Fetal cardiac axis in 1st trimester

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Fetal cardiac axis in 1st trimester

  1. 1. Ultrasound Obstet Gynecol 2010; 36: 676–681 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.8814 Defining the fetal cardiac axis between 11 + 0 and 14 + 6 weeks of gestation: experience with 100 consecutive pregnancies E. SINKOVSKAYA*, S. HORTON*, E. M. BERKLEY*, J. K. COOPER*, S. INDIKA† and A. ABUHAMAD* *Division of Maternal-Fetal Medicine of the Department of Obstetrics & Gynecology and †Epidemiology and Biostatistics Core, Eastern Virginia Medical School, Norfolk, VA, USA KEYWORDS: cardiac axis; echocardiography; fetal heart; first trimester; heart defects ABSTRACT Objective The purpose of this study was to establish normal fetal cardiac axis values during the first and early second trimesters of pregnancy. Methods This was a prospective observational cohort study in which the fetal cardiac axis was assessed during ultrasound examinations in 100 consecutive fetuses between 11 + 0 and 14 + 6 weeks of gestation. Transabdominal, and, when indicated, transvaginal, approaches were used. Intraobserver and interobserver reproducibility were calculated. Results The cardiac axis ranged from 34.5 to 56.8◦ (mean (SD) 47.6 ± 5.6◦) in 94 fetuses with normal cardiac anatomy. The fetal cardiac axis tended to be significantly higher in fetuses at 11 + 0 to 11 + 6 weeks of gestation than in fetuses at 12 + 0 to 14 + 6 weeks of gestation. Congenital heart defects were found in six out of 100 fetuses, four of which had abnormal cardiac axis values at 11 + 0 to 14 + 6 weeks of gestation. Conclusion Cardiac axis measurement is possible in the first and early second trimesters of pregnancy. The assessment of cardiac axis at an early gestational age may help to identify pregnancies at high risk for congenital heart defects. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION The ability to obtain images of the fetal heart, at an early gestational age, of sufficient clarity to diagnose cardiac malformations, was made possible by the advent of high-resolution transvaginal and transabdominal ultrasonography. Furthermore, the growing acceptance of nuchal translucency (NT) thickness measurements made between 11 and 14 weeks’ gestation to assess the risk for chromosomal abnormalities led to the identification of fetuses at high risk for major congenital heart disease (CHD)1 . Detailed evaluation of the fetal heart in early gestation may therefore allow the early detection of CHD2–4 . Evaluation of the fetal cardiac axis (CAx) is part of the fetal cardiac examination performed in the mid-second and third trimesters of pregnancy5. In this gestational age window, the normal CAx is defined at a 45◦ angle to the left of the midline with a range of plus or minus 20◦6 . Several studies have suggested fetal CAx measurement as a possible screening tool for CHD, with a reported sensitivity of 79.3% and a specificity of 97.6%7 . Left CAx deviation is largely associated with cardiac abnormalities, especially conotruncal anomalies, which are commonly difficult to detect from the four-chamber view alone8,9. It was also demonstrated that an abnormally narrow CAx with a normal cardiac position may occur in cases of cardiac anomalies10 . The specific embryologic event that results in an abnormal CAx in some fetuses with cardiac abnormalities is not currently known; however, an over-rotation of the bulboventricular loop in early embryogenesis has been proposed as the underlying mechanism6,7 . The aim of this prospective study was to establish normal fetal CAx values during the first and early second trimesters of normal pregnancy as well as to determine if routine assessment of the CAx in early gestation may identify fetuses with CHD. Correspondence to: Dr E. Sinkovskaya, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 825 Fairfax Avenue, Suite 310, Norfolk, VA 23507, USA (e-mail: sinkove@evms.edu) Accepted: 18 August 2010 Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER
  2. 2. Fetal cardiac axis 677 METHODS This study was approved by the Human Investigation Board of the Eastern Virginia Medical School (EVMS), and was conducted at EVMS’s Division of Maternal-Fetal Medicine ultrasound laboratories. After receiving writ- ten informed consent, a total of 100 consecutive women, ≥ 18 years of age and with singleton pregnancies between 11 + 0 and 14 + 6 weeks’ gestation, were enrolled in the study. Exclusion criteria included maternal obesity (body mass index (BMI) ≥ 30) and refusal to participate in the study. Transabdominal ultrasound was initially performed in all study patients to examine the fetus. The transvaginal approach was used if visualization of the fetus (because of its position) was insufficient or if suboptimal transabdom- inal images were obtained. All ultrasound examinations were performed using Voluson 730 Expert and Voluson E8 ultrasound equipment (GE Healthcare Ultrasound, Zipf, Austria) with a 4–8-MHz transabdominal trans- ducer and a 5–9-MHz transvaginal transducer. The ultrasound examination included a crown–rump length (CRL) measurement of the fetus followed by a NT measurement when requested by the patient. The CAx was assessed by obtaining an axial view of the fetal chest at the level of the four-chamber view with a single full rib visible on each side and then by measuring the CAx as the angle of two lines. The first line started at the spine posteriorly and ended in mid-chest anteriorly, bisecting the chest into two equal halves. The second line traced the long axis of the heart and ran through the interventricular septum (IVS) (Figure 1). Color or power Doppler was occasionally used to confirm the location of the IVS, which then guided the accurate placement of the intersecting angle line when the IVS was not clearly imaged on two-dimensional (2D) ultrasound (Figure 2). In each case one of the authors (E.S.) measured the CAx three times. The average of these three measurements was used to represent the CAx for each participant. In addition, the CAx was also measured by another author (S.H.). Both investigators were blinded to each other’s results. In addition to measurement of the CAx, an evaluation of the fetal heart was performed, which included imaging of the four-chamber view and the outflow tracts. All patients underwent ultrasound examination during the second and/or third trimesters, which included a targeted evaluation of fetal anatomy, fetal echocardiography and CAx measurement. Postnatal follow up was obtained for all patients by reviewing the medical records and by telephone interview. Statistical analysis Statistical analysis was performed using the SAS 9.1.3 software (SAS, Cary, NC, USA). Normal distribu- tion of continuous variables was assessed using the Kolmogorov–Smirnov test. Continuous variables are reported as mean ± SD or as median (range), depending on the data distribution. Categorical data are expressed Figure 1 Cardiac axis measurement in a fetus at 13 + 4 weeks’ gestation. The angle shown in this case is 43◦ (normal). LV, left ventricle; RV, right ventricle; S, spine. as frequencies and percentages. A P < 0.05 was consid- ered significant. The Tukey test was applied to examine the variance of the CAx at different gestational ages. The effect of CRL on the CAx was evaluated using regres- sion analyses. Repeated-measures ANOVA was used to assess intraobserver variations. Interobserver repro- ducibility was evaluated by calculating the limits of agreement using the Bland–Altman analysis11 and the coefficient of variation (CV). The following formula was used to assess the CV: CV (%) = (SD/mean of measure- ment (Observer 1; Observer 2)) × 100. RESULTS Demographic characteristics, gestational age and NT measurements at first presentation of the study patients are shown in Table 1. Seventy-two patients underwent first-trimester screening with NT measurement for chromosome abnormalities. Of the 72 fetuses in which NT thickness was measured, 2/72 had an NT of ≥ 3.5 mm and both had CHD. A transabdominal ultrasound alone was performed in 81/100 (81%) of cases, and a combined transabdominal and transvaginal approach was used in 19/100 (19%) of cases. The four-chamber view was visualized in all fetuses in early gestation. In 94 fetuses heart anatomy was normal. The CAx value in this group of normal fetuses ranged from 34.5 to 56.8◦ (mean (SD) 47.6 ± 5.6◦ ). Based on our results, a CAx of < 35◦ and > 60◦ represents 2 SD outside our mean measurement and should be considered abnormal. The relationship between CAx and gestational age is shown in Figure 3. The CAx showed a tendency to be significantly higher (levorotation) at a gestational age of 11 + 0 to 11 + 6 weeks compared with a gestational age of between 12 + 0 and 14 + 6 weeks (Table 2). Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.
  3. 3. 678 Sinkovskaya et al. Figure 2 Assessment of the cardiac axis using high-definition power Doppler in a normal fetus at 12 + 6 weeks’ gestation. (a) Right and left ventricles are colored bright red and separated by a dark line, which represents the interventricular septum (arrows). (b) Cardiac axis measurement is shown. LV, left ventricle; RV, right ventricle; S, spine. Table 1 Demographics, gestational age and nuchal translucency (NT) measurements at first presentation (n = 100) Parameter Value Maternal age (years) 31.1 ± 6.4 Race Caucasian 59 African–American 31 Asian 8 Hispanic 2 Gravidity 3 (1–13) Parity 1 (0–4) Body mass index (kg/m2) 24.2 ± 3.5 Gestational age (weeks) 11 + 0 to 11 + 6 18 12 + 0 to 12 + 6 40 13 + 0 to 13 + 6 26 14 + 0 to 14 + 6 16 NT* (mm) 1.5 (0.9–4.6) Values given as mean ± SD, median (range) or %. *n = 72. Repeated-measures ANOVA showed no significant differences in the three separate measurements of CAx made by the same observer (P = 0.3). Figure 4 presents a Bland–Altman plot of interobserver reproducibility. The mean difference in CAx measurements performed by Observer 1 (E.S.) and Observer 2 (S.H.) was close to zero, and no significant difference was obtained. Based on the CV, the interobserver variation for CAx measurements was 2.8%. CHDs were diagnosed prenatally in six out of 100 fetuses and were confirmed postnatally or by autopsy. In four cases the CHDs were found during the initial scan at the first trimester and included heterotaxy syndrome with complex CHD, hypoplastic left heart syndrome, 40 35 40 45 50 55 50 60 CRL (mm) CAx(°) 70 80 90 Figure 3 Scatter plot presenting cardiac axis (CAx) measurement plotted against crown–rump length (CRL). Individual values for the CAx of normal fetuses and the reference range (mean, 5th and 95th centiles) are shown. tetralogy of Fallot and atrioventricular septal defect. All fetuses had abnormal CAx measurements. In three of these cases left deviation of the CAx (74, 97 and 68◦ ) was noted, and one fetus had mesocardia with the CAx = 0◦ (Table 3). Figures 5 and 6 show CAx measurements in two fetuses with left axis deviations in early gestation (12 + 2 and 13 weeks, respectively). In addition, two fetuses were first diagnosed with CHDs during fetal echocardiography in the second and third trimesters of pregnancy. In these two fetuses, CAx measurements in the first trimester were within the normal range. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.
  4. 4. Fetal cardiac axis 679 Table 2 Cardiac axis (CAx) measurements in fetuses with normal heart anatomy CAx (◦) GA (weeks) n Mean ± SD 95% CI 11 + 0 to 11 + 6* 17 52.0 ± 2.9 46.2–57.8 12 + 0 to 12 + 6 38 47.3 ± 2.4 42.4–52.2 13 + 0 to 13 + 6 24 48.8 ± 3.0 39.9–51.8 14 + 0 to 14 + 6 15 45.6 ± 5.0 35.6–55.7 *Multiple comparison using the Tukey test showed a significant (P < 0.05) difference between the 11 + 0 to 11 + 6 group compared with the three other groups (i.e. between 12 + 0 and 14 + 6 weeks’ gestation). GA, gestational age. DISCUSSION CHD is the most common congenital abnormality in the human fetus, and it accounts for more than half of the deaths from congenital abnormalities in childhood12 . Sev- eral risk factors for CHD, including maternal and fetal factors, have been reported13 . Most neonates born with CHD, however, have no preidentified risk factors14 . In fact, of all pregnancies referred for fetal echocardio- graphy, the highest rate of CHD (50%) is found in pregnancies with a suspected CHD on a routine ultra- sound examination15 . The four-chamber view of the heart is included in the basic obstetric ultrasound examination and has been pro- posed as a screen for CHD in the second trimester of pregnancy5 . Specialized ultrasound skills are not required because the heart is easily imaged in a transverse view of the fetal chest. Detection of an abnormal four-chamber view, axis or position of the fetal heart should be con- sidered as an indication for fetal echocardiography in the second trimester7,16. In recent years, fetal heart evaluation has become feasible in the first and early second trimesters of pregnancy because of improvements in the resolution of transvaginal and transabdominal probes. Measurement of NT is offered routinely in many countries and thickened 30 DifferenceinCAx(°) −3 −1 1 3 40 Mean CAx (°) 50 60 +2SD Mean −2SD Figure 4 Bland–Altman plot of interobserver variation (mean ± SD, 0.4 ± 1.1) in measurements of the fetal cardiac axis (CAx). NT is associated with cardiac anomalies. Recently- published data show that, in comparison to other views, the four-chamber view has the highest visualization rate at each gestational age and can be obtained in 85–100% of first-trimester ultrasound examinations17,18 . Based on our experience, a combined transabdominal and transvaginal approach allows visualization of the four-chamber view in all cases between 11 + 0 and 14 + 6 weeks of gestation. The normal CAx does not change significantly between 16 and 40 weeks of gestation and lies at a 45◦ angle to the left of the midline6. The present study shows the CAx to be significantly higher at 11 + 0 to 11 + 6 weeks of gesta- tion than later in pregnancy. The reason for a levorotated CAx in early gestation is currently unclear. Defining left axis deviation as > 75◦ , one study noted fetal anomalies in 76% of fetuses9 in the second trimester. In left CAx deviation, tetralogy of Fallot, coarctation of the aorta and Ebstein anomaly are the most common cardiac lesions, whereas double-outlet right ventricle, atrioventricular septal defect and common atrium are the most common cardiac lesions in right axis deviation8,10,19 . Our findings in early gestation were similar. Three Table 3 Cardiac axis (CAx) values in six fetuses diagnosed with congenital heart defect (CHD) First-trimester scan CAx at Case CAx (◦) NT (mm) second/third-trimester scan (◦) GA at diagnosis (weeks) Type of congenital heart defect 1 74 2.2 67 12 + 2 Tetralogy of Fallot 2 97 3.7 92 12 + 6 Hypoplastic left heart syndrome 3 68 4.6 79 13 + 0 AVSD, dominant RV 4 0 1.3 2 13 + 6 Heterotaxy syndrome, mesocardia, complex CHD (AVSD, common atrium, infracardiac TAPVC to the portal vein) 5 44 1.1 45 23 + 4 Muscular VSD 6 48 NM 68 33 + 2 Coarctation of the aorta, small VSD AVSD, atrioventricular septal defect; GA, gestational age; NM, not measured; RV, right ventricle; TAPVC, total anomalous pulmonary venous connection; VSD, ventricular septal defect. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.
  5. 5. 680 Sinkovskaya et al. Figure 5 Cardiac axis measurement in a fetus with tetralogy of Fallot at 12 + 2 weeks’ gestation. The angle shown in this case is 74◦ (left axis deviation). RV, right ventricle; S, spine. Figure 6 Cardiac axis measurement in a fetus with an unbalanced atrioventricular septal defect at 13 + 0 weeks’ gestation. Left axis deviation, with an angle of 68◦, is present. RV, right ventricle; S, spine. fetuses with left axis deviations had hypoplastic left heart syndrome, tetralogy of Fallot and unbalanced atrioventricular septal defect in our small series. Right deviation of CAx was found in the fetus with heterotaxy syndrome. Of note, two of four fetuses in our study which had CAx deviation in the first trimester and CHD had a normal NT measurement and thus CHD could have escaped detection by NT screening alone. In one case of coarctation of the aorta in our series, CAx was normal in the first trimester and left deviated in the third trimester. Isolated ventricular septal defect did not affect the CAx significantly. The interobserver reproducibility for measuring the CAx in our study was similar to that previously reported by Crane et al.7 in fetuses in the second and third trimesters (CV: 2.8% vs. 3%). Intraobserver agreement in measurement of the CAx was also noted in our study. Currently there are no approved indications for patient referral for early fetal echocardiography. Based upon our experience and that of others, an enlarged NT, the pres- ence of a major extracardiac malformation, the presence of reversed flow in the ductus venosus and the detection of tricuspid and/or mitral regurgitation or an abnor- mal CAx can be considered indications for early fetal echocardiography20–22. Limitations of the study Maternal body habitus and in utero fetal position play a critical role in the image obtained during the ultrasound examination in early pregnancy. The ability to perform an evaluation of the fetal CAx in difficult-to-image patients (BMI > 30) is challenging and remains to be determined. To our knowledge this is the first study to evaluate prospectively the CAx during the first and early second trimesters of pregnancy. The value of the CAx in early gestations for the prenatal diagnosis of CHD remains to be established in larger studies. However, our initial results are promising. In this study, we demonstrated the feasibility of CAx assessment in the first and early second trimesters of pregnancy and its potential clinical applica- bility. Further prospective studies in a clinical setting are needed to confirm the value of CAx measurement as a screening test for CHD in early gestation. REFERENCES 1. Johnson B, Simpson LL. Screening for congenital heart disease: a move toward earlier echocardiography. Am J Perinatol 2007; 24: 449–456. 2. Smrcek JM, Berg C, Geipel A, Fimmers R, Axt-Fiedner R, Diedrich K, Gembruch U. Detection rate of early fetal echocar- diography and in utero development of congenital heart defects. J Ultrasound Med 2006; 25: 187–196. 3. Huggon IC, Ghi T, Cook AC, Zosmer N, Allan LD, Nico- laides KN. Fetal cardiac abnormalities identified prior to 14 weeks gestation. Ultrasound Obstet Gynecol 2002; 20: 22–29. 4. Haak MC, van Vugt JM. Echocardiography in early pregnancy: review of literature. J Ultrasound Med 2003; 22: 271–280. 5. Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan. Ultrasound Obstet Gynecol 2006; 27: 107–113. 6. Comstock CH. Normal fetal heart axis and position. Obstet Gynecol 1987; 70: 255. 7. Crane JM, Ash K, Fink N, Desjardins C. Abnormal fetal cardiac axis in the detection of intrathoracic anomalies and congenital heart disease. Ultrasound Obstet Gynecol 1997; 10: 90–93. 8. Shipp TD, Bromley B, Hornberger LK, Nadel A, Benacer- raf BR. Levorotation of the fetal cardiac axis: a clue for the presence of congenital heart disease. Obstet Gynecol 1995; 85: 97–102. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.
  6. 6. Fetal cardiac axis 681 9. Smith RS, Comstock CH, Kirk JS, Lee W. Ultrasonographic left cardiac axis deviation: a marker for fetal anomalies. Obstet Gynecol 1995; 85: 187–191. 10. Comstock CH, Smith R, Lee W, Kirk JS. Right fetal cardiac axis: clinical significance and associated findings. Obstet Gynecol 1998; 91: 495–499. 11. Bland JM, Altman DG. Applying the right statistics: analyses of measurement studies. Ultrasound Obstet Gynecol 2003; 22: 85–93. 12. Hoffman JIE, Christianson R. Congenital heart disease in a cohort of 19,502 births with long-term follow-up. Am J Cardiol 1978; 42: 641–647. 13. Small M, Copel JA. Indications for fetal echocardiography. Pediatr Cardiol 2004; 25: 210–222. 14. Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AM, Anderson RH, Cook AC, Fagg NL. Prospective diagnosis of 1,006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol 1994; 23: 1452–1458. 15. Copel JA, Pilu G, Green J, Hobbins JC, Kleinman CS. Fetal echocardiographic screening for congenital heart disease: the importance of the four-chamber view. Am J Obstet Gynecol 1987; 157: 648–655. 16. Allan LD, Lockhart S. Intrathoracic cardiac position in the fetus. Ultrasound Obstet Gynecol 1993; 3: 93–96. 17. Haak MC, Twisk JWR, van Vugt JMG. How successful is fetal echocardiographic examination in the first trimester of pregnancy? Ultrasound Obstet Gynecol 2002; 20: 9–13. 18. Smrcek JM, Berg C, Geipel A, Fimmers R, Diedrich K, Gem- bruch U. Early fetal echocardiography: heart biometry and visualization of cardiac structures between 10 and 15 weeks’ gestation. J Ultrasound Med 2006; 25: 173–182. 19. Abuhamad A, Chaoui R. Fetal cardiac axis. In A Practical Guide to Fetal Echocardiography: Normal and Abnormal Hearts. Lippincott Williams & Wilkins: Philadelphia, PA, 2010; 34–36. 20. Matias A, Huggon I, Areias JC, Montenegro N, Nicolaides KH. Cardiac defects in chromosomally normal fetuses with abnormal ductus venosus blood flow at 10–14 weeks. Ultrasound Obstet Gynecol 1999; 14: 307–310. 21. Martinez JM, Comas M, Borrell A, Bennasar M, Gomez O, Puerto B, Gratacos E. Abnormal first-trimester ductus venosus blood flow: a marker of cardiac defects in fetuses with normal karyotype and nuchal translucency. Ultrasound Obstet Gynecol 2010; 35: 267–272. 22. Smrcek JM, Krapp M, Axt-Fliedner R, Kohl T, Geipel A, Diedrich K, Gembruh U, Berg C. Atypical ductus venosus blood flow pattern in fetuses with severe tricuspid valve regurgitation. Ultrasound Obstet Gynecol 2005; 26: 180–182. Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

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