Lead and generator dysfunction in children and adolescents with epicardial pacemaker and implantable cardioverter defibrillator systems: The challenge of early recognition.

BACKGROUND: A major issue of cardiac implantable electronic device therapy in pediatric patients is the high incidence of lead dysfunctions and associated reinterventions. This study aims to analyze the timing and mode of generator and lead dysfunction. METHODS: Retrospective single-center analysis of 283 children and young adults with an epicardial pacemaker or implantable cardioverter defibrillator therapy from 1998 to 2018. RESULTS: Mean age at implant was 6.1 years (SD ± 5.8 years) and median follow-up 6.4 years (IQR, 3.4-10.4 years) with a total of 1998.1 patient-years of cardiac device therapy. A total of 120 lead-related complications were observed in 82 patients (29.0%). They were detected by device interrogation (n = 86), symptoms (n = 13), intraoperative findings (n = 7), routine chest radiography (n = 5), routine ECG (n = 4), patient alert sound by device (n = 3), and physical examination (n = 2). It was possible to find the date of the event on the device memory in 21 out of 120 lead dysfunctions (18%) with a median time interval between occurrence and detection of 1.3 months (IQR, 0.2-5.0 months). Moreover, 20 generator-related complications were found in 13 patients. CONCLUSIONS: Early recognition of lead and generator dysfunction remains challenging in pediatric patients. As symptoms are relatively rare conditions in the context of PM and ICD dysfunction, close patient monitoring is mandatory, even in asymptomatic patients with a good clinical course. To further improve the safety of pediatric pacing systems, more durable epicardial electrodes are desirable.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: Results from a European Collaboration.

OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.

Risk Factors and Outcomes of Children with Congenital Heart Disease on Extracorporeal Membrane Oxygenation-A Ten-Year Single-Center Report.

For children born with congenital heart defects (CHDs), extracorporeal life support may be necessary. This retrospective single-center study aimed to investigate the outcomes of children with CHDs on extracorporeal membrane oxygenation (ECMO), focusing on various risk factors. Among the 88 patients, 36 (41%) had a single-ventricle heart defect, while 52 (59%) had a biventricular defect. In total, 25 (28%) survived, with 7 (8%) in the first group and 18 (20%) in the latter. A p-value of 0.19 indicated no significant difference in survival rates. Children with biventricular hearts had shorter ECMO durations but longer stays in the intensive care unit. The overall rate of complications on ECMO was higher in children with a single ventricle (odds ratio [OR] 1.57, 95% confidence interval [CI] 0.67-3.7); bleeding was the most common complication in both groups. The occurrence of a second ECMO run was more frequent in patients with a single ventricle (22% vs. 9.6%). ECMO can be effective for children with congenital heart defects, including single-ventricle patients. Bleeding remains a serious complication associated with worse outcomes. Patients requiring a second ECMO run within 30 days have lower survival rates.

Risk Factors and Outcome of Pulmonary Artery Stenting After Bidirectional Cavopulmonary Connection (BDCPC) in Single Ventricle Circulation.

After bidirectional cavopulmonary connection (BDCPC) central pulmonary arteries (PAs) of single ventricle (SV) patients can be affected by stenosis or even closure. Aim of this study is to compare SV patients with and without PA-stent implantation post-BDCPC regarding risk factors for stent implantation and outcome. Single center, retrospective (2006-2021) study of 136 SV consecutive patients with and without PA-stent implantation post-BDCPC. Patient characteristics, risk factors for PA-stent implantation and PA growth were assessed comparing angiographic data pre-BDCPC and pre-TCPC. A total of 40/136 (29%) patients underwent PA-stent implantation at median (IQR) 14 (1.1-39.0) days post-BDCPC. 37/40 (92.5%) underwent LPA-stenting. Multiple regression analysis showed single LV patients to receive less likely PA-stents than single RV patients (OR 0.41; p = 0.05). Reduced LPA/BSA (mm/m2) and larger diameter of neo-ascending aorta pre-BDCPC were associated with an increased likelihood of PA-stent implantation post-BDCPC (OR 0.89, p = 0.03; OR 1.05, p = 0.001). Stent re-dilatation was performed in 36/40 (89%) after 1 (0.8-1.5) year. Pulmonary artery diameters pre-BDCPC were lower in the PA-stent group: McGoon (p < 0.001), Nakata (p < 0.001). Indexed pulmonary artery diameters increased equally in both groups but remained lower pre-TCPC in the PA-stent group: McGoon (p < 0.001), Nakata (p = 0.009), and Lower Lobe Index (p = 0.003). LPA and RPA grew symmetrically in both groups. Single RV, larger neo-ascending aorta, and small LPA pre- BDCPC are independent risk factors for PA-stent implantation post-BDCPC. Pulmonary artery diameters after PA-stent implantation and stent re-dilatation showed significant growth together with the contralateral side, but the PA-system remained symmetrically smaller in the stent group.

Transannular bovine jugular vein monocusp for the reconstruction of severe right ventricular outflow tract obstruction.

Objective: Severe right ventricular outflow tract obstruction in tetralogy of Fallot and variants necessitates the use of transannular patch in a significant proportion of children undergoing repair. We have used a Contegra monocusp together with delamination of native leaflet tissue in order to create a functioning pulmonary valve. Methods: In total, 18 (2017-2022) consecutive Contegra monocusp implantations were included. Median age and weight were 3.65 [2.00; 9.43] months and 6.12 [4.30; 8.22] kg, respectively. Nine of 18 patients had undergone palliation. Native pulmonary leaflet tissue was recruited to create a single posterior cusp. Contegra monocusp selection was based on the goal to achieve a neoannulus of Z value ≈ 0. Monocusp sizes implanted were 16 [14; 18] mm. Patch plasty of left pulmonary artery (LPA) (9), right pulmonary artery (RPA) (2), and both LPA-RPA (5) were often performed. Results: All patients survived the operation and were discharged home in good health. Median ventilation time and hospital stay were 2 [1; 9] and 12.5 [9; 54] days, respectively. Follow-up duration was 30.68 [3.47; 60.47] months and 100% complete. One patient with well-corrected right ventricular outflow tract died 9.4 months postoperatively, possibly of aspiration. One child with membranous pulmonary atresia needed reoperation (conduit insertion) at 3.5 months of follow-up. Five needed catheter interventions: supravalvar stent (2), LPA stent (3), and RPA stent (1), most of them in the earlier half of the experience. Pulmonary annulus changed from preoperative -3.91 [-5.98; -2.23] to -0.10 [-1.44; 1.92] at discharge; growing proportionally to -0.13 [-3.52; 2.73] at follow-up. Kaplan-Meier freedom from composite dysfunction was 79.25 (95% confidence interval, +13.68%, -31.44%) at 36 months. Conclusions: Recruitment of native leaflets, optimal Contegra monocusp, and commissuroplasty provide an easily replicable technique for achieving a competent, proportionally growing neopulmonary valve. Longer follow-up is needed to determine its impact on delaying a pulmonary valve replacement.

Realignment of the ventricular septum in tetralogy of Fallot using (partial) direct closure of the ventricular septal defect: Long-term follow-up and comparison to conventional patch repair.

Objectives: Aortic dilatation and regurgitation after surgical repair of tetralogy of Fallot (TOF) is known, and beside other factors, mainly addressed to an intrinsic aortopathy. In 2011, we reported the influence of realingement of the left ventricular outflow tract (LVOT) by (partial) direct closure of the ventricular septal defect (VSD) in TOF on aortic structures and function. We now evaluated the further follow-up of this cohort and compared the results to a matched group of TOF patients with classical VSD patch closure. Patients and Methods: Forty patients with TOF treated between 2003 and 2008 are included in the study, with 20 patients each in the VSD (a) (partial) direct closure and (b) patch closure group. Follow-up time after surgery was 12.3 years (11.3-13.0). Results: Patient characteristics, echocardiographic measurements, and surgical and intensive care unit parameters were not significantly different between both groups. After surgery and during long-term follow-up, realignement of the LVOT, shown by the angle between the interventricular septum and the anterior aortic annulus in long axis view in echocardiography, was lower in Group A (34 vs. 45°, P < 0.0001). No differences in LVOT or aortic annulus size, aortic regurgitation, or dilation of the ascending aorta and right ventricular outflow tract gradients were found. Transient rhythm disturbances were found in 3 patients in each group, with only one persistent complete atrioventricular block in Group B. Conclusion: (Partial) direct closure of the VSD in TOF leads to a better realignement of the LVOT and showed comparable short- and long-term results without higher risk for rhythm disturbances during follow-up.

Management of a fusiform brachial artery aneurysm associated with birth trauma.

Brachial artery aneurysms in children are rare. Surgical treatment is generally recommended.We present the case of a female toddler with a pulsatile swelling on the medial aspect of the right upper arm without history of recent trauma. Medical history revealed a traumatic birth with labour arrest. Postnatally diffuse trunk and arm haematomas as well as a temporary right arm discolouration were detected. Preoperative ultrasound revealed a true brachial artery aneurysm. A full-body MRI ruled out any accompanying lesions. Primary resection and end-to-end anastomosis were performed. Recovery was uneventful. 6-month and 12-month follow-up showed normal motor function and arterial patency; ultrasound also demonstrated harmonious growth of the anastomosed vessel segments.No other publication has associated birth trauma with brachial artery aneurysm yet. Correct diagnosis and prompt curative surgery are key to prevent severe complications. Further reports and data on long-term outcome are needed to optimise clinical management.

Safety issues with an inter-hospital transport of a patient with a Berlin Heart Excor biventircular assist device.

BACKGROUND: Interhospital transfers of pediatric patients on the Berlin Heart Excor have been published on an occasional basis. METHODS: Nowadays medicine evolves away from just feasibility towards quality and safety issues. Management tools like risk analysis have found their way into clinical practice. RESULTS: Exemplary, we present a case of a 20 months old boy on a Berlin Heart BiVAD Excor who underwent a 224 km ground transport. After a systematic review of the published literature, we describe our safety management with the aim was to provide highest quality of care for the transport. CONCLUSION: Besides a risk analysis, we also describe our training and simulation protocol.

Surgical correction of partial anomalous left superior pulmonary venous connection to the innominate vein.

Partial anomalous pulmonary venous connection is reported to occur in 0.4 to 0.7% of children. Only 3% of these cases involve an anomalous left-sided pulmonary venous connection to the innominate vein [1]. In this video tutorial, we present the technique of reimplantation of the partial anomalous left superior pulmonary venous connection to the left atrial appendage through a median sternotomy and with a cardioplegic heart. We debate the merits of our strategy with respect to our ultimate goal of achieving long-term patency.

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration.

BACKGROUND: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06-4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23-5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20-21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05-1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58-67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20-6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28-95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08-13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07-1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.

Balloon angioplasty and stent implantation within 30 days postcongenital heart surgery (CHS) in children.

OBJECTIVES: This study aims to assess balloon angioplasty (BAP) and stent implantation (SI) procedures early after congenital heart surgery (CHS) in children. BACKGROUND: These interventions are considered potential high-risk procedures and often avoided or postponed. METHODS: This is a retrospective, single centre study of all BAP and SI procedures within 30 days after CHS (01/2001 until 01/2021). RESULTS: A total of 127 (96 SI, 31 BAP) procedures were performed in 104 patients at median 6.5 days (interquartile range: 1-15) after CHS. Balloon-to-stenosis ratio and balloon-to-reference vessel ratio were significantly smaller compared to stent-to-stenosis ratio and stent-to-reference vessel ratio (p < .001 and p = .005). There was a greater rise in absolute vessel diameter, greater rise in vessel diameter in relation to the stenosis and vessel diameter in relation to the reference vessel with SI (p < .001, p = .01, and p < .001). Up to 94% SIs fulfilled both success criteria (increase of vessel diameter ≥50% of minimal vessel diameter or achievement ≥75% of the reference vessel diameter). Major adverse events were more frequent in the BAP group (p = .05). Intraprocedural complications were 5/31 (16%) in the BAP group and 13/96 (13%) in the SI group (p = .77). CONCLUSION: BAP and SI procedures within 30 days post-CHS can be performed safely, with a greater stent-to-stenosis ratio and a greater rise in vessel diameter with stent implantation.

Bridging with Veno-Arterial Extracorporeal Membrane Oxygenation in Children: A 10-Year Single-Center Experience.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is frequently used in children with and without congenital heart disease (CHD). This study, of a single-center and retrospective design, evaluated the use and timing of V-A ECMO in a pediatric cohort who underwent V-A ECMO implantation between January 2009 and December 2019. The patients were divided into a pre-/non-surgical group and a post-surgical group. Among the investigated variables were age, gender, weight, duration of ECMO, ECMO indication, and ventricular physiology, with only the latter being statistically relevant between the two groups. A total of 111 children (58 male/53 female), with a median age of 87 days (IQR: 7-623) were supported using V-A ECMO. The pre-/non-surgical group consisted of 59 patients and the post-surgical group of 52 patients. Survival at discharge was 49% for the pre-/non-surgical group and 21% for the surgical group (p = 0.04). Single-ventricle physiology was significant for a worse outcome (p = 0.0193). Heart anatomy still has the biggest role in the outcomes of children on ECMO. Nevertheless, children with CHD can be successfully bridged with ECMO to cardiac operation.

Findings and Outcome of Transcatheter Right Ventricular Endomyocardial Biopsy and Hemodynamic Assessment in Children with Suspected Myocarditis or Cardiomyopathy.

OBJECTIVE: The study objective is assessing findings and outcome in children with suspected cardiomyopathy (CMP) or myocarditis undergoing cardiac catheterization with transcatheter right ventricular endomyocardial biopsy (RV-EMB). METHODS: All consecutive children undergoing cardiac catheterization with RV-EMB for suspected CMP/myocarditis between 2002-2021 were analysed regarding clinical presentation, cardiac biomarkers, periprocedural management, hemodynamic, histological/immunohistological findings, and outcome. RESULTS: Eighty-five RV-EMBs were performed in 81 patients at a median age of 6.8 (IQR 9.9) years and a bodyweight of 20 (32.2) kg. Histological/immunohistological findings of RV-EMB revealed dilated CMP in 10 (12%), chronic myocarditis in 28 (33%), healing myocarditis in 5 (6%), acute myocarditis in 9 (11%), other heart muscle diseases in 23 (27%) (7 restrictive CMP, 5 hypertrophic CMP, 4 toxic/anthracycline-induced CMP, 4 endocardfibroelastosis, 1 arrhythmogenic right ventricular CMP, 1 laminin CMP, 1 haemangioma), no conclusive histology in 7 (8%), and normal histology in 3 (4%) patients. Median LVEDP was 17 mmHg (IQR 9), LAP 15 mmHg (10), and PVR 1.83 (1.87) Wood Units/m2. There were 3 major complications (3%), all patients recovered without any sequelae. At follow-up (median 1153, IQR 1799 days) 47 (59%) patients were alive, 11 (13%) dead, 15 (18%) underwent cardiac transplantation, and 8 (9%) were lost to follow-up. Death/cardiac transplantation occurred within 3 years from RV-EMB. All patients with an acute myocarditis survived. NT-pro-BNP, echo parameters, and invasive hemodynamics correlate independently with death/cardiac transplant. CONCLUSION: Hemodynamic invasive data and morphological findings in RV-EMB complete clinical diagnosis in children with suspected CMP/myocarditis and provide important information for further clinical management.

Repair of a remote pericommissural anomalous left coronary artery from the pulmonary artery.

We demonstrate a classic trapdoor technique to correct a late-presenting remote pericommissural anomalous left coronary artery from the pulmonary artery. The merits of the technique compared to alternative techniques are explained. The impact of late diagnosis on left ventricular function as well as on papillary muscle ischemia-induced mitral regurgitation is evident. The child's recovery without the need for a temporary ventricular assist device supports the efficacy of  the technique, despite the residual mitral regurgitation.

5-Year results from the prospective European multi-centre study on decellularized homografts for pulmonary valve replacement ESPOIR Trial and ESPOIR Registry data.

OBJECTIVES: Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH). METHODS: A 5-year analysis of ESPOIR Trial patients was performed to provide an insight into the midterm DPH performance. ESPOIR Trial and Registry patients were matched with cryopreserved homografts (CH) patients considering patient age, type of heart defect and previous procedures to present the overall experience with DPH. RESULTS: A total of 121 patients (59 female) were prospectively enrolled (8/2014-12/2016), median age 16.5 years (interquartile range 11.2-29.8), and median DPH diameter 24 mm. One death (73 year-old) occurred during a median follow-up of 5.9 years (5.4-6.4), in addition to 2 perioperative deaths resulting in an overall mortality rate of 2.5%. One case of endocarditis in 637 patient-years was noticed, resulting in an incidence of 0.15% per patient-year. At 5 years, the mean peak gradient was 19.9 mmHg (9.9), mean regurgitation 0.9 (0.6, grade 0-3) and freedom from explantation/any reintervention 97.5% (1.5). The combined DPH cohort, n = 319, comprising both Trial and Registry data, showed significantly better freedom from explantation for DPH 95.5% (standard deviation 1.7) than CH 83.0% (2.8) (P < 0.001) and less structural valve degeneration at 10 years when matched to 319 CH patients [DPH 65.5% (standard deviation 4.4) and CH 47.3% (3.7), P = 0.11]. CONCLUSIONS: The 5-year data of the prospective ESPOIR Trial show excellent performance for DPH and low rates of adverse events. ESPOIR Registry data up to 15 years, including a matched comparison with CH, demonstrated statistically significant better freedom from explantation.

Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year.

OBJECTIVES: The significance of intraoperative cerebral desaturation (CD) measured by near-infrared spectroscopy (NIRS) to predict neurological outcome after congenital heart surgery is uncertain. The goal of this study was to compare brain structure changes and neurodevelopmental outcome in patients with severe congenital heart disease with and without intraoperative CD. METHODS: Neonates requiring congenital heart surgery were enrolled in a cohort study. NIRS data from their first cardiac operation were collected. Pre- and postoperative brain magnetic resonance imaging results and Bayley-III scores at 1 year were compared between patients with and without CD, defined by 2 NIRS thresholds: regional cerebral oxygen saturation (rSO2) of 45% (45%rSO2) and rSO2 below 20% of baseline value (20%BLrSO2). RESULTS: Thirty-two patients (72% male) with d-transposition of the great arteries (n = 24, 75%) and other complex types of congenital heart diseases (n = 8, 25%) were analysed. Perioperative relative lateral ventricle volume change was increased in patients with versus without intraoperative CD (P = 0.003 for 45%rSO2, P = 0.008 for 20%BLrSO2). For 45%rSO2, the effect of CD remained significant after adjusting for age at postoperative scan, time between scans and cardiac diagnosis (P = 0.019). New intracranial lesions occurred predominantly in CD groups (6/6 patients for 45%rSO2, 5/6 patients for 20%BLrSO2). Neurodevelopmental outcome at 1 year was not associated with intraoperative CD. CONCLUSIONS: This study demonstrates the clinical relevance of NIRS monitoring during congenital heart surgery. The occurrence of intraoperative CD is associated with perioperative lateral ventricle volume change and new intracranial lesions.

Absent left main coronary artery in a case of pulmonary atresia-intact ventricular septum and right ventricle-dependent coronary circulation.

Right ventricle-dependent coronary circulation coexisting with left main coronary atresia in the setting of pulmonary atresia-intact ventricular septum is rare. In the case described, the left coronary artery (LCA) origin from the aorta could not be found on conventional angiography or cardiac magnetic resonance imaging. During surgery, multiple LCA branches originating from the finger-like continuum of the primitive right ventricular sinusoidal network were observed. A Damus-Kaye-Stansel anastomosis and an aortopulmonary shunt operation were performed. Shunt takedown and a bidirectional Glenn anastomosis followed at 3 months of age. At 18 months follow-up, the child is thriving with stable hemodynamics and a saturation of 85%. Awareness about this rare coronary artery anomaly is necessary to prevent catastrophic consequences. The challenges, complications, and lessons learned while treating this rare variant are discussed.

Novel Combination of Surface Markers for the Reliable and Comprehensive Identification of Human Thymic Epithelial Cells by Flow Cytometry: Quantitation and Transcriptional Characterization of Thymic Stroma in a Pediatric Cohort.

Thymic epithelial cells (TECs) are essential in supporting the development of mature T cells from hematopoietic progenitor cells and facilitate their lineage-commitment, proliferation, T-cell receptor repertoire selection and maturation. While animal model systems have greatly aided in elucidating the contribution of stromal cells to these intricate processes, human tissue has been more difficult to study, partly due to a lack of suitable surface markers comprehensively defining human TECs. Here, we conducted a flow cytometry based surface marker screen to reliably identify and quantify human TECs and delineate medullary from cortical subsets. These findings were validated by transcriptomic and histologic means. The combination of EpCAM, podoplanin (pdpn), CD49f and CD200 comprehensively identified human TECs and not only allowed their reliable distinction in medullary and cortical subsets but also their detailed quantitation. Transcriptomic profiling of each subset in comparison to fibroblasts and endothelial cells confirmed the identity of the different stromal cell subsets sorted according to the proposed strategy. Our dataset not only demonstrated transcriptional similarities between TEC and cells of mesenchymal origin but furthermore revealed a subset-specific distribution of a specific set of extracellular matrix-related genes in TECs. This indicates that TECs significantly contribute to the distinct compartmentalization - and thus function - of the human thymus. We applied the strategy to quantify TEC subsets in 31 immunologically healthy children, which revealed sex-specific differences of TEC composition early in life. As the distribution of mature CD4- or CD8-single-positive thymocytes was correspondingly altered, the composition of the thymic epithelial compartment may directly impact on the CD4-CD8-lineage choice of thymocytes. We prove that the plain, reliable strategy proposed here to comprehensively identify human TEC subpopulations by flow cytometry based on surface marker expression is suitable to determine their frequency and phenotype in health and disease and allows sorting of live cells for downstream analysis. Its use reaches from a reliable diagnostic tool for thymic biopsies to improved phenotypic characterization of thymic grafts intended for therapeutic use.