Development of the Residual Lesion Score for congenital heart surgery: the RAND Delphi methodology.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Family Function, Quality of Life, and Well-Being in Parents of Infants With Hypoplastic Left Heart Syndrome.

Survival for hypoplastic left heart syndrome (HLHS) has improved dramatically. Little is known about early family function, quality of life (QOL), or well-being/adjustment for parents of infants with HLHS. Parent/family outcomes over time, predictors, and differences in 143 mothers and 72 fathers were examined. Parents reported better family function compared with published norms, but 26% experienced family dysfunction. QOL and well-being were significantly lower than adult norms. QOL scores generally declined over time, whereas self-reported well-being improved. Responses from mothers and fathers showed different trends, with mothers having worse scores on most measures and at most time points. Being a single parent was a risk factor for poorer family function, but not for lower individual QOL or well-being. Family characteristics, stress, and coping skills were predictive of outcomes. Parents' psychosocial responses to the challenges of life with infants with HLHS change over time. Individually tailored psychosocial support is needed.

Longitudinal study of anthropometry in Fontan survivors: Pediatric Heart Network Fontan study.

BACKGROUND: Growth abnormalities in single-ventricle survivors may reduce quality of life (QoL) and exercise capacity. METHODS: This multicenter, longitudinal analysis evaluated changes in height and body mass index (BMI) compared to population norms and their relationship to mortality, ventricular morphology, QoL, and exercise capacity in the Pediatric Heart Network Fontan studies. RESULTS: Fontan 1 (F1) included 546 participants (12 ±â€¯3.4 years); Fontan 2 (F2), 427 (19 ±â€¯3.4 years); and Fontan 3 (F3), 362 (21 ±â€¯3.5 years), with ~60% male at each time point. Height z-score was -0.67 ±â€¯-1.27, -0.60 ±â€¯1.34, and- 0.43 ±â€¯1.14 at F1-F3, lower compared to norms at all time points (P ≤ .001). BMI z-score was similar to population norms. Compared to survivors, participants who died had lower height z-score (P ≤ .001). Participants with dominant right ventricle (n = 112) had lower height z-score (P ≤ .004) compared to dominant left (n = 186) or mixed (n = 64) ventricular morphologies. Higher height z-score was associated with higher Pediatric Quality of Life Inventory for the total score (slope = 2.82 ±â€¯0.52; P ≤ .001). Increase in height z-score (F1 to F3) was associated with increased oxygen consumption (slope = 2.61 ±â€¯1.08; P = .02), whereas, for participants >20 years old, an increase in BMI (F1 to F3) was associated with a decrease in oxygen consumption (slope = -1.25 ±â€¯0.33; P ≤ .001). CONCLUSIONS: Fontan survivors, especially those with right ventricular morphology, are shorter when compared to the normal population but have similar BMI. Shorter stature was associated with worse survival. An increase in height z-score over the course of the study was associated with better QoL and exercise capacity; an increase in BMI was associated with worse exercise capacity.

Lessons learned in the use of clinical registry data in a multi-centre prospective study: the Pediatric Heart Network Residual Lesion Score Study.

BACKGROUND: Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology. OBJECTIVES: We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders' perspectives, and provide recommendations to guide future studies using this methodology. METHODS: The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff. RESULTS: Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes. CONCLUSIONS: Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.

Early Neurodevelopmental Outcomes in Children Supported with ECMO for Cardiac Indications.

Extracorporeal membrane oxygenation (ECMO) is lifesaving for many critically ill children with congenital heart disease (CHD). However, limited information is available about their ensuing neurodevelopmental (ND) outcomes. We describe early ND outcomes in a cohort of children supported with ECMO for cardiac indications. Twenty-eight patients supported with ECMO at age < 36 months underwent later ND testing at 12-42 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). ND scores were compared with normative means and with ND outcomes of a matched cohort of 79 children with CHD undergoing cardiac surgery but not requiring ECMO support. Risk factors for worse ND outcomes were identified using multivariable linear regression models. Cardiac ECMO patients had ND scores at least one standard deviation below the normative mean in the gross motor (61%), language (43%), and cognitive (29%) domains of the Bayley-III. Cardiac ECMO patients had lower scores on the motor, language, and cognitive domains as compared to the matched non-ECMO group and clinically important (1/2 SD) differences in the motor domain persisted after controlling for primary caregiver education and number of cardiac catheterizations. Risk factors of worse ND outcomes among cardiac ECMO patients in more than one developmental domain included older age at first cannulation and more cardiac catheterization and cardiac surgical procedures prior to ND assessment. Overall, children supported on ECMO for cardiac indications have significant developmental delays and warrant close ND follow-up.

Longitudinal Associations between Neurodevelopment and Psychosocial Health Status in Patients with Repaired D-Transposition of the Great Arteries.

OBJECTIVE: To examine associations between measurements of neurodevelopment and psychosocial health status at age 8 and 16 years in patients with repaired dextro-transposition of the great arteries. STUDY DESIGN: In the 16-year follow-up of the Boston Circulatory Arrest Study, 137 parents completed the Child Health Questionnaire-Parent Form-50, of whom 135 had completed the Child Health Questionnaire-Parent Form-50 when their child was age 8 years. Psychosocial and physical summary scores were used to assess change in health status from age 8 to 16 years. A comprehensive battery of neurodevelopmental testing was performed at ages 8 and 16 years to examine associations with adolescent health status. RESULTS: Lower psychosocial summary scores of 16 year old subjects with dextro-transposition of the great arteries were highly associated with numerous concurrent domains of neurodevelopmental function, most notably with higher (worse) scores on the Conners' Attention Deficit Hyperactivity Disorder/Diagnostic and Statistical Manual-4th Edition Scales (parent: r = -0.62, P < .001; adolescent: r = -0.43, P < .001) and the Behavior Rating Inventory of Executive Function Global Executive Composite (parent: r = -0.66, P < .001; adolescent: r = -0.39, P < .001). Psychosocial and physical summary scores tracked from ages 8 to 16 years (r = 0.44 and 0.47, respectively, P < .001 for each). Higher (worse) scores of multiple attention measures at age 8 years predicted worse psychosocial summary scores at age 16 years. CONCLUSIONS: Attention deficits at age 8 years were highly predictive of worse psychosocial health status in adolescence. Further studies are needed to assess whether treatment of childhood attention deficit hyperactivity disorder could improve adolescent well-being.

Neurodevelopmental assessment of infants with congenital heart disease in the early postoperative period.

OBJECTIVE: Mortality rates for children with congenital heart disease (CHD) have significantly declined, resulting in a growing population with associated neurodevelopmental disabilities. American Heart Association guidelines recommend systematic developmental screening for children with CHD. The present study describes results of inpatient newborn neurodevelopmental assessment of infants after open heart surgery. OUTCOME MEASURES: We evaluated the neurodevelopment of a convenience sample of high-risk infants following cardiac surgery but before hospital discharge using an adaptation of the Newborn Behavioral Observation. Factor analysis examined relationships among assessment items and consolidated them into domains of development. RESULTS: We assessed 237 infants at a median of 11 days (interquartile range [IQR]: 7-19 days) after cardiac surgery and median corrected age of 21 days (IQR: 13-33 days). Autonomic regulation was minimally stressed or well organized in 14% of infants. Upper and lower muscle tone was appropriate in 33% and 35%, respectively. Appropriate response to social stimulation ranged between 7% and 12% depending on task, and state regulation was well organized in 14%. The vast majority (87%) required enhanced examiner facilitation for participation. Factor analyses of assessment items aligned into four domains of development (autonomic, motor, oral motor, and attention organization). CONCLUSION: At discharge, postoperative infants with CHD had impairments in autonomic, motor, attention, and state regulation following cardiac surgery. Findings highlight the challenges faced by children with CHD relative to healthy peers, suggesting that neurodevelopmental follow-up and intervention should begin early in infancy.

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial.

BACKGROUND: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. METHODS: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. RESULTS: Transplant-free survival for the RVPAS versus modified Blalock-Taussig shunt groups did not differ at 6 years (64% versus 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS versus modified Blalock-Taussig shunt treatment effect had nonproportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48-0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86-2.17; P=0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33-1.74; P=0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P<0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00-3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures. CONCLUSIONS: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock-Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Utilisation of early intervention services in young children with hypoplastic left heart syndrome.

OBJECTIVE: Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services. METHODS: Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations. RESULTS: Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52-69%) were not receiving services at any age assessed, whereas 20-32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1-3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18-43% of children at ages 3 and 4. CONCLUSION: Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.

Reproducibility of Left Ventricular Dimension Versus Area Versus Volume Measurements in Pediatric Patients With Dilated Cardiomyopathy.

BACKGROUND: Multiple echocardiographic methods are used to measure left ventricular size and function. Clinical management is based on individual evaluations and longitudinal trends. The Pediatric Heart Network VVV study (Ventricular Volume Variability) in pediatric patients with dilated cardiomyopathy has reported reproducibility of several of these measures, and how disease state and number of beats impact their reproducibility. In this study, we investigated the impact of observer and sonographer variation on reproducibility of dimension, area, and volume methods to determine the best method for both individual and sequential evaluations. METHODS AND RESULTS: In 8 centers, echocardiograms were obtained on 169 patients prospectively. During the same visit, 2 different sonographers acquired the same imaging protocol on each patient. Each acquisition was analyzed by 2 different observers; first observer analyzed the first acquisition twice. Intraobserver, interobserver, interacquisition, and interobserver-acquisition (different observers and different acquisition) reproducibility were assessed on measurements of left ventricular end-diastolic dimension, area, and volume. Left ventricular shortening fraction, ejection fraction, mass, and fractional area change were calculated. Percent difference was calculated as (interobservation difference/mean)×100. Interobserver reproducibility for both acquisitions was better for both volume and dimension measurements (P≤0.002) compared with area measurements, whereas intraobserver, interacquisition (for both observers), and interobserver-acquisition reproducibilities (for both observer-acquisition sets) were best for volume measurements (P≤0.01). Overall, interobserver-acquisition percent differences were significantly higher than interobserver and interacquisition percent differences (P<0.001). CONCLUSIONS: In pediatric patients with dilated cardiomyopathy, compared with dimension and area methods, left ventricular measurements by volume method have the best reproducibility in settings where assessment is not performed by the same personnel. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00123071.

Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome.

OBJECTIVE: To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. STUDY DESIGN: Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. RESULTS: Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P < .001) and similar to published reports in patients with hypoplastic left heart syndrome without fetal intervention; scores in the single ventricular versus biventricular group were 97 ± 19 vs 89 ± 14, respectively (P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life (P = .001) and, when forced into the model, biventricular status (P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. CONCLUSION: Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes.

Completeness and Accuracy of Local Clinical Registry Data for Children Undergoing Heart Surgery.

BACKGROUND: Data routinely captured in clinical registries may be leveraged to enhance efficiency of prospective research. The quality of registry data for this purpose has not been studied, however. We evaluated the completeness and accuracy of perioperative data within congenital heart centers' local surgical registries. METHODS: Within 12 Pediatric Heart Network (PHN) sites, we evaluated 31 perioperative variables (and their subcategories, totaling 113 unique fields) collected via sites' local clinical registries for submission to The Society of Thoracic Surgeons Database, compared with chart review by PHN research coordinators. Both used standard STS definitions. Data were collected on 10 subjects for 2 to 5 procedures/site and adjudicated by the study team. Completeness and accuracy (agreement of registry data with medical record review by PHN coordinator, adjudicated by the study team) were evaluated. RESULTS: A total of 56,500 data elements were collected on 500 subjects. With regard to data completeness, 3.1% of data elements were missing from the registry, 0.6% from coordinator-collected data, and 0.4% from both. Overall, registry data accuracy was 98%. In total, 94.7% of data elements were both complete/non-missing and accurate within the registry, although there was variation across data fields and sites. Mean total time for coordinator chart review per site was 49.1 hours versus 7.0 hours for registry query. CONCLUSIONS: This study suggests that existing surgical registry data constitute a complete, accurate, and efficient information source for prospective research. Variability across data fields and sites also suggest areas for improvement in some areas of data quality.

Factors affecting Fontan length of stay: Results from the Single Ventricle Reconstruction trial.

BACKGROUND: In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation. METHODS: Fontan postoperative course was ascertained from medical record review. Cox proportional hazards modeling was used to identify factors associated with LOS. RESULTS: Of 327 subjects who underwent Fontan, 323 were analyzed (1 death, 1 biventricular repair, 2 with missing data). Median age and weight at Fontan were 2.8 years (interquartile range [IQR]: 2.3, 3.4) and 12.7 kg (IQR: 11.4, 14.1), respectively. Fontan type was extracardiac in 55% and lateral tunnel in 45%; 87% were fenestrated. The RVPAS and MBTS subjects had similar LOS (median 11 days [IQR: 9, 18] vs 10 days [IQR: 9, 13]; P = .23). Independent risk factors for longer LOS were treatment center (P < .01), LOS at stage II (hazard ratio [HR] 1.02 for each additional day; P < .01), and pre-Fontan complications (HR 1.03 for each additional complication; P = .04). Use of deep hypothermic circulatory arrest at Fontan (HR 0.64; P = .02) was independently associated with shorter LOS. When center was excluded from the model, pre-Fontan complications and use of circulatory arrest were no longer significant; instead, older age at stage II (HR 1.08 for each additional month; P = .01) predicted longer LOS. In 254 subjects who had a pre-Fontan echocardiogram, at least moderate tricuspid regurgitation was independently associated with longer LOS, both with center (HR 1.72; P < .01) and without center in the model (HR 1.49; P = .02). CONCLUSIONS: In this multicenter prospective cohort of subjects with HLHS, Norwood shunt type was not associated with Fontan LOS. Rather, global measures of earlier medical complexity indicate greater likelihood of longer LOS after the Fontan operation.

Neuropsychological Status and Structural Brain Imaging in Adolescents With Single Ventricle Who Underwent the Fontan Procedure.

BACKGROUND: Few studies have described the neuropsychological outcomes and frequency of structural brain or genetic abnormalities in adolescents with single ventricle who underwent the Fontan procedure. METHODS AND RESULTS: In a cross-sectional, single-center study, we enrolled 156 subjects with single ventricle, mean age 14.5±2.9 years, who had undergone the Fontan procedure. Scores in the entire cohort on a standard battery of neuropsychological tests were compared with those of normative populations or to those of a group of 111 locally recruited healthy adolescents. They also underwent brain magnetic resonance imaging and were evaluated by a clinical geneticist. Genetic abnormalities were definite in 16 subjects (10%) and possible in 49 subjects (31%). Mean Full-Scale IQ was 91.6±16.8, mean Reading Composite score was 91.9±17.2, and mean Mathematics Composite score was 92.0±22.9, each significantly lower than the population means of 100±15. Mean scores on other neuropsychological tests were similarly lower than population norms. In multivariable models, risk factors for worse neuropsychological outcomes were longer total support and circulatory arrest duration at first operation, presence of a genetic abnormality, more operations and operative complications, more catheterization complications, and seizure history. The frequency of any abnormality on magnetic resonance imaging was 11 times higher among Fontan adolescents than referents (66% versus 6%); 19 (13%) patients had evidence of a stroke, previously undiagnosed in 7 patients (40%). CONCLUSIONS: The neuropsychological deficits and high frequencies of structural brain abnormalities in adolescents who underwent the Fontan procedure highlight the need for research on interventions to improve the long-term outcomes in this high-risk group.

Predictors of health-related quality of life in adolescents with tetralogy of Fallot.

OBJECTIVE: To assess health-related quality of life (HRQoL) of adolescents with repaired tetralogy of Fallot (TOF) and whether impairments in HRQoL domains are associated with neurocognitive and medical factors. STUDY DESIGN: Parents of subjects with TOF and healthy referents 13-16 years of age completed the Child Health Questionnaire-Parent Form 50, generating psychosocial (PsS) and physical (PhS) health summary scores. Adolescents completed the Child Health Questionnaire-Child Form 87 and concurrent in-person neurocognitive testing. We analyzed relationships of PsS and PhS scores with neurocognitive performance and medical factors. RESULTS: Compared with referents (n = 85), adolescents with TOF without a genetic diagnosis (n = 66) had lower PsS (50.9 ± 9.4 vs 57.2 ± 4.2, P < .001) and PhS scores (49.4 ± 9.5 vs 55.8 ± 4.9; P < .001). Compared with a normative sample, these adolescents with TOF had similar PsS scores (P = .52) but significantly lower PhS scores (P = .01). Within adolescents with TOF without genetic disorders, lower PsS scores were highly associated with worse neurocognitive measures, particularly the parent-reported Behavior Rating Inventory of Executive Function composite (r = -0.66, P < .001) and Parent Conners' attention deficit-hyperactivity disorder Index T score (r = -0.54, P < .001), whereas associations of PhS scores with neurocognitive measures were weaker. CONCLUSIONS: Psychosocial health status in adolescents with TOF without genetic disorders was worse than in healthy referents without risk factors for brain injury but similar to a normative sample; physical health status was worse in these adolescents than in either comparison group. Within these subjects with TOF, worse psychosocial health status was most highly associated with concurrent executive dysfunction and attention deficit-hyperactivity disorder. Optimizing HRQoL constitutes another indication for attention to neurodevelopment in children with congenital heart disease.

Adolescents with tetralogy of Fallot: neuropsychological assessment and structural brain imaging.

BACKGROUND: Few data are available on the neuropsychological, behavioural, or structural brain imaging outcomes in adolescents who underwent corrective surgery in infancy for tetralogy of Fallot. METHODS: In this single-centre cross-sectional study, we enrolled 91 adolescents (13-16 years old) with tetralogy of Fallot and 87 referent subjects. Assessments included tests of academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition, as well as brain magnetic resonance imaging. RESULTS: Genetic abnormalities or syndromes were present in 25% of tetralogy of Fallot patients, who had markedly greater neuropsychological morbidities than did patients without a syndrome. However, even patients without a syndrome performed significantly worse than the referent group or population norms in all of the neuropsychological domains assessed. In multivariable regression in those without a genetic/phenotypic syndrome, the strongest predictors of adverse late neurodevelopmental outcomes included a greater number of complications at the first operation, more total surgical complications across all operations, and occurrence of post-operative seizures. The presence of at least one abnormality on structural magnetic resonance imaging was more frequent in tetralogy of Fallot patients than the referent group (42% versus 8%). CONCLUSIONS: Adolescents with tetralogy of Fallot are at increased neurodevelopmental risk and would benefit from ongoing surveillance and educational supports even after childhood.

Technical performance score is associated with outcomes after the Norwood procedure.

OBJECTIVES: The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial. METHODS: We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization. Multivariable regression examined the association of the TPS with interval to first extubation, Norwood length of stay, death or transplantation, unplanned postdischarge reinterventions, and neurodevelopment at 14 months old. RESULTS: Of 549 patients undergoing a Norwood procedure, 356 (65%) had an echocardiogram adequate to assess atrial septal restriction or arch obstruction or an unplanned reintervention, enabling calculation of the TPS. On multivariable regression, adjusting for preoperative variables, a better TPS was an independent predictor of a shorter interval to first extubation (P=.019), better transplant-free survival before Norwood discharge (P<.001; odds ratio, 9.1 for inadequate vs optimal), shorter hospital length of stay (P<.001), fewer unplanned reinterventions between Norwood discharge and stage II (P=.004), and a higher Bayley II psychomotor development index at 14 months (P=.031). The TPS was not associated with transplant-free survival after Norwood discharge, unplanned reinterventions after stage II, or the Bayley II mental development index at 14 months. CONCLUSIONS: TPS is an independent predictor of important outcomes after Norwood and could serve as a tool for quality improvement.

Longitudinal assessment of growth in hypoplastic left heart syndrome: results from the single ventricle reconstruction trial.

BACKGROUND: We sought to characterize growth between birth and age 3 years in infants with hypoplastic left heart syndrome who underwent the Norwood procedure. METHODS AND RESULTS: We performed a secondary analysis using the Single Ventricle Reconstruction Trial database after excluding patients <37 weeks gestation (N=498). We determined length-for-age z score (LAZ) and weight-for-age z score (WAZ) at birth and age 3 years and change in WAZ over 4 clinically relevant time periods. We identified correlates of change in WAZ and LAZ using multivariable linear regression with bootstrapping. Mean WAZ and LAZ were below average relative to the general population at birth (P<0.001, P=0.05, respectively) and age 3 years (P<0.001 each). The largest decrease in WAZ occurred between birth and Norwood discharge; the greatest gain occurred between stage II and 14 months. At age 3 years, WAZ and LAZ were <-2 in 6% and 18%, respectively. Factors associated with change in WAZ differed among time periods. Shunt type was associated with change in WAZ only in the Norwood discharge to stage II period; subjects with a Blalock-Taussig shunt had a greater decline in WAZ than those with a right ventricle-pulmonary artery shunt (P=0.002). CONCLUSIONS: WAZ changed over time and the predictors of change in WAZ varied among time periods. By age 3 years, subjects remained small and three times as many children were short as were underweight (>2 SD below normal). Failure to find consistent risk factors supports the strategy of tailoring nutritional therapies to patient- and stage-specific targets. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/. Unique identifier: NCT00115934.

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. METHODS AND RESULTS: In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. CONCLUSIONS: Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543309.

Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial.

BACKGROUND: In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. METHODS AND RESULTS: Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80). CONCLUSIONS: By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.