The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology.

A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the “final” Residual Lesion Score.

The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the “final” Residual Lesion Score.

Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network’s Residual Lesion Score study.

To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications.

Retrospective cohort study of children aged 0–18 years hospitalised at a tertiary children’s hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis.

Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications.

Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

CHD is an important phenotypic feature of chromosome 22q11.2 copy number variants. Biventricular repair is usually possible, however there are rare reports of patients with chromosome 22q copy number variants and functional single ventricle cardiac disease.

This is a single centre retrospective review of patients with chromosome 22q copy number variants who underwent staged single ventricle reconstructive surgery between 1 July, 1984 and 31 December, 2020.

Seventeen patients met inclusion criteria. The most common diagnosis was hypoplastic left heart syndrome (n = 8) and vascular anomalies were present in 13 patients. A microdeletion of the chromosome 22 A-D low-copy repeat was present in 13 patients, and the remaining had a duplication. About half of the patients had documented craniofacial abnormalities and/or hypocalcaemia, and developmental delay was very common. Fifteen patients had a Norwood operation, 10 patients had a superior cavopulmonary anastomosis, and 7 patients had a Fontan. Two patients had cardiac transplantation after Fontan. Overall survival is 64% at 1 year, and 58% at 5 and 10 years. Most deaths occurred following Norwood operation (n = 5).

CHD necessitating single ventricle reconstruction associated with chromosome 22q copy number variants is not common, but typically occurs as a variant of hypoplastic left heart syndrome with the usual cytogenetic microdeletion. The most common neonatal surgical intervention performed is the Norwood, where most of the mortality burden occurs. Associated anomalies and medical issues may cause additional morbidity after cardiac surgery, but survival is similar to infants with other types of single ventricle disease.

The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.

Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.

Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.

Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury.

Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score.

Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0–4) versus 0 (0–0), p = 0.02).

Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.

Veno-arterial extracorporeal membrane oxygenation is frequently used in patients with cardiac disease. We evaluated short-term outcomes and identified factors associated with hospital mortality in cardiac patients supported with veno-arterial extracorporeal membrane oxygenation.

A retrospective review of patients supported with veno-arterial extracorporeal membrane oxygenation at a university-affiliated children’s hospital was performed.

A total of 253 patients with cardiac disease managed with extracorporeal membrane oxygenation were identified; survival to discharge was 48%, which significantly improved from 39% in an earlier era (1995–2001) (p=0.01). Patients were categorised into surgical versus non-surgical groups on the basis of whether they had undergone cardiac surgery before or not, respectively. The most common indication for extracorporeal membrane oxygenation was extracorporeal cardiopulmonary resuscitation: 96 (51%) in the surgical group and 45 (68%) in the non-surgical group. In a multiple covariate analysis, single-ventricle physiology (p=0.01), duration of extracorporeal membrane oxygenation (p<0.01), and length of hospital stay (p=0.03) were associated with hospital mortality. Weekend or night shift cannulation was associated with mortality in non-surgical patients (p=0.05).

We report improvement in survival compared with an earlier era in cardiac patients supported with extracorporeal membrane oxygenation. Single-ventricle physiology continues to negatively impact survival, along with evidence of organ dysfunction during extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, and length of stay.

We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.

This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.

Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).

These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.

Pulmonary lymphangiectasia associated with hypoplastic left heart syndrome with an intact or restrictive atrial septum may result from increased left atrial pressure, and is associated with worse outcomes following staged reconstruction due to lung dysfunction and significant hypoxaemia. Our objective was to characterise the incidence of pulmonary lymphangiectasia in cases of early mortality following stage 1 reconstructions.

An institutional cardiac surgical database was retrospectively searched for patients who died within 30 days following a stage 1 reconstruction between 1 January, 1984 and 31 December, 2013. During that period, 1669 stage 1 procedures were performed. Autopsy lung specimens were reviewed by a paediatric pathologist. Patients who died of suspected technical issues were excluded.

A total of 54 patients were included, and of these seven cases (8.5%) of pulmonary lymphangiectasia were identified. The mean estimated gestational age was 38.2±2.4 weeks, and the mean birth weight was 3.0±0.6 kg. The median interval between surgery and death was 1 day (with a range from 0 to 18 days). The atrial septum was intact in one patient (14.3%), restrictive in three patients (42.9%), and unrestrictive in three patients (42.9%).

Pulmonary lymphangiectasia may develop in hypoplastic left heart syndrome with or without a restrictive atrial septum. As standard prenatal diagnostic evaluations and treatment methods for pulmonary lymphangiectasia are limited, this may be an important contributor to early and late mortality following stage 1 reconstruction for hypoplastic left heart syndrome.

With improvements in early survival following congenital heart surgery, it has become increasingly important to understand longer-term outcomes; however, routine collection of these data is challenging and remains very limited. We describe the development and initial results of a collaborative programme incorporating standardised longitudinal follow-up into usual care at the Children’s Hospital of Philadelphia (CHOP) and University of Michigan (UM).

We included children undergoing benchmark operations of the Society of Thoracic Surgeons. Considerations regarding personnel, patient/parent engagement, funding, regulatory issues, and annual data collection are described, and initial follow-up rates are reported.

The present analysis included 1737 eligible patients undergoing surgery at CHOP from January 2007 to December 2014 and 887 UM patients from January 2010 to December 2014. Overall, follow-up data, of any type, were obtained from 90.8% of patients at CHOP (median follow-up 4.3 years, 92.2% survival) and 98.3% at UM (median follow-up 2.8 years, 92.7% survival), with similar rates across operations and institutions. Most patients lost to follow-up at CHOP had undergone surgery before 2010. Standardised questionnaires assessing burden of disease/quality of life were completed by 80.2% (CHOP) and 78.4% (UM) via phone follow-up. In subsequent pilot testing of an automated e-mail system, 53.4% of eligible patients completed the follow-up questionnaire through this system.

Standardised follow-up data can be obtained on the majority of children undergoing benchmark operations. Ongoing efforts to support automated electronic systems and integration with registry data may reduce resource needs, facilitate expansion across centres, and support multi-centre efforts to understand and improve long-term outcomes in this population.

Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.

Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.

We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.

Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.