Bluthochdruck gilt als wichtiger Risikofaktor für das Auftreten von kardiovaskulären Folgeerkrankungen. Die Prävalenz der arteriellen Hypertonie im Kindes- und Jugendalter ist zwar niedrig – es bestehen jedoch zunehmend Hinweise darauf, dass geringfügig erhöhte Blutdruckwerte im Kindesalter häufiger als bisher gedacht sind. Bluthochdruck ist im Kindes- und Jugendalter häufig asymptomatisch, daher wird er meist leicht und lange übersehen.

Rationale: Cardiac organoids have the potential to overcome the limitations of cell-based therapies for myocardial infarction, particularly by improving cell engraftment. Methods: Differentiation of iPSCs into COs with matured-like action potentials and sarcomere lengths was achieved within 20 days. COs comprised cardiomyocytes, cardiac fibroblasts and endothelial cells. Transmission electron microscopy and light microscopy revealed organized sarcomeres and the presence of potential gap junctions. Furthermore, we validate a bioreactor-assisted upscaling strategy to produce the high cell densities necessary for cardiac regenerative medicine. The transplantation of COs into acutely infarcted pig hearts was successfully achieved, serving as a preclinical model for cardiac cell therapy. Results: A modest quantity of 3,500 organoids was used, and notable levels of engraftment into the infarcted area of the pig's heart were observed. In the 8-to 30-day follow-up period, the administration of CO did not result in the occurrence of arrhythmic events. Furthermore, CO-treated pigs exhibited an enhancement in cardiac function and a reduction in scar size when compared to the control group. Spatial transcriptomics demonstrates the downregulation of pro-fibrotic signalling in day 30 implanted COs. Conclusions: In summary, this study presents a novel technology for generating cardiac organoids composed of the primary cell types of functional myocardium, offering a platform for developing cell-based heart therapies.

BACKGROUND:In patients with right ventricular (RV) outflow tract stenosis and pulmonary regurgitation (PR), percutaneous pulmonary valve implantation (PPVI) aims to preserve RV and left ventricular (LV) integrity and function. Our study aimed to assess acute changes in biventricular intrinsic myocardial function occurring with PPVI. METHODS:Twenty patients with RV outflow tract dysfunction (mean±1 SD; age, 23.0±10.9 years; mean peak echocardiographic RV outflow tract gradient, 64±25 mm Hg) underwent PPVI with biventricular assessment of pressure-volume loops using the conductance catheter technique during the same cardiac catheterization. Load-independent parameters of ventricular contractility (ventricular elastance) and ventricular compliance function, as well as pulmonary/systemic arterial elastance and ventriculoarterial coupling, were assessed before and directly after PPVI. Cardiac magnetic resonance for quantification of biventricular volumes, function, and PR was also performed. RESULTS:After PPVI, both RV ventricular elastance (median [interquartile range], 0.26 [0.16-0.83] to 0.19 [0.13-0.42] mm Hg/mL per m2; P=0.029) and pulmonary systemic arterial elastance (0.32±0.20 to 0.25±0.19 mm Hg/mL per m2; P<0.001) decreased significantly, while right ventriculoarterial coupling (1.14±0.61 to 1.10±0.59; P=0.76) did not change statistically significant. LV ventricular elastance (1.31±0.93 to 1.23±0.72 mm Hg/mL per m2; P=0.68) and left ventriculoarterial coupling (0.75 [0.51-1.23] to 0.82 [0.53-1.10]; P=0.98) were not affected by PPVI although systemic arterial elastance increased significantly (0.83±0.26 to 0.90±0.34 mm Hg/mL per m2; P=0.032). Both RV (P=0.37) and LV (P=0.20) compliance showed no significant change after PPVI. Patients with relevant PR (≥25%; n=10) had lower RV ventricular elastance (P=0.043) before and higher LV compliance (P=0.010) after PPVI compared with patients with minor PR (<25%; n=10), whereas ventriculoarterial coupling was similar between the 2 groups. CONCLUSIONS:Acute reduction of RV overload by PPVI is accompanied by an instantaneous decline in RV contractility with persistent and inefficient ventriculoarterial coupling. The LV adequately adapts to an increase in pre- and post-load with nonsignificant changes in LV intrinsic function and ventriculoarterial coupling. The relevance of these response patterns on long-term biventricular remodeling requires further investigation.

The electrocardiogram (ECG) in humans during childhood is somewhat paralleling the development of the human being: very complex and important changes over time. The adaptation from intra-utero live to live after birth generates significant changes and differences in comparison to the ECG of the adult. The screening for congenital or acquired myocardial diseases using the ECG provide rather easy ways of finding underlying threats for patients. In the setting of dysrhythmias the ECG is mandatory. The use of the ECG in diagnosis and treatment of congenital heart disease (CHD), has a lower importance - as morphology/function is of superior value - given by ultrasound, MRI/CT or catheter based data, but the ECG is useful in the follow-up of individuals with CHD. The variation of the normal ECG in children remains a challenge and urge a further request for larger data sets. Materials: Overview of ECG studies in different age groups in children and young adults with congenital heart disease. Results: Data provide a possible risk stratification in either CHD and congenital or acquired myocardial diseases. ECG - screening in children is implemented in many countries at rather low cost and significant benefit. Artificial intelligence-enhanced electrocardiogram analysis adds additional specificity and sensitivity in diagnosis of diseases and prediction of risks for arrhythmias. Discussion: The ECG in children is very important. Due to the rather large variation of normal ECG presentation in children, more data is needed in the care and prevention.

Background: Aortic valve procedures in the pediatric cardiac surgery considered a vital procedure for the hemodynamic performance and the potential of growth. The Ross/Ross–Konno operation is considered as one of the surgery of choice for nonreparable aortic valve diseases and cases of obstruction of the left ventricle outflow tract (LVOTO). The current study represents an analysis of the mid- and long-term clinical results of over 20-year experience with Ross/Ross–Konno procedure.

Undetected respiratory infections may adversely affect the intrapulmonary resistance after Stage 2 or Stage 3 Fontan palliation. A few studies describe a higher risk for viral pneumonia during respiratory virus season, but none of them have focused on the effect of symptomatic viral pneumonia on in-hospital clinical course after bidirectional Glenn shunt. We analysed 77 patients who underwent bidirectional Glenn shunt surgery. Six patients were detected with pneumonia and proof of viral ribonucleic acid in tracheal mucus in the very early postoperative time. We compared them retrospectively to the remaining 71 patients regarding preoperative inflammatory signs, mortality, paediatric ICU length of stay, and ventilation time. The infection rate was not seasonal dependent. Ventilation time was significantly elongated in the pneumonia group (558 h +/- 634 vs. 8.7 h +/- 1.9;p < 0.0001) and so was the paediatric ICU length of stay (29 days +/- 26 vs. 3 days +/- 1; p = 0.007). Significantly more patients in the pneumonia group required extracorporeal cardiac life support postoperatively. The mortality was significantly increased in patients with pneumonia. Even subclinical viral pneumonia may cause ventilation-to-perfusion mismatch by raising intrapulmonary resistance. Recorded parameters of postoperative paediatric ICU therapy showed a significant impact of a viral pneumonia on patients after bidirectional Glenn shunt. The respiratory syncytial virus vaccination does not protect these patients from infection with other respiratory viruses. The focus should be put on preoperative diagnosis of pulmonary infections in the vulnerable group of patients with univentricular hearts.

Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo‐arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure‐volume loop analysis. Load‐independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end‐systolic pressure/stroke volume) and ventriculo‐arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 μg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11–2.52) to 1.00 (0.20–5.10) mm Hg/mL/m 2 ( P <0.0001), whereas ventricular compliance remained rather unchanged (0.16±0.10 mm Hg/mL/m 2 to 0.12±0.07 mm Hg/mL/m 2 ; P =0.10). Ventriculo‐arterial coupling Ea/Ees was abnormal at rest and did not improve significantly under dobutamine (1.7 [0.6–6.7] to 1.3 [0.5–4.9], P =0.70) due to a simultaneous rise in Ea from 0.71 (0.37–2.82) to 1.10 (0.52–4.03) mm Hg/mL/m 2 ( P <0.0001). Both Ees and ventricular compliance were significantly associated with Ea at baseline and under dobutamine infusion. Conclusions Patients who underwent heart transplantation show impaired ventriculo‐arterial coupling at rest and under inotropic stimulation despite preserved left ventricular contractile reserve. An abnormal response in vascular function resulting in increased afterload seems to represent an important factor that may play a role for the development of late graft failure.

Background: Thyroid dysfunction may have adverse effects on Fontan hemodynamics. Data on thyroid function in pediatric Fontan patients with or without protein-losing enteropathy (PLE) are limited. Methods: This retrospective multicenter study included 67 Fontan patients (median age 10.9 years; 35.8% female; 28.4% PLE) in whom thyroid function testing was performed. Results: Subclinical hypothyroidism (SHT) was present in 16 (23.9%) patients. Subjects with SHT had significantly lower systolic blood pressure (p = 0.014) and body weight z-score (p = 0.006), were in a worse New York Heart Association (NYHA) functional class (p = 0.004), were more often pacing dependent (p = 0.007), and were more likely to have PLE (p = 0.033, 8/19 (42.1%) patients). Serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with NYHA class >= II (p = 0.005), significant atrioventricular valve regurgitation (p = 0.023), elevated serum natriuretic peptides (p = 0.031), and in those with PLE (p = 0.002). Patients with active PLE had significantly higher TSH levels than those in remission (p = 0.003). A strong inverse relationship was found between lower free triiodothyronine (fT3) levels and natriuretic peptides (r:-0.599, p = 0.040). Using binary logistic regression analysis we found that worse NYHA class was an independent predictor of SHT (OR 4.2; 95% CI 1.1-16.1, p = 0.036). Conclusions: Subclinical thyroid dysfunction is common in Fontan, particularly in patients with hemodynamic derangements and PLE. Future studies are needed to address the prognostic implications of thyroid dysfunction in the Fontan population.

Background: Dilatation of the right cardiac cavities can have different reasons. Sometimes, there is rare differential diagnosis beneath common cases (e.g., atrial septal defect).

Objective Criss-cross heart (CCH) is a rare congenital cardiac defect defined by crossing of ventricular inflow streams contributing to less than 0.1% of all congenital heart anomalies. Due to its rarity and complexity, prenatal diagnosis in these patients remains challenging. We sought to describe prenatal findings and postnatal course in eight cases of prenatally diagnosed CCH. Methods This is a retrospective case series of prenatally diagnosed CCH in three centers between 2010-2017. We reviewed fetal echocardiograms as well as postnatal clinical charts and surgical reports. Results 8 cases of CCH were included. The median gestational age at diagnosis was 27 weeks. 7 patients were found with situs solitus, one fetus with situs ambiguous. In all patients, the four-chamber view was abnormal. There was atrioventricular discordance in half of the patients, while all patients showed ventriculoarterial discordance. All patients were found with additional cardiac anomalies, including ventricular septal defect, double outlet right ventricle, right aortic arch, atrial septal defect and pulmonary stenosis. Three patients underwent amniocentesis without pathological findings. All patients were born alive at a median gestational age of 38+2 weeks and survived our median follow-up of 181 days. Conclusion CCH can be diagnosed prenatally by detailed fetal echocardiography when observing an abnormal four-chamber view with crossing of inflow streams into both ventricles and a lack of parallel orientation of the atrioventricular valve axis due to a clockwise or counterclockwise rotation of the ventricular mass along its axis. With the help of prenatal ultrasound, parental guidance and counselling as well as postnatal pediatric cardiac management can be warranted.

Background: We report a novel nonsurgical palliation for newborns with hypoplastic left heart syndrome (HLHS), HLHS variants, and hypoplastic left heart complex (HLHC). The aim of this transcatheter approach is replacing Norwood and open-chest hybrid procedures as well as complex biventricular repairs in the neonatal period, postponing them to infancy, therefore reducing the overall risks of these complex cases.

Aims Inefficient ventricular-arterial (V-A) coupling has been described in Fontan patients and may result in adverse haemodynamics. A varying amount of aortopulmonary collateral (APC) flow is also frequently present that increases volume load of the single ventricle. The aim of the study was to assess changes in V-A coupling and APC flow during exercise CMR. Methods and results Eighteen Fontan patients (age 24 +/- 3 years) and 14 controls (age 23 +/- 4 years) underwent exercise CMR using a cycle ergometer. Ventricular volumetry and flow measurements in the ascending aorta (AAO), inferior (IVC), and superior (SVC) vena cava were assessed using real-time sequences during stepwise increases in work load. Measures of systemic arterial elastance Ea, ventricular elastance Ees, and V-A coupling (Ea/Ees) were assessed. APC flow was quantified as AAO - (SVC + IVC). Ea remained unchanged during all levels of exercise in both groups (P = 0.39 and P = 0.11). Ees increased in both groups (P = 0.001 and P < 0.001) with exercise but was lower in the Fontan group (P = 0.04). V-A coupling was impaired in Fontan patients at baseline (P = 0.04). Despite improvement during exercise (P = 0.002) V-A coupling remained impaired compared with controls (P = 0.001). Absolute APC flow in Fontan patients did not change during exercise even at maximum work load (P = 0.98). Conclusions Inefficient V-A coupling was already present at rest in Fontan patients and aggravated during exercise due to a limited increase in ventricular contractility which demonstrates the importance of a limited functional reserve of the single ventricle. APC flow remained unchanged suggesting no further increase in volume load during exercise.

Background: Adverse fibrotic myocardial remodeling has been reported in patients after heart transplantation (HT). The aim of our study was to quantify diffuse myocardial fibrosis using CMR in a cohort of children and adolescents after HT to identify potential underlying factors that are related to increased fibrosis and to assess its hemodynamic relevance.

Background: PDA stenting is a technically feasible and effective palliation in congenital heart disease with duct-dependent pulmonary circulation. Serious complications can result from arterial access by the introduced sheath. Smaller sheath sizes could result in reduction of vessel injuries.

Background: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. Methods: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. Results: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. Conclusions: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24–30 weeks) and 3 (> 30 weeks). 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Synkopen sind ein häufiges Problem im Kindes- und Jugendalter. Meist handelt es sich um gutartige Reflexsynkopen, doch müssen potenziell gefährliche Ursachen ausgeschlossen werden und andere differenzialdiagnostisch in Frage kommende Ursachen für einen plötzlichen Bewusstseinsverlust bedacht werden.

Newborns with hypoplastic left heart (HLH) are usually palliated with the Norwood procedure or a hybrid stage I procedure. Hybrid is our preferred approach. Given the critical relationship between stage I, interstage, and comprehensive stage II or advanced biventricular repair, we hypothesized that appropriate drug treatment is a significant therapeutic cornerstone, especially for the management of the high-risk interstage. We report a single-center observational study addressing the cardiovascular effects of, in particular, oral β-blockers and the additional use of angiotensin-converting enzyme (ACE) and mineralocorticoid inhibitors. In total, 51 newborns—30 with HLH syndrome (HLHS) and 21 with HLH complex (HLHC)—with a median bodyweight of 3.0 kg (range 1.9–4.4; nine with bodyweight ≤ 2500 g) underwent an uneventful “Giessen hybrid approach” using a newly approved duct stent. All patients were discharged home with a single, double or triple therapy consisting of ß-blockers, ACE and mineralocorticoid inhibitors; 90% of the patients received bisoprolol, 10% received propranolol, 72% received lisinopril, and 78% received spironolactone. Resting heart rate decreased from 138 bpm (range 112–172; n = 51) at admission to 123 bpm (range 99–139; n = 51) at discharge and 110 bpm before stage II/biventricular repair/heart transplantation (range 90–140; n = 37) accompanied by favorable bodyweight gain. No side effects were evident. In view of drug risk/benefit profiles, as well as the variable morphology and hemodynamics, the highly selective β1-adrenoceptor blocker bisoprolol is our preferred drug for treatment of HLHS/HLHC in the interstage. We avoid using ACE inhibitor monotherapy and exclude potential risks for coronary and cerebral perfusion pressure beforehand.