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Background: Congenital heart disease (CHD) is a risk factor for developmental delay and for attention-deficit hyperactivity disorder (ADHD). The Cardiac Neurodevelopmental Outcome Collaborative has developed recommendations for ongoing monitoring of this at-risk population to be able to detect developmental, learning, and behavioral concerns, as they become apparent as a child ages., Case Presentation: A 4-year-old boy with tetralogy of Fallot with a ventricular septal defect repaired in infancy was followed periodically in the cardiac neurodevelopmental follow-up clinic and diagnosed with autism spectrum disorder as well as additional developmental and medical issues. He received early childhood special education and therapeutic interventions as well as social skills training and applied behavior analysis. At age 4 years, Alex presented with symptoms of hyperactivity, inattention, impulsivity, and immediate safety concerns for elopement. The clinician diagnosed him with ADHD-combined type. He was recommended to start medication in addition to behavioral and developmental supports. Managing medications in a child with CHD and ADHD presents unique challenges, and medication decisions were carefully made in collaboration with the child's cardiologist. After some medication adjustments and ongoing behavioral therapy to address behaviors associated with ADHD and autism spectrum disorder, the child is doing well academically and socially., Conclusion: Attention-deficit hyperactivity disorder medications can be safely prescribed in patients with CHD. However, pharmacotherapy for co-occurring ADHD and CHD needs an additional level of oversight and collaboration between cardiology and prescribing clinicians. Behavioral therapies can be transdiagnostic and address challenges associated with autism and symptoms related to ADHD., Competing Interests: K.E. Wallis has served as a consultant for Thomas Jefferson University and for Healthy Steps. She has received honoraria from Connecticut Children's Hospital, Cincinnati Children's Hospital, Monell Chemical Senses Center, Southern Connecticut State University, and Wellspan Health. The remaining authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Left atrial (LA) volume and peak longitudinal strain (LA strain) are indicators of left ventricular (LV) diastolic function in adults, but little is known about LA volume and strain in pediatric patients with hypertension (HTN). We evaluated LA volume and strain in pediatric cases with HTN compared to age-, sex-, and race/ethnicity-matched controls. This was a retrospective matched case-control study of patients who presented to the HTN clinic at CHOP from 12/2011 to 9/2018. Coarctation of the aorta, cardiomyopathy or heart transplantation cases were excluded. HTN was defined by an abnormal ambulatory blood pressure result. LA volume was measured by biplane area-length method and indexed to body surface area (BSA). LA strain and strain rate were measured using TOMTEC® software. Left ventricular mass index (LVMI) was measured by M-mode and the 5/6 area-length method indexed to height 2.7 . LV global longitudinal strain (LV GLS) was measured during the echocardiographic examination on the GE ultrasound machine for cases and offline using TOMTEC® software for controls. Measurements were compared using Chi-square, McNemar, or Wilcoxon signed rank tests. We included 47 cases and 47 controls. There was no difference in LA volume z-scores (- 1.9 vs. - 0.9, p = 0.068), LA strain (37.8% vs. 38.0%, p = 0.735) or LA strain rate (1.4 vs. 1.5, p = 0.852) in cases compared to controls. LVMI by M-mode and 5/6 area-length method was higher in cases compared to controls (40.0 vs. 33.7 g/m 2.7 , p < 0.001 and 29.9 vs 24.4 g/m 2.7 , p =  < 0.001, respectively). LV GLS was decreased (less negative) in cases compared to controls. In summary there was no difference in LA volume or LA strain in cases compared to controls. In cases, LVMI was significantly elevated and LV GLS was significantly decreased, which may be the first response to HTN, prior to affecting LA size., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Black patients with tetralogy of Fallot (TOF) have higher mortality than White patients. Health disparities related to other patient-important outcomes, such as exercise performance, have not been studied in this population. We aimed to determine if there are racial disparities related to exercise performance in patients with TOF and to investigate possible mediators of those disparities. We conducted a retrospective single center study of patients aged 8-25 years with repaired TOF who completed maximal cardiorespiratory exercise tests between 2007 and 2020. The primary outcome was percent predicted oxygen consumption at peak exercise. We used linear regression to determine if race was associated with exercise performance. We used mediation analysis to investigate insurance coverage and neighborhood Child Opportunity Index as possible mediators of this relationship. The study cohort included 163 patients with TOF (136 non-Hispanic/Latinx White and 27 non-Hispanic/Latinx Black). In multivariable analysis, Black patients had a lower percent predicted peak oxygen consumption than White patients by 6.71 percentage points (95% CI - 12.71, - 0.70; p = 0.029). Mediation analysis revealed that the indirect effect of race through insurance coverage accounted for 34.1% of the decrease in exercise performance. Child Opportunity Index was not a statistically significant mediator. Black patients with TOF had worse exercise performance than White patients. Differences in insurance coverage accounted for a significant portion of this difference. Exercise performance is an important outcome for patients with TOF, and further investigation is needed to better understand this disparity and develop interventions to address it., (© 2024. The Author(s).)

Neurodevelopmental sequelae are prevalent and debilitating for patients with congenital heart defects. Patients born with tetralogy of Fallot (TOF) are susceptible for abnormal neurodevelopment as they have several risk factors surrounding the perinatal and perioperative period. Some risk factors have been well described in other forms of congenital heart defects, including transposition of the great arteries and single ventricle heart disease, but they have been less studied in the growing population of survivors of TOF surgery, particularly in infancy and childhood. Adolescents with TOF, even without a genetic syndrome, exhibit neuro-cognitive deficits in executive function, visual-spatial skills, memory, attention, academic achievement, social cognition, and problem-solving, to mention a few. They also have greater prevalence of anxiety disorder, disruptive behavior and attention-deficit hyperactivity disorder. These deficits impact their academic performance, social adjustment, and quality of life, thus resulting in significant stress for patients and their families. Further, they can impact their social adjustment, employment and career development as an adult. Infants and younger children can also have significant deficits in gross and fine motor skills, cognitive deficits and abnormal receptive language. Many of the risk factors associated with abnormal neurodevelopment in these patients are not readily modifiable. Therefore, patients should be referred for evaluation and early intervention to help maximize their neurodevelopment and improve overall outcomes. More study is needed to identify potentially modifiable risk factors and/or mediators of neurodevelopment, such as environmental and socio-economic factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mercer-Rosa and Favilla.)

Background: Global longitudinal strain (GLS) is an echocardiographic method to identify left ventricular (LV) dysfunction after cardiac arrest that is less sensitive to loading conditions. We aimed to identify the frequency of impaired GLS following pediatric cardiac arrest, and its association with hospital mortality., Methods: This is a retrospective single-center cohort study of children <18 years of age treated in the pediatric intensive care unit (PICU) after in- or out-of-hospital cardiac arrest (IHCA and OHCA), with echocardiogram performed within 24 hours of initiation of post-arrest PICU care between 2013 and 2020. Patients with congenital heart disease, post-arrest extracorporeal support, or inability to measure GLS were excluded. Echocardiographic LV ejection fraction (EF) and shortening fraction (SF) were abstracted from the chart. GLS was measured post hoc; impaired strain was defined as LV GLS ≥ 2 SD worse than age-dependent normative values. Demographics and pre-arrest, arrest, and post-arrest characteristics were compared between subjects with normal versus impaired GLS. Correlation between GLS, SF and EF were calculated with Pearson comparison. Logistic regression tested the association of GLS with mortality. Area under the receiver operator curve (AUROC) was calculated for discriminative utility of GLS, EF, and SF with mortality., Results: GLS was measured in 124 subjects; impaired GLS was present in 46 (37.1%). Subjects with impaired GLS were older (median 7.9 vs. 1.9 years, p < 0.001), more likely to have ventricular tachycardia/fibrillation as initial rhythm (19.6% versus 3.8%, p = 0.017) and had higher peak troponin levels in the first 24 hours post-arrest (median 2.5 vs. 0.5, p = 0.002). There were no differences between arrest location or CPR duration by GLS groups. Subjects with impaired GLS compared to normal GLS had lower median EF (42.6% versus 62.3%) and median SF (23.3% versus 36.6%), all p < 0.001, with strong inverse correlation between GLS and EF (rho -0.76, p < 0.001) and SF (rho -0.71, p < 0.001). Patients with impaired GLS had higher rates of mortality (60% vs. 32%, p = 0.009). GLS was associated with mortality when controlling for age and initial rhythm [aOR 1.17 per 1% increase in GLS (95% CI 1.09-1.26), p < 0.001]. GLS, EF and SF had similar discrimination for mortality: GLS AUROC 0.69 (95% CI 0.60-0.79); EF AUROC 0.71 (95% CI 0.58-0.88); SF AUROC 0.71 (95% CI 0.61-0.82), p = 0.101., Conclusions: Impaired LV function as measured by GLS after pediatric cardiac arrest is associated with hospital mortality. GLS is a novel complementary metric to traditional post-arrest echocardiography that correlates strongly with EF and SF and is associated with mortality. Future large prospective studies of post-cardiac arrest care should investigate the prognostic utilities of GLS, alongside SF and EF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background Poor interstage weight gain is a risk factor for adverse outcomes in infants with hypoplastic left heart syndrome. We sought to examine the association of neighborhood social vulnerability and interstage weight gain and determine if this association is modified by enrollment in our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP). Methods and Results We performed a retrospective single-center study of infants with hypoplastic left heart syndrome before (2007-2010) and after (2011-2020) introduction of the ISVMP. The primary outcome was interstage weight gain, and the secondary outcome was interstage growth failure. Multivariable linear and logistic regression models were used to examine the association between the Social Vulnerability Index and the outcomes. We introduced an interaction term into the models to test for effect modification by the ISVMP. We evaluated 217 ISVMP infants and 111 pre-ISVMP historical controls. The Social Vulnerability Index was associated with interstage growth failure ( P =0.001); however, enrollment in the ISVMP strongly attenuated this association ( P =0.04). Pre-ISVMP, as well as high- and middle-vulnerability infants gained 4 g/d less and were significantly more likely to experience growth failure than low-vulnerability infants (high versus low: adjusted odds ratio [aOR], 12.5 [95% CI, 2.5-62.2]; middle versus low: aOR, 7.8 [95% CI, 2.0-31.2]). After the introduction of the ISVMP, outcomes did not differ by Social Vulnerability Index tertile. Infants with middle and high Social Vulnerability Index scores who were enrolled in the ISVMP gained 4 g/d and 2 g/d more, respectively, than pre-ISVMP controls. Conclusions In infants with hypoplastic left heart syndrome, high social vulnerability is a risk factor for poor interstage weight gain. However, enrollment in the ISVMP significantly reduces growth disparities.

Introduction: Racial and ethnic disparities in resource use among children with CHD remain understudied. We sought to evaluate associations between race, ethnicity, and resource utilisation in children with CHD., Materials and Methods: Annual data from the National Health Interview Survey were collected for years 2010-2018. Children with self-reported CHD and Non-Hispanic White race, Non-Hispanic Black race, or Hispanic ethnicity were identified. Resource use in the preceding year was identified with four measures: primary place of care visited when sick, receiving well-child checkups, number of emergency department visits, and number of office visits. Cohort characteristics were compared across racial and ethnic groups using Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to determine the association of race and ethnicity with likelihood of having an emergency department visit., Results: We identified 209 children for the primary analysis. Non-Hispanic Black children had significantly more emergency department visits in the prior year, with 11.1% having ≥6 emergency department visits compared to 0.7% and 5.6% of Non-Hispanic White and Hispanic children. Further, 35.2% of Hispanic children primarily received care at clinics/health centres, compared to 17% of Non-Hispanic White children and 11.1% of Non-Hispanic Black children (p = 0.03). On multivariable analysis, Black race was associated with higher odds of emergency department visit compared to White race (odds ratio = 4.19, 95% confidence interval = 1.35 to 13.04, p = 0.01)., Conclusion: In a nationally comprehensive, contemporary cohort of children with CHD, there were some significant racial and ethnic disparities in resource utilisation. Further work is needed to consider the role of socio-economics and insurance status in perpetuating these disparities.

Right ventricular (RV) dysfunction early after tetralogy of Fallot (TOF) increases post-operative morbidity. We investigated associations of circulating biomarkers and socioeconomic factors with early post-operative RV systolic function. Single-center prospective cohort study of infants undergoing TOF repair. Six serologic biomarkers of myocardial fibrosis and wall stress collected at the time of surgery were measured with immunoassay. Geocoding was performed for socioeconomic factors. Multivariate adaptive regression splines (MARS) models identified factors associated with RV function parameters: fractional area change (FAC), global longitudinal strain and strain rate, and free wall strain and strain rate. Seventy-one patients aged 3.5 months (IQR 2.4, 5.2) were included. Galectin-3 was the highest ranked predictor for FAC, global longitudinal strain, and free wall strain, and procollagen type-I carboxy-terminal propeptide (PICP) was the highest ranked predictor for global longitudinal strain rate and free wall strain rate. Several neighborhood characteristics were also highly ranked. Models adjusted R 2 ranged from 0.71 to 0.85 (FAC, global longitudinal strain/strain rate), and 0.55-0.57 (RV free wall strain/strain rate). A combination of serologic biomarkers, socioeconomic, and clinical variables explain a significant proportion of the variability in RV function after TOF repair. These factors may inform pre-operative risk-stratification for these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Right ventricular (RV) dysfunction is an independent predictor of poor outcomes in patients with tetralogy of Fallot (TOF), and global longitudinal strain (GLS) is a well-validated echocardiographic technique to measure RV function. Although trends in RV GLS have been examined in patients with TOF, they have not been studied specifically in those with ductal-dependent TOF, a group in which there is not a clear consensus on the best surgical strategy. The aim of this study was to assess the midterm trajectory of RV GLS in patients with ductal-dependent TOF, drivers of this trajectory, and differences in RV GLS between repair strategies., Methods: This was a retrospective two-center cohort study of patients with ductal-dependent TOF who underwent repair. Ductal dependence was defined as being initiated on prostaglandin therapy and/or undergoing surgical intervention on or before 30 days of life. RV GLS was measured on echocardiography preoperatively, early after complete repair, and at 1 and 2 years of age. RV GLS was trended over time and compared between surgical strategies and with control subjects. Mixed-effects linear regression models were used to evaluate the factors associated with changes in RV GLS over time., Results: Forty-four patients with ductal-dependent TOF were included in the study, of whom 33 (75%) underwent primary complete repair and 11 (25%) underwent staged repair. Complete TOF repair was performed at a median of 7 days in the primary-repair group and 178 days in the staged-repair group. RV GLS improved over time from post-complete repair echocardiography through 2 years of age (-17.4% [interquartile range, -15.5% to -18.9%] vs -21.5% [interquartile range, -18.0% to -23.3%], P < .001). However, compared with age-matched control subjects, patients had worse RV GLS at all time points. There was no difference in RV GLS between the staged and primary complete repair groups at 2-year follow-up. Shorter intensive care unit length of stay after complete repair was independently associated with improvement in RV GLS over time. Strain improved by 0.07% (95% CI, 0.01 to 0.12) for each fewer day in the intensive care unit (P = .03)., Conclusions: RV GLS improves over time among patients with ductal-dependent TOF, though it is consistently reduced compared with control subjects, suggesting an altered deformation pattern in patients with ductal-dependent TOF. There was no difference in RV GLS between the primary- and staged-repair groups at midterm follow-up, suggesting that repair strategy is not a risk factor for worse RV strain in the mid postoperative period. A shorter complete-repair intensive care unit length of stay is associated with an improved trajectory of RV GLS., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background The impact of home monitoring on unanticipated interstage readmissions in infants with hypoplastic left heart syndrome has not been previously studied. We sought to examine the association of our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP) with readmission frequency, cumulative readmission days, and readmission illness severity and to identify patient-level risk factors for readmission. Methods and Results We performed a retrospective single-center cohort study comparing infants with hypoplastic left heart syndrome enrolled in ISVMP (December 2010-December 2019) to historical controls (January 2007-November 2010). The primary outcome was number of readmissions per interstage days. Secondary outcomes were cumulative interstage readmission days and occurrence of severe readmissions. Inverse probability weighted and multivariable generalized linear models were used to examine the association between ISVMP and the outcomes. We compared 198 infants in the ISVMP to 128 historical controls. Infants in the ISVMP had more than double the risk of interstage readmission compared with controls (adjusted incidence rate ratio, 2.38 [95% CI, 1.50-3.78]; P =0.0003). There was no difference in cumulative interstage readmission days (adjusted incidence rate ratio, 1.02 [95% CI, 0.69-1.50]; P =0.90); however, infants in the ISVMP were less likely to have severe readmissions (adjusted odds ratio, 0.28 [95% CI, 0.11-0.68]; P =0.005). Other factors independently associated with number of readmissions included residing closer to our center, younger gestational age, genetic syndrome, and discharge on exclusive enteral feeds. Conclusions Infants in the ISVMP had more frequent readmissions but comparable readmission days and fewer severe unanticipated readmissions. These findings suggest that home monitoring can reduce interstage morbidity without increasing readmission days.

Primary Hypothesis: We hypothesized that higher alveolar dead space fraction (AVDSf) at pediatric acute respiratory distress syndrome (PARDS) onset would be associated with right ventricular (RV) systolic dysfunction within the first 24 h of PARDS., Study Design and Methods: We performed a retrospective single-center cohort study of PARDS patients with clinically obtained echocardiograms within 24 h. Primary exposure was AVDSf at PARDS onset. Primary outcome was RV systolic dysfunction as defined by RV global longitudinal strain (GLS) (>-18%). Secondary outcomes included pulmonary hypertension (PH) and RV systolic dysfunction as defined by other echocardiogram parameters, and measures of oxygenation. Unadjusted and adjusted logistic and linear regression were used to investigate AVDSf associations with outcomes., Results: Ninety-one patients were included: median age 6.2 years, 46% female, and 65% with moderate or severe PARDS. Median AVDSf was 0.2 (interquartile range [IQR] 0.0-0.3), 33% had RV dysfunction, and 21% had PH. Unadjusted and adjusted logistic regression showed no association between AVDSf and RV systolic dysfunction or PH by any echocardiographic measure, but unadjusted and adjusted linear regression did show an association between AVDSf and PaO 2 /FiO 2 ., Conclusion: AVDSf at PARDS onset was not associated with RV systolic dysfunction or PH within 24 h but was associated with PaO 2 /FiO 2 ratio and may be more reflective of pulmonary causes of ventilation-perfusion mismatch. Future investigations should focus on clarifying the clinical utility of AVDSf in relation to existing metrics throughout the course of PARDS., (© 2022 Wiley Periodicals LLC.)

Objectives: Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiography., Study Design: Prospective, observational study enrolling infants born at less than 32 weeks gestation and in whom (1) iNO therapy was initiated after admission to our institution, or (2) at the outside institution less than 48 h before transfer and received an echocardiogram prior to iNO initiation, and (3) had severe BPD. Data were collected at three time-points: (1) before iNO; (2) 12-48 h after initiation of iNO; and (3) 48-168 h after initiation of iNO. The primary outcome was the effect of iNO on pulmonary artery pressure measured by echocardiography in patients with severe BPD between 48 and 168 h after initiating iNO therapy., Results: Of 37 enrolled, 81% had echocardiographic evidence of pulmonary arterial hypertension (PAH) before iNO and 56% after 48 h of iNO (p = 0.04). FiO2 requirements were significantly different between time-points (1) and (3) (p = 0.05). There were no significant differences between Tricuspid Annular Plane Systolic Excursion (TAPSE) Z-Scores, time to peak velocity: right ventricular ejection time (TPV:RVET), and ventilator changes., Conclusions: Although we found a statistically significant reduction of PAH between time-point (1) and (3), future trials are needed to further guide clinical care., (© 2023 S. Karger AG, Basel.)

Objective: To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH)., Study Design: Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood., Result: After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001]., Conclusion: In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Despite favorable short-term outcomes, Fontan palliation is associated with comorbidities and diminished quality of life (QOL) in the years after completion. We hypothesized that poor Fontan hemodynamics and ventricular function are associated with worse QOL., Methods: This was a single-center study of Fontan survivors aged more than 12 years. Subjects completed a cardiac magnetic resonance scan and QOL questionnaire. Cardiac magnetic resonance-derived variables included Fontan geometry, and hemodynamics. Computational fluid dynamics simulations quantified power loss, pressure drop, and total cavopulmonary connection resistance across the Fontan. Quality of life was assessed by completion of the Pediatric Quality of Life Inventory. Longitudinal and cross-sectional comparisons were made between cardiac magnetic resonance and computational fluid dynamics parameters with patient-reported QOL., Results: We studied 77 Fontan patients, median age 19.7 years (interquartile range, 17.1 to 23.6), median time from Fontan completion 16 years (interquartile range, 13 to 20). Longitudinal data were available for 48 patients; median time between cardiac magnetic resonance and QOL was 8.1 years (interquartile range, 7 to 9.4). Median patient-reported Pediatric Quality of Life Inventory total score was 80 (interquartile range, 67.4 to 88). Greater power loss and smaller left pulmonary artery diameter at baseline were associated with worse QOL at follow-up. Greater pressure drop was associated with worse QOL at the same time point., Conclusions: For Fontan survivors, measures of computational fluid dynamics hemodynamics and geometry are associated with worse QOL. Interventional strategies targeted at optimizing the Fontan may improve QOL., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Diastolic dysfunction after repair for Tetralogy of Fallot (TOF) is associated with adverse long-term outcomes. Right atrial (RA) mechanics as a proxy of right ventricular (RV) diastolic function in the early post-operative period after surgical repair for TOF has not been reported. We sought to evaluate RA and RV strain prior to hospital discharge after TOF repair and to identify important patient factors associated with strain using a machine learning method. Single center retrospective cohort study of TOF patients undergoing surgical repair, with analysis of RA and RV strain from pre-and post-operative echocardiograms. RA function was assessed by the peak RA strain, systolic RA strain rate, early diastolic RA strain rate and RA emptying fraction. RV systolic function was measured by global longitudinal strain. Pre- and post-operative values were compared using Wilcoxon rank sum test. Gradient boosted machine (GBM) models were used to identify the most important predictors of post-operative strain. In total, 153 patients were enrolled, median age at TOF repair 3.5 months (25th-75th percentile: 2.2- 5.2), mostly male (67%), and White (64.1%). From pre-to post-operative period, there was significant worsening in all RA parameters and in RV strain. GBM models identified patient, anatomic, and surgical factors that were strong predictors of post-operative RA and RV strain. These factors included pulmonary valve and branch pulmonary artery Z scores, birth weight, gestational age and age at surgery, pre-operative RV fractional area change and oxygen saturation, type of outflow tract repair, duration of cardiopulmonary bypass, and early post-operative partial arterial pressure of oxygen. There is significant worsening in RA and RV strain early after TOF repair, indicating early alteration in diastolic and systolic function after surgery. Several patient and operative factors influence post-operative RV function. Most of the factors described are not readily modifiable, however they may inform pre-operative risk-stratification. The clinical application of RA strain and the prognostic implication of these early changes merit further study., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Serum biomarkers of myocardial fibrosis are considered markers of adverse outcome in adults with heart disease. Associations between biomarkers and clinical parameters in tetralogy of Fallot (TOF) has been understudied. We compared serum biomarker profiles with clinical and cardiac magnetic resonance (CMR) parameters of ventricular remodeling in patients with repaired TOF., Methods: Serum biomarkers [metalloproteinases MMP1 and MMP9, galectin-3, micro-RNA21 (miR21)), ST2, procollagen type I carboxy-terminal propeptide (PICP), and NTproBNP] were measured in TOF patients undergoing CMR. Associations between biomarkers and clinical and CMR variables were assessed using correlation coefficients, and linear and logistic regression., Results: Sixty patients were investigated, of which 47% were male. Age at CMR and TOF repair was 15 years [interquartile range (IQR) 9, 22] and 3.2 months (IQR 0.8, 6.2), respectively. Twelve (20%) had prior pulmonary valve replacement (PVR). MMP1 values were higher among those with prior PVR (16.7 (IQR 7.9, 25.5) vs 14.4 (IQR 9.9, 24.9), p = 0.02). When stratifying MMP1 into low and high groups, higher MMP1 was associated with higher indexed right (RV) and left ventricular (LV) mass and RV mass:volume ratios after adjusting for PVR. No other associations between biomarkers and CMR parameters were identified., Conclusions: Only MMP1 was associated with markers of RV remodeling after TOF repair. As an enzyme involved in extracellular matrix degradation, MMP1 could be associated with fibrotic processes underlying RV remodeling, including dilation and hypertrophy. The additional biomarkers may not be specific towards cardiac remodeling. These findings merit further correlations with myocardial fibrosis measurements by CMR., (Copyright © 2022 Elsevier B.V. All rights reserved.)

BACKGROUND Children with single ventricle heart disease have significant morbidity and mortality. The maternal-fetal environment (MFE) may adversely impact outcomes after neonatal cardiac surgery. We hypothesized that impaired MFE would be associated with an increased risk of death after stage 1 Norwood reconstruction. METHODS AND RESULTS We performed a retrospective cohort study of children with hypoplastic left heart syndrome (and anatomic variants) who underwent stage 1 Norwood reconstruction between 2008 and 2018. Impaired MFE was defined as maternal gestational hypertension, preeclampsia, gestational diabetes, and/or smoking during pregnancy. Cox proportional hazards regression models were used to investigate the association between impaired MFE and death while adjusting for confounders. Hospital length of stay was assessed with the competing risk of in-hospital death. In 273 children, the median age at stage 1 Norwood reconstruction was 4 days (interquartile range [IQR], 3-6 days). A total of 72 children (26%) were exposed to an impaired MFE; they had more preterm births (18% versus 7%) and a greater percentage with low birth weights <2.5 kg (18% versus 4%) than those without impaired MFE. Impaired MFE was associated with a higher risk of death (hazard ratio [HR], 6.05; 95% CI, 3.59-10.21; P <0.001) after adjusting for age at surgery, Hispanic ethnicity, genetic syndrome, cardiac diagnosis, surgeon, and birth era. Children with impaired MFE had almost double the risk of prolonged hospital stay (HR, 1.95; 95% CI, 1.41-2.70; P <0.001). CONCLUSIONS Children exposed to an impaired MFE had a higher risk of death following stage 1 Norwood reconstruction. Prenatal exposures are potentially modifiable factors that can be targeted to improve outcomes after pediatric cardiac surgery.

Background: Little is known regarding right ventricular (RV) remodeling immediately after Tetralogy of Fallot (TOF) repair. We sought to describe myocardial deformation by cardiac magnetic resonance imaging (CMR) after TOF repair and investigate associations between these parameters and early post-operative outcomes., Methods: Fifteen infants underwent CMR without sedation as part of a prospective pilot study after undergoing complete TOF repair, prior to hospital discharge. RV deformation (strain) was measured using tissue tracking, in addition to RV ejection fraction (EF), volumes, and pulmonary regurgitant fraction. Pearson correlation coefficients were used to determine associations between both strain and CMR measures/clinical outcomes., Results: Most patients were male (11/15, 73%), with median age at TOF repair 53 days (interquartile range, 13,131). Most patients had pulmonary stenosis (vs. atresia) (11/15, 73%) and 7 (47%) received a transannular patch as part of their repair. RV function was overall preserved with mean RV EF of 62% (standard deviation [SD], 9.8). Peak radial and longitudinal strain were overall diminished (mean ± SD, 33.80 ± 18.30% and -15.50 ± 6.40%, respectively). Longer hospital length of stay after TOF repair was associated with worse RV peak radial ventricular strain (correlation coefficient (r), -0.54; p = 0.04). Greater pulmonary regurgitant fraction was associated with shorter time to peak radial RV strain (r = -0.55, p = 0.03)., Conclusions: In this small study, our findings suggest presence of early decrease in RV strain after TOF repair and its association with hospital stay when changes in EF and RV size are not yet apparent., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022 Korean Society of Echocardiography.)

Introduction: Tetralogy of Fallot (TOF) repair is associated with excellent operative survival. However, a subset of patients experiences post-operative complications, which can significantly alter the early and late post-operative course. We utilized a machine learning approach to identify risk factors for post-operative complications after TOF repair. Methods: We conducted a single-center prospective cohort study of children <2 years of age with TOF undergoing surgical repair. The outcome was occurrence of post-operative cardiac complications, measured between TOF repair and hospital discharge or death. Predictors included patient, operative, and echocardiographic variables, including pre-operative right ventricular strain and fractional area change as measures of right ventricular function. Gradient-boosted quantile regression models (GBM) determined predictors of post-operative complications. Cross-validated GBMs were implemented with and without a filtering stage non-parametric regression model to select a subset of clinically meaningful predictors. Sensitivity analysis with gradient-boosted Poisson regression models was used to examine if the same predictors were identified in the subset of patients with at least one complication. Results: Of the 162 subjects enrolled between March 2012 and May 2018, 43 (26.5%) had at least one post-operative cardiac complication. The most frequent complications were arrhythmia requiring treatment ( N = 22, 13.6%), cardiac catheterization ( N = 17, 10.5%), and extracorporeal membrane oxygenation (ECMO) ( N = 11, 6.8%). Fifty-six variables were used in the machine learning analysis, of which there were 21 predictors that were already identified from the first-stage regression. Duration of cardiopulmonary bypass (CPB) was the highest ranked predictor in all models. Other predictors included gestational age, pre-operative right ventricular (RV) global longitudinal strain, pulmonary valve Z-score, and immediate post-operative arterial oxygen level. Sensitivity analysis identified similar predictors, confirming the robustness of these findings across models. Conclusions: Cardiac complications after TOF repair are prevalent in a quarter of patients. A prolonged surgery remains an important predictor of post-operative complications; however, other perioperative factors are likewise important, including pre-operative right ventricular remodeling. This study identifies potential opportunities to optimize the surgical repair for TOF to diminish post-operative complications and secure improved clinical outcomes. Efforts toward optimizing pre-operative ventricular remodeling might mitigate post-operative complications and help reduce future morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Faerber, Huang, Zhang, Song, DeCost, Mascio, Ravishankar, O'Byrne, Naim, Kawut, Goldmuntz and Mercer-Rosa.)

The importance of preoperative cardiac function in pediatric lung transplantation is unknown. We hypothesized that worse preoperative right ventricular (RV) systolic and worse left ventricular (LV) diastolic function would be associated with a higher risk of primary graft dysfunction grade 3 (PGD 3) between 48 and 72 hours. We performed a single center, retrospective pilot study of children (<18 years) who had echocardiograms <1 year prior to lung transplantation between 2006 and 2019. Conventional and strain echocardiography parameters were measured, and PGD was graded. Area under the receiver operating characteristic (AUROC) curves and logistic regression were performed. Forty-one patients were included; 14 (34%) developed PGD 3 and were more likely to have pulmonary hypertension (PH) as the indication for transplant (P = .005). PGD 3 patients had worse RV global longitudinal strain (P = .01), RV free wall strain (FWS) (P = .003), RV fractional area change (P = .005), E/e' (P = .01) and lateral e' velocity (P = .004) but not tricuspid annular plane systolic excursion (P = .61). RV FWS (AUROC 0.79, 95% CI 0.62-0.95) and lateral e' velocity (AUROC 0.87, 95% CI 0.68-1.00) best discriminated PGD 3 development and showed the strongest association with PGD 3 (RV FWS OR 3.87 [95% CI 1.59-9.43], P = .003; lateral e' velocity OR 0.10 [95% CI 0.01-0.70], P = .02). These associations remained when separately adjusting for age, weight, primary PH diagnosis, ischemic time, and bypass time. In this pilot study, worse preoperative RV systolic and worse LV diastolic function were associated with PGD 3 and may be modifiable recipient risk factors in pediatric lung transplantation., (© 2020 Wiley Periodicals LLC.)

Neurodevelopmental sequelae are prevalent among patients with congenital heart defects (CHD). In a study of infants and children with repaired tetralogy of Fallot (TOF), we sought to identify those at risk for abnormal neurodevelopment and to test associations between socioeconomic and medical factors with neurodevelopment deficits. Single-center retrospective observational study of patients with repaired TOF that were evaluated at the institution's Cardiac Kids Developmental Follow-up Program (CKDP) between 2012 and 2018. Main outcomes included neurodevelopmental test scores from the Bayley Infant Neurodevelopmental Screener (BINS), Peabody Developmental Motor Scale (PDMS), and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Mixed effects linear regression and marginal logistic regression models tested relationships between patient characteristics and outcomes. Sub-analyses were conducted to test correlations between initial and later neurodevelopment tests. In total, 49 patients were included, predominantly male (n = 33) and white (n = 28), first evaluated at a median age of 4.5 months. Forty-three percent of patients (n = 16) had deficits in the BINS, the earliest screening test. Several socioeconomic parameters and measures of disease complexity were associated with neurodevelopment, independently of genetic syndrome. Early BINS and PDMS performed in infancy were associated with Bayley-III scores performed after 1 year of age. Early screening identifies TOF patients at risk for abnormal neurodevelopment. Socioeconomic factors and disease complexity are associated with abnormal neurodevelopment and should be taken into account in the risk stratification and follow-up of these patients. Early evaluation with BINS and PDMS is suggested for detection of early deficits.

Background Children with congenital heart disease (CHD) are known to consume a disproportionate share of resources, yet there are limited data concerning trends in resource use and mortality among admitted children with CHD. We hypothesize that charges in CHD-related admissions increased but that mortality improved over time. Methods and Results This study, including patients <18 years old with CHD, examined inpatient admissions from the nationally representative Kids' Inpatient Database from 2003 to 2016 in order to assess the frequency, medical complexity, and outcomes of CHD hospital admissions. A total of 859 843 admissions of children with CHD were identified. CHD admissions increased by 31.8% from 2003 to 2016, whereas overall pediatric admissions decreased by 13.4%. Compared with non-CHD admissions, those with CHD were more likely to be <1 year of age (80.5% versus 63.3%), and to have ≥1 complex chronic condition (39.7% versus 9.3%). For CHD admissions, mortality was higher (2.97% versus 0.31%) and adjusted median charges greater ($48 426 [interquartile range (IQR), $11.932-$161 048] versus $4697 [IQR, $2551-$12 301]) ( P <0.0001 for all). Among CHD admissions, whereas adjusted median charges increased from $35 577 (IQR, $9303-$110 439) to $61 696 (IQR, $15 212-$219 237), mortality decreased from 3.2% to 2.7% ( P for trend <0.0001). CHD admissions accounted for an increased proportion of all inpatient deaths, from 18.0% in 2003 to 24.5% in 2016. Conclusions Children admitted with CHD are 10 times more likely to die than those without CHD and have higher charges. Although the rate of mortality in CHD admissions decreased, children with CHD accounted for an increasing proportion of all pediatric inpatient deaths. Effective resource allocation is critical to optimize outcomes in these high-risk patients.

Background: Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health., Methods: Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical-4 chamber (LS A4C ) and midpoint circumferential strain (CS mid ) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health., Results: Average SLE disease duration was 3.2 years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LS A4C was significantly reduced in pSLE subjects compared to controls (mean -18.3 [SD 3.2] vs -21.8% [SD 2.2], P-value <.001). There was no significant difference in CS mid (-24.8 [SD 3.7] vs -25.7% [SD 3.4], P = .29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r -0.59, P = .01)., Conclusions: Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow-up of patients with pSLE., (© 2020 Wiley Periodicals LLC.)

Rationale: Brain-type natriuretic peptide (BNP) correlates with pulmonary hypertension as demonstrated by echocardiogram in congenital diaphragmatic hernia (CDH); however, its association with right ventricular (RV) function and mortality is unknown. Objectives: To characterize the relationships between echocardiogram-derived RV strain, BNP, and mortality in diaphragmatic hernia. Methods: We performed a single-center retrospective cohort study of infants with CDH and at least one BNP-echocardiogram pair within a 24-hour period. RV global longitudinal strain (GLS) and free-wall strain (FWS) were measured on existing echocardiograms. Associations among strain, BNP, and mortality were tested using mixed-effect linear and logistic regression models. Survival analysis was stratified by BNP and strain abnormalities. Results: There were 220 infants with 460 BNP-echocardiogram pairs obtained preoperatively ( n  = 237), ≤1 week postoperatively ( n  = 35), and >1 week postoperatively ("recovery"; n  = 188). Strain improved after repair ( P  < 0.0001 for all periods). Higher BNP level was associated with worse strain in recovery but not before or immediately after operation (estimate [95% confidence interval] for recovery: GLS, 1.03 [0.50-1.57]; P  = 0.0003; FWS, 0.62 [0.01-1.22]; P  = 0.047). BNP and strain abnormalities were associated with an extracorporeal-membrane oxygenation requirement. Higher BNP level in recovery was associated with greater mortality (odds ratio, 11.2 [1.2-571.3]; P  = 0.02). Abnormal strain in recovery had high sensitivity for detection of mortality (100% for GLS; 100% for FWS) but had low specificity for detection of mortality (28% for GLS; 48% for FWS). Conclusions: Persistent RV dysfunction after CDH repair may be detected by a high BNP level and abnormal RV strain.

The principal aim of this study was to evaluate changes in systolic function in the single right ventricle (SRV), during progression of the same patient through the three stages of surgical repair for hypoplastic left heart syndrome and during a 5-year follow-up. We hypothesize that, SRV global longitudinal strain (GLS) will be low during 3 stages of repair even in stable patients. We retrospectively evaluated 140 echocardiograms in 20 patients with HLHS (ages 0-11.3 years), before and after 3 stages of surgical palliation. Five-year follow-up data were available in all 20 patients. Controls with structurally normal hearts and in the same age group were used for comparison. We utilized speckle-tracking imaging for assessment of SRV segmental and global longitudinal and circumferential strains, from previously acquired 4-chamber and mid-cavity short-axis views prior to and within 1-3 months of each surgical stage. Longitudinal strain (LS) remained low through all 3 stages of repair and during follow-up. The pre-Fontan stage demonstrated significant interstage improvement compared to the post-Glenn stage despite similar volume status. Global LS was (- 15.6 ± 4.5% after Fontan surgery and remained similar (- 15.32 ± 3.2%) 5 years later. The SRV also showed increased dominance of circumferential strain compared to the normal RV, where the longitudinal deformation was dominant. In SRV, longitudinal strain may be a useful clinical index for evaluating both segmental and global function in an objective manner. Due to lack of significant clinical deterioration over a 10-year period, we speculate that a "lower-than-normal" longitudinal strain may be used as an objective measure of SRV function in clinically stable patients, particularly after the Fontan operation. Compensatory mechanisms where the longitudinal pattern of contraction switches to a more circumferential pattern, may play a role in asymptomatic patients with HLHS.

Background: Left atrioventricular valve regurgitation (LAVVR) after atrioventricular canal (AVC) repair remains a significant cause of morbidity. Papillary muscle arrangement may be important. To investigate the implications of left mural leaflet morphology, we examined anatomic characteristics of the LAVV to determine possible associations with postoperative LAVVR., Methods: All patients with biventricular AVC repair at our institution between January 1, 2011, and December 31, 2016, with necessary imaging were retrospectively reviewed. We assessed papillary muscle structure and novel measures of the left mural leaflet from preoperative echocardiograms and the degree of LAVVR from the first and last available follow-up echocardiograms. Associations with degree of early and late postoperative LAVVR were assessed with t tests, analysis of variance, or χ 2 or Fisher exact tests, and multivariable logistic regression., Results: There were 58 of 156 patients (37%) with significant (moderate or severe) early postoperative LAVVR, and 30 of 93 (32%) had significant LAVVR after 6 or more months. Fewer patients with closely spaced or asymmetric papillary muscles had moderate or severe late LAVVR vs those with widely spaced papillary muscles (17% vs 40%, P = .019). Controlling for weight at operation, genetic syndromes, and bypass time, widely spaced papillary muscles increased the odds ratio for late LAVVR to 3.6 (P = .026). Larger mural leaflet area was also associated with late LAVVR on univariable (P = .019) and multivariable (P = .023) analyses. One-third of patients with significant late LAVVR had no significant early postoperative regurgitation., Conclusions: Mural leaflet and papillary muscle anatomy are associated with late LAVVR after AVC repair. Late regurgitation can develop in the absence of early LAVVR, suggesting different mechanisms., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: While numerous indices have been developed in an attempt to quantify ventricular function in patients with single ventricle heart disease after Fontan, there are little data on how these parameters change over time., Methods: A retrospective observational study was performed of individuals who underwent Fontan operation at Children's Hospital of Philadelphia (CHOP) in 2006 and 2007. Measurements of fractional area change (FAC), tricuspid annular planar systolic excursion (TAPSE), myocardial performance index (MPI), systolic to diastolic (s/d) ratio, and myocardial strain and strain rate were made offline. A composite outcome of protein-losing enteropathy (PLE), plastic bronchitis, transplant, or death was created, and change in function was compared between those who did and those who did not meet the outcome., Results: There were 312 echocardiograms from 40 unique patients (75% male, 55% dominant right ventricle). The aggregate mean values for most assessed parameters were worse than what would be expected for a healthy age-matched population. The global longitudinal strain rate increased (worsened) by 0.014 (1/s) per year (P = .02), and the global circumferential strain rate increased (worsened) by 0.011 (1/s) per year (P = .01). There was no difference in the rate of change of ventricular function in the 6 patients who met the composite endpoint vs those who did not., Conclusion: This study demonstrates that global longitudinal strain rate and global circumferential strain rate decrease over 10 years following Fontan operation. These measures of ventricular performance may be early signs of cardiac dysfunction that predate more obvious echocardiographic signs of deterioration., (© 2020 Wiley Periodicals, Inc.)

Background Despite excellent operative survival, correction of tetralogy of Fallot frequently is accompanied by residual lesions that may affect health beyond the incident hospitalization. Measuring resource utilization, specifically cost and length of stay, provides an integrated measure of morbidity not appreciable in traditional outcomes. Methods and Results We conducted a retrospective cohort study, using de-identified commercial insurance claims data, of 269 children who underwent operative correction of tetralogy of Fallot from January 2004 to September 2015 with ≥2 years of continuous follow-up (1) to describe resource utilization for the incident hospitalization and subsequent 2 years, (2) to determine whether prolonged length of stay (>7 days) in the incident hospitalization was associated with increased subsequent resource utilization, and (3) to explore whether there was regional variation in resource utilization with both direct comparisons and multivariable models adjusting for known covariates. Subjects with prolonged incident hospitalization length of stay demonstrated greater resource utilization (total cost as well as counts of outpatient visits, hospitalizations, and catheterizations) after hospital discharge ( P <0.0001 for each), though the number of subsequent operative and transcatheter interventions were not significantly different. Regional differences were observed in the cost of incident hospitalization as well as subsequent hospitalizations, outpatient visits, and the costs associated with each. Conclusions This study is the first to report short- and medium-term resource utilization following tetralogy of Fallot operative correction. It also demonstrates that prolonged length of stay in the initial hospitalization is associated with increased subsequent resource utilization. This should motivate research to determine whether these differences are because of modifiable factors.

Background: Loss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring (ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE)., Methods: Twenty subjects 9-19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures., Results: The majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (r 0.5, p = 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6, p = 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (ρ 0.6, p = 0.01 and ρ 0.7, p < 0.01, respectively), but not with endothelial function or intima-media thickness., Conclusion: In a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.

Rationale : Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups. Objectives : To define the frequency of three disease components: moderate-severe parenchymal disease, pulmonary hypertension (PH), or large airway disease, in a referral cohort of preterm infants with severe BPD. The association between each component and a primary composite outcome of death before hospital discharge, tracheostomy, or home pulmonary vasodilator therapy was assessed. Methods : This was a retrospective, single-center cohort study of infants born at <32 weeks' gestation with severe BPD who underwent both chest computed tomography with angiography (CTA) and echocardiography between 40 and 50 weeks postmenstrual age between 2011 and 2015. Moderate-severe parenchymal lung disease was defined as an Ochiai score ≥8 on CTA. PH was diagnosed by echocardiogram using standard criteria. Large airway disease was defined as tracheomalacia or bronchomalacia on bronchoscopy and/or tracheoscopy or CTA. Measurements and Main Results : Of 76 evaluated infants, 73 (96%) were classifiable into phenotypic subgroups: 57 with moderate-severe parenchymal disease, 48 with PH, and 44 with large airway disease. The presence of all three disease components was most common ( n  = 23). Individually, PH and large airway disease, but not moderate-severe parenchymal disease, were associated with increased risk for the primary study outcome. Having more disease components was associated with an incremental increase in the risk for the primary outcome (2 vs. 1: odds ratio, 4.9; 95% confidence interval, 1.4-17.2 and 3 vs. 1: odds ratio, 12.8; 95% confidence interval, 2.4-70.0). Conclusions : Infants with severe BPD are variable in their predominant pathophysiology. Disease phenotyping may enable better risk stratification and targeted therapeutic intervention.

Although the Cone procedure has improved outcomes for patients with Ebstein´s anomaly (EA), neither RV systolic function recovery in long-term follow-up nor the best echocardiographic parameters to assess RV function are well established. Thus, we evaluated RV performance after the Cone procedure comparing two-dimensional (2DEcho) and three-dimensional (3DEcho) echocardiography to cardiac magnetic resonance (CMR). We assessed 27 EA patients after the Cone procedure (53% female, median age of 20 years at the procedure, median post-operative follow-up duration of 8 years). Echocardiography was performed 4 h apart from the CMR. RV global longitudinal strain (GLS), fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index and tissue Doppler S' velocity were assessed using 2DEcho, whereas 3DEcho was used to evaluate RV volumes and ejection fraction (RVEF). Echocardiographic variables were compared to CMR-RVEF. All patients were in the NYHA functional class I. Median TAPSE was 15.9 mm, FAC 30.2%, and RV-GLS -15%; median RVEF by 3DEcho was 31.9% and 43% by CMR. Among 2DEcho parameters, RV-GLS and FAC had a substantial correlation with CMR-RVEF (r =  - 0.63 and r = 0.55, respectively); from 3DEcho, the indexed RV volumes and RVEF were closely correlated with CMR (RV-EDVi, r = 0.60, RV-ESVi, r = 0.72; and RVEF r = 0.60). RV systolic function is impaired years after the Cone procedure, despite a good clinical status. FAC and RV-GLS are useful 2DEcho tools to assess RV function in these patients; however, 3DEcho measurements appear to provide a better RV assessment.

Objectives: In adult in-hospital cardiac arrest, pulmonary hypertension is associated with worse outcomes, but pulmonary hypertension-associated in-hospital cardiac arrest has not been well studied in children. The objective of this study was to determine the prevalence of pulmonary hypertension among children with in-hospital cardiac arrest and its impact on outcomes., Design: Retrospective single-center cohort study., Setting: PICU of a quaternary care, academic children's hospital., Patients: Children (<18 yr old) receiving greater than or equal to 1 minute of cardiopulmonary resuscitation (cardiopulmonary resuscitation) for an index in-hospital cardiac arrest with an echocardiogram in the 48 hours preceding in-hospital cardiac arrest, excluding those with cyanotic congenital heart disease., Interventions: None., Measurements and Main Results: Of 284 in-hospital cardiac arrest subjects, 57 (20%) had evaluable echocardiograms, which were analyzed by a cardiologist blinded to patient characteristics. Pulmonary hypertension was present in 20 of 57 (35%); nine of 20 (45%) had no prior pulmonary hypertension history. Children with pulmonary hypertension had worse right ventricular systolic function, measured by fractional area change (p = 0.005) and right ventricular global longitudinal strain (p = 0.046); more right ventricular dilation (p = 0.010); and better left ventricular systolic function (p = 0.001). Children with pulmonary hypertension were more likely to have abnormal baseline functional status and a history of chronic lung disease or acyanotic congenital heart disease and less likely to have sepsis or acute kidney injury. Children with pulmonary hypertension were more likely to have an initial rhythm of pulseless electrical activity or asystole and were more frequently treated with inhaled nitric oxide (80% vs 32%; p < 0.001) at the time of cardiopulmonary resuscitation. On multivariable analysis, pulmonary hypertension was not associated with event survival (14/20 [70%] vs 24/37 [65%]; adjusted odds ratio, 1.30 [CI95, 0.25-6.69]; p = 0.77) or survival to discharge (8/20 [40%] vs 10/37 [27%]; adjusted odds ratio, 1.17 [CI95, 0.22-6.44]; p = 0.85)., Conclusions: Pulmonary hypertension physiology preceding pediatric in-hospital cardiac arrest may be more common than previously described. Among this cohort with a high frequency of inhaled nitric oxide treatment during cardiopulmonary resuscitation, pulmonary hypertension was not associated with survival outcomes.

Background: The optimal management of tetralogy of Fallot (TOF) in symptomatic neonates remains unknown. We compared outcomes for those undergoing palliation vs complete repair in the neonatal period., Methods: In a retrospective cohort study of symptomatic neonates with TOF who had a neonatal complete repair (group 1, n = 112) or staged repair (group 2, n = 26) from 2000 to 2013, we compared outcomes at 4 time points: neonatal complete repair vs palliation (group 1 vs 2A), neonatal vs later complete repair (group 1 vs 2B), the single vs combined admissions to achieve a complete repair (group 1 vs group 2A + 2B), and cumulative events 2 years after complete repair for both groups., Results: Demographics, anatomy, comorbidities, surgical approach, and mortality were similar between groups 1 and 2. Group 1 had a longer duration of cardiopulmonary bypass and deep hypothermic circulatory arrest and more postprocedure cardiac events compared with group 2A; a longer duration of intubation, intensive care, and postprocedure hospital stay compared with groups 2A and 2B; and a longer total hospital stay compared with group 2B. With combined admissions for group 2, there was no difference in the total duration of intensive care, total hospital stay, or reinterventions compared with group 1., Conclusions: Both management options result in similar survival; however, early morbidity was greater with neonatal complete repair. The impact of increased neonatal exposures, such as cardiopulmonary bypass, deep hypothermic circulatory arrest, and intensive care, on neurocognitive development requires further study but should be considered when choosing an optimal strategy., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The trajectory and importance of right ventricular systolic function and pulmonary hypertension during the course of pediatric acute respiratory distress syndrome are unknown. We hypothesized that new or persistent right ventricular systolic dysfunction and pulmonary hypertension would be associated with worse patient outcomes., Design: Retrospective, single-center cohort study., Setting: Tertiary care, university-affiliated PICU., Patients: Children who had at least two echocardiograms less than 8 days following pediatric acute respiratory distress syndrome diagnosis., Interventions: None., Measurements and Main Results: Between July 1, 2012, and April 30, 2018, 74 children met inclusion criteria. The first echocardiogram was performed a median of 0.61 days (interquartile range, 0.36-0.94 d) and the second echocardiogram was performed a median of 2.57 days (interquartile range, 1.67-3.63 d) after pediatric acute respiratory distress syndrome diagnosis. Univariate analyses showed that new or persistent right ventricular systolic dysfunction as defined by global longitudinal strain or free wall strain was associated with a greater number of ICU days in survivors (global longitudinal strain p = 0.04, free wall strain p = 0.04), lower ventilator-free days at 28 days (global longitudinal strain p = 0.03, free wall strain p = 0.01), and higher rate of PICU death (global longitudinal strain p = 0.046, free wall strain p = 0.01). Mixed-effects multivariate modeling showed that right ventricular global longitudinal strain and right ventricular fractional area change stayed relatively constant over the course of the first 8 days in nonsurvivors and that there was a linear improvement in global longitudinal strain (p = 0.037) and fractional area change (p = 0.05) in survivors. Worsening right ventricular dysfunction at the time of repeat echocardiogram as defined by global longitudinal strain and free wall strain were independently associated with decreased probability of extubation (subdistribution hazard ratio, 0.30 [0.14-0.67]; p = 0.003 and subdistribution hazard ratio, 0.47 [0.23-0.98]; p = 0.043, respectively). In univariate and multivariate analyses, pulmonary hypertension had no significant associations with outcomes in his cohort., Conclusions: New or persistent right ventricular systolic dysfunction over the first week following pediatric acute respiratory distress syndrome onset is associated with worse patient outcomes, including decreased probability of extubation and higher PICU mortality.

Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.

Objective: Children with single ventricle cardiac disease (SVCD) have poor growth in early life. Tube-assisted feeding (TF) is used to improve weight gain, but its impact on long-term growth remains unknown. We sought to compare the longitudinal growth of SVCD patients receiving TF after initial cardiac surgery with those fed entirely by mouth., Design: We conducted a retrospective cohort study of SVCD patients who underwent initial surgical palliation between 1999 and 2009. We defined TF as the use of nasogastric, gastrostomy, or jejunostomy TF. We compared maximal attained growth z-scores for each year of life between TF and non-TF patients. A secondary analysis compared surgical and clinical factors between groups., Results: A total of 134 patients were included; 64% were male and 68% underwent the Norwood operation. One third of patients (44) received TF. Adjusting for age, TF patients had an average of 0.56 lower weight-for-age z-score (WAZ) than non-TF patients (P = 0.007) through the age of 6 years. Longitudinal height was not affected by TF status (P = 0.15). In a subanalysis of Norwood patients, TF patients had lower WAZ at initial hospital discharge despite longer LOS. TF patients had diminished WAZ after adjusting for complications, interstage hospitalizations, and timing of subsequent operations., Conclusions: In this single-center study, patients with SVCD requiring TF at discharge from initial surgical palliation had diminished WAZ at discharge and on long-term follow-up, despite controlling for other identifiable risk factors. Further investigation is needed to understand the mechanisms underlying this phenomenon and to risk stratify infants who go home on TF., (© 2019 Wiley Periodicals, Inc.)

Background: There is ongoing debate about the best strategy to treat patients with tetralogy of Fallot who are symptomatic in the neonatal period., Objectives: The aim of this study was to compare the outcomes of complete versus staged surgery (i.e., initial palliative procedure for possible later complete repair)., Methods: A retrospective cohort study was performed using the Pediatric Health Information System database, including patients who underwent complete or staged tetralogy of Fallot repair prior to 30 days of age. The primary outcome was death during 2-year follow-up after the initial procedure. Inverse probability-weighted Cox and logistic regression models were used to examine the association between surgical approach group and mortality while accounting for patient- and hospital-level factors. Causal mediation analyses examined the role of intermediate variables., Results: A total of 2,363 patients were included (1,032 complete and 1,331 staged). There were 239 deaths. Complete neonatal repair was associated with a significantly higher risk for mortality during the 2-year follow-up period (hazard ratio: 1.51; 95% confidence interval: 1.05 to 2.06), between 7 and 30 days after the initial procedure (hazard ratio: 2.29; 95% confidence interval: 1.18 to 4.41), and during the initial hospital admission (odds ratio: 1.72; 95% confidence interval: 1.15 to 2.62). Post-operative cardiac complications were more common in the complete repair group and mediated the differences in 30-day and 2-year mortality., Conclusions: Complete surgical repair for neonates with tetralogy of Fallot is associated with a significantly higher risk for early and 2-year mortality compared with the staged approach, after accounting for patient and hospital characteristics. Post-operative cardiac complications mediated these findings., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Studies suggest that right ventricular (RV) fibrosis is associated with RV remodeling and long-term outcomes in patients with tetralogy of Fallot (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible factor-1-alpha (HIF1α) and promote transforming growth factor β1 (TGFβ1)-mediated fibrosis. We hypothesized that there would be associations between: (1) RV fibrosis and RV function, (2) HIF1α variants and RV fibrosis, and (3) HIF1α variants and RV function among post-surgical TOF cases., Methods: We retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic score) from 237 TOF cases who had existing cardiovascular magnetic resonance imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). Genetic data were available in 125 cases. Analyses were conducted using multivariable linear mixed-effects regression with a random intercept and multivariable generalized Poisson regression with a random intercept., Results: Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of the 48 HIF1α polymorphisms (representing two unique signals) were associated with fibrotic score. None of the HIF1α polymorphisms were associated with indexed fibrotic volume, RVEDVI, or RVEF., Conclusion: The association of some HIF1α polymorphisms and fibrotic score suggests that HIF1α may modulate the fibrotic response in TOF.

Objective: We sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin., Methods: In a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 - 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane's effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes., Results: Early after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 - 2 years after doxorubicin therapy., Conclusions: Early, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects., Competing Interests: Competing interests: None declared.

Pulmonary vein stenosis (PVS) is a rare condition that has been linked to prematurity and congenital heart disease (CHD). Despite these associations, treatment options are limited and outcomes are guarded. We investigated differences in PVS outcomes based on the presence of CHD and prematurity, and risk factors for mortality or lung transplantation in PVS. Single-center retrospective cohort study of patients diagnosed with PVS between January 2005 and May 2016 and identified by ICD codes with chart validation. Cox proportional hazard models assessed risk factors for the composite outcome of mortality or lung transplantation. Ninety-three patients with PVS were identified: 65 (70%) had significant CHD, 32 (34%) were premature, and 14 (15%) were premature with CHD. Sixty-five (70%) underwent a PVS intervention and 42 (46%) underwent ≥2 interventions. Twenty-five subjects (27%) died or underwent lung transplant 5.8 months (interquartile range [IQR] 1.1, 15.3) after diagnosis. There was no difference in age at diagnosis or mortality based on presence of CHD or prematurity. PVS diagnosis before age 6 months and greater than 1 pulmonary vein affected at diagnosis were associated with higher mortality (hazards ratio [HR] 3.4 (95% confidence interval 1.5, 7.5), P = 0.003, and HR 2.1 per additional vein affected (95% confidence interval 1.3, 3.4), P = 0.004, respectively). Survival in children with PVS is poor, independent of underlying CHD or prematurity. Younger age and greater number of veins affected at diagnosis are risk factors for worse outcome. Understanding causal mechanisms and development of treatment strategies are necessary to improve outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The timing and etiology of diastolic impairment in pediatric-onset systemic lupus erythematosus (SLE) are poorly understood. We compared echocardiographic metrics of left ventricular diastolic function in children at SLE diagnosis to controls and identified factors associated with diastolic indices. Echocardiograms of children aged 5-18 years within 1 year of SLE diagnosis and age-/sex-matched controls were retrospectively read by blinded cardiologists. Clinical characteristics were abstracted separately. Z-scores for diastolic indices (E/A, e', E/e', and isovolumetric relaxation time (IVRT)) were calculated using published normative data and study controls, and compared using linear mixed-effects models adjusted for blood pressure. Pericardial effusions and valvular disease were also evaluated. Linear regression was used to identify factors associated with diastolic measures. 85 children with incident SLE had echocardiograms performed a median of 6 days after diagnosis (interquartile range (IQR) 1-70). Prior cumulative prednisone exposure was minimal (median 60 mg, IQR 0-1652). SLE cases had lower E/A, lower e', higher E/e', and longer IVRT compared to controls. Though none met criteria for Grade I diastolic dysfunction, Z-scores for e', E/e', and IVRT were abnormal in 30%, 25%, and 6% of SLE cases, respectively. Greater disease activity was associated with lower septal e' (p < 0.01), higher E/e' (p = 0.02), and longer IVRT (p < 0.01). Children with incident SLE have worse diastolic indices at diagnosis compared to peers without SLE, independent of blood pressure and prior to significant prednisone exposure. Longitudinal studies will determine whether diastolic dysfunction develops in this population over time.

Background In shunt-dependent, single-ventricle patients, mortality remains high in the interstage period between discharge after neonatal surgery and stage 2 operation. We sought to evaluate the impact of our infant single-ventricle management and monitoring program ( ISVMP ) on interstage mortality and stage 2 outcomes. Methods and Results This retrospective single-center cohort study compared patients enrolled in ISVMP at hospital discharge with historical controls. The relationship of ISVMP to interstage mortality was determined with a bivariate probit model for the joint modeling of both groups, using an instrumental variables approach. We included 166 ISVMP participants (December 1, 2010, to June 30, 2015) and 168 controls (January 1, 2007, to November 30, 2010). The groups did not differ by anatomy, gender, race, or genetic syndrome. Mortality was lower in the ISVMP group (5.4%) versus controls (13%). An ISVMP infant compared with a historical control had an average 29% lower predicted probability of interstage death (adjusted probability: -0.29; 95% CI , -0.52 to -0.057; P=0.015). On stratified analysis, mortality was lower in the hypoplastic left heart syndrome subgroup undergoing Norwood operation (4/84 [4.8%] versus 12/90 [14%], P=0.03) but not in those with initial palliation of shunt only ( P=0.90). ISVMP participants were younger at the time of the stage 2 operation (138 versus 160 days, P<0.001), with no difference in postoperative mortality or length of stay. Conclusions In this single-center study, we report significantly lower interstage mortality for participants with hypoplastic left heart syndrome enrolled in ISVMP . Younger age at stage 2 operation was not associated with postoperative mortality or longer length of stay.

Background: Tricuspid regurgitation (TR) is a significant contributor to morbidity and mortality in patients with hypoplastic left heart syndrome. The goal of this study was to characterize the dynamic annular motion of the tricuspid valve in patients with HLHS with a Fontan circulation and assess the relation to tricuspid valve function., Methods: Tricuspid annuli of 48 patients with HLHS with a Fontan circulation were modeled at end-diastole, mid-systole, end-systole, and mid-diastole using transthoracic three-dimensional echocardiography and custom code in 3D Slicer. The angle of the anterior papillary muscle (APM) relative to the annular plane in each systolic phase was also measured., Results: Imaging was performed 5.0 years (interquartile range, 2-11 years) after Fontan operation. The tricuspid annulus varies in shape significantly throughout the cardiac cycle, changing in sphericity (P < .001) but not in annular height or bending angle. In univariate modeling, patients with significant TR had larger changes in septolateral diameter, lateral quadrant area, and posterior quadrant area (P < .05 for all) as well as lower (more laterally directed) APM angles (P < .001) than patients with mild or less TR. In multivariate modeling, a 1 mm/(body surface area) 0.5 increase in the maximum change in septolateral diameter was associated with a 1.7-fold increase in having moderate or greater TR, while a 10° decrease in APM angle at mid-systole was associated with an almost 2.5-fold increase in moderate or greater TR (P ≤ .01 for all)., Conclusions: The tricuspid annulus in patients with HLHS with a Fontan circulation changes in shape significantly throughout the cardiac cycle but remains relatively planar. Increased change in septolateral diameter and decreased APM angle are strongly associated with the presence of TR. These findings may inform annuloplasty methods and subvalvular interventions in these complex patients., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)