Dextro-transposition Of The Great Arteries Research Articles

A meta-analysis of the effects of sacubitril-valsartan on surrogate markers of systemic right ventricular dysfunction in congenital heart disease

Abstract Introduction Dysfunction of systemic right ventricle (sRV) in adult congenital heart disease (ACHD) patients is expectable and often associated with heart failure and other dismal cardiovascular events. Despite limited evidence, several neurohormonal modulators approved for heart failure with reduced ejection fraction (HFrEF) have been used off-label in patients with RV dysfunction1. Sacubitril-valsartan (ARNI) effects on sRV remains poorly studied, with current evidence being limited to small cohorts. Purpose Review and summarize current evidence about the effects of ARNI in ACHD patients with sRV. Methods We performed a systematic review on MEDLINE, EMBASE, COCHRANE, and SCOPUS for articles that included "systemic right ventricle" and "sacubitril valsartan" until January 2024. Two investigators screened the literature and extracted data. Treatment effects were measured by Cohen's d effect-size (EZ) pre and post-ARNI, with a 95% confidence interval (CI), using a restricted maximum likelihood model. Results From 197 publications screened, five studies fulfilled our criteria, comprising a total of 135 patients. Follow-up after ARNI therapy ranged from 12 to 27 months. No randomized clinical trials were found, and only two studies had a prospective design. Dextro-transposition of the great arteries (D-TGA) after atrial switch operation was the most common type of congenital heart disease with sRV (n=95; 70%). Meta-analysis demonstrates that ARNI reduced NT-proBNP levels during follow-up (EZ= -0.34, CI -0.59 to 0.08; p=0.01; I2=4.0%). Regarding RV function, ARNI improved RV fractional area change (RVFAC) (EZ= 0.75, CI 0.01 to 1.50; p= 0.048; I2=85.0%). A trend for RV global longitudinal strain improvement was also observed with ARNI (EZ= 1.74, CI -0.05 to 3.54; p=0.06; I2=95.9%) but not for tricuspid annular plane systolic excursion (EZ= -0.07, CI -0.33 to 0.20; p=0.62; I2=0.0%). RV diastolic diameter did not change significantly with ARNI (EZ= 0.07, CI -0.43 to 0.56; p=0.79; I2=68.2%). A trend for improvement on the 6-minute walk test was observed (EZ= 1.89, CI -0.13 to 3.91; p=0.07; I2=96.3%), but no effect on exercise oxygen consumption (VO2) (EZ= -0.09, CI -1.32 to 1.15; p=0.89; I2=91.4%). During follow-up ARNI did not change significantly systolic blood pressure (EZ= -0.32, CI -0.74 to 0.11; p=0.15; I2=58.4%) or serum creatinine (EZ= 0.23, CI -0.04 to 0.49; p=0.09; I2=0.0%). Conclusions Despite heterogeneity among these studies, this meta-analysis demonstrates that ARNI might improve NT-proBNP levels and RV function. ARNI seems safe and well tolerated, with no significant effect on blood pressure and renal function. More well-powered studies are needed to confirm the beneficial effects of ARNI in ACHD with sRV.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Prenatal Detection of D-TGA and Novel Interventional Program Decrease Time to Balloon Septostomy.

Infants with dextro-transposition of the great arteries (d-TGA) are at high risk for hemodynamic compromise in the immediate postnatal period due to dependence on intracardiac mixing for oxygen delivery. This period of profound hypoxemia may have long-term implications, as previous studies demonstrated patients with d-TGA are at increased risk for neurocognitive delays despite effective surgical correction in the neonatal period. Balloon atrial septostomy (BAS) is an established intervention that improves intracardiac mixing and perioperative hemodynamics. This retrospective study aimed to quantify the time from birth to BAS and compare short-term outcomes for patients with prenatal and postnatal diagnoses of d-TGA. We identified 68 newborns born with d-TGA who were admitted to our facility between 2013 and 2022 and required BAS within 48h after birth. Halfway through this study, our cardiac interventional team began traveling to a nearby delivery center where a bedside BAS could be performed prior to transferring the patient. We divided the patients into 3 groups-postnatal diagnosis (n = 27), prenatal diagnosis with rapid transport (n = 24), and prenatal diagnosis with interventional team performing a BAS at the delivery hospital (n = 17). The time from birth to BAS was significantly shorter for patients in the interventional program group (1.1h) compared to the rapid transport (4.5h) and postnatal diagnosis groups (9.3h, p value < 0.01). The interventional program group also had lower lactate levels and less acidotic pH compared to the other groups. There was no significant difference in lowest oxygen saturation level, pre-surgical neurologic complication rate, time to surgery, or hospital length of stay. The interventional program proved to be a safe and effective model, as there were no procedural complications and the time to BAS decreased. Long-term follow-up is needed to determine if abating this initial period of hemodynamic instability will lead to improved neurodevelopmental outcomes.

Characteristics of altered biventricular hemodynamics after arterial switch operation for patients with d-transposition of the great arteries with preserved ejection fraction: a four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) study.

The long-term monitoring of biventricular function is essential to identify potential functional decline in patients following the arterial switch operation (ASO). The underlying pathophysiological mechanisms responsible for altered biventricular hemodynamics in ASO patients are not yet well understood. This study sought to: (I) compare the biventricular kinetic energy (KE) and vorticity of ASO patients and age- and sex-matched controls; (II) investigate the associations of four-dimensional (4D) flow biventricular hemodynamics parameters and neo-aortic root dilation, supravalvular pulmonary stenosis, and pulmonary artery transvalvular pressure difference. A total of 34 patients with dextro-transposition of the great arteries (D-TGA) who underwent ASO, and 17 age- and gender-matched healthy controls were prospectively recruited for this study. All the subjects underwent cine and 4D flow and late gadolinium enhancement scans, and all the patients underwent echocardiography within two weeks of cardiovascular magnetic resonance (CMR) imaging. The following four flow components were analyzed: direct flow, retained inflow, delayed ejection flow, and residual volume. In addition, the following six phasic blood flow KE parameters, normalized to the end-diastolic volume (EDV) and vorticity, were analyzed for both the left ventricle (LV) and right ventricle (RV): peak systolic phase, average systolic phase, peak diastolic phase, average diastolic phase, peak E-wave phase, and peak A-wave phase. The independent sample Student's t-test, Mann-Whitney U-test, univariable and multivariable stepwise regression analyses, intra and inter-observer variability analyses were used to compare patients and controls. In relation to the LV, the D-TGA patients had significantly decreased average vorticity, peak systolic vorticity, systolic vorticity, diastolic vorticity, and peak A-wave vorticity compared to the controls (all P<0.01). In relation to the RV, the pulmonary stenosis group had significantly increased peak E- and A-wave kinetic energy normalized to the end-diastolic volume (KEiEDV), and peak and average vorticity compared to the non-pulmonary stenosis group (all P<0.05). in the multivariable logistic regression model analysis, diastolic KEiEDV, peak E-wave KEiEDV peak A-wave KEiEDV, and average vorticity were associated a with transvalvular pressure difference (β=13.54, P<0.001 for diastolic KEiEDV; β=105.26, P<0.001 for peak E-wave KEiEDV; β=-49.36, P=0.027 for peak A-wave KEiEDV; and β=-56.37, P<0.001 for average vorticity). We found that 4D flow biventricular hemodynamics were more sensitive markers than the ejection fraction in the postoperative D-TGA patients. The RV diastolic KEiEDV parameters and average vorticity were risk factors for pulmonary artery obstruction in the multivariable model.

Low birth weight associations with cardiac structure and function in adults after arterial switch for transposition of the great arteries

Background and aimsThe objective of this study was to assess the associations of birth weight with cardiac structure and function in adults with dextro-transposition of the great arteries (D-TGA) who underwent the arterial switch operation (ASO). Methods and resultsThirty-nine ASO patients (age 24.4 ± 3.3 years) were included during routine clinical follow-up from July 2019 to December 2021. All patients underwent cardiopulmonary exercise testing and cardiac magnetic resonance imaging at rest and during exercise. Early-life characteristics, including birth weight, were extracted from electronic medical health records. Linear regression analysis showed that lower birth weight was associated with smaller left ventricular (LV) and right ventricular (RV) end-diastolic volume index (LV: −14.5 mL/m2 [95 % confidence interval, CI: −26.5 to −2.5] per 1-kg decrease in birth weight, p = 0.04; RV: −11.2 mL/m2 [-20.7 to −1.7] per 1-kg decrease in birth weight, p = 0.03). Lower birth weight was associated with greater LV and RV ejection fraction at rest (LV: +8.5 % [+4.4 to +12.5] per 1-kg decrease in birth weight, p < 0.001); RV: +8.1 % [+2.8 to +13.4] per 1-kg decrease in birth weight, p = 0.005). Furthermore, lower birth weight was associated with an attenuated increase in LV stroke volume index from rest to peak exercise (−5.2 mL/m2 [-9.3 to −1.2] per 1-kg decrease in birth weight, p = 0.02). ConclusionsBirth weight may be a novel risk factor for adverse cardiac remodeling in adult ASO patients. Further research is needed to delineate the mechanisms underlying the associations between birth weight and cardiac remodeling ASO patients as well as the broader adult CHD population.

Paradoxical cerebral embolism three decades after mustard surgery in a patient with complete transposition of the great arteries: a case report.

Atrial switch procedures such as the Mustard operation were previously popular for the complete transposition of the great arteries (i.e. dextro-transposition of the great arteries [d-TGA]). Patients with d-TGA who underwent atrial switch procedures approximately three decades ago have now entered adulthood. A female patient in her 30s with d-TGA had a paradoxical embolic stroke following the initiation of a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea. She underwent Mustard surgery when she was 2 years old. Following a series of procedures including implantation of a permanent pacemaker that was required because of sinus node dysfunction, she had reached adulthood, was living by herself and working independently. One month after taking the low-dose oestrogen plus progesterone oral pill, venous thrombosis occurred in the left soleus and left peroneal veins; and she experienced an acute ischaemic stroke in the right middle cerebral artery area. Transoesophageal echocardiography revealed that the shunt was present only during the Valsalva manoeuvre. Based on the examinations, the patient was diagnosed with juvenile ischaemic stroke as a result of a paradoxical embolism. These findings suggest that paradoxical cerebral embolism can occur as a late complication in patients with d-TGA who underwent the Mustard operation as children.

The illness severity scores can predict the need for respiratory and inotropic support in newborns with critical congenital heart malformations

Background and objectives. The illness severity scoring systems have been developed and validated to assess mortality risks based on clinical conditions and aid critical patient decision-making. Dextro-transposition of the great arteries (D-TGA) and coarctation of the aorta (CoA) are critical congenital heart defects that require medical treatment from birth and surgical repair in the neonatal period. The study aimed to compare the values of three scoring systems in predicting the need for respiratory and inotropic support for newborns with D-TGA and CoA. Materials and methods. An observational study was conducted on inborn infants diagnosed with D-TGA and CoA admitted to the newborn intensive care unit (NICU) within 12 hours of birth at a referral unit for congenital heart disease between January 2018 and December 2020. Newborns with D-TGA and CoA who died within the first 24 hours of birth, outborn infants, and those with a late diagnosis were excluded. For each patient, the Clinical Risk Index of Babies (CRIB-II), Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology-Perinatal Extension-II (SNAPPE-II) were calculated. Results. A total of 69 newborns were included in the current study, 30 (43.48 %) of whom were infants with D-TGA (D-TGA Group) and 39 (56.52 %) with CoA (CoA group). Newborns who required respiratory support had significantly higher CRIBII scores (3.03 ± 0.63 vs. 1.34 ± 0.19; p = 0.001), SNAP-II scores (26.61 ± 13.96 vs. 12.43 ± 9.98; p = 0.001), and SNAPPE-II scores (33.04 ± 2.91 vs. 14.47 ± 12.35; p = 0.001) compared to those who did not require it. Significantly higher CRIB-II (3.22 ± 0.67 vs. 1.56 ± 0.23; p = 0.003), SNAP-II (22.91 ±14.57 vs. 14.28 ± 1.58; p = 0.003), and SNAPPE-II (28.82 ± 17.95 vs. 16.58 ± 13.85; p = 0.003) scores were also associated with the need for inotropic support. When comparing the predictive efficiency of illness severity scores for detecting the risk of needing respiratory and inotropic support, they are more effective at predicting the need for ventilation and less effective at predicting the need for inotropes. Conclusions. The illness severity scores can effectively predict the need for pre-surgery interventions. Their simplicity makes them suitable for routine use.

Effects of Prostaglandin E1 and Balloon Atrial Septostomy on Cerebral Blood Flow and Oxygenation in Newborns Diagnosed with Transposition of the Great Arteries.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO2 and crSO2.

Impact of Persistent Pulmonary Hypertension of the Newborn in Neonates with Dextro-transposition of the Great Arteries

This study aimed to assess the impact of persistent pulmonary hypertension of the newborn (PPHN) on perioperative morbidity and mortality in patients with dextro-transposition of the great arteries. Secondarily, we evaluated the association between postoperative outcomes and intraoperative variables including the duration of cardiopulmonary bypass, cerebral oxygen desaturation, and hypotension. Retrospective observational study. Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands, over a 14-year period from January 2005 to December 2018. The study included 99 consecutive patients with simple dextro-transposition of the great arteries with or without a ventricular septal defect. All patients received preoperative management including intravenous prostaglandin E1 and, when necessary, a balloon atrial septostomy. Patients were then scheduled for an arterial switch operation. Patients were divided into a PPHN and a non-PPHN group. The outcomes assessed included mortality (overall, preoperative, 30-day postoperative and late mortality) and postoperative morbidity (length of ventilatory support, intensive care unit and hospital stay, delayed sternal closure and resternotomy). PPHN was present in 31% of patients. Overall mortality was 8.1%, with no difference between PPHN and non-PPHN patients (9.7 v 7.4%, p = 0.70). PPHN had no effect on morbidity outcomes. A lower weight at birth was associated with preoperative mortality. Duration of cardiopulmonary bypass and intraoperative hypotension were associated with longer intensive care unit stay. Intraoperative hypotension and cerebral oxygen desaturation had no significant impact on mortality. PPHN did not significantly affect perioperative morbidity and mortality in d-TGA patients, suggesting a more favorable prognosis than previously reported.

Pathogenesis and Surgical Treatment of Dextro-Transposition of the Great Arteries (D-TGA): Part II.

Dextro-transposition of the great arteries (D-TGA) is the second most common cyanotic heart disease, accounting for 5-7% of all congenital heart defects (CHDs). It is characterized by ventriculoarterial (VA) connection discordance, atrioventricular (AV) concordance, and a parallel relationship with D-TGA. As a result, the pulmonary and systemic circulations are separated [the morphological right ventricle (RV) is connected to the aorta and the morphological left ventricle (LV) is connected to the pulmonary artery]. This anomaly is included in the group of developmental disorders of embryonic heart conotruncal irregularities, and their pathogenesis is multifactorial. The anomaly's development is influenced by genetic, epigenetic, and environmental factors. It can occur either as an isolated anomaly, or in association with other cardiac defects. The typical concomitant cardiac anomalies that may occur in patients with D-TGA include ventriculoseptal defects, patent ductus arteriosus, left ventricular outflow tract obstruction (LVOTO), mitral and tricuspid valve abnormalities, and coronary artery variations. Correction of the defect during infancy is the preferred treatment for D-TGA. Balloon atrial septostomy (BAS) is necessary prior to the operation. The recommended surgical correction methods include arterial switch operation (ASO) and atrial switch operation (AtrSR), as well as the Rastelli and Nikaidoh procedures. The most common postoperative complications include coronary artery stenosis, neoaortic root dilation, neoaortic insufficiency and neopulmonic stenosis, right ventricular (RV) outflow tract obstruction (RVOTO), left ventricular (LV) dysfunction, arrhythmias, and heart failure. Early diagnosis and treatment of D-TGA is paramount to the prognosis of the patient. Improved surgical techniques have made it possible for patients with D-TGA to survive into adulthood.

Assessing subaortic right ventricle function after atrial switch repair through myocardial work analysis

BackgroundThe Mustard and Senning operations for dextro-transposition of the great arteries (D-TGA) establish a biventricular physiology with a subaortic right ventricle (sRV). While prolonged QRS has been associated with worse prognosis in these patients, current echocardiographic tools fall short in adequately assessing the (mal)performance and function decline of the sRV during follow-up. The present study is the first to characterize Myocardial Work (MW) indices of the sRV in D-TGA patients after Mustard/Senning repair. Methods and resultsAll adult D-TGA patients at follow-up in the University Hospital of Leuven between 2018 and 2022 were screened for inclusion. We retrospectively collected the most recent electrocardiogram parameters, 2D echocardiographic images and serum biomarkers’ values. Offline calculations of MW indices were performed. We established correlations between all variables and categorized patients into QRS<120 ms and QRS≥120 ms for further analysis. A total of 51 D-TGA patients were included (13 Mustard, 33 male, 39 ± 6 years). QRS duration increased with age and was correlated with sRV dimensions and serum levels of troponins (R = 0.42, p < 0.01) and NT-proBNP (R = 0.31, p = 0.03). However, no significant correlation was found between QRS duration and intraventricular desynchrony or conventional functional echocardiographic parameters. QRS prolongation was associated with a deterioration in septal, but not lateral, MW parameters. Patients with QRS≥120 ms had significantly larger ventricles and higher levels of troponins and NT-proBNP. ConclusionQRS prolongation after Mustard/Senning repair is linked to ventricular dilatation and worse performance, particularly affecting the septal wall. Global and regional MW analysis may be useful to assess the subclinical deterioration of sRV function.

Revisiting the Role of Balloon Atrial Septostomy Prior to the Arterial Switch Operation.

Patients with dextro-transposition of the great arteries (d-TGA) frequently undergo balloon atrial septostomy (BAS) prior to the arterial switch operation (ASO) to promote atrial-level mixing. Balloon atrial septostomy has inherent risks as an invasive procedure and may not always be necessary. This study revisits the routine utilization of BAS prior to ASO. Single-center, retrospective review of d-TGA patients undergoing the ASO from July 2018 to March 2023. Preoperative patient characteristics, pulse oximetry oxygen saturations (SpO2), cerebral/renal near-infrared spectroscopy (NIRS) readings along with prostaglandin status at the time of the ASO were analyzed with descriptive and univariate statistics. Thirty patients underwent the ASO. Of these, 7 (23%) were female, 25 (83%) were white, and median weight at ASO was 3.2 kg (range 0.8-4.2). Twenty-two (73%) patients underwent BAS. There were no demographic differences between BAS and no-BAS patients. Of those who underwent BAS, there was a significant increase in SpO2 (median 83% [range 54-92] to median 87% [range 72-95], P = .007); however, there was no change in NIRS from pre-to-post BAS. Six (27%) patients in the BAS group were prostaglandin-free at ASO. Balloon atrial septostomy patients underwent the ASO later compared with no-BAS patients (median 8 [range 3-32] vs 4 [range 2-10] days old, P = .016) and had a longer hospital length of stay (median 13 [range 7-43] vs 10 [range 8-131] days, P = .108). While BAS is an accepted preoperative procedure in d-TGA patients to improve oxygen saturations, it is also an additional invasive procedure, does not guarantee prostaglandin-free status at the time of ASO, and may increase the interval to ASO. Birth to direct early ASO, with prostaglandin support, should be revisited as an alternative, potentially more expeditious strategy.

Correlates of Resilience in Families of Children With Dextro-Transposition of the Great Arteries

Correlates of Resilience in Families of Children With Dextro-Transposition of the Great Arteries

High Reimplantation of Coronary Arteries After the Switch Procedure and Associated Stenoses.

Surgical repair through the arterial switch operation (ASO) is the only definitive treatment in patients with dextro-transposition of the great arteries (d-TGA). A crucial step during the reimplantation process is transfer of coronary arteries (CA) to the neo-aorta. A potential cause of CA stenosis is the presence of a high implantation of CA(HICA), defined by the presence of coronary ostium located above the sinotubular junction (STJ) of the aorta. We conducted a retrospective study on 157 patients (82 had digitally preserved angiograms) with d-TGA between 2010 and 2018 in a tertiary pediatric hospital in Canada. Of the 82 cases, 56 (68%) had HICA above the STJ. The mean distance from the STJ was + 7.1 ± 3.4mm for the RCA, and + 6.8 ± 3.1mm for the LMCA. Out of the 56 patients with HICA, 4 patients (7%) had stenosis, and out of 26 patients with in-sinus reimplanted CA, one patient (4%) had stenosis (p = 0.16). Patients in the HICA group with stenosis had a lower height of reimplantation of the CA compared to those without stenosis (+ 4.5 ± 1.3mm vs. + 6.8 ± 3.1mm, respectively; p < 0.05). This is a rare study assessing the rates of stenosis in the context of in-sinus versus HICA in the ASO. Reimplanting the coronary ostia at a higher level than the expected natural level does not seem to be associated with a significant risk in compromising CA perfusion.

Transcatheter Cardiac Interventions in Neonates with Congenital Heart Disease: A Single Centre Experience

Objective: To analyze the outcome among neonates undergoing transcatheter balloon atrial septostomy for various kinds of congenital heart diseases. Study Design: Prospective longitudinal study. Place and Duration of Study: National Institute of Cardiovascular Diseases, Karachi Pakistan, from Feb 2020 to May 2021. Methodology: A total of 28 neonates of both genders with echocardiography proven diagnosis of Tricuspid Atresia with restrictive Patent Foramen Ovale, Dextro-Transposition of Great Arteries with Intact Ventricular Septum, complex cyanotic congenital heart disease with inadequate mixing or hypoplastic left heart syndrome with restrictive PFO and a non-significant Patent Ductus Arteriosus, undergoing transcatheter balloon atrial septostomy were included. Demographic data along with diagnosis, clinical presentation, echocardiographic findings, procedural outcome (successful/unsuccessful), duration of the procedure, complication (if any), post-procedural echocardiographic findings, duration of hospital stay, further treatment plan and 3-months follow up outcomes were recorded among all neonates. Results: Most common diagnosis was Dextro-Transposition of the Great Arteries with IVS observed in 14(50.0%) neonates. Procedural outcome was found to be successful among 23(82.1%) neonates. There were 19(67.9%) neonates who did not show any post-procedure complication. At 3-months follow up, improvement in blood saturation and weight gain were reported among 12(42.9%) neonates each. Overall, mortality was noted in 7(25.0%) neonates, of whom 4(57.1%) neonates were having hypoplastic left heart syndrome. Conclusion: Transcatheter atrial septostomy done in neonatal period was found to have positive outcomes. Mortality remains high among neonates undergoing transcatheter atrial septostomy having hypoplastic left heart syndrome.

High-Throughput Genomics Identify Novel FBN1/2 Variants in Severe Neonatal Marfan Syndrome and Congenital Heart Defects.

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.

Echocardiographic imaging of neonatal transposition of great arteries: Rare case report and review of literature

Transposition of the great arteries (TGA) is a congenital conotruncal abnormality characterized by discordant connections between the ventricles and great arteries, with the aorta originating from the right ventricle (RV), and the pulmonary artery (PA) originating from the left ventricle (LV). The two main types of TGA are complete transposition or dextro-transposition of the great arteries (D-TGA), commonly referred to as D-loop, and congenitally corrected transposition (CCTGA), commonly referred to as L-loop or L-TGA. In D-TGA, the connections between the ventricles and atria are concordant, whereas in CCTGA they are discordant, with the left atrium connected to the RV, and the right atrium connected to the LV. Imaging plays an important role in the evaluation of TGA, both before and after surgery, for helping define the anatomy, quantify hemodynamics, and evaluate complications. Transthoracic echocardiography is the first-line imaging modality for pre-surgical planning in children with TGA. MRI provides comprehensive morphologic and functional information, particularly in adults after surgery. CT is performed when MRI is contraindicated or expected to generate artifacts. We are reporting an extremely rare and unique case of 25-day old male neonate, suffering from TGA with a side to side alignment of great arteries, accompanied by a moderate sized restrictive atrial septal defect (ASD) and an ascending aortic aneurysm (AAA).

Role of maternal hyperoxygenation in predicting need for postnatal balloon atrial septostomy in fetal d-transposition of the great arteries.

Predicting whether postnatal balloon atrial septostomy (BAS) will be necessary for fetuses with dextro-transposition of the great arteries (d-TGA) remains challenging. We sought to determine whether fetal echocardiographic measurements obtained during maternal hyperoxygenation (MH) can improve our ability to predict the need for postnatal BAS. This was a retrospective, single-institution review of d-TGA fetuses whose mothers had undergone MH at 33-38 weeks' gestation at the Children's Hospital of Philadelphia, between 1 January 2017 and 30March2020. All fetal d-TGA cases had either an intact ventricular septum or small ventricular septal defect measuring < 3 mm. Patent foramen ovale (PFO) size, measured by two-dimensional imaging (2D) and by color Doppler, and patent ductus arteriosus (PDA) shunting (antegrade vs bidirectional) were assessed in room air (RA) and during MH. BAS status and timing were recorded. Of 41 fetal d-TGA cases in the cohort, 23 underwent postnatal BAS, while 18 did not, and 14 subjects underwent emergent BAS within 3 h of delivery. On univariate analysis, PFO size measured both in RA and during MH and antegrade shunting in the PDA during MH predicted BAS. During MH, median PFO size by 2D was significantly smaller in fetuses which underwent emergent BAS compared to fetuses which did not undergo BAS (2.5 (interquartile range (IQR), 2.0-3.0) mm vs 4.1 (IQR, 3.4-5.0) mm; P < 0.001). On cut-point analysis, PFO size by 2D during MH of ≤ 3.2 mm predicted the need for emergent BAS with a sensitivity of 93% (95% CI, 66-100%) and a specificity of 78% (95% CI, 58-91%). In fetuses with d-TGA, measurement of PFO size and direction of PDA shunting during MH improves our ability to predict the need for postnatal BAS, although additional study is needed. We propose incorporating third-trimester MH when planning delivery of a d-TGA fetus. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Characteristics and Outcomes of a Single-Centre Cohort of Adult Congenital Heart Disease Patients Referred for Heart Transplant

Adult congenital heart disease (ACHD) services increasingly encounter heart failure (HF) in the ageing ACHD population. Optimal timing of referral for heart transplant (HTx) evaluation in this heterogeneous population is complex and ill-defined. We aim to outline the characteristics and outcomes of ACHD patients referred for HTx from a large Australian ACHD centre. Retrospective review of ACHD patients referred for HTx from a primary ACHD centre (1992-2021). Database analysis of patient demographics, characteristics, wait-listing, and transplantation outcomes was performed. A total of 45 patients (mean age 37±9.9 years old; 69% male) were referred for HTx with a mean follow-up of 5.9±6.3 years. Of these, 22 of 45 (49%) were listed and transplanted, including one heart-lung transplant. The commonest diagnosis was dextro-transposition of the great arteries (13/45, 29%). Most patients, 33 of 45 (73.3%) had undergone at least one cardiac surgery in childhood. Indications for HTx referral included HF in 34 of 45 (75%), followed by pulmonary hypertension in 7 of 45 (11%). Median transplant wait-list time was 145 days (interquartile range, 112-256). Of the 23 patients not wait-listed, the reasons included clinical stability in 13 of 45 (29%), psychosocial factors in 2 of 45 (4.4%) and prohibitive surgical risk, including multiorgan dysfunction, in 8 of 45 (17.7%). Transplant was of a single organ in most, 21 of 22 (95.5%). Overall mortality was 5 of 22 (22.7%) in those after HTx, and 14 of 23 (60.9%) in those not listed (p=0.0156). Increasingly, ACHD patients demonstrate the need for advanced HF treatments. HTx decision-making is complex, and increased mortality is seen in those not wait-listed. Ultimately, the referral of ACHD patients for HTx is underpinned by local decision-making and experience, wait-list times and outcomes.

Abstract 13332: Assessment of Myocardial Oxygenation Response to Vasoactive Breathing Maneuvers in Patients With Repaired Dextro-Transposition of the Great Arteries an OS-CMR Study

Introduction: Long-term outcomes of patients with repaired Dextro-transposition of the great arteries (D-TGA) by arterial switch operation (ASO) are excellent. However, studies have suggested impaired myocardial blood flow reserve. Oxygen-sensitive cardiac magnetic resonance (OS-CMR) with vasoactive breathing maneuvers (BM) offers a contrast-free tool for evaluating myocardial oxygenation. Hypothesis: Evaluate myocardial oxygenation reserve and microvascular function in repaired D-TGA post-ASO using OS-CMR with BM. Methods: In this single-center study, we analyzed OS-CMR images (basal and mid-left ventricular slices) of 9 D-TGA post-ASO patients (mean age 29 ±6.52yrs, 33.3% females) and 10 healthy participants (mean age 33 ±8.9 yrs, 40% females) who completed the BM. The BM consisted of free breathing, then hyperventilation, causing vasoconstriction, then breath hold, causing vasodilatation. End-systolic OS-CMR signal intensity (SI) was measured at baseline, after hyperventilation (closest to 0 sec of breath hold), and at closest to 30 sec of breath hold. Changes in SI (ΔSI) in % were calculated in response to the different periods and compared using independent samples t-test. Results: In the D-TGA cohort, the coronary response to hyperventilation was abnormal compared to healthy subjects (5.8±19.9% vs -15.1±13.3%, p=0.01). No difference was observed in ΔSI% during breath hold (mean TGA:3.0±10.5% vs mean healthy:5.7±6%, p=0.5). No differences were observed in mid-slices for either period. Conclusions: Our findings suggest patients with D-TGA may have an impaired vasoconstrictor response to a hyperventilation maneuver. Further studies should explore the associated pathophysiology and potential impact on clinical management.