Quantitative evaluation of fetal right and left ventricular fractional area change using speckle-tracking technology.

OBJECTIVES: To measure, using speckle-tracking technology, the fractional area change (FAC) of the right and left ventricles in normal fetal hearts between 20 and 40 weeks of gestation. METHODS: The four-chamber view of the fetal heart was obtained in 200 normal fetuses between 20 and 40 weeks of gestation. FAC was computed from the ventricular areas (((end-diastolic area - end-systolic area)/end-diastolic area) × 100) for the right and left ventricles, and regressed against seven independent biometric and age variables. FAC was correlated with longitudinal fractional shortening (LFS) (((end-diastolic longitudinal length - end-systolic longitudinal length)/end-diastolic longitudinal length) × 100) obtained from the mid-ventricular basal-apical lengths of the right and left ventricular chambers and with transverse fractional shortening (TFS) (((end-diastolic transverse length - end-systolic transverse length)/end-diastolic transverse length) × 100) from three transverse positions (base, mid, apical) located within each ventricular chamber. To evaluate potential clinical utility, FAC, LFS and TFS results were examined in nine fetuses with a congenital heart defect (CHD). RESULTS: Regression analysis demonstrated significant associations between FAC and the independent biometric and age variables (R2  = 0.13-0.15). FAC was significantly correlated with LFS (R2  = 0.18-0.28) and TFS (R2  = 0.13-0.33). Examination of the fetuses with CHD revealed that six of the nine had abnormal FAC Z-score values for the index pathological ventricle. When abnormal LFS and TFS values were compared to the FAC in these fetuses, the FAC was either abnormally low or normal. CONCLUSIONS: This study reports results from measuring the FAC of the right and left ventricles, and demonstrates a correlation with LFS and TFS. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal Annular Systolic Displacement Compared to Global Strain in Normal Fetal Hearts and Those With Cardiac Abnormalities.

OBJECTIVES: The purpose of this study was to compare a new technique that measures the midventricular basal-apical longitudinal diastolic and systolic lengths, computes the longitudinal displacement fractional shortening, and compares it to global strain. METHODS: Two hundred control fetuses were examined between 20 and 40 weeks' gestation, in whom the longitudinal displacement fractional shortening was computed from end-diastolic and end-systolic lengths measured from the apex to the mid portion of the distance between the level of the basal lateral and septal walls using 2-dimnsional speckle tracking. In addition, global strain was computed using speckle tracking. A correlation analysis was used to compare the longitudinal displacement fractional shortening to global strain. The longitudinal displacement fractional shortening of the right ventricle (RV) and left ventricle (LV) was measured in 10 fetuses with heart abnormalities. RESULTS: The longitudinal displacement fractional shortening for the RV (mean ± SD, 22.94% ± 4.73%) and LV (21.05% ± 4.21%) was independent of gestational age and other biometric growth parameters, as was global strain (RV, -22.7% ± 4.07%); LV, -22.93% ± 3.52%). The RV longitudinal displacement fractional shortening was greater than that of the LV (P < .024). The correlations between the longitudinal displacement fractional shortening and global strain were 0.95 for the RV and 0.97 for the LV. Comparing the longitudinal displacement fractional shortening and global strain in fetuses with abnormal cardiac findings showed concordant findings in 9 of 10 fetuses. CONCLUSIONS: The RV and LV longitudinal displacement fractional shortening can be computed from 2-dimensional images of the 4-chamber view and correlated with global strain. The longitudinal displacement fractional shortening was significantly greater for the RV than the LV and was abnormal in fetuses with RV and LV cardiac abnormalities.

Adverse perinatal environment contributes to altered cardiac development and function.

Epidemiological observations report an association between intrauterine growth restriction (IUGR) and cardiovascular diseases. Systemic maternal inflammation is the most common stress during pregnancy, leading to IUGR. We hypothesized that perinatal inflammation and hyperoxygenation induce discernible alterations in cardiomyocyte contractility and calcium signaling, causing early cardiac dysfunction. Pregnant C3H/HeN mice were injected with LPS or saline on embryonic day 16. Newborn mice were placed in 85% O2 or room air (RA) for 14 days. Pups born to LPS-injected dams had reduced birth weight. Echocardiographic measurements revealed that in vivo LV function was compromised in LPS/O2 mice as early as 3 days of life. Isolated cardiomyocytes from LPS/O2 mice at day 14 exhibited decreased sarcomere fractional shortening, along with decreased time-to-90% peak shortening. Calcium transient amplitude was greatest in LPS/O2 mice. SERCA2a mRNA and protein levels were increased and phospholamban mRNA levels were decreased in LPS/O2 mice. Phosphorylation of phospholamban was increased, along with Sorcin mRNA levels in LPS/O2 mice. Combined exposure to perinatal inflammation and hyperoxia resulted in growth restriction, in vivo and in vitro cardiac dysfunction, coinciding with humans and animal models of cardiac dysfunction. Expression of calcium handling proteins during the neonatal period was similar to that observed during fetal stages of development. Our data suggest that perinatal inflammation and hyperoxia exposure alter fetal development, resulting in early cardiac dysfunction.

Fetal cardiac function: M-mode and 4D spatiotemporal image correlation.

Fetal cardiac function has been shown to be a marker of disease severity in many conditions, including intrauterine growth restriction, congenital heart defects or disease (CHD), twin-to-twin transfusion syndrome, idiopathic hydrops, fetal arrhythmias, and others. It is often targeted for evaluation of patient management, for providing complete and accurate diagnoses in CHD, for patient counseling, or in referring for fetal cardiac interventions. In this review we will describe the use of M-mode and 4D spatiotemporal image correlation in fetal cardiac evaluation, the parameters that can be measured, and their application to clinical practice.

Evaluation of conventional Doppler fetal cardiac function parameters: E/A ratios, outflow tracts, and myocardial performance index.

Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.

Fetal cardiac function: technical considerations and potential research and clinical applications.

Fetal echocardiography was initially used to detect structural anomalies but has more recently also been proposed to assess fetal cardiac function. This review summarizes technical issues and limitations in fetal cardiac function evaluation, as well as its potential research and clinical applications. Functional echocardiography has been demonstrated to select high-risk populations and to be associated with outcome in several fetal conditions including intrauterine growth restriction, twin-to-twin transfusion syndrome, maternal diabetes, and congenital diaphragmatic hernia. Fetal heart evaluation is challenging due to the smallness and high heart rate of the fetus and restricted access to the fetus far from the transducer. Due to these limitations and differences in cardiac function which are related to fetal maturation, cardiovascular parameters should be validated in the fetus and used with caution. Despite these precautions, in expert hands and with appropriate ultrasound equipment, evaluation of cardiac function is feasible in most fetuses. Functional fetal echocardiography is a promising tool that may soon be incorporated into clinical practice. Research is warranted to further refine the contribution of fetal cardiac assessment to the diagnosis, monitoring, or prediction of outcomes in various fetal conditions.

Color Doppler myocardial imaging demonstrates reduced diastolic tissue velocity in growth retarded fetuses with flow redistribution.

OBJECTIVES: In fetuses suffering from intrauterine growth retardation with cerebroplacental redistribution (IUGR CPR), the diastolic heart function may be particularly susceptible to hypoxemia as described in postnatal pathological conditions. Using the newly introduced ultrasound technique, color Doppler myocardial imaging (CDMI), we investigated the correlation between diastolic tissue velocities and diastolic blood flow velocities and compared diastolic myocardial tissue velocities in fetuses with IUGR CPR and normal fetuses. STUDY DESIGN: Peak early and active atrial tissue velocities (E' and A') were acquired from both ventricular free walls in 18 fetuses with IUGR CPR and 42 normal fetuses. In 35 normal fetuses, blood flow across the atrio-ventricular valves was also recorded. Umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) flows were obtained in all fetuses. Nonparametric tests were used for statistical analysis. RESULTS: There was a tendency towards increased E' and A' with fetal age in normal pregnancies. No correlation between tissue velocity and blood flow velocity was established. IUGR CPR fetuses had significantly lower E' and A', but when indexing to heart length, only A' remained significantly lower. E'/A' ratio was increased in the left ventricle but unchanged in the right. CONCLUSION: CDMI is easily applicable during standard fetal echocardiography and provides new information on the diastolic properties of the fetal myocardium. In fetuses with IUGR CPR, diastolic tissue velocities are abnormal and especially A' may be a marker of diastolic dysfunction.

Increased periconceptual maternal glycated haemoglobin in diabetic mothers reduces fetal long axis cardiac function.

OBJECTIVE: To compare ventricular long axis function in fetuses of diabetic mothers (FDM) with contemporaneously studied normal controls (N) and to assess the effect of pre-pregnancy diabetic control on these measurements. DESIGN: Long axis function was compared in 41 FDM and 159 N fetuses in a cross sectional observational study. SETTING: Fetal medicine unit. METHODS AND RESULTS: Echocardiography confirmed structural normality. Pulsed wave valvar Doppler velocimetry, lengthening and shortening myocardial velocities, and amplitude of ventricular long axis movement were recorded at the base of the left and right ventricular free walls and septum. Periconceptual diabetic control was assessed by haemoglobin A1c (HbA1c) in early pregnancy. Doppler and myocardial velocities were negatively related and myocardial thickness was positively related with HbA1c. In both cohorts all variables except mitral and tricuspid late filling (A wave) velocities were dependent on gestational age. FDM gestational age related values were higher for most variables and robust analysis of covariance showed significantly different maturation patterns in mitral valve E:A ratio (p = 0.036) and pulmonary velocity (p = 0.04), late lengthening myocardial velocities (left p = 0.016 and right p = 0.066), left myocardial shortening velocities (p = 0.008), and left free wall (p = 0.03) and septal (p = 0.04) amplitude of motion. FDM septal thickness was significantly increased throughout gestation (p < 0.0001). CONCLUSION: Periconceptual diabetic control influences fetal cardiac performance and myocardial hypertrophy but, unlike the pathophysiology of adult ventricular hypertrophy, is accompanied by functional adaptation. It is unlikely to explain the increased rate of late stillbirth observed in diabetic pregnancies.

Acute cardiovascular effects of fetal surgery in the human.

BACKGROUND: Prenatal surgery for congenital anomalies can prevent fetal demise or alter the course of organ development, resulting in a more favorable condition at birth. The indications for fetal surgery continue to expand, yet little is known about the acute sequelae of fetal surgery on the human cardiovascular system. METHODS AND RESULTS: Echocardiography was used to evaluate the heart before, during, and early after fetal surgery for congenital anomalies, including repair of myelomeningocele (MMC, n=51), resection of intrathoracic masses (ITM, n=15), tracheal occlusion for congenital diaphragmatic hernia (CDH, n=13), and resection of sacrococcygeal teratoma (SCT, n=4). Fetuses with MMC all had normal cardiovascular systems entering into fetal surgery, whereas those with ITM, CDH, and SCT all exhibited secondary cardiovascular sequelae of the anomaly present. At fetal surgery, heart rate increased acutely, and combined cardiac output diminished at the time of fetal incision for all groups including those with MMC, which suggests diminished stroke volume. Ventricular dysfunction and valvular dysfunction were identified in all groups, as was acute constriction of the ductus arteriosus. Fetuses with ITM and SCT had the most significant changes at surgery. CONCLUSIONS: Acute cardiovascular changes take place during fetal surgery that are likely a consequence of the physiology of the anomaly and the general effects of surgical stress, tocolytic agents, and anesthesia. Echocardiographic monitoring during fetal surgery is an important adjunct in the management of these patients.

Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development.

Connexin43 (Cx43) is the principal connexin isoform in the mouse ventricle, where it is thought to provide electrical coupling between cells. Knocking out this gene results in anatomic malformations that nevertheless allow for survival through early neonatal life. We examined electrical wave propagation in the left (LV) and right (RV) ventricles of isolated Cx43 null mutated (Cx43(-/-)), heterozygous (Cx43(+/)(-)), and wild-type (WT) embryos using high-resolution mapping of voltage-sensitive dye fluorescence. Consistent with the compensating presence of the other connexins, no reduction in propagation velocity was seen in Cx43(-/-) ventricles at postcoital day (dpc) 12.5 compared with WT or Cx43(+/)(-) ventricles. A gross reduction in conduction velocity was seen in the RV at 15.5 dpc (in cm/second, mean [1 SE confidence interval], WT 9.9 [8.7 to 11.2], Cx43(+/)(-) 9.9 [9.0 to 10.9], and Cx43(-/-) 2.2 [1.8 to 2.7; P<0.005]) and in both ventricles at 17.5 dpc (in RV, WT 8.4 [7.6 to 9.3], Cx43(+/)(-) 8.7 [8.1 to 9.3], and Cx43(-/-) 1.1 [0.1 to 1.3; P<0.005]; in LV, WT 10.1 [9.4 to 10.7], Cx43(+/)(-) 8.3 [7.8 to 8.9], and Cx43(-/-) 1.7 [1.3 to 2.1; P<0.005]) corresponding with the downregulation of Cx40. Cx40 and Cx45 mRNAs were detectable in ventricular homogenates even at 17.5 dpc, probably accounting for the residual conduction function. Neonatal knockout hearts were arrhythmic in vivo as well as ex vivo. This study demonstrates the contribution of Cx43 to the electrical function of the developing mouse heart and the essential role of this gene in maintaining heart rhythm in postnatal life.