Doppler assessment of fetal aortic isthmus blood flow in two different sonographic planes during the second half of gestation

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1 Ultrasound Obstet Gynecol 2005; 26: Published online in Wiley InterScience ( DOI: /uog.1955 Doppler assessment of fetal aortic isthmus blood flow in two different sonographic planes during the second half of gestation M. DEL RÍO,J.M.MARTÍNEZ, F. FIGUERAS, M. BENNASAR, M. PALACIO, O. GÓMEZ, O. COLL, B. PUERTO and V. CARARACH Department of Obstetrics and Gynecology, ICGON, Hospital Clinic, University of Barcelona, Barcelona, Spain KEYWORDS: aortic arch; fetal aortic isthmus; intraclass correlation coefficient; reliability of results; three vessels and trachea view ABSTRACT Objective To compare the reliability of Doppler blood flow measurements of the fetal aortic isthmus (AoI) according to whether the sampling plane is obtained from the traditional longitudinal aortic arch (LAA) view or the more recently described three vessels and trachea (3VT) view of the fetal upper mediastinum. Methods Doppler blood flow measurements of pulsatility index (PI), resistance index (RI), peak systolic (PSV), enddiastolic (EDV) and time-averaged maximum (TAMXV) velocities were performed in the AoI of 40 fetuses between 24 and 36 weeks of gestation. All measurements were sampled in two different sonographic planes of the AoI: the LAA view, at a few millimeters beyond the origin of the left subclavian artery, and the 3VT view, just before the V-shaped junction of the aortic and ductal arches. All scans were performed by the same observer. The reliability of Doppler blood flow measurements was assessed by calculating intraclass correlation coefficients (ICCs) and limits of agreement between the two different sonographic sites evaluating the AoI. Results Mean values of PI, RI, PSV, EDV and TAMXV were similar in the LAA and 3VT views. The PI and vascular velocities were reliably measured from both sonographic sites. ICCs for variability of measurements were 0.78, 0.63, 0.63, 0.60 and 0.55 for PI, RI, PSV, EDV and TAMXV, respectively. Limits of agreement revealed minimal disagreement between the two sites of evaluation of the AoI for all measurements. Conclusions On the basis of our observations, Doppler blood flow measurements across the fetal AoI can be reliably obtained from both the 3VT and the traditional LAA sonographic views. Since the transverse upper thoracic 3VT plane is achievable in most fetal positions, Doppler study of the AoI appears to be easier than expected. Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION The aortic isthmus (AoI) is the vascular segment located between the origin of the left subclavian artery and the aortic end of the ductus arteriosus. Since the fetal circulation is based on two systems arranged in parallel and a shunt is defined as the juncture of two points of a network diverting part of the flow, the AoI has recently been suggested to be the only arterial shunt or connection between the right and left fetal vascular systems instead of the ductus arteriosus 1. Certainly, as Fouron et al. state, blood flow through the ductus arteriosus should be considered physiological in fetal life and not as blood diverted from the right circulation to the left. However, retrograde blood flow in the AoI would always represent abnormal flow ejected by the right ventricle into a vascular territory usually perfused by the left ventricle 1. Several experimental 2 4 and clinical 5,6 studies have demonstrated the usefulness of the AoI Doppler flow pattern as an indicator of fetoplacental hemodynamic disturbances, providing useful information on global fetal cardiocirculatory dynamics 7,8. Other authors have suggested that AoI morphology should be integrated into the routine fetal cardiac examination, in order to improve the detection rate of aortic arch abnormalities 9,10.Such increasing interest in evaluation of the AoI blood flow has motivated the study and establishment of normal values Correspondence to: Dr M. Del Río, Urgel , 1 b, Barcelona, Spain ( maria331973@hotmail.com) Accepted: 16 November 2004 Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 Fetal aortic isthmus blood flow measurement 171 of different Doppler flow parameters 11,12. However, Doppler evaluation of the fetal AoI has been regarded as being difficult to perform since the longitudinal aortic arch (LAA) view is not always obtainable and is highly dependent on the level of expertise of the examiner as well as on fetal position. To the best of our knowledge, all studies of the AoI have been performed using the standard LAA view. We propose the recently described three vessels and trachea (3VT) view of the fetal upper mediastinum 13 as a valid sonographic plane to measure Doppler flow parameters of the AoI. The aim of the present study was to examine the reliability of AoI blood flow impedance indices and velocity measurements according to sampling plane. METHODS Our study population comprised 40 consecutive women with singleton pregnancies undergoing either routine second- or third-trimester scans. Inclusion criteria were: (1) gestational age confirmed by sonography in the first trimester, (2) absence of structural malformations or chromosomal abnormality and (3) normal fetal growth (> 10 th and < 90 th percentile growth curve) with normal umbilical artery blood flow pattern. The research protocol was approved by the local ethics committee and all subjects gave their informed consent. Image-directed pulsed and color Doppler equipment (Aspen Advanced, Acuson, Mountain View, CA, USA) with a multifrequency sector array transabdominal transducer was used. All Doppler measurements were sampled at random at two different sonographic planes of the aortic arch, without the examiner being aware of the previous measurements in either site. In the traditional LAA view, the range gate was placed a few millimeters beyond the origin of the left subclavian artery, as described by Bonnin et al. 3. The 3VT view was obtained at the level of the fetal mediastinum by moving the transducer obliquely cephalad from the fourchamber view, as described by Yagel et al. 13. At this point, the pulmonary trunk, ductus arteriosus, aortic arch, AoI and superior vena cava are clearly demonstrated, with the aortic and ductal arches forming a V-configuration pointing to the posterior spine. The characteristic V-shape shows the convergence of the AoI and the arterial duct, making it easy to identify where the range gate must be placed along the aortic arch (Figure 1). The color Doppler maximal velocity setting was adjusted to high velocities so that the great vessels blood flow was homogeneous in color and showed no aliasing. The high-pass filter was set at 50 Hz and energy output levels were lower than 50 mw/cm 2. The scanning plane was adjusted to obtain an insonation angle as close to 0 as possible, and always < 30. Recordings were performed during the absence of fetal movements. Flow velocity waveforms were recorded three times from both sonographic planes, and peak systolic (PSV), end-diastolic (EDV) and time-averaged maximum (TAMXV) velocities were noted. Five to seven consecutive Figure 1 Three vessels and trachea view showing both the aortic isthmus (AoI) and the ductus arteriosus joining in a V-shape. Color Doppler encodes flow in blue for both vessels, and pulsed Doppler shows the typical flow velocity waveform in the AoI. waveforms were analyzed each time and the results averaged, using a conventional microcomputerized program linked to the equipment that calculated the pulsatility (PI) and resistance index (RI) as PSV EDV/TAMXV and PSV EDV/SV, respectively. Hard copies of each recording were encoded on a printer device. Statistical analysis Differences between measurements of AoI velocities and impedance indices (PI and RI) performed at each particular site were compared using paired t-tests. Pearson s linear coefficient of correlation was used to calculate the correlation between the impedance indices and the gestational age. A sample size estimation was made for reliability assessment by means of an intraclass correlation coefficient (ICC) with α = 0.05 and β = We aimed for an optimum reliability of at least 0.75 and accepted a reliability of 0.4 as a criterion for moderate agreement 15. Hence, we defined H 0 : ρ = 0.4 and H 1 : ρ = 0.75, meaning a sample size of 33 cases. In order to allow for missing data, a total cohort of 40 cases was finally designed. To assess reliability between Doppler flow measurements of the AoI at the two different sites all scans were performed by a single examiner in order to minimize sources of variability other than the sampling sonographic plane. Reliability between measurements in both sonographic planes was assessed by the ICCs and their 95% CIs. A two-way mixed model (targets conceived as random samples) was chosen for agreement analysis. The

3 172 Del Río et al. ICC is a measure of concordance for continuous variables, correcting correlation for systematic bias and measuring the extent to which those variables will yield the same score when assessed in different locations. An ICC of 1 for repeated measurements indicates perfect reproducibility between measurements, while a value of 0 is interpreted as reproducibility that is no better or worse than that expected by chance. We considered repeated measurements with an ICC value between 0.4 and 0.7 as being clinically useful 15. The degree of agreement was also examined using the limits of agreement method or Bland Altman test 16,17, which allows calculation of the range in which 95% of the disagreement between observers is likely to occur and is defined as the mean difference ± t n 1 SD, where t n 1 is the probability point of the t distribution with n 1 degrees of freedom, and SD the standard deviation of the mean difference. Another test used to examine the degree of agreement was the Passing and Bablok regression 18, a procedure that tests the hypothesis at constant and proportional differences between two measurement methods. Values of P < 0.05 were considered to be significant for the above mentioned tests. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS 10.1, SPSS Inc., Chicago, IL, USA). RESULTS Satisfactory flow velocity waveforms of the AoI for optimal analysis were successfully obtained in both sonographic planes in all cases. The mean maternal age in the study group was 30.5 ± 5.3 years and the median gestational age was 31.6 (range, 24 36) weeks at the time of the scan. The AoI PI (r = 0.05, P = 0.75 and r = 0.06, P = 0.72) and the AoI RI (r = 0.02, P = 0.91 and r = 0.13, P = 0.45) were found to be independent of gestational age at both 3VT and LAA sites, respectively. AoI PI values in each site along the pregnancy are shown in Figure 2. No significant differences were found when comparing the mean values of velocities and indices between the 3VT and LAA sonographic planes of the AoI, these results being provided in Table 1. Doppler blood flow measurements within the two different sonographic planes of the AoI AoI PI Gestational age (weeks) Figure 2 Paired fetal aortic isthmus pulsatility index (AoI PI) values at the three vessels and trachea view (ž) and the longitudinal aortic arch view (+) by gestational age in weeks. were shown to be highly repeatable, as measured by the mean ICCs and 95% CIs, which are shown in Table 2. In the Bland Altman plot the mean difference between paired measurements of the AoI PI was 0.04 and the 95% limits of agreement were 0.37 to 0.45 (Figure 3). The Passing Bablok regression showed neither constant nor proportional significant differences between both 3VT and LAA measurements (Figure 4). DISCUSSION Recently, the utility of the study of fetal AoI blood flow has been widely discussed, and appears to be a useful indicator Table 2 The reliability of measurements of pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (TAMXV) as measured by the mean intraclass correlation coefficient (ICC) and its 95% CI (n = 40) Parameter Mean ICC 95% CI PI RI PSV EDV TAMXV Table 1 Descriptive statistics: mean (SD) and range for impedance indices and absolute velocities measured at the three vessels and trachea (3VT) and longitudinal aortic arch (LAA) views on the aortic isthmus (n = 40) 3VT view LAA view Parameter Mean (SD) Range Mean (SD) Range P PI 2.55 (0.30) (0.33) RI 0.91 (0.02) (0.03) PSV (cm/s) 1.03 (0.22) (0.25) EDV (cm/s) 0.09 (0.02) (0.03) TAMXV (cm/s) 0.36 (0.06) (0.10) EDV, end-diastolic velocity; PI, pulsatility index; PSV, peak systolic velocity; RI, resistance index; TAMXV, time-averaged maximum velocity.

4 Fetal aortic isthmus blood flow measurement 173 AoI PI LAA view AoI PI 3VT view SD 0.37 Mean SD Average of AoI PI LAA view and AoI PI 3VT view Figure 3 Bland Altman plot of the difference vs. the mean of paired measurements of the aortic isthmus pulsatility index (AoI PI) in the two different sonographic planes. 3VT, three vessels and trachea; LAA, longitudinal aortic arch. AoI PI LAA view AoI PI 3VT view Figure 4 Passing-Bablok (P-B) regression showing no significant deviation from linearity (P > 0.10) , theoretical P-B regression line with 95% interval confidence;, observed P-B regression line. 3VT, three vessels and trachea; AoI PI, aortic isthmus pulsatility index; LAA, longitudinal aortic arch. of fetoplacental hemodynamic disturbances 7,8 as well as of fetal aortic arch abnormalities 9,10.Inmanycenters, evaluation of the aortic arch in the traditional long-axis view is regarded to be one of the most difficult and timeconsuming parts of the fetal heart examination. Aware of such difficulty, and taking into account that the 3VT view has already been accepted as an accurate method with which to examine the aortic arch in a transverse view 13,we considered this plane as an easier and less time-consuming way of measuring different Doppler parameters of the AoI. There is no doubt that anatomically the AoI is being equally assessed in both planes as long as the gate range is placed in the distal aorta of the 3VT view, at the point at which the aortic and ductal arches converge in a V- configuration, making sure the gate sample is placed near the apex of the V-shape (Figure 1). The present study of reliability was designed in order to demonstrate that Doppler blood flow measurements in both sonographic planes are repeatable. We used the ICCs to assess reliability since there is enough consensus in the scientific literature to consider that values for ICC between 0.4 and 0.7 or > 0.7 reflect low or very low measurement error, respectively 15. Our study found an ICC value above 0.7 for PI, and values higher than 0.55 for the remaining parameters. These values reveal a more than acceptable repeatability and reproducibility of these parameters in general, and a very good one for the PI in particular. At present, the small diameter of the AoI precludes measurement of actual blood flow volume and so we propose using the PI, which is likely to be the best index to assess blood flow through fetal vessels. Indeed, the PI is angle-independent and analyzes blood flow over time taking into account the downstream impedance during the whole cardiac cycle. Therefore, the PI is particularly useful for detecting fetal hemodynamic changes throughout pregnancy, being equally sensitive to any alteration of the net blood flow in the AoI, such as absent or reversed end-diastolic flow. Others 3 have also proposed using the PI to assess the AoI and, more recently, Ruskamp et al. 12 describe a semiqualitative parameter, the isthmic flow index (IFI), which would be particularly sensitive to changes in the amount and direction of diastolic flow. This is a practical and intuitive system, since IFI values are negative if retrograde diastolic flow is greater than systolic flow, between 0 and 1 if there is reverse diastolic flow but less dominant than systolic forward flow, and higher than 1 if the flow is mainly antegrade during the whole cycle. However, we have found no single case with reversed or absent flow in our cohort of normal cases, whilst absent or reversed flow have only been detected in growth-restricted fetuses with abnormal umbilical artery blood flow in the ongoing study we are performing. In such cases, the longitudinal assessment of the PI would be an easier method to detect AoI flow deterioration than would the IFI, while the qualitative assessment of absent or retrograde flow would be performed in the same way as is usually performed for umbilical artery or ductus venosus waveform analysis. The PI would increase substantially, being much higher than the extreme percentiles. Once this quantitative assessment has been performed, the flow waveform might be qualitatively assessed, indicating the presence of a predominant retrograde net blood flow. Although the fetal aortic arch morphology has been evaluated from both the longitudinal and transverse views, to the best of our knowledge this is the first study to demonstrate that both sonographic planes of the fetal AoI, the 3VT and LAA view, can be reliably used to acquire Doppler blood flow measurements at this fetal vascular segment. The introduction of this transverse upper thoracic plane offers an easy and accurate method for identifying and studying the blood flow of the AoI in most fetal positions, reducing the time that is required to perform them. It would be especially useful later in gestation, when the spine is calcified and

5 174 Del Río et al. visualization of the aortic arch is technically more difficult and challenging, making the study of this segment of the aorta accessible to the majority of examiners. The real significance of an abnormal AoI PI needs further investigation and is the subject of an ongoing study we are performing in our unit. REFERENCES 1. Fouron JC. The unrecognized physiological and clinical significance of the fetal aortic isthmus. Ultrasound Obstet Gynecol 2003; 22: Fouron JC, Teyssier G, Maroto E, Lessard M, Marquette G. Diastolic circulatory dynamics in the presence of elevated placental resistance and retrograde diastolic flow in the umbilical artery. A Doppler echographic study in lambs. Am J Obstet Gynecol 1991; 164: Bonnin P, Fouron JC, Teyssier G, Sonesson SE, Skoll A. Quantitative assessment of circulatory changes in the fetal aortic isthmus during progressive increase of resistance to umbilical blood flow. Circulation 1993; 88: Fouron JC, Skoll A, Sonesson SE, Lessard M, Pfizenmaier M, Jaeggi E. Relationship between the flow through fetal aortic isthmus and cerebral oxygenation during placental circulatory insufficiency. Am J Obstet Gynecol 1999; 181: Sonesson SE, Fouron JC. Doppler velocimetry of the aortic isthmus in human fetuses with abnormal velocity waveforms in the umbilical artery. Ultrasound Obstet Gynecol 1997; 10: Fouron JC, Gosselin J, Amiel-Tison C, Infante-Rivard C, Fouron C, Skoll A, Veilleux A. Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years. Am J Obstet Gynecol 2001; 184: Makikallio K, Jouppila P, Rasanen J. Retrograde net blood flow in the aortic isthmus in relation to human fetal arterial and venous circulations. Ultrasound Obstet Gynecol 2002; 19: Makikallio K, Jouppila P, Rasanen J. Retrograde aortic isthmus net blood flow and human fetal cardiac function in placental insufficiency. Ultrasound Obstet Gynecol 2003; 22: Achiron R, Zimand S, Hegesh J, Lipitz S, Zalel Y, Rotstein Z. Fetal aortic arch measurements between 14 and 38 weeks gestation: in-utero ultrasonographic study. Ultrasound Obstet Gynecol 2000; 15: Nomiyama M, Ueda Y, Toyota Y, Kawano H. Fetal aortic isthmus growth and morphology in late gestation. Ultrasound Obstet Gynecol 2002; 19: Fouron JC, Zarelli M, Drblik SP, Tawile C, Lessard M. Normal flow velocity profile through the fetal aortic isthmus. Am J Cardiol 1994; 74: Ruskamp J, Fouron JC, Gosselin J, Raboisson MJ, Infante- Rivard C, Proulx F. Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy. Ultrasound Obstet Gynecol 2003; 21: Yagel S, Arbel R, Anteby EY, Raveh D, Achiron R. The three vessels and trachea view (3VT) in fetal cardiac scanning. Ultrasound Obstet Gynecol 2002; 20: Walter SD, Eliasziw M, Donner A. Sample size and optimal designs for reliability studies. Stat Med 1998; 17: Fleiss JL. Statistical Methods for Rates and Proportions (2nd edn). John Wiley: New York, NY, Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1 (8476): Bland JM, Altman DG. Applying the right statistics: analyses of measurement studies. Ultrasound Obstet Gynecol 2003; 22: Passing H, Bablok W. A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, Part I. J Clin Chem Clin Biochem 1983; 21: