Effect of patient factors, center, and era on Fontan timing: An observational study using the Pediatric Health Information Systems Database.

BACKGROUND: There are no consensus guidelines defining optimal timing for the Fontan operation, the last planned surgery in staged palliation for single-ventricle heart disease. OBJECTIVES: Identify patient-level characteristics, center-level variation, and secular trends driving Fontan timing. METHODS: A retrospective observational study of subjects who underwent Fontan from 2007 to 2021 at centers in the Pediatric Health Information Systems database was performed using linear mixed-effects modeling in which age at Fontan was regressed on patient characteristics and date of operation with center as random effect. RESULTS: We included 10,305 subjects (40.4% female, 44% non-white) at 47 centers. Median age at Fontan was 3.4 years (IQR 2.6-4.4). Hypoplastic left heart syndrome (-4.4 months, 95%CI -5.5 to -3.3) and concomitant conditions (-2.6 months, 95%CI -4.1 to -1.1) were associated with younger age at Fontan. Subjects with technology-dependence (+4.6 months, 95%CI 3.1-6.1) were older at Fontan. Black (+4.1 months, 95%CI 2.5-5.7) and Asian (+8.3 months, 95%CI 5.4-11.2) race were associated with older age at Fontan. There was significant variation in Fontan timing between centers. Center accounted for 10% of variation (ICC 0.10, 95%CI 0.07-0.14). Center surgical volume was not associated with Fontan timing (P = .21). Operation year was associated with age at Fontan, with a 3.1 month increase in age for every 5 years (+0.61 months, 95%CI 0.48-0.75). CONCLUSIONS: After adjusting for patient-level characteristics there remains significant inter-center variation in Fontan timing. Age at Fontan has increased. Future studies addressing optimal Fontan timing are warranted.

Cardiovascular magnetic resonance reference values of right ventricular volumetric variables in patients with hypoplastic left heart syndrome.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has established itself as the gold standard for serial assessment of systemic right ventricular (RV) performance but due to the lack of standardized RV reference values for hypoplastic left heart syndrome (HLHS) patients, the interpretation of RV volumetric data in HLHS remains difficult. Therefore, this study aimed to close this gap by providing CMR reference values for the systemic RV in HLHS patients. METHODS: CMR scans of 160 children, adolescents, and young adults (age range 2.2-25.2 years, 106 males) with HLHS were retrospectively evaluated. All patients were studied following total cavopulmonary connection. Short-axis stacks were used to measure RV end-diastolic and end-systolic volumes (RVEDV, RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), and RV end-diastolic myocardial mass (RVEDMM). Univariable and multiple linear regression analyses were performed to assess associations between RV parameters and demographic and anthropometric characteristics. Following the results of the regression analysis, reference graphs and tables were created with the Lambda-Mu-Sigma method. RESULTS: Multiple linear regression analysis showed strong associations between body height and RVEDV, RVESV as well as RVSV. Age was highly associated with RVEDMM. Therefore, percentile curves and tables were created with respect to body height (RVEDV, RVESV, RVSV) and age (RVEDMM). The influence of demographic and anthropometric parameters on RVEF was mild, thus no percentile curves and tables for RVEF are provided. CONCLUSION: We were able to define CMR reference values for RV volumetric variables for HLHS patients. These data might be useful for the assessment and interpretation of CMR scans in these patients and for research in this field.

Mitral valve orifice area predicts outcome after biventricular repair in patients with hypoplastic left ventricles.

BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

Fetal aortic valvuloplasty as the first step in a complex therapeutic strategy.

BACKGROUND: Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis. OBJECTIVE: to report our experience on FAV as the first step in a complex therapeutic strategy. METHOD: Series of patients with FAV over an 18-year period. RESULTS: 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28 days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28 days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up. CONCLUSION: FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28 days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy.

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.

OBJECTIVES: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. METHOD: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. RESULTS: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. CONCLUSION: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

Detection of hypoplastic left heart syndrome anatomy from cardiovascular magnetic resonance images using machine learning.

OBJECTIVE: The prospect of being able to gain relevant information from cardiovascular magnetic resonance (CMR) image analysis automatically opens up new potential to assist the evaluating physician. For machine-learning-based classification of complex congenital heart disease, only few studies have used CMR. MATERIALS AND METHODS: This study presents a tailor-made neural network architecture for detection of 7 distinctive anatomic landmarks in CMR images of patients with hypoplastic left heart syndrome (HLHS) in Fontan circulation or healthy controls and demonstrates the potential of the spatial arrangement of the landmarks to identify HLHS. The method was applied to the axial SSFP CMR scans of 46 patients with HLHS and 33 healthy controls. RESULTS: The displacement between predicted and annotated landmark had a standard deviation of 8-17 mm and was larger than the interobserver variability by a factor of 1.1-2.0. A high overall classification accuracy of 98.7% was achieved. DISCUSSION: Decoupling the identification of clinically meaningful anatomic landmarks from the actual classification improved transparency of classification results. Information from such automated analysis could be used to quickly jump to anatomic positions and guide the physician more efficiently through the analysis depending on the detected condition, which may ultimately improve work flow and save analysis time.

From Surgical to Total Transcatheter Stage I Palliation: Exploring Evidence and Perspectives.

Neonates with single ventricle physiology and ductal-dependent systemic circulation, such as those with hypoplastic left heart syndrome, undergo palliation in the first days of life. Over the past decades, variations on the traditional Stage 1 palliation, also known as Norwood operation, have emerged. These include the hybrid palliation and the total transcatheter approach. Here, we review the current evidence and data on different Stage 1 approaches, with a focus on their advantages, challenges, and future perspectives. Overall, although controversy remains regarding the superiority or inferiority of one approach to another, outcomes after the Norwood and the hybrid palliation have improved over time. However, both procedures still represent high-risk approaches that entail exposure to sternotomy, surgery, and potential cardiopulmonary bypass. The total transcatheter Stage 1 palliation spares patients the surgical and cardiopulmonary bypass insults and has proven to be an effective strategy to bridge even high-risk infants to a later palliative surgery, complete repair, or transplant. As the most recently proposed approach, data are still limited but promising. Future studies will be needed to better define the advantages, challenges, outcomes, and overall potential of this novel approach.

Inpatient Resource Utilization for Hypoplastic Left Heart Syndrome from Birth Through Fontan.

Completing 3-stage palliation for hypoplastic left heart syndrome requires significant resources. An analysis of recent data has not been performed. We aimed to determine total charges necessary to complete all 3 stages of single-ventricle palliation, including interstage encounters. We also aimed to determine overall resource utilization, including hospital days, interstage admissions, and interstage procedures. We performed a retrospective cohort study using data from the Pediatric Health Information System database between 2016 and 2021, including all patients who completed 3-stage palliation for hypoplastic left heart syndrome. We identified 199 patients who underwent 3-stage palliation of hypoplastic left heart syndrome between 2016 and 2021. Median total adjusted charges (interquartile range, IQR) over the course of 3-stage palliation were $1,475,800 ($1,028,900-2,191,700). Median adjusted charges (IQR) for stage 1, 2, and 3 hospitalizations were $604,300 ($419,000-891,400), $234,000 ($164,300-370,800), and $256,260 ($178,300-345,900), respectively. Median hospital length of stay (IQR) for stages 1, 2, and 3 was 36 (26,53), 9 (6,17), and 10 (7,14) days, respectively. Pulmonary artery stenosis was the most common admitting diagnosis for interstage hospitalizations (3.4% of hospitalizations). Cardiac catheterization (24.1% of procedures) and feeding tube placement (10.0% of procedures) were the most common principal procedures during interstage hospitalizations. Total inpatient charges incurred throughout 3-stage palliation of hypoplastic left heart syndrome are substantial and have risen since prior studies. Gastrointestinal comorbidities and feeding optimization contribute considerably to this resource utilization.

Prognostic Value of RV Function Analysis During the Interstage Period in Patients with Hypoplastic Left Heart Syndrome.

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4-8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > -15.6 (AUC 0.79), RVFWS > -18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period.

Assessing enrollment of eligible infants in the national pediatric cardiology quality improvement collaborative (NPC-QIC) through linkage to the pediatric cardiac critical care consortium (PC4) registry.

BACKGROUND: The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) lacks a rigorous enrollment audit process, unlike other collaborative networks. Most centers require individual families to consent to participate. It is unknown whether there is variation across centers or biases in enrollment. METHODS: We used the Pediatric Cardiac Critical Care Consortium (PC4) registry to assess enrollment rates in NPC-QIC for those centers participating in both registries using indirect identifiers (date of birth, date of admission, gender, and center) to match patient records. All infants born 1/1/2018-12/31/2020 and admitted 30 days of life were eligible. In PC4, all infants with a fundamental diagnosis of hypoplastic left heart or variant or who underwent a surgical or hybrid Norwood or variant were eligible. Standard descriptive statistics were used to describe the cohort and center match rates were plotted on a funnel chart. RESULTS: Of 898 eligible NPC-QIC patients, 841 were linked to 1,114 eligible PC4 patients (match rate 75.5%) in 32 centers. Match rates were lower in patients of Hispanic/Latino ethnicity (66.1%, p = 0.005), and those with any specified chromosomal abnormality (57.4%, p = 0.002), noncardiac abnormality (67.8%, p = 0.005), or any specified syndrome (66.5%, p = 0.001). Match rates were lower for patients who transferred to another hospital or died prior to discharge. Match rates varied from 0 to 100% across centers. CONCLUSIONS: It is feasible to match patients between the NPC-QIC and PC4 registries. Variation in match rates suggests opportunities for improvement in NPC-QIC patient enrollment.

Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Acute kidney injury in hypoplastic left heart syndrome patients following the comprehensive stage two palliation.

BACKGROUND: An alternative surgical approach for hypoplastic left heart syndrome is the Hybrid pathway, which delays the risk of acute kidney injury outside of the newborn period. We sought to determine the incidence, and associated morbidity, of acute kidney injury after the comprehensive stage 2 and the cumulative incidence after the first two operations in the Hybrid pathway. DESIGN: A single centre, retrospective study was conducted of hypoplastic left heart patients completing the second-stage palliation in the Hybrid pathway from 2009 to 2018. Acute kidney injury was defined utilising Kidney Diseases Improving Global Outcomes criteria. Perioperative and post-operative characteristics were analysed. RESULTS: Sixty-one patients were included in the study cohort. The incidence of acute kidney injury was 63.9%, with 36.1% developing severe injury. Cumulatively after the Hybrid Stage 1 and comprehensive stage 2 procedures, 69% developed acute kidney injury with 36% developing severe injury. The presence of post-operative acute kidney injury was not associated with an increase in 30-day mortality (acute kidney injury 7.7% versus none 9.1%; p = > 0.9). There was a significantly longer median duration of intubation among those with acute kidney injury (acute kidney injury 32 (8, 155) hours vs. no injury 9 (0, 94) hours; p = 0.018). CONCLUSIONS: Acute kidney injury after the comprehensive stage two procedure is common and accounts for most of the kidney injury in the first two operations of the Hybrid pathway. No difference in mortality was detected between those with acute kidney injury and those without, although there may be an increase in morbidity.

Impact of calorie intake and weight gain after Norwood procedure on the outcome of stage II palliation.

BACKGROUND: This study aimed to assess the impact of caloric intake and weight-for-age-Z-score after the Norwood procedure on the outcome of bidirectional cavopulmonary shunt. METHODS: A total of 153 neonates who underwent the Norwood procedure between 2012 and 2020 were surveyed. Postoperative daily caloric intake and weight-for-age-Z-score up to five months were calculated, and their impact on outcome after bidirectional cavopulmonary shunt was analysed. RESULTS: Median age and weight at the Norwood procedure were 9 days and 3.2 kg, respectively. Modified Blalock-Taussig shunt was used in 95 patients and right ventricle to pulmonary artery conduit in 58. Postoperatively, total caloric intake gradually increased, whereas weight-for-age-Z-score constantly decreased. Early and inter-stage mortality before stage II correlated with low caloric intake. Older age (p = 0.023) at Norwood, lower weight (p < 0.001) at Norwood, and longer intubation (p = 0.004) were correlated with low weight-for-age-Z-score (< -3.0) at 2 months of age. Patients with weight-for-age-Z-score < -3.0 at 2 months of age had lower survival after stage II compared to those with weight-for-age-Z-score of -3.0 or more (85.3 versus 92.9% at 3 years after stage II, p = 0.017). There was no difference between inter-stage weight gain and survival after bidirectional cavopulmonary shunt between the shunt types. CONCLUSION: Weight-for-age-Z-score decreased continuously throughout the first 5 months after the Norwood procedure. Age and weight at Norwood and intubation time were associated with weight gain. Inter-stage low weight gain (Z-score < -3) was a risk for survival after stage II.

An extreme case of cor triatriatum mimicking hypoplastic left heart syndrome and combined pulmonary vein stenosis.

A 65-day-old girl presented to the emergency room with lethargy, requiring emergency venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. Initially, hypoplastic left heart syndrome was suspected. However, cor triatriatum with a pinpoint opening on the membrane was diagnosed based on a detailed echocardiographic examination. After membrane resection, the left heart size was restored. However, follow-up echocardiography performed 4 months later showed occlusion of both upper pulmonary veins and stenosis in both lower pulmonary veins. Hybrid balloon angioplasty was performed in all pulmonary veins, and stents were inserted into the right upper and lower pulmonary veins. Despite repeated balloon angioplasty, all pulmonary vein stenosis progressed over 6 months and the patient expired while waiting for a heart-lung transplant. Even after successful repair of cor triatriatum, short-term close follow-up is required for detecting the development of pulmonary vein stenosis.

Center-level factors associated with shorter length of stay following stage 1 palliation: An analysis of the national pediatric cardiology quality improvement collaborative registry.

BACKGROUND: Stage 1 single ventricle palliation (S1P) has the longest length of stay (LOS) of all benchmark congenital heart operations. Center-level factors contributing to prolonged hospitalization are poorly defined. METHODS: We analyzed data from infants status post S1P included in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry. Our primary outcome was patient-level LOS with days alive and out of hospital before stage 2 palliation (S2P) used as a balancing measure. We compared patient and center-level characteristics across quartiles for median center LOS, and used multivariable regression to calculate center-level factors associated with LOS after adjusting for case mix. RESULTS: Of 2,510 infants (65 sites), 2037 (47 sites) met study criteria (61% male, 61% white, 72% hypoplastic left heart syndrome). There was wide intercenter variation in LOS (first quartile centers: median 28 days [IQR 19, 46]; fourth quartile: 62 days [35, 95], P < .001). Mortality prior to S2P did not differ across quartiles. Shorter LOS correlated with more pre-S2P days alive and out of hospital, after accounting for readmissions (correlation coefficient -0.48, P < .001). In multivariable analysis, increased use of Norwood with a right ventricle to pulmonary artery conduit (aOR 2.65 [1.1, 6.37]), shorter bypass time (aOR 0.99 per minute [0.98,1.0]), fewer additional cardiac operations (aOR 0.46 [0.22, 0.93]), and increased use of NG tubes rather than G tubes (aOR 7.03 [1.95, 25.42]) were all associated with shorter LOS centers. CONCLUSIONS: Modifiable center-level practices may be targets to standardize practice and reduce overall LOS across centers.

Attributable mortality benefit of digoxin treatment in hypoplastic left heart syndrome after the Norwood operation: An instrumental variable-based analysis using data from the Pediatric Health Information Systems Database.

BACKGROUND: Observational studies have demonstrated an association between the use of digoxin and reduced interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS). Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix. Instrumental variable analyses have the potential to overcome unmeasured confounding, the major limitation of previous observational studies and to generate an estimate of the attributable benefit of treatment with digoxin. METHODS: A cohort of neonates with HLHS born from January 1, 2007 to December 31, 2021 who underwent Norwood operation at Pediatric Health Information Systems Database hospitals and survived >14 days after operation were studied. Using hospital-specific, 6-month likelihood of administering digoxin as an instrumental variable, analyses adjusting for both unmeasured confounding (using the instrumental variable) and measured confounders with multivariable logistic regression were performed. RESULTS: The study population included 5,148 subjects treated at 47 hospitals of which 63% were male and 46% non-Hispanic white. Of these, 44% (n = 2,184) were prescribed digoxin. Treatment with digoxin was associated with superior 1-year transplant-free survival in unadjusted analyses (85% vs 82%, P = .02). This survival benefit persisted in an instrumental-variable analysis (OR: 0.71, 95% CI: 0.54-0.94, P = .01), which can be converted to an absolute risk reduction of 5% (number needed to treat of 20). CONCLUSIONS: In this observational study of patients with HLHS after Norwood using instrumental variable techniques, a significant benefit in 1-year transplant-free survival attributable to digoxin was demonstrated. In the absence of clinical trial data, this should encourage the use of digoxin in this vulnerable population.

Preterm Birth Is Associated With Adverse Cardiac Remodeling and Worse Outcomes in Patients With a Functional Single Right Ventricle.

OBJECTIVE: To assess the effects of preterm birth on cardiac structure and function and transplant-free survival in patients with hypoplastic left heart syndrome and associated anomalies throughout the staged palliation process. STUDY DESIGN: Data from the Single Ventricle Reconstruction trial were used to assess the impact of prematurity on echocardiographic measures at birth, Norwood, Stage II, and 14 months in 549 patients with a single functional right ventricle. Medical history was recorded once a year using medical records or telephone interviews. Cox regression models were applied to analyze transplant-free survival to age 6 years. Causal mediation analysis was performed to estimate the mediating effect of birth weight within this relationship. RESULTS: Of the 549 participants, 64 (11.7%) were born preterm. Preterm-born participants had lower indexed right ventricle end-diastolic volumes at birth but higher volumes than term-born participants by age 14 months. Preterm-born participants had an increased risk of death or heart transplantation from birth to age 6 years, with an almost linear increase in the observed risk as gestational age decreased below 37 weeks. Of the total effect of preterm birth on transplant-free survival, 27.3% (95% CI 2.5-59.0%) was mediated through birth weight. CONCLUSIONS: Preterm birth is associated with adverse right ventricle remodeling and worse transplant-free survival throughout the palliation process, in part independently of low birth weight. Further investigation into this vulnerable group may allow development of strategies that mitigate the impact of prematurity on outcomes in patients with hypoplastic left heart syndrome.

The Relationship of Family Factors to Psychosocial Outcomes in Children with Hypoplastic Left Heart Syndrome at 6 Years of Age.

OBJECTIVE: The objective of this study was to describe the relationships between family factors and outcomes for children with hypoplastic left heart syndrome (HLHS). STUDY DESIGN: This cross-sectional study was ancillary to the Pediatric Heart Network Single Ventricle Reconstruction Extension Study to examine family factors including parental mental health, quality of life (QOL), family resources, function and management, and their relationships to child psychosocial outcomes (adaptive behavior, internalizing and externalizing behaviors and health-related quality of life [HRQOL]) at 6 years of age. RESULTS: Participants were parents (115 mothers, 71 fathers) of children with HLHS. Parents reported anxiety, QOL and family resources that were worse than the general population; 33% reported family dysfunction. There were no meaningful differences between reports from mothers and fathers. Parental perception of better child health was associated with better family management of the condition (P < .05). Several family management factors explained a moderate amount of variance in adaptive behavior (ΔR2 = 0.08-0.14), adaptive skills (ΔR2 = 0.19-0.21), and HRQOL scores (ΔR2 = 0.04-0.18); little variance was explained in internalizing problems (ΔR2 = 0.02-0.03) (all P < .05) above and beyond demographic and clinical variables. CONCLUSIONS: HLHS has a significant impact on both children and families. Relationships between child and family characteristics may impose risk or protection. Improved understanding of these associations should guide counseling and tailored interventions.

Prolonged Enteral Tube Feeding in Infants With a Functional Single Ventricle Is Associated With Adverse Outcomes After Fontan Completion.

OBJECTIVES: To define the baseline characteristics of long-term tube-fed (TF) single ventricle patients, investigate associations between long-term enteral tube feeding and growth, and determine associations with long-term outcomes after Fontan procedure. STUDY DESIGN: We performed a retrospective cohort study of patients in the Australia and New Zealand Fontan Registry undergoing treatment at the Royal Children's Hospital, the Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. Patients were defined as TF or non-tube-fed (NTF) based on enteral tube feeding at the age of 90 days. Feeding groups were compared regarding body mass index (BMI) trajectory, BMI at last follow-up, and long-term incidence of severe Fontan failure. RESULTS: Of 390 patients (56 [14%] TF, 334 [86%] NTF), TF was associated with right ventricular dominance, hypoplastic left heart syndrome, Norwood procedure, increased procedures prior to Fontan, extracardiac conduit Fontan, Fontan fenestration, and atrioventricular valve repair/replacement. TF patients were less likely to be in the higher compared with lowest 0-6 month BMI trajectory (P < .01; P = .03), had lower 6 month weight-for-age z-scores (P < .01) and length-for-age z-scores (P = .01). TF were less likely to be overweight/obese at pediatric follow-up (hazard ratio [HR] = 0.31, 95% CI: 0.12-0.80; P = .02) and more likely to be underweight at adult follow-up (HR = 16.51; 5% CI: 2.70-101.10; P < .01). TF compared with NTF was associated with increased risk of severe Fontan failure (HR = 4.13; 95% CI = 1.65-10.31; P < .01). CONCLUSIONS: Prolonged infant enteral tube feeding is an independent marker of poor growth and adverse clinical outcomes extending long-term post-Fontan procedure.

Support with Single Ventricle-Ventricular Assist Device (sVAD) in Patients with Functionally Univentricular Circulation Prior to Fontan Operation.

Some patients with functionally univentricular circulation develop cardiac failure refractory to maximal management and are supported with a ventricular assist device (VAD). The purpose of this manuscript is to summarize our previous publications related to single ventricle-ventricular assist device (sVAD) support in patients with functionally univentricular circulation and to describe our current institutional approach at University of Florida to sVAD support in neonates, infants, and children prior to Fontan. Our programmatic philosophy at University of Florida is to strive to identify the minority of neonates with functionally univentricular circulation who are extremely high-risk prior to initiating staged palliation and to stabilize these neonates with primary preemptive sVAD in preparation for cardiac transplantation; our rationale for this approach is related to the challenges associated with failed staged palliation and subsequent bail-out sVAD support and transplantation. A subset of extremely high-risk neonates and infants with functionally univentricular ductal-dependent circulation undergo primary preemptive sVAD insertion and subsequent cardiac transplantation. Support with VAD clearly facilitates survival on the waiting list during prolonged wait times and optimizes outcomes after Norwood (Stage 1) by providing an alternative pathway for extremely high-risk patients. Therefore, the selective utilization of sVAD in extremely high-risk neonates facilitates improved outcomes for all patients with functionally univentricular ductal-dependent circulation. At University of Florida, our programmatic approach to utilizing sVAD support as a bridge to transplantation in the minority of neonates with functionally univentricular circulation who are extremely high-risk for staged palliation is associated with Operative Mortality after Norwood (Stage 1) Operation of 2.9% (2/68) and a one-year survival of 91.1% (82/90) for all neonates presenting with hypoplastic left heart syndrome (HLHS) or HLHS-related malformation with functionally univentricular ductal-dependent systemic circulation. Meanwhile, at University of Florida, for all 82 consecutive neonates, infants, and children supported with pulsatile paracorporeal VAD: Kaplan-Meier survival estimated one year after VAD insertion = 73.3% (95% confidence interval [CI] = 64.1-83.8%), and Kaplan-Meier survival estimated five years after VAD insertion = 68.3% (95% CI = 58.4-79.8%). For all 48 consecutive neonates, infants, and children at University of Florida with biventricular circulation supported with pulsatile paracorporeal VAD: Kaplan-Meier survival estimated one year after VAD insertion = 82.7% (95% CI = 72.4-94.4%), and Kaplan-Meier survival estimated five years after VAD insertion = 79.7% (95% CI = 68.6-92.6%). For all 34 consecutive neonates, infants, and children at University of Florida with functionally univentricular circulation supported with pulsatile paracorporeal sVAD: Kaplan-Meier survival estimated one year after VAD insertion = 59.7% (95% CI = 44.9-79.5%), and Kaplan-Meier survival estimated five years after VAD insertion = 50.5% (95% CI = 35.0-73.0%). These Kaplan-Meier survival estimates for patients supported with pulsatile paracorporeal VAD are better in patients with biventricular circulation in comparison to patients with functionally univentricular circulation both one year after VAD insertion (P=0.026) and five years after VAD insertion (P=0.010). Although outcomes after VAD support in functionally univentricular patients are worse than in patients with biventricular circulation, sVAD provides a reasonable chance for survival. Ongoing research is necessary to improve the outcomes of these challenging patients, with the goal of developing strategies where outcomes after sVAD support in functionally univentricular patients are equivalent to the outcomes achieved after VAD support in patients with biventricular circulation.