Hypoplastic Left Heart Syndrome Research Articles

Abstract 17152: Use and Outcomes of the Medical Hybrid Procedure for Stage 1 Palliation in Infants With Hypoplastic Left Heart Syndrome and Variants

Background: Staged palliation of hypoplastic left heart syndrome (HLHS) and variants typically begins with the Norwood operation or the hybrid procedure. Hybrid palliation is used in 13% of patients nationally and is often reserved for high-risk patients. A stented hybrid (SH) consists of bilateral pulmonary artery bands (bPAB) and a ductal stent while a ‘medical hybrid’ (MH) consists of bPAB and prostaglandins. MH use and outcomes have not been well described. Hypothesis: MH is used in higher-risk patients and therefore has lower survival than other stage 1 strategies. Aims: Compare use and outcomes of MH, SH, and surgical stage 1 (SS1) using a multicenter database. Methods: Patients from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) database were categorized by initial intervention: MH, SH, or SS1. Other/unclear procedures were excluded. Results: The study included 2423 patients from 65 centers: 277 (11%) MH, 133 (5%) SH, 2013 (83%) SS1. MH had the lowest birth weight (BW) and gestational age (GA), most non-cardiac anomalies, and most preoperative risk factors (PRF). Most centers performed MH in a minority of cases, though use ranged from 0% to 82% at centers with ≥10 patients. Transplant-free survival at 1 year was 56% for MH, 66% for SH, and 81% for SS1 (p<0.0001). Using multivariable logistic regression, predictors of MH vs SS1 were lower BW (p<0.001), lower GA (p<0.001), genetic syndrome (p=0.010), non-cardiac anomaly (p=0.031), and ≥4/12 PRF (p<0.001). Predictors of MH vs SH were HLHS (p=0.044) and ≥4/12 PRF (p=0.045). Cox proportional hazards regression was used to compare risk-adjusted outcomes, excluding one center that performed >50% SH: MH had higher risk of one-year mortality/transplant compared to SS1 (HR = 1.89, 95% CI 1.47-2.42) and no difference compared to SH (HR = 1.16, 95% CI 0.76-1.79). Conclusions: Survival after MH is similar to SH and worse than SS1. This may be due to patient risk factors not controlled for in this study.

Abstract 11801: Timing of Critical Congenital Heart Defect (CCHD) Detection at 7 U.S. Sites, the Birth Defects Study to Evaluate Pregnancy Exposures (BD-STEPS), 2014-2018

Background: CCHD detection prenatally or at birth hospitalization may reduce infant mortality and morbidity, yet little is known about prevalence and characteristics associated with timing of detection. Objective: To examine prevalence and characteristics associated with prenatal and late (>3 days after birth) detection of CCHD among infants in BD-STEPS, a multi-site population-based case-control study of risk factors for birth defects. Methods: Liveborn infants with non-syndromic CCHD without genetic causes born 2014-2018 with interviewed mothers were included. Timing of detection was based on date of earliest fetal or postnatal echocardiogram. Multivariable log-binomial models calculated adjusted prevalence ratios (aPR) for prenatal (vs postnatal) and late (vs not late) CCHD detection, by clinical and demographic characteristics. Log-linear models evaluated trends over time. Results: Among the 588/672 infants with CCHD and complete data, most infants’ mothers were Non-Hispanic White (53.4%), had some prenatal insurance (94.4%), and were multiparous (74.5%). Prenatal detection increased from 2014 to 2018 (24.7% to 40.1%) while late detection decreased (22.4% to 8.7%, Fig 1). Hypoplastic left heart syndrome had the highest prenatal detection (58.6%); late detection was highest for coarctation of the aorta (41.7%). Prenatal detection was more likely in infants of mothers 30-34 vs. 25-29 years at delivery (aPR=1.4, 95% confidence interval 1.0-1.9), and with additional non-cardiac defects (1.2, 1.1-1.4), and less likely among infants of mothers with <11 years of education vs. > bachelor’s degree (0.6, 0.3-1.0). Late detection was more likely among infants of mothers without prenatal insurance (1.8, 1.1-3.1), and less likely among those with non-cardiac defects (0.4, 0.2-0.8). Conclusion: From 2014 to 2018, prenatal detection increased and late detection decreased. Yet, disparities in detection by maternal insurance and education were observed.

Abstract 13952: Neurodevelopmental Outcomes in Early Adolescence: The Pediatric Heart Network’s Single Ventricle Reconstruction Trial

Introduction: Neurodevelopmental (ND) and functional impairments for survivors of palliated hypoplastic left heart syndrome (HLHS) are among the most consequential morbidities, resulting in an increased risk of poor school performance and lower reported quality of life. Longitudinal follow-up of those enrolled in the Single Ventricle Reconstruction (SVR) III study provides opportunity to measure important outcomes such as ND, and understand associated risk factors. Goals/Aims: Describe and identify predictors of ND outcomes at 10-12 years of age in participants enrolled in SVR. Methods: Transplant-free survivors from the SVR III trial were invited to complete in-person ND assessments, including the Wechsler Intelligence Scale for Children-V, Wechsler Individual Achievement Test-III, and the Behavior Rating Inventory of Executive Function (BRIEF). Descriptive and regression analyses were performed. Results: Of the 237 enrolled in SVR III, 200 (84%) received a ND assessment. Participants who did vs did not undergo assessment were more likely to be male (63% vs 51%), white (87% vs 76%) and have a higher Child Opportunity Index (61 ±26 vs 46 ±39). Mean Full Scale IQ for the cohort was almost 1 standard deviation (SD) below the normative mean (88 ±18), with 39% >1 and 15% >2 SD below the normative mean. Similar patterns were seen for Reading (38% >1 SD and 16% > 2SD) and Math Composites (38% >1 SD, 19% > 2SD). Executive functions measured with the BRIEF were similarly affected, with 25% to 45% of individuals showing clinically significant (T score >65) Plan/Organization problems on parent and teacher forms, respectively. Measures of socioeconomic status, number of complications, and requirement for a gastrostomy-tube were all independent predictors for multiple ND outcomes. Conclusions: In early adolescence, transplant-free survivors of surgical palliation for HLHS show clinically significant ND concerns across multiple domains of functioning. The distribution of outcomes is broad. Our findings support the American Heart Association recommendations for screening and evaluation in middle school to inform interventions that promote academic success and quality of life.

Abstract 14634: Hybrid vs. Norwood: Analysis of the NPC-QIC Database to Determine Optimal Approach for High-Risk Single Ventricle Patients

Background: Infants w/ high risk hypoplastic left heart syndrome and variants (HR-HLHS) due to low birth weight or gestational age experience worse outcomes. Optimal management remains unknown. We sought to 1. compare primary Norwood to hybrid strategies in HR-HLHS 2. identify predictors of futility. Hypothesis: Primary Norwood offers improved outcomes compared to hybrid strategies. Very low birth weight and other anomalies may represent futility. Methods: We reviewed HR-HLHS from the National Pediatric Cardiology Quality Improvement Collaborative database. Patients with birth weight <2.5kg or gestation <35 weeks, and age ≤ 30 days at admission were included (N=398). Norwood (n=225), hybrid (pulmonary artery band (PAB) + ductal stent, n=76), and PAB w/ prostaglandin (PAB/PGE, n=77) were compared. Transplantation referral (n=1) and comfort care (n=19) occurred. Baseline factors, 1-year survival, and stage 2 completion were reviewed. Results: Table shows baseline HR-HLHS features. Norwood had higher risk adjusted 1-year survival and stage 2 completion than hybrid strategies, including in < 2.1 kg (Figure). On multivariable analysis, hybrid (HR 2.8), genetic abnormality (HR 1.5), and ECMO (HR: 7.2) were significantly associated w/ decreased 1-year survival and stage 2 completion, while higher birth weight (HR: 1.5) was associated w/ increased stage 2 completion. Less than 25% of HR-HLHS w/ birthweight < 2.1 kg and ≥ 1 genetic abnormality was alive with stage 2 at the end of follow-up. Conclusions: HR-HLHS have better outcomes following primary Norwood than hybrid palliation. In patients w/ birth weight < 2.1 kg and genetic abnormalities, hybrid or Norwood may be futile.

Defining the Spectrum of Hypoplastic Left Heart Syndrome (HLHS).

The 2021 International Paediatric and Congenital Cardiac Code and the Eleventh Revision of the International Classification of Diseases provide the following definition for hypoplastic left heart syndrome (HLHS): "Hypoplastic left heart syndrome (HLHS) is defined as a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch." Although HLHS with intact ventricular septum (HLHS + IVS) and HLHS with ventricular septal defect (HLHS + VSD) are different cardiac phenotypes, both of these lesions are part of the spectrum of HLHS.

Modified Aortic Arch Reconstruction Combined With Pulmonary Artery Reconstruction in the Comprehensive Stage II Operation Following a Hybrid Stage I for Hypoplastic Left Heart Syndrome

The hybrid approach for hypoplastic left heart syndrome is a well-accepted alternative strategy to the conventional staged surgical approach. However, in the typical comprehensive stage II operation, bilateral branch pulmonary artery stenosis is a risk factor for postoperative catheter and/or surgical interventions. In addition to addressing the stenosis from the bands, the branch pulmonary arteries are at risk of compression from the dilated main pulmonary trunk and the resultant large neo-aorta. Here, we present a new aortic arch reconstruction technique combined with the pulmonary artery reconstruction in the comprehensive stage II operation to address these issues. In our experience of 11 patients who underwent hybrid strategy, Fontan completion was achieved in 8 cases (73%) during a median follow-up duration of 84 months (range; 45-161 months), and the 3-year, 5-year, and 10-year survival rates were 73% each. While 6 of 8 cases (75%) required catheter interventions to the branch pulmonary arteries, the Nakata Index was 204±11 before the stage II and 185±19 before Fontan completion, indicating that good pulmonary artery growth. Our modified comprehensive stage II technique optimizes the pulmonary arteries for the Fontan and beyond by addressing both anatomic stenoses and external compression for future growth.

Impact of Optimal Fenestration Size on Outcomes of High-Risk Fontan Patients.

We aimed to analyze mid-term outcomes of the fenestrated Fontan procedure, focusing on the fenestration size. We retrospectively reviewed the outcomes of the fenestrated Fontan procedure. Among 165 patients who underwent the Fontan procedure from 2011 to 2021, fenestration was created in 27 patients with the highest risks, including those with hypoplastic left heart syndrome, hypoplastic pulmonary arteries, heterotaxy syndrome with high pulmonary vascular resistance, and pulmonary arterial pressure >15 mm Hg. The patients underwent the procedure at a median age of three years (body weight, 11.4 kg; body surface area, 0.54 m2). Fenestration sizes were 3.5 to 5 mm. Spontaneous fenestration closure occurred within one year postoperatively in nine patients. Among them, three experienced Fontan failure, necessitating refenestration. Although fenestration size did not differ, the size corrected by body surface area at the time of surgery was smaller in patients with fenestration closure (6.4 mm/m2 vs 8.3 mm/m2, P < .05). Patients with a fenestration <7 mm/m2 were more likely to have fenestration closure within one year postoperatively, and those with a fenestration >9 mm/m2 were more likely to have severe desaturation and require home oxygen therapy following discharge. Spontaneous fenestration closure affected the frequency of Fontan complications. A very small fenestration size corrected by body surface area was a significant risk factor for spontaneous closure. Conversely, a very large fenestration size corrected by body surface area resulted in severe desaturation. The optimal fenestration size to prevent early spontaneous closure and severe desaturation is approximately 8 mm/m2.

Combined ventricular dysfunction and atrioventricular valve regurgitation after the Norwood procedure are associated with attrition prior to superior cavopulmonary connection

BackgroundInfants with hypoplastic left heart syndrome (HLHS) or a variant are at risk of ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) prior to superior cavopulmonary connection (SCPC). Although the impact of these complications in isolation has been described, their effect in combination on attrition is poorly defined. MethodsA retrospective observational study of patients with HLHS or variants undergoing a Norwood procedure between 2008 and 2020 at a single center was performed. VD and AVVR were defined as moderate or severe when seen on 2 sequential echocardiograms outside the perioperative period. Attrition was defined as death, listing for heart transplant, or unsuitability for SCPC or transplant. Descriptive statistics and regression models were used for analysis. ResultsA total of 397 patients were included, of whom 75% had HLHS and 57% had received a Blalock-Thomas-Taussig shunt. Isolated VD occurred in 9% of patients, AVVR occurred in 13%, and both occurred in 6%. Attrition prior to SCPC occurred in 19% of the overall cohort, in 52% of patients with combined VD and AVVR (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.3-12.0; P < .01), 26% of those with VD (OR, 1.5; 95% CI, 0.7-3.3; P = .32), 25% of those with AVVR (OR, 1.5; 95% CI, 0.7-2.9; P = .27), and 15% in those with neither (OR, 0.3; 95% CI, 0.2-0.6; P < .01). Other factors associated with attrition included prematurity, total bypass time at Norwood, and extracorporeal membrane oxygenation after Norwood, whereas later year of Norwood was protective (P < .01 for all). ConclusionsThe presence of combined VD and AVVR markedly increases the likelihood of attrition prior to SCPC, identifying a high-risk group.

Higher Cumulative Dose of Opioids and Other Sedatives are Associated with Extubation Failure in Norwood Patients.

The primary purpose of this study is to evaluate the relationship between sedation usage and extubation failure, and to control for the effects of hemodynamic, oximetric indices, clinical characteristics, ventilatory settings pre- and post-extubation, and echocardiographic (echo) findings in neonates with hypoplastic left heart syndrome (HLHS) post-Norwood procedure. Single-center, retrospective analysis of Norwood patients during their first extubation post-surgery from January 2015 to July 2021. Extubation failure was defined as reintubation within 48 h of extubation. Demographics, clinical characteristics, ventilatory settings, echo findings (right ventricular function, tricuspid regurgitation), and cumulative dose of sedation medications before extubation were compared between patients with successful or failed extubation. The analysis included 130 patients who underwent the Norwood procedure with 121 (93%) successful and 9 (7%) failed extubations. Univariate analyses showed that vocal cord anomaly (p = 0.05), lower end-tidal CO2 (p < 0.01), lower pulse-to-respiratory quotient (p = 0.02), and ketamine administration (p = 0.04) were associated with extubation failure. The use of opioids, benzodiazepines, dexmedetomidine, and ketamine are mutually correlated in this cohort. On multivariable analysis, the vocal cord anomaly (OR = 7.31, 95% CI 1.25-42.78, p = 0.027), pre-extubation end-tidal CO2 (OR = 0.80, 95% CI 0.65-0.97, p = 0.025), and higher cumulative dose of opioids (OR = 10.16, 95% CI 1.25-82.43, p = 0.030) were independently associated with extubation failure while also controlling for post-extubation respiratory support (CPAP/BiPAP/HFNC vs NC), intubation length, and echo results. Higher cumulative opioid doses were associated with a greater incidence of extubation failure in infants post-Norwood procedure. Therefore, patients with higher cumulative doses of opioids should be more closely evaluated for extubation readiness in this population. Low end-tidal CO2 and low pulse-to-respiratory quotient were also associated with failed extubation. Consideration of the pulse-to-respiratory quotient in the extubation readiness assessment can be beneficial in the Norwood population.

The use of health care databases for surveillance of congenital anomalies: A EUROlinkCAT study

Abstract Background Although health care databases were not designed for research or surveillance, they are increasingly used by researchers to investigate the epidemiology of congenital anomalies (CAs). Identifying specific CAs that can be accurately identified in hospital databases and those that are poorly recorded will enable surveillance of CAs. We evaluated the accuracy and the quality of the coding of CAs in hospital databases compared to EUROCAT data. Methods The EUROlinkCAT project linked data from eleven EUROCAT registries I eight countries to electronic hospital databases. The coding of specific CAs in hospital databases was compared to the codes in the EUROCAT registries (gold standard). For birth years 2010-2014 all linked live birth CA cases and all children identified in the hospital databases with a CA code were analysed. Registries calculated sensitivity and Positive Predictive Value (PPV) for 17 selected CAs. Pooled estimates for sensitivity and PPV were then calculated for each anomaly using random effects meta-analyses. Results Most registries linked more than 85% of their cases to hospital data. Gastroschisis, cleft lip with or without cleft palate and Down syndrome were recorded in hospital databases with high accuracy (sensitivity and PPV &amp;gt;85%). Hypoplastic left heart syndrome, spina bifida, Hirschsprung's disease, omphalocele and cleft palate showed high sensitivity (&amp;gt;85%), but low or heterogeneous PPV, indicating that hospital data were complete but may contain false positives. The remaining anomaly subgroups showed low or heterogeneous sensitivity and PPV, indicating that the information in the hospital database was incomplete and of variable validity. Conclusions Electronic health care databases cannot replace CA registries, although they can be used as an additional ascertainment source for CA registries. CA registries are still the most appropriate data source to study the epidemiology of CAs. Key messages • European hospital databases can accurately record a limited number of anomalies that are visible at birth, diagnosed prenatally and/or require hospitalisation or surgery in the first year of life. • Additional data sources are needed to capture all children with CAs as hospital databases have limited information or codes to identify pregnancies that result in termination for fetal anomaly.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

School age and adolescent heart failure following the Norwood procedure

Heart failure results in significant morbidity and mortality for young children with hypoplastic left heart syndrome (HLHS) following the Norwood procedure. The trajectory in later childhood is not well described. We studied the outcome into adolescence of participants enrolled in the Single Ventricle Reconstruction trial who underwent the Fontan procedure or survived to 6years without having undergone Fontan procedure. The primary outcome was heart failure events, defined as heart transplant listing or death attributable to heart failure. Symptomatic heart failure for participants surviving 10 or more years was also assessed utilizing the Pediatric Quality of Life Inventory (PedsQL). Of the 345 participants who underwent a Fontan operation or survived to 6years without Fontan, 25 (7.2%) had a heart failure event before the age of 12years. Among these, 21 were listed for heart transplant, and 4 died from heart failure. Nineteen participants underwent heart transplant, all of whom survived to age 12years. Factors associated with a heart failure event included longer Norwood hospital length of stay, aortic atresia, and no Fontan operation by age 6years. Assessment of heart failure symptoms at 12years of age revealed that 24 (12.2%) of 196 PedsQL respondents "often" or "almost always" had difficulty walking more than one block. Heart failure events occur in over 5% of children with palliated HLHS between preschool age and adolescence. Outcomes for children listed for transplant are excellent. However, a substantial portion of palliated HLHS children have significant symptoms of heart failure at 12years of age.

Low pre-albumin but not thiamine predicts cognitive deficits in adolescents post-Fontan and healthy controls.

Low pre-albumin, body mass index, and thiamine levels have been associated with poor nutritional status and cognitive/memory deficits in adult heart failure patients. However, the relationship of these nutritional/dietary intake biomarkers to cognition has not been assessed in adolescents post-Fontan procedure and healthy controls. This is a cross-sectional study. Adolescents (14-21 years of age) post-Fontan completion were recruited from paediatric cardiology clinics and controls from the community. The Montreal Cognitive Assessment was administered (normal ≥ 26), and blood draw (thiamine [normal 70-110 nmol/L] and pre-albumin levels [adolescent normal 23-45 mg/dL]) and the Thiamine Food Frequency Questionnaire were completed by all participants. Seventy subjects, 40 post-Fontan (mean age 16 ± 1.6, female 51%, Hispanic 44%, hypoplastic left heart syndrome 26%) and 30 controls (mean age 16.8 ± 1.9, female 52%, Hispanic 66%), were participated. Post-Fontan group had lower median total cognitive scores (23 versus 29, p < 0.001), pre-albumin levels (23 versus 27, p = 0.013), and body mass index (20 versus 24, p = 0.027) than controls. Post-Fontan group had higher thiamine levels than controls (127 versus 103, p = 0.033). Lower pre-albumin levels (< 23) and underweight body mass index were associated with abnormal total cognitive scores (p = 0.030). Low pre-albumin level (p = .038) was an independent predictor of worse cognition. Lower pre-albumin was an independent predictor for worse cognition in adolescents post-Fontan. Lower pre-albumin levels may reflect chronic liver changes or protein-losing enteropathy seen in Fontan physiology. These findings highlight the possibility for nutrition-induced cognitive changes.

Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.

Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8-25 per 100,000 neonates globally. Clinical interventions, primarily surgical, have improved the life expectancy of the affected subjects substantially over the years. However, the etiological basis of HLHS remains fundamentally unclear to this day. Based upon the existing paradigm of studies, HLHS exhibits a multifactorial mode of etiology mediated by a complicated course of genetic and signaling cascade. This review presents a detailed outline of the HLHS phenotype, the prenatal and postnatal risks, and the signaling and molecular mechanisms driving HLHS pathogenesis. The review discusses the potential limitations and future perspectives of studies that can be undertaken to address the existing scientific gap. Mechanistic studies to explain HLHS etiology will potentially elucidate novel druggable targets and empower the development of therapeutic regimens against HLHS in the future.

Discussion to: Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome

Discussion to: Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome

Development of weight and height age z-score after total cavopulmonary connection.

We aimed to analyze somatic growth of patients after total cavopulmonary connection (TCPC) as well as to identify factors influencing postoperative catch-up growth. A total of 309 patients undergoing TCPC at 4 years old or less between 1994 and 2021 were included. Weight-for-age z-score (WAZ) and height-for-age-z-score (HAZ) at TCPC and at postoperative time between 1 to 3 years were calculated. Factors influencing somatic growth were analyzed. Most frequent diagnosis and initial palliation were hypoplastic left heart syndrome (HLHS) (34%) and the Norwood procedure (51%), respectively. Median age and weight at TCPC was 2.0 (IQR: 1.7-2.5) years and 11.3 (10.5-12.7) kg, respectively. Median 519 days after TCPC, significant increase in WAZ (-0.4 to -0.2, p<0.001) was observed, but not in HAZ (-0.6 to -0.6, p=0.38). Older age at TCPC (p<0.001, OR: 2.6) and HLHS (p=0.007, OR: 2.2) were risks for low WAZ after TCPC. Older age at TCPC (p=0.009. OR: 1.9) and previous Norwood procedure (p=0.021, OR: 2.0) were risks for low HAZ after TCPC. Previous bidirectional cavopulmonary shunt (BCPS) was a protective factor for both WAZ (p=0.012, OR: 0.06) and HAZ (p=0.028, OR: 0.30) at TCPC. In patients undergoing TCPC at the age of 4 years or less, a significant catch-up growth was observed in weight-for-age z-score after TCPC, but not in height-for-age-z-score. Previous BCPS resulted to be a protective factor for a better somatic development at TCPC. HLHS undergoing Norwood were considered as risks for somatic development after TCPC.

Use of the Transcultural Integrative Ethical Decision-Making Model in the Care of a Rohingya Infant With Hypoplastic Left Heart Syndrome

Objective:Concerns have been expressed about the challenges of upholding traditional Westernized psychological ethical boundaries while honoring the cultural and religious values of diverse cultures.Method:The Transcultural Integrative Ethical Decision-Making Model was utilized to resolve ethical dilemmas related to a refugee Rohingya family during a pediatric hospitalization.Results:Culturally informed case conceptualization and peer consultation were critical in assisting the decision-making process to balance psychological ethical guidelines and the distinctive needs of the family.Conclusion:The Transcultural Integrative Ethical Decision-Making Model can serve as a guide for psychologists to help make ethical decisions while working with families from diverse cultures that may not share the values associated with a Westernized mental healthcare approach.

Impact of home monitoring program on interstage mortality after the Norwood procedure.

While early outcome after the Norwood operation for hypoplastic left heart syndrome has improved, interstage mortality until bidirectional cavopulmonary shunt (BCPS) remains a concern. Our aim was to institute a home monitoring program to (HMP) decrease interstage mortality. Among 264 patients who survived Norwood procedure and were discharged before BCPS, 80 patients were included in the HMP and compared to the remaining 184 patients regarding interstage mortality. In patients with HMP, events during the interstage period were evaluated. Interstage mortality was 8% (n = 21), and was significantly lower in patients with HMP (2.5%, n = 2), compared to those without (10.3%, n = 19, p = 0.031). Patients with interstage mortality had significantly lower birth weight (p < 0.001) compared to those without. Lower birth weight (p < 0.001), extra corporeal membrane oxygenation support (p = 0.002), and lack of HMP (p = 0.048) were risk factors for interstage mortality. Most frequent event during home monitoring was low saturation (<70%) in 14 patients (18%), followed by infection in 6 (7.5%), stagnated weight gain in 5 (6.3%), hypoxic shock in 3 (3.8%) and arrhythmias in 2 (2.5%). An unexpected readmission was needed in 24 patients (30%). In those patients, age (p = 0.001) and weight at BCPS (p = 0.007) were significantly lower compared to those without readmission, but the survival after BCPS was comparable between the groups. Interstage HMP permits timely intervention and led to an important decrease in interstage mortality. One-third of the patients with home monitoring program needed re-admission and demonstrated the need for earlier stage 2 palliation.

Fetal circulatory physiology and brain development in complex congenital heart disease: A multi-modal imaging study.

Fetuses with complex congenital heart disease have altered physiology, contributing to abnormal neurodevelopment. The effects of altered physiology on brain development have not been well studied. We used multi-modal imaging to study fetal circulatory physiology and brain development in hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (TGA). This prospective, cross-sectional study investigated individuals with fetal congenital heart disease and controls undergoing fetal echocardiography and fetal brain MRI. MRI measured total brain volume and cerebral oxygenation by the MRI quantification method T2*. Indexed cardiac outputs (CCOi) and vascular impedances were calculated by fetal echocardiography. Descriptive statistics assessed MRI and echocardiogram measurement relationships by physiology. Sixty-six participants enrolled (control=20; HLHS=25; TGA=21), mean gestational age 33.8weeks (95% CI: 33.3-34.2). Total brain volume and T2* were significantly lower in fetuses with cardiac disease. CCOi was lower in HLHS, correlating with total brain volume - for every 10% CCOi increase, volume increased 8mm3 (95% CI: 1.78-14.1; p=0.012). Echocardiography parameters and cerebral oxygenation showed no correlation. TGA showed no CCOi or aortic output correlation with MRI measures. In HLHS, lower cardiac output is deleterious to brain development. Our findings provide insight into the role of fetal cardiovascular physiology in brain health.

A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region.

Pathogenic single-nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving the FOXF1 transcription factor gene or CNV deletions of its distant lung-specific enhancer are responsible for alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a rarely diagnosed lethal lung developmental disorder in neonates. In contrast to SNVs within FOXF1 and CNV deletions involving only the FOXF1 enhancer, larger-sized deletions involving FOXF1 and the adjacent, oppositely oriented lncRNA gene FENDRR have additionally been associated with hypoplastic left heart syndrome and single umbilical artery (SUA). Here, in an ACDMPV infant without any congenital heart defect or SUA, we identified a small 5 kb CNV deletion that removed the paternal allele of FOXF1 and its promoter, leaving FENDRR and its promoter intact. Reporter assay in the IMR-90 fetal cell line implied that the deletion may indeed not have significantly affected FENDRR expression. It also showed a polarization of the FOXF1-FENDRR inter-promoter region consisting of its ability to increase the transcription of FENDRR but not FOXF1. Interestingly, this transcription-stimulating activity was suppressed in the presence of the FOXF1 promoter. Our data shed more light on the interactions between neighboring promoters of FOXF1-FENDRR and possibly other divergently transcribed mRNA-lncRNA gene pairs.