Paediatric and adult congenital cardiology education and training in Europe.

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.

Biallelic variants of ATP13A3 cause dose-dependent childhood-onset pulmonary arterial hypertension characterised by extreme morbidity and mortality.

BACKGROUND: The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the ATP13A3 gene were recently identified as a new cause of adult-onset PAH. However, the contribution of ATP13A3 risk alleles to child-onset PAH remains largely unexplored. METHODS AND RESULTS: We report three families with a novel, autosomal recessive form of childhood-onset PAH due to biallelic ATP13A3 variants. Disease onset ranged from birth to 2.5 years and was characterised by high mortality. Using genome sequencing of parent-offspring trios, we identified a homozygous missense variant in one case, which was subsequently confirmed to cosegregate with disease in an affected sibling. Independently, compound heterozygous variants in ATP13A3 were identified in two affected siblings and in an unrelated third family. The variants included three loss of function variants (two frameshift, one nonsense) and two highly conserved missense substitutions located in the catalytic phosphorylation domain. The children were largely refractory to treatment and four died in early childhood. All parents were heterozygous for the variants and asymptomatic. CONCLUSION: Our findings support biallelic predicted deleterious ATP13A3 variants in autosomal recessive, childhood-onset PAH, indicating likely semidominant dose-dependent inheritance for this gene.

Rezidivierende fulminante Myokarditis mit wiederholtem Einsatz der ECMO bei einem Kind.

Recurrent myocarditis is rare with only few reports having been published for paediatric cases. Repeated use of extracorporeal membrane oxygenation is also uncommon. In this paper we will present a very rare case of a 7-year old girl with recurrent fulminant myocarditis with heart failure requiring cardiopulmonary resuscitation and mechanical circulatory support with extracorporeal membrane oxygenation. Both episodes were precipitated by a viral upper respiratory tract infection, and in both cases the cardiac function eventually completely recovered. The second episode of fulminant myocarditis was particularly complex with markedly elevated markers of myocardiocytolysis, multiorgan dysfunction and the need for prolonged mechanical circulatory support. Nevertheless, the patient made a remarkable recovery. A comprehensive diagnostic workup pointed towards an aberrant immune response as the likely cause of the girl's susceptibility for fulminant myocarditis.

Acute rheumatic fever outbreak in southern central European country.

A decline in the incidence of acute rheumatic fever (ARF) in developed countries over the past century can be attributed to the improved public hygiene and to widespread use of antibiotics. ARF seemed to be a rare disease in southern central European country, Slovenia, up to 2010 when we noticed an increase in the number of patients with ARF. In order to assess the current incidence of ARF, we performed a retrospective study of all patients with ARF treated at the University Children's Hospital Ljubljana from January 2008 until the end of December 2014. In a period of 7 years, 19 patients with ARF were identified. The estimated annual incidence of ARF during the study period was 1.25 cases per 100,000 children. Carditis was present in all patients, arthritis in 37 % and Sydenham chorea in 32 %. CONCLUSION: Recent ARF outbreak in Slovenia revealed that this disease is still present in southern central Europe with an estimated annual incidence of 1.25 cases per 100,000 children. Unrecognized or inadequately treated ARF could be the cause of acquired heart disease and must be even nowadays included among the differential diagnoses in a febrile child with arthritis, heart murmur or movement disorder. What is Known: • Acute rheumatic fever (ARF) is diagnosed based on the major and minor Jones Criteria. • A decline in the incidence of ARF in developed countries over the past century can be attributed to the improved public hygiene and to widespread use of antibiotics. What is New: • In the last decade, an increase in the incidence of ARF was observed in Slovenia which has a central European geographic position. • Our paper highlights the importance of including ARF in the differential diagnosis of a febrile child with arthritis/arthralgia and/or heart murmur and/or acute chorea.

Safe use of alteplase in a 10 months old infant with cardio-embolic stroke.

The knowledge about safety and efficacy of thrombolysis in paediatric stroke is limited, especially for very young children. We present an infant with cardioembolic stroke treated with alteplase. He had hypoplastic left heart syndrome since birth. He underwent Norwood operation, followed by bidirectional cavopulmonary anastomosis at 3 months. On aspirin therapy he was well until heart failure developed at the age of 9 months with 2 thrombi in the right ventricle. During the course of enoxaparin therapy sudden acute left-sided haemiplegia occurred. The emergency brain CT scan was normal. Informed consent was obtained from parents after explaining the alteplase treatment protocol and possible complications. Alteplase was administered i.v. according to standard adult stroke regimen. A control CT scan obtained 24 h later was negative for intracranial haemorrhage but the hypodense area in insula, internal capsule and subcortical area of the right parietal region were indicative of ischaemic stroke. Anticoagulation therapy was continued. He recovered hand functions after 5 days and full repertoire of movements on his left side 3 weeks later. A neurological examination performed 2 months after indicated mild residual haemiparesis and a modified Rankin scale score of 1. Three months later, the patient died of progressive heart failure. An international multicentre prospective trial is ongoing to investigate the safety and appropriate dose of alteplase for paediatric ages 2-17 years. The aim of this paper is to report safe use of alteplase even in a very young child.

A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study.

Noonan syndrome is a relatively common and heterogeneous genetic disorder, including congenital heart defect in more than half of the cases. If the defect is not large, life expectancy is normal. Here we report on a case of an infant with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene. This heterozygous unclassified missense variant in exon 3: c.179G> T (p.Gly60Val) might be associated with a lethal form of Noonan syndrome. The malignant clinical course of the disease and the lethal outcome in an infant only a few months old might be connected to RAS-mitogen-activated protein kinase pathway hyperactivation, consequently promoting cell growth and proliferation, leading to rapidly progressive hypertrophic cardiomyopathy. Further biochemical and functional studies are needed to confirm this hypothesis.

Can prenatal detection of Down syndrome be improved by enhancing obstetricians' skills of performing adequate foetal cardiac examination at the primary level?

AIMS: To evaluate the prevalence of congenital heart defects (CHDs) in live-born infants with Down syndrome (DS) and to investigate whether these CHDs might be detected during routine second trimester ultrasound screening performed at the primary level. METHODS: A retrospective analysis of 66 cases of DS in live-born infants. The infants with DS underwent a detailed echocardiographic examination to evaluate cardiac morphological characteristics and function. RESULTS: Thirty-six live-born DS infants (54.5%) had associated CHDs. According to the apical four-chamber view at the first postnatal echocardiographic examination, we estimated that 20 (55.6%) of the 36 patients with associated CHDs should have been identified during the routine second-trimester prenatal scan [17 infants with complete atrioventricular septal defect (AVSD), two with partial AVSD, and one with non-restrictive perimembranous ventricular septal defect] if the results had been correctly interpreted. An additional seven patients with associated CHDs should have been identified if the evaluation of both outflow tracts had been included into the screening protocol. CONCLUSION: Our data suggest that the prenatal DS detection rate can be significantly increased by improving obstetricians' skills of performing adequate foetal cardiac examination as part of the routine 18- to 23-week ultrasound examination at the primary level.

Diagnosis, clinical features, management, and post-natal follow-up of fetal tachycardias.

OBJECTIVE: To evaluate the diagnosis, clinical features, management and post-natal follow-up in consecutive fetuses identified with tachycardia. METHODS: We reviewed consecutive fetuses with tachycardia identified in a single tertiary institution between January, 2001, and December, 2008. We considered several options for management, including no treatment but close surveillance, trans-placental antiarrhythmic therapy in fetuses presenting prior to 36 weeks of gestation, and delivery and treatment as a neonate for fetuses presenting after 36 weeks of gestation. Data was gathered by a review of prenatal and postnatal documentation. RESULTS: Among 29 fetuses with tachycardia, 21 had supraventricular tachycardia with 1 to 1 conduction, 4 had atrial flutter, 3 had atrial tachycardia, while the remaining fetus had ventricular tachycardia. Of the group, 8 fetuses (27.6%) were hydropic. Transplacental administration of antiarrhythmic drugs was used in just over half the fetuses, delivery and treatment as a neonate in one-quarter, and no intervention but close surveillance in one-sixth of the case. Twenty-six of 29 fetuses (89.7%) were born alive. Only patients with fetal hydrops suffered mortality, with 37.5% of this group dying, this being statistically significant, with the value of p equal to 0.03, when compared to non-hydropic fetuses. Only 3 patients (11.5%) were receiving antiarrhythmic prophylaxis beyond the first year of life. CONCLUSION: A significant proportion of fetal tachycardias recognized before 36 weeks of gestation can be treated successfully by transplacental administration of antiarrhythmic drugs. Fetuses presenting after 36 weeks of gestation can be effectively managed postnatally. The long-term prognosis for fetuses diagnosed with tachycardia is excellent, with the abnormal rhythm resolving spontaneously during the first year of life in most of them.

Balloon dilation of neonatal critical aortic valvar stenosis via the umbilical artery.

OBJECTIVES: To report our experience with balloon dilation of critical aortic valvar stenosis in neonates via the umbilical artery using currently available catheters. BACKGROUND: There is no agreement regarding the optimal vascular approach for balloon dilation of critical aortic valvar stenosis in neonates. METHODS: Since June of 2005, we have attempted to obtain umbilical arterial access within the first week after birth in all neonates with critical aortic valvar stenosis. In patients in whom umbilical artery access was obtained, we proceeded with an attempt at balloon dilation. RESULTS: We were presented with 5 patients with critical aortic valvar stenosis within the first week after birth, and the umbilical arterial approach was obtained in all, with effective relief of the stenosis achieved in 4. CONCLUSIONS: The umbilical arterial approach should always be considered for balloon dilation of neonatal critical aortic valvar stenosis. Using currently available catheters, the procedure is safe, simple, and effective even in patients weighing less than 2.5 kilograms. Further experience using this approach is warranted.

First-degree heart block in the fetus of an anti-SSA/Ro-positive mother: reversal after a short course of dexamethasone treatment.

Isolated congenital heart block is almost invariably associated with the presence of antibodies to SSA/Ro and SSB/La antigens in the maternal circulation. Once established, third-degree congenital heart block is permanent. However, a lesser degree of autoantibody-associated heart block in a fetus can be reversed if it is recognized and treated early enough with fluorinated glucocorticosteroids. The only method available clinically for the recognition of first-degree heart block in a fetus is measurement of the mechanical PR interval by pulsed Doppler echocardiography. This is the first report of a fetus in whom a diagnosis of first-degree heart block and the consequent decision to intervene were based solely on this technique. In addition, the first-degree heart block resolved completely after only 2 weeks of dexamethasone treatment, and the heart rhythm remained stable throughout the remainder of the pregnancy despite early discontinuation of therapy due to oligohydramnios.

A novel mutation in the G4.5 (TAZ) gene in a kindred with Barth syndrome.

Barth syndrome is an X-linked recessive disorder characterised by dilated cardiomyopathy and a variable expression of skeletal myopathy, short statue and neutropenia. Molecular genetic analysis is currently the most reliable diagnostic method. A kindred with a novel 535delC mutation in the G4.5 (TAZ) gene responsible for Barth syndrome is presented. Beside the patient, the same mutation was detected in patient's mother and grandmother. In contrast to the so far reported patients with mutations in the same region of G4.5 (TAZ) gene, the patient described here has only a mild and transitory clinical presentation. This could be attributed to alternative splicing of G4.5 (TAZ) gene, since mRNA lacking exon 6 (with 535delC mutation) was detected. Genetic analysis of the G4.5 (TAZ) gene was helpful for establishing the precise diagnosis of Barth syndrome and for adequate genetic counselling. Predicting the phenotype on the basis of mutations is unreliable especially if mutations are localised in alternatively spliced exons of the G4.5 (TAZ) gene which may result in a milder clinical presentation than expected.