Prediction of postnatal circulation in pulmonary atresia/critical stenosis with intact ventricular septum: systematic review and external validation of models.

OBJECTIVE: A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort. METHODS: This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated. RESULTS: Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models. CONCLUSIONS: Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis, associated findings and postnatal outcome in fetuses with congenitally corrected transposition of the great arteries.

PURPOSE: To analyze anatomic features and associated malformations in 37 prenatally detected cases of congenitally corrected transposition of the great arteries (ccTGA) and to evaluate the prenatal course, neonatal outcome and mid-term follow-up. METHODS: Retrospective analysis of prenatal ultrasound of 37 patients with ccTGA in two tertiary centers between 1999 and 2019. All fetuses received fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports. RESULTS: Isolated ccTGA without associated cardiac anomalies was found in 13.5% (5/37), in all other fetuses additional defects such as VSD (73.0%), pulmonary obstruction (35.1%), tricuspid valve anomalies (18.9%), aortic arch anomalies (13.5%), ventricular hypoplasia (5.4%) or atrioventricular block (5.4%) were present. The rate of extracardiac malformations or chromosomal aberrations was low. There were 91.9% (34/37) live births and postnatal survival rates reached 91.2% in a mean follow-up time of 4.98 years. The prenatal diagnosis of ccTGA was confirmed postnatally in all but one documented live birth and the prenatal counselling regarding the expected treatment after birth (uni- versus biventricular repair) was reassured in the majority of cases. The postnatal intervention rate was high, 64.7% (22/34) received surgery, the intervention-free survival was 36.7%, 35.0% and 25.0% at 1 month, 1 year and 10 years, respectively. CONCLUSIONS: ccTGA is a rare heart defect often associated with additional heterogeneous cardiac anomalies that can be diagnosed prenatally. The presented study demonstrates a favorable outcome in most cases but the majority of patients require surgical treatment early in life.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

PURPOSE: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. RESULTS: 39 cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range, 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 21 of 24 (87.5%) cases and of TAC subtype in 19 of 21 (90.5%) cases. Prenatal diagnosis of TAC was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect postnatally, one had hypoplastic right ventricle with dextro Transposition of the Great Arteries with coartation of the aorta and a third newborn had Tetralogy of Fallot with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These three cases were excluded from further analysis. In 9 of 34 (26.5%) cases, TAC was an isolated finding. 13 (38.2%) fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in 3 (8.8%) and in 20 (58.8%) cases, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 6 (17.6%) cases. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range, 6-104). Postoperative health status among survivors was excellent in 11 (78.6%) infants, but 5 (46.2%) of them needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 3 (21.4%) survivors were significantly impaired due to non-cardiac problems. CONCLUSION: TAC is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative short- and medium-term health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

PURPOSE: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. RESULTS: Thirty nine cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 87.5% and of TAC subtype in 90.5%. Prenatal diagnosis was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect (VSD) postnatally, one had hypo-plastic right ventricle with dextro transposition of the great arteries (d-TGA) with coarctation of the aorta and a third newborn had tetralogy of fallot (TOF) with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These 3 cases were excluded from further analysis. In 26.5% of cases, TAC was an isolated finding. 38.2% of fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in between 8.8% and 58.8%, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 17.6%. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range 6-104). Postoperative health status among survivors was excellent in 78.6%, but 46.2% needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 21.4% of survivors were significantly impaired due to non-cardiac problems. CONCLUSION: Truncus arteriosus communis is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of absent pulmonary valve syndrome from first trimester onwards: novel insights into pathophysiology, associated conditions and outcome.

OBJECTIVE: To assess the spectrum of associated anomalies, intrauterine course and outcome in fetuses with absent pulmonary valve syndrome (APVS). METHODS: All cases with a prenatal diagnosis of APVS at two centers over a period of 13 years were analyzed retrospectively. APVS was diagnosed in the presence of rudimentary or dysplastic pulmonary valve leaflets with to-and-fro blood flow in the pulmonary trunk on color and pulsed-wave Doppler ultrasound. Data on demographic characteristics, presence of associated conditions, Doppler studies and pregnancy outcome were reviewed. RESULTS: During the study period, 40 cases of APVS were diagnosed prenatally. Thirty-seven (92.5%) cases were associated with tetralogy of Fallot (TOF) and three (7.5%) had an intact ventricular septum. Patency of the ductus arteriosus (DA) was found in 17/37 (45.9%) TOF cases and in all three cases with an intact ventricular septum. Mean gestational age at diagnosis was 19.7 (range, 12-34) weeks with 10 (25.0%) cases (all with TOF) diagnosed in the first trimester. TOF was an isolated finding in 15 (37.5%) cases. Chromosomal anomalies, cardiac defects and extracardiac anomalies were present in 18 (45.0%), four (10.0%) and three (7.5%) cases, respectively. Among the 40 cases, there were 19 (47.5%) terminations of pregnancy, six (15.0%) intrauterine deaths, four (10.0%) neonatal deaths and 11 (27.5%) survivors. Patency of the DA, reversed flow during atrial contraction in the ductus venosus, umbilical artery or fetal middle cerebral artery, and hydrops/increased nuchal translucency thickness were significantly associated with non-survival. All 10 cases diagnosed in the first trimester had a patent DA and abnormal Doppler parameters, eight had hydrops and/or increased nuchal translucency, six were associated with trisomy 13 or 18 and none survived. CONCLUSION: APVS diagnosed in the first trimester is significantly associated with TOF, patency of the DA, abnormal Doppler parameters, lethal trisomies and intrauterine mortality. Cases of APVS with isolated TOF and agenesis of the DA have a better outcome than those with additional anomalies, with > 80% survival. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Extracardiac anomalies in prenatally diagnosed heterotaxy syndrome.

OBJECTIVE: To assess the incidence and impact of extracardiac anomalies on the prognosis of fetuses with heterotaxy syndrome. METHODS: All fetuses diagnosed with heterotaxy syndrome by three experienced examiners over a period of 14 years (1999-2013) were reviewed retrospectively. RESULTS: In total, 165 fetuses with heterotaxy syndrome were diagnosed in the study period. One hundred and fifty (90.9%) had cardiac defects; extracardiac anomalies that did not involve the spleen were present in 26/165 (15.8%) cases. Of the total study cohort, termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were alive at the latest follow-up, resulting in a total perinatal and pediatric mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac anomalies with significant impact on the postnatal course: one neonate died following repair of an encephalocele, six had successful treatment for various types of intestinal malrotation and/or atresia and one underwent hiatal hernia repair; the remaining seven had biliary atresia, of which five died and the two survivors are awaiting liver transplantation. The status of the spleen was assessed in 93/105 liveborn children and was found to be abnormal in 84/93 (90.3%). There were three cases of lethal sepsis, all associated with asplenia. Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an extracardiac cause and in two (5.2%) the reason was uncertain. CONCLUSIONS: Although the leading causes of death in fetuses and children with heterotaxy syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with significant impact on outcome. These anomalies often escape prenatal detection, and therefore neonates at risk should be monitored for bowel obstruction, biliary atresia and immune dysfunction in order to allow timely intervention through a multidisciplinary approach. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Spatiotemporal accuracy of real-time 3D echocardiography in the neonatal and pediatric setting--validation studies using small dynamic test objects.

UNLABELLED: The precision of real-time 3D-echocardiography (RT3DE) is not sufficiently validated for small, fast-moving structures such as the neonatal and pediatric heart. PURPOSE: To assess the spatiotemporal accuracy of RT3DE in small, moving test objects. MATERIALS AND METHODS: Small, calibrated test objects in the size of neonatal and pediatric heart chambers were made from polyurethane foam or metal wire mesh and moved in a water bath through a calibrated dynamic test system. Using matrix transducers (X7-2, ie33 and X4-1, Sonos 7500, Philips, Andover, USA), 2 D and live 3 D datasets under variation of the motion speed (0.033 - 0.133 m/s corresponding to 50 - 200 heart cycles/minute), the volume rate and transducer position were recorded and analyzed (QLab 7.0, Philips). RESULTS: 3 D datasets of the moving test objects showed relevant spatial distortion, which was obviously related to the sequential scanning technology of the matrix transducer. Different segments of a test object were not recorded simultaneously, but rather row-by-row, so that there was a time delay between the first and the last-recorded voxel of a single 3 D volume (mean±SD: 28.9 ±â€Š7.82 m/s or 80 ±â€Š7 % of the time duration of a 3 D volume). With increasing motion speed of the test object and reduced 3 D volume rate, the distortion artifacts increased significantly. CONCLUSION: 3 D acquisitions using matrix technology demonstrate relevant spatiotemporal inaccuracies. This may lead to misinterpretations during the evaluation of the synchronicity of valvular or ventricular motion and incorrect definition of volume estimations. In particular, at higher heart rates and higher rates of movement, these limitations have to be taken into account in clinical practice.

Fitness to fly for children and adolescents after Fontan palliation.

Introduction: At cruising altitude, the cabin pressure of passenger aircraft needs to be adjusted and, therefore, the oxygen content is equivalent to ambient air at 2,500 masl, causing mild desaturation and a rising pulmonary vascular resistance (PVR) in healthy subjects. For Fontan patients with passive pulmonary perfusion, a rising PVR can cause serious medical problems. The purpose of this fitness to fly investigation (FTF) is to assess the risk of air travel for children and adolescents after Fontan palliation. Methods: We investigated 21 Fontan patients [3-14y] in a normobaric hypoxic chamber at a simulated altitude of 2,500 m for 3 h. Oxygen saturation, heart rate, and regional tissue saturation in the forehead (NIRS) were measured continuously. Before entering the chamber, after 90 and 180 min in the hypoxic environment, blood gas analysis and echocardiography were performed. Results: Heart rate and blood pressure did not show significant intraindividual changes. Capillary oxygen saturation (SaO2) decreased significantly after 90 min by a mean of 5.6 ± 2.87% without further decline. Lactate, pH, base excess, and tissue saturation in the frontal brain did not reach any critical values. In the case of open fenestration between the tunnel and the atrium delta, P did not increase, indicating stable pulmonary artery pressure. Conclusion: All 21 children finished the investigation successfully without any adverse events, so flying short distance seems to be safe for most Fontan patients with good current health status. As the baseline oxygen saturation does not allow prediction of the maximum extent of desaturation and adaption to a hypoxic environment takes up to 180 min, the so-called hypoxic challenge test is not sufficient for these patients. Performing an FTF examination over a period of 180 min allows for risk assessment and provides safety to the patients and their families, as well as the airline companies.

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis]. / Neurologische und psychomotorische Entwicklung von Feten und Neugeborenen mit angeborenen Herzfehlern--Ursachen und Prävalenz von Störungen im Langzeitverlauf.

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population.

[Fetal cardiac interventions]. / Kardiale Interventionen bei Feten.

Fetal cardiac interventions are being performed with growing success by a minimally invasive percutaneous and transthoracic approach. The primary aim of these interventions is to minimise postnatal morbidity and mortality, rarely also to achieve intrauterine survival. Valvuloplasty in utero for severe aortic stenosis is performed in order to achieve sufficient growth of the left ventricle and to make a later biventricular repair possible. In rare cases with hydrops secondary to massive left ventricular dilatation and mitral insufficiency it is used as a salvage therapy. Premature obstruction of the foramen ovale can be treated by balloon atrioseptoplasty or stenting of the atrial septum with the aim to attain a decompression of the left atrium and consequently of the pulmonary veins. This might reduce the extent of pulmonary hypertension and the resulting vascular and parenchymal changes in affected infants. Intrauterine valvuloplasty of a highly stenotic pulmonary valve or a pulmonary atresia with intact ventricular septum in order to prevent hypoplasia of the right ventricle and to enable postnatal biventricular repair is only rarely justified. Currently these intrauterine cardiac interventions are limited to a small group of fetuses with cardiac defects. However, with enhanced imaging modalities and equipment and with growing experience, fetal cardiac interventions are likely to increase in the next years.

Echocardiography in the fetus--a systematic comparative analysis of standard cardiac views with 2D, 3D reconstructive and 3D real-time echocardiography.

PURPOSE: The aim of our study was to assess the feasibility and reliability of fetal three-dimensional reconstructive echocardiography using freehand technique (3DR) and 3D real-time echocardiography using matrix technology (RT-3D) in consecutive series of pregnancies and to compare the findings with the gold standard 2D ultrasound, as well as postnatal findings. MATERIALS AND METHODS: Fifty consecutive pregnant women (gestational age 19+3 to 37+0) including 10 fetuses with cardiac malformations were scanned prospectively with 2D, 3DR and RT-3D. 3D data sets were evaluated by a blinded independent examiner. The visualization rates for standard cardiac views and structures were determined and the quality and diagnostic accuracy of each modality were calculated. RESULTS: In RT-3D, the visualization rate of fetal cardiac views was equivalent to 2D, but was significantly lower for 3DR (4cv: 2D 98%, RT-3D 100%, 3DR 96% RVOT: 2D 96%, RT-3D 98%, 3DR 84%). Short-axis views or views of the complete aortic or ductal arch were more readily identified in RT-3D than in 2D (2D 70%, RT-3D 82%). 3DR was more susceptible than RT-3D to artifacts during acquisition and post-processing. The sensitivity and overall accuracy were significantly higher for 2D and RT-3D than for 3DR, when prenatal data was compared with postnatal findings. CONCLUSION: 3D freehand reconstruction has significantly lower visualization rates and overall accuracy compared to 2D and RT-3D. RT-3D echo is a feasible and reliable method for imaging the fetal heart. Offering the opportunity of data post-processing and evaluation, RT-3D is a promising method for improving the accuracy of sonographic analysis of fetal cardiac morphology and function.

Volumetry of fetal hearts using 3D real-time matrix echocardiography - in vitro validation experiments and 3D echocardiographic studies in fetuses.

PURPOSE: The aim of this study was to assess the feasibility, accuracy and reliability of 3D real-time echocardiography for fetal heart volumetry. MATERIALS AND METHODS: Fifty unselected and consecutive fetuses, including 14 with cardiac malformations, were scanned prospectively using real-time 3D matrix technology and 2D echocardiography to determine ventricular volumes. Small phantoms as well as modified balloons (0.5 - 20 ml) were used to assess the validity of 2D and 3D distance, area and volume calculations and to study potential sources of error during data acquisition and analysis. The data was evaluated by two blinded observers. RESULTS: In vitro, real-time 3D and 2D underestimated the actual volumes by -5.49 % (3D) and -6.86 % (2D). The intraobserver and interobserver variability were excellent. In vivo, real-time 3D was superior to 2D with regard to intraobserver and interobserver variability (mean coefficient of variation 8.28 % (3D) versus 13.96 % (2D), and mean intraclass correlation coefficient 0.997 (3D) versus 0.885 (2D) for left ventricular volumes). Similar to in vitro, in vivo 2D volumes were calculated smaller than 3D volumes (mean difference -0.39 to -0.94 ml). The ventricular volumes and stroke volumes increased exponentially with gestation. Secondary to poor imaging windows in advanced gestation or inadequate delineation of endocardial borders in small hearts at less than 19 weeks, 3D data could not be analyzed sufficiently in 6 / 50 fetuses. CONCLUSION: Real-time 3D using a matrix transducer is a feasible, reliable and valid method for volume determination in the fetus beyond 19 weeks of gestation. If compared to 2D, real-time 3D echocardiography provides improved accuracy of cardiac volumetry, decreases intraobserver and interobserver variability and is a promising tool for the accurate assessment of cardiac size and function.

Prenatal diagnosis of tricuspid atresia: intrauterine course and outcome.

OBJECTIVE: To evaluate the intrauterine course and outcome of tricuspid atresia detected in the fetus. METHODS: This was a retrospective review of all confirmed cases of tricuspid atresia detected prenatally between 1998 and 2006 in three tertiary referral centers in Germany. RESULTS: Fifty-four cases of tricuspid atresia were detected prenatally during the study period and confirmed postnatally: 28 (51.9%) cases had a concordant ventriculoarterial connection of which 14 also had pulmonary outflow obstruction; 25 (46.3%) cases had a discordant ventriculoarterial connection of which 14 also had aortic outflow obstruction, six had pulmonary outflow tract obstruction and two had other associated intracardiac anomalies; and one (1.9%) had a common arterial trunk. The peak velocity index for veins in the ductus venosus was significantly elevated in 19 of the 37 (51.4%) cases assessed; however, this finding did not correlate with adverse intrauterine outcome. There were associated extracardiac anomalies in 12 cases: five with chromosomal anomalies, two with VACTERL association, one with unilateral renal agenesis, one with hypospadia, one with hydrothorax, one with megacystis and one with agenesis of the ductus venosus. Seventeen of the 54 (31.5%) cases underwent termination of pregnancy, two (3.7%) died in utero, two (3.7%) died in infancy and 33 (61.1%) children survived with a median follow-up of 26 (range, 12-120) months. Prenatal echocardiography correctly anticipated the postnatal course and the need for neonatal intervention in 29/35 (82.9%) continued pregnancies; in the remaining six (17.1%) cases the right outflow tract obstruction had been underestimated. CONCLUSIONS: Tricuspid atresia and the frequently associated intracardiac anomalies can be diagnosed in the fetus with considerable accuracy. A thorough search for extracardiac malformations should be performed in order to rule out chromosomal anomalies and multiple malformation syndromes. Elevated pulsatility in the ductus venosus does not indicate cardiac failure. The short-term overall survival in continued pregnancies in our study exceeded 89%, with the greatest rate of loss being in the first year of postnatal life.

Atrioventricular septal defect in the fetus--associated conditions and outcome in 246 cases.

PURPOSE: To evaluate the associated conditions and the outcome of atrioventricular septal defects (AVSD) detected in fetal life. MATERIALS AND METHODS: Retrospective review of all cases of AVSD detected prenatally between 1998 and 2006 in two tertiary referral centers in Germany. RESULTS: 246 cases of AVSD were detected in the study period: 129 (52.4 %) chromosomal anomalies; 72 (29.3 %) heterotaxy syndromes; 17 (6.9 %) non-chromosomal malformation syndromes; 16 (6.5 %) isolated complex cardiac malformations; 5 (2.0 %) singular extracardiac malformations; 7 (2.8 %) isolated AVSD. Chromosomal anomalies were detected significantly earlier in pregnancy (p < 0.01). Associated intracardiac malformations were present in 109/246 (44.3 %) cases. Fetuses with trisomy 21 were significantly associated with balanced ventricular morphology and isolated AVSD (p < 0.01). Among the 246 cases, 144 (58.5 %) underwent termination of pregnancy, 18 (7.3 %) died in utero, 17 (6.9 %) in the neonatal period and 19 (7.7 %) in infancy. Forty-eight children (19.5 %) survived with a mean follow-up of 34.94 +/- 18.6 months. After exclusion of lethal malformations, the survival rate among live births was 64.9 % (48 / 74). Fetuses with trisomy 21 had significantly better survival rates among continued pregnancies (p < 0.01) and significantly higher rates of successful biventricular repair among survivors who received their final corrective procedure (p < 0.01) than fetuses with normal karyotypes. CONCLUSION: Among fetuses with AVSD, those with trisomy 21 are detected earlier in pregnancy, have less distorted cardiac anatomy, higher rates of biventricular repair and better survival rates. Due to the limited sample size in euploid fetuses, it remains unclear whether this apparent protection afforded to Down syndrome accounts also for cohorts with isolated and balanced AVSD.

Clinical spectrum of fetal long QT syndrome: a single-center experience.

OBJECTIVE: A considerable proportion of unexplained intrauterine fetal deaths are attributed to long QT syndrome (LQTS) susceptibility. Additionally, the estimated prevalence of LQTS in newborns is 1 in 2000. Still, prenatal diagnosis of LQTS is very rare. The aim of this study was to assess the frequency of prenatal diagnosis of LQTS at our institution, present the cases, compare our findings with the existing literature and propose a possible screening approach. METHODS: We searched our fetal database between 2006 and 2013 for cases with suspected diagnosis of LQTS. RESULTS: During the investigation period around 26 000 fetuses were evaluated and three cases of suspected fetal LQTS identified. Two cases of familial LQTS had no or mild intrauterine manifestation of the condition, the third fetus had a de-novo mutation with severe, early-onset disease. CONCLUSIONS: LQTS continues to be a challenging prenatal diagnosis. In fetuses who present with complex arrhythmias, a high degree of suspicion is required, and close surveillance and timely delivery in the presence of a multidisciplinary team are necessary. For asymptomatic cases or screening purposes, routine fetal heart rate registration and detailed assessment of cases with a low for gestational age baseline may be an option.

Adenocarcinoma of the lung. Immunohistochemical findings (keratin/CEA).

The reaction patterns in 80 adenocarcinomas of the lung were examined with PAP-method using a monoclonal antibody against keratin and one against carcinoembryonic antigen (CEA) and a polyclonal antiserum against CEA. Almost all tumors showed a positive reaction to the antibodies which, however, varied quantitatively. Even though a reliable correlation of positive immunohistochemical reaction with the different light microscopical types was not possible according to WHO subtypes and degrees of differentiation, specific localization of the reaction within the tumor cells was seen with increasing differentiation. There was no correlation between the immunohistochemical reactions and 14 clinically measured plasma CEA levels. The plasma CEA level not only depends on CEA production by the tumor but also on other factors.

Imaging in fetal cardiology.

Early detection and accurate diagnosis of fetal cardiac disease is a central approach in perinatal medicine. The purpose of this review is to evaluate current imaging modalities for the assessment of the fetal heart and its function. Conventional fetal 2D- and color-Doppler echocardiography as a screening tool as well as a diagnostic modality has been proven to be safe, easy and cost-effective for the diagnosis of structural heart disease. Cardiac function can be assessed by M-mode and intra- and extra-cardiac Doppler-echocardiography on a routine basis, but remains challenging in subclinical pathology. Tissue-Doppler, speckle tracking, dynamic three-dimensional (4D) echocardiography, and fetal cardiac magnetic resonance imaging are advanced modalities for the assessment of cardiac structure and function. Implementation of these new technologies is far from routine, but these approaches have already shown promising results and may allow a more detailed evaluation of cardiac function. In this review, we provide a brief overview of currently available techniques, and their benefits and limitations in the clinical assessment of the fetal heart.