Doppler Ultrasound Examination of the Fetal Coronary Circulation

Introduction

The coronary circulation provides blood to the myo- cardium. Matching myocardial blood flow and de- mand is critical to ensure cardiac function over a wide variety of physiologic and pathologic condi- tions. For this reason examination of coronary vascu- lar dynamics in various fetal conditions is becoming increasingly relevant to the perinatal medicine spe- cialist. Ultrasound examination of the fetal coronary circulation has become possible through advances in ultrasound technology and a better understanding of human fetal cardiovascular physiology. Although not yet standard clinical practice, continuing trends in ul- trasound technology and spreading familiarity with the examination and interpretation is likely to expand clinical applications in the future [1].

Ultrasound examination of the fetal coronary sys- tem utilizes gray-scale, zoom and cine-loop tech- niques and requires optimal spatial and temporal set- tings of the Doppler modalities. A proper setup of the ultrasound system is therefore a necessary prere- quisite. Traditional ultrasound planes used in cardiac scanning are modified to provide the best visualiza- tion of the coronary vessels. A comprehensive survey of extracardiac vascular dynamics is often necessary to provide the clinical context for interpretation of in- tracardiac and coronary flow dynamics. This chapter reviews embryology, functional anatomy, ultrasound technique, and clinical utility of ultrasound evalua- tion of the fetal coronary circulation.

Embryology and Functional

Anatomy of the Coronary Circulation

Oxygenated blood is delivered to the myocardium through the right coronary artery (RCA) and left coronary artery (LCA) arising from the right anterior and left posterior aortic sinuses, respectively, and the left anterior descending branch (LAD) of the LCA [2, 3]. Venous return from the left ventricle drains mainly through a superficial system through the coro- nary sinus and anterior cardiac veins carrying ap-

proximately two-thirds of myocardial venous return.

The deep system, consisting of arterioluminal vessels, arteriosinusoidal vessels, and thebesian veins, receives the remaining venous return and drains directly into the cardiac chambers [2±4].

In embryonic life endothelial cells migrate from the septum transversarium in the hepatic region of the embryo to form epicardial blood islands which eventually coalesce into vascular networks extending throughout the epicardium and myocardium [5, 6].

Concurrently, the RCA and LCA originate as micro- vessels that penetrate the outflow tracts and acquire a muscular coat in this process. The primitive coronary arterial circulation is established when main-stem coronary arteries and myocardial vascular channels connect. Venous drainage develops independently of the arterial system and becomes fully functional when the coronary sinus, as a remnant of the left horn of the sinus venosus, becomes incorporated into the inferior wall of the right atrium and thebesian veins gain access to the ventricular cavities. The coro- nary circulation is completely functional by the fifth to sixth week of embryonic life and ensures myocar- dial blood supply by the time the embryonic circula- tion is established.

Coronary vascular development can be modulated by various stimuli. Such stimuli include local oxygen tension, mechanical wall stress, and myocardial and vascular shear forces [6±9]. As a result, the coronary circulation is subject to great anatomic and functional variation that is manifested in several ways. Under physiologic conditions modulation of vascular growth enables matching coronary vascular development to myocardial growth [10]. This ensures a balanced rela- tionship between ventricular mass and vascular den- sity. Prolonged or progressive tissue hypoxemia may lead to an exaggeration of this physiologic process with a subsequent marked increase in vascular cross- sectional area in the coronary circulation [11±14].

Under these circumstances vascular reactivity to physiologic stimuli is also altered, often resulting in amplified responses [15]. Similarly, abnormal intra- cardiac pressure relationships, such as those found in outflow tract obstructive lesions, may force the devel- opment of accessory vascular channels between the

Doppler Ultrasound Examination of the Fetal Coronary Circulation

Ahmet Alexander Baschat

coronary vessels and the ventricular cavity (ventricu- lo-coronary fistulae) [16]. The plasticity of the coro- nary circulation is responsible for the variation in myocardial vascular territories and blood flow found in various fetal conditions and illustrates the critical importance of myocardial oxygenation for proper car- diac function.

Myocardial metabolism is almost exclusively aero- bic and in the presence of adequate oxygen various substrates, including carbohydrates, glucose, lactate, and lipids, can be metabolized [17±20]. In fetal life, myocardial glycogen stores and lactate oxidation con- stitute the major sources of energy while fatty acid oxidation rapidly becomes the primary energy source after birth. To maintain metabolism myocardial oxy- gen extraction is as high as 70%±80% in the resting state. Consequently, a coronary atrioventricular O

difference of 14 ml/dl exceeds that of most other vas- cular beds and allows little further extraction of O

unless blood flow is significantly augmented; there- fore, coronary blood flow is closely regulated to match myocardial oxygen demands.

The regulation of myocardial perfusion operates at several levels and time frames. The unique parallel arrangement of the fetal circulation allows for deliv- ery of well-oxygenated blood through the ductus ve- nosus to the left ventricle and thus the ascending aor- ta. In the fetal lambthe coronary circulation receives approximately 8% of the left ventricular output at rest in this manner [21]. This proportion may be higher in the human fetus and may be further altered by modulating the degree of shunting through the duc- tus venosus [22]. Once blood enters the coronary ves- sels from the ascending aorta the pressure difference to the right atrium becomes the primary driving force for coronary blood flow. This perfusion pressure is further subjected to changes in vascular tone and extravascular pressure. Autonomic innervation of co- ronary resistance vessels regulates overall vascular tone [23, 24], but ventricular contractions are the main contributor to extravascular resistance with sig- nificant impact on the flow velocity waveform [25±

27]. Myocardial perfusion predominantly occurs dur- ing diastole when the ventricles relax and pose little extravascular resistance. This diastolic timing of pre- dominant perfusion is unique to the coronary circula- tion and distinguishes it from other vascular beds in the human body. In the adult, increases above a rest- ing heart rate of 70 beats per minute result in a dis- proportional shortening of diastole. Fetal heart rates of 120±160 beats per minute place special demands on dynamic vascular mechanisms to regulate myocar- dial blood flow volume.

Efficiency of myocardial oxygen delivery is further enhanced by active autoregulatory control mecha- nisms ensuring optimal myocardial blood flow de-

spite fluctuations in arterial perfusion pressure [28, 29]. This is achieved through caliber adjustment of precapillary resistance vessels allowing channeling of blood flow to areas of greatest oxygen demand [30, 31]. With maximal dilatation of these sphincters myo- cardial blood flow may be elevated four times above basal flow. The increase in blood flow volume that can be achieved under these circumstances is the myocardial blood flow reserve. If myocardial oxyge- nation cannot be sustained, long-term adaptation with formation of new blood vessels may be invoked thus increasing the myocardial blood flow reserve [32±34]. Such elevated myocardial blood flow reserve allows marked augmentation of blood flow during periods of acutely worsening hypoxemia or increased cardiac work and increases as high as 12 times the basal flow have been reported [15, 35, 36].

Ultrasound Examination Technique

Ultrasound Setup

The setup of the ultrasound system is of major im- portance for successful examination of the fetal coro- nary arteries. Gray-scale ultrasound, color-, and pulsed-wave Doppler are used in a complementary manner and machine settings need to be optimized to provide the best spatial and temporal resolution.

Although visualization of coronary vessels can be

achieved using 4-MHz transducers, higher frequencies

are likely to improve resolution and therefore detec-

tion. The dynamic range of the gray-scale image

should be set to an intermediate level that is generally

used in cardiac setups. Zoom magnification of the

area of interest limits the computing power that

needs to be allocated to the generation of the gray-

scale image. These two maneuvers will improve the

frame repetition rate and should therefore be applied

before adding color Doppler imaging. When adding

color Doppler imaging the filter should be set to a

high degree of motion discrimination and the color

box and gate are kept as small as possible to optimize

spatial and temporal resolution of this Doppler mo-

dality. The lateral dimension of the color box has the

greatest impact on computing power and therefore

frame rate. The color amplification gain is set to

eliminate background noise on the screen. The persis-

tence is set to a low level to minimize frame aver-

aging. The color velocity scale is adjusted to a range

that allows visualization of intra- and extracardiac

flows without aliasing and suppression of wall-motion

artifacts. A useful velocity range for coronary arteries

is between 0.3 and 0.7 m/s for coronary arteries and

between 0.1 and 0.3 m/s for the coronary sinus. Since

initial detection of the coronary arteries relies on col-

or Doppler, these aspects of the setup are essential preliminary steps. Once the coronary vessel is identi- fied using these techniques the transducer position should be adjusted to provide an insonation angle close to 08 prior to obtaining pulsed-wave measure- ments. The pulsed-wave Doppler gate should be ad- justed to exclude other cardiac and extracardiac flows and should be the only active display when measure- ments are taken. Concurrent activation of multiple image modalities (duplex or triplex mode) drastically increases computing requirements and affects the spatial and temporal resolution of the spectral Dop- pler waveform.

Examination of Coronary Arteries

Using gray-scale ultrasound the coronary ostia are discernable in late gestation (Fig. 29.1). Before this time, the size of the main-stem arteries is below 1 mm in diameter and thus frequently below the re- solution threshold of current sonographic equipment in the majority of cases [37]. For this reason color and pulsed-wave Doppler ultrasound are necessary to detect and verify coronary artery blood flow. The Doppler examination of the fetal coronary vessels has been adopted from techniques developed for infants and neonates [38]. The main-stem right and left coro- nary arteries are best examined in a long-axis view of the left ventricular outflow tract and ascending aorta or a precordial short-axis view of the aorta. The LAD branch of the LCA is best identified from an apical short-axis view. In the standard precordial short-axis view the left coronary artery courses forward towards the transducer, whereas the right coronary artery runs more parallel. This view therefore facilitates ex- amination of the LCA. In the lateral, or long-axis, view of the left ventricular outflow tract the RCA is more readily imaged if imaged from the right side of the fetus. In this view it may also be possible to vi- sualize both coronary arteries (Fig. 29.2) [39, 40].

The LAD may be identified scanning from the apical four-chamber view. From this view the transducer is tilted towards the head until the level of the superior cardiac surface and interventricular groove is reached [41]. Cardiac wall motion, high blood flow velocities in the ventricles and ventricular outflow tracts and movement of pericardial fluid can all interfere with the relatively low coronary blood flow velocities on color Doppler imaging. Back and forward motion of pericardial fluid outlining the ventricular walls in particular may be mistaken for a coronary artery [42]. For these reasons identification of coronary ar- tery blood flow by color Doppler imaging should al- ways be followed by verification of the typical wave- form pattern by pulsed-wave Doppler to provide as- surance that the coronary arteries have indeed been identified.

Spectral Doppler measurement of coronary blood flow velocities is easiest proximally since vessel diam- eter is greatest and motion during the cardiac cycle is less than distally. After coronary vessels are identi- fied by color Doppler, the pulsed-wave Doppler gate is positioned at the origin of the vessel. The gate may require adjustment to achieve continuous sampling of the waveform allowing for the movement of the aor- tic root in the cardiac cycle. The coronary artery flow velocity waveform has a biphasic pattern with systolic and diastolic peaks and antegrade flow throughout the cardiac cycle (Fig. 29.3). Predominant diastolic perfusion produces a unique waveform pattern with higher velocities during diastole than systole. In nor- mal fetuses coronary blood flow has been visualized from 29 weeks onwards (median gestational age of 33Ô6 weeks). The median systolic and diastolic peak blood flow velocities are 0.21 and 0.43 m/s, respec- tively, and show little change during the latter part of gestation (Figs. 28.4, 28.5) [43]. Gestational age at vi- sualization and coronary artery blood flow velocities are in part determined by the fetal condition (see be- low).

Fig. 29.1. The fetal heart is ex- amined in a short-axis view of the aorta at 34Ô2 weeks gesta- tion (a) and in a long-axis view of the left ventricular outflow tract at 35Ô5 weeks' gestation (b). The ostia of the left and right coronary arteries are dis- cernible in a (arrows) in the area of the left posterior and right anterior aortic sinus. (From [87]).

In b the ostium of the left coro-

nary artery is discernible (arrow)

Examination of the Coronary Sinus

The larger size of the coronary sinus and its anatomic course greatly facilitate its ultrasound examination [44, 45]. The coronary sinus runs in the atrioventric- ular groove and enters the right atrium below the lev- el of the foramen ovale just above the valve of the in- ferior vena cava. Because of its position, apical or ba- sal four-chamber views provide the best opportunity for gray-scale biometry, whereas lateral four-chamber views provide a more favorable insonation angle for color- and spectral Doppler imaging (Figs. 29.6, 29.7).

Gray-scale and M-mode echocardiography have both been used to obtain normative data on the

length and diameter of the coronary sinus. The cali- ber of the coronary sinus undergoes cyclic changes with the cardiac cycle being smallest at the beginning of diastole and largest in mid-systole with maximal descent of the arteriovenous ring. M-mode echocar- diography allows precise documentation of caliber and dynamic changes (Fig. 29.8). The coronary sinus has a maximum diameter ranging from 1 to 3 mm with advancing gestation. The method utilized to ob- tain these measurements does influence the reference limits [45, 46]. Figures 29.9 and 29.10 show gesta- tional reference ranges for the maximal diastolic and systolic dimensions that were measured using the M- mode technique. Appreciating the phenomenon of variations in coronary sinus diameter may call for Fig. 29.2. The origin of the great vessels and the atrioven-

tricular valves shows the course of the left and right coro- nary arteries (RCA and LCA, respectively) in relationship to the aorta (AO), pulmonary artery (P), mitral valve (MV), and tricuspid valve (TV). The angle of insonation and type of cardiac axis determines the orientation of the coronary ar- teries on the ultrasound image. Short-axis views facilitate examination of the left coronary artery (B) and may enable

visualization of both coronary arteries (C) occasionally also

allowing demonstration of the origin of the left anterior

descending branch (B, C). Although the right coronary ar-

tery can be examined in the short-axis view (A), it is easier

to identify this vessel in a right lateral long-axis view of the

left ventricular outflow tract (E). This view also allows si-

multaneous visualization of both coronary arteries (D)

Fig. 29.3a±c. Pulsed-wave Doppler images of the left coro- nary (LCA), left anterior descending (LAD), and right coro- nary arteries (RCA) obtained in a 29-week fetus. Of note is

the predominance of blood flow during diastole that is ob- served in all three vessels. (From [87])

Fig. 29.4. The median and 95% confidence interval for the peak systolic velocity (PSV) in the coronary artery of appro- priately grown fetuses in relation to gestational age (GA).

(From [43])

Fig. 29.5. The median and 95% confidence interval for the

peak diastolic velocity (PDV) in the coronary artery of ap-

propriately grown fetuses in relation to gestational age

(GA). (From [43])

Fig. 29.6. The fetal heart shows the course of the coronary sinus in the right lateral four-chamber view. The coronary sinus runs in the atrioventricular groove and opens into the right atrium near the atrioventricular valve, in close proximity to the inferior vena cava (IVC) and foramen ovale (FO). In this imaging plane, the direction of blood flow is towards the transducer beam. (From [47])

Fig. 29.7. The fetal heart imaged in the apical four-cham- ber view shows the left and right ventricles (LV and RV) and the corresponding atria (LA and RA). The coronary si- nus runs in the atrioventricular groove parallel to the mitral valve leaflets. The coronary sinus is visualized by tilting the transducer towards the inferior cardiac surface until the valve leaflets disappear. (From [45])

Fig. 29.8. The fetal heart imaged in an apical four-chamber view at 28Ô4 weeks' gestation. The coronary sinus (arrows) can be seen running in the atrioventricular groove be- tween the left ventricle (LV) and atrium. Using the cine- loop technique a difference in diameter between end-sys-

tolic (A) and mid-systolic (B) diameters can be appreciated.

M-mode tracing obtained from a normal coronary sinus at

29 weeks' gestation demonstrating fluctuations during sys-

tole and diastole (C). The cursors are placed on the anterior

and posterior walls of the coronary sinus. (From [45])

verification using this M-mode technique when dila- tation of the coronary sinus is suspected.

Color Doppler identification of coronary sinus blood flow is successful in approximately 50% of nor- mal fetuses. During diastole the direction of blood flow from the coronary sinus is towards the right at- rium, whereas blood flow across the foramen ovale is directed towards the left atrium (Fig. 29.11) [47]. De- spite its straight course, exact placement of the sam- ple volume spectral Doppler measurements is only possible in approximately 10% of fetuses. This low success rate is partly due to lower coronary sinus blood flow velocities and interference caused by in-

tra-atrial blood flows and/or cardiac and atrioventric- ular valve movement. The coronary sinus flow veloc- ity waveform has a triphasic pattern with systolic and diastolic antegrade flow and occasional reversal dur- ing atrial contraction (Fig. 29.11). Similar to the coro- nary arteries, diastolic forward velocities (median 0.38 m/s) exceed systolic velocities (median 0.18 m/s).

These velocities are related to the periods of predom- inant myocardial blood flow. Methods to relate coro- nary sinus velocities to myocardial flow reserve have been described in neonates and adults [48, 49], but these are currently not practicable for validation in the human fetus.

Fig. 29.9. Individual measurements, and the mean and 95% confidence interval of the maximum systolic diameter of the coronary sinus with respect to gestational age (y=0.1373x+1.6072; r

=0.9849). (From [45])

Fig. 29.10. Individual measurements, and the mean and 95% confidence interval of the maximum diastolic diame- ter of the coronary sinus with respect to gestational age (y=0.0765x+0.9242; r

=0.9701). (From [45])

Fig. 29.11. The fetal heart is imaged in

a lateral four-chamber view and coro-

nary sinus blood flow towards the right

atrium (RA) is identified with color Dop-

pler imaging (a). Pulsed-wave Doppler

shows a triphasic flow profile with a

small systolic (S) and a larger diastolic

peak (D) followed by brief reversal dur-

ing atrial contraction (b). (From [87])

Clinical Applications in Fetuses with Normal Cardiac Anatomy

In fetuses with normal cardiac anatomy disorders are frequently only apparent through alterations in cardi- ovascular status. Under these circumstances coronary blood flow dynamics may be altered to accommodate changes in myocardial oxygen requirements. Since spectral Doppler of the coronary sinus is rarely achieved, clinical observations revolve primarily around color- and pulsed-wave Doppler characteris- tics in coronary arterial vessels.

The ªHeart-Sparing Effectº in Fetal Growth Restriction

Severe fetal growth restriction (IUGR) can progress to decompensation of cardiovascular status. Such de- terioration can be documented through progressive deterioration of arterial and venous Doppler studies [50]. This progression often accompanies the dete- rioration of acid±base status from chronic hypoxemia to acidemia [51±54]. Under these circumstances the combination of elevated central venous pressure, ele- vated afterload, and worsening oxygenation places unique demands on myocardial oxygen balance. Ele- vated afterload increases myocardial oxygen demand because of an increase in cardiac work. Elevated cen- tral venous pressure and aortic pressures decrease the pressure difference across the coronary vascular bed and therefore diminish the driving force for coronary perfusion. The summation of these factors has detri- mental effects on coronary perfusion at a time when myocardial oxygen balance and fetal metabolic state are critical. Consequently, adaptive mechanisms need to be evoked in order to maintain myocardial oxygen balance. The necessary augmentation of coronary blood flow can be achieved in two principal ways.

One way is to increase the proportion of oxygenated left ventricular output available for myocardial deliv- ery. The second way is through autoregulation- mediated coronary vasodilatation.

Several mechanisms operate in IUGR fetuses that increase the potential delivery of oxygenated blood to the myocardium. Under conditions of elevated plac- ental resistance the relative proportion of left ventri- cular output increases [55±57]. Decreases in oxygen tension may further increase the proportion of oxyge- nated umbilical venous blood that is delivered through the ductus venosus to the left side of the heart [58, 59]. Prolonged chronic myocardial hypox- emia allows for angiogenesis and increases in vascu- lar cross-sectional area and therefore myocardial flow reserve. These responses constitute chronic heart sparing in IUGR. When acute worsening of cardio-

vascular status and/or oxygenation is superimposed the only mechanism to significantly augment myocar- dial blood flow is marked coronary vasodilatation with massive recruitment of coronary vascular re- serve. This vascular response is more acute, often oc- curring over the course of 24 h, and is most consis- tently associated with severe elevation of precordial venous Doppler indices [60, 61].

The chronic initial phase of heart sparing can be implied by demonstrating certain Doppler abnormali- ties in the arterial and venous circulations. These in- clude absent or reversed umbilical artery end-diastol- ic velocity and/or end-diastolic blood flow reversal in the aortic isthmus [62]. In the second trimester the magnitude of coronary blood flow may still be below the visualization threshold of ultrasound equipment;

therefore, augmentation of coronary blood flow can- not be documented by spectral Doppler measurement of coronary arteries. With acute worsening of fetal cardiovascular and respiratory status color- and pulsed-wave Doppler measurement of coronary artery blood flow is readily achieved as a reflection of maxi- mal augmentation of coronary blood flow ± now ex- ceeding the visualization threshold [40]. In IUGR both diastolic and systolic coronary artery peak blood flow velocities are significantly higher than in appropriately grown fetuses providing additional evi- dence of blood flow augmentation. There are no asso- ciated changes in the coronary sinus diameter as evi- dence of increased coronary venous return [63]. Since coronary artery blood flow may be visualized in nor- mal and IUGR fetuses at overlapping gestational ages, concurrent examination of the arterial and venous circulations is mandatory to assess fetal status. Clini- cal management cannot be based on the evaluation of coronary vascular dynamics alone. In IUGR fetuses with abnormal arterial and venous Doppler, heart- sparing prognosis is poor with a high perinatal mor- tality and a high risk for acidemia and neonatal cir- culatory insufficiency requiring the highest level of neonatal care.

Fetal Anemia

Severe fetal anemia can result in reduction of oxygen-

carrying capacity and subsequently impaired myocar-

dial oxygenation. Fetal hydrops with tricuspid insuffi-

ciency and abnormal precordial venous flow is asso-

ciated with elevated right-heart pressures and a de-

cline in coronary perfusion pressure. Under these cir-

cumstances short-term augmentation of myocardial

blood flow of four to five times basal flow can be

achieved through autoregulation. Color- and spectral

Doppler measurement of coronary artery blood flow

velocities has been successful in circumstances of

acute fetomaternal hemorrhage, non-immune hy-

drops, and hemolytic disease [43, 64]. Peak diastolic velocities as high as 1 m/s and peak systolic velocities of 0.5 m/s may be observed, significantly exceeding those observed in any other fetal condition. Blood flow velocities are responsive to maternal oxygen therapy and fetal blood transfusion and fall below the visualization threshold after normalization of the fetal hematocrit (Fig. 29.12). With the development of fetal hydrops, a decrease in coronary sinus dynamics is observed. This finding is analogous to observations in adults with heart failure where coronary sinus cali- ber changes are attenuated presumably due to eleva- tions in coronary venous pressures [45].

Ductus Arteriosus Constriction

Constriction of the ductus arteriosus is one of the re- ported fetal complications of maternal indomethacin therapy for preterm labor. As a conduit for the right ventricle to the systemic circulation, constriction of this vessel raises afterload and therefore cardiac work and oxygen requirement. In severe constriction tri- cuspid insufficiency and abnormal venous indices may develop. In such severe cases color- and pulsed- wave Doppler of coronary artery blood flow is possi- ble. While the peak velocities are not significantly elevated, the gestational age at visualization is deter- mined by the onset of the clinical condition. With resolution of ductus arteriosus constriction following discontinuation of indomethacin, coronary blood flow could no longer be visualized.

Other Fetal Conditions

Acute changes in fetal oxygenation and cardiac pre- and afterload also cause arterial and venous redistri- bution in favor of the organs essential for fetal life.

These ªheart-, brain-, and adrenal gland-sparingº phenomena have been described in different animal models. The few observations made by Doppler ultra- sound in the human fetus support the presence of the same protective mechanisms. Transient ªbrain- and heart-sparingº phenomena were observed in a 30- week fetus following acute bradycardia after umbilical fetal blood sampling. Sudden visualization of coro- nary blood flow, ªbrain-sparing,º and highly pulsatile precordial venous flow persisted for a long period after the 12-min bradycardia [65]. Changes in coro- nary sinus dynamics have been documented in a fe- tus with supraventricular tachycardia [45]. It is likely that more observations of alterations in coronary ar- terial and venous dynamics will be reported as famil- iarity with the examination technique and advances in ultrasound technology facilitate examination.

Clinical Applications

in Fetal Cardiac Abnormalities

Due to the vascular properties of the coronary arteri- al circulation abnormalities frequently develop in car- diac lesions that are associated with disturbed intra- cardiac pressure/volume relationships during organo- genesis. Owing to the embryologic development of coronary sinus abnormalities involving this vessel, anomalous central venous drainage (both systemic and/or pulmonary) is frequently present. Ultrasound biometry and assessment of coronary sinus dynamics has clinical relevance and may be the only apparent clue pointing in the direction of such anomalies.

Ventriculocoronary Connections in the Human Fetus

Ventriculocoronary connections are frequently noted in fetuses and newborns with pulmonary atresia, hy- poplastic right ventricle, intact ventricular septum, or restrictive ventricular septal defect [66]. In cases of hypoplastic left heart with aortic atresia, intact ven- tricular septum and patent mitral valve ventriculoco- ronary connections may also be present but are less common. The genesis of these vascular abnormalities is discussed above. The abnormal coronary channels may provide a conduit to release intraventricular pressures and may partially avert hypoplasia and fi- broelastosis; however, coronary blood flow dynamics may be significantly compromised, impacting on prognosis and approach to postpartum surgical man- Fig. 29.12. Systolic and diastolic peak blood flow measure-

ments in three cases of severe fetal anemia. In cases 1 and

3 velocities were obtained in hydropic fetuses prior to

transfusion. In case 1 a hematocrit of 9% was corrected to

39.8% and in case 3 from 14% to 42.8%. In the second

case of maternal trauma, repeated transfusions were neces-

sary on days 1 and 5 for hematocrit levels of 21% and

24%, respectively. (From [43])

agement [67±69]. While coronary perfusion may be well maintained in utero, the situation may change after birth. Right ventricular dependent coronary cir- culation may occur and result in acute or chronic global myocardial ischemia or infarction due to coro- nary steal and segmental vascular obstruction. Be- cause of these potential impacts, prenatally detected outflow tract obstructive lesions with relatively pre- served ventricular architecture should prompt the search for ventriculocoronary fistula.

Prenatal diagnosis of ventriculocoronary fistula is achieved by demonstration of high-velocity bi-direc- tional flow in the coronary artery by color Doppler flow mapping and verified by pulsed-wave Doppler examination. A severely dilated coronary artery may also be imaged by two-dimensional echocardiogra-

phy. In cases of right ventricular outflow tract ob- struction, diastolic flow from the aortic sinus is di- rected toward the hypoplastic right ventricle. Pres- sures are reversed during ventricular systole and blood flows from the right ventricle to the aorta (Fig.

29.13) [66, 70, 71].

Coronary Arteriovenous Fistula in the Human Fetus

Congenital coronary fistulae may occur occasionally if cardiac anatomy is otherwise normal; the majority of these involve a single coronary artery, less often multiple branches. Connections may involve the coro- nary arterial tree, right atrium, coronary sinus, caval veins, right ventricle, and the pulmonary trunk.

Drainage into a low-pressure system can result in a large left-to-right shunt already causing symptoms in childhood such as congestive heart failure, myocar- dial ischemia from coronary artery steal, right-cham- ber enlargement, arrhythmia, thrombosis with con- secutive embolization, and bacterial endocarditis [72]. In the majority of cases symptoms appear in the second and third decade of life. In a 20-week fetus prenatal detection of an isolated coronary fistula con- necting to the right ventricle has been reported with demonstration of a progressive increase in size as well as tortuosity of the fistula during gestation [73].

A similar case with a fistula between the LCA and the right atrium has also been recently described [74].

The shunting blood caused a high-velocity flow in the dilated coronary sinus. In addition to the prenatal findings a persistent left superior vena cava and a small ventricle septum defect were also identified postnatally. Following coil embolization of the coro- nary fistula further clinical course was reported as uneventful.

Idiopathic Arterial Calcification in the Human Fetus

The idiopathic arterial calcification has an unknown etiology and is characterized by generalized arterial calcification and stenoses especially of the walls in the arterial trunk of the pulmonary artery and aorta [75, 76]. Most commonly the coronary arteries are also affected, but peripheral arteries of gastrointesti- nal tract, liver, kidneys, brain, extremities, and pla- centa may also be involved. Severe myocardial dys- function may cause severe fetal hydrops, tissue isch- emia, and fetal death in the late second or third tri- mester [77]. In less severe cases, especially in the ab- sence of hydrops, palliative treatment post-partum may be started with steroids and bisphosphonates in order to stop or delay the progression of the disease [78]; however, most infants with idiopathic arterial Fig. 29.13. The fetal heart is imaged in a lateral ªfive-

chamberº view including the left ventricular outflow tract.

A large tortuous vessel is seen originating from the aorta

connecting into the right ventricular cavity, which is of

moderate size (a). Pulsed-wave Doppler with the gate in

the ventriculocoronary fistula shows the characteristic bi-

directional flow pattern with systolic flow towards the aor-

ta (below the baseline) and diastolic flow towards the right

ventricle (above the baseline; b). (From [16])

calcification die within the first year of life compli- cated by cardiac and pulmonary failure, severe hyper- tension, renal infarction, peripheral gangrene, and bowel infarction [76].

Critical Aortic Stenosis

Critical aortic stenosis in fetal life can be associated with a marked decrease in left ventricular output and reversal of shunting across the foramen ovale. Under these circumstances coronary perfusion pressure is affected by a decrease in arterial pressure and an ele- vation of right atrial pressure thereby decreasing the driving force across the coronary vascular bed. Con- currently, left ventricular work and therefore myocar- dial oxygen demand are increased. Development of acute heart sparing has been documented in a fetus presenting with severe left ventricular outflow tract obstruction and non-immune hydrops due to critical aortic stenosis. While these findings were ameliorated initially by transplacental digoxin therapy, visualiza- tion of coronary blood flow became visible at 39 weeks coinciding with shunt reversal across the fora- men ovale [79].

Persistent Left Superior Vena Cava

While Doppler examination of the coronary sinus has limited utility in the human fetus, substantial dilata- tion may result from volume overload from a persis- tent left superior vena cava draining into the coro- nary sinus [80±82]. The frequency of a persistence of the left vena cava is 1±2 per 1000 but may be as high as 9% in the presence of congenital heart defects [83]. The degree of dilatation is often marked and lies appreciably above normal reference limits. This dila- tation appears to be predominantly related to vascular volume changes and is independent of associated car- diac defects [63]. Other causes of coronary sinus dila- tation in the human fetus may be a coronary arterio- venous fistula and anomalous pulmonary vein drain- age into the coronary sinus. It is important to note that because of its close proximity to the insertion of the atrioventricular valve, a dilated coronary sinus has been mistaken for an atrial septal defect of os- tium primum type and/or an atrioventricular septal defect, respectively [84±86]. Coronary sinus dynamics may be attenuated in fetal conditions associated with elevated right-heart pressures, severe fetal cardiac dysfunction, and hydrops. These alterations in dy- namics may indicate elevated coronary sinus pres- sures or changes in coronary blood flow [45].

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