Human Genetics of d-Transposition of Great Arteries.

Although several genes underlying occurrence of transposition of the great arteries have been found in the mouse, human genetics of the most frequent cyanotic congenital heart defect diagnosed in neonates is still largely unknown. Development of the outflow tract is a complex process which involves the major genes of cardiac development, acting on myocardial cells from the anterior second heart field, and on mesenchymal cells from endocardial cushions. These genes, coding for transcription factors, interact with each other, and their differential expression conditions the severity of the phenotype. A precise description of the anatomic phenotypes is mandatory to achieve a better comprehension of the complex mechanisms responsible for transposition of the great arteries.

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration.

BACKGROUND: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06-4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23-5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20-21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05-1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58-67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20-6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28-95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08-13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07-1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.

Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease.

OBJECTIVE: Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. METHODS: From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. RESULTS: HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. INTERPRETATION: Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.

Modeling Transposition of the Great Arteries with Patient-Specific Induced Pluripotent Stem Cells.

The dextro-transposition of the great arteries (d-TGA) is one of the most common congenital heart diseases. To identify biological processes that could be related to the development of d-TGA, we established induced pluripotent stem cell (iPSC) lines from two patients with d-TGA and from two healthy subjects (as controls) and differentiated them into endothelial cells (iPSC-ECs). iPSC-EC transcriptome profiling and bioinformatics analysis revealed differences in the expression level of genes involved in circulatory system and animal organ development. iPSC-ECs from patients with d-TGA showed impaired ability to develop tubular structures in an in vitro capillary-like tube formation assay, and interactome studies revealed downregulation of biological processes related to Notch signaling, circulatory system development and angiogenesis, pointing to alterations in vascular structure development. Our study provides an iPSC-based cellular model to investigate the etiology of d-TGA.

Congenitally Corrected Transposition of the Great Arteries: Anatomic, Physiologic Repair, and Palliation.

Congenitally corrected transposition of the great arteries (ccTGA) is a lesion that rarely occurs in isolation. The presenting physiology of ccTGA is predominantly secondary to the concurrent cardiac lesions; however, as the child ages, unrepaired ccTGA results in progressive failure of the morphologic right ventricle under the strain of maintaining a systemic pressure. Repair of ccTGA was initially focused on rectification of the underlying physiologic aberrations, but in recent years, the focus of repair has shifted toward anatomic correction to avoid failure of the morphologic right ventricle. This anatomic repair is commonly associated with improved long-term mortality at the cost of increased short-term mortality. Key preoperative considerations such as morphologic left ventricular pressure, tricuspid valve competency, and out flow tract obstructions can assist in determining the optimal repair for individual patients. An alternative, single ventricle, pathway has been proposed for any patient without optimal preoperative anatomy to improve long-term survival. Adjunctive repair options including pulmonary artery banding and one-and-a-half ventricle repairs have also been proposed to augment the survival curves.

Inter- and intra-ventricular dyssynchrony in the systemic right ventricle is a surrogate marker of major cardiac events in mildly symptomatic patients.

The aim of the study was to evaluate systemic right ventricular (RV) dyssynchrony in patients with congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA) with New York Heart Association functional class (NYHA FC) < III. We used cardiac magnetic resonance (CMR) to evaluate the dyssynchrony and assessed whether RV dyssynchrony can be predictive of major cardiac events in their early stages in these patients. We enrolled 71 consecutive, NYHA FC < III patients with systemic RV who underwent CMR between April 1995 and December 2016. We measured intra- and inter-ventricular dyssynchrony using a feature-tracking method of cine magnetic resonance imaging. The predictors of major cardiac events were analyzed using the Cox hazard analysis. The data from 36 patients with CCTGA and 35 patients with TGA after an atrial switch were analyzed. Seven (19.4%) patients with CCTGA and 6 (17.1%) patients with TGA showed a QRS duration of ≥ 130 ms. There were significant intra- and inter-dyssynchrony in the systemic RV groups, compared to healthy controls. The average follow-up period was 5.1 ± 3.9 years. From among patients with CCTGA, 9 (25.0%) had major cardiac events. The parameters including NYHA FC, indexed RV volume, longitudinal early diastolic strain rate, and intra- and inter-ventricular dyssynchrony were predictive of major cardiac events. From among patients with TGA, 12 (34.3%) had major cardiac events. Age, NYHA FC, QRS duration, RV volume, RV mass index, LV volume, global longitudinal/circumferential strain and intraventricular dyssynchrony, were all predictive of major cardiac events. Systemic RV in NYHA FC < III patients with CCTGA and TGA, have obvious intra- and inter-dyssynchrony, suggesting ineffective wall motion and potential RV dysfunction. Intraventricular dyssynchrony can be an adjunct predictor of major cardiac events in mildly symptomatic patients with both CCTGA and TGA.

Anatomical Classifications of the Coronary Arteries in Complete Transposition of the Great Arteries and Double Outlet Right Ventricle with Subpulmonary Ventricular Septal Defect.

Objective To discuss the anatomical morphologies of the coronary arteries and frequencies of unusual coronary arteries in complete transposition of the great arteries and double outlet right ventricle (DORV) associated with a subpulmonic ventricular septal defect (VSD). Methods Between March 1999 and August 2012, 1,078 patients with complete transposition of the great arteries or DORV with subpulmonary VSD underwent arterial switch operations (ASOs) and were visually evaluated to classify their coronary artery morphology during open heart surgery. Results The coronary arteries could be classified into five patterns with several subtypes. Unusual coronary arteries were observed in 248 of the 1,078 cases, providing a frequency of 23.01%. The frequencies of the patients with transposition of the great arteries with intact ventricular septum (TGA/IVS), TGA/VSD, and DORV with subpulmonary VSD were 17.65, 23.28, and 31.84%, respectively. The most common morphologies were the right coronary artery (RCA) originating from sinus 1 and circumflex (CX) originating from sinus 2 (1R, AD; 2CX; 26.50%); the CX originating from sinus 2 (1AD; 2R, CX; 21.36%); the RCA, left anterior descending artery, and CX originating from single sinus 2 (2R, AD, CX; 13.24%). The in-hospital mortalities of the patients with or without unusual coronary arteries after ASO were 14.1 and 6.02%, respectively. Conclusion Patients with complete transposition of the great arteries or DORV with subpulmonary VSD have a high frequency of unusual coronary arteries, which might greatly impact on the mortality for ASO. Improving the preoperative diagnostic criteria for coronary artery morphology may significantly increase the success rate for ASOs.

Prenatal diagnosis, hospital characteristics, and mortality in transposition of the great arteries.

BACKGROUND: The role of prenatal diagnosis in reducing neonatal mortality from transposition of the great arteries (TGA) is controversial. Factors affected by prenatal diagnosis such as proximity at birth to a cardiac surgical center (CSC) and CSC volume are associated with mortality in congenital heart disease. The purpose of the study was to determine the associations between prenatal diagnosis, distance from birthplace to a CSC, CSC TGA volume, and neonatal mortality in patients with TGA. METHODS: The Texas Birth Defects Registry was queried for all live born infants with TGA from 1999 to 2007. Four hundred sixty-eight cases of TGA were included. RESULTS: Forty-eight patients (10.3%) were prenatally diagnosed, and 20 patients died before age 28 days (4.3%). Neither prenatal diagnosis nor close proximity to a CSC at birth (p > 0.05) were associated with decreased mortality. Low CSC TGA volume was associated with increased mortality (p < 0.0002). Mortality at the CSCs with <5 patients per year was 9.6%; CSCs with 5 to 10 patients per year had 0% mortality, and those with >10 patients per year had 2.3% mortality. In multivariable logistic regression, only preterm birth (odds ratio, 7.05; 95% confidence interval, 4.13-12.05) and lower CSC volume (p < 0.001) were associated with neonatal mortality, although prenatal diagnosis attenuated the detrimental association of lower volume CSCs with higher mortality (p for interaction = 0.047). CONCLUSION: Lower CSC TGA patient volume was associated with higher neonatal mortality. Prenatal diagnosis may improve survival in lower volume CSCs. Birth Defects Research (Part A) 106:739-748, 2016. © 2016 Wiley Periodicals, Inc.

Twenty-five-year survival for aboriginal and caucasian children with congenital heart defects in Western Australia, 1980 to 2010.

BACKGROUND: Australian Aboriginal children have increased infant and childhood mortality compared with Caucasian children, but their mortality related to congenital heart defects (CHDs) throughout life is unknown. METHODS: We conducted a retrospective cohort study using data on 8,110 live born, singleton infants with CHDs born January 1980 to December 2010 from the Western Australian Register of Developmental Anomalies. Vital status was determined from death and medical records. Data for infants with chromosomal anomalies (except Down syndrome) were excluded. Kaplan-Meier Product-Limit estimates and 95% confidence intervals (CIs) were computed by Aboriginality. Hazard ratios (HRs) and 95% CIs were calculated from multivariable Cox-Proportional Hazard Regression models. RESULTS: Aboriginal children had lower survival than Caucasians for all CHDs combined but most notably during the neonatal period for functional single ventricle (50.0% vs. 86.1%; p = 0.015) and during the postneonatal period for tetralogy of Fallot (87.0% vs. 97.4%; p = 0.021) and atrioventricular septal defect (60.0% vs. 94.6%; p = 0.010). After adjusting for covariates except remoteness and socioeconomic status (SES), Aboriginal children with all CHDs combined (HR = 1.4; 95% CI, 1.0-1.9), with transposition of the great arteries (HR = 4.3; 95% CI, 1.0-18.9) or functional single ventricle (HR = 8.6; 95% CI, 1.3-57.9) had increased risk of mortality compared with Caucasian children. When remoteness and SES were included, the risks were not statistically significant. CONCLUSION: Long-term survival was lower for Aboriginal children with CHDs, and Aboriginal children with specific CHD phenotypes had increased risk of mortality throughout life. Increased risk may be due to SES and environmental factors. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1016-1031, 2016. © 2016 Wiley Periodicals, Inc.

Impact of prenatal diagnosis on the outcome of patients with a transposition of great arteries: A 24-year population-based study.

BACKGROUND: Transposition of great arteries (TGA) defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections is one of the most common congenital heart defects. Prenatal diagnosis of TGA remains difficult. To determine the impact of antenatal diagnosis we evaluated the sensitivity of antenatal detection and the neonatal mortality of TGA considering two study periods and two major types of TGA. METHODS: A cross-sectional study was performed. Data were collected from a French population-based birth defect registry. From 1988 to 2012, 94 fetuses with TGA were registered. The study period was subdivided into the 1988 to 1999 period and the 2000 to 2012 period. Two types of TGA were considered: isolated TGA (n = 66) and associated TGA (n = 28). A stratified analysis was performed considering the study periods and the types of TGA. RESULTS: Considering the study periods, the sensitivity of prenatal detection of TGA increased significantly (9.8% vs. 51.5%, p = 0.0001). The same trend was found for associated TGA (4.8% vs. 33.3%, p = 0.002) and isolated TGA (21.1% vs. 100%, p < 0.001). A late diagnosis of TGA (7 days after birth) was observed in 13.2% of cases. Neonatal mortality decreased significantly over time for isolated TGA (25.0% vs. 0 p = 0.01). Prenatal diagnosis of both types of TGA did not improve survival. CONCLUSION: We demonstrated that prenatal diagnosis and neonatal mortality of TGA varied greatly according to the malformation type and the study period. This could be explained by an improvement in terms of medical management.

The morphology of the coronary sinus in patients with congenitally corrected transposition: implications for cardiac catheterisation and re-synchronisation therapy.

Patients with congenitally corrected transposition frequently benefit from re-synchronisation therapy or ablation procedures. This is likely to require catheterisation of the coronary sinus. Its anatomy, however, is not always appreciated, despite being well-described. With this caveat in mind, we have evaluated its location and structure in hearts with congenitally corrected transposition in order to reinforce the guidance needed by the cardiac interventionist. We dissected and inspected the coronary sinus, the oblique vein of the left atrium, and the left-sided-circumflex venous channel in eight heart specimens with corrected transposition and eight controls, measuring the orifice and length of the sinus and the atrioventricular valves. In two-thirds of the malformed hearts, the sinus deviated from its anticipated course in the atrioventricular groove, ascending obliquely on the left atrial inferior wall to meet the left oblique vein. The maximal deviation coincided in all hearts with the point where the left oblique vein joined the left-sided-circumflex vein to form the coronary sinus. We describe a circumflex vein, rather than the great cardiac vein, as the latter venous channel is right-sided in the setting of corrected transposition. The length of the sinus correlated positively with the diameter of the tricuspid valve (p=0.02). Compared with controls, the left oblique vein in the malformed hearts joined the circumflex venous channel significantly closer to the mouth of the sinus. The unexpected course of the coronary sinus in corrected transposition and the naming of the cardiac veins have important implications for venous cannulation and interpretation of images.

Klippel-Feil syndrome and levo-looped transposition of the great arteries.

Klippel-Feil syndrome is a skeletal disorder characterised by low hairline and a short neck due to abnormal fusion of two or more cervical vertebrae. Although congenital heart and lung defects are infrequent, some abnormalities such as cor triatriatum, coarctation of the aorta, total anomalous pulmonary venous connection, or lung agenesis have been reported. The challenge of recognising Klippel-Feil syndrome lies in the fact that there is an association of this syndrome with other significant conditions such as skeletal, genitourinary, neurological, ear, and some cardiac defects. We report a Klippel-Feil syndrome type III 14-year-old patient with a levo-looped transposition of the great arteries. In addition, the patient had agenesis of the left upper-lung lobe.

[Infantile segmental hemangioma without facial involvement: A cutaneous marker of vascular malformations such as in PHACE syndrome?]. / Hémangiome infantile segmentaire extra-facial : un marqueur cutané de malformations vasculaires comme au cours du syndrome PHACE ?

BACKGROUND: Herein we report a case of a possible PHACE syndrome without hemangioma of the head but with a large segmental hemangioma of the trunk. PATIENTS AND METHODS: A 17-year-old female patient with a medical history of transposition of the great arteries with ventricular septal defect diagnosed at 3 days of life and of coarctation of the aorta diagnosed at 14 years was seen in the dermatology department for a long-standing large rectangular, segmental, atrophic and telangiectasic lesion on her back. The lesion appeared to be a sequel of infantile segmental hemangioma of the trunk, and this was confirmed by history-taking. DISCUSSION: This case raises the question of a link between infantile segmental hemangioma and underlying cardiovascular disorders. Infantile segmental hemangioma could be a marker of an underlying vascular development defect. The presence of infantile segmental hemangioma, regardless of site, should prompt vascular explorations.

[Transposition of Great Artery].

Transposition of the great artery is one of common congenital cardiac disease resulting cyanosis. Death occurs easily in untreated patients with transposition and intact ventricular septal defect (VSD) in infancy at a few days of age when posterior descending coronary artery (PDA) closed. Since there are 2 parallel circulations, flow from pulmonary to systemic circulation is necessary for systemic oxygenation, and Balloon atrial septostomy or prostaglandin infusion should be performed especially if patient do not have VSD. Although the advent of fetal echocardiography, it is difficult to diagnose the transposition of the great arteries (TGA) as abnormality of great vessels is relatively undistinguishable. The diagnosis of transposition is in itself an indication for surgery, and arterial switch procedure is performed in the case the left ventricle pressure remains more than 2/3 of systemic pressure. Preoperative diagnosis is important as associated anomalies and coronary artery branching patterns are important to decide the operative indication and timing of surgery.

Polymorphisms of VEGF, TGFß1, TGFßR2 and conotruncal heart defects in a Chinese population.

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-ß1 (TGFß1), TGFß receptor II (TGFßR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFß1 rs1800469 C>T, TGFßR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFß1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification analyses, the TGFß1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI 0.24-0.83). Our findings suggest that TGFß1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFßR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.

Great vessel root and artery dimensions in transposition of the great arteries repaired with atrial switch operation.

To describe great-vessel dimensions in patients with D-loop transposition of the great arteries (TGA) who have undergone atrial switch operation (ATSO). Patients who have undergone arterial switch operation for TGA have a high incidence of dilation of the neoaortic root. The incidence and degree of great artery dilation in patients who have undergone ATSO for TGA has not previously been described. A retrospective database review identified patients with TGA and intact ventricular septum who underwent ATSO at <1 year of age with cardiac magnetic resonance (CMR) within the previous 5 years (n = 39). A control group of patients referred for CMR with normal findings was identified for comparison (n = 40). Measurements of the annulus, root, sinotubular junction, and great vessels were performed, and interobserver/intraobserver variability was assessed. Median age of subjects at ATSO was 3 months (range 1-12) with median age at CMR of 29 years (range 18-40). For aortic measurements, mean z scores (± SDs) for patients relative to body surface area (BSA)-adjusted normal controls were as follows: annulus 1.41 (0.80), root 2.04 (1.48), sinotubular junction 2.16 (1.26), and great vessel 1.86 (1.53). For pulmonary measurements, similar values were as follows: annulus 1.82 (1.42), root 3.25 (2.01), sinotubular junction 2.47 (1.79), and great vessel 3.96 (3.08). In all cases, the p value was <0.001, and no confidence interval included the value 0. Adult patients with TGA repaired with ATSO in infancy have a greater incidence of dilation of both great vessels, particularly the pulmonary artery. These results may indicate abnormalities in the vascular structure of both great arteries in TGA that may predispose to progressive arterial dilation.

Decreased incidence of supravalvar pulmonary stenosis after arterial switch operation.

BACKGROUND: Supravalvar pulmonary stenosis (SVPS) is frequently observed after arterial switch. Traditionally the coronary arteries are removed from the neopulmonic root by excising the entire sinus of Valsalva. As a result, reconstruction of the neopulmonic root requires a pericardial patch encompassing two-thirds of the anastomosis between the neopulmonic root and pulmonary artery. We present a technique where the coronary arteries are removed as limited buttons of sinus tissue, leaving the transected edge of the neopulmonic root intact. We hypothesize that maintaining native arterial tissue in the anastomosis between the neopulmonic root and the pulmonary artery bifurcation reduces postoperative SVPS. METHODS AND RESULTS: We performed a retrospective review of neonates with D-transposition of the great arteries undergoing arterial switch procedure from 1996 to 2009. Charts were reviewed, and clinical outcomes recorded for each patient. Most recent echocardiograms were evaluated for right ventricular outflow tract obstruction. A total of 120 patients received arterial switch using this technique. There was 99% survival and no injuries to the coronary arteries regardless of anatomy. Total follow-up was 564 patient-years. Mean follow-up at last clinical visit was 66 ± 46 months. Evaluation of the most recent outpatient echocardiogram revealed an average peak instantaneous gradient across the neopulmonic root of 22.5 ± 5 mm Hg. Only 7 (5%) patients required reintervention (balloon dilation, n=5; surgery, n=2). CONCLUSIONS: Our technique of removing the coronary arteries as limited buttons, and anastomosis of the pulmonary artery using only native arterial tissue provides excellent midterm results with minimal SVPS.

Rightward convexity of the great vessel arising from the anterior ventricle: a novel fetal marker for transposition of the great arteries.

OBJECTIVES: Traditionally transposition of the great arteries (TGA) is suggested by bifurcation of the great vessel arising from the posterior ventricle and the parallel course of the great vessels as they leave the heart. These findings may be difficult to demonstrate, requiring additional fetal echocardiographic features to indicate TGA. In this study, we investigated a new marker of TGA, namely rightward convexity of the great vessel arising from the anterior ventricle. METHODS: We reviewed fetal studies from 2006 to 2010 in which an antenatal diagnosis of TGA was confirmed postnatally. We specifically viewed images obtained by scanning the great vessel arising from the anterior ventricle cranially to the superior mediastinum at the level of the three vessels and trachea view and compared them with similar views in normal hearts. RESULTS: In 21 cases of confirmed TGA, the great vessel arising from the anterior ventricle (aorta) coursing cranially demonstrated an abnormal convexity to the right. This was in contrast to convexity to the left or lack of convexity of the great vessel (pulmonary artery) arising from the anterior ventricle in fetuses with a normal heart. In two fetuses rightward vessel convexity from the anterior ventricle was the clue on the initial scan suggesting TGA, which was subsequently confirmed. In addition, only two vessels, the superior vena cava and aorta, were demonstrated in fetuses with TGA, the pulmonary artery and ductus arteriosus lying below (caudal to) the transverse arch. CONCLUSIONS: Noting the rightward convexity of the great vessel arising from the anterior ventricle may aid in the prenatal diagnosis of TGA. Furthermore, the relative simplicity of this sign may make it valuable in fetal screening for this cardiac defect.

Severe left heart obstruction with retrograde arch flow influences fetal cerebral and placental blood flow.

OBJECTIVE: Decreased middle cerebral artery (MCA) pulsatility index (PI) is a marker of fetal brain-sparing in placental insufficiency and it is also found in fetuses with severe congenital heart disease. This study sought to explore the impact of anatomical subtypes in fetal heart disease on MCA-PI and head growth. METHODS: We retrospectively reviewed fetal echocardiograms of pregnancies complicated by fetal hypoplastic left heart syndrome (HLHS; n = 42) with and without anatomic coarctation (n = 28 and n = 10, respectively), isolated severe aortic coarctation (n = 21), D-transposition of the great arteries (TGA; n = 11) and pulmonary outflow tract obstruction without forward flow across the pulmonary valve (POTO; n = 15), comparing observations with gestational age-matched controls (n = 89). No fetus had major extracardiac pathology or aneuploidy. MCA and umbilical artery (UA) PI, the cerebral placental ratio (CPR = MCA-PI/ UA-PI) and neonatal head circumference were obtained and expressed as Z-scores. RESULTS: Lower MCA-PI, higher UA-PI and lower CPR were observed in fetal HLHS and isolated coarctation with reversed arch flow (n = 6) (P < 0.001) but not TGA, POTO or isolated coarctation with antegrade arch flow (n = 15) compared with controls. No difference was found between HLHS with anatomical coarctation and those without; however, MCA-PI correlated positively with neonatal head circumference in HLHS with reversed distal arch flow (r = 0.33, P < 0.05). CONCLUSIONS: Severe left heart obstruction with reversed aortic arch flow is associated with altered fetal cerebral blood flow, and in these conditions, MCA-PI positively correlates with head growth. Anatomical arch obstruction itself may not be a contributing factor to altered MCA flow in fetal HLHS.

Occult coronary ostial obstruction late after arterial switch operation.

Occult coronary artery obstruction can be a late source of morbidity and mortality following the arterial switch operation for transposition of the great arteries. We describe a case of undiagnosed left coronary ostial obstruction in a teenager which may have contributed to perioperative ventricular dysfunction and subsequent mortality following a reoperation many years after arterial switch.