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ZusammenfassungDie pulmonale Hypertension (PH) ist eine progressive Gefäßerkrankung und führt über eine Widerstands- und/oder Druckerhöhung im kleinen Kreislauf zu einem fortschreitenden Rechtsherzversagen. Auch wenn mithilfe aktueller medikamentöser Therapien eine deutliche Verbesserung der Lebensqualität und des Überlebens der Betroffenen erreicht werden konnte, bleibt die PH eine zumeist nichtheilbare Erkrankung, die im fortgeschrittenen Stadium eine Lungentransplantation notwendig macht. Interventionelle Verfahren, wie die Anlage eines interatrialen Shunts (z. B. durch atriale Septostomie oder den Atrial Flow Regulator) oder eines Reversed Potts Shunt, verbessern die RV-Funktion und die ventrikuläre Interaktion durch Schaffung einer prä- oder posttrikuspidalen „Eisenmenger-Physiologie“ und stellen eine Überbrückung oder sogar Alternative zur Lungentransplantation dar. Bei Patienten mit segmentaler PH oder chronisch thrombembolischer pulmonaler Hypertension (CTEPH) stellt die Ballonangioplastie eine bereits etablierte Intervention zur Verbesserung der pulmonalen Perfusion und damit rechtsventrikulären (RV-)Funktion dar. Dagegen ist die pulmonalarterielle Denervation ein neuartiges Verfahren, mit dem Ziel, die neurohumorale Dysregulation bei PH positiv zu beeinflussen. Der individuelle Einsatz solcher Interventionen, additiv zu den bereits etablierten medikamentösen Therapien, erweitert die Behandlungsmöglichkeiten und kann die Prognose betroffener Patienten noch weiter verbessern.

Copeptin is a cleavage product of vasopressin. This study aimed to figure out if copeptin would be a suitable biomarker in patients with congenital heart disease in the postoperative course.The primary outcome endpoint of this study was the change in copeptin concentration perioperatively in patients with congenital heart disease after surgery, with the use of a cardiopulmonary bypass. Three blood samples were taken from 81 patients up to 6 years of age in order to evaluate changes in copeptin concentration.Significant increase of copeptin concentration was shown between the first and second blood draws as well as between the first and third blood draws (Ps.001). Additionally, positive and significant correlations (r ≥ .27) between the cardiopulmonary bypass times, The Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery mortality category, the inotropic score, the duration of mechanical ventilation, the length of stay at the intensive care unit (ICU), the length of stay at the hospital, and the preoperative as well as the ICU copeptin levels were found.Copeptin showed a tendency to predict the clinical outcome of patients after congenital heart surgery. Patients with higher copeptin levels underwent more complex procedures, had longer cardiopulmonary bypass times, required more catecholamine support, needed longer time of invasive ventilation, and had longer overall stay and ICU stay.

OBJECTIVE Heterotaxy or isomerism of the atrial appendages is a congenital disorder with variable presentation, associated with both cardiac and non-cardiac anomalies, which may have a serious impact on fetal outcome. The aim of this exploratory study was to assess the value of fetal magnetic resonance imaging (MRI), as a complementary tool to ultrasound, for describing the morphological spectrum encountered in heterotaxy. METHODS This retrospective study included 27 fetuses that underwent fetal MRI following prenatal suspicion of heterotaxy on ultrasound from 1998 to 2019 in a tertiary referral center. Heterotaxy was classified as left atrial isomerism (LAI) or right atrial isomerism (RAI) based on fetal echocardiography (FE) examination. In addition to routine prenatal ultrasound, fetal MRI was offered routinely to enhance the diagnosis of non-cardiac anomalies, which might have been missed on ultrasound. Prenatal findings on ultrasound, FE and MRI were reviewed systematically and compared with those of postnatal imaging and autopsy reports. RESULTS Twenty-seven fetuses with heterotaxy and cardiovascular pathology, of which 19 (70%) had LAI and eight (30%) had RAI, were included. Seven (7/19 (37%)) fetuses with LAI had normal intracardiac anatomy, whereas all fetuses with RAI had a cardiac malformation. All 27 fetuses had non-cardiac anomalies on fetal MRI, including situs and splenic anomalies. In 12/19 (63%) fetuses with LAI, a specific abnormal configuration of the liver was observed on MRI. In three fetuses, fetal MRI revealed signs of total anomalous pulmonary venous connection obstruction. An abnormal bronchial tree pattern was suspected on prenatal MRI in 6/19 (32%) fetuses with LAI and 3/8 (38%) fetuses with RAI. CONCLUSIONS Visualization on MRI of non-cardiac anomalies in fetuses with suspected heterotaxy is feasible and can assist the complex diagnosis of this condition, despite its limitations. This modality potentially enables differentiation of less severe cases from more complex ones, which may have a poorer prognosis. Fetal MRI can assist in prenatal counseling and planning postnatal management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Within the last decades the treatment options for patients with arrhythmias have developed from a purely conservative drug treatment to a really curative treatment with removal of the arrhythmogenic substrate by continuously more sophisticated possibilities in the sense of electrophysiological techniques and ablation. Parallel to this, special outpatient departments of cardiac rhythmology for the care of patients with ion channelopathies have also become established in pediatric cardiology centers. Their task is the intergenerational care of whole families, with the aim of primarily preventing malignant arrhythmias by appropriate counselling and guidance.

Background Neuromonitoring using plasmatic biomarkers such as S100B and near-infrared spectroscopy (NIRS) represents a standard procedure for detecting cerebral damage after cardiac surgery. Their use in pediatric clinical assessment, however, is negligible. Objectives The goal of this study was to evaluate the predictive role of S100B levels and cerebral oxygenation in postoperative pediatric cardiac patients for survival and potential cerebral injuries. Methods A retrospective cohort study of infants after cardiac surgery. Primary outcome was survival until discharge. Intra/postoperative vital signs and laboratory data were measured and statistically analyzed. Results Seven out of 226 infants were non-survivors. Non-survivors had significantly lower cerebral saturation than survivors, as well as elevated S100B values at admission, associated with lower arterial pressure and higher serum lactate levels. Conclusion Although significant differences of S100B and crO2 values between survivors and non-survivors were found, no critical thresholds could be established from the data. Nevertheless, changes from the norm in these parameters should raise awareness for critical clinical development.

Background:Limited data exist on training of European paediatric and adult congenital cardiologists.Methods:A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.Results:Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).Conclusion:Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Background Intra- or extrahepatic porto-caval shunts (PCSs) can account for multiorgan dysfunction with pulmonary arterial hypertension and portosystemic encephalopathy as the most serious consequences of bypass of the hepatic circulation. The ductus venosus (DV) represents a rare foetal PCS and might be persistently patent in newborns after birth. Treatment strategies include surgical ligation and percutaneous device closure. The degree of portal vein hypoplasia limits therapy making liver transplantation the only option in some of them. Case summary In a newborn female patient a huge persistently patent DV, known already prenatally, resulted in severe secondary portal vein hypoplasia. She presented with hyperammonaemia, elevated liver enzymes, and pulmonary hypertension. With only diminutive portal venous branches and exceedingly high portal venous pressures during test-occlusion of the DV, shunt closure was not possible. At the age of 2 years more favourable portal venous pressures allowed transcatheter device closure with a nitinol atrial septal defect occlusion device. Pulmonary artery pressures and ammonia levels normalized after the procedure without any signs of portal hypertension. Discussion The case highlights the importance of meticulous imaging using balloon occlusion angiography of PCSs like the DV, to search for intrahepatic portal veins. Moreover, portal vein pressure during test-occlusion can identify patients amenable for surgical or endovascular shunt closure. Occlusion devices licensed for other indications like atrial septal defect closure can be used safely in huge PCS vessels in a one-step or staged procedure. Optimal timing of the intervention should be tailored to the patient’s needs

Valve repair is the procedure of choice for congenital aortic valve disease. With increasing experience, the surgical armamentarium broadened from simple commissurotomy to more complex techniques. We report our 30-year experience with pediatric aortic valve repair.A retrospective chart review of all patients aged less than 18 years who underwent aortic valve repair from May 1985 to April 2020 was conducted. Mortality was cross-checked with the national health insurance database (96% complete mortality follow-up in April 2020). Primary study endpoints were survival and incidence of reoperations.From May 1985 until April 2020, 126 patients underwent aortic valve repair at a median age of 1.8 years (interquartile range, 0.2-10). Early mortality was 5.6% (7 of 126). All early deaths occurred in neonates with critical aortic stenosis undergoing commissurotomy. No early deaths were observed after 2002. Kaplan-Meier estimated survival was 90.8% (95% CI, 84.0-94.8) at 10 years, 86.9% (95% CI, 78.7-92.2) at 20 years, and 83.5% (95% CI, 71.7-90.6) at 30 years. The cumulative incidence of aortic valve replacement was 37% (95% CI, 27.7-46.3) at 10 years, 62.2% (95% CI, 50.1-72.1) at 20 years, and 67.4% (51.2-79.2) at 30 years. Nine patients had undergone re-repair of the aortic valve. The majority of valve replacements were Ross procedures.Our results support a repair-first strategy for patients with congenital heart disease and underline that aortic valve reconstruction can be a successful long-term solution. Longevity did not differ between aortic valve commissurotomy and complex aortic valve reconstruction.

Zusammenfassung Eine pathologische Druckerhöhung im pulmonalen Gefäßsystem (pulmonale Hypertonie, PH) wurde bisher definiert durch einen invasiv gemessenen mittleren pulmonalarteriellen Druck (mPAP) ≥25 mm Hg in Ruhe. Auf dem 6th World Symposium on Pulmonary Hypertension (WSPH) in Nizza 2018 wurde eine neue Definition der PH vorgeschlagen, die die Senkung der Obergrenze des normalen mPAP von 24 auf 20 mm Hg beinhaltet. Obwohl keine Evidenz aus pädiatrischen Studien hierfür vorliegt, wurde diese neue PH-Definition (mPAP >20 mm Hg) aus Gründen der Einheitlichkeit auch von der pädiatrischen „Task Force“ des WSPH 2018 übernommen. Die vorliegende Stellungnahme der Arbeitsgemeinschaft Pulmonale Hypertonie (AGPH) der Deutschen Gesellschaft für Pädiatrische Kardiologie und angeborene Herzfehler e. V. (DGPK) erläutert die zugrunde liegende Rationale und mögliche Konsequenzen dieser Definitionsänderung. Insbesondere stellt sie klar, dass diese Änderung der Definition aktuell keinen Einfluss auf die Verschreibung von Medikamenten zur gezielten spezifischen Therapie der pulmonalarteriellen Hypertonie hat.

Therapy of children with post‐transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) can be challenging. In this retrospective study, we investigated PD‐L1 and PD1 expression in all PTLD categories of childhood and adolescence to see whether checkpoint inhibition with PD‐L1/PD1 inhibitors may serve as a therapy option. We included 21 patients aged 19 years or younger (at date of transplant) with PTLD following SOT or HSCT having adequate tumor samples available (n = 29). Using immunohistochemistry, we evaluated PD‐L1/PD1 expression on both tumor cells and cells of the microenvironment in all samples. Availability of consecutively matched tumor samples during 6 of 21 patients' disease courses also allowed an intra‐individual assessment of PD‐L1/PD1 expression. We observed lower PD‐L1 and higher PD1 expression in non‐destructive lesions, and higher PD‐L1 and lower PD1 expression in polymorphic and, in particular, in monomorphic PTLD, mostly diffuse large B‐cell lymphomas (DLBCL, n = 10/21). The amount of PD‐L1‐ and PD1‐positive cells changed in the opposite way in sequential biopsies of the same individual correlating well with the PTLD category. This is the first comprehensive pediatric study assessing PD‐L1 and PD1 expression on tumor cells and in the microenvironment of PTLD including not only monomorphic, but also non‐destructive early lesions. PD‐L1 expression of the tumor cells inversely correlated with PD1 expression in surrounding tissues, with the highest expression in DLBCL. Since PTLD can be therapeutically challenging, our results indicate a potential efficacy of checkpoint inhibitors if standard immune‐ and/or chemotherapy fail or are impossible. We therefore recommend routine staining of PD‐L1 and PD1 in all PTLD categories.

Marfan syndrome is caused by mutations of the fibrillin-1 gene, which weakens the connective tissue integrity. Since 2003, bioavailability regulations of TGF-ß through fibrillin alterations have been presumed of being the culprit mechanisms for aortic aneurysm development. We present the analysis of our single-center Marfan children and adolescents cohort to assess the influence of age, sex, degree of cardiovascular involvement and dosage on losartan effectivity. This prospective longitudinal registered echocardiographical investigation (EudraCT 2009-016139-36) of 49 patients with an average follow-up of 72 months focused on aortic root z-scores, elasticity, and yearly progression rates. The 33 patients under medication with losartan showed an aortic root z-score reduction during the first 36 months compared to 22 patients without medication presenting constant mild progression. Yet, results diminished under losartan thereafter, adding up to similar progressions over 72 months in both groups (0.07 ± 0.10/year versus 0.04 ± 0.11/year). Although male patients exhibited higher root z-scores, progression with and without medication was comparable to females and not age-dependent. In conclusion, losartan evoked a significant aortic root z-score regression in young Marfan patients over the first 3 years, but this effect mitigated thereafter. The initial improvement concurred with ameliorated elasticity; lower stiffness levels predicted better clinical outcome, but likewise only up to 36 months. Sex differences in dilatation severity were observed but neither age nor sex had significant influence on progression rates. Losartan dosages were gradually increased in more severely affected patients and provided an equal rate of root progression over 72 months in comparison to patients under losartan treatment with lesser baseline dilatation severity.

Background Management of pediatric post‐transplantation lymphoproliferative disorder (PTLD) after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) is challenging. Aim This study of 34 PTLD patients up to 19‐years old diagnosed in Austria from 2000 to 2018 aimed at assessing initial characteristics, therapy, response, and outcome as well as prognostic markers of this rare pediatric disease. Methods and results A retrospective data analysis was performed. Types of allografts were kidney (n = 12), liver (n = 7), heart (n = 5), hematopoietic stem cells (n = 4), lungs (n = 2), multi‐visceral (n = 2), small intestine (n = 1), and vessels (n = 1). Eighteen/34 were classified as monomorphic PTLD, with DLBCL accounting for 15 cases. Polymorphic disease occurred in nine, and non‐destructive lesions in six cases. One patient had a non‐classifiable PTLD. Thirteen/34 patients are surviving event‐free in first remission (non‐destructive, n = 4/6; polymorphic, n = 4/9; monomorphic, n = 6/18). Fourteen/34 patients lacked complete response to first‐line therapy, of whom seven died. Four/34 patients relapsed, of whom two died. In 3/34 patients, death occurred as a first event. The 5‐year overall and event‐free survival rates were 64% ± 9% and 35% ± 9% for the whole cohort. Among all parameters analyzed, only malignant disease as the indication for transplantation had a significantly poor influence on survival. Conclusions This study shows PTLD still to be a major cause of mortality following SOT or HSCT in children. A continued understanding of the molecular biology of the disease shall allow to decrease treatment intensity for lower risk patients and to identify patients who may benefit from newer therapy approaches to improve outcome and decrease morbidity.

Background Mechanical circulatory support (MCS) in pediatric patients remains challenging because of small body size, limited availability of approved devices, and the variety of etiologies, including biventricular and univentricular physiologies. We report our single-center experience with MCS in pediatric patients in terms of survival and adverse events. Methods Outcome, etiologic, and demographic data of pediatric patients implanted with a long-term MCS device between 2011 and 2019 at the Medical University of Vienna were retrospectively collected and analyzed. Overall survival and freedom of treatment-related adverse events at 1 year were investigated by Kaplan–Meier analyses and stratified for circulation (biventricular vs univentricular), age group ( 6 years), and pump technology (pulsatile ventricular assist device [p-VAD] vs continuous flow pump [cf-VAD]). Results One-year survival of all 33 pediatric patients (median, 4 years; interquartile range, 0-13 years) was 73%, with a tendency toward better outcomes in patients with biventricular circulation than in those with univentricular circulation (80%; n = 25 vs 50%; n = 8; P = .063). The trends toward better survival probability in older patients and in patients with cf-VADs did not reach statistical significance (63.2% vs 85.7%; P = .165 and 82.4% vs 62.5%; P = .179, respectively). Freedom from adverse events was higher in older patients (57.1% vs 5.6%; P Conclusions MCS is a promising therapy for a broad spectrum of pediatric patients, irrespective of heart failure etiology, age, and pump type. With increasing experience, improved devices, and patient selection, MCS may become a valuable treatment option for patients with univentricular hearts.

While the current definition of pulmonary hypertension (PH) is still based on haemodynamic variables, transthoracic echocardiography is the most important diagnostic clinical tool for the first assessment and evaluation of a patient, in whom PH is suspected. In addition, it is the most important clinical modality in long term follow-up and the utility of echocardiography has widely been demonstrated in patients with PH. Echocardiography not only reveals the underlying cardiac morphology and diagnosis of any associated cardiac defects. In most patients with PH right ventricular (RV) pressure estimation is feasible. In addition, ventricular systolic and diastolic function, as well as ventricular-ventricular interactions of both ventricles can be assessed by using echocardiography. Maximizing the use of echocardiography by reporting several measures to gain information and quantitatively describe the parameters, that are linked to prognosis, seem particularly appealing in these children, in whom other advanced imaging modalities requiring anaesthesia is associated with a considerable risk. Herein we provide a practical approach and a concise and clinically applicable echocardiographic guidance and present basic variables, which should be obtained at any assessment. Moreover, we present additional advanced echocardiographic measures, that can be applied in a research or clinical setting when progressive PH needs a deeper insight to assess heart function, estimation of pulmonary artery pressures among others, by echocardiography. Finally, clinically relevant studies in view of the prognostic properties with a focus on the most important echocardiographic variables in pediatric PH are summarized.

The COVID-19 pandemic has had a huge influence in almost all areas of life, affecting societies, economics, and health care systems worldwide. The paediatric cardiology community is no exception. As the challenging battle with COVID-19 continues, professionals from the Association for the European Paediatric and Congenital Cardiology receive many questions regarding COVID-19 in a Paediatric and Congenital Cardiology setting. The aim of this paper is to present the AEPC position on frequently asked questions based on the most recent scientific data, as well as to frame a discussion on how to take care of our patients during this unprecedented crisis. As the times are changing quickly and information regarding COVID-19 is very dynamic, continuous collection of evidence will help guide constructive decision-making.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Background To the best of our knowledge, this is the first report of a successful one-stage double atrioventricular valve (AVV) replacement using two Melody™ transcatheter valves in an infant. Case summary We report a successful case of double AVV replacement with Melody™ transcatheter valves in a 9-month-old infant with a right ventricular dominant atrioventricular septal defect (AVSD). The boy initially presented with borderline sized left-sided heart structures, congenital left AVV stenosis, ventricular displacement of the right AVV with high-grade insufficiency and moderate valvar pulmonary stenosis. Double AVV replacement was performed 2 months after an unsuccessful attempt to repair the defect with persisting left AVV stenosis, underfilling of the small left ventricle and high-grade right AVV, and pulmonary valve regurgitation, resulting in low cardiac output. During double Melody™ AVV replacement, the right ventricular outflow tract was replaced with a pulmonary homograft. The boy was discharged on post-operative Day 28 and presented with competent valves, no ventricular outflow tract obstruction and no paravalvular leak at 11 months of follow-up. Discussion The presented innovative approach allowed for biventricular correction of an unbalanced AVSD with unfavourable anatomy for standard techniques. The heart team should decide individualized, after careful assessment of cardiac anatomy and function, if the benefits of replacement of AVVs with Melody™ transcatheter valves may outweigh the benefits of univentricular palliation in case of unbalanced AVSD.

Macitentan is a safe and effective substance for treatment of adults with pulmonary arterial hypertension. Data on its use in paediatric patients are limited. In this single-centre prospective study, we report on our experience with macitentan in children focusing on applicability and practical aspects. Between December 2014 and July 2018, macitentan was introduced to paediatric patients according to a dosing protocol adjusted to body weight. Blood pressure, heart rate, saturation and clinical symptoms were recorded daily during introduction. Liver function parameters and haemoglobin levels were measured at baseline, four weeks and three months after initiation and after one year of treatment. Twenty-four patients (14 male, 10 female) were enrolled for treatment with macitentan. The mean age was 10.7 ± 7.6 years (range: 0.1 year–23 years). Fifteen out of 24 patients were World Health Organization functional class (FC) II, 7 patients in FC III and 2 patients in FC IV. Twenty out of 24 patients (83%) received additional advanced therapy with sildenafil and/or prostacyclines. We had two early discontinuations because of clinical relevant oedema. In the remaining 22 patients, macitentan was well tolerated. Liver function parameters and blood count levels remained stable during the observational time. The introduction of macitentan was feasible and mostly well tolerated in paediatric patients. Special attention should be paid to oedema during introduction of the drug. To the best of our knowledge, this is the first study to report on its applicability in infants and children. However, larger prospective trials are warranted to verify these preliminary findings.

The Melody valve (Medtronic, Minneapolis, MN, USA) is a stented bovine jugular vein graft that was primarily approved for transcatheter implantation in a pulmonary valve position. The prosthetic valve can also be implanted in an atrioventricular position in infants and young children, and in these cases it must be modified appropriately. In this tutorial we demonstrate the surgical preparation of a stented transcatheter Melody valve for implantation in the atrioventricular position. Additionally, we present a safe and effective method for surgical valve-in-valve implantation in a 3-year-old patient with hypoplastic left heart syndrome.

Aberrant origin of the subclavian artery (SCA) is a well-known vascular anomaly as part of congenital heart diseases with the left subclavian artery (LSCA) being more frequently affected than the right subclavian artery (RSCA). Complete isolation of the SCA is an even more infrequent aortic arch anomaly, occurring in less than 1% for the LSCA and even less for the RSCA. Isolation of the RSCA in patients with d-transposition of the great arteries (D-TGA) is even scanter with only a hand full of cases being reported in the literature. However, isolation of the RSCA has important implications on hemodynamics and surgical strategies. In this case report, we present a newborn patient with D-TGA which presented with distinct differential cyanosis. While the right upper extremity appeared pink with an oxygen saturation of 100%, the rest of the body was cyanotic. At first, this appearance was interpreted as the Harlequin phenomenon during primary care. However, detailed echocardiography revealed an aberrant origin of the RSCA from the right pulmonary artery, which led to the differential cyanosis. The patient underwent arterial switch operation on day of life two including dissection and reimplantation of the RSCA. The special hemodynamic situation of this is discussed in terms of pathophysiology and as well as its impact on perioperative and surgical management.

Turner syndrome (TS) is a common genetic disorder in females with high incidence of ascending aortic dilatation and even dissection occurring as early as in the second decade. Known risk factors (RF) are bicuspid aortic valves (BAV), coarctation of the aorta (CoA), and arterial hypertension. Since 10% of dissections occur in patients without RF, an intrinsic aortic wall abnormality has been postulated. This study aimed to investigate the elasticity of the ascending aorta as a surrogate marker of aortic wall texture. Forty-six pediatric patients with genetically proven TS were prospectively examined for the morphology of their aortic valve, and size and elasticity indices of the adjacent aorta. Cohorts of 46 female subjects with tricuspid aortic valves (TAV) and ten non-syndromic females with BAV were investigated as separate control groups. Comparison of healthy controls with TS patients revealed significantly deteriorated elasticity indices in those with TS. Furthermore, normalized aortic dimensions were greater in TS patients, but dilatations of the ascending aorta with z-score levels above two were restricted to those with BAV (14/46). Deteriorated elasticity indices were measured in TS patients, independent of aortic dilatation, BAV, and CoA, and were comparable to those of patients with isolated, non-syndromic BAVs. By measuring elasticity levels as a surrogate for aortic wall texture, we were able to gather evidence that TS presents with an intrinsic abnormality of the ascending aorta even in patients without concomitant BAV, CoA or dilatations as early as in childhood.

Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.

Background Unfractionated heparin (UFH) is used for prophylaxis and treatment of thrombosis in children. Laboratory monitoring of UFH is needed to prevent over- or under-anticoagulation. Objectives Study objectives were to investigate i) the association between UFH dose and UFH effect as monitored by anti-IIa, ii) the relationship of anti-IIa and anti-Xa effects, and iii) the influence of patients’ age and other factors on UFH effect. Patients and methods Randomized controlled trial in children during cardiac catheterization, comparing high-dose UFH (100 units/kg bolus) versus low-dose UFH (50 units/kg bolus). Blood samples were drawn at baseline, after 30, 60 and 90 minutes. For the purpose of this study, 49 children and 117 blood samples were evaluated. Results The anti-IIa assay discriminated well between high and low-dose UFH. Multiple regression demonstrated a significant influence of UFH dose and age on anti-IIa levels. Younger children had lower anti-IIa levels than older children, an effect more pronounced at low-dose UFH. Anti-Xa/anti-IIa ratios were equal at low-dose UFH. However, anti-Xa levels were relatively increased over anti-IIa in infants and after high-dose UFH bolus. Conclusion The UFH effect on anti-IIa levels is lower in infants compared to older children. This influence of age appears to be dose-dependent, more pronounced at low-dose UFH. Anti-Xa versus anti-IIa levels are not equal, particularly in infants and after high dose UFH. Monitoring UFH using solely anti-Xa assays may not be sufficient in children and the anti-IIa assay may provide important complementary information. This article is protected by copyright. All rights reserved.

The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.

Pediatric heart failure (HF) is rare. The prognosis is generally poor. HF is most frequently related to cardiomyopathy or congenital heart disease (CHD). Associated phenotypes are HF with preserved (HFpEF) or reduced ejection fraction (HFrEF); both in children with biventricular or univentricular circulation. Cardiac growth, differentiation, proliferation and consecutively regenerative and repair mechanisms are inversely related to the patient’s age; edaphic and circulating cardiac progenitor cells as well; in sum, there are enormous endogenous potentials repairing a diseased heart in particular in young children. Efforts supporting pediatric cardiac regeneration are clearly justified; cell-based therapies have been addressed in small series of children with end-stage HF of either the left or right ventricle, more recently in randomized clinical trials. Different cell populations like autologous bone marrow mononuclear cells, progenitor cells or cardiac derived cells have been injected into coronaries or directly into the myocardium. Beneficial at least transient improvement of cardiac function was observed in patients with dilative cardiomyopathy and CHD, mainly hypoplastic left heart syndrome (HLHS). Cellular repopulation and possibly more crucial, paracrine effects contributed in slowing down progression of pediatric end-stage HF. Our review summarizes the current knowledge in different scenarios of HF by cell-based cardiac therapies in critically ill children. Based on the actual clinical experience future work to distinguish responders from non-responders among other refinements will lead to individualized precision treatment of HF in children, what means a lot to a child on a long list waiting for heart transplantation (HTX).

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

Background Blood-based biomarkers reflecting different components of cardiovascular pathophysiology are now used increasingly in patients with Fontan circulation due to univentricular congenital heart disease. Feeding alters haemodynamics significantly and, thus, may affect biomarker levels. As the haemodynamic responses to a meal differ between Fontan patients and normal subjects, we hypothesised that biomarker kinetics may also vary between these populations. Methods In 15 patients with Fontan physiology, and 15 matched healthy volunteers, 4 heart failure biomarkers were measured under fasting conditions, and 3 after additional timepoints over 2 h following ingestion of a standardised liquid meal. Changes in biomarker levels over time and the effect of Fontan physiology, sex and age were tested using repeated-measures mixed models. Results Under fasting conditions, high-sensitivity C-reactive protein (hsCRP), mid-regional pro-adrenomedullin (MR-proADM) and C-terminal pro-endothelin-1 (CT-proET-1) were raised significantly in Fontan patients compared to controls. Postprandially, mid-regional pro-atrial natriuretic peptide (MR-proANP) decreased significantly in patients (max. mean decrease ∼7% after 120 min). Conversely, it increased in normal subjects (max. mean increase ∼8% after 60 min). The remaining biomarkers did not change significantly. Conclusions The ingestion of food triggers contrary deflections of MR-proANP levels in patients with Fontan circulation compared to normal subjects. Therefore, this parameter should be assessed under fasting conditions in order to correct for postprandial variability.

Realistic training of cardiologic interventions in a heart catheter laboratory is hardly achievable with simple tools and requires animal experiments. Therefore, first a simple mock circuit connected to a porcine heart mimicking the natural heart motion was developed. In a second step the setup was duplicated to drive both sides of the heart independently to generate motion and physiologic pressures and flows. Using this simple setup cardiologic interventions (arterial and ventricular septal defects ASD/VSD closure) were performed successfully and allowed realistic training under the C-arm, echocardiography, placement of catheters and repair of ASD/VSD. With the second setup flows of up to 4 l/min were achieved in both sides of the heart at maximum left and right ventricular pressures of 80 mm Hg and 30 mm Hg respectively. This method is inexpensive and represents a realistic alternative to training in animal experiments.

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9–24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.