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Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P =0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P =0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

Background Children with congenital heart defects (CHD) usually undergo elective surgical repair of haemodynamically relevant shunt lesions within the first year of life. Due to susceptibility for pulmonary arterial hypertension (PAH) in patients with Down syndrome, repair is usually aimed for no later than 6 months of life. However, with rising immigration from developing countries to Europe, more patients with unrepaired CHD are diagnosed at a later age. Anatomical repair may be precluded, when advanced pulmonary vascular disease has been established. Case summary We report a 39-month-old male patient with Down syndrome with a large non-restrictive perimembranous ventricular septal defect, a large patent ductus arteriosus, and a secundum-type atrial septal defect with a prominent left-to-right shunting. Haemodynamic assessment revealed only a mild increase of pulmonary artery pressures (mPAP) with low pulmonary vascular resistance index (PVRi). Vasodilator testing led to a further increase of the left-to-right shunt and decrease of PVRi, suggesting operability. After careful consideration, the patient underwent complete surgical repair with a good post-operative clinical outcome. Cardiac catheterization 6 months after corrective repair showed a normal mPAP. No signs of PAH have been detected in the medium-term follow-up. Discussion Expertise, increased physician awareness, and a thorough pre-operative multidisciplinary evaluation are paramount to determine the best treatment approach for patients, who may present late with multiple shunts, and—in our case—underlying Down syndrome. Long-term close post-surgical follow-up in an expert centre is warranted to promptly diagnose and treat a possible late presentation of PAH appropriately.

Ventricular assist devices (VAD) are increasingly used in patients with end-stage heart failure due to acquired heart disease. Limited data exists on the use and outcome of this technology in children.All children (18 years of age) with VAD support included in the German National Register for Congenital Heart Defects were identified and data on demographics, underlying cardiac defect, previous surgery, associated conditions, type of procedure, complications and outcome were collected.Overall, 64 patients (median age 2.1 years; 45.3% female) receiving a VAD between 1999 and 2015 at 8 German centres were included in the analysis. The underlying diagnosis was congenital heart disease (CHD) in 25 and cardiomyopathy in 39 children. The number of reported VAD implantations increased from 13 in the time period 2000-2004 to 27 implantations in the time period 2010-2014. During a median duration of VAD support of 54 days, 28.1% of patients experienced bleeding complications (6.3% intracerebral bleeding), 14.1% thrombotic (10.9% VAD thrombosis) and 23.4% thromboembolic complications (including cerebral infarction in 18.8% of patients). Children with cardiomyopathy were more likely to receive a cardiac transplantation (79.5% vs. 28.0%) compared to CHD patients. Survival of cardiomyopathy patients was significantly better compared to the CHD cohort (p 0.0001). Multivariate Cox-proportional analysis revealed a diagnosis of CHD (hazard ratio [HR] 4.04, p = 0.001), age at VAD implantation (HR 1.09/year, p = 0.04) and the need for pre-VAD extracorporeal membrane oxygenation (ECMO) support (HR 3.23, p = 0.03) as independent predictors of mortality.The uptake of VAD therapy in children is increasing. Morbidity and mortality remain high, especially in patients with congenital heart disease and those requiring ECMO before VAD implantation.

Background Implantable cardioverter-defibrillator (ICD) systems are established therapy for prevention of sudden cardiac death. Long-term data on ICD systems in children and adolescents is rare. The present study displays a long-term single-center follow-up of children and adolescents with ICD systems. Methods and results The present study represents a single-center experience of patients younger than 18 years who received an ICD (n = 58). Follow-up data included in-house follow-up as well as examinations of collaborating specialists. Mean age at implantation was 14.0 ± 3.3 years and 33 patients (56.9%) were male. A transvenous ICD system was implanted in 54 patients (93.1%). In 33 patients (56.9%) electrical heart disease or idiopathic ventricular fibrillation represented the underlying condition of ICD implantation. Median follow-up duration was 70 months (45; 94). 3 patients (5.2%) died during the observation period. None of these deaths was associated with ICD failure. Appropriate shocks occurred in 32 patients (55.2%). Inappropriate shock delivery was recorded in 17 patients (29.3%). Supraventricular tachycardia represented the most frequent cause of inappropriate shock delivery (9 patients, 52.9%). T-wave oversensing led to inappropriate shock delivery in 3 patients (17.6%). In 5 patients (29.4%), lead failure caused inappropriate shock delivery. Of note, during follow-up lead failure was reported in 15 patients (25.9%) leading to surgical revision. Conclusion ICD therapy in children and adolescents is effective for prevention of sudden cardiac death. The rate of appropriate shock deliveries was significantly higher as compared with large ICD trials. Inappropriate therapies occurred frequently. In particular supraventricular tachycardia, T-wave oversensing and lead failures were responsible for these episodes.

Rationale and Objectives Congenital heart diseases (CHD) belong to the leading causes of infant mortality worldwide. Prognostic improvements result from multimodal therapy strategies leading to an increased demand for noninvasive imaging. The aim of the study was to further optimize cardiac CT radiation dose by omitting the test bolus or bolus tracking scan, which can have a relevant share of radiation exposure, especially in neonates. Materials and Methods This retrospective study included 25 neonates with CHD who received a CT angiography (CTA) from 2009 to 2018. The examinations were performed as a high-pitch CTA (pitch 3.4, 80 kV) with manual contrast administration (1.5 ml/kg body weight) and fixed scan delay depending on the respective heart defect. Diagnosis, adverse events, radiation dose parameters, objective (contrast-to-noise ratio) and subjective (4-point Likert scale) image quality as well as diagnostic accuracy compared to intraoperative findings was assessed. Results All examinations were diagnostically evaluable without adverse events. The median CT dose index volume (CTDIvol) was 0.50 mGy (range, 0.15–0.94), the median dose-length product was 8 mGy × cm (range, 3–17). The estimation of the effective dose by Monte Carlo simulation revealed lower median dose levels 0.66 mSv (range, 0.25–1.40 mSv) than previously published in comparable groups. All examinations achieved a very good mean image quality score of 1.2 ± 0.4 with only minimal image noise and mean contrast-to-noise ratio of 16.1 ± 7.0. Diagnostic accuracy was 100 % as cardiac anatomy revealed no new diagnoses or significant differences in the subsequent cardiac surgery. Conclusion Cardiac high-pitch CTA of neonates with CHD can be performed safely and dose-reducing without additional test bolus or bolus tracking scan. With very good image quality, it provides a detailed insight into the cardiac anatomy and thus enables a differentiated, noninvasive therapy planning.

We describe a newborn with single-ventricle malformation and anomalous origin of both coronary arteries from single ostium in the middle portion of the right pulmonary artery whose coronary anatomy was discovered during the operation and who underwent successful staged operative management. This report presents a unique anatomic association, proposes a means of management, and highlights the importance of intraoperative analysis.

The clinical experience with Loeys-Dietz syndrome (LDS) reveals fateful natural history with intracerebral incidents and aortic dissections. A newborn child was referred to our hospital with significantly dilated aortic root and clinical signs of LDS phenotype later genetically confirmed as LDS type I. A therapy with antihypertensive medicines was initiated to postpone the surgery. Despite that, aortic root dilatation progressed to 33 mm (z-score +9.3). To avoid aortic rupture, a valve sparing aortic root replacement was performed at patient age of 8 months. The purpose of this report is to share our dilemmas and experience in the treatment of this child.

Early extubation appears to have beneficial effects on the Fontan circulation. The goal of this study was to assess the impact of extubation on the operating table in comparison with extubation during the first hours after Fontan operation (FO) on the early postoperative course. Between 2013 and 2016, 114 children with a single ventricle heart malformations (mean age, 3.8 ± 2.3 years) underwent FO: 60 patients were extubated in the operating room (ORE) and 54 in the intensive care unit (ICUE) in the median time of 195 min (range 30–515 min) after procedure. Pre-, peri-, and postoperative records were retrospectively analyzed. The hospital survival rate was 100%. One patient from the ORE group needed an immediate reintubation because of laryngospasm. The ORE group showed lower heart rate (106.5 vs. 120.3 bpm; p

Objective To assess feasibility, safety and effectiveness of right ventricular outflow tract (RVOT) stenting in symptomatic young infants. Methods Multicentre evaluation of 35 patients intended to undergo RVOT stenting in 11 pediatric cardiac centres from 2009 to August 2011. Results Median age and weight at the time of first stent implantation were 8 weeks and 3.3 kg, with 40% of patients

Objectives Somatic development is impaired in children with congenital heart defects (CHDs), and head circumference seems to be a strong predictor of neurodevelopmental prognosis. The aim of this study was to generate up-to-date reference values for the somatic development (head circumference, body weight, and length/height) of children with CHDs. Study design Our study population consisted of all patients included in the PAN study (Pravalenz angeborener Herzfehler bei Neugeborenen in Deutschland), which was conducted prospectively over a 3-year study period by the Competence Network for Congenital Heart Defects. All children with mild, moderate, and severe CHDs born in 2006-2009 in Germany were enrolled. For computing of z-scores, only children with the following characteristics were included: appropriate for gestational age, nonsyndromic disease, term or post-term delivery, and no cardiac surgery. Results There were 2818 patients included. New z-scores for the described somatic measures of children with mild, moderate, and severe CHDs were computed. Comparisons with the KiGGS study (Gesundheit von Kindern und Jugendlichen in Deutschland) and the Berlin Longitudinal Study revealed significantly lower measurements for all measures—most notably in children with severe CHDs and/or cardiac surgery. In our cohort, no catch-up growth was seen after cardiac surgery. Conclusion Children with severe CHDs demonstrated the most abnormal pattern in growth, including head circumference before and after cardiac surgery, which is indicative of accompanying brain pathology unrelated to operative injury.

Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. To determine the molecular etiology of this disease, we performed whole-exome sequencing and targeted Sanger sequencing. We identified a common missense mutation, c.2465G>A (p.Arg822Gln), in interferon induced with helicase C domain 1 (IFIH1, encoding melanoma differentiation-associated protein 5 [MDA5]) in four SMS subjects from two families and a simplex case. IFIH1 has been linked to a number of autoimmune disorders, including Aicardi-Goutières syndrome. Immunohistochemistry demonstrated the localization of MDA5 in all affected target tissues. In vitro functional analysis revealed that the IFIH1 c.2465G>A mutation enhanced MDA5 function in interferon beta induction. Interferon signature genes were upregulated in SMS individuals’ blood and dental cells. Our data identify a gain-of-function IFIH1 mutation as causing SMS and leading to early arterial calcification and dental inflammation and resorption.

Hintergrund Die Beurteilung, ob Wachstum zeitgerecht verlauft, ist eine wichtige Aufgabe bei der Behandlung von herzkranken Kindern, da Therapieentscheidungen davon abhangig sind. Die in der Padiatrie ubliche Dokumentation von Wachstum mit Perzentilenkurven ist fur kinderkardiologische Belange zu wenig sensitiv.

Primary repair of tetralogy of Fallot (TOF) has been favored in many centers for years now and results and advantages of this management seem to verify this procedure. The authors wanted to know, if the age at the time of surgery and the surgical techniques had an influence on the long-term results. Between 1992 and 2003, 124 patients underwent complete repair of TOF at the University Hospital Munster, Germany. Patients were subdivided into two groups based on their age ( 1 year of age). Patients in whom a transannular patch (TAP) was used were compared with those without (NTAP), or in whom a conduit was used. Overall mortality was 8%, with an average age of death of 9.53 years (range 0.06–19.77 years). The patients’ age at the time of surgery affected their survival as only two cases of death were reported among the group of children < 1 year of age (3.2%) whereas eight patients were older (12.9%; p = 0.0483). Six patients died within the first 30 days post surgery. Reoperation had to be performed in 21 cases, 13 (61.9%) of these patients were < 1 year of age at the time of surgery, eight were older (38.1%). A TAP, NTAP or conduit treatment did not show significant differences in long-term survival or freedom from reoperation. Early repair of TOF within the 1st year of life can be recommended, because mortality is lower than in patients treated at a higher age. There seems no significant difference in the reintervention rate between patients treated within the 1st year of life or later.

German Research Foundation (DFG) Telethon-Italy Associazione ONLUS Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. the NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. in a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects. Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, Germany Univ Hosp Munster, Dept Human Genet, Munster, Germany Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada Universidade Federal de São Paulo, São Paulo, Brazil Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England Univ Cattolica, Inst Med Genet, Rome, Italy Univ Kentucky, Coll Med, Div Cardiol, Dept Pediat, Lexington, KY USA Ist Super Sanita, Dipartimento Biol Cellulare & Neurosci, I-00161 Rome, Italy Royal Childrens Hosp, Genet Hlth Queensland, Herston, Qld, Australia Max Planck Inst Mol Genet, Berlin, Germany Univ Hosp Rostock, Med Genet Unit, Dept Pediat, Rostock, Germany Univ Hosp Dusseldorf, Dept Human Genet, Dusseldorf, Germany Univ Hosp Munster, Dept Pediat Cardiol, Munster, Germany Univ Hosp Essen, Dept Human Genet, Essen, Germany Wroclaw Med Univ, Dept Maxilla Facial Surg, Wroclaw, Poland Wroclaw Med Univ, Dept Genet, Wroclaw, Poland Mater Pathol Serv, Brisbane, Qld, Australia Univ Hosp Charite, Dept Med Genet, Berlin, Germany Universidade Federal de São Paulo, São Paulo, Brazil German Research Foundation (DFG): Ze 524/4-1 Telethon-Italy: GGP07115 Web of Science

s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany 16-17 April 2015 This supplement has not been sponsored. Meeting abstracts Meeting abstract Singleton-Merten Syndrome (SMS) is a rare autosomal-dominant disorder characterized by a variety of symptoms including extreme calcifications of the ascending aorta and cardiac valves, dental anomalies (early onset periodontitis, root resorption), psoriasis and widened medullary cavities of the phalanges with focal osteoporosis. Employing whole exome sequencing of five SMS individuals of three families we identified the missense mutation, c.2465G>A (p.Arg822Gln) in the interferon induced with helicase C domain 1 (IFIH1) gene. Additional Sanger sequencing confirmed co-segregation of the mutation with the disorder. IFIH1, encoding melanoma differentiation-associated protein 5 (MDA5), is a member of the RIG-I-like receptor family and functions as a cytoplasmic pattern recognition receptor recognizing viral double stranded RNA (dsRNA). Immunohistochemistry demonstrated the localization of MDA5 in all affected target tissues including heart, skin and cartilage. Functional analysis revealed that the IFIH1 c.2465G>A mutation enhanced MDA5 function in interferon beta induction after polyinosinic:polycytidylic acid (poly (I:C)) stimulation in vitro. This indicates that SMS-MDA5 is hyperactive to non-self dsRNA. According to additional in vitro studies, interferon signature genes including SIGLEC1 were upregulated in blood and dental cells derived from SMS individuals. Taken together, our data demonstrate that the MDA5 gain-of-function mutation p.Arg822Gln causes the autosomal dominant disorder SMS through dysregulation of the human innate immune response.

To assess feasibility, safety and effectiveness of right ventricular outflow tract (RVOT) stenting in symptomatic young infants.Multicentre evaluation of 35 patients intended to undergo RVOT stenting in 11 pediatric cardiac centres from 2009 to August 2011.Median age and weight at the time of first stent implantation were 8 weeks and 3.3 kg, with 40% of patients3 kg. A total of 19 patients had suffered from hypoxemic spells, 8 patients were ventilated, 6 on inotropic support and 5 on prostaglandin infusion. Severe concomitant malformations were present in 11 patients, and acute infections in 2. Stenting of the RVOT was successfully performed in 33 patients, improving oxygen saturation from a median of 77 to 90% 2 days after intervention. Besides the 2 patients in whom RVOT stenting was not successful for technical reasons, there were no procedural complications. In 17 of 33 patients, 1-3 reinterventions were performed during follow-up, less than half of those were reinterventions in the RVOT. A total of 27 patients have undergone successful surgical repair 4-162 (median 19.5) weeks after initial RVOT stent implantation, 2 patients are still waiting. There were no perioperative deaths.Stenting of the RVOT provides a safe and effective management strategy for initial palliation in symptomatic young infants, including those patients not suitable or at higher risk for surgical therapy.

Congenital heart disease (CHD) occurs in 0.4-0.9% of newborn infants. In Germany approximately 6500 infants per year are born with a CHD and approximately 5500 children can expect to live into adulthood. Therefore, in thenear future an increasing number of adults with CHD will be treated by anaesthesiologists for cardiac and non-cardiac surgeries. Echocardiography is the mainstay in diagnosis of most patients with CHD and useful for monitoring cardiac function. During surgery, transoesophageal echocardiography can provide real-time assessment of ventricular function, intracardiac shunting, preload and valve function. After a brief review of the epidemiology and pathophysiology of different CHD defects, this article focuses on the role of echocardiography for cardiac monitoring of adult patients with CHD. The different uses of transthoracic and transoesophageal echocardiography are also discussed.

A few weeks after orthotopic heart transplantation, a male adolescent developed atrial arrhythmias of the donor heart due to an atypical recipient atrial flutter with a recipient-to-donor transatrial conduction resulting in an absolute arrhythmia. Under medication with propafenone, the atrial flutter of the donor heart could be terminated with cardioversion.

Hypoplastic left heart syndrome (HLHS) is a challenge for the pediatric cardiologist and the surgeon. It is generally assumed that the postoperative outcome after surgery for congenital heart disease is influenced by the institutional size. We present the results of 43 patients with true HLHS (situs solitus and atrioventricular and ventriculoarterial concordance) referred for operation between 1992 and 2002 in our center. Two children had atrioseptostomy: one died soon after the operation, and the other one was transplanted successfully but died at the age of 6 months following acute rejection. The remaining 41 underwent Norwood I palliation, 21 stage II palliation, and 10 stage III palliation. Early mortality was 29% after stage I operation, 4.7% after stage II palliation, and 0% after stage III operation. Overall mortality was 39% after stage I, 9.5% after stage II, and 10% after stage III operation. Low birth weight was associated with a higher mortality (p < 0.05). Mortality declined with increasing experience, comparable to the results of very large cardiosurgical centers with many more patients. The quality of surgery and perioperative management in smaller pediatric cardiosurgical centers can reach the level of very large centers.

Noonan syndrome (NS) is a relatively common, but genetically heterogeneous autosomal dominant malformation syndrome. Characteristic features are proportionate short stature, dysmorphic face, and congenital heart defects. Only recently, a gene involved in NS could be identified. It encodes the non-receptor protein tyrosine phosphatase SHP-2, which is an important molecule in several intracellular signal transduction pathways that control diverse developmental processes, most importantly cardiac semilunar valvulogenesis. We have screened this gene for mutations in 96 familial and sporadic, well-characterised NS patients and identified 15 different missense mutations in a total of 32 patients (33%), including 23 index patients. Most changes clustered in one exon which encodes parts of the N-SH2 domain. Five of the mutations were recurrent. Interestingly, no mutations in the PTPN11 gene were detected in five additional patients with cardio-facio-cutaneous (CFC) syndrome, which shows clinical similarities to NS.

We present the case of a 10-year-old girl with cardiomyopathy who received a heart transplant. Due to organ rejection, the dosage of immunosuppressive agents was increased postoperatively. The patient complained of intermittent headaches in the following days and developed a haemorrhagic necrosis of the left thalamus. A week later, an oral dose of cyclosporin A was accidentally given intravenously, and 2 weeks later a recurrent subarachnoid haemorrhage of unknown origin was diagnosed. The clinical course was then characterised by progressive deterioration resulting in coma, fluctuating brain stem symptoms and the development of a massive cerebral oedema with subsequent brain death. A coroner's autopsy was instigated to investigate a claim of medical misadventure. Neuropathological investigations found a focal infiltration of fungal hyphae in the left posterior cerebral artery resulting in necrosis of the vascular wall and thus explaining the source of the recurrent subarachnoid haemorrhage which eventually resulted in the girl's death. Medical misadventure due to the administration of cyclosporin was not directly responsible for the death of this patient. This case illustrates that it is of paramount importance to copiously sample and investigate the basal cerebral arteries in cases of subarachnoid haemorrhage of unknown origin, in particular in a medico-legal context.

A 16-year-old girl presented with atrial fibrillation. Transesophageal echocardiography revealed a right atrial leiomyosarcoma. Her past medical history was remarkable for incessant atrial ectopic tachycardia (AET) beginning in early infancy and continuing throughout childhood and adolescence that was refractive to medical and nonpharmacological treatment. After combined surgical and medical therapy, normal sinus rhythm was restored and the patient is currently in complete remission with no recurrent symptoms or atrial arrhythmias at 31 months after surgery and 23 months after the discontinuation of chemotherapy. Atrial tachycardia may be the first, and for prolonged periods, the only manifestation of a cardiac tumor and should prompt thorough investigation of its underlying morphological substrate.

To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in children with an estimated risk of vascular occlusion reported to range from 7% to 16%, we conducted a prospective study in infants and children with underlying cardiac disease. One hundred and twenty-five children (neonate — 16 years) were investigated. In 9 infants out of the 125 children vascular occlusion occurred, closely related to cardiac catheterisation and arterial or venous lines during major cardiac surgery. Six of the nine neonates and infants with (n=6) and without (n=3) prothrombotic risk factors showed evidence of a basically impaired fibrinolytic system. Five of the nine infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the plasminogen activator-1 promoter polymorphism along with elevated t-PA concentration before the first diagnostic cardiac catheterisation was performed. One infant presented with increased t-PA concentration only. Five of the six children with reduced fibrinolytic capacity had further prothrombotic risk factors. Conclusion: Data of this study indicate that neonates and infants with underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination with further prothrombotic risk factors are at high risk of developing early thromboembolism during cardiac catheterisation.

The 3DHeartView project produced an advanced software application for time-variant 3D cardiac modelling based on back projection of rotational X-ray angiographic sequences. Due to standard DICOM 3.0 interface, the software can be used as an add-on to any modern digital angiographer. The system accuracy has been measured and the approach has been validated with static and dynamic phantom object studies. The prototype has been tested in a clinical routine environment as well. In this paper we present the main features of the system, the methodology of 3D angiographic modelling, and certain testing and operation results. We also describe the application of high-performance computing technology in the modelling process.

Background . Until recently, newborns with medically intractable cardiac failure caused by congenital malformations were mostly doomed to death because of the severity of the disease, which precludes a palliative operation, or because of fatal deterioration before availability of a suitable donor heart. Methods . The recently developed paracorporeal pneumatically driven Medos HIA ventricular assist device offers a therapeutic option for these small infants because it is manufactured in various sizes and is even suitable for cardiac assistance in neonates with a body surface area less than 0.3 m 2 . Results . We report our initial experience with this device, which we used for univentricular bridging to total orthotopic cardiac transplantation in 3 infants. The device was inserted to support the left ventricle in two instances and to support the right heart in one. Successful bridging to transplantation was achieved in 2 infants for periods of 2 and 7 weeks. Conclusions . Our experience demonstrates the feasibility of univentricular mechanical support followed by successful cardiac transplantation in infants and newborns.

Einleitung: Die toxische Kardiomyopathie (toxKMP) ist auch bei Kindern eine gefahrliche Komplikation einer Chemotherapie maligner Erkrankungen. Die Zeitspanne zwischen Chemotherapie und dem Auftreten einer toxKMP ist sehr variabel. Eine erfolgreiche Therapie der toxKMP wiederum ist abhangig von einer fruhzeitigen Erfassung der Erkrankung. Unsere Fragestellung war, inwieweit myokardiale Dysfunktionen mithilfe der 2D-Strain-Echokardiografie im Vergleich mit konventionellen Echokardiografieverfahren sensitiver erfasst werden konnen. Methoden: 18 Kinder und Jugendliche mit toxKMP nach Chemotherapie wurden verglichen mit 14 altersgematchten Patienten nach Chemotherapie ohne toxKMP, sowie 18 herzgesunden Kindern. Untersucht wurden die Gruppen mittels verschiedener Strain-Imaging-Parameter und konventioneller Echo-Methoden. Die Daten wurden mit der EchoPAC- und SPSS-Software ausgewertet. Ergebnisse: Die Gruppe mit toxKMP zeigte gegenuber den Patienten ohne toxKMP und herzgesunden Kindern eine signifikante Reduktion des globalen radialen linksventrikularen Strain (23 vs. 31 vs. 43%, p < 0,05) und des regionalen septalen longitudinalen Strain (16 vs,18 vs. 21%, p < 0,05). Im Gegensatz dazu konnte mittels der Ejektionsfraktion (LVEF) nicht zwischen allen Gruppen ein signifikanter Unterschied festgestellt werden. Schlussfolgerung: Mit dem 2D strain imaging, speziell der longitudinalen septalen Verkurzung, konnen systolische Dysfunktionen sensitiver als mit herkommlichen echokardiographischen Messmethoden detektiert werden.

Zusammenfassung:Thrombosen und Embolien sind im Kindesalter nicht zu unterschätzen. Typische Ursachen sind zentrale Katheter, Herzkatheteruntersuchungen mit Intervention, größere operative Eingriffe neben primären oder sekundären Mangelzuständen von Gerinnungsinhibitoren. Geschätzt wird eine Inzidenz von etwa 5 auf 10000 hospitalisierte Kinder mit einer Mortalität von 2%, einer Rezidivrate von 7-18% sowie der Entwicklung postthrombotischer Syndrome in 20% der Fälle. Die Erfahrungen mit thrombolytischen Therapieformen im Kindesalter sind begrenzt. In mehreren Studien gut dokumentiert sind Thrombolysen von akuten Verschlüssen der Femoralarterien nach Herzkatheruntersuchungen: In 10 Studien wurden 147 von 164 (90%) Patienten erfolgreich lysiert, lokale Blutungen traten bei 41 von 164 (25%) auf. Auf kleinere Studien begrenzt sind Therapien von Thrombosen in den Nierenvenen, den zentralvenösen Gefäßen sowie im rechten Atrium. Erfahrungen mit Lysen linksatrialer, linksventrikulärer oder aortaler Thrombosen sowie Lungenembolien im Kindesalter liegen bisher nur in Form von Kasuistiken vor.

A 10-month-old boy with major left atrial thrombus following cardiac surgery was treated with intravenously administered recombinant tissue-type plasminogen activator (rt-PA; Actilyse, Thomae-Behring, Germany). The left atrial thrombus was diagnosed by Doppler echocardiography 8 days after completecorrection of a ventricular septal defect. rt-PA therapy was administered over a 10-day period. Significant hemopericardium occurred 50 h after the start of thrombolytic therapy. rt-PA infusion was discontinued for 20 h to insert a pericardial drainage. The initial rt-PA dose was 0.1 mg/kg over 10 min followed by a continuous daily infusion of 1.7 mg/kg together with low-dose heparin. Thrombolytic therapy was restarted 20 h after pericardial drainage was inserted. The daily rt-PA dose was gradually raised to 3 mg/kg (total dose: 18 mg/kg). On day 7 and 8 a clear decrease in P-plasminogen and P-antithrombin occurred, requiring additional fresh frozen plasma and P-antithrombin concentrate substitution. One day later, without furtherside side effects, complete thrombolysis occurred. Although hemopericardium demanded discontinuation of thrombolytic therapy, rt-PA administration, closely monitored by Doppler echocardiography, was continued, leading to complete thrombolysis of the left atrial thrombus in the early postoperative period. We consider the literature dealing with rt-PA thrombolysis in infancy we discuss this case report.

Resistance to activated protein C (APCR), in the majority of cases due to the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of venous thromboembolism. Using an activated thromboplastin time (aPTT) based method in the presence of APC together with a DNA technique based on the polymerase chain reaction, we investigated 37 children with venous (V: n=19) or arterial (A: n=18) thromboembolism and 196 age-matched healthy controls for the presence of this mutation. In the control group 10 children were detected to be heterozygous for the factor V Leiden mutation, indicating a prevalence of 5.1%. 10/19 children (52%) with venous thrombosis and 7/18 (38%) patients with arterial thromboembolism showed the common factor V gene mutation. Additional inherited coagulation disorders were found in 1/10 (V:10%) and 2/7 (A:28%) APC-resistant patients. Inherited coagulation disorders without APCR were diagnosed in 3/9 (V: 33%) and 2/11 (A:18%) children. Furthermore, we diagnosed exogenous risk factors in 6/10 (V: 60%) and 2/7 (A: 28%) children with thrombosis and APCR. These data are evidence that APCR combined with exogenous reasons may play an important role in the early manifestation of thromboembolism during infancy and childhood.

In 1973, Singleton and Merten described two females with abnormal dentition, unique radiographic changes especially of the hands, and severe calcification and intimal weakening of the aortic arch and valve. Since then three additional cases with similar features have been reported and the diagnosis was suggested in another three individuals. We present an update of one case and the detailed clinical phenotype of six other cases with Singleton-Merten syndrome. The occurrence of the disorder in six members of two families and vertical male-to-male transmission indicate an autosomal dominant pattern of inheritance. Variability in phenotype, also within a single family, is significant. Core manifestations are marked aortic calcification, dental anomalies (delayed eruption and immature root formation of primarily the anterior permanent teeth, and early loss of permanent teeth due to short roots, acute root resorption, high caries, and aggressive alveolar bone loss), osteopenia and acro-osteolysis, and to a lesser extend also glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical characteristics described here include particular facial characteristics (high anterior hairline, broad forehead, smooth philtrum, thin upper vermillion) and abnormal joint and muscle ligaments. The cause and pathogenesis of this syndrome remain unknown. © 2013 Wiley Periodicals, Inc.

Congenital absence of aortic cusps leads to severe aortic regurgitation. We present a newborn with this rare entity with extreme mitral stenosis. Hemodynamic features were those of hypoplastic left heart syndrome. Surgical management consisted of initial modified Norwood procedure followed by orthotopic heart transplantation.

Left ventricular assist device (LVAD) implantation has become an established therapy in adults as well as in children as a bridge to heart transplantation or to aid myocardial recovery. We describe the first case worldwide of an infant suffering from Bland-White-Garland syndrome successfully treated with a left ventricular assist device (Berlin Heart(R); Excor(R) Pediatric) as a bridge to heart transplantation for a period of more than one year.

Ein 17-jahriger Patient erleidet beim Freizeit-Walking eine Synkope. Ein herbeigerufener Notarzt stellt bei dem somnolenten Patienten eine monomorphe ventrikulare Tachykardie mit einer Herzfrequenz von ca. 210/min fest. Durch sofortige Kardioversion wird ein Sinusrhythmus mit breiten QRS-Komplexen und haufigen monomorphen ventrikularen Extrasystolen erreicht. Daraufhin erfolgt eine einmalige intravenose Applikation von 300 mg Amiodaron (4 mg/kg). Aufgrund seiner eingeschrankten Bewusstseinslage (Glasgow-Coma Scale

Isolated noncompaction of the left ventricular myocardium is a rare cardiomyopathy typically showing a "spongy" myocardium on ultrasound. We report on the ultrasonic and pathomorphological characteristics of an infant who, at the age of 40 days, was treated by heart transplantation for isolated noncompaction. Noncompaction should be suspected in newborns with otherwise unexplained cardiomyopathy and a "spongy" left ventricle. However, ultrasonic and pathological findings may be much less pronounced at this age than later in life.

The following study describes the discovery of a new inherited metabolic disorder, dolichol kinase (DK1) deficiency. DK1 is responsible for the final step of the de novo biosynthesis of dolichol phosphate. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C- and O-mannosylation. We identified four patients who were homozygous for one of two mutations (c.295T--A [99Cys--Ser] or c.1322A--C [441Tyr--Ser]) in the corresponding hDK1 gene. The residual activity of mutant DK1 was 2%-4% when compared with control cells. The mutated alleles failed to complement the temperature-sensitive phenotype of DK1-deficient yeast cells, whereas the wild-type allele restored the normal growth phenotype. Affected patients present with a very severe clinical phenotype, with death in early infancy. Two of the patients died from dilative cardiomyopathy.

Angeborene Herz- und Gefasfehler treten bei 0,4–0,9% aller neugeborenen Kinder auf. Von den in Deutschland pro Jahr geborenen 6500 Kindern mit Herz- und Gefasmissbildungen werden ca. 5500 das Erwachsenenalter erreichen. Diese Zahlen machen deutlich, dass die Wahrscheinlichkeit, Patienten im Erwachsenenalter mit einem Herz- und Gefasfehler anasthesiologisch fur eine chirurgische Intervention betreuen zu mussen, kunftig deutlich groser wird. Die meisten angeborenen Herzfehler werden mit Hilfe der Echokardiographie diagnostiziert. Besonders die transosophageale Echokardiographie bietet die Moglichkeit, auch intraoperativ kontinuierlich wichtige kardiale Parameter wie die linksventrikulare Funktion, Vorlast, intrakardiale Shunts und die Klappenfunktion zu beurteilen. Im Rahmen dieses Artikels sollen epidemiologische und pathophysiologische Grundlagen angeborener Herzvitien kurz dargestellt und die Rolle der Echokardiographie bei der Uberwachung von Patienten mit angeborenen Vitien erlautert werden. Dabei werden auch die unterschiedlichen Indikationen fur die Anwendung der transthorakalen und der transosophagealen Echokardiographie besprochen.