly near term, is an important component of prenatal diagnosis and may be even considered mandatory [24]. A similar result was presented by DeVore et al., suggesting that the late third trimester could be the last chance not to miss d-TGA cases [9]. Some signs of circulatory failure in the fetus may appear at the end of pregnancy, often preceded by heart dysfunction and remodeling, which can be detected through echocardiographic examination [25]. Moreover, not all CHD are detected during second-trimester ultrasound. Abnormal fetal heart dimensions could potentially help to identify patients who will require further specialized evaluation and both prenatal and postnatal care [26]. Certain forms of heart defect, such as Ebstein’s anomaly, are particularly associated with cardiac enlargement. Nevertheless, diagnosis of Ebstein’s anomaly is relatively straightforward compared to the d-TGA. Diagnosing d-TGA requires obtaining images of the outflow tracts and visualizing the ventriculo-arterial connections. The prenatal detection rate of d-TGA in obstetrical ultrasound varies between 50 and 75 %, depending on the center and the examiner. Because many examiners are not comfortable with the outflow tract examination, as demonstrated in our study, 4CV TW ED may serve as a screening tool for further echocardiographic evaluation (Figure 5). This simple method identified increased 4CV TW ED values in 68 % of d-TGA. Mild cardiomegaly is often the only feature visible in the four-chamber view of fetal d-TGA. The prenatal detection of d-TGA is crucial for several reasons: medical (it may be beneficial for the newborn), legal (in case of late postnatal detection and newborn transportation to referral center, one may avoid problem of malpractice, as the newborn eventually would be appropriately treated) and family-related (in cases where the mother wishes to terminate the pregnancy based on prenatal diagnosis). For d-TGA, prenatal detection is particularly valuable due to the urgent need for balloon atrial septostomy after birth in about half of the cases. Missing the prenatal diagnosis may lead to postnatal hemodynamic deterioration, hypoxia and an unfavorable prognosis. The detection of CHD can also be used to assess the quality and experience of the primary care obstetrician performing routine ultrasound scans.

Advances in ultrasound technology have made it possible to detect congenital heart defects as early as the first trimester or between 18 and 20 weeks of gestation. Abnormal heart position in the chest (such as dextrocardia), abnormal heart axis (such as zero axis or 90° axis), or abnormal four-chamber view or three-vessels view may suggest the presence of CHD. The detection rate of CHD in routine obstetric ultrasound is around 40 % in low-risk populations [27]. Numerous factors can hinder or distort the examination, but there is a significant difference between basic obstetrical ultrasound and targeted fetal echocardiography. In specialized centers, the detection rate of CHD increases with fetal echocardiography. Image quality substantially decreases with increasing maternal BMI, and detection rate is unlikely to exceed 20 % in such cases [28]. Additionally, fetal position can affect the accuracy of CHD diagnosis [29]. Our simple 4CV TW ED measurement was incorrect in up to 68 % of d-TGA cases. This suggests that 4CV TW ED could be an effective method for indicating the need for further targeted echocardiographic examination in the third-trimester ultrasonography. Prenatal diagnosis improves the quality of perinatal care and allows for better preparation for a complicated postnatal period [30], 31]. The Polish Society of Gynecologists and Obstetricians recommends the last fetal anatomical ultrasound between 28th to 32nd week of gestation. They recommend assessing FHS, noting that the heart area should be about one-third of the fetal thorax area [32]. In case of d-TGA, the heart-to-chest area ratio may still be within normal values. The 4CV TW ED method seems much quicker and easier, making it especially useful for late scans after 28 weeks. In this context, our method could have a potential impact on d-TGA detection because even an inexperienced sonographer can easily classify a fetus to high-risk (the group that need further echocardiographic evaluation) using simple graph estimation. There are many causes of fetal heart mild cardiomegaly. One potential cause is d-TGA, but regardless of the underlying cause, all cases of cardiomegaly should be further evaluated with targeted fetal echocardiography. A similar finding was firstly presented by DeVore et al., although in this study, they focused on the Tetralogy of Fallot [33]. Our findings suggest that even simple ultrasound machines-without special fetal echocardiography software (such as 4D scans or artificial intelligence) [34], 35] – remain essential in daily practice for CHD screening. Given its potential clinical value, 4CV TW ED measurement could be incorporated into every fetal ultrasound examination, especially after the 28th week of gestation.

An interesting observation was that fetuses with d-TGA who showed cardiomegaly prenatally more often required an urgent Rashkind procedure after birth. The prenatal prediction of the need for an urgent Rashkind procedure in the context of fetal d-TGA has been studied before. However, 4CV TW ED was not as satisfactory a predictor as other parameters and did not present statistical significance [36], [37], [38], [39] (Supplementary 1).

Conclusions

4CV TW ED measurement is a simple parameter that directly shows fetal heart size. Using 4CV TW ED measurement during third-trimester scans as a cardiac screening tool in obstetric practice may help to detect d-TGA and indicate the need for further echocardiographic examination in case of d-TGA suspicion. However, 4CV TW ED was not useful in predicting the necessity for a neonatal Rashkind procedure.