Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

Oxygen Uptake Efficiency Slope is Strongly Correlated to VO2peak Long-Term After Arterial Switch Operation.

After the arterial switch operation (ASO) for transposition of the great arteries (TGA), many patients have an impaired exercise tolerance. Exercise tolerance is determined with cardiopulmonary exercise testing by peak oxygen uptake (VO2peak). Unlike VO2peak, the oxygen uptake efficiency slope (OUES) does not require a maximal effort for interpretation. The value of OUES has not been assessed in a large group of patients after ASO. The purpose of this study was to determine OUES and VO2peak, evaluate its interrelationship and assess whether exercise tolerance is related to ventricular function after ASO. A cardiopulmonary exercise testing, assessment of physical activity score and transthoracic echocardiography (fractional shortening and left/right ventricular global longitudinal peak strain) were performed to 48 patients after ASO. Median age at follow-up after ASO was 16.0 (IQR 13.0-18.0) years. Shortening fraction was normal (36 ± 6%). Left and right global longitudinal peak strain were reduced: 15.1 ± 2.4% and 19.5 ± 4.5%. This group of patients showed lower values for all cardiopulmonary exercise testing parameters compared to the reference values: mean VO2peak% 75% (95% CI 72-77) and mean OUES% 82(95% CI 77-87); without significant differences between subtypes of TGA. A strong-to-excellent correlation between the VO2peak and OUES was found (absolute values: R = 0.90, p < 0.001; normalized values: R = 0.79, p < 0.001). No correlation was found between cardiopulmonary exercise testing results and left ventricle function parameters. In conclusion, OUES and VO2peak were lower in patients after ASO compared to reference values but are strongly correlated, making OUES a valuable tool to use in this patient group when maximal effort is not achievable.

Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries.

BACKGROUND: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD. METHODS: Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups. RESULTS: Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms. CONCLUSIONS: Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities.

Identification and analysis of KLF13 variants in patients with congenital heart disease.

BACKGROUND: The protein Kruppel-like factor 13 (KLF13) is a member of the KLF family and has been identified as a cardiac transcription factor that is involved in heart development. However, the relationship between KLF13 variants and CHDs in humans remains largely unknown. The present study aimed to screen the KLF13 variants in CHD patients and genetically analyze the functions of these variants. METHODS: KLF13 variants were sequenced in a cohort of 309 CHD patients and population-matched healthy controls (n = 200) using targeted sequencing. To investigate the effect of variants on the functional properties of the KLF13 protein, the expression and subcellular localization of the protein, as well as the transcriptional activities of downstream genes and physical interactions with other transcription factors, were assessed. RESULTS: Two heterozygous variants, c.487C > T (P163S) and c.467G > A (S156N), were identified in two out of 309 CHD patients with tricuspid valve atresia and transposition of the great arteries, respectively. No variants were found among healthy controls. The variant c.467G > A (S156N) had increased protein expression and enhanced functionality compared with the wild type, without affecting the subcellular localization. The other variant, c.487C > T (P163S), did not show any abnormalities in protein expression or subcellular localization; however, it inhibited the transcriptional activities of downstream target genes and physically interacted with TBX5, another cardiac transcription factor. CONCLUSION: Our results show that the S156N and P163S variants may affect the transcriptional function of KLF13 and physical interaction with TBX5. These results identified KLF13 as a potential genetic risk factor for congenital heart disease.

Myocardial blood flow and cardiac sympathetic innervation in young adults late after arterial switch operation for transposition of the great arteries.

BACKGROUND: The arterial switch operation (ASO) for repair of transposition of the great arteries (TGA) requires transection of the great arterial trunks and re-implantation of the coronary arteries into the neoaortic root resulting in cardiac sympathetic denervation which may affect myocardial blood flow (MBF) regulation. The aims of the present study were to evaluate sympathetic (re-)innervation in young adults after ASO and its impact on MBF. METHODS: Twelve patients (age 22.5 ±â€¯2.6 years) after ASO for TGA in the neonatal period and ten healthy controls (age 22.0 ±â€¯1.7 years) were included. Positron emission tomography (PET) was used for measuring cardiac sympathetic innervation with [11C]meta-hydroxyephedrine (mHED) and MBF with [15O]H2O PET at rest, during adenosine stimulation, and during sympathetic stimulation with cold pressor test. Cold pressor-induced MBF response capacity was calculated as maximal global MBF over peak rate-pressure product multiplied by 10'000. RESULTS: Global [11C]mHED uptake was significantly lower in patients compared to controls (7.0 ±â€¯2.3 versus 11.8 ±â€¯2.1%/min, p < 0.001). Global MBF was lower in patients compared to controls at rest and during adenosine-induced hyperemia (0.66 ±â€¯0.08 versus 0.82 ±â€¯0.15 ml/min/g, p = 0.005; 2.23 ±â€¯1.19 versus 3.36 ±â€¯1.04 ml/min/g, p = 0.030, respectively). Interestingly, MBF during cold pressor test did not differ between patients and controls (0.99 ±â€¯0.20 versus 1.07 ±â€¯0.16 ml/min/g, p = 0.330). However, cold pressor-induced MBF response capacity was significantly lower for patients as compared to controls (1.09 ±â€¯0.35 versus 1.44 ±â€¯0.39 ml/g/10,000 mmHg, p = 0.040). CONCLUSIONS: With only partial sympathetic re-innervation of the coronary arteries, maximal dilator capacity of the coronary microvasculature and cold pressor-induced MBF response capacity remain substantially impaired in young adults after ASO compared to healthy controls.

Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

INTRODUCTION: Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress. OBJECTIVE: We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery. METHODS: We studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry. RESULTS: Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change. CONCLUSIONS: This is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.

A high-efficiency MUF method benefits postoperative hemodynamic stability and oxygen delivery in neonates with transposition of great arteries.

OBJECTIVE: To minimize the postoperative hemodynamic changes in neonates with transposition of great arteries (TGA) by modifying the circuit and efficiency of traditional modified ultrafiltration (MUF). METHODS: Ninety-one patients (<5 kg) underwent arterial switch operations, which were randomized to a traditional MUF (tMUF) group (N = 38) or a modified MUF (mMUF) group (N = 53). MUF of both the groups lasted for 8 to 12 minutes, during which the near-infrared spectroscopy was used to monitor cerebral tissue oxygenation parameters. RESULTS: The cerebral oxygenation was significantly improved after MUF in both groups. The tissue hemoglobin concentration index (THI) was proportional to the total cerebral hemoglobin during MUF. The ascending velocity of THI was faster in the mMUF group. The mean change range in the mMUF group was 0.90 ± 0.44 mM/cm, while that in the tMUF group was 0.51 ± 0.35 mM/cm (P = 0.028). Quantitative changes in the cerebral concentration of oxygenated hemoglobin increased faster in the mMUF group, in which a nadir of low efficacy MUF was not observed. The rising velocity of the tissue oxygenation index was faster in the mMUF group. All mMUF cases had stable hemodynamics during MUF. The tMUF was aborted in two patients because of unstable hemodynamics. At the end of MUF, hematocrit was significantly greater in the mMUF group than in the tMUF group (40.33 ± 5.43% vs 34.41 ± 5.11%; P < 0.01) CONCLUSION: The mMUF circuit is more miniaturized and less prime, which leads to more efficient ultrafiltration. It benefits postoperative hemodynamic stability and oxygen delivery in neonates with TGA.

Analysis of DICER1 in familial and sporadic cases of transposition of the great arteries.

OBJECTIVE: We previously identified a pathogenic germline DICER1 variant in a child with transposition of the great arteries who was a member of a family with DICER1 syndrome. In view of a report linking Dicer1 knockout in murine cardiomyocytes to cardiac outflow defects, we investigated the involvement of DICER1 in transposition of the great arteries. DESIGN: We used Fluidigm access array followed by next generation sequencing to screen for variants in the coding exons, their exon/intron boundaries and the 3' untranslated region of DICER1 in patient DNA. CASES: Germline DNA was collected from 129 patients with either sporadic or familial forms of transposition of the great arteries from two sites in Australia and Italy. RESULTS: Most cases (85%) did not have any germline DICER1 variants. In the remaining 15% of cases, we identified 16 previously reported variants (5 synonymous, 6 intronic, and 5 missense) and 2 novel variants (1 intronic and 1 missense). None of the identified variants were predicted to be pathogenic. CONCLUSIONS: Here, we report that neither likely pathogenic nor pathogenic variants in DICER1 appear to play a major role in transposition of the great arteries.

Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering.

Small-diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross-linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8-octamethylene citrate)-co-cysteine is hybridized to the ECM, forming a polymer-ECM composite that allows for heparin immobilization via maleimide-thiol "click" chemistry. Heparinized composites reduce platelet adhesion by >60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM-only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2-fold) and increased macrophage infiltration (3.5-fold) compared to ECM-only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted.

Impaired development of left anterior heart field by ectopic retinoic acid causes transposition of the great arteries.

BACKGROUND: Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. METHODS AND RESULTS: We placed a retinoic acid-soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid-soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid-exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. CONCLUSIONS: The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries.

Oxygen supply to the fetal cerebral circulation in hypoplastic left heart syndrome: a simulation study based on the theoretical models of fetal circulation.

Hypoxia due to congenital heart diseases (CHDs) adversely affects brain development during the fetal period. Head circumference at birth is closely associated with neuropsychiatric development, and it is considerably smaller in newborns with hypoplastic left heart syndrome (HLHS) than in normal newborns. We performed simulation studies on newborns with CHD to evaluate the cerebral circulation during the fetal period. The oxygen saturation of cerebral blood flow in newborns with CHD was simulated according to a model for normal fetal circulation in late pregnancy. We compared the oxygen saturation of cerebral blood flow between newborns with tricuspid atresia (TA; a disease showing univentricular circulation and hypoplasia of the right ventricle), those with transposition of the great arteries (TGA; a disease showing abnormal mixing of arterial and venous blood), and those with HLHS. The oxygen saturation of cerebral blood flow in newborns with normal circulation was 75.7 %, whereas it was low (49.5 %) in both newborns with HLHS and those with TA. Although the oxygen level is affected by the blood flow through the foramen ovale, the oxygen saturation in newborns with TGA was even lower (43.2 %). These data, together with previous reports, suggest that the cerebral blood flow rate is decreased in newborns with HLHS, and the main cause was strongly suspected to be retrograde cerebral perfusion through a patent ductus arteriosus. This study provides important information about the neurodevelopmental prognosis of newborns with HLHS and suggests the need to identify strategies to resolve this unfavorable cerebral circulatory state in utero.

The ubiquitin/SUMO pathway and radial ray deficiency syndromes.

Protein regulation is the function of several pathways and enzyme systems in the human body. One of these pathways is the ubiquitin/SUMO pathway. The author has noted that almost all known syndromes of radial ray deficiency are related to this pathway. In this article, these syndromes are reviewed with special attention to their relationship with the ubiquitin/SUMO pathway. This opens a new insight into the pathogenesis of radial ray deficiency syndromes.

Disturbed myocardial connexin 43 and N-cadherin expressions in hypoplastic left heart syndrome and borderline left ventricle.

OBJECTIVES: Borderline left ventricle is the left ventricular morphology at the favorable end of the hypoplastic left heart syndrome. In contrast to the severe end, it is suitable for biventricular repair. Wondering whether it is possible to identify cases suitable for biventricular repair from a developmental viewpoint, we investigated the myocardial histology of borderline and severely hypoplastic left ventricles. METHODS: Postmortem specimens of neonatal, unoperated human hearts with severe hypoplastic left heart syndrome and borderline left ventricle were compared with normal specimens and hearts from patients with transposition of the great arteries. After tissue sampling of the lateral walls of both ventricles, immunohistochemical and immunofluorescence stainings against cardiac troponin I, N-cadherin, and connexin 43, important for proper cardiac differentiation, were done. RESULTS: All severely hypoplastic left hearts (7/7) and most borderline left ventricle hearts (4/6) showed reduced sarcomeric expressions of troponin I in left and right ventricles. N-cadherin and connexin 43 expressions were reduced in intercalated disks. The remaining borderline left ventricle hearts (2/6) were histologically closer to control hearts. CONCLUSIONS: Four of 6 borderline left ventricle hearts showed myocardial histopathology similar to the severely hypoplastic left hearts. The remainder were similar to normal hearts. Our results and knowledge regarding the role of epicardial-derived cells in myocardial differentiation lead us to postulate that an abnormal epicardial-myocardial interaction could explain the observed histopathology. Defining the histopathologic severity with preoperative myocardial biopsy samples of hearts with borderline left ventricle might provide a diagnostic tool for preoperative decision making.

Myocardial perfusion and exercise capacity 12 years after arterial switch surgery for D-transposition of the great arteries.

Peak exercise myocardial perfusion was evaluated in patients with D-transposition of the great arteries 12 years after the arterial switch operation (SWITCH) to evaluate coronary perfusion. Gas-exchange measurements were used to assess cardiac limiting factors to exercise capacity in SWITCH patients when compared to healthy gender-matched controls (CON). Peak myocardial perfusion was evaluated in 42 patients 12 years post-SWITCH, using technetium-99 m (Tetrofosmin). SWITCH exercise data was compared to 42 gender-matched controls (CON). One symptomatic and one asymptomatic SWITCH patient had abnormal exercise myocardial perfusion; both patients had variant coronary anatomy preoperatively. SWITCH patients had lower VO(2peak) (p < 0.01), peak heart rates (p = 0.01), percentages of age-predicted peak heart rates (p < 0.01), and peak oxygen pulses indexed to body surface area (p < 0.01) than CON patients. Exercise testing with myocardial perfusion imaging helped to identify the rare SWITCH patient with coronary insufficiencies. This study demonstrates that exercise testing with myocardial perfusion scans can help identify patients at risk for myocardial events. This study also demonstrated that SWITCH patients have a mildly diminished VO(2peak) when compared to CON patients.

The outflow tract in transposition of the great arteries: an anatomic and morphologic study.

BACKGROUND: Neoaortic root dilatation is observed after the arterial switch operation for transposition of the great arteries. Although structural differences in the vessel wall of these patients may be of influence, we hypothesize that a histomorphologic difference in composition and embedding of the fibrous annulus in transposition of the great arteries may play a role in neoaortic root dilatation. METHODS: Two normal human hearts and two unoperated human hearts with transposition of the great arteries, 1 day postnatal, were studied. Histologic sections stained for collagen, myocardium, and elastin were prepared, and three-dimensional reconstructions of the outflow tracts were made to enable comparison of the morphologic structures between the normal hearts and those with transposition of the great arteries. RESULTS: The amount of collagen in the arterial roots was diminished in hearts with transposition of the great arteries compared with the normal hearts. In addition, the anchorage and embedding of both arterial roots in the myocardium was less extensive in transposition of the great arteries. The changed position of the arteries in the malformed hearts results in less support for the roots from the surrounding atrioventricular myocardium. CONCLUSIONS: The combination of the observed histomorphologic differences in amount of collagen and myocardial support may be an explanation for the neoaortic root dilatation observed after the arterial switch operation. The developmental background of the observed deficient fibrous annulus formation may originate from an epicardial problem.

Anatomical variants of transposition of the main vessels and their relationship with the content of chemical elements in heart ventricles.

Cardiometrical characteristics of anatomical variants of the main vessels transposition are determined by different functional load of heart compartments and are associated with metabolic processes of different intensity, which is confirmed by the content of chemical elements in the right- and left-ventricular myocardium. It was shown that the content of chemicals was virtually the same in both cardiac ventricles in case of main vessels transposition and isolated atrial septal defect. Positive correlations between the degree of left-ventricular hypertrophy and content of S, K, Fe, and Sr in it and a negative correlation between this hypertrophy and Cu content were revealed. Transposition of the main vessels and defects of atrial and ventricular septa were associated with different levels of chemical elements in both ventricles, particularly of Zn, Mn, Fe, and Ca.

Extravasation of albumin after cardiopulmonary bypass in newborns.

OBJECTIVE: The systemic inflammatory response to cardiopulmonary bypass (CPB) possibly increases microvascular permeability to plasma proteins, leading to capillary leak syndrome. The study was conducted to elucidate any protein leakage in newborns using Evans blue dye as tracer. DESIGN: Prospective controlled study. SETTING: University-affiliated heart center. PARTICIPANTS: Eleven neonates with transposition of the great arteries. INTERVENTIONS: Plasma interleukin-6 (IL-6), IL-10, fractional escape rate (FER) of an intravenous bolus of Evans blue, and colloid osmotic pressure (COP) were assessed before and after surgery (statistics: median and 25th-75th percentile, Friedman's 2-way analysis of variance, and Wilcoxon matched-pairs signed-rank test [before and after surgery]). MEASUREMENTS AND MAIN RESULTS: All patients had an uneventful intraoperative course. The demographic and operative data were age 11 (10-13) days, body weight 3.2 (3.0-3.3) kg, CPB time 132 (123-144) minutes, and aortic cross-clamp time 66 (64-78) minutes. The proinflammatory IL-6 increased 60-fold and the anti-inflammatory IL-10 only 3-fold after CPB. FER, however, was not changed, whereas COP was significantly reduced after CPB. CONCLUSIONS: In contrast to the expectation, the escape rate of Evans blue, reflecting the extravasation of albumin, was not increased after CPB. However, reduced COP, hypothermia, and also a reduced lymphatic drainage may contribute to edema formation. The present data do not support the hypothesis of a capillary leak after CPB in newborns.

Metabolic alterations and neurodevelopmental outcome of infants with transposition of the great arteries.

Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

Transposition of great arteries with aortopulmonary window: an unusual cause of prepared left ventricle at 11 months.

In patients with transposition of great arteries, presence of aortopulmonary window is very uncommon and associated with high morbidity and mortality. This report describes the case of an 11-month-old female patient in which aortopulmonary window was restrictive, and protected the patient from developing pulmonary vascular disease. The patient underwent successful arterial switch and repair of aortopulmonary window.

Comparison of pulmonary arterial flow phenomena in spiral and Lecompte models by computational fluid dynamics.

OBJECTIVES: The transposed great arteries are simply reversed by means of a conventional arterial switch operation with the Lecompte maneuver without resumption of their spiral relationship. We seek to clarify the functional implications of the spiral relationship of the great arteries by means of mathematic modeling. METHODS: Computational fluid dynamics is used to compare flow phenomena of the spiral and Lecompte (nonspiral) models under various body surface areas. RESULTS: The velocity profile and wall-shear stress distribution are more uniform for the spiral than for the Lecompte model. The pressure drop and power loss ratio are smaller for the spiral than the Lecompte model for all the body surface areas investigated. The power loss ratio increases abruptly starting from 0.43 m2 of body surface area for the Lecompte model. At that specific stage, after arterial switch operation with the Lecompte maneuver, suprapulmonary stenoses occur most frequently. CONCLUSIONS: Reconstructing the great arteries in spiral fashion might be recommended because the blood flow patterns are more streamlined than those of the Lecompte maneuver. Initiation of stenosis might be minimized to some extent.