Editorial. Color and pulsed Doppler in fetal echocardiography A. ABUHAMAD

Ultrasound Obstet Gynecol 2004; 24: 1 9 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.1096 Editorial Color and pulsed Doppler in fetal echocardiography A. ABUHAMAD Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Norfolk, Virginia 23507, USA (e-mail: AbuhamAZ@evmsmail.evms.edu) OPTIMIZING YOUR IMAGE Adequate imaging of the fetal heart is essential for accurate diagnosis. Several steps can be taken to improve ultrasound imaging when faced with suboptimal scanning conditions. Resort to the echocardiography settings on your ultrasound equipment as the first step in optimizing your image. These settings allow for enhanced image contrast and tissue characterization and a faster frame rate, which improve cardiac imaging. Other steps include minimizing the depth on the display monitor, insonating the heart through an angle that avoids shadowing by the fetal ribs and sternum, adjusting the focal zones to the area of interest and, most importantly, enlarging the area of interest (zoom) which allows visualization of details within the heart. These simple steps result in adequate visualization of the fetal heart in most conditions (Figure 1). When adding color Doppler to your grayscale image, select high-velocity scales given that the velocity of cardiac blood flow is higher than that of the peripheral fetal circulation. By adjusting your filters to a high setting and by directing the angle of insonation of your ultrasound beam parallel to the direction of blood flow, the color Doppler image is optimized and wall motion artifact is significantly reduced (Figure 2). COLOR DOPPLER AND FETAL ECHOCARDIOGRAPHY Color Doppler adds significantly to our ability to diagnose congenital heart disease. Flow patterns across the atrioventricular and semilunar valves can be evaluated by color Doppler and abnormalities suspected on gray-scale imaging can be confirmed. Atrioventricular valves can be evaluated thoroughly by a simple application of color Doppler at the level of the four-chamber view. Normal diastolic blood flow across the atrioventricular valves can be noted easily (Figure 3a) and the presence of a common atrioventricular valve can be confirmed (Figure 3b). The presence of decreased or absent flow across the mitral or tricuspid valves during diastole on color Doppler suggests the presence of valvular stenosis or atresia (Figure 3c). The diagnosis of tricuspid regurgitation is dependent on the application of color or pulsed Doppler across the tricuspid valve. Tricuspid regurgitation may represent a normal finding and it is seen in 6.2% of fetuses 1. As a normal finding, tricuspid regurgitation is part systolic with little spatial expansion, is commonly a transient observation, and its peak velocity is usually less than 2 m/s (Figure 4a) 1. Differential diagnosis of tricuspid regurgitation includes tricuspid or pulmonary valvular disease, indomethacin exposure with ductal narrowing, fetal hypoxemia with growth restriction (Figure 4b), fetal arrhythmias, or in association with severe twin twin transfusion syndrome (Figure 4c) 1. A careful search for tricuspid regurgitation may be an important aspect of the evaluation of the early fetus (11 14 weeks), as an association with karyotypic abnormalities was noted in a high-risk population 2. Color Doppler can also confirm the presence of a ventricular septal defect, when suspected on gray-scale ultrasound. For this application, I find color Doppler most helpful during systole and in apical or axial cardiac orientation at the level of the four-chamber view (Figure 5). In this setting a high-velocity jet is seen during systole across the septal defect, typically from the right to the left ventricle. This right-to-left flow direction across the septal defect is a result of higher systolic pressure in the right ventricle of the fetus in contrast to that in postnatal life. Other applications of color Doppler in fetal echocardiography include assessing blood flow patterns across the foramen ovale (Figure 6) and the direction of flow in the great vessels at the level of the three-vessel view (Figure 7), and confirming the diagnosis of an interrupted inferior vena cava in heterotaxic syndromes (Figure 8). Color Doppler can also be used to confirm the presence of a minimal to moderate amount of pericardial effusion (Figure 9). Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. E D ITORIAL

2 Abuhamad Figure 2 Color Doppler ultrasound applied at the level of the four-chamber view during diastole in a fetus at 22 weeks gestation. The presence of flow across the mitral and tricuspid valves and across the foramen ovale (F.O.) is clearly outlined. Flow from one pulmonary vein into the left atrium (LA) is also seen. LV, left ventricle; RA, right atrium; RV, right ventricle. Figure 1 (a) A suboptimal ultrasound image of the fetal heart obtained at 18 weeks gestation at the level of the four-chamber view. (b) The four-chamber view in the same fetus following image optimization. PULSED DOPPLER AND FETAL ECHOCARDIOGRAPHY The Doppler effect describes the apparent variation in frequency of a light or a sound wave as its source approaches or moves away, relative to an observer. Applying this clinically, when an ultrasound beam with a certain transmitted frequency is used to insonate a blood vessel, the reflected frequency or frequency shift is directly proportional to the speed with which the red blood cells are moving (blood flow velocity) within that particular vessel. Given that the blood velocity in a particular vascular bed is inversely proportional to the downstream impedance to flow, the frequency shift therefore provides information on the downstream impedance to flow of whichever vascular bed is being studied. The frequency shift is also dependent on the cosine of the angle that the ultrasound beam makes with the targeted blood vessel. Angle-independent indices have been developed to quantitate Doppler waveforms given that the insonating angle is difficult and impractical to measure. These angle-independent indices, which include the systolic/diastolic (S/D) ratio, the resistance index (RI) and the pulsatility index (PI), are commonly used for evaluating the peripheral fetal vasculature. Doppler indices in fetal echocardiography are quantitative parameters and the majority are angledependent. In order to obtain accurate Doppler indices in fetal echocardiography, the sample volume is placed distal to the respective valves, the insonating angle should be within 15 20 of the direction of blood flow, Doppler waveforms should be obtained during fetal apnea, and multiple measurements should be made. Color Doppler is used to direct placement of the sample volume; placing the sample volume at the brightest colors of the blood flow segment will ensure the best measurements. Figures 10 13 show Doppler indices commonly used in fetal echocardiography. The fetal circulation is different from the adult circulation in many respects. The fetal circulation is in parallel rather than in series, and the right ventricular cardiac output is greater than the left ventricular cardiac output 3,4. The progressive development of organs during gestation influence blood distribution and vascular impedance 3. With advancing gestation, ventricular compliance is increased, total peripheral

Editorial 3 Figure 3 Color Doppler ultrasound applied at the level of the four-chamber view during diastole. (a) A normal heart with blood entering the ventricles through two channels corresponding to the mitral and tricuspid valves. (b) A heart with an atrioventricular canal defect with blood entering the ventricles through a single central channel. (c) A heart with tricuspid atresia with blood entering the ventricles through a single peripheral channel across the mitral valves, with no flow detected across the tricuspid valves. resistance is decreased, preload is increased and combined cardiac output is increased 3. Compliance of the fetal left heart increases more rapidly than does compliance of the fetal right heart with advancing gestation 3.The pulmonary vascular resistance is high in the fetus and the pulmonary arterial pressure is almost systemic 5,6. Flow to the pulmonary vascular bed is maintained at a low rate with a noted increase towards the end of gestation 4,5. Cardiac output in the fetus is mainly affected by preload and ventricular compliance 3. The presence of right-to-left shunts at the level of the foramen ovale and ductus arteriosus has a significant impact on cardiac flow patterns and affects the distribution of blood and oxygen to various organs. Flow across the foramen ovale contributes to the majority of blood entering the left ventricle and more than two thirds of right ventricular output is directed to the ductus arteriosus 4,7. This shunting mechanism ensures the delivery of blood with high oxygen content to the coronary and cerebral circulations. Doppler waveforms across the atrioventricular valves are bicuspid in shape (Figure 14). The first peak (E-wave) corresponds to early ventricular filling of diastole, and the second peak (A-wave) corresponds to atrial systole or the atrial kick. Unlike in postnatal life, in the fetus the velocity of the A-wave is higher than that of the E-wave 3,8.This highlights the importance of the role that atrial systole plays in cardiac filling in the fetus. The E/A ratio increases with advancing gestation and reflects ventricular diastolic function 3,8. E and A velocity peaks are higher in the right ventricle and this right ventricular dominance is evident from the first trimester 3,8,9. Shifting to left ventricular dominance starts in utero towards the end of gestation 3. The E/A ratio is an index of ventricular preload and compliance 3. Doppler waveforms across the semilunar valves are uniphasic in shape (Figure 15). Indices most commonly used for the semilunar Doppler waveforms include the peak systolic velocity (PSV) and the time-to-peak velocity (TPV). PSV and TPV increase with advancing gestation across the semilunar valves 3,7,10 13. PSV is higher across the aorta than it is across the pulmonary artery due to a decreased afterload and a smaller diameter across the

4 Abuhamad Figure 4 Tricuspid regurgitation (TR) detected by color Doppler ultrasound. (a) Transient TR in a normal fetus. (b) TR associated with fetal hypoxemia. (c) TR in a recipient twin in severe twin twin transfusion syndrome. Arrows point to the tricuspid valves. aorta 3,7,10 13. These Doppler indices reflect ventricular contractility, arterial pressure and afterload. Intrauterine growth restriction (IUGR) is associated with several changes at the level of the fetal heart involving preload, afterload, ventricular compliance and myocardial contractility. An increase in afterload is seen at the level of the right ventricle due to increased placental impedance 14. A decrease in afterload is noted at the level of the left ventricle due to decreased cerebral impedance associated with the brain-sparing reflex 14. These changes in afterload result in a redistribution of the cardiac output from right to left ventricle 14. Preload is reduced at both atrioventricular valves due to hypovolemia and decreased filling associated with IUGR 11,15 17. This decrease in preload is reflected by a decrease in the E/A ratio, decreased atrial peak and decreased time-velocity integral at the mitral and tricuspid valves 11,15,16. Other investigators, however, reported an unchanged E/A ratio in the compromised fetus 17.These controversial data may have resulted from different study populations or internal variability of results. Although the reduction in E/A ratios in IUGR fetuses may result from a reduced preload, overall diastolic function impairment is related to a dysfunction in myometrial relaxation at the cellular level 18,19. Ventricular compliance, assessed by the ratio of the time-velocity integral of the A-wave over the time-velocity integral of the total wave of the atrioventricular valve, is decreased in IUGR fetuses 3,14. The right ventricle is more affected by reduced compliance than is the left ventricle 3,14. Reduced PSV at the level of the semilunar valves is also noted in many IUGR fetuses 20. This may result from a reduced preload and an increased afterload of the right

Editorial 5 Figure 7 Color Doppler ultrasound of the three-vessel view obtainedat21weeks gestationinafetuswithsevereaortic stenosis. Note the presence of retrograde flow in the aorta (red). Figure 5 Color Doppler ultrasound of an apical four-chamber view obtained at 22 weeks gestation during systole, confirming the presence of a muscular ventricular septal defect. Figure 6 Color Doppler ultrasound confirming the presence of restricted flow across the foramen ovale in a fetus at 23 weeks gestation. Note the presence of turbulence at the foramen ovale on color Doppler. ventricle 20. An increase in TPV across the aorta is seen in IUGR fetuses and suggests a decrease in mean arterial pressure in that vessel 10. In contrast, a decrease in TPV across the pulmonary artery is noted in IUGR fetuses and may result from an increase in pulmonary and peripheral impedance in these fetuses 10. Evidence of reduced myocardial contractility in the presence of severe IUGR has also been reported. Ventricular ejection force, an index of ventricular systolic function that is independent of preload and afterload, is decreased at the level of the right and left ventricles in fetal growth restriction 21. IUGR fetuses with reduced ventricular ejection force have a shorter time to delivery, a higher incidence of non-reassuring fetal heart rate tracing and a lower ph at birth when compared with controls 21. A significant correlation between the severity of fetal acidosis at cordocentesis and ventricular ejection force values validates the association of this index and the severity of fetal compromise 21. Myocardial cell damage, demonstrated by elevated levels of cardiac troponin-t, is seen in some fetuses with severe growth restriction 14. This advanced stage of fetal compromise is associated with signs of increased systemic venous pressure, a change in the distribution of cardiac output, a rise in right ventricle afterload, and a high incidence of tricuspid regurgitation 14. These findings suggest that Doppler abnormalities in the proximal venous system of the growth-restricted fetus indicate fetal myocardial cell damage and increased systemic venous pressure 14. The fetal heart plays a central role in the adaptive mechanisms for hypoxemia and placental insufficiency. Longitudinal data on the hemodynamic sequence of the natural history of fetal growth restriction show that Doppler waveforms of the umbilical and middle cerebral arteries are the first variables to become abnormal 18.

6 Abuhamad Figure 8 Color Doppler ultrasound applied at the level of the aortic arch in a sagittal view of a fetus at 20 weeks gestation with heterotaxic syndrome. (a) A vessel (azygous) with flow towards the heart. (b) Pulsed Doppler confirmed venous flow patterns. These findings confirm the presence of an azygous vein in association with an interrupted inferior vena cava. Figure 9 Minimal pericardial effusion confirmed on color Doppler ultrasound in a fetus at 23 weeks gestation. (a) The pericardial fluid (arrows) is seen moving towards the apex during systole. (b) The fluid (arrows) is seen moving towards the atria during diastole. These arterial Doppler abnormalities are followed by abnormalities in the right cardiac diastolic indices, followed by the right cardiac systolic indices and finally by both left diastolic and systolic cardiac indices 18. Preserving the left systolic function as the last variable to become abnormal ensures adequate output of the left ventricle, which supplies the cerebral and coronary circulations. Several of the Doppler changes seen in association with fetal IUGR in the peripheral circulation are related directly to the adaptation of the fetal heart. The current

Editorial 7 Figure 10 Peak velocity represents the maximum velocity achieved by the Doppler waveforms. It is expressed in cm/s and is typically obtained at the aortic and pulmonary valves. It reflects contractility and afterload. Figure 12 The time-velocity integral is the integral of the planimetric area under the Doppler curve. It expresses the distance that red blood cells would have to cover with a constant area of the flow section. It is expressed in cm. however, that those changes in the central venous circulation reflect an advanced stage of fetal compromise, commonly associated with myocardial dysfunction and damage. REFERENCES Figure 11 The time-to-peak or acceleration time (AT) is the time between the beginning of the Doppler wave and its peak velocity. It is expressed in ms and is typically obtained at the aortic and pulmonary valves. It is an index of mean arterial pressure. management of IUGR involves Doppler ultrasound at the peripheral arterial circulation (middle cerebral and umbilical arteries), central venous vessels (ductus venosus and inferior vena cava) and cardiotocography. Adding cardiac Doppler may improve management of the IUGR fetus, but studies are lacking on the prospective clinical evaluation with cardiac Doppler of the IUGR fetus. It is becoming more obvious, AT 1. Gembruch U, Smrcek JM. The prevalence and clinical significance of tricuspid valve regurgitation in normally grown fetuses and those with intrauterine growth retardation. Ultrasound Obstet Gynecol 1997; 9: 374 382. 2. Huggon IC, DeFigueiredo DB, Allan LD. Tricuspid regurgitation in the diagnosis of chromosomal anomalies in the fetus at 11 14 weeks of gestation. Heart 2003; 89: 1071 1073. 3. Chang CH, Chang FM, Yu CH, Liang RI, Ko HC, Chen HY. Systemic assessment of fetal hemodynamics by Doppler ultrasound. Ultrasound Med Biol 2000; 26: 777 785. 4. Mielke G, Norbert B. Cardiac output and central distribution of blood flow in the human fetus. Circulation 2001; 103: 1662 1668. 5. Mielke G, Benda N. Blood flow velocity waveforms of the fetal pulmonary artery and the ductus arteriosus: reference ranges from 13 weeks to term. Ultrasound Obstet Gynecol 2000; 15: 213 218. 6. Hong Y, Choi J. Doppler study on pulmonary venous flow in the human fetus. Fetal Diagn Ther 1999; 14: 86 91. 7. Brezinka C. Fetal hemodynamics. J Perinat Med 2001; 29: 371 380. 8. Harada K, Rice MJ, Shiota T, Ishii M, McDonald RW, Reller MD, Sahn DJ. Gestational age and growth related alternations

8 Abuhamad FT ET Figure 13 (a) Filling time (FT) is the diastolic time of the cardiac cycle and is expressed in seconds. (b) Ejection time (ET) is the systolic time of the cardiac cycle and is expressed in seconds. E A E A Aorta Figure 14 Doppler waveforms obtained across the mitral (a) and tricuspid (b) valves. These Doppler waveforms are biphasic in shape with the first phase (E-wave) corresponding to fast ventricular filling and the second phase (A-wave) corresponding to the atrial kick. These Doppler waveforms reflect ventricular diastolic function and are indices of ventricular preload and compliance. in fetal right and left ventricular diastolic filling patterns. Am J Cardiol 1997; 79: 173 177. 9. Ben-Ami M, Peleg D, Haddad S, Perlitz Y. Normal cardiac flow velocities at 14 16 weeks gestation measured by transvaginal ultrasound. Ultrasound Obstet Gynecol 2002; 19: 47 50. 10. Severi FM, Rizzo G, Bocchi C, D Antona D, Verzuri MS, Arduini D. Intrauterine growth retardation and fetal cardiac function. Fetal Diagn Ther 2000; 15: 8 19. 11. Rizzo G, Arduini D, Romanini C. Doppler echocardiographic assessment of fetal cardiac function. Ultrasound Obstet Gynecol 1992; 2: 434 445. 12. Groenenberg IAL, Stijnen T, Wladimiroff JW. Flow velocity waveforms in the fetal cardiac outflow tract as a measure of fetal well-being in intrauterine growth retardation. Pediatr Res 1990; 27: 379 382.

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