Balloon atrial septostomy in d-Transposition of the Great Arteries-predictive discriminators for intervention

Balloon atrial septostomy in d-Transposition of the Great Arteries-predictive discriminators for intervention | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Balloon atrial septostomy in d-Transposition of the Great Arteries-predictive discriminators for intervention Sinead Burke, Siobhan Coughlan, Martina Healy, Jennifer J Brady, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6494276/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: Balloon Atrial Septostomy (BAS) is performed in a subset of patients with D-Transposition of the Great Arteries (dTGA). We sought to identify discriminators for those requiring a BAS pre-Arterial Switch Operation (ASO). Methods: We reviewed all patients with simple dTGA between 2019 and 2023 undergoing an ASO at our institution. Clinical outcome variables were compared between those undergoing a BAS or not using paired and unpaired Student's T tests, Ordinary one-way ANOVA, and Mixed-effects analysis. Results: 55 patients with dTGA were included (85.7% male), of which 26 required a BAS (mean age 1.3 days). The mean atrial septal communication size was significantly different in those that required a BAS (2.4mm) to those that did not (4.3mm), p = 0.0001. Of those patients with dTGA that required a BAS, they had higher mean blood lactates (3.79 mmol/L V’s 2.52 mmol/L; p = 0.043), were slightly more acidotic (pH 7.239 V’s 7.29; p = 0.0496) but the mean PaC02 values, albeit elevated compared to normal range in both groups, were not statistically different (7.58 kPa V’s 6.96 kPa; p = 0.28). There was no effect on day of ASO surgery (5.61 days V’s 4.90 days; p = 0.21), post-ASO length of ICU stay (6.73 days in BAS cohort V’s 8.66 days; p = 0.072) or total days of ICU ventilation (7.15 days V’s 7.00 days; p = 0.882). Conclusions: Only the lactate values and atrial septal communication size are significant discriminators between those requiring a BAS or not with no impact thereafter on day-of-life for ASO, total days of ventilation or post-operative intensive care length-of-stay. Arterial Switch Operation Transposition of the Great Vessels Lactic acid balloon atrial septostomy blood gas Figures Figure 1 Figure 2 Introduction D-Transposition of the Great Arteries (dTGA) is the commonest form of cyanotic congenital heart disease with 1 in 3,596 Irish infant live births in 2022 undergoing a surgical procedure for this diagnosis annually.[1,2] All forms of dTGA accounted for 24.6% of neonatal surgical volume in 2022 with an average of 16.2 cases per year over the last 10 years nationally. Since the development of the Arterial Switch Operation (ASO), the long-term prognosis and event-free survival for patients with dTGA has dramatically improved to the point where most infants born with this diagnosis can expect to survive with no or minimal ongoing cardiovascular morbidity into adulthood. [3] Similarly, whilst a proportion of infants with dTGA deliver in good clinical condition and require no intervention prior to ASO, a subset of patients have inadequate left-to-right shunting at atrial level in the first hours of life manifesting with worsening metabolic acidosis and systemic hypoxaemia. The temporising intervention to allow better atrial mixing in those with a restrictive foramen ovale prior to definitive arterial switch operation, the Balloon Atrial Septostomy (BAS), has been life-saving in reducing dTGA mortality. [4] Creating an enlarged atrial fenestration by performing a BAS allows augmented left to right shunting at atrial level and improves both systemic oxygenation and subsequent end-organ perfusion. However, a significant risk of neurological morbidity has been identified from fetal life onwards in these patients with the pathophysiological exposure to de-oxygenated blood throughout fetal life and the resultant impact on somatic brain growth and white matter injury thought to be contributary. [5,6] Selecting which patients with dTGA in whom to perform a BAS and optimising their clinical status pre-operatively remains a cornerstone of current management. There is a dearth of recent published data on patient response to BAS in dTGA and whether there are discriminators in this data between those that ultimately went on to have a BAS pre-ASO and those that did not. Aim(s) We hypothesized that threshold blood gas values may predict the need for BAS prior to ASO. We also hypothesized that C02 clearance (as measured on PaC02 on a blood gas) may be a currently over-looked marker of inadequate mixing in those that subsequently require a BAS. Finally, we wished to understand the relationship, if any, of the effective orifice dimension of the atrial septal communication on trans-thoracic echocardiography between those requiring BAS and those that did not. The impact on intensive care unit length of stay, age at surgery as a surrogate of medical ‘readiness’, and days of ventilation post-operatively between those with dTGA undergoing a BAS or not, were recorded as secondary endpoints. Materials and methods Patient population and study design Data is collected on all cardiac surgery patients at our single site, all-island tertiary cardiac surgery unit as part of outcome compliance with the National Institute for Cardiovascular Outcomes Research (NICOR). This was a retrospective study analysing five years of data from 2019 until 2023. Our inclusion criteria specified full-term infants (greater than 36 WGA) with a confirmed diagnosis of isolated (or ‘simple’) dTGA that had undergone an arterial switch operation as their first cardiac surgery in the neonatal period. Exclusion criteria included complex additional congenital heart disease that may complicate interpretation of results, prematurity (under 36 WGA) & low birth weight (under 2.5kg) that may alter clinical decision-making from the standard pathway, significant airway or lung parenchymal disease, major other pre-operative clinical co-morbidity involving another organ system (e.g. necrotising enterocolitis), or pre-operative sepsis (confounder of acidosis). Capillary, arterial or central venous blood gas results were recorded from the Clinisys WinPath report archive and the archive of the blood gas analyser machines in the biochemistry department. Capillary and arterial blood gas results, only, were used for Pa02 analysis. Blood gas samples included for analysis were taken on day-of-life 1 (DOL#1) in all dTGA patients. For those patients who underwent a BAS, three additional blood gas samples were collected for analysis- immediately prior to BAS, immediately after the BAS, and one day after the BAS. Normative threshold of blood gas values (all parameters) were defined from the age-adjusted Mosby’s Diagnostic and Laboratory Test Reference, 15th edition[7]. The pH normal values for neonates were defined as 7.32 to 7.49. The bicarbonate normal values for neonates were defined as 13–22 mEq/L. Normal lactate values were taken as under 2 mmol/L. The normal range PaC02 values for neonates were defined as between 4.7 to 6.0 kPa.[8] Given the variable range of sources of blood gases (arterial, capillary and central venous), it was necessary to define whether the samples could be analysed collectively for statistical purposes. There is relative agreement on the correlation of arterial and central venous blood gas samples based on simultaneous comparison in intensive care patients. In a study by Hynes et al., the venous-arterial (AV) difference were very similar for pH (-0.04), bicarbonate (-0.37 mmol/l) and lactate (+ 0.16 mmol/l)[9]. The AV difference for PaC02 had wide 95% limits of agreement even if the mean values were comparative (+ 0.85 kPa). Central venous PaC02 values of under 6 kPa, however, can be accurately (100% sensitivity) and reliably (100% negative predictive value) used to rule out hypercarbia, hence this was defined as the upper limit normal value in this study.[9,10] The effective atrial septal communication diameter was independently measured by a trained echocardiographer (S.G.) in all patients on their first trans-thoracic echocardiogram (TTE) archived (Intellispace Cardiovascular) at our institution with the operator blinded to those that required subsequent BAS. On completion of this dataset, the atrial communication diameter was measured again in those patients that underwent a BAS on their first TTE post-BAS. The study was approved by the institutional research ethics board and the authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Analyses Statistical analysis was performed using GraphPad Prism version 10.4.0. Descriptive statistics, fraction of total, paired and unpaired T tests, mixed-effects analysis and Ordinary one-way ANOVA statistical tools were used to describe, analyse and graph the data. Unpaired T tests (two-tailed) were used for column comparative statistics, assuming Gaussian distribution and assuming both populations have the same standard deviation. For analysis of unmatched multiple columns of data, Ordinary one-way ANOVA was utilised. To analyse trends in matched values over time, a one-way ANOVA mixed effects model was used, that also allowed for any randomly missing matched values, assuming Gaussian distribution and not assuming sphericity. The mean of each column of results was compared to the mean of a specified control column. Results 55 patients met inclusion criteria with a gestation > 36 weeks and a diagnosis of simple dTGA born between 2019 and 2023 inclusive undergoing a subsequent ASO at our institution. Of those patients meeting inclusion criteria, 47 were male (85.7%) and had an average gestation and birth weight of 38 + 5 weeks and 3.43kg, respectively. 93% (n = 51) had an antenatal diagnosis of dTGA and had a planned delivered in a tertiary NICU affiliated with our cardiology programme ( Supplementary Figure S1 ). Just under a half of the patients (n = 26) required a BAS in the first days of life pre-operatively (mean 1.3 days), of whom 77% (n = 20) were ventilated prior to their BAS ( Supplementary Figure S2 ). The mean atrial septal communication size was significantly different in those that required a BAS (2.4mm) to those that did not (4.3mm), p = 0.0001 ( Supplementary Figure S3a ). There was no difference in mean birth weight or gestation between those undergoing a BAS (3.559kg; 9.23 days from due date) or not (3.314kg; 9.03 days from due date), p = 0.065 & p = 0.914, respectively ( Table 1 ). Mean pre-operative ICU length of stay was significantly longer for those undergoing a BAS (3.04 days) compared to those that did not require a BAS (1.41 days), p = 0.0025. Of those patients with dTGA that required a BAS compared to those that did not, on DOL#1 they had higher median blood lactate concentrations of 2.6 mmol/L (interquartile range 4.13 mmol/L) V’s 2 mmol/L (interquartile range 1.46 mmol/L) (Fig. 1 ). They were slightly more acidotic (mean pH 7.239 V’s 7.29; p = 0.0496) but the mean PaC02 values, albeit elevated compared to normal range in both groups, were not statistically different (7.58 kPa V’s 6.96 kPa; p = 0.28). Bicarbonate values were at the upper limit normal neonatal range in dTGA patients (normal range 13–22 mEq/L) and not significantly different in those undergoing a BAS or not (19.81 mEq/L V’s 21.53 mEq/L; p = 0.055). There was no effect on mean day of ASO surgery between those undergoing BAS or not (5.61 days V’s 4.90 days; p = 0.21) ( Table 1, Supplementary Figure S4 ). Similarly, post-ASO mean length of ICU stay was not different between the two groups (6.73 days in BAS cohort V’s 8.66 days; p = 0.073) nor was mean total days of ICU ventilation (7.15 days V’s 7.00 days; p = 0.883). In those patients with dTGA undergoing a BAS, there was a significant reduction in lactate, and PaC02 values from the value obtained on DOL#1 to the values obtained after BAS (Fig. 2 ). Mean fall in lactate was from 3.79 mmol/L to 2.1 mmol/L (p = 0.041); Mean fall in PaC02 was from 7.578 kPa to 5.46 kPa (p = 0.0013). There also was a concomitant rise in pH post BAS from a mean of 7.23 to 7.366 (p = 0.003). Bicarbonate values showed a non-significant trend towards normalization post-BAS from 19.81 mEq/L to 22.27 mEq/L (p = 0.161). After BAS, there was no significant difference in the atrial septal communication size between those that had undergone a BAS (5.0mm) and those that had not clinically required one (4.3mm), p = 0.19 ( Supplementary Figure S3a ). The atrial communication diameter was, therefore, significantly augmented BAS ( Supplementary Figure S3b ). Discussion The National Institute for Cardiovascular Outcomes Research (NICOR) is a UK & Ireland voluntary audit body that has been collecting outcome data on all children in all centres with congenital heart disease at least as far back as 2012 and is a publicly available resource.[2] Of the 65 neonates undergoing cardiac surgery at our institution between 2022–2023, there were 12 ASO’s performed, representing 18.5% of all neonatal cases. Our 10-year average of ASO’s is 11.3 per year. Over the same time period across all centres in the UK and Ireland, there were a total 106 ASO’s performed, representing 13.6% of all neonatal cardiac surgery. It remains one of the most common complex forms of cyanotic congenital heart disease that cardiac centres care for. Between 2020 to 2023, up to 85.5% of dTGA-IVS cases were prenatally diagnosed, representing a relatively high percentage and a clinical opportunity to deliver best care. Optimising the management of neonates with dTGA from postnatal admission and prior to definitive surgical repair is a central tenet in pre-operative care. Central venous, capillary or arterial blood gas analysis allows the clinician to interrogate the physiological stress the neonate with dTGA is under and what next management steps to make. It assists with decision-making around those who require a balloon atrial septostomy to allow better intra-cardiac mixing. The dTGA patients in this study were more acidotic, had elevated lactate levels and had inadequate C02 clearance compared to normal, age-matched reference range values. There were significantly more male infants with dTGA than females with a ratio of 5.87:1. This is a sex-distribution trend reported in the literature but is skewed towards male sex significantly more than reported by others.[11,12] The aetiology of this over-representation of male sex is currently unclear. In those dTGA patients that underwent a BAS prior to ASO compared to those that did not, birth weight or gestation played no role, acknowledging that gestation under 36 weeks was an exclusion criteria for this study. There was, however, a statistically significant difference in the DOL#1 lower pH values & higher blood lactates. Interestingly, there was no difference in PaC02 values, the mean of which was elevated in both those undergoing a BAS and those that were not, inferring inadequate C02 clearance with transposition physiology prior to ASO. DOL#1 PaC02 could not, in our study, be used as a discriminator between those subsequently needing a BAS or not. The PaC02 value did trend towards normal range within a day after the BAS and prior to ASO, reflecting ongoing appropriate ICU management in improving C02 clearance. The patients who required a BAS had, not surprisingly, a significantly smaller atrial communication compared to those that did not require a BAS and this highlights the significance of the restrictive atrial communication on resultant metabolic acidosis primarily. The BAS was extremely effective in ‘correcting’ the size of the atrial communication to the same as those infants who had not required BAS intervention. The concept of reduced effective pulmonary blood flow in dTGA was reported by Shaher et al. in 1964, with resultant elevation in intravascular PaC02 and reduced end-tidal C02.[13,14] Early era cardiac catheterization data reported on PaC02 but the numbers of patients were very small and they were, by-and-large, well outside the neonatal age bracket.[15] Our study provides up-to-date data on PaC02 values in patients with dTGA on admission after birth. Of those patients who went on to require a BAS prior to ASO, the pH & C02 were already trending towards normal range with appropriate ICU management prior to their BAS, showing the value of concomitant medical efforts at physiological optimisation in addition to the BAS. There was further normalisation of blood gas values immediately after BAS and, again, one day after the BAS. This infers a continuum of a trajectory of recovery that begins after admission to the cardiac centre and results in ongoing optimisation of the patient even up to the day after their BAS. Besides a longer pre-operative ICU occupancy, there was no difference in day of ASO surgery, total days of ventilation or post-operative ICU length-of-stay in those undergoing a BAS compared to those that did not. Outcome for children with a diagnosis of dTGA is, in the current era, also focused on long-term neurodevelopmental prognosis. This is particularly well-studied internationally in children with dTGA as they have a relatively comparable neonatal and peri-operative course across centres with a low re-intervention rate, generally. Simply having a diagnosis of dTGA alone places a patient at risk of neurodevelopmental delay with the effect of deoxygenated blood re-circulating to the brain for the 9 months of pregnancy. Infants with dTGA have a known delay in brain maturation and significantly smaller brains, by head circumference at birth, than controls.[5,16] Length of ICU stay and hospital stay or need for cardiopulmonary resuscitation at any time point are recognised risk factors for developmental delay in patients with congenital heart disease, especially in those neonates undergoing open heart surgery in the first week of life.[17] Clinical efforts to advance all aspects of pre-operative care will hopefully result in optimal neurodevelopmental outcome in the long-term for infants with dTGA. Limitations: There were insufficient arterial or capillary blood gas samples pre-BAS (n = 7) to contribute to a comparison of Pa02 between those undergoing a BAS or not. Oxygen saturation data was highly variable in individual patients over time and not comparable given the confounding factors of supplemental oxygen and ventilation. Conclusion In patients with a diagnosis of simple d-TGA, the significant majority of patients on DOL#1 are acidotic with an elevated lactate and PaC02 in spite of an antenatal diagnosis and planned delivery in an affiliated tertiary neonatal intensive care unit. With current standards of care, only the lactate values and atrial septal communication size are sufficiently discrepant between those requiring a BAS or not to usefully clinically differentiate between the two cohorts. Standard neonatal pre-operative cardiac care begins to normalise blood gas value derangement that continues in the cohort who go on to require a BAS up until and after their catheter-based intervention. Appropriate selection of dTGA patients requiring a BAS has no impact thereafter on day-of-life for ASO, total days of ventilation or post-operative intensive care length-of-stay. Optimising peri-operative care in those patients with dTGA will hopefully preserve neurodevelopmental outcome potential as current management strategies are increasingly more cognisant of these longer-term metrics. Declarations Acknowledgements. We would like to thank and acknowledge the help of our institutional NICOR database managers, Ms. Rita Butler and Ms. Sara Cullen. Financial support. This project received no specific grant from any funding agency, commercial or not-for-profit sectors. Conflicts of interest. The authors have no relevant financial or non-financial interests to disclose. Author Contribution. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sinead Burke and Siobhan Coughlan. The first draft of the manuscript was written by Terence Prendiville and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Central Statistics Office. NICOR. Santens B, Van De Bruaene A, De Meester P, Gewillig M, Troost E, Claus P, Bogaert J, Budts W (2020) Outcome of arterial switch operation for transposition of the great arteries. A 35-year follow-up study. Int J Cardiol 316: 94-100 Liebman J, Cullum L, Belloc NB (1969) Natural history of transpositon of the great arteries. Anatomy and birth and death characteristics. Circulation 40: 237-262 Hansen T, Henriksen TB, Bach CC, Matthiesen NB (2017) Congenital Heart Defects and Measures of Prenatal Brain Growth: A Systematic Review. Pediatr Neurol 72: 7-18 e11 Kordopati-Zilou K, Sergentanis T, Pervanidou P, Sofianou-Petraki D, Panoulis K, Vlahos N, Eleftheriades M (2022) Dextro-Transposition of Great Arteries and Neurodevelopmental Outcomes: A Review of the Literature. Children (Basel) 9: Pagana KDPEDoNLCWP, Pagana TJ, Pagana TN (2021) Mosby's Manual of Diagnostic and Laboratory Tests - E-Book, 7th edn. Mosby, Messina Z, Patrick H (2024) Partial Pressure of Carbon Dioxide. StatPearls. Treasure Island (FL), Hynes D, Bates S, Loughman A, Klim S, French C, Kelly AM (2015) Arteriovenous blood gas agreement in intensive care patients with varying levels of circulatory compromise: a pilot study. Crit Care Resusc 17: 253-256 Kelly A (2013) Agreement between Arterial and Venous Blood Gases In Emergency Medical Care: A Systematic Review. Hong Kong Journal of Emergency Medicine 20: 166-171 Egbe A, Uppu S, Stroustrup A, Lee S, Ho D, Srivastava S (2014) Incidences and sociodemographics of specific congenital heart diseases in the United States of America: an evaluation of hospital discharge diagnoses. Pediatr Cardiol 35: 975-982 Pugnaloni F, Felici A, Corno AF, Marino B, Versacci P, Putotto C (2023) Gender differences in congenital heart defects: a narrative review. Transl Pediatr 12: 1753-1764 Shaher RM (1964) The Haemodynamics of Complete Transposition of the Great Vessels. Br Heart J 26: 343-353 Janssen PJ (1976) Capnographic impressions of pulmonary perfusion patterns in patients with congenital heart anomalies. Int Anesthesiol Clin 14: 123-156 Shaher RM, Kidd L (1967) Acid-base balance in complete transposition of the great vessels. Br Heart J 29: 207-211 Licht DJ, Shera DM, Clancy RR, Wernovsky G, Montenegro LM, Nicolson SC, Zimmerman RA, Spray TL, Gaynor JW, Vossough A (2009) Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg 137: 529-536; discussion 536-527 Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH, Jr., Li J, Smith SE, Bellinger DC, Mahle WT, American Heart Association Congenital Heart Defects Committee CoCDitYCoCN, Stroke C (2012) Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 126: 1143-1172 Table 1 Table 1 Comparative Demographics and Intensive Care Outcome for Neonates with d-Transposition of the Great Arteries undergoing Balloon Atrial Septostomy (BAS) to those that did not. Req. BAS No BAS p value male (%) 24 (92.3%) 23 (79.3%) Birth weight (mean) 3.559kg 3.314kg p=0.064 Gestation (days to due date) -9.2 days -9 days p=0.914 ICU length of stay (pre-ASO) 3 days 1.4 days p=0.002** Day of ASO surgery 5.6 days 4.9 days p=0.21 Days of invasive ventilation (post-ASO) 7.1 days 7 days p=0.882 ICU length of stay (post-ASO) 6.7 days 8.7 days p=0.072 Total length of ICU stay (pre- and post-ASO) 9.7 days 10.1 days p=0.792 Additional Declarations No competing interests reported. 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Panel (a) comparative lactate values in mmol/L, panel (b) comparative pH values, panel (c) comparative PaC02 values in kPa, panel (d) comparative bicarbonate values in mEq/L.\u003c/p\u003e\n\u003cp\u003eDOL (day-of-life), dTGA (d-transposition of the great arteries), BAS (balloon atrial septostomy), ns (non-significant p value \u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eLactate unpaired t test: * (p value =0.0433); pH unpaired t test: * (p value = 0.0496).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6494276/v1/6061b5e66aa2a0e2cf30312d.png"},{"id":82311074,"identity":"8190e380-ba13-4d4a-9ded-3cb7596b3e8a","added_by":"auto","created_at":"2025-05-09 01:53:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":610305,"visible":true,"origin":"","legend":"\u003cp\u003eTrend in serial blood gas values for those infants with d-transposition of the great arteries that required a balloon atrial septostomy. Panel (a) serial lactate values in mmol/L, panel (b) serial pH values, panel (c) serial PaC02 values in kPa, panel (d) serial bicarbonate values in mEq/L. The four representative blood gas results for each value are from the first recorded sample, immediately prior to balloon atrial septostomy, immediately after balloon atrial septostomy and the following day after balloon atrial septostomy.\u003c/p\u003e\n\u003cp\u003edTGA (d-transposition of the great arteries), BAS (balloon atrial septostomy), ns (non-significant p value \u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eLactate mixed effects analysis: * (p value = 0.041); pH mixed effects analysis: * (p value = 0.0113), ** (p value = 0.003), *** (p value = 0.0006). PaC02 mixed effects analysis: * (p value = 0.0275), ** (p value = 0.0013), *** (p value = 0.0004).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6494276/v1/34c573596572b1124e2e808b.png"},{"id":83086769,"identity":"73dc4871-21e0-4c9e-a049-873928285c7c","added_by":"auto","created_at":"2025-05-20 00:01:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1588283,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6494276/v1/161b6f87-bdbf-45bb-a5fe-55689fc74e28.pdf"},{"id":82311117,"identity":"f6632e4e-11ab-4713-8335-f5d4f34d17ec","added_by":"auto","created_at":"2025-05-09 01:53:43","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1062102,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6494276/v1/fc43243220910bece08a9035.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBalloon atrial septostomy in d-Transposition of the Great Arteries-predictive discriminators for intervention\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eD-Transposition of the Great Arteries (dTGA) is the commonest form of cyanotic congenital heart disease with 1 in 3,596 Irish infant live births in 2022 undergoing a surgical procedure for this diagnosis annually.[1,2] All forms of dTGA accounted for 24.6% of neonatal surgical volume in 2022 with an average of 16.2 cases per year over the last 10 years nationally. Since the development of the Arterial Switch Operation (ASO), the long-term prognosis and event-free survival for patients with dTGA has dramatically improved to the point where most infants born with this diagnosis can expect to survive with no or minimal ongoing cardiovascular morbidity into adulthood. [3]\u003c/p\u003e \u003cp\u003eSimilarly, whilst a proportion of infants with dTGA deliver in good clinical condition and require no intervention prior to ASO, a subset of patients have inadequate left-to-right shunting at atrial level in the first hours of life manifesting with worsening metabolic acidosis and systemic hypoxaemia. The temporising intervention to allow better atrial mixing in those with a restrictive foramen ovale prior to definitive arterial switch operation, the Balloon Atrial Septostomy (BAS), has been life-saving in reducing dTGA mortality. [4] Creating an enlarged atrial fenestration by performing a BAS allows augmented left to right shunting at atrial level and improves both systemic oxygenation and subsequent end-organ perfusion. However, a significant risk of neurological morbidity has been identified from fetal life onwards in these patients with the pathophysiological exposure to de-oxygenated blood throughout fetal life and the resultant impact on somatic brain growth and white matter injury thought to be contributary. [5,6] Selecting which patients with dTGA in whom to perform a BAS and optimising their clinical status pre-operatively remains a cornerstone of current management. There is a dearth of recent published data on patient response to BAS in dTGA and whether there are discriminators in this data between those that ultimately went on to have a BAS pre-ASO and those that did not.\u003c/p\u003e\n\u003ch3\u003eAim(s)\u003c/h3\u003e\n\u003cp\u003eWe hypothesized that threshold blood gas values may predict the need for BAS prior to ASO. We also hypothesized that C02 clearance (as measured on PaC02 on a blood gas) may be a currently over-looked marker of inadequate mixing in those that subsequently require a BAS. Finally, we wished to understand the relationship, if any, of the effective orifice dimension of the atrial septal communication on trans-thoracic echocardiography between those requiring BAS and those that did not. The impact on intensive care unit length of stay, age at surgery as a surrogate of medical \u0026lsquo;readiness\u0026rsquo;, and days of ventilation post-operatively between those with dTGA undergoing a BAS or not, were recorded as secondary endpoints.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient population and study design\u003c/h2\u003e \u003cp\u003eData is collected on all cardiac surgery patients at our single site, all-island tertiary cardiac surgery unit as part of outcome compliance with the National Institute for Cardiovascular Outcomes Research (NICOR). This was a retrospective study analysing five years of data from 2019 until 2023. Our inclusion criteria specified full-term infants (greater than 36 WGA) with a confirmed diagnosis of isolated (or \u0026lsquo;simple\u0026rsquo;) dTGA that had undergone an arterial switch operation as their first cardiac surgery in the neonatal period. Exclusion criteria included complex additional congenital heart disease that may complicate interpretation of results, prematurity (under 36 WGA) \u0026amp; low birth weight (under 2.5kg) that may alter clinical decision-making from the standard pathway, significant airway or lung parenchymal disease, major other pre-operative clinical co-morbidity involving another organ system (e.g. necrotising enterocolitis), or pre-operative sepsis (confounder of acidosis).\u003c/p\u003e \u003cp\u003eCapillary, arterial or central venous blood gas results were recorded from the Clinisys WinPath report archive and the archive of the blood gas analyser machines in the biochemistry department. Capillary and arterial blood gas results, only, were used for Pa02 analysis. Blood gas samples included for analysis were taken on day-of-life 1 (DOL#1) in all dTGA patients. For those patients who underwent a BAS, three additional blood gas samples were collected for analysis- immediately prior to BAS, immediately after the BAS, and one day after the BAS. Normative threshold of blood gas values (all parameters) were defined from the age-adjusted Mosby\u0026rsquo;s Diagnostic and Laboratory Test Reference, 15th edition[7]. The pH normal values for neonates were defined as 7.32 to 7.49. The bicarbonate normal values for neonates were defined as 13\u0026ndash;22 mEq/L. Normal lactate values were taken as under 2 mmol/L. The normal range PaC02 values for neonates were defined as between 4.7 to 6.0 kPa.[8] Given the variable range of sources of blood gases (arterial, capillary and central venous), it was necessary to define whether the samples could be analysed collectively for statistical purposes. There is relative agreement on the correlation of arterial and central venous blood gas samples based on simultaneous comparison in intensive care patients. In a study by Hynes et al., the venous-arterial (AV) difference were very similar for pH (-0.04), bicarbonate (-0.37 mmol/l) and lactate (+\u0026thinsp;0.16 mmol/l)[9]. The AV difference for PaC02 had wide 95% limits of agreement even if the mean values were comparative (+\u0026thinsp;0.85 kPa). Central venous PaC02 values of under 6 kPa, however, can be accurately (100% sensitivity) and reliably (100% negative predictive value) used to rule out hypercarbia, hence this was defined as the upper limit normal value in this study.[9,10]\u003c/p\u003e \u003cp\u003eThe effective atrial septal communication diameter was independently measured by a trained echocardiographer (S.G.) in all patients on their first trans-thoracic echocardiogram (TTE) archived (Intellispace Cardiovascular) at our institution with the operator blinded to those that required subsequent BAS. On completion of this dataset, the atrial communication diameter was measured again in those patients that underwent a BAS on their first TTE post-BAS.\u003c/p\u003e \u003cp\u003e The study was approved by the institutional research ethics board and the authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnalyses\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using GraphPad Prism version 10.4.0. Descriptive statistics, fraction of total, paired and unpaired T tests, mixed-effects analysis and Ordinary one-way ANOVA statistical tools were used to describe, analyse and graph the data. Unpaired T tests (two-tailed) were used for column comparative statistics, assuming Gaussian distribution and assuming both populations have the same standard deviation. For analysis of unmatched multiple columns of data, Ordinary one-way ANOVA was utilised. To analyse trends in matched values over time, a one-way ANOVA mixed effects model was used, that also allowed for any randomly missing matched values, assuming Gaussian distribution and not assuming sphericity. The mean of each column of results was compared to the mean of a specified control column.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e55 patients met inclusion criteria with a gestation\u0026thinsp;\u0026gt;\u0026thinsp;36 weeks and a diagnosis of simple dTGA born between 2019 and 2023 inclusive undergoing a subsequent ASO at our institution. Of those patients meeting inclusion criteria, 47 were male (85.7%) and had an average gestation and birth weight of 38\u0026thinsp;+\u0026thinsp;5 weeks and 3.43kg, respectively. 93% (n\u0026thinsp;=\u0026thinsp;51) had an antenatal diagnosis of dTGA and had a planned delivered in a tertiary NICU affiliated with our cardiology programme (\u003cb\u003eSupplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eJust under a half of the patients (n\u0026thinsp;=\u0026thinsp;26) required a BAS in the first days of life pre-operatively (mean 1.3 days), of whom 77% (n\u0026thinsp;=\u0026thinsp;20) were ventilated prior to their BAS (\u003cb\u003eSupplementary Figure S2\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eThe mean atrial septal communication size was significantly different in those that required a BAS (2.4mm) to those that did not (4.3mm), p\u0026thinsp;=\u0026thinsp;0.0001 (\u003cb\u003eSupplementary Figure S3a\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eThere was no difference in mean birth weight or gestation between those undergoing a BAS (3.559kg; 9.23 days from due date) or not (3.314kg; 9.03 days from due date), p\u0026thinsp;=\u0026thinsp;0.065 \u0026amp; p\u0026thinsp;=\u0026thinsp;0.914, respectively (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e). Mean pre-operative ICU length of stay was significantly longer for those undergoing a BAS (3.04 days) compared to those that did not require a BAS (1.41 days), p\u0026thinsp;=\u0026thinsp;0.0025.\u003c/p\u003e \u003cp\u003eOf those patients with dTGA that required a BAS compared to those that did not, on DOL#1 they had higher median blood lactate concentrations of 2.6 mmol/L (interquartile range 4.13 mmol/L) V\u0026rsquo;s 2 mmol/L (interquartile range 1.46 mmol/L) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). They were slightly more acidotic (mean pH 7.239 V\u0026rsquo;s 7.29; p\u0026thinsp;=\u0026thinsp;0.0496) but the mean PaC02 values, albeit elevated compared to normal range in both groups, were not statistically different (7.58 kPa V\u0026rsquo;s 6.96 kPa; p\u0026thinsp;=\u0026thinsp;0.28). Bicarbonate values were at the upper limit normal neonatal range in dTGA patients (normal range 13\u0026ndash;22 mEq/L) and not significantly different in those undergoing a BAS or not (19.81 mEq/L V\u0026rsquo;s 21.53 mEq/L; p\u0026thinsp;=\u0026thinsp;0.055).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere was no effect on mean day of ASO surgery between those undergoing BAS or not (5.61 days V\u0026rsquo;s 4.90 days; p\u0026thinsp;=\u0026thinsp;0.21) (\u003cb\u003eTable\u0026nbsp;1, Supplementary Figure S4\u003c/b\u003e). Similarly, post-ASO mean length of ICU stay was not different between the two groups (6.73 days in BAS cohort V\u0026rsquo;s 8.66 days; p\u0026thinsp;=\u0026thinsp;0.073) nor was mean total days of ICU ventilation (7.15 days V\u0026rsquo;s 7.00 days; p\u0026thinsp;=\u0026thinsp;0.883).\u003c/p\u003e \u003cp\u003eIn those patients with dTGA undergoing a BAS, there was a significant reduction in lactate, and PaC02 values from the value obtained on DOL#1 to the values obtained after BAS (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Mean fall in lactate was from 3.79 mmol/L to 2.1 mmol/L (p\u0026thinsp;=\u0026thinsp;0.041); Mean fall in PaC02 was from 7.578 kPa to 5.46 kPa (p\u0026thinsp;=\u0026thinsp;0.0013). There also was a concomitant rise in pH post BAS from a mean of 7.23 to 7.366 (p\u0026thinsp;=\u0026thinsp;0.003). Bicarbonate values showed a non-significant trend towards normalization post-BAS from 19.81 mEq/L to 22.27 mEq/L (p\u0026thinsp;=\u0026thinsp;0.161).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter BAS, there was no significant difference in the atrial septal communication size between those that had undergone a BAS (5.0mm) and those that had not clinically required one (4.3mm), p\u0026thinsp;=\u0026thinsp;0.19 (\u003cb\u003eSupplementary Figure S3a\u003c/b\u003e). The atrial communication diameter was, therefore, significantly augmented BAS (\u003cb\u003eSupplementary Figure S3b\u003c/b\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe National Institute for Cardiovascular Outcomes Research (NICOR) is a UK \u0026amp; Ireland voluntary audit body that has been collecting outcome data on all children in all centres with congenital heart disease at least as far back as 2012 and is a publicly available resource.[2] Of the 65 neonates undergoing cardiac surgery at our institution between 2022\u0026ndash;2023, there were 12 ASO\u0026rsquo;s performed, representing 18.5% of all neonatal cases. Our 10-year average of ASO\u0026rsquo;s is 11.3 per year. Over the same time period across all centres in the UK and Ireland, there were a total 106 ASO\u0026rsquo;s performed, representing 13.6% of all neonatal cardiac surgery. It remains one of the most common complex forms of cyanotic congenital heart disease that cardiac centres care for. Between 2020 to 2023, up to 85.5% of dTGA-IVS cases were prenatally diagnosed, representing a relatively high percentage and a clinical opportunity to deliver best care. Optimising the management of neonates with dTGA from postnatal admission and prior to definitive surgical repair is a central tenet in pre-operative care. Central venous, capillary or arterial blood gas analysis allows the clinician to interrogate the physiological stress the neonate with dTGA is under and what next management steps to make. It assists with decision-making around those who require a balloon atrial septostomy to allow better intra-cardiac mixing.\u003c/p\u003e \u003cp\u003eThe dTGA patients in this study were more acidotic, had elevated lactate levels and had inadequate C02 clearance compared to normal, age-matched reference range values. There were significantly more male infants with dTGA than females with a ratio of 5.87:1. This is a sex-distribution trend reported in the literature but is skewed towards male sex significantly more than reported by others.[11,12] The aetiology of this over-representation of male sex is currently unclear.\u003c/p\u003e \u003cp\u003eIn those dTGA patients that underwent a BAS prior to ASO compared to those that did not, birth weight or gestation played no role, acknowledging that gestation under 36 weeks was an exclusion criteria for this study. There was, however, a statistically significant difference in the DOL#1 lower pH values \u0026amp; higher blood lactates. Interestingly, there was no difference in PaC02 values, the mean of which was elevated in both those undergoing a BAS and those that were not, inferring inadequate C02 clearance with transposition physiology prior to ASO. DOL#1 PaC02 could not, in our study, be used as a discriminator between those subsequently needing a BAS or not. The PaC02 value did trend towards normal range within a day after the BAS and prior to ASO, reflecting ongoing appropriate ICU management in improving C02 clearance. The patients who required a BAS had, not surprisingly, a significantly smaller atrial communication compared to those that did not require a BAS and this highlights the significance of the restrictive atrial communication on resultant metabolic acidosis primarily. The BAS was extremely effective in \u0026lsquo;correcting\u0026rsquo; the size of the atrial communication to the same as those infants who had not required BAS intervention. The concept of reduced effective pulmonary blood flow in dTGA was reported by Shaher et al. in 1964, with resultant elevation in intravascular PaC02 and reduced end-tidal C02.[13,14] Early era cardiac catheterization data reported on PaC02 but the numbers of patients were very small and they were, by-and-large, well outside the neonatal age bracket.[15] Our study provides up-to-date data on PaC02 values in patients with dTGA on admission after birth.\u003c/p\u003e \u003cp\u003eOf those patients who went on to require a BAS prior to ASO, the pH \u0026amp; C02 were already trending towards normal range with appropriate ICU management prior to their BAS, showing the value of concomitant medical efforts at physiological optimisation in addition to the BAS. There was further normalisation of blood gas values immediately after BAS and, again, one day after the BAS. This infers a continuum of a trajectory of recovery that begins after admission to the cardiac centre and results in ongoing optimisation of the patient even up to the day after their BAS. Besides a longer pre-operative ICU occupancy, there was no difference in day of ASO surgery, total days of ventilation or post-operative ICU length-of-stay in those undergoing a BAS compared to those that did not.\u003c/p\u003e \u003cp\u003eOutcome for children with a diagnosis of dTGA is, in the current era, also focused on long-term neurodevelopmental prognosis. This is particularly well-studied internationally in children with dTGA as they have a relatively comparable neonatal and peri-operative course across centres with a low re-intervention rate, generally. Simply having a diagnosis of dTGA alone places a patient at risk of neurodevelopmental delay with the effect of deoxygenated blood re-circulating to the brain for the 9 months of pregnancy. Infants with dTGA have a known delay in brain maturation and significantly smaller brains, by head circumference at birth, than controls.[5,16] Length of ICU stay and hospital stay or need for cardiopulmonary resuscitation at any time point are recognised risk factors for developmental delay in patients with congenital heart disease, especially in those neonates undergoing open heart surgery in the first week of life.[17] Clinical efforts to advance all aspects of pre-operative care will hopefully result in optimal neurodevelopmental outcome in the long-term for infants with dTGA.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLimitations:\u003c/h2\u003e \u003cp\u003eThere were insufficient arterial or capillary blood gas samples pre-BAS (n\u0026thinsp;=\u0026thinsp;7) to contribute to a comparison of Pa02 between those undergoing a BAS or not. Oxygen saturation data was highly variable in individual patients over time and not comparable given the confounding factors of supplemental oxygen and ventilation.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn patients with a diagnosis of simple d-TGA, the significant majority of patients on DOL#1 are acidotic with an elevated lactate and PaC02 in spite of an antenatal diagnosis and planned delivery in an affiliated tertiary neonatal intensive care unit. With current standards of care, only the lactate values and atrial septal communication size are sufficiently discrepant between those requiring a BAS or not to usefully clinically differentiate between the two cohorts. Standard neonatal pre-operative cardiac care begins to normalise blood gas value derangement that continues in the cohort who go on to require a BAS up until and after their catheter-based intervention. Appropriate selection of dTGA patients requiring a BAS has no impact thereafter on day-of-life for ASO, total days of ventilation or post-operative intensive care length-of-stay. Optimising peri-operative care in those patients with dTGA will hopefully preserve neurodevelopmental outcome potential as current management strategies are increasingly more cognisant of these longer-term metrics.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements.\u0026nbsp;\u003c/strong\u003eWe would like to thank and acknowledge the help of our institutional NICOR database managers, Ms. Rita Butler and Ms. Sara Cullen.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFinancial support.\u0026nbsp;\u003c/strong\u003eThis project received no specific grant from any funding agency, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConflicts of interest.\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor Contribution.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sinead Burke and Siobhan Coughlan. The first draft of the manuscript was written by Terence Prendiville and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCentral Statistics Office.\u003c/li\u003e\n\u003cli\u003eNICOR.\u003c/li\u003e\n\u003cli\u003eSantens B, Van De Bruaene A, De Meester P, Gewillig M, Troost E, Claus P, Bogaert J, Budts W (2020) Outcome of arterial switch operation for transposition of the great arteries. A 35-year follow-up study. Int J Cardiol 316: 94-100\u003c/li\u003e\n\u003cli\u003eLiebman J, Cullum L, Belloc NB (1969) Natural history of transpositon of the great arteries. Anatomy and birth and death characteristics. Circulation 40: 237-262\u003c/li\u003e\n\u003cli\u003eHansen T, Henriksen TB, Bach CC, Matthiesen NB (2017) Congenital Heart Defects and Measures of Prenatal Brain Growth: A Systematic Review. Pediatr Neurol 72: 7-18 e11\u003c/li\u003e\n\u003cli\u003eKordopati-Zilou K, Sergentanis T, Pervanidou P, Sofianou-Petraki D, Panoulis K, Vlahos N, Eleftheriades M (2022) Dextro-Transposition of Great Arteries and Neurodevelopmental Outcomes: A Review of the Literature. Children (Basel) 9:\u003c/li\u003e\n\u003cli\u003ePagana KDPEDoNLCWP, Pagana TJ, Pagana TN (2021) Mosby\u0026apos;s Manual of Diagnostic and Laboratory Tests - E-Book, 7th edn. Mosby,\u003c/li\u003e\n\u003cli\u003eMessina Z, Patrick H (2024) Partial Pressure of Carbon Dioxide. StatPearls. Treasure Island (FL),\u003c/li\u003e\n\u003cli\u003eHynes D, Bates S, Loughman A, Klim S, French C, Kelly AM (2015) Arteriovenous blood gas agreement in intensive care patients with varying levels of circulatory compromise: a pilot study. Crit Care Resusc 17: 253-256\u003c/li\u003e\n\u003cli\u003eKelly A (2013) Agreement between Arterial and Venous Blood Gases In Emergency Medical Care: A Systematic Review. Hong Kong Journal of Emergency Medicine 20: 166-171\u003c/li\u003e\n\u003cli\u003eEgbe A, Uppu S, Stroustrup A, Lee S, Ho D, Srivastava S (2014) Incidences and sociodemographics of specific congenital heart diseases in the United States of America: an evaluation of hospital discharge diagnoses. Pediatr Cardiol 35: 975-982\u003c/li\u003e\n\u003cli\u003ePugnaloni F, Felici A, Corno AF, Marino B, Versacci P, Putotto C (2023) Gender differences in congenital heart defects: a narrative review. Transl Pediatr 12: 1753-1764\u003c/li\u003e\n\u003cli\u003eShaher RM (1964) The Haemodynamics of Complete Transposition of the Great Vessels. Br Heart J 26: 343-353\u003c/li\u003e\n\u003cli\u003eJanssen PJ (1976) Capnographic impressions of pulmonary perfusion patterns in patients with congenital heart anomalies. Int Anesthesiol Clin 14: 123-156\u003c/li\u003e\n\u003cli\u003eShaher RM, Kidd L (1967) Acid-base balance in complete transposition of the great vessels. Br Heart J 29: 207-211\u003c/li\u003e\n\u003cli\u003eLicht DJ, Shera DM, Clancy RR, Wernovsky G, Montenegro LM, Nicolson SC, Zimmerman RA, Spray TL, Gaynor JW, Vossough A (2009) Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg 137: 529-536; discussion 536-527\u003c/li\u003e\n\u003cli\u003eMarino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH, Jr., Li J, Smith SE, Bellinger DC, Mahle WT, American Heart Association Congenital Heart Defects Committee CoCDitYCoCN, Stroke C (2012) Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 126: 1143-1172\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Comparative Demographics and Intensive Care Outcome for Neonates with d-Transposition of the Great Arteries undergoing Balloon Atrial Septostomy (BAS) to those that did not.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003eReq. BAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNo BAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep value\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emale (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e24 (92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e23 (79.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight (mean)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e3.559kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e3.314kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestation (days to due date)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-9.2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e-9 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.914\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay (pre-ASO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e3 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1.4 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.002**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay of ASO surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e5.6 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e4.9 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays of invasive ventilation \u0026nbsp;(post-ASO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e7.1 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.882\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay (post-ASO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e6.7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e8.7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 356px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal length of ICU stay (pre- and post-ASO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e9.7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e10.1 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep=0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Arterial Switch Operation, Transposition of the Great Vessels, Lactic acid, balloon atrial septostomy, blood gas","lastPublishedDoi":"10.21203/rs.3.rs-6494276/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6494276/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eBalloon Atrial Septostomy (BAS) is performed in a subset of patients with D-Transposition of the Great Arteries (dTGA). We sought to identify discriminators for those requiring a BAS pre-Arterial Switch Operation (ASO).\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eWe reviewed all patients with simple dTGA between 2019 and 2023 undergoing an ASO at our institution. Clinical outcome variables were compared between those undergoing a BAS or not using paired and unpaired Student's T tests, Ordinary one-way ANOVA, and Mixed-effects analysis.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003e55 patients with dTGA were included (85.7% male), of which 26 required a BAS (mean age 1.3 days). The mean atrial septal communication size was significantly different in those that required a BAS (2.4mm) to those that did not (4.3mm), p\u0026thinsp;=\u0026thinsp;0.0001. Of those patients with dTGA that required a BAS, they had higher mean blood lactates (3.79 mmol/L V\u0026rsquo;s 2.52 mmol/L; p\u0026thinsp;=\u0026thinsp;0.043), were slightly more acidotic (pH 7.239 V\u0026rsquo;s 7.29; p\u0026thinsp;=\u0026thinsp;0.0496) but the mean PaC02 values, albeit elevated compared to normal range in both groups, were not statistically different (7.58 kPa V\u0026rsquo;s 6.96 kPa; p\u0026thinsp;=\u0026thinsp;0.28). There was no effect on day of ASO surgery (5.61 days V\u0026rsquo;s 4.90 days; p\u0026thinsp;=\u0026thinsp;0.21), post-ASO length of ICU stay (6.73 days in BAS cohort V\u0026rsquo;s 8.66 days; p\u0026thinsp;=\u0026thinsp;0.072) or total days of ICU ventilation (7.15 days V\u0026rsquo;s 7.00 days; p\u0026thinsp;=\u0026thinsp;0.882).\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eOnly the lactate values and atrial septal communication size are significant discriminators between those requiring a BAS or not with no impact thereafter on day-of-life for ASO, total days of ventilation or post-operative intensive care length-of-stay.\u003c/p\u003e","manuscriptTitle":"Balloon atrial septostomy in d-Transposition of the Great Arteries-predictive discriminators for intervention","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 01:53:17","doi":"10.21203/rs.3.rs-6494276/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fa136c49-ba6e-4251-965c-0add54931cd0","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-19T23:53:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 01:53:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6494276","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6494276","identity":"rs-6494276","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}