Prenatal diagnosis of maternal uniparental disomy 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction in the fetus.

OBJECTIVE: We present prenatal diagnosis of maternal uniparental disomy (UPD) 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction (IUGR) in the fetus. CASE REPORT: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XX,+16[2]/46,XX[54]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 14% mosaicism for trisomy 16 and a paternally inherited 319-kb microdeletion of 15q11.2 encompassing the genes of TUBGCP5, CYFIP1, NIPA2 and NIPA1. Prenatal ultrasound revealed persistent left superior vena cava, pericardial effusion and severe IUGR. Cordocentesis at 23 weeks of gestation revealed a karyotype of 46,XX, but polymorphic DNA marker analysis revealed maternal UPD 16. Repeat amniocentesis was performed at 27 weeks of gestation and revealed a karyotype of 46, XX in 21/21 colonies. Molecular cytogenetic analysis on uncultured amniocytes revealed 22.4% mosaicism (26/116 cells) for trisomy 16 on interphase fluorescence in situ hybridization (FISH) analysis, and 20% mosaicism for trisomy 16 on aCGH. Polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods revealed maternal UPD 16. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism and severe IUGR. The umbilical cord had a karyotype of 47,XX,+16[28]/46,XX[16]. Polymorphic DNA marker analysis on placenta confirmed a maternal origin of trisomy 16. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Prenatal diagnosis of mosaic trisomy 16 should alert the association of maternal UPD 16 which may be associated with congenital heart defects and severe IUGR on prenatal ultrasound.

Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial.

Importance: Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion. Objective: To determine whether vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation. Design, Setting, and Participants: The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial was an investigator-initiated, National Institutes of Health-funded, randomized, single-blinded trial conducted in 12 centers in the United States. Patients (N = 350) with persistent AF referred for first ablation were enrolled from October 2013 through June 2018. Follow-up concluded in June 2019. Interventions: Patients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures. Main Outcomes and Measures: The primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both 6 and 12 months. Outcome assessment was blinded to randomization treatment. There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, perimitral block, and others. Results: Of the 343 randomized patients (mean [SD] age, 66.5 [9.7] years; 261 men), 316 (92.1%) completed the trial. Vein of Marshall ethanol was successfully delivered in 155 of 185 patients. At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2% (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38% (60/158) in the catheter ablation alone group (difference, 11.2% [95% CI, 0.8%-21.7%]; P = .04). Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3% vs 67.9%; difference, 10.4% [95% CI, 2.9%-17.9%]; P = .01), freedom from AF after multiple procedures (65.2% vs 53.8%; difference, 11.4% [95% CI, 0.6%-22.2%]; P = .04), and success achieving perimitral block (80.6% vs 51.3%; difference, 29.3% [95% CI, 19.3%-39.3%]; P < .001) were significantly improved in vein of Marshall-treated patients. Adverse events were similar between groups. Conclusions and Relevance: Among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Further research is needed to assess longer-term efficacy. Trial Registration: ClinicalTrials.gov Identifier: NCT01898221.

Left superior vena cava: cross-sectional imaging overview.

Persistent left-sided superior vena cava (PLSVC) is the commonest systemic venous anomaly in the thorax with a reported prevalence of up to 0.5% in otherwise normal population and up to 10% in patients with congenital heart disease (CHD). In the absence of associated CHD, it is usually asymptomatic, discovered incidentally. It may complicate catheter or pacemaker lead placement. PLSVC typically drains into the right atrium through the coronary sinus. In children with CHD, the presence of a PLSVC may affect the choice of certain surgical procedures. PLSVC is significantly more common in association with situs ambiguous than with situs solitus or inversus, up to 60-70%. In patients with situs ambiguous, the drainage of LSVC is variable, more commonly directly into the atria rather than through the coronary sinus (CS). Rarely, there is a PLSVC draining into the CS with absent right SVC. PLSVC draining into the right atrium via the CS will not usually cause blood shunting between the right and the left sides. However, shunting occurs when PLSVC is associated with unroofed CS, or when it directly drains into the left atrium. With an increased use of CT and MRI for chest and cardiac imaging, PLSVC is being more encountered by radiologists than before. In this article, we will discuss the embryology of PLSVC, its anatomic course and drainage pathways, as well as its clinical relevance and relation to congenital heart disease and viscero-atrial situs.

Left Superior Vena Cava in the Fetus: A Rarely Isolated Anomaly.

The frequency of chromosomal anomalies among fetuses with isolated persistent left superior vena cava (PLSVC) is still debated. The objective of the present study was to assess the prevalence of genetic and morphological anomalies identified in fetuses with PLSVC. We conducted a single-center retrospective study including all fetuses diagnosed with a PLSVC between 2010 and 2017. PLSVC was categorized as isolated or associated according to antenatal diagnosis of associated congenital heart defects, hypoplastic aortic isthmus, abnormal venous/arterial connections, and extracardiac anomalies. Among 229 fetuses diagnosed with PLSVC, 39 cases (17%) were strictly isolated and no syndromic/genetic anomaly or aortic coarctation was diagnosed. Seventy-two fetuses had a cardiovascular defect with a rate of genetic anomalies of 22%, 29 had an extracardiac malformation, and 89 had both an extracardiac and a cardiovascular defect. Among fetuses with abnormal development of the arterial/venous system as the only associated anomaly such as aberrant right subclavian artery or absent ductus venosus, 22% had a genetic anomaly. Overall, sixty-five fetuses or infants had a genetic concern, including 23 aneuploidies, 15 pathogenic micro-deletions/duplications, and 5 variants of unknown significance; 12 patients had VACTERL association, and 12 heterotaxy syndrome. Seven infants had an aortic coarctation diagnosed at birth.In conclusion, a thorough prenatal ultrasound examination is paramount, and the identification of variants of the venous/arterial system in addition to PLSVC should raise suspicion for genetic or morphologic abnormalities. Invasive prenatal diagnosis with array-CGH should be offered when PLSVC is non-isolated, after a detailed ultrasound evaluation in a tertiary center.

The Fetal 3-Vessel Views: An Illustrative Case-Based Tutorial.

In 2018, the American Institute of Ultrasound in Medicine revised its obstetric Practice Parameter for the second-trimester fetal anatomic survey. The 2018 Practice Parameter recommends incorporation of the 3-vessel view and 3-vessel and trachea view "if technically feasible." Sonographers and other medical providers may require additional training and education to develop greater proficiency in obtaining and interpreting these views. This pictorial essay, including ultrasound images alongside their respective schematic diagrams, provides an up-to-date, practical, and clinically oriented review of the 3-vessel view and 3-vessel and trachea view and their most common presentations in the context of congenital heart disease.

Multidetector-row CT imaging evaluation of superior and inferior vena cava normal anatomy and caval variants: Report of our cases and literature review with embryologic correlation.

OBJECTIVE: To assess the potential of multidetector-row computed tomography imaging and its reformations in the evaluation of the superior and inferior vena cava normal anatomy and their anatomical variants, and to make a brief review of caval embryogenesis and developmental errors. METHODS: We retrospectively reviewed a total of 1000 whole-body computed tomography scans performed between January 2010 and December 2016 to assess the normal superior and inferior vena cava anatomy and their variants. RESULTS: The normal superior and inferior vena cava anatomy was found in 88.9% of patients, whereas multiple variants were found, ranging from the superior or inferior vena cava duplication, to the azygos continuation of the inferior vena cava. CONCLUSIONS: Computed tomography is a powerful tool to analyse superior and inferior vena cava anatomical variants. The knowledge and assessment of normal caval anatomy and of its anatomical variants is mandatory in the correct pre-operative planning in surgical and radiological interventions. Knowledge of caval variants is helpful in the differential diagnosis of abdominal or mediastinal masses, to avoid misdiagnosis, as well as in the screening of associated congenital pathologic conditions.

Magnetic resonance imaging of fetal persistent left superior vena cava.

This study aimed to evaluate the diagnostic accuracy of fetal magnetic resonance imaging (MRI) for persistent left superior vena cava (LSVC). Prenatal echocardiography (echo) and/or ultrasound (US) and MRI data for 49 fetuses with persistent LSVC, confirmed via postnatal diagnoses between January 2010 and October 2015, were retrospectively reviewed. All prenatal MRI was performed at 1.5 T. Imaging sequences included steady-state free-precession (SSFP), single-shot turbo spin echo (SSTSE), and other sequences. All 49 cases of fetal persistent LSVC were correctly diagnosed via MRI, but only 34 cases (69.4%) were correctly diagnosed via an initial US and/or echo before MRI. Of the 15 cases that were not correctly diagnosed via US and/or echo, 8 had congenital heart diseases (CHDs) and 7 were without CHDs; however, they were associated with extracardiac abnormalities or maternal obesity. Thirty-five cases were associated with other cardiovascular abnormalities; 8, with extracardiac abnormalities; and 6, with no associated condition. In 44 (89.8%) cases, the innominate veins were absent; the remaining cases had innominate veins. In 14.3% of patients (7 cases), the persistent LSVC drained directly into the atrium. Fetal MRI can detect persistent LSVC and play an adjunctive role along with US in the evaluation of persistent LSVC.

Prenatal diagnosis and prognosis of accelerated idioventricular rhythm.

OBJECTIVES: As postnatal identification of accelerated idioventricular rhythm (AIVR) relies on specific electrocardiographic patterns, prenatal diagnosis of this condition is challenging and its true incidence is unknown. The objectives of this study were to evaluate the performance of prenatal ultrasonography in identifying intrauterine cardiocirculatory events linked to specific electrocardiographic signs of postnatal AIVR, including left or right ventricular origin, and to assess the prenatal prognosis of this arrhythmia. METHODS: We reviewed Doppler tracings from the superior vena cava/ascending aorta (SVC/Ao), ductus venosus (DV), ductus arteriosus (DA) and aortic isthmus (AoI), as well as simultaneous M-mode recordings of septal and left ventricular wall motions of fetuses diagnosed with AIVR from January 2004 to December 2014. RESULTS: Three cases of AIVR were identified among 27 912 fetuses. SVC/Ao Doppler flow recordings revealed atrioventricular dissociation (ventricular rates within 20% of atrial rates) in all three fetuses and episodes of isorhythmic atrioventricular dissociation in one, while M-mode confirmed normal left ventricular shortening fraction in all cases. Fusion beats were observed on AoI tracing in one fetus, while simultaneous recordings of AoI and DA revealed signs of right bundle branch block in one case and left bundle branch block in the other two. On DV Doppler recordings, retrograde a-waves in the presence of simultaneous atrial and ventricular contractions were observed in all three fetuses, leading to an increase in central venous pressure in all and hydrops fetalis in two cases without evidence of ventricular dysfunction. CONCLUSIONS: Echocardiographic criteria required for postnatal diagnosis of AIVR can be documented in utero using specific ultrasonographic approaches. During fetal life, AIVR may not be a benign entity. Hydrops fetalis is frequently associated with AIVR because of increase in central venous pressure related to simultaneous atrioventricular contractions; thus, the ultrasonographic investigation protocol of fetuses with unexplained hydrops fetalis should aim at ruling out AIVR and include Doppler flow recordings in SVC/Ao, DV, AoI, DA and umbilical vein. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Absent right superior caval vein in situs solitus.

UNLABELLED: Introduction In up to 0.07% of the general population, the right anterior cardinal vein obliterates and the left remains open, creating an absent right superior caval vein and a persistent left superior caval vein. Absent right superior caval vein is associated with additional congenital heart disease in about half the patients. We wished to study the consequences of absent right superior caval vein as an incidental finding on prenatal ultrasonic malformation screening. Material and methods This is a retrospective case series study of all foetuses diagnosed with absent right superior caval vein at the national referral hospital, Rigshospitalet, Denmark, from 2009 to 2012. RESULTS: In total, five cases of absent right superior caval vein were reviewed. No significant associated cardiac, extra-cardiac, or genetic anomalies were found. Postnatal echocardiographies confirmed the diagnosis and there were no postnatal complications. All children were found to have healthy hearts at follow-up. CONCLUSIONS: In all cases, the findings proved to be a benign condition with no clinical manifestations or complications. Although isolated absent right superior caval vein does not seem to affect the outcome, associated anomalies may be serious. Absent right superior caval vein should, therefore, prompt a search for additional malformations. Furthermore, the diagnosis of an isolated absent right superior caval vein is important, because knowledge of the anomaly can prevent future problems when invasive procedures are necessary.

Comprehensive Imaging Review of the Superior Vena Cava.

The superior vena cava (SVC) is the largest central systemic vein in the mediastinum. Imaging (ie, radiography, computed tomography [CT], magnetic resonance [MR] venography, and conventional venography) plays an important role in identifying congenital variants and pathologic conditions that affect the SVC. Knowledge of the basic embryology and anatomy of the SVC and techniques for CT, MR imaging, and conventional venography are pivotal to accurate diagnosis and clinical decision making. Congenital anomalies such as persistent left SVC, partial anomalous pulmonary venous return, and aneurysm are asymptomatic and may be discovered incidentally in patients undergoing imaging evaluation for associated cardiac abnormalities or other indications. Familiarity with congenital abnormalities is important to avoid image misinterpretation. Acquired abnormalities such as intrinsic and extrinsic strictures, fibrin sheath, thrombus, primary neoplasms, and trauma can produce mild narrowing to complete occlusion, the latter leading to SVC syndrome. Each imaging modality plays a role in evaluation of the SVC, helping to determine the site, extent, and cause of pathologic conditions and guide appropriate management. Commonly performed interventional procedures for fibrin sheath and benign and malignant strictures include low-dose thrombolytic infusion, fibrin sheath disruption, venous angioplasty, and stent placement.

[Prenatal three-vessel and tracheal view: normal features]. / Coupe des trois vaisseaux et de la trachée en période prénatale: aspects normaux.

Congenital heart disease (CG) are mostly from a low-risk population. Their screening should be based on reproducible and easy to use methods. Prenatal echocardiographic analysis is based primarily on the analysis of the four chambers and great vessels. The study of general admission pathways generalized since the 1980s is performed on an axial section while that of great vessels is performed in most countries more recently using several views and remains difficult. We review the features, under normal circumstances, of the three-vessel and tracheal view that allows via an axial section of the fetal thorax to assess at the same time the trunk of the main pulmonary artery and its branches, the convergence of the ductus arteriosus and the aortic arches, the superior vena cava, and the trachea. Furthermore, the use of color Doppler mode optimizes the information obtained by this view.

[Embryology of the heart walls]. / Embryologie des cloisons du cœur.

Although anatomically simple structures, the atrial septum and the ventricular septum have complex embryological origins. Recent findings in molecular biology allowed better comprehension of their formation. As soon as the heart tube is formed, cells migrate from several cardiogenic fields to take part in the septation. Elongation, ballooning, and later inflexion of the heart tube create chamber separating grooves, facing the future septa. The systemic venous tributaries conflate at the venous pole of the heart; it will partially involute while contributing to the atrial septum. The primary atrial septum grows from the atrial roof towards the atrioventricular canal. It fuses there with the atrioventricular cushions, while its upper margin breaks down to form the ostium secundum. Then a deep fold develops from the atrial roof and partly covers the ostium secundum, leaving a flap-like interatrial communication through the oval foramen. It will close at birth. The interventricular septum has three embryological origins. The ventricular septum primum, created during the ballooning process, origins from the primary heart tube. It will form the trabecular septum and the inlet septum. The interventricular ring, surrounding the interventricular foramen, will participate in the inlet septum and also form the atrioventricular conduction axis. The outflow cushions will separate the outflow tract in the aorta and pulmonary artery, and grow to create the outlet septum. After merging with the atrioventricular cushions, they will also be part of the membranous septum.

Fetal diagnosis of superior vena cava aneurysm.

Superior vena cava aneurysm is a rare intrathoracic vascular lesion with only 27 cases reported in the literature. The majority are fusiform and can be associated with cystic hygroma due to the close embryonic relationship between lymphatic vessels and systemic veins. This is the first report of superior vena cava aneurysm diagnosed with fetal echocardiography in a fetus with a cystic hygroma. There is a need of a prospective registry to further delineate all aspects of this condition and establish the most appropriate therapeutic approach.

Lineage tree for the venous pole of the heart: clonal analysis clarifies controversial genealogy based on genetic tracing.

RATIONALE: Genetic tracing experiments and cell lineage analyses are complementary approaches that give information about the progenitor cells of a tissue. Approaches based on gene expression have led to conflicting views about the origin of the venous pole of the heart. Whereas the heart forms from 2 sources of progenitor cells, the first and second heart fields, genetic tracing has suggested a distinct origin for caval vein myocardium, from a proposed third heart field. OBJECTIVE: To determine the cell lineage history of the myocardium at the venous pole of the heart. METHODS AND RESULTS: We used retrospective clonal analyses to investigate lineage segregation for myocardium at the venous pole of the mouse heart, independent of gene expression. CONCLUSIONS: Our lineage analysis unequivocally shows that caval vein and atrial myocardium share a common origin and demonstrates a clonal relationship between the pulmonary vein and progenitors of the left venous pole. Clonal characteristics give insight into the development of the veins. Unexpectedly, we found a lineage relationship between the venous pole and part of the arterial pole, which is derived exclusively from the second heart field. Integration of results from genetic tracing into the lineage tree adds a further temporal dimension to this reconstruction of the history of venous myocardium and the arterial pole.

Comparison of PR intervals determined by fetal magnetocardiography and pulsed Doppler echocardiography.

OBJECTIVE: In clinical practice, measurement of mechanical PR interval (mPR) with pulsed Doppler echocardiography is a standard method used to estimate the atrioventricular conduction time in the fetus. However, fetal echocardiography does not directly reflect the electrical properties of the heart. Technological advances in fetal magnetocardiography (fMCG) have allowed recording of the electrical PR interval (ePR) with high time resolution. The aim of this study was to clarify the differences between ePR and mPR. METHODS: The study subjects were 295 normal human fetuses (gestational age, range 20.4-41.4 weeks) who underwent fMCG, and 135 of them underwent fetal echocardiography 15-90 min before or after fMCG. The ePR was measured using the fMCG, and the mPR was determined by two pulsed Doppler methods, simultaneous recording of the left ventricular inward and outward flow (LV in/out) (n = 135) and superior vena cava and ascending aorta (SVC/aAo) (n = 84). RESULTS: The ePR showed a significant, but weak, positive correlation with gestational age (r = 0.162, p = 0.0053). The mPR was significantly longer than the ePR (p < 0.0001), with mean differences of 14.6% (95% limits of agreement -10.7, 39.9) for the LV in/out method and 14.7% (95% limits of agreement -8.6, 38.0) for the SVC/aAo method. CONCLUSION: Our results point to the risk of overestimation of the atrioventricular conduction time when the mPR is used, and the need for careful interpretation of PR prolongation determined by mPR.