- [Show abstract] [Hide abstract] ABSTRACT: Introduction: Determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus. Material and methods: Ventricular stroke volumes were calculated as the product of the cross-sectional area of the corresponding semi-lunar valve and the flow velocity integral through these valves. Volume flow in ductus arteriosus (QDA ) was evaluated using the same technique. Flow through the lungs (QLUNGS ) was calculated by subtracting net QDA from flow in main pulmonary artery (net QDA = QDA minus retrograde ductus arteriosus (DA) diastolic flow). Relative performance of each ventricle expressed as percentage of combined cardiac output was also indirectly assessed by the aortic isthmus systolic index (ISI) (nadir of incisura/peak systolic of the Doppler waveforms in the isthmus); the relation between ISI and QLUNGS was investigated. Results: Fifty-one fetuses with TGA were compared to 74 normal controls matched for gestational age. TGA fetuses had higher QLV at T2 (58.6±9.4 vs. 43.4±5.0%, p<0.001) and T3 (53.7±8.9 vs. 43.9±5.7%, p<0.001). QLUNGS was higher in fetuses with TGA, in the second (50.4±16.3 vs. 39.0±16.8%, p=0.007) and third trimesters of gestation (52.8± 22.0 vs. 37.1±16.3%, p=0.005). No difference was found between ISI values from normal and TGA groups. A significant inverse correlation was observed between ISI and QLUNGS (r = -0.55, p=0.006). Conclusion: Central distribution of combined cardiac output of fetuses with simple TGA is characterized by a greater QLUNGS leading to a dominant LV. In prenatal TGA, changes in QLUNGS could be monitored by measuring ISI. The clinical importance of this last observation deserves further investigations. This article is protected by copyright. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Fetal echocardiography is now the standard approach for detailed investigations of fetal cardiac anatomy and function. Available studies proposing reference values for pulsed-wave Doppler (PWD) measurements are often focused on few parameters. Furthermore, the methodology used for validating these proposed reference values is sometimes insufficiently described, and parameters necessary to compute Z scores are not always available. Improved definition of reference values with adequate statistical validation is needed for proper interpretation of PWD measurements in a clinical setting. In this study, the authors propose a comprehensive set of reference values and Z score equations for fetal PWD and M-mode measurements with thorough assessment of Z score quality and validity. Methods: Women with normal singleton pregnancies between 18 and 39 weeks of gestational age were included. A set of 57 measurements was performed, including PWD, M-mode measurements, and calculation of systolic, diastolic, and global function indices. Several parametric regressions were tested to model each measurement against gestational age. The SD was also modeled to account for heteroscedasticity. Z score equations were computed, and the proposed reference values were tested for residual association, residual heteroscedasticity, and departure from the normal distribution. Results: One hundred four uncomplicated singleton pregnancies with normal fetal hearts were included. Nonlinear relationships with gestational age were found for most measurements. Parametric normalization was successful for most measurements analyzed, and it was possible to compute Z score equations with minimal residual association with gestational age, no residual heteroscedasticity, and no significant departure from the normal distribution. Conclusions: The authors propose a comprehensive set of Z score equations for 57 fetal functional measurements, some of which do not have any published reference values. These Z score equations will allow echocardiographers to more accurately identify measurements that diverge from normal and thus detect earlier potential alterations in fetal heart function.
- [Show abstract] [Hide abstract] ABSTRACT: Abstract Objective: Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both foetuses share the same maternal environment. Methods: This prospective cohort study involved dichorionic twin pairs, with one co- twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin. Results: Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly. Conclusion: Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxydative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.
- [Show abstract] [Hide abstract] ABSTRACT: Congestive fetal heart failure, defined as inability of the heart to deliver adequate blood flow to organs such as the brain, liver, and kidneys, is a common final outcome of many intrauterine disease states that may lead to fetal demise. Advances in fetal medicine during the past 3 decades now provide the diagnostic tools to detect and also treat conditions that may lead to fetal heart failure. Fetal echocardiographic findings depend on severity of diastolic and systolic dysfunction of both ventricles. At an advanced stage, findings include cardiomegaly; valvar regurgitation; venous congestion; fetal edema and effusions; oligohydramnios; and preferential shunting of blood flow to the brain, heart, and adrenals in the distressed fetus. A useful diagnostic tool to quantify severity of heart failure is the cardiovascular profile score, which is a composite score based on 5 different echocardiographic parameters. To predict outcomes, the score should be interpreted in the context of the underlying disease, as different causes of intrauterine heart failure may have highly variable outcomes. Low fetal cardiac output may result from a myocardial disease (cardiomyopathy, myocarditis, ischemia), abnormal loading conditions (arterial hypertension, obstructive structural heart disease, atrioventricular malformations, twin-to-twin transfusion), arrhythmia, or external cardiac compression (pleural and/or pericardial effusions, cardiac tumours). Treatment options are available for several of these conditions.
- [Show abstract] [Hide abstract] ABSTRACT: We describe a fetus at 36 weeks with long QT syndrome presenting with variable types of atrioventricular blocks, ventricular premature beats, and torsades de pointes. All these diagnoses were made with the superior vena cava-aorta Doppler approach and confirmed with postnatal electrocardiography.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to evaluate whether changes of uterine arteries and aortic isthmus Doppler blood flow recordings could enhance the prediction of necrotizing enterocolitis. Doppler characteristics of the uterine artery, umbilical and middle cerebral arteries, ductus venosus, and aortic isthmus were reviewed in 123 growth-restricted fetuses who were then divided into 2 groups: with and without necrotizing enterocolitis. Twelve of 123 newborn infants (9%) expressed necrotizing enterocolitis. This group showed significant association between necrotizing enterocolitis and bilateral notching on the uterine artery (83.3% vs 29.7%; P < .001), uterine artery mean resistance index (83.3% vs 36.9%; P < .002), aortic isthmus diastolic blood flow velocity integrals (Z score: -7.32 vs -3.99; P = .028), and absent or negative "a" wave on the ductus venosus (17% vs 1.8%; P = .021). With the use of logistic regression, uterine bilateral notching could predict necrotizing enterocolitis with a sensitivity of 83.3% and a specificity of 70.3%. More than any other variable, uterine bilateral notching should be recognized as a strong risk factor for necrotizing enterocolitis.
- [Show abstract] [Hide abstract] ABSTRACT: Pregnancy is associated with significant cardiac adaptations. The regulatory mechanisms involved in functional cardiac adaptations during pregnancy are still largely unknown. In pathologic conditions, mineralocorticoids have been shown to mediate structural as well as functional remodelling of the heart. However, their role in cardiac physiological conditions is not completely understood. Here, we examined cardiac cell metabolic remodelling in the late stages of rat pregnancy, as well as mineralocorticoid involvement in this regulation. We have applied rapid video imaging, echocardiography, patch clamp technique, confocal microscopy, and time-resolved fluorescence spectroscopy. Our results revealed that cardiac cells undergo metabolic remodelling in pregnancy. Inhibition of mineralocorticoid receptors during pregnancy elicited functional alterations in cardiac cells: blood levels of energy substrates, particularly lactate, were decreased. As a consequence, the cardiomyocyte contractile response to these substrates was blunted, without modifications of L-type calcium current density. Interestingly, this response was associated with changes in the mitochondrial metabolic state, which correlated with modifications of bound reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H levels. We also noted that mineralocorticoid receptor inhibition prevented pregnancy-induced decrease in transient outward potassium current. This study demonstrates that in pregnancy, mineralocorticoids contribute to functional adaptations of cardiac myocytes. By regulating energy substrate levels, in particular lactate, in the plasma and metabolic state in the cells, mineralocorticoids affect the contractility responsiveness to these substrates. In the future, understanding cardiac adaptations during pregnancy will help us to comprehend their pathophysiological alterations.
- [Show abstract] [Hide abstract] ABSTRACT: We verified whether oxidative stress indices (oxidized low-density lipoproteins and malondialdehyde) and inflammatory biomarkers (circulating C-reactive protein, interleukin-6, tumour necrosis factor-α, serum amyloid A and soluble intercellular vascular cell adhesion molecule) are increased in the umbilical vein of placental insufficiency induced intra-uterine growth restricted neonates. The prospective cohort study, involving 3 tertiary care centers, consists of 200 consecutively recruited pregnant women carrying twins. We chose the twin pregnancy model because both fetuses share the same maternal environment, thereby avoiding potential confounding factors when comparing oxidative stress and inflammation biomarkers. We analysed only twin pairs with one with intra-uterine growth restriction (N=38) defined as fetal growth<10th percentile with abnormal Doppler of the umbilical artery. Blood samples were taken at birth from the umbilical vein. Intra-pair comparisons on the biomarkers were performed using the Student paired t-test. We observed increased cord blood levels of oxidized low-density lipoproteins, (2.394 ± .412 vs 1.296 ± .204, p=.003) but not of malondialdehyde in growth restricted neonates when compared to their normal counterparts. Although indices of inflammation tended to be increased in cord blood from growth restricted newborns, the difference did not reach statistical significance. In the twin model, intra-uterine growth restriction is associated with low-density lipoprotein oxidation without apparent dysregulation of inflammation biomarkers. Increased oxidized low-density lipoproteins are observed in growth restricted twins compared to their co-twins with normal growth at birth.
- [Show abstract] [Hide abstract] ABSTRACT: The objective of the study was to evaluate the reliability of the 2 most commonly used ultrasonographic approaches for monitoring fetal atrioventricular conduction time (AVCT): (1) superior vena cava/ascending aorta (SVC/AA), and (2) left ventricular inflow/outflow tract (LVI/O) Doppler recordings. Echographic studies from fetuses followed up for first-degree atrioventricular block (AVB-1) between 1998 and 2008 were reviewed. The ability to identify atrial contractions in the same fetuses by the SVC/AA and LVI/O approaches was analyzed. Sixty-six studies of 13 fetuses with AVB-1 were available. Atrial contractions were visible in all SVC/AA studies. With the LVI/O approach, atrial contractions could not be identified in 26 studies (39%). AVCT delay was significantly greater in the nonidentifiable compared with the identifiable atrial contraction group (P < .001). Differences in heart rate and gestational age were not significant. The LVI/O is unsuitable for prenatal screening of conduction system anomalies.
- [Show abstract] [Hide abstract] ABSTRACT: Cardiac rhabdomyomas are benign cardiac tumours with few cardiac complications, but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. We have analysed the long-term cardiac and neurological outcomes of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counselling, basing our findings on the records of all patients seen prenatally and postnatally with an echocardiographic diagnosis of cardiac rhabdomyoma encountered from August, 1982, to September, 2007. We analysed factors such as the number and the location of the tumours to establish their association with a diagnosis of tuberous sclerosis, predicting the cardiac and neurologic outcomes for the patients.Cardiac complications include arrhythmias, obstruction of the ventricular outflow tracts, and secondary cardiogenic shock. Arrhythmias were encountered most often during the neonatal period, with supraventricular tachycardia being the commonest rhythm disturbance identified. No specific dimension or location of the cardiac rhabdomyomas predicted the disturbances of rhythm.The importance of the diagnosis of tuberous sclerosis is exemplified by the neurodevelopmental complications, with four-fifths of the patients showing epilepsy, and two-thirds having delayed development. The presence of multiple cardiac tumours suggested a higher risk of being affected by tuberous sclerosis. The tumours generally regress after birth, and cardiac-related problems are rare after the perinatal period. Tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture, and should form an important aspect of the prenatal counselling of parents.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: The purpose of this review is to explain why it is now time to create an International Society for Fetal and Perinatal Cardiovascular Disease. Recent findings: Rapid advances in four domains that involve the professionals caring for patients with congenital cardiac disease all point to the fact that it is now time to create an International Society for Fetal and Perinatal Cardiovascular Disease: fetal diagnosis - the improved ability to diagnose prenatal cardiovascular disease due to education and improved ultrasound technology; subspecialization - the development of perinatal cardiology as a true subspecialty of the professions of pediatric cardiology and perinatology; analysis of outcomes - the multidisciplinary international efforts in the areas of nomenclature and databases for the analysis of outcomes of treatments for patients with congenitally malformed hearts, efforts that span traditional geographic and subspecialty boundaries; globalization - the rapidly evolving global organization of professionals caring for patients with congenital heart disease. Summary: Healthcare professionals caring for the pregnant woman and fetus with congenital cardiac disease would be enthusiastic about the creation of an International Society for Fetal and Perinatal Cardiovascular Disease in order to achieve multiple objectives: to discuss the management of prenatal and perinatal cardiovascular disease (not exclusively cardiac malformations); to benefit from educational programs covering prenatal and perinatal physiology and pathophysiology, clinical and technical topics, as well as genetic, ethical, and psychosocial aspects of this relatively new discipline; and finally to share our basic science, translational, and clinical research interests.
- [Show abstract] [Hide abstract] ABSTRACT: To evaluate the cardiovascular impact of fetal anemia. We reviewed 53 echo-Doppler studies from 24 fetuses with anemia due to alloimmunization. There was no difference between the severe and nonsevere anemia for heart rate, cardiothoracic ratio, and contractility. There was an increased left ventricular dimension, peak velocities of the middle cerebral artery (MCA) and a decreased pulsatility index of the umbilical artery (UAPI) in the severe group. The combination of MCA and UAPI had a high sensitivity (86%), specificity (91%), positive (80%) and negative (94%) predictive value as well as positive predictive likelihood ratio (9.6) to detect severe anemia. Standard echocardiograhic parameters are not useful to correlate anemia. The combination of MCA and UAPI improves the accuracy to detect severe anemia.
- [Show abstract] [Hide abstract] ABSTRACT: The systemic pressor response to bolus injections of Angiotensin I (A-I) into the pulmonary artery (PA) and the aortic root (Ao) was compared in 11 children during routine left and right heart catheterization; five had a left-to-right shunt and 6 had no hemodynamic abnorm'alities. An additional 4 children with normal hemodynamics were tested with Angiotensin I1,(A-II). Systemic pressor peaks to PA injections of A-I were slightly higher than those resulting from Ao injections. A study of the time course of the pressor responses showed that the intervals from the injection to onset of response, and from injection to half peak, were significantly prolonged after injection of A-I into the aorta, as compared with injections of A-I1 by the same route. Such a difference was not observed when A-I and A-I1 were given into the PA. These results indicate that conversion occurs to a considerable degree in the peripheral circulation, with a delay that is most probably due to the process of activation. When this peripheral conversion is maximal, the systemic pressor response assay is unable to detect pulmonary conversion solely on the basis of the height of pressor peaks, because the responses are equal after PA and Ao injections. PA injections of Angiotensin I and I1 had no effect on pulmonary artery pressure. It is concluded that: (1) pulmonary conversion occurs in all children with and without shunt; (2) peripheral (systemic) conversion occurs to a considerable degree and can account for most of the overall conversion of Angiotensin I, so that the role of the lung in the renin-angiotensin system seems unlikely.
- [Show abstract] [Hide abstract] ABSTRACT: Unlabelled: The new physiological concept: because of the parallel disposition of the fetal ventricles and of their respective arterial outlet, the flow through the aortic isthmus represents the only arterial shunt in the fetal circulation. The low resistance of the placental circulation explains the forward systolic and diastolic flows normally observed through the isthmus. Clinical implications: (1) assessment of individual performances of each ventricle : left ventricle causes forward flow while the right ventricle has a retrograde influence; (2) any changes of flow and/or resistances affecting one of the two fetal arterial systems organized in parallel should influence the flow pattern within the isthmus. Examples : peripheral arterio-venous fistula, increase in placental vascular resistance leading to intra-uterine growth restriction, etc. Conclusion: doppler flow recordings in the fetal aortic isthmus: (1) provides information on the global condition of the fetal cardiocirculatory system; (2) is a good indicator of fetal individual ventricular performance; (3) allows assessment of hemodynamic consequences of abnormalities of the peripheral circulatory systems.
- [Show abstract] [Hide abstract] ABSTRACT: Pulmonary valve stenosis or atresia with intact ventricular septum represents a spectrum of severity. This study aimed to identify ultrasound markers of biventricular versus non-biventricular outcome. The fetal echocardiograms of 41 fetuses diagnosed with pulmonary stenosis or atresia and right ventricular (RV)/left ventricular (LV) length ratios >0.4 from 17 to 31 weeks of gestation were reviewed. Of 27 live-born patients with intention to treat, 8 had non-biventricular outcomes and 19 had biventricular circulation. At the time of diagnosis, poor RV function, flow reversal in the arterial duct, the degree of tricuspid valve (TV) regurgitation, and inferior vena cava Doppler flow pattern did not differ between the 2 outcome groups. However, RV sinusoids, the RV/LV length ratio, the TV/mitral valve ratio, and TV inflow duration were significantly different. Cut-off values derived from receiver-operating characteristic curves yielding the best sensitivity and specificity for a non-biventricular outcome were TV/mitral valve ratio <0.7, RV/LV length ratio <0.6, TV inflow duration <31.5% of cardiac cycle length, and the presence of RV sinusoids. If 3 of these 4 criteria were fulfilled, this predicted a non-biventricular outcome with sensitivity of 100% and specificity of 75%. In conclusion, in fetuses < or =31 weeks of gestation with pulmonary stenosis or atresia and intact ventricular septum, progression to a non-biventricular outcome can be predicted by a 4-criterion scoring system. The criteria may be useful in selecting fetuses for prenatal catheter intervention to prevent progressive RV hypoplasia.
Université de Montréal
Montréal, Quebec, Canada
- Department of Pediatrics