Reference ranges for two-dimensional echocardiographic

Transcription

1 Ultrasound Obstet Gynecol 2000; 15: 219±225. Reference ranges for two-dimensional echocardiographic examination of the fetal ductus arteriosus G. MIELKE* and N. BENDA² Departments of *Obstetrics and Gynaecology and ²Medical Biometry, University of Tuebingen, Tuebingen, Germany KEYWORDS: Cardiovascular malformations, Ductus arteriosus, Fetal heart, Pulmonary artery ABSTRACT Objectives To establish reference ranges for 2D-echocardiographic examination of the fetal ductus arteriosus and its relationship to the main pulmonary artery and the aorta. Methods A prospective cross-sectional echocardiographic study was performed in 222 normal fetuses from 13 to 41 weeks of gestation using high resolution/color Doppler ultrasound equipment. Results Gestational age-specific reference ranges are given for the diameter of the pulmonary valve anulus, diameter of the ductus arteriosus at its beginning, middle, and end, ductal length, ductal diameter-to-pulmonary valve anulus diameter ratio, and the spatial relationship of the ductus arteriosus to the main pulmonary artery and to the aorta. Conclusions The presented data derived from a study group of 222 normal fetuses provide in-vivo insights into the morphology of the ductus arteriosus and its relationship to the adjacent vessels. The reference ranges may be helpful in prenatal diagnosis of cardiac malformations and abnormalities of the ductus arteriosus, such as obstruction or aneurysm from 13 to 41 weeks of gestation. INTRODUCTION In fetal life, the majority of right ventricular output bypasses the high resistance pulmonary circuit via the ductus arteriosus (DA). Abnormalities of the DA can be demonstrated prenatally by 2D-echocardiography in cases of cardiac malformations, ductal obstruction, and ductal aneurysm 1±4. Furthermore, determination of ductal diameters may be helpful in the estimation of volume of blood flow across the fetal ductus arteriosus 5. However, only few reports of sonographic imaging of the fetal DA and its relationship to the adjacent vessels have been published. For this reason, a prospective cross-sectional study was performed in order to establish reference ranges for 2D-echocardiographic examination of the fetal DA. METHODS Population In this cross-sectional study 2D- and Doppler-echocardiography was performed by one physician (G.M.) in 222 normal singleton fetuses from 13 to 41 (median 25) weeks of gestation. Criteria of inclusion in the study were: gestational age confirmed by sonographic biometry in early pregnancy, no malformation, appropriate for gestational age in size, normal amniotic fluid volume, fetal rest, fetal apnoea, healthy mother without hypertension, proteinuria, smoking or drug intake±including tocolytics, prostaglandin synthetase inhibitors or glucocorticoids± which might influence the cardiovascular system. Patients gave their informed consent. Ultrasound equipment In all cases, high-resolution ultrasound equipment (ATL HDI 3000/ATL UM9 HDI, Advanced Technology Laboratories, Washington, DC, USA) with 4±2 MHz, 5±3 MHz, and 7±4 MHz broadband transducers was used. The spatial peak temporal average intensities were below 100 mw/cm 2 in all cases. Echocardiography Two-dimensional imaging of atrial inflow, four-chamber view, long-and short axis views of the ventricular outflow tracts and great arteries, aortic arch and DA was followed by color Doppler imaging. Views of the main pulmonary artery and the DA were obtained from an oblique transverse plane of the fetal thorax 6 (Figures 1±4) and a Correspondence: PD Dr Gunther Mielke, Department of Obstetrics and Gynaecology, Prenatal Medicine, University of Tuebingen, Schleichstrasse 4, Tuebingen, Germany ( grmielke@med.uni-tuebingen.de) Received , Revised , Accepted ORIGINAL PAPER 219

2 Figure 3 Transverse scan of the fetal thorax showing the pulmonary arteries and the DA. Determination of the ductal diameter at its beginning (1), middle (2), and end (3), and measurement of the ductal length (4). Determination of deviation of the DA from the long axis of the main pulmonary artery (MPA) is shown in this plane. RPA ˆ right pulmonary artery, LPA ˆ left pulmonary artery, DA ˆ ductus arteriosus, DAO ˆ descending aorta, S ˆ spine. Figure 1 Power Doppler imaging of the pulmonary arteries and the ductus arteriosus (arrow) in the transverse scan of the fetal thorax. RV ˆ right ventricle, MPA ˆ main pulmonary artery, RPA ˆ right pulmonary artery, LPA ˆ left pulmonary artery, DA ˆ ductus arteriosus, DAO ˆ descending aorta, L ˆ left, R ˆ right, S ˆ spine. sagittal scan of the fetus (short axis of the fetal heart) (Figure 5). The following anatomic features were measured in the transverse plane of the fetal thorax: pulmonary valve diameter (mm) (during systole, inner diameter, insonation perpendicular to the long axis) 7,8 (Figure 2); inner diameter of the DA at its beginning, middle, and end (mm) (insonation perpendicular to the long axis) (Figure 3); length of the DA (mm) (beginning distally of the left pulmonary artery, ending at the insertion into the descending part of the aortic arch) (Figure 3); deviation of the DA from the long axis of the main pulmonary artery (degrees) (Figure 3), deviation of less than 58 were considered as `no deviation'; angle between the DA and the aortic isthmus (degrees) (Figure 4). Diameters at the ductal beginning, middle, and end were compared. The DA-diameter (middle)-to-pulmonary valve diameter ratio was calculated. The following features were determined in the short axis view: deviation of the DA from the long axis of the main pulmonary artery (degrees) (Figure 5); angle between the DA and the descending aorta (degrees) (Figure 5). The findings were documented on videoprints. Twodimensional measurements were performed on site using the ultrasound machine's calipers. Angle determination was obtained from the videoprints. Due to fetal presentation not all measurements could be performed in all patients. Figure 2 Measurement of the diameter of the pulmonary valve anulus in the transverse scan of the fetal thorax. RV ˆ right ventricle, MPA ˆ main pulmonary artery, S ˆ spine. Figure 4 Imaging of the DA and the aortic arch (AOA). Determination of the angle between the DA and the aortic isthmus is shown in this plane. MPA ˆ main pulmonary artery, LPA ˆ left pulmonary artery, DA ˆ ductus arteriosus, DAO ˆ descending aorta, S ˆ spine. 220 Ultrasound in Obstetrics and Gynecology

3 0.9 DA diameter, middle (cm) n = Figure 7 Individual values and the calculated centiles (5, 10, 50, 90, and 95) of the diameter of the ductus arteriosus (DA) at its middle. Figure 5 Short axis view showing the aortic valve anulus (AO), right ventricle (RV), main pulmonary artery (MPA), ductus arteriosus (DA), and descending aorta (DAO). Determination of deviation of the DA from the long axis of the main pulmonary artery and determination of the angle between the DA and the descending aorta are shown in this plane. Statistical analyses Age-related quantiles were calculated according to Altman 9,10 : cubic regression either on the original or a logscale yielded the median curve y(t). Estimation of agerelated standard deviation by quadratic regression of the absolute values of the residuals and multiplying the predicted values by p p/2 yielded an estimation of agerelated standard deviation s(t). Using the statistical program GAUSS quantiles were estimated either by y(t) 1 u s(t) or by exp (y(t) 1 u s(t)) when a log-transformation was used, where u is the corresponding quantile of the standardized normal distribution. The ratios of DA-diameters were analysed after logarithmic transformation. Results were retransformed to original scale. RESULTS Diameter of the pulmonary valve anulus, DA-diameter, DA-length With advancing gestational age an increase of the diameters of the pulmonary valve anulus (Figure 6) and the DA (Figure 7) together with an increase in length of the DA (Figure 8) were found. The median ratio DA-diameter (middle)/da-diameter (proximal) was estimated as (9 confidence interval 0.988±1.011, range 0.813±1.278, n ˆ 162). A significant association between this ratio and gestational age was not found (P ˆ 0.87). The two diameters were not significantly different (P. 0.05). The median ratio DA-diameter (middle)/da-diameter (distal) was estimated as (9 confidence interval 0.965±0.985, range 0.813±1.222, n ˆ 162). A significant association between this ratio and gestational age was not found (P ˆ 0.18). These two diameters were significantly different (P, 0.05). The median ratio DA-diameter (distal)/da-diameter (proximal) was estimated as (9 confidence PV diameter (cm) n = DA length (cm) n = Figure 6 Individual values and the calculated centiles (5, 10, 50, 90, and 95) of the diameter of the pulmonary valve anulus. Figure 8 Individual values and the calculated centiles (5, 10, 50, 90, and 95) of the ductal length. Ultrasound in Obstetrics and Gynecology 221

4 1 1 Probability of DA without deviation (transverse) Probability of DA without deviation (short axis) Figure 9 Probability of a ductus arteriosus (DA) without a deviation from the long axis of the main pulmonary artery in the transverse scan of the fetal thorax with gestational age. Figure 10 Probability of a ductus arteriosus (DA) without a deviation from the long axis of the main pulmonary artery in the short axis view. interval 1.012±1.040, range 0.818±1.500, n ˆ 162). A significant association between this ratio and gestational age was not found (P ˆ 0.41). These two diameters were significantly different (P, 0.05). In summary, there was no significant difference between the diameters of the DA at its beginning and middle, but the distal diameter was significantly greater by 2. than the proximal part and the middle. The ratios were independent of gestational age. The mean ratio DA-diameter (middle)/pulmonary valve diameter was 0.67 (SD 0.1, n ˆ 206). A significant association between this ratio and gestational age was not found (P ). DA-isthmus angle (degrees) n = Spatial relationship of the DA to the main pulmonary artery and to the aorta Deviation of the DA from the long axis of the main pulmonary artery (MPA) was determined both in the transverse plane of the fetal thorax and in the sagittal plane (short axis of the fetal heart). In the transverse plane of the fetal thorax no deviation of the DA from the long axis of the MPA was seen in 4 (94/209) of cases. With advancing gestational age, the probability of a DA without deviation from the MPA decreased significantly (P, ) (Figure 9). In 5 (115/209) of cases a deviation was found. This deviation was directed dorsally to the aorta within a range of (median 308). With advancing gestational age a significant increase in the deviation was found (P ˆ 0.007). In the sagittal plane no deviation of the DA from the long axis of the MPA was seen in 48% (92/191) of cases. With advancing gestational age, the probability of a DA without a deviation from the MPA decreased significantly (P ˆ 0.015) (Figure 10). In 51.3% (98/191) of cases a caudally directed deviation of the DA from the MPA (median 228, range ) was found. In one case, the deviation was cranially directed (258). In this plane there was no significant association between the dimension of the deviation and gestational age (P ˆ 0.61). The mean angle between the DA and the aortic isthmus was (SD 9.38, range ). There was a Figure 11 Individual values and the calculated centiles (5, 10, 50, 90, and 95) of the angle between the ductus arteriosus (DA) and the aortic isthmus. DA-desc. aorta angle (degrees) n = Figure 12 Individual values and the calculated centiles (5, 10, 50, 90, and 95) of the angle between the ductus arteriosus (DA) and the descending aorta. significant association between this angle and gestational age (P, 0.001) (Figure 11). The mean angle between the DA and the descending aorta was (SD 12.58). There was a significant association between this angle and gestational age (P, 0.01) (Figure 12). 222 Ultrasound in Obstetrics and Gynecology

5 Tortuosity of the DA was not observed in the study group. DISCUSSION The study establishes gestational age-specific reference ranges for 2D-echocardiographic examination of the DA, the pulmonary valve anulus, and the spatial relationship of the DA to the main pulmonary artery and to the aorta. These ranges were derived from a prospective crosssectional study of 222 fetuses from 13 to 41 weeks of gestation. The calculated centiles for the pulmonary valve diameter are similar to the results of previous studies 11±15. However, the present data are based on examinations of more than 200 fetuses beginning from 13 weeks of gestation. In pulmonary valve stenosis, reduced diameters of the pulmonary valve anulus are observed 16. Reference ranges for cardiac dimensions in the first half of the second trimester of pregnancy are rare but increasingly important, as early diagnosis of congenital heart defects has become possible 17,18. Until now, there are no data available concerning prenatal assessment of the length of the DA. In the present study, an increase of the length of the DA with advancing gestational age was found. The data are similar to results of morphological studies 19. The few published studies concerning prenatal sonographic determination of the ductal diameter are based on a small number of cases (Tan et al , n ˆ 38; Sutton et al , n ˆ 21; Rasanen et al , n ˆ 63). In the present study, an increase of the diameter of the DA with advancing gestational age was observed. There was no significant difference between the DA-diameter at its beginning and its middle, but the diameter determined at the ductal end was 2. greater independent of gestational age. Although this difference was statistically significant, methodological problems with measurements of vessels of this small size must be taken into account. In an anatomical study, the middle/proximal DA ratio was 0.86/1 and the distal/proximal DA ratio was 0.94/1 19.In another anatomical study performed in 61 cases with an gestational age from 9 to 18 weeks, the diameter of the proximal part of the ductus was greater than the diameter of the distal part 21. In-vivo postmortem changes might explain these differences. Reference charts derived from morphological studies are often unreliable for in-vivo measurements. For example, in the present sonographic study the mean diameter of the DA at its middle determined at 40 weeks of gestation was 5.7 mm, whereas in an anatomical study it was 3 mm 19. Similar differences are found comparing the diameters of the DA and the pulmonary valve anulus determined in the present study with those of further anatomical studies 22,23. Also the DAdiameter/pulmonary valve diameter ratio differs substantially between the present sonographic study (0.67, SD 0.1) and the ratio of 0.35±0.4 in an anatomical study 23.In anatomical studies, the diameter of the DA is smaller than the diameter of the aortic isthmus 19,21,23±25, whereas in a sonographic study a significant difference could not be found 24. Postnatally, during functional ductal closure there is a rapid reduction of the DA-diameter from about 5 mm at1hofageto1±3mmat8hofage 26±28. Maturation of the ductal wall with intimal thickenings or cushions protruding into the lumen of the ductus has been described histologically. However, there is no strict relation between gestational age or birth weight and histological maturation 29. In the present study, diameters of the ductal lumen increased with advancing gestational age. The mean DA-diameter (middle)-to-pulmonary valve diameter ratio of 0.67 was not associated with gestational age. Therefore, no measurable process of ductal narrowing with advancing gestational age could be observed. Determination of the ductal diameter may be helpful in the prenatal diagnosis of intrauterine ductal closure 2,3, aneurysm of the DA 4,30 and cardiac malformations 16,31. Furthermore, the volume of blood flow across the DA and through the pulmonary vascular bed can be estimated from the addition of Doppler measurements 5. Morphologically in the fetus the DA is a direct continuation of the main pulmonary trunk, connecting to the aorta distal to the left subclavian artery. The angle formed by the DA and the aortic isthmus is acute. In contrast, the angle formed by the DA and the descending aorta is obtuse 32. In anatomical studies, the angle between the DA and the isthmus is within the range of 258 to ,33 and the angle between the DA and the descending aorta 808 to There are few sonographic studies concerning the morphological aspect of the fetal DA and its spatial relationship to the main pulmonary artery and to the aorta. In a sonographic study of 52 fetuses between 14 and 27 weeks of gestation, the mean angle between the DA and the thoracic spine was 938 (SD 68, range 858 ± 1158) 33. Controversy exists regarding the sonographic appearance of the ductal shape in the structurally normal fetal heart 1,34±36. In a study of 198 fetuses from 20 weeks of gestation onwards, an increasing ductal curvature with advancing gestational age in the oblique transverse scan of the fetal thorax was reported 37. However, in that study the ductal appearence in the sagittal plane and the spatial relationship of the DA to the main pulmonary artery and to the aorta were not taken into account. In the present study, the DA was examined both in the transverse plame of the fetal thorax and in the sagittal plane. In the transverse plane, a posteriorly directed deviation of the DA from the long axis of the main pulmonary artery was found in 5 of cases. A significantly increasing frequency and increasing dimension of the deviation with advancing gestational age were found. However, a kinking or a s-shape of the DA was not observed in the study group. In the sagittal plane, a deviation of the DA from the long axis of the main pulmonary artery was observed in 52% of cases. The deviation was caudally directed in all cases except one. A significant increasing frequency of the deviation with advancing gestational age was found. The mean angle formed by the DA and the descending aorta Ultrasound in Obstetrics and Gynecology 223

6 was (SD 12.58), similar to the results of anatomical studies 33. As in the transverse plane, ductal tortuosity was not observed. The mean angle formed by the DA and the aortic isthmus was (SD 9.38). This is within the range reported in anatomical studies. However, both sonographic and morphologic determination of this angle is difficult because of the curved shape of the aortic arch. Recent experiences of the authors have shown that the ductal course can be well demonstrated by 3D power Doppler. The ductal course has to be taken into account for accurate determination of blood flow velocities by Doppler sonography. Furthermore, in cases of severe pulmonary stenosis or atresia, changes of the ductal shape and of the angles between the DA and the aorta can be found indicating hemodynamically induced morphological adaption to left-to-right shunting across the DA in early fetal life 16,38,39. 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