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.

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.

Activating PPARα prevents post-ischemic contractile dysfunction in hypertrophied neonatal hearts.

RATIONALE: Post-ischemic contractile dysfunction is a contributor to morbidity and mortality after the surgical correction of congenital heart defects in neonatal patients. Pre-existing hypertrophy in the newborn heart can exacerbate these ischemic injuries, which may partly be due to a decreased energy supply to the heart resulting from low fatty acid ß-oxidation rates. OBJECTIVE: We determined whether stimulating fatty acid ß-oxidation with GW7647, a peroxisome proliferator-activated receptor-α (PPARα) activator, would improve cardiac energy production and post-ischemic functional recovery in neonatal rabbit hearts subjected to volume overload-induced cardiac hypertrophy. METHODS AND RESULTS: Volume-overload cardiac hypertrophy was produced in 7-day-old rabbits via an aorto-caval shunt, after which, the rabbits were treated with or without GW7647 (3 mg/kg per day) for 14 days. Biventricular working hearts were subjected to 35 minutes of aerobic perfusion, 25 minutes of global no-flow ischemia, and 30 minutes of aerobic reperfusion. GW7647 treatment did not prevent the development of cardiac hypertrophy, but did prevent the decline in left ventricular ejection fraction in vivo. GW7647 treatment increased cardiac fatty acid ß-oxidation rates before and after ischemia, which resulted in a significant increase in overall ATP production and an improved in vitro post-ischemic functional recovery. A decrease in post-ischemic proton production and endoplasmic reticulum stress, as well as an activation of sarcoplasmic reticulum calcium ATPase isoform 2 and citrate synthase, was evident in GW7647-treated hearts. CONCLUSIONS: Stimulating fatty acid ß-oxidation in neonatal hearts may present a novel cardioprotective intervention to limit post-ischemic contractile dysfunction.

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.

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.

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.

Endothelin axis is upregulated in human and rat right ventricular hypertrophy.

RATIONALE: Right ventricular (RV) function is the most important determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). Endothelin (ET)-1 receptor antagonists (ERAs) are approved therapies for PAH. It is not known whether ERAs have effects on the RV, in addition to their vasodilating/antiproliferative effects in pulmonary arteries. OBJECTIVE: We hypothesized that the ET axis is upregulated in RV hypertrophy (RVH) and that ERAs have direct effects on the RV myocardium. METHODS AND RESULTS: RV myocardial samples from 34 patients with RVH were compared with 16 nonhypertrophied RV samples, and from rats with normal RV versus RVH attributable to PAH. Confocal immunohistochemistry showed that RVH myocardial ET type A (but not type B) receptor and ET-1 protein levels were increased compared with the nonhypertrophied RVs and positively correlated with the degree of RVH (RV thickness/body surface area; r(2)=0.838 and r(2)=0.818, respectively; P<0.01). These results were recapitulated in the rat model. In modified Langendorff perfusions, ERAs (BQ-123 and bosentan 10(-7,-6,-5) mol/L) decreased contractility in the hypertrophied, but not normal RV, in a dose-dependent manner (P<0.01). CONCLUSIONS: Patients and rats with PAH have an upregulation of the myocardial ET axis in RVH. This might be a compensatory mechanism to preserve RV contractility, as the afterload increases. ERAs use might potentially worsen RV function, and this could explain some of the peripheral edema noted clinically with these agents. Further studies are required to evaluate the effects of ERAs on the RV in patients with RVH and PAH.

Refractory cardiogenic shock in a patient with ß-thalassemia major requiring mechanical circulatory support: Case report and literature review.

Iron overload cardiomyopathy secondary to ß-thalassemia major is a potentially reversible condition managed with chelation and medical hemodynamic support, as bridge-to-recovery or transplant. We describe our experience, and challenges faced, in a pediatric patient with iron overload cardiomyopathy secondary to ß-thalassemia major, requiring biventricular MCS.

Mechanical circulatory support in univentricular hearts: current management.

Failing single-ventricle patients have now come into focus as the next cohort where improvement in outcomes for mechanical circulatory support can be realized. There is a paucity of published patient reports or management protocols in this patient population. Increased interest exists in finding answers of how to bridge these patients to transplant. We review the current literature and describe our approach to the patient with univentricular heart needing mechanical circulatory support.

Neurocognitive outcomes at kindergarten entry after surgical repair of total anomalous pulmonary venous connection in early infancy.

The objective of this study was to determine neurocognitive outcomes 4.5 years after surgery for TAPVC in infancy and predictors of these outcomes. A cohort having TAPVC repair at age ≤6 weeks between 1998 and 2007 were followed by the Complex Pediatric Therapies Follow-up Program at 4.5 years. Outcomes include mortality, full-scale intelligence quotient (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), visual motor integration (VMI), and general adaptive composite of the Adaptive Behavior Assessment System (GAC). There were 51 infants with simple TAPVC [4 year mortality 4 (8%)], and 16 with complex TAPVC [4 year mortality 7 (44%)], hazard ratio (HR) 7.02 (95% CI 2.05-24.07, p = 0.002). Of the 47 survivors after simple TAPVC, FSIQ (SD) was 92 (17), VIQ 92 (17), PIQ 94 (15), VMI 92 (15), and GAC 92 (15). Independent predictors of neurocognitive outcome included father's socioeconomic status, mother's years of schooling, gender, post-operative base deficit, and deep hypothermic circulatory arrest (DHCA) time. Complex TAPVC was associated on univariate analysis only with PIQ [81.9 (10.2) vs. 93.6 (15.4); p = 0.012] and FSIQ [80.7 (10.1) vs. 92.0 (17.7); p = 0.017]. Original peoples accounted for 25/51 (49%) of simple and 3/16 (19%) of complex TAPVC. Original peoples race was associated with 4-year mortality [HR 6.85 (95% CI 2.15, 21.76, p = 0.001)]. Survivors of TAPVC repair in early infancy have encouraging neurocognitive outcomes. Few independent predictors of neurocognitive outcome were found, with post-operative acidosis and DHCA time being potentially modifiable. Original peoples account for an unexpected proportion of patients (42%) and have a higher mortality.

The development of a congenital heart programme quality dashboard to promote transparent reporting of outcomes.

In 2001, the Institute of Medicine identified healthcare transparency as a necessity for re-designing a quality healthcare system; however, despite widespread calls for publicly available transparent data, the goal remains elusive. The transparent reporting of outcome data and the results of congenital heart surgery is critical to inform patients and families who have both the wish and the ability to choose where care is provided. Indeed, in an era where data and means of communication of data have never been easier, the paucity of transparent data reporting is paradoxical. We describe the development of a quality dashboard used to inform staff, patients, and families about the outcomes of congenital heart surgery at the Stollery Children's Hospital.

Health-related quality of life in pediatric cardiac extracorporeal life support survivors.

OBJECTIVE: To assess the health-related quality of life of children who received cardiac extracorporeal life support. We hypothesized that extracorporeal life support survivors have lower health-related quality-of-life scores when compared with a healthy sample, with children with chronic conditions, and with children who had surgery for congenital heart disease and did not receive extracorporeal life support. DESIGN: Prospective cohort study. SETTING: Stollery Children's Hospital and Complex Pediatric Therapies Follow-up Program clinics. PATIENTS: Children less than or 5 years old with diagnosis of cardiac disease (congenital or acquired) who received extracorporeal life support at the Stollery Children's Hospital from 1999 to 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Health-related quality of life was assessed using the PedsQL 4.0 Generic Core Scales completed by the children's parents at the time of follow-up. Forty-seven cardiac extracorporeal life support survivors had their health-related quality of life assessed at a median age of 4 years. Compared with a healthy sample, children who received venoarterial extracorporeal life support have significantly lower PedsQL (64.9 vs 82.2; p < 0.0001). The PedsQL scores of children who received extracorporeal life support were also significantly lower than those of children with chronic health conditions (64.9 vs 73.1; p = 0.007). Compared with children with congenital heart disease who underwent cardiac surgery early in infancy and who did not receive extracorporeal life support, extracorporeal life support survivors had significantly lower PedsQL scores (64.9 vs 81.1; p < 0.0001). Multiple linear regression analysis found an independent association between both higher inotrope score in the first 24 hours of extracorporeal life support and longer hospital length of stay, with lower PedsQL scores. CONCLUSIONS: Pediatric cardiac extracorporeal life support survivors showed lower health-related quality of life than healthy children, children with chronic conditions, and children with congenital heart disease who did not receive extracorporeal life support.

Neurotoxicity of sedative and analgesia drugs in young infants with congenital heart disease: 4-year follow-up.

OBJECTIVES/AIM: To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurocognitive and functional outcomes. BACKGROUND: Some animal models suggest neurotoxic effects of anesthetic drugs on the developing brain; however, potential human effects are unknown. Whether these results can be extrapolated to humans is unknown. METHODS/MATERIALS: Prospective follow-up project of all infants ≤6 weeks old having surgery for congenital heart disease between 04/03 and 12/06. Demographic, perioperative, and sedation/analgesia variables were collected. Outcomes at kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II. Multivariable linear regression was used to identify predictor variables. RESULTS: From 135 infants who underwent heart surgery, 19 died, 17 were excluded, 8 were lost to follow-up, leaving 91 children for analysis. Multiple linear regression found days on chloral hydrate [3.5 (3.7) days] was associated with lower performance intelligence quotient (PIQ) (Effect size -1.03; 95% CI -1.96, -0.10; P = 0.03), and cumulative dose [54.2 (60.3) mg·kg(-1) ] of benzodiazepines was associated with lower VMI scores (Effect size -0.07; 95% CI -0.12, -0.01; P = 0.026). No other associations were found between sedation/analgesia variables and full-scale IQ, PIQ, Verbal IQ, VMI, or GAC. CONCLUSION: Assessment of this cohort at kindergarten age found a small statistically significant association between days on chloral hydrate and PIQ, and benzodiazepine cumulative dose and lower VMI. No other association between sedation/analgesia drugs and outcomes was found.

Comparison of two surgical techniques for complete atrioventricular septal defect repair using two- and three-dimensional echocardiography.

Different surgical techniques for complete atrioventricular septal defect (CAVSD) repair have been described, with the double-patch technique being most frequently employed. More recently a newer technique using a modified single-patch repair has been advocated. We hypothesized that the modified single-patch technique would result in an increased incidence of the two major post-repair comorbidities, namely, distortion of the left AV valve (LAVV) leaflets and narrowing of the left-ventricular outflow tract (LVOT). We studied 14 patients with CAVSD who underwent either traditional double-patch technique [group 1 (n = 7)] or modified single-patch technique [group 2 (n = 7)]. Preoperative and immediate postoperative two-dimensional (2D) echocardiograms, as well as follow-up 2D and three-dimensional (3D) studies, were reviewed. For group 1, the median age at repair was 4.1 months with a median duration from surgical repair and last echocardiogram of 44 months. For group 2, the median age at repair was 3 months with a median duration from surgical repair and last echocardiogram of 28 months. The two groups had similar demographics and ventricular septal defect size before surgery. For the LAVV, no significant difference was observed with respect to LAVV annulus size, tenting height, and the size of the vena contracta. Furthermore, there was no significant difference in the 2D echocardiographic areas and volumes of the LVOT between pre-repair and immediate post-repair studies for both groups. At the last evaluation, although there had been growth of the LVOT in both groups, no significant difference between areas and volumes were observed. Areas of the LVOT measured by 3D echocardiography on the final study showed no significant statistical difference between both groups. There was good correlation of the areas measured by 2D and 3D echocardiography within each group. In this small group, modified single-patch technique does not appear to tether the LAVV or promote an increase in regurgitation. In the short term, LVOT growth is unaffected, and the repair does not promote LVOT obstruction. 3D echocardiography is useful for area measurements of the LVOT and showed good correlation with areas measured by assumption of the LVOT shape as determined using 2D techniques.

Health-related quality of life experienced by children with chromosomal abnormalities and congenital heart defects.

Long-term outcomes are fundamental in advising parents about the potential future of their children with congenital heart disease (CHD). No published reports have described the health-related quality of life (HRQL) experienced by children with chromosomal abnormalities who had surgery in early infancy for CHD. A study was undertaken to assess HRQL among children with chromosomal abnormalities and CHD. The authors hypothesized that these children have a worse HRQL than healthy children or a cohort of children matched for CHD diagnosis. Infants with chromosomal abnormalities undergoing cardiac surgery for CHD at 6 weeks of age or younger at the Stollery Children's Hospital between July 2000 and June 2005 were included in the study. The HRQL of these infants was assessed using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales completed by their parents at a 4-year follow-up evaluation. The study compared the scores for 16 children with normative data. The children with chromosomal abnormalities and CHD had significantly lower mean total PedsQL (71.3 vs. 87.3; p < 0.0001), Psychosocial Summary (70.3 vs. 86.1; p < 0.0001), and Physical Summary (74.3 vs. 89.2; p = 0.0006) scores. Compared with the matched children, those with chromosomal abnormalities had a significantly lower median total PedsQL (75.0 vs. 84.6; p = 0.03), Physical Summary (79.5 vs. 96.9; p = 0.007), and School Functioning (68.5 vs. 83.0; p = 0.03) scores. A better understanding of the mechanisms and determinants of HRQL in these children has the potential to yield important implications for clinical practice including clarity for treatment decision making as well as determination of targeted supports and services to meet the needs of these children and their families differentially.

Risk factors for and outcomes of acute kidney injury in neonates undergoing complex cardiac surgery.

OBJECTIVE: To characterize the epidemiology of and identify risk factors for neonatal cardiac surgery-associated acute kidney injury (CS-AKI) and determine its impact on clinical outcomes. STUDY DESIGN: Using secondary analysis of data from an ongoing multiprovincial prospective cohort study, we studied 264 neonates undergoing complex cardiac repair. CS-AKI was defined based on the Acute Kidney Injury Network (AKIN) definition. We used regression modeling and survival analysis (adjusting for covariates) to evaluate associations. RESULTS: CS-AKI occurred in 64% of the neonates in our study cohort. Lower age, longer cardiopulmonary bypass time, hypothermic circulatory arrest, type of repair, lower preoperative serum creatinine (SCr) level, lower gestational age, and preoperative ventilation were independent risk factors for developing CS-AKI. Neonates with CS-AKI had longer times to extubation, intensive care discharge, and hospital discharge, after adjusting for covariates. Mortality was significantly increased in neonates with AKIN stage 2 or higher CS-AKI. The neonates with CS-AKI had a lower z-score for height at 2-year follow-up and were seen by more specialists. CONCLUSION: Neonatal CS-AKI is common and independently predicts important clinical outcomes, including mortality. Many risk factors are similar to those in older children, but some are unique to neonates. The observation that lower baseline SCr predicts CS-AKI merits further study. The AKIN definition, based on preoperative SCr value, is a reasonable method for defining CS-AKI in neonates. Many previous studies of CS-AKI have excluded neonates; we suggest that future intervention studies on approaches to reducing CS-AKI incidence and improving outcomes should include neonates.

Longer term survival of a child with autosomal recessive cutis laxa due to a mutation in FBLN4.

Autosomal recessive cutis laxa (ARCL) is a clinically and genetically heterogeneous group of disorders characterized by loose, inelastic skin and variable systemic involvement and severity. Mutations in the FBLN4 gene are associated with ARCL1B. Fibulin-4 is important in elastic fiber formation and smooth muscle cell differentiation. We describe herein an 8-year-old boy who presented with severe aortic root dilatation and arterial tortuosity at 1 year of age which required surgical repair. His parents were consanguineous and there was a family history of three brothers who died early in life with an unknown type of connective tissue disorder in the 1960s. Both parents of the patient reported here were related to these three boys. We used a homozygosity mapping strategy with a 900K SNP array and identified FBLN4 as a candidate gene in an extended region of homozygosity. We sequenced this gene in the patient and identified a homozygous non-synonymous mutation at c.376G>A (p.Glu126Lys) in exon 5 that was predicted to be damaging. ARCL1B has most typically been associated with early demise but our report suggests that long-term survival is possible. With this longer term survival we are learning more about the natural history of this disorder, which includes baroreceptor reflex failure and low bone mineral density in this patient.

Right ventricular and tricuspid valve remodeling after bidirectional cavopulmonary anastomosis.

BACKGROUND: There are few investigations of the changes in tricuspid valve (TV) and right ventricular (RV) morphology following bidirectional cavopulmonary anastomosis (BCPA). METHODS AND RESULTS: The 2-D echocardiograms of 35 children (male, n=23; female, n=12; median age, 6 months; range, 3-10 months) with hypoplastic left heart syndrome, 1 month before and after BCPA performed between 2005 and 2011, were retrospectively reviewed. Patients who underwent TV repair at BCPA were excluded. From the 4-chamber view, the coaptation length, vena contracta width and RV end-diastolic area before and after BCPA were measured and indexed to surface area. The severity of tricuspid regurgitation was graded qualitatively. After BCPA, RV end-diastolic area decreased from 2,951 ± 584 to 2,580 ± 591 mm(2)/m(2) (P<0.001). The coaptation length of the anterior leaflet (8.8 ± 5.8 vs. 11.0 ± 6.2 mm/m(2), P=0.0014) and of the septal leaflet (13.5 ± 5.3 vs. 15.8 ± 5.4mm/m(2), P=0.0072) increased after BCPA. The vena contracta width decreased (5.8 ± 4.9 vs. 4.3 ± 4.2 mm/m(2), P=0.035), although there was no change in tricuspid regurgitation grade after BCPC (1.4 ± 0.7 vs. 1.4 ± 0.9, P=0.234). CONCLUSIONS: In children with hypoplastic left heart syndrome after BCPA, the coaptation length of the anterior and septal leaflets of the TV improved concomitantly with vena contracta width and RV end-diastolic area despite unchanged tricuspid regurgitation grade. This suggests that favorable RV and TV remodeling accompanies the reduction in RV volume load following BCPA.

Safety of Berlin Heart EXCOR pump changes in the PICU.

OBJECTIVE: To describe whether Berlin Heart EXCOR Pediatric pump changes in the ICU are associated with infection, hemodynamic and ventilatory instability, and neurologic injury. DESIGN: Retrospective, descriptive chart review. SETTING: PICU in a quaternary care children's hospital. PATIENTS: Eight patients were supported on Berlin Heart EXCOR Pediatric pumps due to cardiomyopathy or cardiogenic shock. Two patients were supported with left ventricular assist devices, five had biventricular assist devices, and one required a univentricular assist device. INTERVENTIONS: A team of cardiac surgeons, pediatric intensivists, and operating room nurses conducted sixteen pump changes in the pediatric intensive care unit. Patients were monitored for deleterious effects for 5 days following the change. MEASUREMENT AND MAIN RESULTS: For the first 48 hrs following the EXCOR pump change, no patients exhibited acute neurologic deficits or escalation of hemodynamic or ventilatory support. Over the first 5 days, no blood cultures were positive for microbes. CONCLUSIONS: Berlin Heart EXCOR Pediatric pump changes in the pediatric intensive care unit appear to be a safe procedure when conducted by a highly specialized team.