Complex tracheal anomalies are life threatening without intervention and often require surgery in the neonatal period to establish a stable airway. Variations of slide tracheoplasty using all autologous tissue are the gold standard in tracheal reconstruction. We have encountered 9 patients whose complex tracheal anomalies required significant variations to slide tracheoplasty. Six of these patients presented with bronchus suis with extreme long segment tracheobronchial stenosis which were effectively repaired using a side-to-side bronchus suis tracheobronchoplasty. This technique has the advantage of providing an all-autologous reconstruction with significantly less tension. Recently, we have encountered 3 patients with even more radical anatomies consisting of long segment tracheobronchial stenosis in the context of bilateral bronchus suis or Christmas-tree trachea. We employed bilateral side-to-side bronchus suis tracheoplasty in one and anterior-posterior bilateral bronchus suis tracheoplasty in the remaining 2 cases. These techniques have proven extremely effective in stabilizing the airway while preserving growth potential. Early management of these patients remains challenging, and complications are exponentially magnified by the interplay between complex cardiac physiology and complex tracheal reconstruction.

Introduction Bladder exstrophy-epispadias complex (BEEC) involves osseous pelvic defects and a wide pubic diastasis (PD). PD widens over time after the initial closure, but the degree and impact of this increase is not well delineated. Using the transverse distance between posterior inferior iliac spines (dPIIS) as an internal comparison, we aimed to:1) compare dPIIS, PD, and M-factor (PD/dPIIS) measurements made on radiographs to computed tomography (CT) images and between reviewers; 2) assess the measurements at birth and over time for BEEC and for age- and gender-matched controls; 3) determine how the M-factor compares with the PD over time. Methods This was a single institution, IRB-approved retrospective study of patients with BEEC who underwent a complete primary repair of bladder exstrophy (CPRE) or repair of epispadias or cloacal exstrophy with bilateral osteotomies between 5/1/2013 and 3/1/2020. PD and dPIIS were measured on cases and controls at 4 timepoints: preoperative, intraoperative, early post-operative (6-8 weeks) and late post-operative (greater than 6 months). For statistical analysis intra class correlations were used to assess inter-rater reliability. Mixed model two-way ANOVA was done with subjects as random effect, and group (patient/control), exam time as the two fixed effects. Results Forty-three cases (33 male) ranging in age from 1 day to 129 months (IQR 15.25 months) during the time points were evaluated. There was excellent agreement for measurements among the 6 raters. Following BEEC repair with osteotomies, PD and the M-factor decreased significantly. In the entire cohort, due to early post-operative spreading of the bones, there was no difference between pre-operative and early post-operative PD (35.2 ± 8.6 mm to 34.1 ± 9.8mm, p=0.08), however there was a significant difference in the M-factor between those time points (0.89 ± 0.2 to 0.73 ± 0.2, p < 0.01). With gradual increase in PD over time, there was a significant difference between early and late post-operative PD measurements (35.2 ± 8.6 mm to 39.8 ± 9.9 mm, p < 0.01), but not in the M-factor (0.73 ± 0.2 to 0.75 ± 0.2 (p=0.45). Conclusion PD in patients with BEEC changes over time due to surgery as well as growth, while a ratio of PD to an internal reference (dPIIS), does not change. This M-Factor ratio can better determine the initial extent of PD within the context of the size of the child, as well as standardize assessment of changes after surgery and during growth and development.

Lung allografts are susceptible to myriad injury types, including acute rejection (AR), infectious disease (ID), baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD), that affect outcomes. Donor-derived cell-free DNA (dd-cfDNA) is validated for detecting AR after lung transplantation (LT). However, data are limited regarding the ability of dd-cfDNA or total cell-free DNA (TcfDNA) to detect or differentiate other clinical conditions. This study stratified patients into Stable, AR, CLAD, and ID cohorts. Stable double LT recipients were further stratified into BLAD and non-BLAD over different periods posttransplantation. dd-cfDNA and TcfDNA results were associated with the various cohorts. cfDNA was measured in 354 plasma samples from 66 LT recipients. Median dd-cfDNA was elevated in AR (2.08%; P = 0.014) and ID (1.19%; P = 0.065) versus Stable (0.60%) but not CLAD; TcfDNA was only elevated in the ID cohort (P = 0.0078). dd-cfDNA was analyzed before and after treatment of eight episodes of AR, during which the median dd-cfDNA fraction decreased from 2.41% to 0.80% (P = 0.004). No differences were observed during early time points for BLAD versus non-BLAD, whereas median TcfDNA, but not dd-cfDNA, was elevated for BLAD beyond 12 months (13,843 vs 7768 cp/mL; P = 0.005). Overall, this was the first study that explored dd-cfDNA and TcfDNA levels across AR, ID, BLAD, and CLAD cohorts. These data suggest that cfDNA-based biomarkers have value in assessing allograft dysfunction beyond AR.

Background: MYH6 variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. MYH6 encodes for α-myosin heavy chain (α-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with MYH6 variants. Methods: We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. Results: A total of 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (−1.41%, IQR −2.13, −0.25) vs. controls (−3.53%, IQR −5.53, −1.28; p = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in MYH6 variant carriers only (ASr R = 0.499, p = 0.029; AScd R = 0.469, p = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, p = 0.050; VSs R = 0.419, p = 0.010; VSRs R = 0.410, p = 0.012). Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. MYH6 variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. MYH6 variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial “kick” may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with MYH6 variants.

Purpose:Bladder exstrophy (BE) poses challenges both during the surgical repair and throughout follow-up. In 2013, a multi-institutional BE consortium was initiated, which included utilization of unified surgical principles for the complete primary repair of exstrophy (CPRE), real-time coaching, ongoing video capture and review of video footage, prospective data collection, and routine patient data analysis, with the goal of optimizing the surgical procedure to minimize devastating complications such as glans ischemia and bladder dehiscence while maximizing the rate of volitional voiding with continence and long-term protection of the upper tracts. This study reports on our short-term complications and intermediate-term continence outcomes. Materials and Methods:A single prospective database for all patients undergoing surgery with a BE epispadias complex diagnosis at 3 institutions since February 2013 was used. For this study, data for children with a diagnosis of classic BE who underwent primary CPRE from February 2013 to February 2021 were collected. Data recorded included sex, age at CPRE, adjunct surgeries including ureteral reimplantations and hernia repairs at the time of CPRE, osteotomies, and immobilization techniques, and subsequent surgeries. Data on short-term postoperative outcomes, defined as those occurring within the first 90 days after surgery, were abstracted. In addition, intermediate-term outcomes were obtained for patients operated on between February 2013 and February 2017 to maintain a minimum follow-up of 4 years. Outcomes included upper tract dilation on renal and bladder ultrasound, presence of vesicoureteral reflux, cortical defects on nuclear scintigraphy, and continence status. Bladder emptying was assessed with respect to spontaneous voiding ability, need for clean intermittent catheterization, and duration of dry intervals. All operating room encounters that occurred subsequent to initial CPRE were recorded. Results:CPRE was performed in 92 classic BE patients in the first 8 years of the collaboration (62 boys), including 46 (29 boys) during the first 4 years. In the complete cohort, the median (interquartile range) age at CPRE was 79 (50.3) days. Bilateral iliac osteotomies were performed in 89 (97%) patients (42 anterior and 47 posterior). Of those undergoing osteotomies 84 were immobilized in a spica cast (including the 3 patients who did not have an osteotomy), 6 in modified Bryant's traction, and 2 in external fixation with Buck's traction. Sixteen (17%) patients underwent bilateral ureteral reimplantations at the time of CPRE. Nineteen (21%) underwent hernia repair at the time of CPRE, 6 of which were associated with orchiopexy. Short-term complications within 90 days occurred in 31 (34%), and there were 13 subsequent surgeries within the first 90 days. Intermediate-term outcomes were available for 40 of the 46 patients, who have between 4 and 8 years of follow-up, at a median of 5.7 year old. Thirty-three patients void volitionally, with variable dry intervals. Conclusions:Cumulative efforts of prospective data collection have provided granular data for evaluation. Short-term outcomes demonstrate no devastating complications, that is, penile injury or bladder dehiscence, but there were other significant complications requiring further surgeries. Intermediate-term data show that boys in particular show encouraging spontaneous voiding and continence status post CPRE, while girls have required modification of the surgical technique over time to address concerns with urinary retention. Overall, 40% of children with at least 4 years of follow-up are voiding with dry intervals of > 1 hour.

BACKGROUND:The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS:Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS:A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION:The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Introduction Epispadias, which occurs on the more mild end of the Bladder Exstrophy Epispadias Complex (BEEC) spectrum, presents still with a wide range of severity in boys, from mild glanular epispadias to penopubic epispadias with severe urethral and bladder neck defects. Surgical management ranges from isolated epispadias repair to epispadias repair with bladder neck reconstruction (BNR) with or without pelvic osteotomies. Objectives We aimed to evaluate outcomes in epispadias treated at three institutions prior to formation of a formal collaboration. In addition, we sought to delineate outcomes based on anatomic severity at time of diagnosis, and initial procedure performed in cases of penopubic epispadias. Methods IRB approved databases were retrospectively queried at three institutions for patients who underwent repair of epispadias between 1/1993 and 1/ 2013. Degree of epispadias, age and technique at initial repair, and self -reported continence status at last follow-up were recorded. Continence was categorized as: wet, intermediate (dry 2-3 h), or dry, while also distinguishing those who void and those who require clean intermittent catheterization (CIC). Those not seen since 1/1/2015, younger than 10 years at last follow up, or in whom continence data were not recorded were excluded. Results A total of 48 boys were identified; 36 met inclusion criteria. The epispadias cohort consisted of 8 glanular epispadias (GE) (22%); 8 penile epispadias (PE) (22%), and 20 penopubic epispadias (PPE) (56%) with a median follow-up of 11.3 years (3.2-26.2 years). Overall, 33 of 36 (92%) boys void per urethra. Within the group that voids, 19/33 (58%) are completely dry, while 6/33 (18%) are wet. Among patients who underwent initial epispadias repair without concurrent or subsequent bladder neck reconstruction, continence rates were: GE 63% (5/8); PE 75% (6/8); PPE 71% (5/7). Among the 9 boys with PPE who underwent initial epispadias repair with concurrent BNR, 22% (2/9) were dry with no further surgeries. Overall, 8/20 (40%) of boys with PPE void with complete dryness. Discussion This multi -center retrospective review of continence in epispadias demonstrates that even some boys with glanular and penile epispadias can have challenges with continence, and boys with penopubic epispadias may remain wet despite careful preoperative assessment of bladder neck functionality and concurrent BNR. Conclusion Continence outcomes in boys with all degrees of epispadias can be variable. Even boys with more distal defects may have significant bladder neck deficiency. And those with the most severe form of epispadias may require bladder neck reconstruction to achieve continence.

We demonstrate here that iPSCs derived from patients with Ebstein’s anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling.

BACKGROUND:Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. METHODS:This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. RESULTS:Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). CONCLUSIONS:This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.

Severe right ventricular outflow tract (RVOT) obstruction developed in a 4-year-old boy with Schuurs-Hoeijmakers syndrome and history of double-outlet right ventricle, tetralogy of Fallot type, status post repair with transannular patch augmentation of the RVOT. Echocardiography and computed tomography defined the presence of a 1 × 1-cm sinus of Valsalva aneurysm protruding into the RVOT, causing obstruction. Resection and repair of the aneurysm by a 2-patch technique as well as resection of RVOT muscle bundles and revision of the transannular patch were performed. The postoperative course was uneventful, with no evidence of persistent RVOT obstruction.

Introduction:Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies.Methods:To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521.Results:Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture.Discussion:This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.

Objective: To determine patient characteristics and outcomes after Norwood versus comprehensive stage II (COMPSII) for infants with critical left heart obstruction who had prior hybrid palliation (bilateral pulmonary artery banding +/- ductal stent).Methods: From 23 Congenital Heart Surgeons' Society institutions (2005-2020), 138 infants underwent hybrid palliation followed by either Norwood (n = 73, 53%) or COMPSII (n = 65). Baseline characteristics were compared between Norwood and COMPSII groups. Parametric hazard model with competing risk methodology was used to determine risk and factors associated with outcomes of Fontan, transplantation, or death.Results: Infants who underwent Norwood versus COMPSII had a higher prevalence of prematurity (26% vs 14%, P = .08), lower birth weight (median 2.8 vs 3.2 kg, P < .01) and less frequent ductal stenting (37% vs 99%; P < .01). Norwood was performed at a median age of 44 days and median weight of 3.5 kg, versus COMPSII at 162 days and 6.0 kg (both P<.01). Median follow-up was 6.5 years. At 5 years after Norwood and COMPSII, respectively; 50% versus 68% had Fontan (P = .16), 3% versus 5% had transplantation (P = .70), 40% versus 15% died (P = .10), and 7% versus 11% are alive without transition, respectively. For factors associated with either mortality or Fontan, only preoperative mechanical ventilation occurred more frequently in the Norwood group.Conclusions: Higher prevalence of prematurity, lower birth weight, and other patient-related characteristics in the Norwood versus COMPSII groups may influence differences in outcomes that were not statistically significant for this limited risk-adjusted cohort. The clinical decision regarding Norwood versus COMPSII after initial hybrid palliation remains challenging. (J Thorac Cardiovasc Surg 2023;166:943-54)

BACKGROUND The supported Ross is used to mitigate the neoaortic root dilation that has been described with the unsupported Ross. There is limited literature assessing the efficacy of the supported Ross in young patients. In this study, the fate of the neoaortic root was compared in the supported and unsupported Ross procedure in adolescent patients. METHODS A retrospective review was performed of patients who underwent the Ross procedure between 1996 and 2019. An analysis was conducted of patients aged 10 to 18 years who underwent the supported and unsupported Ross operation, without a Konno enlargement, to assess for longitudinal echocardiographic changes. Given differences in follow-up time, both regression analysis and Mann-Whitney nonparametric tests were used to correct for time from discharge to most recent follow-up. RESULTS The median follow-up time for supported and unsupported Ross patients without a Konno enlargement was 2.90 years (0.21-13.03 years) and 12.13 years (2.63-19.47 years), respectively. Unsupported Ross patients experienced a higher rate of change per year in the aortic annulus (P =.003 and P =.014) and aortic sinus (P =.002 and P =.002) diameters, respectively. There was no significant difference in the rate of change of end-diastolic left ventricular internal diameter (P =.703 and P =.92) and aortic insufficiency (P =.687 and P =.215) between the supported and unsupported Ross patients. CONCLUSIONS Progressive dilation of the neoaortic root in unsupported Ross patients is significantly mitigated with the supported Ross with excellent stability. The supported Ross is safe and effective and may play an increasing role in the management of children with aortic disease. (C) 2023 by The Society of Thoracic Surgeons

BACKGROUND Hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) is an initial management strategy for infants with critical left heart obstruction and serves as palliation until subsequent operations are pursued. OBJECTIVES This study sought to determine patient characteristics and factors associated with subsequent outcomes for infants who underwent hybrid palliation. METHODS From 2005 to 2019, 214 of 1,236 prospectively enrolled infants within the Congenital Heart Surgeons' Society's critical left heart obstruction cohort underwent hybrid palliation across 24 institutions. Multivariable hazard modeling with competing risk methodology was performed to determine risk and factors associated with outcomes of biventricular repair, Fontan procedure, transplantation, or death. RESULTS Preoperative comorbidities (eg, prematurity, low birth weight, genetic syndrome) were identified in 70% of infants (150 of 214). Median follow-up was 7 years, ranging up to 17 years. Overall 12-year survival was 55%. At 5 years after hybrid palliation, 9% had biventricular repair, 36% had Fontan procedure, 12% had transplantation, 35% died without surgical endpoints, and 8% were alive without an endpoint. Factors associated with transplantation were absence of ductal stent, older age, absent interatrial communication, smaller aortic root size, larger tricuspid valve area z-score, and larger left ventricular volume. Factors associated with death were low birth weight, concomitant genetic syndrome, cardiopulmonary bypass use during hybrid palliation, moderate to severe tricuspid valve regurgitation, and smaller ascending aortic size. CONCLUSIONS Mortality remains high after hybrid palliation for infants with critical left heart obstruction. None-theless, hybrid palliation may facilitate biventricular repair for some infants and for others may serve as stabilization for intended functional univentricular palliation or primary transplantation. (J Am Coll Cardiol 2023;82:1427-1441) (c) 2023 by the American College of Cardiology Foundation.

Single-ventricle palliation starting with a Norwood procedure which culminates in a failed Fontan palliation poses certain unique operative challenges for cardiac transplantation. In this manuscript, we describe some of these challenges and our particular approach in management.