Color and pulsed Doppler ultrasonography of the fetal coronary arteries: has the time come for its clinical application?

The development of the coronary system, which begins shortly after looping of the heart, is integrally associated with the development of the epicardium1. The epicardium develops from a mesothelial outpouching of the primordial liver, which then migrates to the heart in early gestation2. Angioblast migration closely follows, and coronary vessels arise from the assembly of progenitors in a vasculogenic process1, 3. The coronary circulation is complex and is comprised of an arterial and venous system4, 5. The main arterial blood supply to the heart is by the left and right coronary arteries, which arise from the aortic sinuses just above the aortic valves. The left coronary artery runs between the pulmonary trunk and the left atrial appendage and divides into the left anterior descending artery and the circumflex. The right coronary artery runs along the right atrioventricular sulcus and divides into the sinoatrial nodal artery and the posterior descending artery. Several variations have been reported in the distribution of the coronary arteries. The venous system is comprised of a superficial and a deep system. The superficial system, which drains into the coronary sinus, carries about two-thirds of the cardiac venous return and primarily drains the left ventricle. The deep system drains directly into the cardiac chambers. The coronary circulation is unique in several features. Coronary blood flow is maximal during diastole when extravascular resistance is at its lowest due to ventricular relaxation6. The myocardial muscle, unlike the skeletal muscle, relies almost exclusively on aerobic mechanisms for its energy source, with fatty acids and lactate being the preferred substrates for metabolism7, 8. Oxygen extraction by the coronary circulation is very high and reaches upwards of 80%, with an arteriovenous oxygen difference of 14 mL/dL during resting states9, 10. Increased myocardial oxygen demands, such as in exercise or in the presence of hypoxemia, are primarily met by increased coronary blood flow11. Animal studies have shown that acute hypoxemia can result in a 4–5-fold increase in coronary blood flow and acute hypoxemia superimposed on chronic hypoxemia can result in a 12-fold increase in coronary blood flow over its basal flow rate11, 12. These studies and others confirm the presence of short-term autoregulation and long-term vascular remodeling in the coronary circulation in the fetus11-14. The right and left coronary arteries are best imaged in a short-axis view of the aorta (Figure 1). In this view the proximal portion of the right coronary artery is seen, with its course almost parallel to the ultrasound beam. Conversely, the course of the left coronary artery is almost perpendicular to the ultrasound beam and thus is more difficult to image on color Doppler ultrasonography. Baschat and Gembruch13-16 have described techniques for the examination of the coronary circulation in the fetus. Zoom magnification is applied to the gray-scale image, the color Doppler filter is set to a high degree of motion discrimination, and the persistence is set to a low level to minimize frame averaging. The optimal color Doppler velocity scale for visualization of the coronary arteries is between 0.30 and 0.70 cm/s. Doppler waveforms of the coronary arteries are biphasic in shape with the initial phase corresponding to systole and the second, larger phase corresponding to diastole. Systolic and diastolic waveform velocities of the coronary arteries show no significant change with gestational age. Flow is antegrade throughout the cardiac cycle and coronary waveforms obtained in the fetus resemble in shape those obtained in neonates and children. (a) The fetal heart is examined in a short-axis view of the aorta at 34 + 2 weeks' gestation. The ostia of the left and right coronary arteries are discernible in the area of the left posterior and right anterior aortic sinus (arrows). (b) Color flow Doppler demonstrating the right coronary artery (blue) in a short-axis view of the aorta. Figure reproduced, with permission, from Baschat and Gembruch15. The largest study to date on the coronary circulation in the fetus is presented in this issue of the journal17. Baschat et al. present a retrospective analysis of 183 measurements of coronary artery peak blood flow velocities from 150 fetuses over a period of 9 years. A total of 76 measurements were obtained from appropriately grown fetuses (AGA), 84 from intrauterine growth-restricted fetuses (IUGR), 12 from fetuses with severe anemia and 11 from fetuses with constriction of the ductus arteriosus. In the authors' experienced hands, coronary blood flow was visualized in AGA fetuses at a median gestational age of 33 + 6 weeks, with 29 + 3 weeks being the lowest gestation at which coronary flow was imaged in AGA fetuses. Visualization of coronary blood flow in IUGR fetuses was achieved at an earlier gestation than in AGA fetuses (median gestational age in IUGR fetuses of 28 + 2 weeks), and IUGR fetuses were found to have significantly higher diastolic and systolic velocities than AGA fetuses. The highest coronary blood velocities were seen in anemic fetuses and these velocities declined following partial correction of the anemia. Several parameters currently preclude the introduction of coronary blood flow assessment in clinical practice. The technique involved in obtaining coronary artery Doppler waveforms is difficult and is dependent on a favorable fetal position. The small size of the coronary arteries, the presence of motion artifact and interference by extra- and intracardiac blood flows make measurement of fetal coronary blood flow challenging15. Significant expertise is therefore required to obtain these Doppler waveforms which may limit its wide applicability. Although IUGR fetuses were shown to have significantly higher systolic and diastolic peak velocities in the coronary arteries than AGA fetuses17, this difference was small and may not be of clinical significance. Both IUGR and AGA fetuses showed a wide range of peak systolic and diastolic velocities with significant overlap17. The current quantitative data, therefore, do not appear to have sufficient discriminatory power to allow for the clinical application of coronary artery Doppler in the management of pregnancies complicated by fetal growth restriction. There are insufficient data at the present time on whether Doppler waveforms of the coronary arteries provide additional information on the cardiovascular status of the growth-restricted fetus over that provided by studying the central venous circulation. In a longitudinal observational study by Baschat et al.13, demonstration of coronary blood flow in severe IUGR fetuses coincided, in all cases, with a significant deterioration of venous indices. Further longitudinal studies are required to assess the temporal relationship of the venous and coronary systems and to compare the value of coronary artery Doppler over that afforded by Doppler of the central venous circulation. The authors should be congratulated on their work in this field. They have demonstrated unequivocally that several adult physiological principles of coronary flow dynamics are operational in the fetus. With improved resolution of sonographic equipment, visualization of coronary arteries in the future may be possible at an earlier gestation and in a greater number of fetuses. With more accumulation of data, Doppler of the coronary circulation may provide assistance in the management of the growth-restricted fetus in the third trimester, a time in gestation when traditional Doppler studies have generally shown a lack of effectiveness18, 19. Finally, the finding of an acute increase in diastolic velocities in coronary arteries in severely anemic fetuses is intriguing and warrants further exploration17.