Neurodevelopment in patients with repaired tetralogy of Fallot.

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.

Racial, ethnic, and socio-economic disparities in neonatal ICU admissions among neonates born with cyanotic CHD in the United States, 2009-2018.

INTRODUCTION: Disparities in CHD outcomes exist across the lifespan. However, less is known about disparities for patients with CHD admitted to neonatal ICU. We sought to identify sociodemographic disparities in neonatal ICU admissions among neonates born with cyanotic CHD. MATERIALS & METHODS: Annual natality files from the US National Center for Health Statistics for years 2009-2018 were obtained. For each neonate, we identified sex, birthweight, pre-term birth, presence of cyanotic CHD, and neonatal ICU admission at time of birth, as well as maternal age, race, ethnicity, comorbidities/risk factors, trimester at start of prenatal care, educational attainment, and two measures of socio-economic status (Special Supplemental Nutrition Program for Women, Infants, and Children [WIC] status and insurance type). Multivariable logistic regression models were fit to determine the association of maternal socio-economic status with neonatal ICU admission. A covariate for race/ethnicity was then added to each model to determine if race/ethnicity attenuate the relationship between socio-economic status and neonatal ICU admission. RESULTS: Of 22,373 neonates born with cyanotic CHD, 77.2% had a neonatal ICU admission. Receipt of WIC benefits was associated with higher odds of neonatal ICU admission (adjusted odds ratio [aOR] 1.20, 95% CI 1.1-1.29, p < 0.01). Neonates born to non-Hispanic Black mothers had increased odds of neonatal ICU admission (aOR 1.20, 95% CI 1.07-1.35, p < 0.01), whereas neonates born to Hispanic mothers were at lower odds of neonatal ICU admission (aOR 0.84, 95% CI 0.76-0.93, p < 0.01). CONCLUSION: Maternal Black race and low socio-economic status are associated with increased risk of neonatal ICU admission for neonates born with cyanotic CHD. Further work is needed to identify the underlying causes of these disparities.

The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.

Neighborhood Social Vulnerability and Interstage Weight Gain: Evaluating the Role of a Home Monitoring Program.

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.

Echocardiographic Assessment of Pulmonary Arterial Hypertension Following Inhaled Nitric Oxide in Infants with Severe Bronchopulmonary Dysplasia.

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.

Impaired echocardiographic left ventricular global longitudinal strain after pediatric cardiac arrest children is associated with mortality.

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.

Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

AIMS: We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). METHODS AND RESULTS: We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. CONCLUSION: In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Association of Home Monitoring and Unanticipated Interstage Readmissions in Infants With Hypoplastic Left Heart Syndrome.

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.

Right Ventricular Strain in Patients With Ductal-Dependent Tetralogy of Fallot.

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.

Biomarkers, Socioeconomic Factors, and Right Ventricular Function After Surgical Repair for Tetralogy of Fallot.

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 R2 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.

Association of race and ethnicity with resource utilisation among children with CHD: an evaluation of the National Health Interview Survey, 2010-2018.

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.

Alveolar dead space fraction is not associated with early RV systolic dysfunction in pediatric ARDS.

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 PaO2 /FiO2 . CONCLUSION: AVDSf at PARDS onset was not associated with RV systolic dysfunction or PH within 24 h but was associated with PaO2 /FiO2 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.

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

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.

Comparison of serum biomarkers of myocardial fibrosis with cardiac magnetic resonance in patients operated for tetralogy of Fallot.

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.

Fontan Geometry and Hemodynamics Are Associated With Quality of Life in Adolescents and Young Adults.

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.

Impact of Maternal-Fetal Environment on Mortality in Children With Single Ventricle Heart Disease.

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.

Right Ventricular Strain Is Associated With Increased Length of Stay After Tetralogy of Fallot Repair.

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.

Right atrial function early after tetralogy of Fallot repair.

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.

Identifying Risk Factors for Complicated Post-operative Course in Tetralogy of Fallot Using a Machine Learning Approach.

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.