Insights from 3D Echocardiography in Hypoplastic Left Heart Syndrome Patients Undergoing TV Repair.

BACKGROUND: Tricuspid regurgitation (TR) in hypoplastic left heart syndrome (HLHS) is associated with morbidity and mortality. TR mechanisms and the impact of tricuspid valve repair (TVR) are unclear. We examined HLHS TR mechanisms, TVR's impact on tricuspid valve (TV), and features of poor TVR durability. METHODS: We retrospectively compared 35 HLHS TVR cases and 35 age/stage-matched HLHS controls who do not undergo TVR. Pre-operative 3-dimensional echocardiography (3DE) assessed overall TV morphology (prolapse, normal, tethered), leaflet morphology, vena contracta area, and TR location. Two-dimensional echocardiography measured TV annulus diameter, RV fractional area change (RVFAC), sphericity, and TR grade at three time points (pre-op, early post-op, and latest follow-up). RESULTS: Pre-op, TVR group, and controls had no difference in age, RV function or shape, or TV dimension. TVR group most commonly had anterior leaflet prolapse followed by septal leaflet prolapse or tethering. TR jet arises centrally (63%) and anterior septally (26%). Posterior annuloplasty (69%), commissuroplasty (37%), and leaflet repair (37%) were surgical techniques commonly performed. At early post-op, TR grade and TV annulus decreased. At latest follow-up, TV annulus remained reduced; however, 50% had significant TR. 25% required TV reoperation. Larger vena contracta at TVR was associated with significant TR. CONCLUSION: HLHS patients undergoing TVR had more anterior leaflet prolapse and central TR. While TVR initially reduces annular size and TR grade, 50% redevelop significant TR despite maintained annular reduction. The association of greater TR severity prior to repair with post-op recurrence raises the consideration for earlier repair of TR in HLHS patients.

Echocardiographic Screening for Postoperative Pericardial Effusion in Children.

Pericardial effusion (PE) after cardiac surgery can be life threatening without timely detection, and the optimal screening method is unknown. We sought to evaluate the role of a surveillance echocardiogram on postoperative day 10 (± 2), determine the incidence of postoperative PE, and identify risk factors. We conducted a retrospective cohort study including all pediatric patients who underwent open heart surgery at a single institution over a 7-month period. To identify risk factors for PE, medical records of patients with PE detected within 6 weeks after surgery (cases) were compared with patients without PE (controls). Of 203 patients, 52 (26%) had PE within 6 weeks; 42 (81%) were trivial-small and 10 (19%) were moderate-large. Twenty-nine (56%) were first detected within 7 days post-operatively, including all cases developing cardiac tamponade (n = 3). An echocardiogram was done 10 (± 2) days post-operatively in 41/52 cases, of which 12/41 (29%) did not have a PE at this time, 24/41 (59%) had a trivial-small PE, and 5/41(12%) had a moderate-large PE; 2 of the latter had no prior detected PE. Closure of an atrial septal defect had the highest incidence of PE (42%). PE cases were associated with postoperative nasopharyngeal detection of a respiratory virus (OR 3.8, p = 0.03). In conclusion, the majority of PE cases were detected within 7 days post-operatively, including all cases subsequently developing cardiac tamponade. Day 10 echocardiography infrequently detected a moderate or large effusion that had previously gone undiagnosed. A positive perioperative nasopharyngeal aspirate for a respiratory virus was associated with postoperative PE.

Tricuspid Regurgitation in Hypoplastic Left Heart Syndrome: Three-Dimensional Echocardiography Provides Additional Information in Describing Jet Location.

BACKGROUND: Twenty-five percent of patients with hypoplastic left heart syndrome (HLHS) require tricuspid valve (TV) repair. The location of tricuspid regurgitation (TR) is important in determining the type of repair performed. Studies using three-dimensional echocardiography (3DE) have reported a high incidence of error on two-dimensional echocardiography (2DE) for the identification of TV leaflets. The aim of this study was to compare assessment of TR on 3DE and 2DE in patients with HLHS (jet location, TR grade, and reproducibility). METHODS: A retrospective, single-center review was performed. Fifty-six patients with HLHS with available two-dimensional and three-dimensional echocardiograms, and mild or greater TR, were included. TR location, grade, vena contracta area, and TV annular diameter were measured on 2DE and 3DE. Reproducibility was assessed by blinded reviewers. RESULTS: Three-dimensional echocardiography identified the primary jet location as central (57%) followed by anteroseptal (36%). There was poor agreement between findings on 3DE and 2DE for jet location (κ = 0.05; 95 CI, -0.08 to 0.19). Interobserver reproducibility for location on 3DE was excellent (κ = 0.8), whereas reproducibility for 2DE was poor (κ = 0.32). The most common jet location pre-Norwood and pre-Glenn was central (70%), whereas pre-Fontan and post-Fontan, jet location was central (45%) and anteroseptal (48%). Vena contracta area on 2DE correlated moderately with vena contracta area on 3DE (r = 0.60, P < .0001). TV annular diameters on 2DE and 3DE for lateral (r = 0.85, P < .0001) and anteroposterior (r = 0.74, P = .001) dimensions were strongly correlated. CONCLUSIONS: In children with HLHS, assessment of TR location on 2DE had poor agreement with assessment on 3DE and was poorly reproducible. In contrast, TR jet location on 3DE was highly reproducible. Pre-Glenn, a central TR jet was the most common, while post-Glenn, central and anteroseptal locations were equal, highlighting the importance of preoperative identification of TR jet location in patients with HLHS.

Fetal Umbilical Arterial Pulsatility Correlates With 2-Year Growth and Neurodevelopmental Outcomes in Congenital Heart Disease.

BACKGROUND: Children with congenital heart disease (CHD) are at risk of adverse long-term neurodevelopmental outcomes, believed to be, in part, secondary to prenatal insults. Placental pathology and altered fetal middle cerebral arterial (MCA) flow suggestive of brain sparing have been documented in fetal CHD. In the present study we investigated the relationship between MCA and umbilical arterial (UA) flow patterns in fetal transposition of the great arteries (d-TGA) and hypoplastic left heart syndrome (HLHS) and growth and 2-year neurodevelopmental outcomes. METHODS: We included children with d-TGA and HLHS who had third-trimester fetal echocardiograms between 2004 and 2014, at which time umbilical artery (UA) and MCA pulsatility indices (PIs) were measured, and who underwent 2-year growth and neurodevelopmental assessments. RESULTS: We identified 24 children with d-TGA and 36 with HLHS. Mean age at fetal echocardiography was 33.8 ± 3.5 weeks. At 2-year follow-up, head circumference z score (standard deviation [SD]) was -0.09 (1.07) and 0.17 (1.7) for the d-TGA and HLHS groups, respectively. Bayley III mean (SD) cognitive, language, and motor scores were 97.7 (10.8), 94.7 (13.4), and 98.6 (8.6) for the d-TGA group and 90.3 (13.9), 87.2 (17.5), and 85.3 (16.2) for the HLHS group. On multivariate linear regression analysis, UA-PI was associated (effect sizes [95% CI]) with length (-1.45 [-2.7, -0.17], P = 0.027), weight (-1.46 [-2.6 to -0.30], P = 0.015) and cognitive scores (-14.86 [-29.95 to 0.23], P = 0.05) at 2 years of age. MCA PI showed no statistically significant correlation. CONCLUSIONS: In fetal d-TGA and HLHS, a higher UA-PI in the third trimester, suggestive of placental insufficiency-but not MCA-PI-is associated with worse 2-year growth and neurodevelopment.

Survival, Neurocognitive, and Functional Outcomes After Completion of Staged Surgical Palliation in a Cohort of Patients With Hypoplastic Left Heart Syndrome.

Background Management of patients with hypoplastic left heart syndrome has benefited from advancements in medical and surgical care. Outcomes have improved, although survival and long-term functional and cognitive deficits remain a concern. Methods and Results This is a cohort study of all consecutive patients with hypoplastic left heart syndrome undergoing surgical palliation at a single center. We aimed to examine demographic and perioperative factors from each surgical stage for their association with survival and neurocognitive outcomes. A total of 117 consecutive patients from 1996 to 2010 underwent surgical palliation. Seventy patients (60%) survived to the Fontan stage and 68 patients (58%) survived to undergo neurocognitive assessment at a mean (SD) age of 56.6 months (6.4 months). Full-scale, performance, and verbal intelligence quotient, as well as visual-motor integration mean (SD) scores were 86.7 (16.1), 86.3 (15.8), 88.8 (17.2), and 83.2 (14.8), respectively. On multivariable analysis, older age at Fontan, sepsis peri-Norwood, lowest arterial partial pressure of oxygen postbidirectional cavopulmonary anastomosis, and presence of neuromotor disability pre-Fontan were strongly associated with lower scores for all intelligence quotient domains. Older age at Fontan and sepsis peri-Norwood remained associated with lower scores for all intelligence quotient domains in a subgroup analysis excluding patients with disability pre-Fontan or with chromosomal abnormalities. Conclusions Older age at Fontan and sepsis are among independent predictors of poor neurocognitive outcomes for patients with hypoplastic left heart syndrome. Further studies are required to identify the appropriate age range for Fontan completion, balancing a lower risk of acute and long-term hemodynamic complications while optimizing long-term neurocognitive outcomes.

A Unique Intracardiac Shunt: Identifying Complex Anatomy in Reoperative Adult Congenital Heart Disease.

Adult patients with repaired congenital heart disease are presenting with previously unseen types of residual lesions and consequences of prior repair. Patients with d-transposition of the great arteries repaired with atrial switch operations are returning with dysrhythmias and atrioventricular valve disease requiring intervention. We present the challenging case of a young adult with a residual shunt identified on preoperative three-dimensional transthoracic echocardiography, the precise anatomy of which was only characterized intraoperatively.

Avoiding Furosemide Ototoxicity Associated With Single-Ventricle Repair in Young Infants.

OBJECTIVE: To reduce bilateral delayed-onset progressive sensory permanent hearing loss using a systems-wide quality improvement project with adherence to best practice for the administration of furosemide. DESIGN: Prospective cohort study with regular audiologic follow-up assessment of survivors both before and after a 2007-2008 quality improvement practice change. SETTING: The referral center in Western Canada for complex cardiac surgery, with comprehensive multidisciplinary follow-up by the Complex Pediatric Therapies Follow-up Program. PATIENTS: All consecutive patients having single-ventricle palliative cardiac surgery at age 6 weeks old or younger. INTERVENTIONS: A 2007-2008 quality improvement practice change consisted of a Parenteral Drug Monograph revision indicating slow IV administration of furosemide, an educational program, and an evaluation. MEASUREMENTS AND MAIN RESULTS: The outcome measure was the prevalence of permanent hearing loss by 4 years old. Firth multiple logistic regression compared pre (1996-2008) to post (2008-2012) practice change occurrence of permanent hearing loss, adjusting for confounding variables, including all hospital days, extracorporeal membrane oxygenation, cardiopulmonary bypass time, age at first surgery, dialysis, and sepsis. From 1996 to 2012, 259 infants had single-ventricle palliative surgery at age 6 weeks old or younger, with 173 (64%) surviving to age 4 years. Of survivors, 106 (61%) were male, age at surgery was 11.6 days (9.0 d), and total hospitalization days by age 4 years were 64 (42); 18 (10%) had cardiopulmonary resuscitation and 38 (22%) had sepsis at any time. All 173 (100%) had 4-year follow-up. Pre- to postpractice change permanent hearing loss dropped from 17/100 (17%) to 0/73 (0%) of survivors. On Firth multiple logistic regression, the only variable statistically associated with permanent hearing loss was the pre- to postpractice change time period (odds ratio, 0.03; 95% CI, 0-0.35; p = 0.001). CONCLUSIONS: A practice change to ensure slow IV administration of furosemide eliminated permanent hearing loss. Centers caring for critically ill infants, particularly those with single-ventricle anatomy or hypoxia, should review their drug administration guidelines and adhere to best practice for administration of IV furosemide.

Acetylation contributes to hypertrophy-caused maturational delay of cardiac energy metabolism.

A dramatic increase in cardiac fatty acid oxidation occurs following birth. However, cardiac hypertrophy secondary to congenital heart diseases (CHDs) delays this process, thereby decreasing cardiac energetic capacity and function. Cardiac lysine acetylation is involved in modulating fatty acid oxidation. We thus investigated what effect cardiac hypertrophy has on protein acetylation during maturation. Eighty-four right ventricular biopsies were collected from CHD patients and stratified according to age and the absence (n = 44) or presence of hypertrophy (n = 40). A maturational increase in protein acetylation was evident in nonhypertrophied hearts but not in hypertrophied hearts. The fatty acid ß-oxidation enzymes, long-chain acyl CoA dehydrogenase (LCAD) and ß-hydroxyacyl CoA dehydrogenase (ßHAD), were hyperacetylated and their activities positively correlated with their acetylation after birth in nonhypertrophied hearts but not hypertrophied hearts. In line with this, decreased cardiac fatty acid oxidation and reduced acetylation of LCAD and ßHAD occurred in newborn rabbits subjected to cardiac hypertrophy due to an aortocaval shunt. Silencing the mRNA of general control of amino acid synthesis 5-like protein 1 reduced acetylation of LCAD and ßHAD as well as fatty acid oxidation rates in cardiomyocytes. Thus, hypertrophy in CHDs prevents the postnatal increase in myocardial acetylation, resulting in a delayed maturation of cardiac fatty acid oxidation.

Neurocognitive outcomes after heart transplantation in early childhood.

BACKGROUND: Children requiring heart transplantation (HTx) for congenital heart disease (CHD) or failing anatomically normal hearts (CMP) face different challenges pre-HTx. We compared the neurocognitive capabilities in pre-school-age children receiving HTx for CHD vs CMP and determined factors predicting outcomes. METHODS: Data were collected within a prospective multi-provincial project from children who underwent HTx ≤4 years of age between 1999 and 2011. At age 54 ± 3 months, we obtained scores from the Wechsler Preschool and Primary Scales of Intelligence for full-scale intelligence quotient (FSIQ) verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ), and from the Beery-Buktenica Developmental Test for visual-motor integration (VMI). Possible predictive factors were collected prospectively from transplant listing. RESULTS: Of the 76 patients included in the study, 61 survived to assessment, 2 were lost to follow-up and 4 were excluded for genetic disorders or heart-lung transplant. The CHD patients (n = 32) had significantly more previous surgeries, more severe kidney injuries, more days on ventilator and in intensive care, broader human leukocyte antigen (HLA) sensitization, longer cardipulmonary bypass (CPB) times and higher inotropic scores than CMP patients (n = 23). Mean IQ scores for the HTx children were below population norms and significantly lower in children with CHD. Intellectual disability (FSIQ <70) was more common in the CHD group (p = 0.036). The lower VMI in CHD patients approached significance. Lower FSIQ and VMI were independently associated with higher pre-HTx creatinine and lactate, longer stay in intensive care and lower socioeconomic status. CONCLUSIONS: Children post-HTx showed IQ and VMI scores within the borderline to low-average range, with CHD children ranging significantly lower. Low scores are associated with a more difficult pre- and peri-transplant course. Careful follow-up is required to warrant early detection of deficits and introduction of interventions and supportive measures.

Hypoplastic Left Heart Syndrome Is Not a Predictor of Worse Intermediate Mortality Post Fontan.

BACKGROUND: An increasing proportion of those living with single ventricle physiology have hypoplastic left heart syndrome (HLHS). Our objective was to assess the association between HLHS and outcomes post Fontan operation. METHODS: All pediatric patients who underwent a Fontan procedure at the University of Alberta between 1996 and 2016 were included. Follow-up clinical data collected included early and late surgical or catheter reintervention, echocardiography, and long-term transplant-free survival. Characteristics were compared between those with and without HLHS, and the association between outcomes and HLHS were assessed. RESULTS: A total of 320 children (median age 3.3 years, interquartile range 2.8 to 3.9 years; 121 [43.4%] female) underwent a Fontan procedure over the course of the study. Nearly one third of subjects had HLHS (107, 33.4%). Patients with HLHS were more likely to have abnormal ventricular function (19.6% versus 7.0%, p = 0.003) and worse than mild atrioventricular valve (AVV) regurgitation (23.4 versus 9.2%, p = 0.001) preoperatively. HLHS was not predictive of in-hospital Fontan failure (odds ratio 0.82, 95% CI 0.28, 2.39), late reintervention (hazard ratio [HR] 1.08, 95% CI 0.66, 1.76), or transplant-free survival (HR 1.58, 95% CI 0.72, 3.44). Subjects with HLHS were more likely to have more than mild AVV regurgitation (31.6% versus 13.3%, p = 0.028) and abnormal ventricular function (29.8% versus 10.7%, p < 0.0001) at late follow-up. CONCLUSIONS: Patients with HLHS who survive to the Fontan procedure do no worse with the operation than those with other anatomy. Given worse late ventricular function and AVV regurgitation, equivalent survival may not persist throughout a patient's life course.

Post-operative Outcomes in Children Undergoing Fontan Palliation in a Regionalized Surgical System.

Evidence suggests that outcomes in pediatric cardiac surgery are improved by consolidating care into centers of excellence. Our objective was to determine if outcomes are equivalent in patients across a large regional referral base, or if patients from centers without on-site surgery are at a disadvantage. Since 1996, all pediatric cardiac surgery has been offered at one of two centers within the region assessed, with the majority being performed at Stollery Children's Hospital. All patients who underwent a Fontan between 1996 and 2016 were included. Follow-up data including length of stay (LOS), repeat surgical interventions, and transplant-free survival were acquired for each patient. The association between post-operative outcomes and home center was assessed using Kaplan-Meier survival analysis and Cox proportional Hazards models. 320 children (median age 3.3 years, IQR 2.8-4.0) were included; 120 (37.5%) had the surgical center as their home center. Cardiac anatomy was hypoplastic left heart syndrome in 107 (33.4%) subjects. Median LOS was 11 days (IQR, 8-17), and there were 8 in-hospital deaths. There were 17 deaths and 11 transplants over the course of follow-up. Five-year transplant-free survival was 92.5%. There was no difference in hospital re-intervention, late re-intervention, or survival by referral center (all p > 0.05). In multivariable analysis, home center was not predictive of either LOS (R 2 = -0.40, p = 0.87) or transplant-free survival (1.52, 95%CI 0.66, 3.54). In children with complex congenital heart disease, a regionalized surgical care model achieves good outcomes, which do not differ according to a patient's home base.

Glutaraldehyde Treatment of Allografts and Aortic Outcomes Post-Norwood: Challenging Surgical Decision.

BACKGROUND: Glutaraldehyde (GA) treatment of allografts used for arch reconstruction prevents the immunologic sensitization that occurs with untreated allografts, but its use may cause tissue changes that predispose to recurrent obstruction. The objective was to determine whether GA treatment of allografts used in Norwood procedures increases the risk of recurrent aortic obstruction. METHODS: All infants who underwent a Norwood procedure between 2000 and 2015 were included. Cryopreserved pulmonary allografts were used for all arch reconstructions; starting in 2005 all were treated with GA before use. Complete follow-up was obtained, including survival, transplantation, and all repeat procedures. Competing risks analyses were used to assess for differences in aortic reintervention over time. RESULTS: Two hundred six infants (132 male) were included. There were 60 deaths and 14 transplantations; 5-year transplantation-free survival was 71.9%. GA treatment of patches (n = 142, 68.9%) was not predictive of death (hazard ratio [HR] 1.38, 95% confidence interval [CI]: 0.61 to 3.08). Fifty-five patients had at least one aortic reintervention and 31 patients (15.0%) required surgical aortic reintervention. At 1-year, freedom from all aortic reintervention was similar between patients with and without treated patches, but freedom from surgical aortic reintervention was lower in the treated group (87.6% versus 95.3%, p = 0.0256). GA treatment was not associated with the combined end point of catheter-based or surgical reintervention but was associated with specific need for surgical reintervention (HR 4.05, 95% CI: 1.19 to 13.77). CONCLUSIONS: GA treatment is associated with increased late surgical aortic reintervention. The advantages of decreased sensitization with GA treatment need to be balanced against the risk of aortic reobstruction.

Hypoplastic Left Heart Syndrome is not Associated with Worse Clinical or Neurodevelopmental Outcomes Than Other Cardiac Pathologies After the Norwood-Sano Operation.

There is evidence to suggest that patients undergoing a Norwood for non-HLHS anatomy may have lower mortality than classic HLHS, but differences in neurodevelopmental outcome have not been assessed. Our objective was to compare survival and neurodevelopmental outcome during the same surgical era in a large, well-described cohort. All subjects who underwent a Norwood-Sano operation between 2005 and 2014 were included. Follow-up clinical, neurological, and developmental data were obtained from the Western Canadian Complex Pediatric Therapies Follow-up Program database. Developmental outcomes were assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development (Bayley-III). Survival was assessed using Kaplan-Meier analysis. Baseline characteristics, survival, and neurodevelopmental outcomes were compared between those with HLHS and those with non-HLHS anatomy (non-HLHS). The study comprised 126 infants (75 male), 87 of whom had HLHS. Five-year survival was the same for subjects with HLHS and those with non-HLHS (HLHS 71.8%, non-HLHS 76.9%; p = 0.592). Ninety-three patients underwent neurodevelopmental assessment including Bayley-III scores. The overall mean cognitive composite score was 91.5 (SD 14.6), language score was 86.6 (SD 16.7) and overall mean motor composite score was 85.8 (SD 14.5); being lower than the American normative population mean score of 100 (SD 15) for each (p-value for each comparison, <0.0001). None of the cognitive, language, or motor scores differed between those with HLHS and non-HLHS (all p > 0.05). In the generalized linear models, dominant right ventricle anatomy (present in 117 (93%) of patients) was predictive of lower language and motor scores. Comparative analysis of the HLHS and non-HLHS groups undergoing single ventricle palliation including a Norwood-Sano, during the same era, showed comparable 2-year survival and neurodevelopmental outcomes.

An Unusual Cause of Hemopericardium 22 Years After a Fontan Procedure.

Late tamponade after cardiac operations is rare but reasonably well described. We report a case of exceedingly late tamponade secondary to a spontaneous coronary bleed 22 years after a Fontan operation, which was repaired with catheter intervention.

Neurologic, Neurocognitive, and Functional Outcomes in Children Under 6 Years Treated with the Berlin Heart Excor Ventricular Assist Device.

The objective of this study is to describe the neurologic, neurocognitive, and functional outcomes of children aged under 6 years supported on the Berlin Heart EXCOR ventricular assist device (VAD) followed in the Complex Pediatric Therapies Follow-up Program (CPTFP). Sixteen patients were prospectively followed through this longitudinal, developmental program. The patients were evaluated with neurologic physical examination. Intelligence quotients (IQ) and functional outcome scores (ABAS-II scores) were obtained. Neuroimaging reports from before, during, and after VAD implantation were retrospectively reviewed for reported brain injury (BI). Twelve patients (75%) had neuroimaging documented BI at some point in their life (i.e., before, during, or after VAD support). Five patients (31%) had neuroimaging evidence of acute BI incurred while on the VAD. The high overall number of patients with neuroimaging documented BI at any point in their life illustrates that the risk for BI also exists outside the window of VAD support. Patients with abnormal neurologic physical examination at follow-up had lower IQ and ABAS-II scores compared with patients with normal neurologic physical examination (mean full-scale IQ 66.9 vs. 95.0, p = 0.001; mean ABAS-II 66.3 vs. 94.2, p < 0.001).

Suprasternal Approach Aortopexy Relieves Tracheal Compression After Nikaidoh Procedure.

Tracheal obstruction secondary to vascular and soft tissue compression, after Nikaidoh procedure, can effectively be managed with aortopexy from a suprasternal incision.

Early childhood language outcomes after arterial switch operation: a prospective cohort study.

BACKGROUND: Developmental and language outcomes at 2 years of age of children who had arterial switch operation (ASO) for transposition of the great arteries 2004-2010 are described. METHODS: In this prospective cohort study, 91/98 (93 %) children who underwent ASO were assessed at 2 years of age with the Bayley Scales of Infant & Toddler Development-3rd Edition. Outcomes were compared by patient and perioperative variables using bivariate and multivariate regression analyses to identify predictors of language delay. RESULTS: Infants without ventricular septal defect (VSD) (n = 60) were more likely to be outborn (73 vs 58 %, p = 0.038), require septostomy (80 vs 58 %, p = 0.026), have a shorter cross clamp time (min) (62.7 vs 73.0, p = 0.019), and a lower day 1 post-operative plasma lactate (mmol/L) (3.9 vs 4.8, p = 0.010). There were no differences in cognitive, motor and language outcomes based on presence of a VSD. Language delay (<85) of 29 % was 1.8 times higher than the normative sample; risk factors for this in multivariate analyses included <12 years of maternal education (AOR 19.3, 95 % CI 2.5-148.0) and cross-clamp time ≥70 min (AOR 14.5, 95 % CI 3.1-68.5). Maternal education <12 years was associated with lower Language Composite Scores (-20.2, 95 % CI -32.3 to -9.1). CONCLUSIONS: Outcomes at 2 years of age in children who undergo ASO are comparable to the normative sample with the exception of language. There is a risk of language delay for which maternal education and cross-clamp duration are predictors. These findings suggest that focused post-operative early language interventions could be considered.

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart.

Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid ß-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and ß-hydroxyacyl-CoA dehydrogenase (ß-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid ß-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and ß-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation.

Clinical and Functional Developmental Outcomes in Neonates Undergoing Truncus Arteriosus Repair: A Cohort Study.

BACKGROUND: Truncus arteriosus (TA) is an uncommon congenital cardiac lesion that portends an exceedingly poor prognosis if not repaired. The objective of this study was to assess the clinical and developmental outcomes in a prospective cohort of patients who underwent TA repair. METHODS: All patients who underwent a TA repair between 1996 and 2012 were included. Follow-up clinical, neurologic, and developmental data were obtained from the Western Canadian Complex Pediatric Therapies Follow-up Program database. Functional developmental outcomes were assessed at 21.1 ± 2.5 months of age with the Adaptive Behavior Assessment System-II, General Adaptive Composite (GAC) score. Survival and outcomes were compared between those with and without chromosomal abnormalities (CA). Survival and freedom from reintervention were assessed by Kaplan-Meier analysis. RESULTS: The study comprised 36 infants (19 male). CA was identified in 13, with 22q11.2 deletion in 10 patients. Patients underwent TA repair at a median age of 10 days; 5 patients underwent concomitant interrupted arch repair. There were 8 deaths, 2 of which occurred in the hospital. The 5-year survival was 79.4%. Survival was similar between those with and without CA. At 5 years, freedom from reoperation was 77.2%. The mean GAC was higher in the patients without CA (93.6 ± 12.8 vs 76.1 ± 13.1, p = 0.0016). CONCLUSIONS: Patients with surgically repaired TA continue to have significant postoperative mortality. Reoperation and cardiac catheterization are eventualities for a quarter of patients in the first 5 years of life. Functional developmental outcome in patients without CA is good, although it is significantly impaired in those with CA.