Atrial dominance in the human embryonic heart: a study of cardiac function at 6-10 weeks of gestation.

OBJECTIVE: To investigate the difference in forces developed by atrial and ventricular myocardium during contraction in human embryos using a novel method. METHODS: This was a cross-sectional study of 115 pregnancies examined at 6-10 weeks of gestation. Ventricular inflow and outflow velocities were obtained by Doppler echocardiography and the relative force development was evaluated by calculating the ratio between atrial and ventricular ejection force (EF). RESULTS: Data from 97 embryos with monophasic ventricular filling were analyzed. Both inflow and outflow cardiac velocities increased with advancing gestational age (P < 0.001). The mean peak inflow velocity (31.7 ± 10.2 cm/s) was significantly higher (P < 0.0001) than the outflow velocity (19.6 ± 6.1 cm/s). The EFinflow /EFoutflow ratio was more than 1.0 in all but four (96%) cases. CONCLUSION: Our study indicates the possibility of atrial dominance in the embryonic period of heart development, which may have clinical implications, as deviations from this normal pattern may indicate human embryonic cardiac dysfunction.

Comparison between pulsed-wave Doppler- and tissue Doppler-derived Tei indices in fetuses with and without congenital heart disease.

OBJECTIVES: The aim of this study was to compare the right (RV) and left (LV) ventricular Tei indices obtained by pulsed-wave Doppler (PD) and tissue Doppler (TD) methods in fetuses with structurally normal and abnormal hearts. METHODS: This was a retrospective cross-sectional study of 147 fetuses that had a fetal echocardiogram and Tei index measured during a 2-year period. The RV and LV Tei indices were measured using both PD and TD methods. The difference between the two methods of Tei index measurement was tested using paired sample t-test, Pearson correlation coefficient was used to examine their relationship, and the agreement between the methods was tested using Bland-Altman analysis. RESULTS: A total of 87 fetuses had normal hearts and 60 had a congenital heart defect. Both PD and TD Tei indices were measured successfully from at least one ventricle in 123 cases and from both ventricles in 110 cases. The mean TD Tei index was significantly higher than the mean PD Tei index for both ventricles (P < 0.0001). There was a weak but statistically significant correlation between the PD and TD Tei indices of the right ventricle (r = 0.20, P = 0.029), whereas the PD and TD Tei indices of the left ventricle did not correlate significantly (r = 0.04, P = 0.684). When pairs of Tei indices measured by two different methods (123 pairs for the right ventricle and 111 for the left ventricle) were tested with Bland-Altman analysis, the bias and precision were 0.147 and 0.254, respectively, for the right ventricle, and 0.299 and 0.276, respectively, for the left ventricle. CONCLUSIONS: Correlation between Tei indices measured by PD and TD methods is weak and the agreement between individual measurements is poor. Therefore, they should not be used interchangeably in the assessment of fetal cardiac function.

Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction.

OBJECTIVE: To determine whether low cardiovascular profile (CVP) score has prognostic value for predicting neonatal mortality and severe morbidity in human fetuses with growth restriction. METHODS: Seventy-five consecutive growth-restricted fetuses with Doppler examination of cardiovascular hemodynamics within a week prior to delivery comprised the study population. Hydrops, heart size, cardiac function and venous and arterial hemodynamics were evaluated for CVP score. The primary outcome measures were neonatal mortality and cerebral palsy. RESULTS: During the neonatal period, six of 75 neonates died and two had cerebral palsy (Group 1, n = 8). Compared with the fetuses discharged home from hospital (Group 2, n = 67), those in Group 1 were delivered at an earlier gestational age (28 (range, 24-35) weeks vs. 35 (range, 26-40) weeks, P < 0.01) and had lower CVP scores (4 (range, 2-6) vs. 9 (range, 5-10), P < 0.0001). All CVP subscale scores were lower (P < 0.01) in Group 1 than in Group 2 fetuses. Gestational age-adjusted hazard ratios (95% CIs) for adverse neonatal outcome were highest for cardiomegaly (13.9 (1.7-114.3), P = 0.014), monophasic atrioventricular filling pattern or holosystolic tricuspid regurgitation (9.5 (2.3-38.4), P = 0.002) and atrial pulsations in the umbilical vein 7.7 (1.4-41.2), P = 0.017). CONCLUSIONS: Growth-restricted fetuses with adverse neonatal outcome have lower CVP scores than do fetuses with favorable neonatal outcome. The strongest predictors for adverse neonatal outcome in the CVP score were cardiomegaly, abnormal cardiac function with monophasic atrioventricular filling or holosystolic tricuspid regurgitation and increased systemic venous pressure. These assessments have independent prognostic power for adverse neonatal outcome even after adjustment for gestational age.

Doppler study of the embryonic heart in normal pregnant women.

OBJECTIVE: To describe normal fetal cardiac and hemodynamic development in normal early first trimester pregnancies. MATERIALS AND METHODS: Eighty-eight women with singleton, uncomplicated pregnancies were prospectively studied with transvaginal ultrasound, pulsed and color Doppler. Heart diameter, heart rate, and inflow and outflow waveforms with valve signals were documented. The proportion of the cardiac cycle of isovolumetric relaxation time (IRT%) and isovolumetric contraction time (ICT%) as well as Tei index were calculated. RESULTS: Ninety-one percent of studies were successful. Heart diameter and the fetal heart rate showed a positive correlation with increasing gestational age: R = 0.80 (p < 0.000001), R = 0.76 (p < 0.000001), respectively. Mean heart diameter at 6 weeks was 1.28 +/- 0.26 mm and mean fetal heart rate was 117 +/- 6 bpm compared to 3.88 +/- 0.54 mm and 171 +/- 6 bpm at 10 weeks. The inflow waveform was monophasic (atrial contraction) in all cases from 6 to 9 weeks. Eight pregnancies (9%) miscarried between 6 and 12 weeks of gestation and the heart exams were characterized by increased IRT% compared with the survivors. In survivors, IRT% decreased between 7 and 8 weeks, from 32.9 +/- 10.7% to 20.8 +/- 5.7% (p < 0.0001). ICT% decreased from 18.6 +/- 4.4% of the cardiac cycle at 8 weeks to 12.6 +/- 4.4% at 9 weeks (p < 0.0008) (after heart development period). CONCLUSIONS: Doppler examination of the fetal cardiac function is possible after 5 weeks of gestation. After 8 weeks of gestation, the fetal heart is morphologically mature but has not yet achieved effective myocardial compliance. The embryonic human heart is dependent on the atrial contraction for ventricular filling throughout the period of cardiac development. Non-survivors manifest myocardial dysfunction.

Divergent effects of ephedrine and phenylephrine on cardiovascular hemodynamics of near-term fetal sheep exposed to hypoxemia and maternal hypotension.

BACKGROUND: We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses. METHODS: At 115-136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment. RESULTS: During hypotension, fetal PO(2) decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses. CONCLUSIONS: After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration.

Experimental validation of uterine artery volume blood flow measurement by Doppler ultrasonography in pregnant sheep.

OBJECTIVE: To test the hypothesis that Doppler-derived (calculated) uterine artery volume blood flow (cQ(UtA)) reflects accurately volume blood flow measured directly (mQ(UtA)) in an experimental setting. METHODS: Five pregnant sheep were instrumented at 122-130 days of gestation under general anesthesia. After a 4-day recovery period, maternal hemodynamics were varied by administering to the sheep under general anesthesia noradrenaline, beta-blocker, low oxygen gas mixture, epidural bupivacaine and ephedrine, consecutively. The central venous pressure was obtained with the help of a thermodilution catheter. The mean arterial pressure and acid-base status were monitored using a 16-gauge polyurethane catheter inserted into the descending aorta via a femoral artery. A 6-mm transit-time ultrasonic perivascular flow probe was used to measure the mQ(UtA). Doppler ultrasonography of the uterine artery was performed and volume blood flow was obtained simultaneously by the transit-time ultrasonic perivascular flow probe during each phase of the experiment. RESULTS: A total of 31 observations were made. The mQ(UtA) varied between 90 and 800 (mean +/- SD, 419 +/- 206) mL/min during the experiments. The corresponding values for the cQ(UtA) were 110 and 900 (mean +/- SD, 459 +/- 211) mL/min. There was a significant correlation (R = 0.76; P < 0.0001) between mQ(UtA) and cQ(UtA). The mQ(UtA) correlated positively with Doppler-derived uterine artery absolute velocities, i.e. peak systolic (R = 0.50; P = 0.004), end-diastolic (R = 0.53; P = 0.002) and time-averaged maximum (R = 0.69; P < 0.0001) and time-averaged intensity weighted mean (R = 0.75; P < 0.0001) velocities. CONCLUSION: cQ(UtA) correlates well with volume blood flow measured directly. Doppler-derived uterine artery absolute blood flow velocities reflect uteroplacental volume blood flow in pregnant sheep. Published by John Wiley & Sons, Ltd.

First trimester screening for congenital heart disease.

Most obstetrical practices in the United States offer pregnant women at least one ultrasound during pregnancy. This prenatal ultrasound is usually scheduled at around 18 to 20 weeks gestation. Both the American Institute of Ultrasound in Medicine and the American College of Obstetricians and Gynecologists recommend that the four-chamber view be included to screen for congenital heart disease. Recently, many investigators have attempted to screen for congenital heart disease earlier in pregnancy. Fetal nuchal translucency thickness traditionally used to screen for fetal aneuploidy by transvaginal and abdominal ultrasound has also been shown to identify a large proportion of fetuses with congenital heart disease. Recent studies have also reported congenital heart disease in chromosomally normal fetuses with increased nuchal translucency thickness in the first trimester. Advances in ultrasound technology and training over the last 10 years allow greater visualization rates of the four-chamber view and outflow tracks in the late first trimester (up to 90% visualization at 13 weeks). Fetal echocardiography in the first trimester may be indicated for fetuses at risk for congenital heart disease. In this article we present a review of the most recent and ongoing clinical and basic research to support an earlier first trimester approach to diagnosing congenital heart defects.

Guidelines for the evaluation of heart failure in the fetus with or without hydrops.

Fetal echocardiography has progressed to be able to diagnose many forms of congenital heart disease and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. However, the presence of signs of fetal heart failure, such as hydrops or valvular regurgitation, makes the assessment of prognosis difficult. This article outlines a straightforward method for the rapid evaluation of the fetus who may have congestive heart failure. The differentiation of the prehydropic state from normal is illustrated.

Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect.

Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences. CHD fetuses were compared to normal fetuses. Data included cardiac diagnosis, cerebral and umbilical artery Doppler, head circumference, weight, and gestational age. The cerebral-to-placental resistance ratio (CPR) was assessed as a measure of cerebral autoregulation. CPR = cerebral/umbilical resistance index (RI) and RI = systolic-diastolic/systolic velocity (normal CPR > 1). CPR > 1 was found in 95% of normal vs 44% of CHD fetuses. The incidence of CPR < 1 was greatest in hypoplastic left or right heart fetuses. Compared to normal, cerebral RI was decreased in CHD fetuses. The CPR vs gestational age relationship, and the relationship among weight, head circumference, and CPR differed across normal and CHD fetuses. Fetuses > 2 kg with CHD and a CPR < 1 had smaller head circumferences than normal. Brain sparing occurs in CHD fetuses. Fetuses with single ventricular physiology are most affected. Inadequate cerebral flow in CHD fetuses, despite autoregulation, may alter brain growth.

Accuracy of prenatal diagnosis of congenital heart defects.

OBJECTIVES: (1) To evaluate the detection and accuracy of fetal echocardiography for congenital heart defects (CHD). (2) To compare the detection and accuracy of a team of maternal fetal medicine specialists and radiologists (MFM/R) with those of perinatal cardiologists (PC). METHODS: All fetal echocardiograms performed from 1/91 to 6/95 were reviewed retrospectively. CHD diagnoses made prenatally were compared with postnatally-confirmed diagnoses. RESULTS: 106 heat defects were correctly detected prenatally. There were 10 incorrect diagnoses, 6 false-negatives and 4 false-positives. Overall detection rate (sensitivity) was 95%, while overall accuracy was 87%. Detection rate for MFM/R and PC were 91 and 97%, respectively (p = 0.4). Accuracy was 74% for MFM/R and 92% for PC (p = 0.02). CONCLUSIONS: CHD can be identified reliably by prenatal echocardiography. The involvement of a PC in the prenatal diagnosis of these defects may improve diagnostic accuracy.

Right ventricular function in the human fetus.

Fetal RV function is critical for survival and normal cardiovascular development. Doppler can be used to assess function. Combined with wise use of imaging techniques, the cause of abnormalities can be assessed. Both congenital heart defects and other cardiovascular defects can lead to hydrops and death. Serial semi-quantitation of fetal heart failure can be done with a Cardiovascular Profile score.

Fetal congestive heart failure: correlation of Tei-index and Cardiovascular-score.

INTRODUCTION: Congestive heart failure (CHF) may be present in fetuses with hydrops fetalis (HF) and the severity is difficult to quantitate. Differential ventricular dysfunction may be present in the fetus with CHF. A non-geometric measure of ventricular function that is not afterload dependent would be useful to measure the severity of myocardial dysfunction. METHODS: Tei-index (isovolumetric time/ejection time) was measured prenatally in 23 normals (24-34 weeks gestational age-GA) and in 7 with HF (24-34 weeks GA). Prenatal CHF severity was graded by a 10 point cardiovascular (CV) score (2 points each for absence of hydrops, normal venous Doppler, heart function, arterial Doppler, and heart size, and 10/10 = normal). A paired student t-test was used to compare RV and LV and non-paired t-test compared HF and normals. Tei-index and CV score were correlated. RESULTS: Tei-index normals were 0.38 +/- 0.04 in the right ventricle (RV) and 0.41 +/- 0.05 in the left ventricle (LV) and there were no significant RV-LV or gestational age (GA) differences. Among HF fetuses, RV and LV Tei-indices were both significantly increased (0.54 and 0.92) and not significantly different. CV score ranged from 2 to 8 (mean 5.43 out of 10) and correlated inversely with Tei-index (r = -0.52, r = -0.68). CONCLUSION: Hydrops fetalis is associated with biventricular dysfunction and congestive heart failure. Tei-index correlates with CV score obtained within two weeks of delivery or intrauterine death. Tei-index may be useful in the serial assessment of myocardial dysfunction in the fetus with hydrops.

Superior vena caval syndrome: color flow Doppler detection of collateral venous channels.

Thrombosis of the superior vena cava (SVC) is an important clinical problem that requires prompt diagnosis. Confirmation of suspected SVC syndrome requires the use of an imaging study to document the obstruction and presence of collateral venous channels. Echocardiography is often used to evaluate suspected SVC obstruction; however, previous methods have allowed only indirect detection of collateral flow. We describe 3 patients with SVC obstruction in whom color flow Doppler allowed direct demonstration of collateral venous channels.

Fetal cardiac development and hemodynamics in the first trimester.

OBJECTIVE: To describe fetal cardiac and hemodynamic development in the first trimester of pregnancy. SUBJECTS AND METHODS: Forty-eight pregnancies were prospectively studied with transvaginal ultrasound and color Doppler. Fetal heart rate and size were documented together with the presence of inflow and outflow wave-forms and valve signals. RESULTS: Heart rate and size showed a positive correlation with gestational age. At 6 weeks of gestation, 20% of the cardiac cycle was occupied by the isovolumic contraction time (ICT); the isovolumic relaxation time (IRT) occupied 16% and remained unchanged, while the ICT progressively shortened and was not measurable after 12 weeks. The peak inflow velocities had changed from monophasic to biphasic by 10 weeks of gestation. At 7 weeks of gestation, semilunar valves were detected in 10% of examinations and the atrioventricular valves in 3%. The detection rate for both valves at 12 weeks was > or = 90%. In pregnancies that miscarried, the detection rate for both was < 25%. CONCLUSIONS: The Doppler signals that characterize the heart during the first trimester suggest effective heart compliance by 12 weeks. Normal valve development can be inferred from non-invasive Doppler recordings.

The effects of maternal indomethacin therapy on human fetal branch pulmonary arterial vascular impedance.

OBJECTIVE: To examine whether maternal indomethacin therapy affects human fetal pulmonary arterial vascular impedance without constriction of the ductus arteriosus and to determine the changes in the pulmonary arterial vascular impedance in the presence of ductal constriction. STUDY DESIGN: In this cross-sectional study, 52 normal fetuses without maternal medication (control group), 33 fetuses without ductal constriction (Study group I) and 11 fetuses with ductal constriction (Study group II) during maternal indomethacin therapy between 24 and 34 weeks of gestation were examined by Doppler echo-cardiography. Blood velocity waveforms across the proximal right or left pulmonary artery were obtained and the pulsatility index (PI) of the proximal pulmonary arteries was calculated. RESULTS: In the control group, the proximal pulmonary artery PI was higher (p < 0.0001) at 24-25 weeks (n = 7) (3.73 +/- 0.33; mean +/- SD) than at 33-34 week of gestation (n = 11) (2.98 +/- 0.27). The PI was constantly greater (p < 0.005) in Study group I than in the control group. However, in this group the mean average weekly decrease in the PI of the proximal pulmonary arteries was similar to that in the control group. After 26 weeks of gestation, the PI values in Study group II were significantly higher than in the control group (27 weeks: 4.12 vs. 3.34 (p < 0.005); 30 weeks: 4.48 vs. 3.14 (p < 0.0001); 34 weeks: 4.96 vs. 3.00 (p < 0.0001), respectively). CONCLUSIONS: Human fetal pulmonary arterial vascular impedance is increased by maternal indomethacin therapy even without ductal constriction. In the presence of ductal constriction, the magnitude of the increase in the vascular impedance is related to the gestational age.

Cardiac malposition, redistribution of fetal cardiac output, and left heart hypoplasia reduce survival in neonates with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate cardiac position, left ventricular (LV) mass, and distribution of fetal cardiac output in infants with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO), and in control subjects. STUDY DESIGN: Echocardiograms were performed on 23 neonates with CDH shortly after birth, and repeated within 5 days of repair on ECMO in 21 infants,aand on 12 infants receiving ECMO for other diagnoses, and on 10 healthy, term neonates. Cardiac angle between the midline saggital plane and the interventriculak septum was measured, and deviation from normal (45 degrees) was determined. The ratio of cross-sectional areas (proportional to flows) across the pulmonary (PV) and aortic (AV) valves was determined (PV2/AV2) in 19 infants with CDH and in the healthy control subjects. RESULTS: Thirteen (57%) infants with CDH survived and 10 (43%) died, with no difference in cardiac deviation before surgical repair (35 +/- 13 degrees vs Cardiac deviation persisted after repair in nonsurvivors (27 +/- 14 degrees vs 800.01 and LV mass was significantly less (1.68 +/- 0.39 vs 3.05 +/- 1.20 gm/kg, p00.0005). Neonates requiring ECMO for other diagnoses and well term babies did not have cardiac angle deviations; both these groups had a greater LV mass than did the infants with CDH. The PV2/AV2 flow ratios were higher in infants with CDH (median, 1.73; range, 1.25 to 16.50) compared with those of the healthy infants (0.96, 0.79 to 1.69, p < 0.0002). CONCLUSIONS: Cardiac malposition persisted despite CDH repair in nonsurvivors with low LV mass, and fetal cardiac output was redistributed away from the left ventricle. Lung hypoplasia with reduced pulmonary flow returning to the left atrium and altered left atrial hemodynamics may result in LV hypoplasia