First-Trimester Fetal Cardiac Function

Transcription

1 CME Article First-Trimester Fetal Cardiac Function Noirin E. Russell, MRCPI, Fionnuala M. McAuliffe, MD, FRCPI, MRCOG Objective. The purpose of this study was to establish normal values for fetal heart function in the first trimester. Methods. This was a prospective observational study with institutional ethics approval and written maternal consent. Thirty-two healthy pregnant women were recruited, and transabdominal fetal echocardiography was performed between 12 and 14 completed weeks gestation. Myocardial function was assessed with the myocardial performance index to assess combined systolic and diastolic function, isovolumetric contraction time to assess systolic function, and isovolumetric relaxation time to assess diastolic function. Mitral and tricuspid inflows were also assessed by determining the ratio between passive and active ventricular filling. The ventricular outflows were also assessed by peak systolic velocities (PSVs) and time velocity integrals (TVIs). Results. The mean gestational age at the time of echocardiography was 13 weeks, and the mean crown-rump length was 79 mm. All fetuses had a normal nuchal translucency measurement (mean, 1.5 mm). The myocardial performance index was the same in the left and right sides of the heart, 0.5. The mean isovolumetric relaxation time and isovolumetric contraction time on the left side of the heart were 41 and 36 milliseconds, respectively. The mean passive/active ventricular filling ratio was 0.6 at both the mitral and tricuspid valves. The mean aortic PSV was 26 cm/s, and mean pulmonary artery PSV was 32 cm/s. The mean aortic outflow TVI was 3.6 cm, and the mean pulmonary outflow TVI was 4.1 cm. Conclusions. This study establishes normal values for cardiac function at 12 to 14 weeks gestation. These values may assist in assessment of fetal health in early pregnancy. Key words: cardiac function; echocardiography; fetus; first trimester; myocardial performance index. Abbreviations A, active ventricular filling; AV, atrioventricular; E, early passive ventricular filling; ICT, isovolumetric contraction time; IVRT, isovolumetric relaxation time; MPI, myocardial performance index; PSV, peak systolic velocity; TVI, time velocity integral Received October 3, 2007, from the Fetal Medicine Center, Department of Obstetrics and Gynecology, University College Dublin, School of Medicine and Medical Science, National Maternity Hospital, Dublin, Ireland. Revision requested November 5, Revised manuscript accepted for publication November 19, Dr Russell was supported by the Medical Research Fund of the National Maternity Hospital. Address correspondence to Fionnuala M. McAuliffe, MD, FRCPI, MRCOG, University College Dublin, School of Medicine and Medical Science, National Maternity Hospital, Dublin 2, Ireland. fionnuala.mcauliffe@ucd.ie CME Article includes CME test A dvances in ultrasound technology have led to improved visualization of the fetus in the first trimester. This has led to increased interest in examining the fetus for abnormalities, with early fetal echocardiography now offered in many units. A recent article on early fetal echocardiography in firsttrimester fetuses found that a satisfactory cardiac examination was possible in 95% of cases, with sensitivity of 70% and specificity of 98% for detection of cardiac defects. 1 Assessment of cardiac function with Doppler examination of the atrioventricular (AV) valves has been performed in early pregnancy. Those studies found that the proportion of the cardiac cycle occupied by both the isovolumetric relaxation time (IVRT) and isovolumetric contraction time (ICT) reduces during the first trimester. 2 4 The myocardial performance index (MPI) is a useful noninvasive Doppler-derived method of evaluating combined systolic and diastolic function, first described in 2008 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2008; 27: /08/$3.50

2 First-Trimester Fetal Cardiac Function adult patients. 5 The MPI is influenced by cardiac preload and afterload, which change with gestational age. The first use of the MPI to assess cardiac function in the fetus found that both the left and right ventricular MPI decreased with advancing gestational age in all fetuses. 6 This is in contrast to 2 recent studies that found no change in the MPI with increasing gestational age between 18 weeks and term 7,8 and another that found a small increase from 18 to 39 weeks gestation. 9 Although the MPI has been assessed by many authors in the second and third trimesters, there is a paucity of data on the MPI in early pregnancy. 2 Assessment of fetal cardiac function has a role in determining normal physiologic characteristics and underlying pathophysiologic characteristics of fetal conditions. It may have a role in the first trimester in identifying fetuses at an increased risk of miscarriage, prediction of cardiac defects in fetuses with increased nuchal translucency, and also in early detection of the development of twin-to-twin transfusion syndrome in monochorionic twins. However, before assessing fetuses with abnormalities, it is important to establish normal values for indices of cardiac function in the first trimester. Materials and Methods This was a prospective observational study with institutional ethics approval and written maternal consent. Thirty-two women with uncomplicated pregnancies were recruited, and transabdominal fetal echocardiography was performed between 12 and 14 completed weeks gestation. All patients were accurately dated at a previous early first-trimester ultrasound scan. A trained research fellow and a consultant obstetrician performed the examinations. Follow-up data were obtained for all patients; none of the fetuses examined were later found to have a cardiac defect, and all had a normal perinatal outcome. The mean ± SD gestational age at delivery was 39 ± 3 weeks, and the mean birth weight was 3.3 ± 0.9 kg. To confirm accurate placement of the Doppler gate for measurement of cardiac function indices, visualization of cardiac anatomy was also recorded in the 32 studies (Table 1). Ultrasound examinations were performed transabdominally using 2-dimensional and pulsed wave Doppler imaging. The measurements were made with the patient semirecumbent and during fetal quiescence. A curvilinear 2- to 7-MHz probe was used on either a Voluson 730 Expert system (GE Healthcare, Munich, Germany) or a Toshiba Xario system (Toshiba Medical Systems Co, Ltd, Tokyo, Japan). The lowest possible intensities of Doppler energy were used, and the duration of the examination was limited to 30 minutes. Doppler ultrasound was applied in bursts of 15 seconds or less for a maximum total exposure of 2 minutes. The mechanical and thermal indices never exceeded 1. The angle of insonation was less than 30. Three to 5 waveforms were produced, and where possible, 3 consecutive waveforms were analyzed, and an average was obtained. All analyses were performed at the time of the scan, and each measurement was agreed on by the 2 authors. Once a satisfactory 4-chamber view was obtained, the 1- to 3-mm Doppler sample volume was placed immediately inferior to the AV valve during fetal quiescence while slightly tilting the probe toward the outflow tract. Time intervals were measured when the diastolic filling wave and systolic ejection wave were seen simultaneously. Intracardiac maximum velocities were measured with electronic calipers to determine the E- and A-wave peaks (Figure 1), where E represents early passive ventricular filling, and A represents active ventricular filling Table 1. Cardiac Anatomy Visualization in the First Trimester (n = 32) Anatomic Feature Visualization, % (n) Normal general anatomy 100 (32) 4-chamber view 100 (32) 3-vessel view 81 (26) Ventricular function 100 (32) Tricuspid valve 100 (32) Mitral valve 100 (32) Aortic root 84 (27) Main pulmonary artery 75 (24) Left branch pulmonary artery 15 (5) Right branch pulmonary artery 9 (3) Pulmonary vein 3 (1) Aortic arch 81 (26) Ductal arch 69 (22) Inferior vena cava 88 (28) Superior vena cava 88 (28) 380 J Ultrasound Med 2008; 27:

3 Russell and McAuliffe secondary to atrial contraction; thus, the E/A ratio assesses diastolic function. Components of the MPI were individually assessed: the ICT and IVRT. The ICT is the fraction of time between the cessation of diastolic filling and the onset of ventricular ejection (Figure 1). The IVRT is the fraction of time between the cessation of ventricular ejection and the recommencement of ventricular filling. (Figure 1). Both the ICT and IVRT were measured in the left ventricle. The E/A ratio was measured across both the mitral and tricuspid inflows. The peak systolic velocity (PSV) and time velocity integral (TVI) of both outflow tracts were also measured. Global myocardial function was assessed with the MPI, which assesses combined systolic and diastolic function. The MPI was computed for both ventricles by the formula a b/b as previously described by Tei et al 5 (Figure 1). Because of the small size of the fetal ventricles at this gestation, we found that we were able to use a single waveform to compute the MPI for both right and left ventricles. Where possible, we used the modified method of Hernandez-Andrade et al 10 of recording the MPI using valve clicks, which involves using the Doppler signal from the aortic and mitral valves on the left side and pulmonary and tricuspid valves on the right side as reference points to measure different periods for MPI calculation. To evaluate intraobserver variability, the 2 observers independently analyzed the cardiac function measurements in 10 randomly selected patients. Each observer independently performed the measurements without knowledge of the results obtained by the other observer. The interobserver coefficient of variation for measurement of the left MPI was 4.6%, and that for the right MPI was 3.3%. Results Figure 1. Doppler waveform from the left ventricle. ET and b indicate ejection time; and a, period from closing to opening of the AV valves (IVRT + ET + ICT). A total of 32 healthy pregnant women, with a mean age of 30 years (range, years), underwent assessment. The mean gestational age was 13 weeks (range, weeks) with a mean crown-rump length of 79 mm (range, mm). Adequate visualization of cardiac anatomy was possible in all cases via the transabdominal route (Table 1). Table 2 summarizes the results from this study. All fetuses had normal nuchal translucency with a mean measurement of 1.45 mm (range, 1 2 mm). The E/A ratio for both right and left ventricles was the same at this gestation, as was the MPI for both ventricles. The only significant difference between the right and left sides of the heart was that the PSV in the pulmonary artery was higher than the PSV in the aorta (32 ± 14 versus 26 ± 7 cm/s; P <.05). Table 2. Cardiac Function Indices in the First Trimester (n = 32) Parameter Mean ± SD GA, wk 13 ± 0.7 CRL, mm 79 ± 7 FHR, beats/min 154 ± 8 MV E/A ratio 0.6 ± 0.1 MV E V max, cm/s 27 ± 6 MV A V max, cm/s 45 ± 9 IVRT, ms 41 ± 6 ICT, ms 36 ± 9 Left MPI 0.5 ± 0.1 Aortic PSV, cm/s 26 ± 7 Aortic TVI, cm 3.6 ± 1.1 TV E/A ratio 0.6 ± 0.1 TV E V max, cm/s 29 ± 6 TV A V max, cm/s 48 ± 9 Right MPI 0.5 ± 0.1 Pulmonary artery PSV, cm/s 32 ± 14 Pulmonary TVI, cm 4.1 ± 1.9 Nuchal translucency, mm 1.5 ± 0.3 Ductus venosus PI 1.0 ± 0.6 Umbilical artery PI 1.5 ± 0.3 Umbilical vein PSV, cm/s 11 ± 2.4 CRL indicates crown-rump length; GA, gestational age; FHR, fetal heart rate; MV, mitral valve; PI, pulsatility index; TV, tricuspid valve; and V max, maximum velocity. J Ultrasound Med 2008; 27:

4 First-Trimester Fetal Cardiac Function Discussion This study describes in detail normal Dopplerbased cardiac function parameters and MPI values for fetuses from 12 to 14 weeks gestation. We found that the MPI was the same for the right and left ventricles at this early gestation. The mean value of 0.5 was similar to that recorded for mid- and late-gestation fetuses, 7,8 suggesting that the MPI does not change substantially from early through late pregnancy despite dramatic changes in fetal heart dimensions and placental hemodynamic changes. In addition, our results for the MPI, although slightly higher, fall within the SDs of those from another study in the literature from early pregnancy, which found MPIs of ± and ± in the left and right ventricles, respectively. 11 Friedman et al 7 suggested that global left ventricular function could be evaluated from a single Doppler waveform incorporating inflow and outflow simultaneously. We found that this was also possible in the right ventricle because of the proximity of the inflow and outflow tracts at this early gestation. Later in pregnancy, the right ventricular inflows and outflows have to be measured on separate waveforms. 8 In 1996, Splunder 12 found that trans tricuspid valve flow velocities were significantly higher than trans mitral valve flow velocities at all gestational ages, suggesting right ventricular dominance as early as the late first trimester of pregnancy. The authors also found that the atrial contribution to ventricular filling (Awave) was higher at the tricuspid valve than at the mitral valve, suggesting that the right ventricle is less compliant than the left ventricle, possibly because of a larger right ventricle muscle mass. In this study, the only significant difference between the right and left sides of the heart was that the PSV in the pulmonary artery was higher than the PSV in the aorta, which again suggests right heart dominance. Failure to establish adequate cardiac function has been proposed as a cause of first-trimester miscarriage. Leiva et al 3 found that the detection rates for both semilunar and AV valves were less than 25% in first-trimester fetuses that subsequently miscarried compared with greater than 90% visualization in healthy fetuses at 12 weeks, suggesting that cardiac defects may reflect the underlying disease in first-trimester miscarriage. Wloch et al 2 reported an increased MPI and a proportion of the cardiac cycle occupied by an IVRT in those pregnancies that subsequently miscarried. This suggests that myocardial dysfunction may have a role in the etiology of miscarriage. Our patients were recruited after a normal first-trimester dating ultrasound examination had been performed and were thus at low risk for miscarriage. We were able to detect the AV valves in all fetuses, and no fetuses subsequently miscarried. If cardiac function indices are added to routine firsttrimester ultrasound assessment, this may lead to improved prediction of fetuses at risk of miscarriage. The MPI is increasingly being used to assess the sick fetus. It can be used for early and differential diagnosis between twin-to-twin transfusion syndrome and intrauterine growth restriction because both have a similar initial presentation. Raboisson et al 13 found that the MPI increases in recipients twins because of a prolonged IVRT when compared with donor fetuses. Ichizuka et al 14 found an increased MPI in recipients in twin-to-twin transfusion syndrome, large-for-gestational-age fetuses of diabetic mothers, and fetuses with hydrops when compared with control fetuses. Inamura et al 15 used the MPI to predict survival in congenital heart disease and found that both the left and right Tei indices were increased in nonsurvivors compared with survivors. Cardiac function indices may be of use in assessment of fetal health in the first trimester and may help miscarriage, congenital heart disease, and twin-to-twin transfusion syndrome. To diagnose abnormal cardiac function, it is essential to fully assess the healthy fetus in the firsttrimester. Even though the heart is very small in the first trimester, visualization of cardiac anatomy is adequate to allow assessment of cardiac function. References 1. McAuliffe FM, Trines J, Nield LE, Chitayat D, Jaeggi E, Hornberger LK. Early fetal echocardiography. Am J Obstet Gynecol 2005; 193: J Ultrasound Med 2008; 27:

5 Russell and McAuliffe 2. Wloch A, Rozmus-Warcholinska W, Czuba B, et al. Doppler study of the embryonic heart in normal pregnant women. J Matern Fetal Neonatal Med 2007; 20: Leiva MC, Tolosa JE, Binitto CN, et al. Fetal cardiac development and hemodynamics in the first trimester. Ultrasound Obstet Gynecol 1999; 14: Makikallio K, Jouppila P, Rasanen J. Human fetal heart function during the first trimester of pregnancy. Heart 2005; 91: Tei C, Ling LH, Hodge DO, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function a study in normals and dilated cardiomyopathy. J Cardiol 1995; 26: Tsutsumi T, Ishii M, Eto G, Hota M, Kato H. Serial evaluation for myocardial performance in fetuses and neonates using a new Doppler index. Pediatr Int 1999; 41: Friedman D, Buyon J, Kim M, Glickstein JS. Fetal cardiac function assessed by Doppler myocardial performance index (Tei Index). Ultrasound Obstet Gynecol 2003; 21: Eidem BW, Edwards JM, Cetta F. Quantitative assessment of fetal ventricular function: establishing normal values of the myocardial performance index in the fetus. Echocardiography 2001; 18: Hernandez-Andrade E, Figueroa-Diesel H, Kottman C, et al. Gestational-age-adjusted reference values for the modified myocardial performance index for evaluation of fetal left cardiac function. Ultrasound Obstet Gynecol 2007; 29: Hernandez-Andrade E, Lopez-Tenorio J, Figueroa-Diesel H, et al. A modified myocardial performance (Tei) index based on the use of valve clicks improves reproducibility of fetal left cardiac function assessment. Ultrasound Obstet Gynecol 2005; 26: Huggon IC, Turan O, Allan LD. Doppler assessment of cardiac function at weeks gestation in fetuses with normal and increased nuchal translucency. Ultrasound Obstet Gynecol 2004; 24: Splunder V. Fetal atrioventricular flow-velocity waveforms and their relation to arterial and venous flow velocity waveforms at 8 to 20 weeks gestation. Circulation 1996; 94: Raboisson MJ, Fouron J, Lamoureux J, et al. Early intertwin differences in myocardial performance during the twin-totwin transfusion syndrome. Circulation 2004; 110: Ichizuka K, Matsuoka R, Hasegawa J, et al. The Tei index for evaluation of fetal myocardial performance in sick fetuses. Early Hum Dev 2005; 81: Inamura N, Kado Y, Nakajima T, Kayatani F. Left and right ventricular function in fetal tetralogy of Fallot with absent pulmonary valve. Am J Perinatol 2005; 22: J Ultrasound Med 2008; 27: