The Great Arteries Research Articles

Executive functioning of patients with congenital heart disease: 45 years after surgery

BackgroundNowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, long-term impact on neurodevelopment and executive functioning in adults with CHD are not completely understood.PurposeTo investigate the self- and informant-reported executive functioning in adults with CHD operated in childhood.Material and methodsLongitudinal study of a cohort of patients (n = 194, median age: 49.9 [46.1–53.8]) who were operated in childhood (< 15 years old) between 1968 and 1980 (median follow-up time: 45 [40–53] years) for one of the following diagnoses: atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis (PS), tetralogy of Fallot (ToF) or transposition of the great arteries (TGA). Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) questionnaire was used to assess self- and informant-reported executive functioning.Results40–53 years after surgery, the CHD group did show significantly better executive functioning compared to the norm data. No significant difference was found between mild CHD (ASD, VSD and PS) and moderate/severe CHD (ToF and TGA). Higher education, NYHA class 1 and better exercise capacity were associated with better self-reported executive functioning, whereas females or patients taking psychiatric or cardiac medications reported worse executive functioning.ConclusionsOur findings suggest favorable outcomes (comparable to normative data) regarding executive functioning in adults with CHD, both self- and informant-reported. However, further study is warranted to explore more in detail the different cognitive domains of executive functioning in these patients.Graphical abstract

Case report of coexisting transposition of the great arteries with supracardiac total anomalous pulmonary venous connection: focus on computed tomography features

BackgroundThe coexisting of transposition of the great arteries (TGA) with total anomalous pulmonary venous connection (TAPVC) is one of the rare anomalies. The incidence of coexisting TAPVC and TGA is unknown with very few cases ever reported.Case presentationWe reported a case of a 13-month-old female toddler with history of cyanosis. Echocardiography revealed atrioventricular ambiguity with pulmonary atresia, all PVs drain into the innominate vein via vertical vein (VV), ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD) were observed. The CT scan confirmed co-occurrence of TGA and TAPVC. All four confluence PVs behind the small left atrium (LA), drains into an ascending lateral large VV, coursing to innominate vein without any PV access into LA. The superior vena cava, right atrium and right ventricle (RV) were dilated. The RV is the origin of the aortic root. The aorta continues on the right side, with an arterial connection to the right pulmonary aberrant artery at the level of the aortic arch. Main pulmonary artery originates from LV and appears atretic with only connection to the left pulmonary artery. Large ASD and VSD were identified.ConclusionsTGA and TAPVC are a rare combination and should be suspected in mild-cyanotic cases with levocardia with situs solitus. CT angiography is one of the modalities of choice to characterize the vasculature anomalies.

Fifth decennium after the arterial switch operation for transposition of the great arteries

BackgroundFrom 1977 onwards, patients with both simple and complex transposition of the great arteries (TGA) have been treated with the arterial switch operation (ASO) in the Wilhelmina Children's Hospital/University Medical Center Utrecht the Netherlands. In this study, we compared mortality and morbidity between two patient groups: A. operated before and B. after 1991, specifically focusing on late ventricular function and reinterventions. MethodsA single institution retrospective cohort study was performed on patients who had an ASO for either simple or complex TGA. Data were collected from medical records. The entire patient cohort (n = 283) was divided in a group with more than 30 years of follow-up (A) and a group with less than 30 years of follow-up (B). Clinical and standardized echocardiographic follow-up was evaluated. ResultsGroup A consisted of 79 patients, of whom follow-up was available in 59 patients (median follow-up 34.8 years, IQR 33.0–36.9). Group B consisted of 204 patients, of whom 195 long-term survivors (median follow-up 14.9 years, IQR 10.0–21.2). Early survival was best in group B (A: 67.8% vs. B: 96.6%, p < 0.001), whereas late mortality (in total 1.8%) was similar for both groups. Reinterventions, corrected for follow-up time, were more frequent in group A (p = 0.005). In total 65 patients (25.1%) required 105 late reinterventions including 4 late aortic valve replacements. The mode of reinterventions has shifted over time, from surgical to more catheter-based (p = 0.03). The vast majority of patients functioned in NYHA class I. In contrast to the recent cohort, who have a normal average LVEF (%), the average LVEF in the oldest cohort was in the bottom percentile of normal range. ConclusionThe majority of patients in their fifth decade after ASO are in functional class I. Early outcome improved showing reduced mortality and need for reoperation. However, a trend towards reduced left ventricular function and late aortic valve replacements justify further research.

Maternal diabetes as a teratogenic factor for congenital heart defects in infants of diabetic mothers.

Congenital heart defects (CHDs) are shown to have an association with maternal diabetes mellitus. The Bahraini population has a high prevalence of diabetes 16.3% thus putting it at increased risk of developing CHDs in infants of diabetic mothers (IDMs). Describing the prevalence of CHDs in IDM in the Kingdom of Bahrain. A retrospective clinical study. Bahrain Defense Force Hospital, Kingdom of Bahrain. The study took place from January 1998 to January 2020. A history was recorded for all patients who were referred to the only tertiary cardiac center in Bahrain for echocardiography. Data was recorded on an Excel Sheet for analysis. A cardiac anatomy survey was conducted by an experienced pediatric cardiologist for each patient and the defects were categorized into acyanotic and cyanotic lesions. Five thousand five hundred sixty-nine patients were referred for cardiac echocardiography. Three thousand two hundred fifty-six patients were diagnosed with CHDs, 2,987 were non-IDM whereas 269 were IDM. Patients diagnosed with non-structural defects were excluded. Atrial septal defect (ASD) was identified in 744 patients and was more likely to occur in non-IDM (p-value=.005). Hypertrophic obstructive cardiomyopathy (HOCM) was identified in 35 patients and was more likely to occur in IDM (p-value < .001). Transposition of the great arteries (TGAs) was identified in 80 patients and was more likely to occur in IDM (p-value .002). Double inlet left ventricle (DILV), Hypoplastic Left Heart Syndrome (HPLHS), and Other Uni-Ventricular Hearts were all more likely to occur in IDM with p-values < .05. This study showed significant association between fetal exposure to diabetes and the development of ASD, HOCM, TGA, DILV, HPLHS, and Other Uni-Ventricular Hearts.

Impact of different neo-pulmonary artery surgical reconstruction techniques during the arterial switch operation on right ventricular outflow tract obstruction. A multicenter study up to 34-years' follow-up

BackgroundRVOTO remains the most common complication after ASO in simple TGA. ObjectivesTo clarify which neo-pulmonary artery reconstruction surgical technique helps to minimize postoperative right ventricular outflow tract obstruction (RVOTO) after the arterial switch operation (ASO) for transposition of the great arteries (TGA). MethodsPatients with isolated d-TGA were identified in the German Registry for Congenital Heart Defects. ASO for isolated d-TGA at an age younger than 10 days between 1986 and 2015 at 16 centers was performed in 106 registered patients. They were divided into two groups (Group 1 - Pantaloon n = 36, Group 2-non Pantaloon n = 70) depending on the neo-pulmonary surgical reconstruction technique used during ASO. Endpoints were RVOTO development, need for reoperation or reintervention for RVOTO, and death. RVOTO was diagnosed echocardiographically. ResultsMedian follow-up was 9 (4–29) years: the pantaloon group's (group 1) cumulative follow-up was 389 patient-years and 15 (5–34) years, and the non-pantaloon group's (group 2) 1119 patient-years, p = 0.0001. We observed mild RVOTO in 56 % in group 1 and 60 % in group 2 (p-value = 0.53). Group one's moderate RVOTO (3 %) versus 9 % in group 2 (9 %) (p = 0.42). Severe RVOTO was 5 % in group one and 7 % in group two (p = 0.99). There was no difference in freedom from re-operation and survival in both groups. (log-rank p = 0,63, log-rank p = 0,25, respectively). ConclusionDevelopment of mild RVOTO is a common complication in the long-term follow-up after ASO after applying both surgical techniques. We found that both types of neo-pulmonary artery reconstruction techniques were safe in terms of developing severe RVOTO.

Aortic root rotational position associates with aortic valvar incompetence and aortic dilation after arterial switch operation for transposition of the great arteries.

Aortic dilation and valvar regurgitation can develop in transposition of the great arteries (TGA) after the arterial switch operation (ASO). Variation in aortic root rotational position affects flow dynamics in patients without congenital heart disease. The aim of this study was to assess neo-aortic root (neo-AoR) rotational position and its association with neo-AoR dilation, ascending aorta (AAo) dilation, and neo-aortic valvar regurgitation in TGA following ASO. Patients with TGA repaired by ASO who underwent cardiac magnetic resonance (CMR) were reviewed. Neo-AoR rotational angle, neo-AoR and AAo dimensions indexed (to height), indexed left ventricular end diastolic volume (LVEDVI), and neo-aortic valvar regurgitant fraction (RF) were obtained from CMR. Among 36 patients, the median age at CMR was 17.1 years (12.3, 21.9). Neo-AoR rotational angle (range - 52 to + 78°) was clockwise ( ≥ + 15°) in 50%, counterclockwise (<-9°) in 25%, and central (-9 to + 14°) in 25% of patients. A quadratic term for neo-AoR rotational angle, indicating increasing extremes of counterclockwise and clockwise angles, was associated with neo-AoR dilation (R2 = 0.132, p = 0.03), AAo dilation (R2 = 0.160, p = 0.016), and LVEDVI (R2 = 0.20, p = 0.007). These associations remained statistically significant on multivariable analyses. Rotational angle was negatively associated with neo-aortic valvar RF on univariable (p < 0.05) and multivariable analyses (p < 0.02). Rotational angle was associated with smaller bilateral branch pulmonary arteries (p = 0.02). In patients with TGA after ASO, neo-AoR rotational position likely affects valvar function and hemodynamics, leading to a risk of neo-AoR and AAo dilation, aortic valvar incompetence, increasing left ventricular size, and smaller branch pulmonary arteries.

Frequency of Congenital Cardiac Disease in Various Divisions of Khyber Pakhtunkhwa (KPK) Based on a Six-Month Analysis of Inpatients at a Tertiary Care Hospital's Pediatric Cardiology Unit.

To identify the frequency of congenital heart disease (CHD) invarious Khyber Pakhtunkhwa (KPK) divisions. To perform this research, we reviewed the medical records of pediatric cardiology patients hospitalized between January 2022 and July 2022. Data was taken from the cardiology department's computerized data system between January 1 and July 31, 2022. To prevent any errors in diagnosis and address them during input by the ward clerk, patients' addresses, diagnoses, and gender were verified with the computerized medical record. Data were analyzed, and frequency and percentages were calculated. Per the digital mapping of KPK districts, we stratified and examined the data among various KPK divisions. Out Of the 371 patients with CHD who were admitted, 36.98% (137)were from the Peshawar division, 28.84% (107)from the Malakand division, 16.71% (62) from the Mardan division, 6.1% (23) from the Kohat division, 4.3% (16) from the Bannu division, 3.5% (13) from the Dera Ismail Khan division, and 3.5%(13) from the Hazara division. A total of 371 had CHD, of which 234 (63.07%) were cyanotic and 137 (36.92%) were cyanotic. The most prevalent acynotic congenital heart defect waspatent ductus arteriosus (PDA) at 36.32% (85), followed by a ventricular septal defect (VSD) at 35.04 (82). The most frequent acyanotic congenital cardiac abnormality was tetralogy of Fallot (TOF) at 49.63% (68), which was followed by transposition of the great arteries (TGA) at 33.57% (46). In KPK, congenital heart disease is most prevalent in the divisions of Peshawar and Malakand, while it is least prevalent in Hazara.

Critical congenital heart disease beyond HLHS and TGA: neonatal brain injury and early neurodevelopment.

Characterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA. This prospective cohort study included infants with HLHS, TGA, or heterogenous "Other cCHD" including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared. A total of 218 participants were included (HLHS = 60; TGA = 118; "Other cCHD" = 40, including 8 with genetic syndromes). Pre-operative (n = 209) and post-operative (n = 189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with "Other cCHD" had lower cognitive scores (p = 0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders. Frequency of brain injury and neurodevelopmental delay among patients with "Other cCHD" is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated. This study adds to literature on risk of brain injury in patients with critical congenital heart disease (cCHD) diagnoses other than hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), a heterogenous cohort of patients that has often been excluded from imaging studies. Children with cCHD beyond HLHS and TGA have similarly high rates of acquired brain injury. The high rate of neurodevelopmental impairment in this heterogenous group of cCHD diagnoses beyond HLHS and TGA is primarily driven by patients with comorbid genetic syndromes such as 22q11.2 deletion syndrome.

Outcomes of Arterial Switch Operation With Aortic Arch Reconstruction

BackgroundThis study investigated the outcomes and factors associated with reintervention or development of significant pulmonary stenosis (PS) after repair of transposition of the great arteries (TGA) or Taussig-Bing anomaly (TBA) with aortic arch obstruction. MethodsA total of 51 patients with TGA or TBA who underwent an arterial switch operation and aortic arch reconstruction between 2004 and 2020 were included. The outcomes of interest were all-cause death, including heart transplantation, all-cause reintervention, right-sided reintervention, and development of significant PS. ResultsThe median age and body weight at repair were 9 days and 3.2 kg, respectively. Forty-nine patients (96.1%) underwent 1-stage repair. A total of 28 patients (54.9%) had TBA, and 8 patients (15.7%) had interrupted aortic arch. There were 5 early deaths (9.8%) and 2 late deaths during a median follow-up duration of 59 months. The transplant-free survival rate 10 years after repair was 82.6%. A total of 21 reinterventions were required in 10 patients. The significant PS–free survival rate 10 years after repair was 68.8%. In univariable analysis, a higher ratio of the diameter of the main pulmonary artery to the ascending aorta was associated with all-cause reintervention (P = .007) and right-sided reintervention (P = .002). A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS (P = .049). ConclusionsThe rates of overall mortality and reintervention after repair were not negligible. A higher degree of size discrepancy between the 2 great arteries was associated with all-cause or right-sided reintervention. A smaller aortic annulus z-score at the pulmonary position was associated with the development of significant PS.

Long-term follow-up after simultaneous arterial switch operation and aortic arch repair.

Taussig-Bing anomaly (TBA) and transposition of the great arteries (TGA) with hypoplastic or interrupted aortic arch (AA) are rare anomalies. Various operative techniques and a high incidence of reinterventions are described. The aim of this retrospective single-centre study was to evaluate operative data, mortality and reintervention rate with special regard to the AA. At the Children's Heart Center Linz, 50 patients with the above-mentioned diagnosis have been corrected by a simultaneous repair between 2001 and 2022. Thirty-seven children had TBA, 13 had TGA and 5 of them had an interrupted AA. The median age at operation was 7 [interquartile range (IQR) 5-9] days, weight 3.38 (IQR 2.9-3.8) kg and follow-up 9.3 (IQR 3.1-14.5) years. The AA reconstruction was performed without patch material in 49 cases. There was 1 in-hospital mortality in a TBA patient and 1 late mortality (7 years later, neuroblastoma). 14/49 patients needed at least 1 reoperation (28.6%, all TBA) and 3 further patients had catheter reintervention or radiofrequency ablation only (6.1%, 2 TBA). Seventy-five percent of these procedures affected the right heart/pulmonary arteries; there was 1 re-coarctation repair. The simultaneous correction of TBA and TGA with AA obstruction or interruption is a safe operation with very low mortality. The AA reconstruction with minimized use of patch material resulted in a low restenosis rate.

Early Mortality in Infants Born with Neonatally Operated Congenital Heart Defects and Low or Very-Low Birthweight: A Systematic Review and Meta-Analysis.

Mortality outcomes of children with isolated neonatally operated congenital heart defects (CHDs) born with a low (LBW), moderately low (MLBW) or very-low birthweight (VLBW) remain ambiguous. We searched Medline and Embase (inception until October 2021) and included studies that evaluated early mortality. The risk of bias was assessed using the Critical Appraisal Skills Program cohort checklist. Meta-analysis involved random-effects models. We explored variability in mortality across birthweight subgroups, CHD types, and study designs. From 2035 reports, we included 23 studies in qualitative synthesis, and the meta-analysis included 11 studies (1658 CHD cases), divided into 30 subcohorts. The risk of bias was low in 4/11 studies included in the meta-analysis. Summary mortality before discharge or within one month after surgery was 37% (95%CI 27-47). Early mortality varied by birthweight (VLBW 56%, MLBW 15%, LBW 16%; p = 0.003) and CHD types (hypoplastic left heart syndrome (HLHS) 50%, total anomalous pulmonary venous return (TAPVR) 47%, transposition of the great arteries (TGA) 34%, coarctation of the aorta (CoA) 16%; p = 0.13). Mortality was higher in population-based studies (49% vs. 10%; p = 0.006). One-third of infants born with neonatally operated isolated CHDs and LBW, MLBW, or VLBW died within 30 days after surgery. Mortality varied across infant and study characteristics. These results may help clinicians assess neonatal prognosis. PROSPERO registration CRD42020170289.

Biomarker sST2 in Adults with Transposition of the Great Arteries Palliated by Mustard Procedure: A Five-Year Follow-up.

The Mustard procedure was an early cardiac surgery for transposition of the great arteries (TGA). Despite being successful, it has been associated with long-term arrhythmias and heart failure. A key factor complicating management in adults with congenital heart disease (CHD) is the deficiency of biomarkers predicting outcome. Soluble suppression of tumorogenicity-2 (sST2) is secreted by cardiomyocytes in response to mechanical strain and fibrosis. We hypothesized that adults with a Mustard procedure would have higher levels of sST2 than healthy individuals, and this would correlate with clinical outcome. We performed a single-center study in patients managed during childhood with a Mustard procedure versus age-matched controls. Clinical and demographic data were collected and biomarkers (sST2, cTnI, BNP, lipid panel, insulin, and glucose) were obtained. There were 18 patients (12 male) in the Mustard cohort and 18 patients (6 male) in the control group (22-49years, mean of 35.8 vs. mean 32.6years, respectively, p = ns). Nine Mustard subjects were NYHA class II, and 9 subjects were class III. The control group was asymptomatic. sST2 in the Mustard group was elevated in 56% vs. 17% in controls (p = 0.035). Of the Mustard subjects with elevated sST2, 60% had elevated cTnI and BNP, and 90% had low HDL. Over five years, the Mustard patients with elevated sST2 values had greater medication use, arrhythmias, hospitalizations, and ablation/pacer implantations than Mustard subjects with normal sST2. Mustard subjects with elevated sST2 had other biomarker abnormalities and clinically worse outcomes. Thus, sST2 may add a predictive value to cardiac-related morbidity and mortality.

Expression profiling analysis reveals key microRNA-mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles.

Patients with transposition of the great arteries (TGA) have different connected systemic chambers and this determines the long-term morbidities and survival. Limited findings have been reported to systematically identify miRNA and mRNA expression levels in such cohorts of patients. In this study, we aimed to characterize miRNAs, mRNAs, and miRNA-mRNA interaction networks in patients with TGA, with a systemic left (LV) and right ventricle (RV). Large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 TGA-RV patients, 16 TGA-LV patients, and 16 age and gender-matched controls. Using real-time quantitative PCR (RT-qPCR), the differential expression level of a single miRNA was validated. Enrichment analyses of altered miRNA and mRNA expression levels were identified using bioinformatics tools. Altered miRNA and mRNA expression levels were observed between TGA-RV and TGA-LV patients, together or separated, compared to controls. Among the deregulated miRNAs and mRNAs, 39 and 101 miRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Furthermore, 51 miRNAs were identified as significantly differentially expressed in patients with TGA-RV when compared to patients with TGA-LV. RT-qPCR relative expression level was highly consistent with microarray analysis results. Similarly, 36 and 164 mRNAs were identified as significantly differentially expressed in patients with TGA (both TGA-RV and TGA-LV) and TGA-RV, when compared to matched controls. Additionally, miR-140-3p showed a higher expression level in patients with overt heart failure (FC = 1.54; P = 0.001) and miR-502-3p showed a higher expression level in patients died due to cardiac death (FC = 1.41; P = 0.011). Integrative analysis resulted in 21 and 23 target genes with higher and lower expression levels, respectively (r ≥ 0.50 and P < 0.05). These target genes (i.e., 21 and 23 target genes) showed an inverse direction of regulation with miRNA and exhibited a miRNA binding site position within the 3'UTR of the target gene. Our findings provide new insights into a potential molecular biomarker(s) for patients with TGA that may guide better risk stratification and the development of novel targeting therapies. Future studies are needed to investigate the potential significance of miRNAs and mRNAs in TGA-related cardiovascular diseases.

Right ventricular systolic function and associated anatomic risk factors in fetuses with transposition of the great arteries: Evaluation by velocity vector imaging.

The aim of this study was to evaluate right ventricular (RV) systolic function in fetuses with transposition of the great arteries (TGA) using velocity vector imaging (VVI) and to investigate the impact of different factors on RV systolic function in TGA fetuses. This was a retrospective cross-sectional study of fetuses referred to our tertiary center between 2015 and 2019. Maternal and fetal baseline characteristics and conventional echocardiographic and myocardial deformation indices were collected in fetuses with TGA at 20-28 weeks' gestation, which were compared with normal fetuses with comparable gestational age (GA). RV deformational parameters including global and regional longitudinal peak systolic strain, strain rate, and velocity were measured using off-line speckle tracking analysis. The univariate and multivariate linear regression analyses were established to evaluate the independent risk factors for RV global longitudinal systolic strain (RVGLSs) and strain rate (RVGLSRs). In total, 78 fetuses with TGA [including 49 fetuses with complete transposition of the great arteries (d-TGA) and 29 fetuses with Taussig-Bing anomaly (TBA)] and 49 normal fetuses were included. Compared with normal controls, global and most regional RV longitudinal systolic peak velocity, strain, and strain rate were lower in d-TGA and TBA fetuses (P < 0.05). Compared with normal controls, global and most regional RV longitudinal systolic strain was lower in d-TGA fetuses without pulmonary stenosis (PS) and ventricular septal defect (VSD), while RVGLSs and RVGLSRs were lower in TBA fetuses without PS. The VSD was an independent determinant of RVGLSRs (P = 0.024) in the d-TGA group. Additionally, PS was an independent determinant of RVGLSs and RVGLSRs (P = 0.012, P = 0.027) in the TBA group. Early impairment of RV systolic function has already occurred in TGA fetuses during the 2nd trimester of pregnancy. PS, VSD, and foramen ovale (FO) were independent risk factors for decreased RV function.

Trends in newborn hospitalization transfers for hypoplastic left heart and transposition of the great arteries

Neonates with transposition of the great arteries (TGA) and hypoplastic left heart syndrome (HLHS) may benefit from delivery at centers where cardiac surgery can be performed. Prenatal diagnosis may facilitate delivery at referral centers. The primary objective of this study was to analyze trends in newborn transfers for HLHS and TGA. This cross-sectional analysis of newborn hospitalizations in the 2003, 2006, 2009, 2012, and 2019 Kids' Inpatient Database (KID). KID is released approximately every 3 years. Newborn hospitalizations with HLHS and TGA were identified. The proportion of HLHS and TGA deliveries transferred to another hospital for each year of the study was analyzed. Trends in transfers were calculated using joinpoint regression to estimate the average annual percent change (AAPC) with 95% CIs. As a secondary outcome, the proportion of deliveries with HLHS and TGA undergoing the Norwood procedure and arterial switch (respectively) at the hospital of delivery was analyzed by year and trended. Among newborn hospitalizations, 3608 neonates with TGA and 4967 neonates with HLHS were identified. Over the study period, the proportion of transfers for TGA decreased from 69.8% of newborn hospitalizations in 2003 to 44.7% in 2019 (AAPC -3.3%, 95% CI -4.7%, -1.1%). The proportion of transfers for HLHS decreased from 55.5% to 39.7% of newborn hospitalizations (AAPC -2.1%, 95% CI -3.0%, -1.1%) (Figure 1). Over the same period the proportion TGA deliveries undergoing arterial switch at the delivery hospital increased from 10.8% to 29.7% (AAPC 5.9%, 95% CI 3.4%, 8.6%) while the proportion of HLHS deliveries increased from 25.6% to 34.9% (AAPC 1.5%, 95% CI -0.1%, 3.2%) (Figure 2). The proportion of neonates with HLHS and TGA being transferred during a newborn delivery hospitalization decreased over the study period while surgical procedures at the hospital of delivery increased. These findings support that prenatal diagnosis may be increasing likelihood of delivery at referral centers for neonates with these diagnoses.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Computed Tomography Cardiac Veins Evaluation in Congenital Transposition of Great Vessels Prior to Cardiac Resynchronization Therapy (Crt)

Adult patients with transposition of great vessels are often candidates for cardiac resynchronization therapy (CRT). Cardiac vein anatomy is of crucial importance in planning optimal CRT therapy. Cardiac veins are very variable. In congenitally corrected transposition of great vessels coronary arteries have an unusual course but coronary veins although much less studied have much more varieties. In such cases cardiac computed tomography (CT) might offer important information prior to electrophysiological procedures. The objective of this study is to present a series of patients with transposition of the great arteries (TGA) both congenitally corrected TGA and D TGA in which imaging was used to help planning placement of leads for CRT. CT findings are thoroughly described as well as the consequent interventional procedure.

Maternal first trimester metabolic profile in pregnancies with transposition of the great arteries.

Higher maternal body mass index (BMI) and abnormal glucose metabolism during early pregnancy are associated with congenital heart defects in the offspring, but the exact mechanisms are unknown. We evaluated the association between maternal first trimester metabolic profile and transposition of the great arteries (TGA) in the offspring in a matched case-control study with 100 TGA mothers and 200 controls born in Finland during 2004-2014. Cases and controls were matched by birth year, child sex, and maternal age and BMI. Serum samples collected between 10- and 14-weeks of gestation were analyzed for 73 metabolic measures. Conditional logistic regression was used to assess the risk for TGA in the offspring, and a subgroup analysis among mothers with high BMI was conducted. Higher concentrations of four subtypes of extremely large very-low-density lipoprotein (VLDL) particles and one of large VLDL particles were observed in TGA mothers. This finding did not reach statistical significance after multiple testing correction. The pooled odds ratio (OR) of the all metabolic variables was slightly higher in TGA mothers in the subgroup with maternal BMI over 25 (OR 1.25) and significantly higher in the subgroup with maternal BMI over 30 (OR 1.95) compared to the original population (OR 1.18). Our findings indicate that an abnormal maternal early pregnancy metabolic profile might be associated with TGA in the offspring, especially in obese mothers. A trend indicating altered VLDL subtype composition in TGA pregnancies warrants further research.

T1 mapping of the myocardium and liver in the single ventricle population.

Fontan associated liver disease (FALD) is an increasingly recognized complication of the single ventricle circulation characterized by hepatic venous congestion leading to hepatic fibrosis. Within the Fontan myocardium, fibrotic myocardial remodeling may occur and lead to ventricular dysfunction. Magnetic resonance imaging (MRI) T1 mapping can characterize both myocardial and liver properties. The aim of this study was to compare myocardial and liver T1 between single ventricle patients with and without a Fontan and biventricular controls. A retrospective study of 3 groups of patients: 16 single ventricle patients before Fontan (SVpre 2 newborns, 9 pre-Glenn, 5 pre-Fontan, 31% single right ventricle [SRV]), 16 Fontans (56% SRV) and 10 repaired d-transposition of the great arteries (TGA). Native modified Look-Locker inversion T1 times were measured in the myocardium and liver. Cardiac MRI parameters, myocardial and liver T1 values were compared in the three groups. Correlations were assessed between liver T1 and cardiac parameters. Myocardial T1 was higher in SVpre (1,056 ± 48ms) and Fontans (1,047 ± 41ms) compared to TGA (1,012 ± 48ms, P < 0.05). Increased liver T1 was found in both SVpre (683 ± 82ms) and Fontan (727 ± 49ms) patients compared to TGA patients (587 ± 58ms, P < 0.001). There was no difference between single left ventricle (SLV) versus SRV myocardial or liver T1. Liver T1 showed moderate correlations with myocardial T1 (r = 0.48, confidence interval [CI] 0.26-0.72) and ejection fraction (r = -0.36, CI -0.66-0.95) but not with other volumetric parameters. Increased liver T1 at both pre- and post-Fontan stages suggests there are intrinsic liver abnormalities early in the course of single ventricle palliation. Increased myocardial T1 and its relationship to liver T1 suggest a combination of edema from passive venous congestion and/or myocardial fibrosis occurring in this population. Liver T1 may provide an earlier marker of liver disease warranting further study.

APPROACH TO CYANOTIC CONGENITAL HEART DISEASE IN CHILDREN: A SYSTEMATIC REVIEW

Objective: A growing number of research on the approach to children with cyanotic congenital heart diseasehave been undertaken nevertheless, there is no clear consensus on which approach is superior to the other. The goal of this systematic review was to systematically review the available evidence on the approach to children with cyanotic congenital heart disease. Methods: Authors began with recognizing the important examination proof that spots light on the approach to children with cyanotic congenital heart disease. We led electronic writing look in the accompanying data sets: Ovid Medline (2015-present), Ovid Medline Daily Update, Ovid Medline in process and other non-filed references, Ovid Embase (2015-present), The Cochrane Library (latest issue) and Web of Science. Just examinations in English language were incorporated. The precise selection was acted in close collaboration with a clinical examination curator. Results: We included 8studies (956 participants). Although all certainty of evidence was good, approach to children with cyanotic congenital heart disease was similar among all studies. Use of cardiac echography was the modality of diagnosis among all studies. All studies emphasized on the importance of early detection for early intervention. Conclusion: Early detection and treatment of cyanotic congenital heart disease (CCHD) is critical for positive outcomes. CCHD is a general term for a variety of diseases with different etiologies, which affect the clinical manifestations of CCHD. Totally abnormal total pulmonary venous connection (TAPVC) and transposition of the great arteries (TGA) are common in neonates. TOF and related disorders are characterized by squatting, cyanotic episodes, and a calm, resting chest without evidence of congestive heart failure, whereas transposition physiology is characterized by congestive heart failure with cyanosis.

Abstract 14317: The Prevalence of Motile Ciliary Gene Variants in Children With Transposition of the Great Arteries and Tetralogy of Fallot

Introduction: Motile ciliary dysfunction plays a central role in the pathogenesis of respiratory abnormalities and congenital heart disease (CHD). The role of ciliary gene variants in the non-heterotaxic CHD population is not well characterised. Methods: This single-centre retrospective cohort study aimed to determine the prevalence of Primary Ciliary Dyskinesia (PCD) gene variants in children with isolated Transposition of the Great Arteries (TGA) and Tetralogy of Fallot (TOF). Patients with whole genome sequencing between 2008-2018 were included. We identified pathogenic (P) or likely pathogenic (LP) single-nucleotide variants (SNVs) and short insertion/deletions (indels) in coding regions of 45 genes known to cause PCD. Patient characteristics and associated respiratory outcomes were evaluated from chart reviews. Results: PCD gene variants were found in 2.9% (5/172) TGA and 3.8% (10/264) TOF patients. Thirteen probands were heterozygous for P/LP SNVs/ indels; CCDC40 N=6, DNAH11 N=2, SPAG1 N=2 and one each of DNAH8/DNAAF1/ARMC4. Two were compound heterozygotes for variants in DNAH11 and DNAH8. At last follow-up, mean age was 14.5 years (SD 6.8, 57.9% male) and 7 deaths had occurred. Asthma was diagnosed in 10.5% TGAs and 8.1% TOFs with 3.9% and 7.3% respectively requiring hospitalisation for primary respiratory illness. In the variant positive subgroup, 5/15 had respiratory abnormalities - bronchiectasis (N = 1), asthma (N = 2), neonatal cough (N = 1), ventilator-associated pneumonia (N = 2). Additional cardiac anomalies occurred in 53% (8/15) - abnormal systemic veins (N = 3), situs inversus, dextrocardia (N = 1), right arch (N = 5), hypoplastic right ventricle (N = 1). An abnormal coronary pattern was seen in 4/5 TGAs. Vaginal and renal agenesis each occurred in 1 patient. Conclusions: Our findings suggest a high prevalence and potential association of ciliary gene variants with respiratory outcomes and situs anomalies in non-heterotaxy CHD.