mTor-inhibition within the first days after pediatric heart transplantation is a potentially safe option to prevent cardiac allograft vasculopathy.

BACKGROUND: Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX. METHODS: Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low-dose calcineurin inhibitors. RESULTS: Everolimus therapy was started at a median 3.9 (1-14) days after HTX. Median follow-up was 4.3 (range 0.5-11.8) years, cumulative 184 patient years. The estimated 1- and 5-year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post-transplant lymphoproliferative disorder. Five patients suffered relevant wound-healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy. CONCLUSION: Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post-transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients.

Neurological Impact of Slower Rewarming during Bypass Surgery in Infants.

BACKGROUND: Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological sequelae. In this pilot study, we aimed to validate the hypothesis that a slower rewarming rate would lower the risk of cerebral hypoxia and seizures in infants. METHODS: This is a prospective, clinical, single-center study. Infants undergoing cardiac surgery in hypothermia were rewarmed either according to the standard (+1°C in < 5 minutes) or a slow (+1°C in > 5-8 minutes) rewarming strategy. We monitored electrocortical activity via amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation by near-infrared spectroscopy during and after surgery. RESULTS: Fifteen children in the standard rewarming group (age: 13 days [5-251]) were cooled down to 26.6°C (17.2-29.8) and compared with 17 children in the slow-rewarming group (age: 9 days [4-365]) with a minimal temperature of 25.7°C (20.1-31.4). All neonates in both groups (n = 19) exhibited suppressed patterns compared with 28% of the infants > 28 days (p < 0.05). During rewarming, only 26% of the children in the slow-rewarming group revealed suppressed aEEG traces (vs. 41%; p = 0.28). Cerebral oxygenation increased by a median of 3.5% in the slow-rewarming group versus 1.5% in the standard group (p = 0.9). Our slow-rewarming group revealed no aEEG evidence of any postoperative seizures (0 vs. 20%). CONCLUSION: These results might indicate that a slower rewarming rate after hypothermia causes less suppression of electrocortical activity and higher cerebral oxygenation during rewarming, which may imply a reduced risk of postoperative seizures.

Surgically placed radiopaque markers: Proof-of-concept of a novel technique to facilitate percutaneous interventions in neonates and infants.

OBJECTIVES: Aim of this study was to evaluate feasibility and benefit of self-designed, radiopaque markers as a novel technique in neonates and infants with shunt- or duct-dependent lesions. BACKGROUND: Surgically placed radiopaque markers have the potential to facilitate postoperative percutaneous interventions. METHODS: All consecutive children with surgically placed radiopaque markers involving systemic-to-pulmonary artery connections or arterial ducts in the context of hybrid palliation and subsequent cardiac catheterization between January 2013 and March 2019 were included in this analysis. Our primary endpoint was our concept's feasibility, which we defined as a combination of surgical feasibility and the percutaneous intervention's success. Secondary endpoint was the rate of complications resulting from the surgical procedure or during catheterization. RESULTS: Radiopaque markers that reveal the proximal entry of a surgical shunt or the arterial duct proved to be a feasible and beneficial approach in 25 postoperative catheterizations. The markers' high accuracy enabled easy probing and proper stent positioning in 13 neonates with a median age and weight of 121 days (range 9-356) and 4.7 kg (1.6-9.4) at the intervention. No procedural complications or unanticipated events associated with the radiopaque marker occurred. The markers were never lost, never migrated, and caused no local obstructive lesion. Surgical removal was straightforward in all patients. CONCLUSIONS: Radiopaque markers are a promising and refined technique to substantially facilitate target vessel access and enabling the accurate positioning of stents during postoperative percutaneous procedures.

National Survey on Training in Pediatric Cardiology by the "Junges Forum" of the DGPK.

BACKGROUND: This is the first national survey of residents and fellows in pediatric cardiology in Germany evaluating training, research activity, and the general working environment. METHODS: An online questionnaire including 62 questions (SurveyMonkey) was developed by the "Junges Forum" of the German Society of Pediatric Cardiology. Fellows and residents during training and up to 3 years after completing their pediatric cardiology fellowship were invited to participate. RESULTS: A total of 102 pediatric cardiology fellows and residents completed the questionnaire. Many participants complained about their training as being unstructured (47%) and non-transparent (37%). The numbers of technical and catheter interventions required by the national medical board in Germany cannot be achieved, especially regarding invasive procedures. Sixty per cent work more than contractually agreed, usually in Germany it is 40 hours daytime work plus on calls, while 90% of all participants prefer less than 50 weekly working hours; 50% of the participants are engaged in research that is usually done during their spare time. More than 90% are satisfied with their professional relationships with colleagues and coworkers. Seventy-eight per cent describe their career perspectives as promising, and 84% would start a fellowship in pediatric cardiology again. CONCLUSION: The majority of pediatric cardiology fellows and residents are satisfied with their working environment and with their choice of a career in pediatric cardiology. Besides the heavy work load, we identified the urgent desire for better structured transparent clinical training concept including the teaching of manual skills, i.e., invasive procedures and catheterization.

Collateral closure in congenital heart defects with Amplatzer vascular plugs: single-center experience and a simplified delivery technique for exceptional cases.

The study describes our experience with Amplatzer Vascular Plugs (AVP2 and 4) and highlights a more refindes telescopic technique for AVP2 delivery. AVPs are well-established occlusion devices for vascular anomalies in congenital heart disease (CHD). The AVP2 is sometimes preferred to the AVP4 due to its shorter length, flat-profiled retention disks, and the availability of larger diameters, but its profile requires a larger inner lumen for safe delivery. The latter may actually hamper access to target lesions. This is a retrospective analysis of all CHD patients treated with the AVP2 and AVP4 between 12/2012 and 12/2015. Target vessels were characterized, measured, and the device-to-vessel diameter ratio calculated. A modified pigtail technique for AVP2 delivery was frequently used: a floppy wire was simply reinforced by the curved tip of a pigtail catheter (instead of the long sheath's dilator) to guide the required delivery sheath towards the desired landing zone. 59 patients with a median age and bodyweight of 3.0 years (range 0.1-75) and 13.8 kg (range 2.5-80) underwent the implantation of 106 plug-devices (30 AVP2, 76 AVP4) in 91 target vessels. Indications for their use were ductus arteriosus (19%), aortopulmonary (43%) as well as venovenous collaterals (34%) and other miscellaneous lesions (4%). The pigtail-supported AVP2 delivery in six patients proved very convenient. No complications occurred. AVPs are excellent devices for embolizing shunt vessels in CHD patients. Here, we describe a simplified telescoping technique for AVP2 delivery to enter curvy target lesions gently and efficiently.

Implementing and Assessing a Standardized Protocol for Weaning Children Successfully From Extracorporeal Life Support.

Extracorporeal life support (ECLS) weaning is a complex interdisciplinary process with no clear guidelines. To assess ventricular and pulmonary function as well as hemodynamics including end-organ recovery during ECLS weaning, we developed a standardized weaning protocol. We reviewed our experience 2 years later to assess its feasibility and efficacy. In 2015 we established an inter-professional, standardized, stepwise protocol for weaning from ECLS. If the patient did not require further surgery, weaning was conducted bedside in the intensive care unit (ICU). Most of the weaning procedures are guided via echocardiography. Data acquisition began at baseline level, followed by four-step course (each step lasting 10 min), entailing flow-reduction and ending 30 min after decannulation. Moreover, data from the preprotocol era are presented. Between May 2015 and 2017, 26 consecutive patients (18 male), median age 177 days (2 days-20 years) required ECLS with median support of 4 (2-11) days. Excluding eight not weanable patients, 21 standardized weaning procedures were protocolled in the remaining 18 children. Our generally successful protocol-guided weaning rate (with at least 24-h survival) was 89%, with a discharge home rate of 58%. Practical application of the novel standard protocol seems to facilitate ECLS weaning and to improve its success rate. The protocol can be administered as part of standard bedside ICU assessment.

Echocardiographic characteristics in Fontan patients before the onset of protein-losing enteropathy or plastic bronchitis.

BACKGROUND: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB). DESIGN: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations. RESULTS: A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB. CONCLUSION: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB.

Benefit From a Humanitarian Pediatric Congenital Heart Surgery Program Over a 10-Year Period.

Background: The charity organization Kinderherzen retten e.V. (KHR) enables humanitarian congenital heart surgery for pediatric patients from low- and middle-income countries at the University Heart Center Freiburg, Germany. The aim of this study was to assess periprocedural and mid-term outcomes of these patients for evaluation of KHR sustainability. Methods: Part one of the study comprised retrospective medical chart analyses of the periprocedural course of all KHR-treated children from 2008 to 2017, and part two a prospective evaluation of their mid-term outcome, assessed by questionnaires concerning survival, medical history, mental and physical development, and socioeconomic situation. Results: Of the 100 consecutively presented children from 20 countries (median age 3.25 years), 3 patients were not invasively treatable, 89 underwent cardiovascular surgery, and 8 received a catheter intervention only. There were no periprocedural deaths. Median postoperative duration of mechanical ventilation, intensive care stay, and total hospital stay was 7 (interquartile range [IQR] 4-21) hours, 2 (IQR 1-3) days, and 12 (IQR 10-16) days, respectively. Mid-term postoperative follow-up demonstrated a 5-year survival probability of 94.4%. The majority of patients received continued medical care in their home country (86.2% of patients), were in good mental and physical condition (96.5% and 94.7% of patients, respectively), and able to engage in age-appropriate education/employment (98.3% of patients). Conclusions: Cardiac, neurodevelopmental, and socioeconomic outcomes of patients treated via KHR was satisfactory. Thorough pre-visit evaluation and close contact with local physicians are crucial when providing this high-quality, sustainable, and viable therapeutic option for these patients.

Transposition of great arteries with left outflow tract obstruction and non-committed VSD: surgical management and late results.

OBJECTIVES: Transposition of the great arteries with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) is a rare malformation. Our objective was to report on management and results of the cohort with non-committed VSD from a national registry for congenital heart disease. METHODS: Multicentre data were screened in the German National Registry for Congenital Heart Defects (Berlin, Germany) for repairs of transposition of the great arteries-VSD-LVOTO. A subgroup of patients with a remote/non-committed VSD was identified. End points included survival, reoperation and a composite of reoperations for LVOTO-/VSD- or baffle-related problem. RESULTS: N = 47 patients were identified treated in 14 different national centres between 1984 and 2020. The mean age was 14 (standard deviation 9) months, ranging from 7 days to 9.5 years. Nine patients (19%) were treated as neonates, 21 (45%) as infants and 17 children (36%) beyond the age of 1 year. Survival was >90% (80-100%) at 20 years. Freedom from any reoperation was 30% (10-50%) at 20 years. Freedom from the composite end point was 72% (50-90%) at 20 years. Patients after Rastelli underwent more reoperations compared to those without intraventricular baffle (freedom from reoperation 14% vs 50%, P = 0.1). The rates of the composite end point were similar when comparing Rastelli to other techniques (63% vs 83%, P = 0.32). CONCLUSIONS: The Rastelli operation yields robust results in the setting of non-committed VSD. Late results after neonatal arterial switch operation are outstanding. If LVOTO is not resectable and neonatal arterial switch operation suboptimal, interim palliation does not negatively impact outcome, patients can be safely delayed to beyond 1 year of age.

Catheter strategy to ease the procedure and reduce radiation exposure when requiring neck access.

OBJECTIVES: To assess the potential occupational radiation reduction and technical feasibility in patients rotated 180° (upside-down) when requiring neck access for transcervical or trans-subclavian catheterisation. METHODS: Upside-down positioning is defined as rotating patients in supine position by 180°, so that the feet come to rest where the head would otherwise be. We retrospectively evaluated all these procedures performed between March 2016 and May 2019. Furthermore, two different phantoms (paediatric and adult) were used prospectively to quantify the occupational dose between conventional or upside-down positioning. In this context, ambient dose equivalents were measured using real-time dosimeters. Three different projection angles were applied. RESULTS: 44 patients with median age and body weight of 1.0 year (range 0-56) and 9.5 kg (range 1.3-74.3) underwent 63 procedures positioned upside-down. This position proved advantageous for practical reasons, since the length of the examination table could be optimally used. Additionally, it resulted in a significantly lower overall ambient dose equivalent for the primary operator (PO) of 94.8% (mean: 2569±807 vs 135±23 nSv; p<0.01) in the adult, and of 65.5% (mean: 351±104 vs 121±56 nSv; p<0.01) in the paediatric phantom, respectively. CONCLUSION: Upside-down positioning facilitates handling in a straightforward manner when access from the neck is required. Moreover, it significantly reduces local radiation exposure for the PO in the paediatric and, most impressively, in the adult phantom.

Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media - a long-term observational study.

Background The thyroid gland of patients with congenital heart disease may be exposed to large doses of iodine from various sources. We assessed the thyroid response after iodine exposure during conventional angiography in cardiac catheterization and angiographic computer tomography in childhood. Methods Retrospective mid- to long-term follow-up of 104 individuals (24% neonates, 51% infants, 25% children) with a median age and body weight of 104 days [0-8 years] and 5.3 kg [1.6-20]. Serum levels of thyroid-stimulating hormone, free triiodthyronine and free thyroxine were evaluated at baseline and after excess iodine. We also assessed risk factors that may affect thyroid dysfunction. Results Baseline thyroidal levels were within normal range in all patients. The mean cumulative iodinate contrast load was 6.6 ± 1.6 mL/kg. In fact, 75% had experienced more than one event involving iodine exposure, whose median frequency was three times per patient [1-12]. During the median three years follow-up period [0.5-10], the incidence of thyroid dysfunction was 15.4% (n=16). Those patients developed acquired hypothyroidism (transient n=14, long-lasting n=2 [both died]) with 10 of them requiring temporary replacement therapy for transient thyroid dysfunction, while four patients recovered spontaneously. 88 individuals (84.6%) remained euthyroid. Repeated cardiac interventions, use of drugs that interfere with the thyroid and treatment in the intensive care unit at the index date were strong predictors for acquired thyroid dysfunction. Conclusions The incidence of acquired hypothyroidism after iodine excess was 15.4%. However, most patients developed only transient hypothyroidism. Systemic iodine exposure seems to be clinically and metabolically well tolerated during long-term follow-up.

Evaluation of a biocompatible sealant for on-demand repair of vascular defects-a chronic study in a large animal model.

OBJECTIVES: Existing surgical sealants fail to combine design requirements, such as sealing performance, on-demand activation and biocompatibility. The aim of this study was to compare the effectiveness and safety of the SETALIUM™ Vascular Sealant (SVS), a novel, on-demand activatable sealant, with the commercial sealant, BioGlue®, for the repair of vascular defects. METHODS: In an in vivo porcine model, the use of SVS was compared with BioGlue, for sealing 2-mm defects of the carotid artery and jugular vein. Animals were followed for 7 days and 5 weeks (each time point and per experimental group, n = 4), respectively. The degree of stenosis and flow velocity was determined, and the local tissue response was evaluated. RESULTS: In vivo incision closure succeeded in all cases, and SVS was superior in clinical usability, enabled by its on-demand activation. Unlike BioGlue, SVS use did not induce stenosis and was associated with physiological blood flow in all cases. Moreover, closure with SVS was associated with a low inflammatory reaction and no thrombus formation or intima proliferation, in contrast to BioGlue. CONCLUSIONS: SVS demonstrated effective and rapid sealing of 2-mm vascular defects, with favourable biocompatibility compared to BioGlue. Thus, SVS seems to be an effective and safe vascular sealant.

Retrograde transcatheter aortic valve closure in an infant with failing Norwood stage I palliation: a case report.

BACKGROUND: Aortic valve regurgitation leading to coronary steal phenomenon can severely impair cardiac function in hypoplastic left heart syndrome, thus worsening long-term outcome. CASE PRESENTATION: A German infant with borderline aortic and mitral valve, hypoplastic left ventricle, ventricular septal defect, and hypoplastic aortic arch with critical coarctation initially underwent aortic arch reconstruction and aortic valve dilation with the aim of biventricular correction later on. Unfortunately, severe cardiac dysfunction necessitated a change in strategy entailing modified stage I Norwood palliation. Increasing aortic regurgitation with coronary steal was revealed postoperatively, which required redo surgery to oversew the valve. However, pronounced aortic regurgitation recurred, causing severe cardiac decompensation with repeated resuscitation. As a bailout strategy, we performed aortic valve closure via transfemoral retrograde implantation of an Amplatzer Duct Occluder II device. This led to the patient's rapid stabilization while circumventing highly risky renewed surgery in such a critically ill infant. CONCLUSIONS: Retrograde transcatheter aortic valve closure may be considered a feasible alternative in infants with a failing single ventricle due to aortic regurgitation, with critical device evaluation being crucial for successful device implantation in this young age group.

Acquired von Willebrand syndrome in paediatric patients during mechanical circulatory support.

OBJECTIVES: Bleeding signs can become life-threatening complications in patients on mechanical circulatory support (MCS). Clinical phenotyping and comprehensive analyses of the cause of bleeding are, therefore, essential, especially when risk-stratifying patients during MCS workup. We conducted coagulation analyses and determined von Willebrand factor (VWF) parameters in a paediatric cohort on temporary extracorporeal life support, extracorporeal membrane oxygenation or long-term ventricular assist device support. METHODS: We carried out an observational single-centre study including 30 children with MCS (extracorporeal life support, n = 13; extracorporeal membrane oxygenation, n = 5; and ventricular assist device, n = 12). We also assessed the acquired von Willebrand parameters of each study participant: collagen binding capacity (VWF:CB), the ratio of collagen-binding capacity to VWF antigen (VWF:CB/VWF:Ag) and high-molecular-weight VWF multimers. We also documented bleeding events, transfusion requirement, haemolysis parameters and surgical interventions. RESULTS: All children developed AVWS (acquired von Willebrand syndrome) during MCS, usually during the early postoperative course. They presented no AVWS after device explantation. We detected a loss of high-molecular-weight VWF multimers, decreased VWF:CB/VWF:Ag ratios and reduced VWF:CB levels. Twenty of the 30 patients experienced bleeding complications; approximately 53% of them required surgical revision. There were no deaths due to bleeding during support. CONCLUSIONS: The AVWS prevalence in paediatric patients on MCS is 100% regardless of the types of devices tested in this study. The bleeding propensity of AVWS patients widely varies.

Dysfunctional pulmonary artery conduit and co-existing large pseudoaneurysm: well-suited for a percutaneous approach with the Melody valve?

Pseudoaneurysm formation is a rare but potentially life-threatening complication after surgical repair of congenital heart disease. We present a boy with truncus arteriosus communis 14 years after homograft placement in pulmonary position. On follow-up, he presented progressive chronic homograft degeneration. Moreover, a large pseudoaneurysm in the right ventricular outflow tract was surprisingly depicted. We opted for a two-stage interventional approach.

Early prediction of capillary leak syndrome in infants after cardiopulmonary bypass.

OBJECTIVES: As an inflammatory reaction after cardiac surgery involving cardiopulmonary bypass (CPB), capillary leak syndrome (CLS) is associated with increased morbidity, especially in newborns and infants. We investigated whether different cytokines measured via microdialysis can monitor local inflammation in adipose tissue subcutaneously and predict the development of CLS early, before clinical signs appear. Furthermore, we investigated whether there are age-related differences between the inflammatory responses in newborns and infants. METHODS: We performed a prospective study taking serial measurements of the inflammatory response detected in subcutaneous adipose tissue up to 24 h postoperatively. The cohort consisted of 23 neonates and infants (median age 155, range 6-352 days; median body weight 5.4 kg, range 2.6-9.2 kg) who underwent congenital heart surgery with CPB. Microdialysis catheters were introduced in one lateral thigh subcutaneously using a velocity of 1.0 µl/min. Serial microdialysis analyses for cytokines (interleukin [IL]-6, IL-8, IL-10) and complement activation (C3a) were performed. CLS was quantified by X-ray subcutaneous-thoracic ratios. RESULTS: The median bypass time was 150 min (range 42-432 min) and the aortic cross-clamp time 76 min (range 0-188 min). Six out of 23 infants developed postoperative CLS. Younger age (P = 0.02) and longer bypass time (r = 0.48; P = 0.021) correlated strongly with the development of CLS. Pro- and anti-inflammatory cytokines and complement activation were detected subcutaneously in all patients. The highest levels of IL-6 (55.0 pg/ml) and IL-8 (65.9 pg/ml) were detected 2 h after CPB. During surgery, the C3a level rose dramatically (167.1 ng/ml), followed by a release of IL-10 at the end of CPB. Patients with CLS produced a characteristic and significant second peak of C3a at 8 h postoperatively (CLS 63.8 ng/ml vs non-CLS 23.5 ng/ml; P < 0.01). We detected an aged-related difference in the release of IL-6 and C3a. Longer intubation time (r = 0.63; P = 0.001), higher inotropic demand (r = 0.67; P = 0.001) and higher serological lactate levels (r = 0.65; P = 0.001) correlated closely with the development of CLS. CONCLUSION: Diagnostic microdialysis can detect local inflammation and may predict the development of CLS early before severe clinical signs appear.