Preoperative Hemodynamics Impact the Benefit of Fenestration on Fontan Postoperative Length of Stay.

BACKGROUND: Utilization of Fontan fenestration varies considerably by center. OBJECTIVES: Using a multicenter Pediatric Heart Network dataset linking surgical and preoperative hemodynamic variables, the authors evaluated factors associated with use of Fontan fenestration and the impact of fenestration on post-Fontan length of stay (LOS). METHODS: Patients 2 to 6 years old at Fontan surgery from 2010 to 2020 with catheterization<1 year prior were included. Factors associated with fenestration were evaluated using multivariable logistic regression adjusting for key covariates. Restrictive cubic spline analysis was used to evaluate potential cut-points for hemodynamic variables associated with longer postoperative LOS stratified by fenestration with multivariable linear regression to evaluate the magnitude of effect. RESULTS: Fenestration was used in 465 of 702 patients (66.2%). Placement of a fenestration was associated with center (range 27%-93% use, P < 0.0001) and Fontan type (OR: 14.1 for lateral tunnel vs extracardiac conduit, P < 0.0001). No hemodynamic variable was independently associated with fenestration. In a multivariable linear model adjusting for center, a center-fenestration interaction, prematurity, preoperative mean pulmonary artery pressure (mPAP), and cardiac index, fenestration was associated with shorter hospital LOS after Fontan (P = 0.0024). The benefit was most pronounced at mPAP ≥13 mm Hg (median LOS: 9 vs 12 days, P = 0.001). CONCLUSIONS: There is wide center variability in use of Fontan fenestration that is not explained by preoperative hemodynamics. Fenestration is independently associated with shorter LOS, and those with mPAP ≥13 mm Hg at pre-Fontan catheterization benefit the most. We propose this threshold as minimal criteria for fenestration.

Surgical Modulation of Pulmonary Artery Shear Stress: A Patient-Specific CFD Analysis of the Norwood Procedure.

PURPOSR: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. METHODS: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. RESULTS: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. CONCLUSION: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics.

Evaluating registry-based trial economics: Results from the STRESS clinical trial.

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.

Outcomes of the Kawashima: A Society of Thoracic Surgeons Congenital Heart Surgery Database Analysis.

BACKGROUND: We aimed to evaluate the effect of age at operation on postoperative outcomes in children undergoing a Kawashima operation. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried for Kawashima procedures from January 1, 2014, to June 30, 2020. Patients were stratified by age at operation in months: 0 to <4, 4 to <8, 8 to <12, and >12. Subsequently, outcomes for those in whom the Kawashima was not the index operation and for those undergoing hepatic vein incorporation (Fontan completion or hepatic vein-to-azygos vein connection) were evaluated. RESULTS: We identified 253 patients who underwent a Kawashima operation (median age, 8.6 months; median weight, 7.4 kg): 12 (4.7%), 0 to <4 months; 96 (37.9%), 4 to <8 months; 81 (32.0%), 8 to <12 months; and 64 (25.3%), >12 months. Operative mortality was 0.8% (n = 2), with major morbidity or mortality in 17.4% (n = 44), neither different across age groups. Patients <4 months had a longer postoperative length of stay (12.5 vs 9.3 days; P = .03). The Kawashima was not the index operation of the hospital admission in 15 (5.9%); these patients were younger (6.0 vs 8.4 months; P = .05) and had more preoperative risk factors (13/15 [92.9%] vs 126/238 [52.9%]; P < .01). We identified 173 patients undergoing subsequent hepatic vein incorporation (median age, 3.9 years; median weight, 15.0 kg) with operative mortality in 6 (3.5%) and major morbidity or mortality in 30 (17.3%). CONCLUSIONS: The Kawashima is typically performed between 4 and 12 months with low mortality. Morbidity and mortality were not affected by age. Hepatic vein incorporations may be higher risk than in traditional Fontan procedures, and ways to mitigate this should be sought.

Population Pharmacokinetics of Caffeine in Neonates with Congenital Heart Disease and Associations with Acute Kidney Injury.

Cardiac surgery-associated acute kidney injury (CS-AKI) occurs in approximately 65% of neonates undergoing cardiac surgery on cardiopulmonary bypass and contributes to morbidity and mortality. Caffeine may reduce CS-AKI by counteracting adenosine receptor upregulation after bypass, but pharmacokinetics (PK) in this population are unknown. The goal of our analysis is to address knowledge gaps in age-, disease-, and bypass-related effects on caffeine disposition and explore preliminary associations between caffeine exposure and CS-AKI using population PK modeling techniques and an opportunistic, electronic health record-integrated trial design. We prospectively enrolled neonates receiving preoperative caffeine per standard of care and collected PK samples. We retrospectively identified neonates without caffeine exposure undergoing surgery on bypass as a control cohort. We followed US Food and Drug Administration guidance for population PK model development using NONMEM. Effects of clinical covariates on PK parameters were evaluated. We simulated perioperative exposures and used multivariable logistic regression to evaluate the association between caffeine exposure and CS-AKI. Twenty-seven neonates were included in model development. A 1-compartment model with bypass time as a covariate on clearance and volume of distribution best fit the data. Twenty-three neonates with caffeine exposure and 109 controls were included in the exposure-response analysis. Over half of neonates developed CS-AKI. On multivariable analysis, there were no significant differences between CS-AKI with and without caffeine exposure. Neonates with single-ventricle heart disease without CS-AKI had consistently higher simulated caffeine exposures. Our results highlight areas for further study to better understand disease- and bypass-specific effects on drug disposition and identify populations where caffeine may be beneficial.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

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

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

A point-of-care pharmacokinetic/pharmacodynamic trial in critically ill children: Study design and feasibility.

Background: High-quality, efficient, pharmacokinetic (PK), pharmacodynamic (PD), and safety studies in children are needed. Point-of-care trials in adults have facilitated clinical trial participation for patients and providers, minimized the disruption of clinical workflow, and capitalized on routine data collection. The feasibility and value of point-of-care trials to study PK/PD in children are unknown, but appear promising. The Opportunistic PK/PD Trial in Critically Ill Children with Heart Disease (OPTIC) is a programmatic point-of-care approach to PK/PD trials in critically ill children that seeks to overcome barriers of traditional pediatric PK/PD studies to generate safety, efficacy, PK, and PD data across multiple medications, ages, and disease processes. Methods: This prospective, open-label, non-randomized point-of-care trial will characterize the PK/PD and safety of multiple drugs given per routine care to critically ill children with heart disease using opportunistic and scavenged biospecimen samples and data collected from the electronic health record. OPTIC has one informed consent form with drug-specific appendices, streamlining study structure and institutional review board approval. OPTIC capitalizes on routine data collection through multiple data sources that automatically capture demographics, medications, laboratory values, vital signs, flowsheets, and other clinical data. This innovative automatic data collection minimizes the burden of data collection and facilitates trial conduct. Data will be validated across sources to ensure accuracy of dataset variables. Discussion: OPTIC's point-of-care trial design and automated data acquisition via the electronic health record may provide a mechanism for conducting minimal risk, minimal burden, high efficiency trials and support drug development in historically understudied patient populations. Trial registration: clinicaltrials.gov number: NCT05055830. Registered on September 24, 2021.

Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates.

Background: Infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) frequently receive intraoperative methylprednisolone (MP) to suppress CPB-related inflammation; however, the optimal dosing strategy and efficacy of MP remain unclear. Methods: We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014-2017 at our institution. We combined real-world dosing data from the electronic health record (EHR) and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration (Cmax) and area under the concentration-time curve for 24 h (AUC24) for MP and the inflammatory cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10). We evaluated the relationships between post-operative, safety, and other clinical outcomes obtained from the EHR with each predicted exposure using non-parametric tests. Results: A total of 142 infants with median post-natal age 8 (interquartile range [IQR]: 5, 37) days received a total dose of 30 (19, 49) mg/kg of MP. Twelve (8%) died, 37 (26%) met the composite post-operative outcome, 114 (80%) met the composite safety outcome, and 23 (16%) had a major complication. Predicted median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major complications. Predicted median Cmax and AUC24 MP exposure was significantly higher for infants requiring insulin. No exposure was associated with death or other safety outcomes. Conclusions: Pro-inflammatory IL-6, but not MP exposure, was associated with post-operative organ dysfunction, suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical outcomes. Prospective study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

Contemporary Patterns of Care in Tetralogy of Fallot: Analysis of The Society of Thoracic Surgeons Data.

BACKGROUND: Against the background of earlier studies, recent patterns in surgical management of tetralogy of Fallot (TOF) were assessed. METHODS: A retrospective review of The Society of Thoracic Surgeons (STS) Congenital Database (2010-2020) was performed on patients aged <18 years with TOF or pulmonary stenosis and primary procedure TOF surgical repair or palliation. Procedural frequencies were examined by epoch. Demographics, clinical variables, and outcomes were compared between the initial palliation and primary repair groups. Among those operated on at 0 to 60 days of age, variation in palliation rates across hospitals was assessed. RESULTS: The 12,157 operations included 11,307 repairs (93.0%) and 850 palliations (7.0%); 68.5% of all palliations were modified Blalock-Taussig-Thomas shunts. Of 1105 operations on neonates, 45.4% (502) were palliations. Among neonates, palliations declined from 49.0% (331 of 675) in epoch 1 (2010-2015) to 39.8% (171 of 430) in epoch 2 (2016-2020; P = .0026). Overall, the most prevalent repair technique (5196 of 11,307; 46.0%) was ventriculotomy with transanular patch, which was also used in 520 of 894 (58.2%) of repairs after previous cardiac operations. Patients undergoing initial palliation demonstrated more preoperative STS risk factors (50.1% vs 24.3% respectively; P < .0001) and more major morbidity and mortality than patients undergoing primary repair (21.2% vs 7.46%; P < .0001). In the 0- to 60-day age group, risk factor-adjusted palliation rates across centers varied considerably, with 32 of 99 centers performing significantly more or significantly fewer palliations than predicted on the basis of their case mix. CONCLUSIONS: Surgical palliation rates have decreased across all age groups despite increasing prevalence of risk factors. Ventriculotomy with transanular patch remains the most prevalent repair type. The considerable center-level variation in rates of palliation was not completely explained by case mix.

Association of Urine Biomarkers With Acute Kidney Injury and Fluid Overload in Infants After Cardiac Surgery: A Single Center Ancillary Cohort of the Steroids to Reduce Systemic Inflammation After Infant Heart Surgery Trial.

To examine the association between three perioperative urine biomarker concentrations (urine cystatin C [uCysC], urine neutrophil gelatinase-associated lipocalin [uNGAL], and urine kidney injury molecule 1 [uKIM-1]), and cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) in infants with congenital heart disease undergoing surgery on cardiopulmonary bypass. To explore how urine biomarkers are associated with distinct CS-AKI phenotypes based on FO status. DESIGN: Ancillary prospective cohort study. SETTING: Single U.S. pediatric cardiac ICU. PATIENTS: Infants less than 1 year old enrolled in the Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial (NCT03229538) who underwent heart surgery from June 2019 to May 2020 and opted into biomarker collection at a single center. Infants with preoperative CS-AKI were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty infants met inclusion criteria. Median (interquartile) age at surgery was 103 days (5.5-161 d). Modified Kidney Disease Improving Global Outcomes-defined CS-AKI was diagnosed in 22 (55%) infants and 21 (53%) developed FO. UCysC and uNGAL peaked in the early postoperative period and uKIM-1 peaked later. In unadjusted analysis, bypass time was longer, and Vasoactive-Inotropic Score at 24 hours was higher in infants with CS-AKI. On multivariable analysis, higher uCysC (odds ratio [OR], 1.023; 95% CI, 1.004-1.042) and uNGAL (OR, 1.019; 95% CI, 1.004-1.035) at 0-8 hours post-bypass were associated with FO. UCysC, uNGAL, and uKIM-1 did not significantly correlate with CS-AKI. In exploratory analyses of CS-AKI phenotypes, uCysC and uNGAL were highest in CS-AKI+/FO+ infants. CONCLUSIONS: In this study, uCysC and uNGAL in the early postoperative period were associated with FO at 48 hours. UCysC, uNGAL, and uKIM-1 were not associated with CS-AKI. Further studies should focus on defining expected concentrations of these biomarkers, exploring CS-AKI phenotypes and outcomes, and establishing clinically meaningful endpoints for infants post-cardiac surgery.

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred related to difficulties with: 1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and 2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by 1) adding additional study sites, 2) increasing the frequency of meetings with site coordinators and 3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms. Trial registration number: ClinicalTrials.gov Registration Number: NCT02692443.

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.

Prenatal Diagnosis, Management, and Treatment of Fetal Cardiac Disease.

Prenatal diagnosis of congenital heart disease makes it possible to optimize and coordinate care of the fetus and pregnant person. Benefits encompass the full spectrum of pre- and perinatal care, from counseling to optimization of pregnancy care and fetal intervention. Prenatal diagnosis reduces the likelihood of postnatal hemodynamic compromise and improves long-term neurodevelopmental outcomes. Despite the benefits, prenatal diagnosis rates remain suboptimal, particularly for lesions that are not seen on standard 4-chamber imaging views. Improving prenatal diagnosis rates requires education and outreach efforts targeting community practices where most initial screening occurs.

Development of a Novel Society of Thoracic Surgeons Adult Congenital Mortality Risk Model.

BACKGROUND: Operative mortality risk models for adults with congenital heart disease (ACHD) undergoing cardiac operations are essential, given the growing population of these patients, yet they are currently unavailable. Existing adult Society of Thoracic Surgeons (STS) models exclude congenital procedures, whereas existing congenital models exclude operations for acquired disease. We aimed to develop an STS mortality risk model for ACHD patients undergoing cardiac operations. METHODS: Leveraging a comprehensive list of diagnostic and procedure codes, ACHD patients who underwent cardiac operations were identified from the STS Adult Cardiac Surgery Database (versions: v2.73, v2.81, and v2.9) between 2011 and 2019. The model was developed and validated in the ACHD population using a 60/40 development/validation split. Univariate analyses and clinical expertise informed the addition of ACHD-relevant procedure and diagnosis variables to existing STS adult risk model variables. Model performance was assessed overall and in 38 subgroups based on patient demographics, procedures, and diagnoses. RESULTS: Forty-seven procedure and diagnosis variables relevant to ACHD were added to existing STS adult risk model variables. The derived ACHD model for operative mortality was well calibrated within demographic, procedural, and diagnosis subgroups and the overall ACHD population, and discrimination in the validation cohort was excellent (C statistic, 0.815) compared with the model using only existing STS adult risk model variables (C statistic, 0.79; P < .0001). CONCLUSIONS: A novel, high-performing STS ACHD mortality risk model has been developed on the basis of contemporary patient data. The ACHD risk model represents an important expansion of the STS portfolio. Implementation with an online risk calculator is planned.

Variation in Case-Mix Across Hospitals: Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.

BACKGROUND: The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database was queried to document variation of patient characteristics, procedure types, and programmatic case-mix. METHODS: All index cardiac operations in patients less than 18 years of age in the STS Congenital Heart Surgery Database (July 2016 to June 2020) were eligible for inclusion except patients weighing ≤2.5 kg undergoing isolated patent ductus arteriosus closure. At the hospital level, we describe variations in patient and procedural characteristics known from previous analyses to be associated with outcomes. We also report variations across hospitals of programmatic case-mix. RESULTS: Data were analyzed from 117 sites (90 322 total operations, 87 296 total index cardiac operations eligible for STAT [STS-European Association for Cardio-Thoracic Surgery] 2020 Mortality Score). The median annual total index cardiac operations eligible for STAT 2020 Mortality Score per hospital was 157 (interquartile range [IQR], 94-276). Wide variability was documented in total annual index cardiac operations eligible for STAT 2020 Mortality Score per hospital (ratio 90th/10th percentile = 9.01), operations in neonates weighing <2.5 kg (ratio 90th/10th percentile = 4.09), operations in patients with noncardiac anatomic abnormalities (ratio 90th/10th percentile = 3.46), and operations in patients with preoperative mechanical ventilation (ratio 90th/10th percentile = 3.97). At the hospital level, the median percentage of all index cardiac operations in STAT 2020 Mortality Category 5 was 3.7% (IQR, 1.7%-4.9%), the median percentage of all index cardiac operations in STAT 2020 Mortality Category 4 or 5 was 24.4% (IQR, 19.0%-28.4%), the median hospital-specific mean STAT Mortality Category was 2.39 (IQR, 2.20-2.47), and the median hospital-specific mean STAT Mortality Score was 0.86 (IQR, 0.73-0.91). CONCLUSIONS: Substantial variation of patient characteristics, procedure types, and case-mix exists across pediatric and congenital cardiac surgical programs. Knowledge about programmatic case-mix augments data about indirectly standardized programmatic observed-to-expected (O/E) mortality. Indirectly standardized O/E ratios do not provide a complete description of a given pediatric and congenital cardiac surgical program. The indirectly standardized programmatic O/E ratios associated with a given program apply only to its specific case-mix of patients and may represent a quite different case-mix than that of another program.