Fetal cardiac output estimated by Doppler echocardiography during mid- and late gestation

CONGENITAL

HEART DISEASE

Fetal Cardiac Output Estimatedby Doppler EchocardiographyDuring Mid- and late Gestation MARYSE

C.H. De SMEDT, MD, GERARD H.A. VISSER, MD, PhD, and ERIK J. MEIJBOOM, MD, PhD

Fetal cardiac output was quantitated by 2-dimensional (2-D) Doppler echocardiography. Circulatory dynamics in the fetus differ from circulatory dynamics after birth because right and lefl ventricles work in parallel. Therefore, volume flow was estimated over the mitral and tricuspid orifice separately. Serial 2-D echo Doppler studies were performed in 28 normal fetuses at 4-week intervals from 15 to 18 weeks of gestation to the time of parturition. Measurement of blood flow velocities through mitral and tricuspid valve orifices and measurement of the diameter of these valve orifices were obtained from apical 4-chamber views of the fetal heart. Anglecorrected mean temporal blood flow velocities increased linearly with gestational age, whereas the area of blood flow and calculated right and left ventricular output increased exponentially. The right

ventricular blood flow velocities, areas of tricuspid orifice and calculated right ventricular outputs were significantly higher than those for the left ventricle when analyzed by paired f test (0.005 >2p >O.OOl). The ratio of right to left ventricular output decreased from 1.34 f 0.28 (It standard deviation) at 15 weeks to 1.08 f 0.28 at 40 weeks. The combined ventricular output of the fetus near term is approximately 1,735 ml/min, whereas flow indicated for estimated fetal weight is constant at a mean value of 553 f 153 ml/min/kg. Thus, 2-D echo Doppler provided a means of estimating fetal cardiac blood flow at the atrioventricular orifices, and blood flow measured at these orifices increased exponentially during gestation, with a larger output from the right ventricle than from the left ventricle. (Am J Cardiol 1987;80:338-342)

U

ntil very recently information about the fetal circulation was mainly obtained from invasive animal studies.l-3 Since the arrival of high-resolution ultrasound devices capable of evaluating the human fetal circulation, studies have appeared in which volume flow in the descending aorta4F5 and left ventricular stroke volume are estimated.5*6 The purpose of this longitudinal [cohort of simular gestational age) study was to define the gradual changes in right and left volume flow in the normal human fetus. Each fetus was studied serially through the course of middle and late gestation using a technique for quantification of blood flow volume at the atrioventricular (AV) valve orifices.7-g

risk was given. The study consists of 28 cases. Initial investigations were performed between 15 and 18 weeks of gestation and subsequent examinations every 4 weeks until delivery. The duration of gestation was calculated from the first day of the last menstrual period and was verified and adjusted by first-trimester crown-rump length measurements in ultrasound examination. Estimated fetal weight was deduced from birth weight tables according to Brenner et allo (20 to 25 weeks] and Kloostermanll [after 25 weeks]. With the latter, estimated weight was adjusted for parity and gender. Weight was back-calculated using the same weight percentile as was found at birth. Before 20 weeks no deduction of estimated weight was made as data on normal fetal weight this early are too limited. Babies included were normal at birth and appropriate for dates, and no maternal pathologic conditions were present; the birth weights ranged from 2,590 to 5,250 g (mean 3,526 f 587). Normal cardiac anatomy was confirmed by echocardiography. Ultrasound and Doppler methods: The studies were performed with a sector scanner with a rangegated pulsed Doppler unit (ATL, Mark 600, 3- to 5MHz transducers). During the recordings the mothers lay in a semireumbent position. The transducer was oriented in a transverse fetal plane to produce an api-

Methods Patients: Patients gave informed consent after a detailed explanation of the. investigation and associated From the Departments of Obstetrics and Pediatrics, University of Groningen, The Netherlands, and the Department of Pediatrics, University of Maryland, Baltimore, Maryland. This work was supported by a grant from The Netherlands Heart Foundation Manuscript received January 27, 1987; revised manuscript received March 20,1987, accepted March 21,1987. Address for reprints: Erik J. Meijboom, MD, PhD, Department of Pediatrics, University of Maryland Medical Center, 22 South Greene Street, Baltimore, Maryland 21201. 338

August

cal4=chamber view of the fetal heart. To measure the diameter of the AV orifices, 2 optimal 4=chamber views showing the maximized diameters of the AV anuli were stored on freeze frames during the diastolic phase of the cardiac cycle. Insertion of these AV valves into the cardiac skeleton was clearly visualized by echodense dots; reflections of the fibrous skeleton of the AV ring aided in identifying the anulus. The Doppler sample volume was placed in the ventricles just inferior of the AV valve leaflets to measure the Doppler frequency shift. The angle between the Doppler sample volume and the estimated trans=AV valve blood flow was mea= sured from hard-copy freeze frames. All studies were performed at heart rates between 106 and 155 beats/ min (mean 132 f 91, while heart rate differences between left- and right-sided measurements were kept below 10 beats/min. Measurements made during fetal breathing were excluded from the study. Data analysis: Calculations: Blood flow volume through the mitral and tricuspid valve orifice was calculated using the formula: Q = (V X Aj/Cos 8, where V = mean temporal velocity (cm/s), A = estimated area of the AV orifices (cm2], and 0 = angle between the Doppler SV and the direction of blood. The blood flow was calculated according to previously described methods.7J The Doppler frequency shift recordings were assessed visually and only recordings with a normal phasic AV valve flow were used. The area under 3 consecutive cardiac cycles were integrated and timeaveraged [Fig. 1A). From the 2-D freeze frames of the 4=chamber views the diameter of the tricuspid and mitral orifices was measured 5 times from the insertion of the AV valve leaflets at the septal side to their insertion on the free wall [Fig. 1Bj. The angle of interception was measured between a line indicating the direction of blood flow from the center of the valve to the apex parallel to the septum and the superimposed Doppler sample volume on a freeze frame. Angles over 30° were rejected. Statistics: Multiple regression analyses were used to evaluate data. The best-fit correlation between mean temporal velocities and estimated gestational age was a linear function. The areas of flow and ventricular output related to gestational age is expressed in an exponential function, volume flow-corrected for estimated fetal weight as a linear function. Data were regressed to the several functions and 90% confidence limits were calculated. The difference between right and left ventricular flow velocities, area of flow and calculated blood flows was analyzed by paired t test.

Results Of the 188 examinations 146 (78%] showed adequate results for velocity calculations. Volume calculations were successful in only 113 cases (60%]. In 5 fetuses either the right or left AV volume flow but not both could be measured. The success rate of the volume calculations was 44% at 15 to 19 weeks and ranged from 62 to 75% thereafter.

1987

WE AMERICAN

JOURNAL

OF CARDIOLOGY

Volume 50

338-J

The mean intercept angle between the Doppler sample volume and the direction of the blood flow was 10.5 f 7.6’ (range 0 o 30’) [standard deviation]. Angle-corrected mean temporal velocities, areas of mitral and tricuspid orifices and the resulting blood flows as calculated in this study are shown in Table I. The angle-corrected mean temporal velocities for the mitral and tricuspid valves increased from 9.8 f 1.8 cm/s for the mitral and 11.1 f 1.7 cm/s for the tricuspid valve at age 15 to 20 weeks gestation up to 15.2 f 2.3 cm/s for the mitral and 16 f 3.1 cm/s for the tricuspid valve at the 30- to 40=week gestation interval. The area, of the mitral and tricuspid valves are increasing from 0.09 f 0.03 cm2 mitral and 0.1 f 0.04 cm2 for the tricus-

FIGURE 1. Calculation of volume flow. A, mean temporal velocity was calculated by integrating the area of the maximal Doppler frequency shift of 3 consecutive cardiac cycles. The line marks the maximal Doppler frequency shift traced. 6, apical &chamber view of a normal fetal heart. To calculate the area of flow, the diameter of the atrioventricular orifice at the level of the insertion of the valves was measured as indicated by the arrows (mitral valve). LA = left atrium, bV = left ventrtcle; RA = right atrium; RV = right ventricle!.

0

s 0

RIGHT VENTRICULAR

gggggp-gs

LEFT VENTRICULAR

OUTPWML/MlN

OUTPUT(ML/MIN).

1

,

E? 0

R 0

P 6 g

AREA ig

MITRAL

ORIFICE g 2 000000

5

(CM’), s

,-g

=:

TEMPORAL VELOCITY RIGHT VENTRICLE

TEMPORAL VELOCITY LEFT VENTRlCLE

CM/SEC

CM/SEC

\\ .... .-.’ \\ * . *.\\’\.-. . ..... .. ..‘1 \ \ (.. . . . .l ‘t\\‘j,

.*. ~1 . . \.I. ... ...) . ‘) ..\ ’ /\1-..-.. . . . \\\ .... .--...’.. \*\ ......\1 \\.. .I. \‘1 \* .\...........“.’ . .. .:\) \ . . . \“‘Ilttts \ -. -.. !.\

MEAN

MEAN

August TABLE

t

Fetal

Cardiac

Weeks

10 n 11 ”

R Area MO TO output L R RVO/LVO

20-24

f 2 = 24 f2 = 21

AI~ERICAN

11 n 12 n

24-26

f 2 = 30 f 2 = 23

0.1 n 0.1 n

f = + =

0.03 16 0.04 16

0.2 n 0.2 n

f 0.04 = 23 f 0.04 = 24

54 n 67 n 1.3 n

f = f = f =

21 15 25 16 0.3 15

113 n 143 n 1.3 n

f = f = f =

CVO = combined MVO = mitral valve

THE

JOURNAL

OF CARDIOLOGY

Volume

60

345

Output

1.5-20

MTV L

I, 1987

33 23 33 23 0.21 22

ventricular output; orifice; R = right;

28-32

13 n 14 n

f = f =

2 21 2 21

0.3 n 0.3 n

f = f =

0.05 20 0.05 18

f n = 240 f n = 1.2 I n =

56 20 63 18 0.21 18

204

f = f =

3 27 3 27

0.4 n 0.4 n

f = f =

0.08 24 0.08 22

0.6 n 0.7 n

f 0.07 = 18 f 0.24 = 18

ck = f = zk =

74 23 88 22 0.21 22

526 n 613 n 1.1 n

& = f = f =

333 n 372 n 1.1 n

16 n 1s n

30-40

14 n 15 n

L = left; LVO = left ventricular RVO = right ventricular output;

pid valve at 15- to 20-week gestation to 0.9 f 0.16 cm2 for the mitral and 1.0 f 0.20 cm2 for the tricuspid valve at the 3O- to 40-week gestation interval. The increase in mean temporal velocities at the AV orifices from 16 weeks to term, expressed as linear function of gestational age, is shown in Figure 2. The calculated area of both AV orifices increased exponentially [Fig. 2). The calculated ventricular output increased from 54 to -21.4 ml/min and in the left ventricle at 68 f 25.2 ml/ min for the right ventricle at 15 to 20 weeks of gestation to 820 f 164.4 ml/min at the left ventricle and 915 f 229.3 ml/min for the right ventricle at 36 to 40 weeks gestation (Fig. 2), and combined ventricular output at term is approximately 1,730 ml/m. There was a significant (0.005 > 2p >O.OOl) difference between right and left ventricular flow. The mean temporal velocities, areas of flow and resulting blood flows were significantly higher for the right ventricle than the left ventricle [Fig. 3). The ratio of right to left ventricular flow decreased significantly, from 1.3

32-36

f 3 = 21 i 2 = 22

113 18 167 18 0.21 17

1.5 n 16 n

f = f =

2 25 3 25

0.9 n 1.0 n

f = f =

0.16 20 0.20 22

820 ” 915 n 1.1 n

output; MTV = mean temporal TV0 = tricuspid valve orifice.

4~ 164 = 20 f 229 = 21 IO.18 = 19 velocity;

f 0.28 at 15 weeks to 1.1 f 0.28 at 40 weeks, respectively (Fig. 4). Combined ventricular output indicated for fetal weight was constant at a mean value of 553 f 153 ml/min/kg.

Discussion Our purpose was to define the gradual changes in right and left ventricular volume flow in the human fetus. Before discussing the results we will consider a few methodologic aspects of the study. Since the 2 heart sides of the fetus work in parallel and shunting takes place at atria1 and ductal level, 2 sites for fetal ventricular output measurements are available: the AV orifices and the great arteries. We attempted measurements at the AV level because the Doppler frequency shift tracings at the AV orifices are more easily obtained and have a lower velocity,g avoiding the problem in velocity aliasing. In addition, the AV orifice has margins clearly defined by the bright echodense spots of the fibrous AV anulus tissue and has a

1.81

0.61 WEEKS

FIGURE tricular

3. The output

gestational >2

p >O.OOl).

calculated (RVO)

age.

RVO

left and

ventricular

combined

is significantly

OF GESTATION

output ventricular

higher

than

0.4L

(LVO),

rlght

output

(CVO)

LVO

(paired

venf 0.005

, 15

,

I

II,I,,,,,,

20

25 WEEKS

,,,,,,,,,,,

30 OF GESTATION

35

40

vs FIGURE gestation

4. Ratio

of right-to-left

(y = 1.489-0.0.10x,

ventricular 8EE

= 0.2533).

output

in the

course

of

342

FETAL

CARDIAC

OUTPUT

BY DOPPLER

larger diameter than the great artery orifices. The echodense spots allow an accurate diameter measurement, whereas the large diameter reduces the relative impact of errors of diameter measurement on the calculation of blood flow.4 Calculations used to estimate ventricular output are based upon the following assumptions: (11 Blood flow across the AV orifices has a flat profile and the mean temporal velocity calculated from the Doppler frequency shift determined with a single sample volume characterizes this flow. Various studies in the normal human subject support this assumption.12,13The absence of a significant spectral broadening on the recordings (less than lCj% of the Doppler frequency shift] suggests that this flat flow profile assumption also holds for the fetus. (2) The area of flow can be calculated from a diameter measurement wherein we assume that the AV orifices are circular and have a constant size. This simplified method for cardiac output calculations applied in experimental animals as well as in human populations and yields acceptable results for volume flow.7,8p14T15 Ormiston and Tei16!17report variation of the AV orifice site during the cardiac cycle, especially during systole.Therefore, we used the diameters during the diastolic phase; the largest diameter during this phase was measured. Despite these precautions, underestimation of the orifice size is still a matter of concern because limited lateral resolution leads to a decrease in measured orifice diameter.18 Finally, the Doppler frequency shift detected is directly proportional to the cosine of the angle of interception between the direction of flow and the Doppler interrogation beam. The changes in cosine become progressively larger per degree as the angle increases toward 90°. To minimize errors in velocity calculation due to errors in angle measurement, all flows with an intercept angle above 0' were deleted from this study. We tried to minimize the angle in the azimuthal plane by sampling the Doppler frequency shift for least spectral broadening and highest velocity. To minimize the variability of the method we calculated the mean temporal velocity by integrating the Doppler frequency shift on 3 consecutive cardiac cycles and performed these measurements 3 times, the diameter of the AV orifices were measured 5 times averaging the results. The exponential increase of the area of the AV orifices is analogous to the linear increase in the diameter of the ventricles as found both by Allan and St. John Sutton.lgpzO In this study we also found that the area of the tricuspid orifice was larger than that of the mitral orifice [ratio 1.2 at 15 weeks and 1.07 at 40 weeks). There is consistent and significant dominance of right ventricular output compared with left ventricular output. This difference is due to both a larger diameter and a higher blood flow velocity in the right ventricle. These findings are in agreement with those in an earlier cross-sectional study.g A dominance of right ventricular output was also found in fetal lambs.3 The ratio found in this species (1.8) is, however, much larger than that in the human

fetus (range 1.3 at early gestation to 1.1 near term). This is probably due to a larger brain mass and therefore a relatively higher left ventricular output in the human fetus than in the fetal lamb, The calculated total combined ventricular output near term of 1,735 ml/min and of 599 ml/min kg estimated fetal weight is consistent with cardiac output as measured in the fetal lamb.3 The present findings are higher than earlier studies in the human fetus, which may be secondary to use of a different technique where left ventricular stroke volume was calculated from the difference between end-systolic and enddiastolic intracardiac dimensions.596 Acknowledgment We acknowledge the encouragement and advice of Dr. L.D. Allan, Prof. K.K. Bossina and Prof. H.J. Huisjes. Furthermore, our thanks are due to Prof. T. Graham and Dr. R. Wyse for the constructive criticism of the study, L. van der Weele for the statistical analysis and M. Munstra and V. Griffin for typing the manuscript.

References 1. Barcroft J, Flexner LB, McClurkin T. The output of the fetal heart in the goat. l Physiol 1934;82:498-508. 2. Dawes GS, Mott JC. Widdicombe JG. The fetal circulation in the Iamb. J Phvsiol 1954:126:563-587. 3. Rudolph AM, Heymann MA. Circulatory changes during growth in the fetal lamb. Circulation 1976;26:289-299. 4. Eik-Nes SH, Marsal K, Burbakk AO, Kristoffersen K. Ulstein M. UItrasound measurement of human fetal blood flow. J Biomed Eng 1982;4:28-36. 5. Wladimiroff JW, McGhie JS. Ultrasonic assessment of cardiovascular geometry and function in the human fetus. Br J Obstet Gynaec 1981;88:870-875. 6. Wladimiroff JW, Vosters R, McGhie JS. Normal cardiac ventricular geometry and function during the last trimester of pregnancy and early neonatal period. Br J Osbtet Gynaecol 1982;89:839-844. 7. Meijboom EJ, Horwitz S, Valdes-Cruz LM, Sahn DJ, Larson DF, Oliveira Lima C. A Doppler echocardiographic method for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies. Circulation 1985;7:551-556. 8. Meijboom EJ, Horowitz S, Valdes-Crnz LM, Larson DF, Born N, Rijsterborgh H, Lima CO, Sahn DJ. A simplified mitral valve method for twodimensional echo Doppler blood flow calcuiation: validation in an open-chest canine model and initial clinical studies, Am Heart J 1987;113:335-340. 9. Reed KL, Meijboom EJ, Sahn DJ, Scagnelli S, Valdes-Cruz LM, Shenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986;73:41-46. 10. Brenner WE. Edelman DA. Hendricks CH. A standard of fetal growth for the United States of America: Am J Obstet GynecoI 1976;126:555-564. ’ 11. Kloosterman GJ. On intrauterine growth. Int J Cynaecol Obstet 1970; 8:895-913. 12. Lynch PR, Bove AA. Patterns of blood flow through the intact heart and valves. In: Brewer LA, ed. Prosthetic Heart Valves. Springfield, IL: Charles C Thomas, X968:24. 13. Hatle L, Angelsen B. Doppler Ultrasound in Cardiology: Physical Princiriles and Clinical ADoIications. Philadeluhia: Lea 6 Febiger, 1985. i4. Meijboom EJ, Rijsterborgh H, Bot H,‘de Boo JAJ, Roelandt JRTC, Born N. Limits of reproducibility of blood flow measurements by Doppler echocardiography. Am J Cardiol 1967;59:133-137. 15. Loeber CP, Goldberg SJ, Allen HD. Doppler echocardiographic comparison of fIows distal fo the four cardiac valves. JACC 1984;4:268-272. 16. Ormiston JA, Shah PM, Tei C, Wong M. Size and motion of the mitral valve annulus in man. A two-dimensional echocardiographic method and findings in normal subjects. CircuIotion 1981;64:113-120. 17. Tei C, Pilgrim JP, Shah P, Ormiston J, Wong M. The tricuspid valve annulus: study of size and motion in normal subjects and in patients with tricusoid reeuraitation. CircuIation 1982:66:665-671. 18. Martin “R, Rakowski H, Kleinman JH, Beaver W, London E, Popp R. ReIiabiIity and reproducibility of 2-D echographic measurements of stenotic mitral valve orifice area. Am J Cardiol 1979:43:560-568. 19. Allan LD, Joseph MC, Boyd EGCA. Campbell S, Tynan M. M-mode echocardiography ih the developing human fetus. Br Heart I 1982;47:573-583. 20. St. John Sutton MG, Gewitz MH, Shah B, Cohen A, Reicheck N, Gabbe S, Huff DS. Quatitative assessment of growth and function of the cardiac chambers in the normal human fetus: a prospective longitudinal echocardiographic study. Circulation 1984;69:645-654.