Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

Application of a postnatal prediction model of survival in CDH in the era of fetal therapy.

Background: The disease severity in patients with a congenital diaphragmatic hernia (CDH) is highly variable. To compare patient outcomes, set up clinical trials and come to severity-based treatment guidelines, a performant prediction tool early in neonatal life is needed.Objective: The primary purpose of this study was to validate the CDH study group (SG) prediction model for survival in neonates with CDH, including patients who had fetal therapy. Secondary, we aimed to assess its predictive value for early morbidity.Methods: This is a retrospective single-center study at the University Hospitals Leuven on all infants with a diagnosis of CDH live-born between April 2002 and December 2016. The prediction model of the CDHSG was applied to evaluate its performance in determining mortality risk. Besides, we examined its predictive value for early morbidity parameters, including duration of ventilation, respiratory support on day 30, time to full enteral feeding and length of hospital stay.Results: The CDHSG prediction model predicted survival well, with an area under the curve of 0.796 (CI: 0.720-0.871). It had poor value in predicting infants who needed respiratory support on day 30 (area under the curve (AUC) 0.606; CI: 0.493-0.719), and correlated poorly with duration of ventilation, time to full enteral feeding and length of hospital stay.Conclusion: The CDHSG prediction model was in our hands also a useful tool in predicting mortality in neonates with CDH in the fetal treatment era. Correlation with early morbidity was poor.RationaleObjectives: (1) Validation of the CDHSG prediction model for survival in a cohort of neonates with CDH, in whom fetal endoscopic tracheal occlusion was applied according to the severity of lung hypoplasia. (2) Evaluation of performance of the model in the prediction of early morbidity.Main results: (1) Confirmation of the predictive value of the model for survival in neonates with CDH in the era of fetal therapy. (2) No correlation of the model with early morbidity parameters.

Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic & Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology.

All children have a natural need to move, play, and perform activities. Physical activity is necessary for optimal physical, emotional, and psychosocial development for healthy children as well as children with congenital heart disease (CHD). In this paper we provide recommendations for physical activity, recreational sport, and exercise training in children and adolescents with CHD. In general, children with CHD should be advised to comply with public health recommendations of daily participation in 60 min or more of moderate-to-vigorous physical activity that is developmentally appropriate and enjoyable and involves a variety of activities. While all patients with CHD can participate and benefit from physical activity and exercise, those with specific lesions or complications may require counselling regarding precautions and recommendations.

Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects.

Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects (CHDs) are scarce, as cardiac tissue is difficult to obtain, especially in non-affected individuals. We explored the occurrence of copy number differences in monozygotic (MZ) twins discordant for the presence of a CHD, as an illustrative model for chromosomal mosaicism in CHDs. Array comparative genomic hybridization was performed on peripheral blood-derived DNA obtained from 6 discordant MZ twin pairs and on sex-matched reference samples. To identify CNV differences between both twin members as well as potential CNVs in both twins contributing to the phenotype, DNA from each twin was hybridized against its co-twin, and against a normal control. Three copy number differences in 1 out of 6 MZ twin pairs were detected, confirming the occurrence of somatic CNV events in MZ twins. Further investigation by copy number and (epi)genome sequencing analyses in MZ twins, discordant for the presence of CHDs, is required to improve our knowledge on how postzygotic genetic, environmental and stochastic factors can affect human heart development.

Long-term outcome after treatment of isolated pulmonary valve stenosis.

BACKGROUND: Few data are available on very long-term follow-up after treatment for isolated pulmonary valve stenosis (PVS), either surgically or by percutaneous balloon angioplasty (PBA). METHODS AND RESULTS: All patients with isolated PVS were selected from our database of congenital heart defects. Their records were reviewed systematically. We identified 79 surgically treated patients with a median follow-up of 22.5 years (range 0-45 years) and 139 PBA patients with median follow-up of 6.0 years (range 0-21 years). Echocardiographic and catheterization parameters indicate excellent results of both techniques in relieving the transpulmonary gradient. However, after initial surgery 20.3% of patients needed a cardiac re-intervention: 81% for severe pulmonary valve regurgitation, but none for residual pulmonary stenosis. After initial PBA a cardiac re-intervention was needed in 9.4% of patients. In 85% the indication was residual pulmonary stenosis, in none of them pulmonary regurgitation, although almost all patients developed a mild pulmonary regurgitation. Freedom of re-intervention after surgery was 98.4%, 93.5%, 87.7%, 70.9% and 55.7% at 5, 10, 20, 30 and 40 years postoperatively. Freedom of re-intervention in the PBA group was 95.1%, 87.5% and 84.4% at 5, 10 and 20 years post-procedure. CONCLUSIONS: Both surgery and PBA are safe and successful in relieving the acute transpulmonary gradient. Long-term results of surgery are worse than previously thought due to severe PR. After PBA re-interventions for residual stenosis are frequently needed and the incidence of mild PR is high. Very long-term results of PBA are still unknown.

Challenges of interpreting copy number variation in syndromic and non-syndromic congenital heart defects.

Array comparative genomic hybridization (aCGH) has led to an increased detection of causal chromosomal imbalances in individuals with congenital heart defects (CHD). The introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting entails numerous challenges. Based on our own experience as well as those of others described in the literature, we outline the state of the art and attempt to answer a number of outstanding questions such as the detection frequency of causal imbalances in different patient populations, the added value of higher-resolution arrays, and the existence of predictive factors in syndromic cases. We introduce a step-by-step approach for clinical interpretation of copy number variants (CNV) detected in CHD, which is primarily based on gene content and overlap with known chromosomal syndromes, rather than on CNV inheritance and size. Based on this algorithm, we have reclassified the detected aberrations in aCGH studies for their causality for syndromic and non-syndromic CHD. From this literature overview, supplemented with own investigations in a cohort of 46 sporadic patients with severe non-syndromic CHD, it seems clear that the frequency of causal CNVs in non-syndromic CHD populations is lower than that in syndromic CNV populations (3.6 vs. 19%). Moreover, causal CNVs in non-syndromic CHD mostly involve imbalances with a moderate effect size and reduced penetrance, whereas the majority of causal imbalances in syndromic CHD consistently affects human development and significantly reduces reproductive fitness.

Failure of epicardial pacing leads in congenital heart disease: not uncommon and difficult to predict.

AIMS: We evaluate the incidence of epicardial lead failure and try to identify risk factors in patients with congenital heart disease. METHODS: All patients with a congenital heart defect and an epicardial pacing system, implanted within a timeframe of 25 years, were included in this study. Patients' medical records and lead data were reviewed. Lead failure was defined as the primary endpoint. RESULTS: In total 198 active epicardial leads (atrial 40, ventricular 158) were implanted in 93 patients (median age at implantation 4.4 years (range 0-58.6)). During a total follow-up of 1235 lead-years, 29 lead failures (14.6%, 4 atrial, 25 ventricular) were documented in 22 patients (23.7%). Lead failure occurred at a median time period of 4.8 years (range 1.2-24.1) after implantation. Five-year freedom of lead failure was 88%. The only independent predictor for lead failure was the age at implantation (HR 0.44; 95%CI 0.20-0.97, p = 0.04), other characteristics failed to predict lead failure. Sudden cardiac death occurred in four patients (4.3%), in one a lead failure was documented. CONCLUSION: A high incidence of epicardial lead failures is found in patients with congenital heart disease. Unfortunately, it is difficult to predict this potentially life-threatening complication.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

BACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Therapy for foetal pericardial tumours: survival following in utero shunting, and literature review.

We report the first case of foetal pericardial teratoma, treated successfully in utero by pericardio-amniotic shunting, and review the relevant literature. Foetal treatment improves survival in case of hydrops. Foetal pericardio-amniotic shunting could possibly be an alternative to serial pericardiocentesis.

Post-catheterization pseudoaneurysm in a one-year-old child treated by ultrasound-guided human thrombin injection.

We report a successful treatment of iatrogenic post-catheterization pseudoaneurysm of the right common femoral artery in a one-year-old boy with ultrasound-guided percutaneous injection of human thrombin under general anesthesia. Physical examination after 2 months follow-up showed complete disappearance of the pulsating lump.

Transapical left ventricular access for difficult to reach interventional targets in the left heart.

OBJECTIVE: Interventional targets may be virtually "excluded" due to vascular access problems or complex previous surgical procedures. This study reviews our experience using transapical ventricular puncture to gain direct access to the systemic ventricle. PATIENTS: Patient 1 (74 years, 2 previous sternotomies), patient 2 (66 years, 5 previous sternotomies), and patient 5 (69 years, 3 previous sternotomies) with prosthetic valves had paravalvular mitral valve leaks. Patient 3 (6.3 years, 2 previous sternotomies) with an extracardiac Fontan conduit, had a significant residual leak after two previous surgical attempts of patch closure of a severely regurgitant right atrioventricular valve. Patient 4 (10 months) had failure of standard ablation of the posteroseptal region of the mitral valve with persistent life-threatening episodes of ventricular tachycardia. METHODS: Procedures were performed under general anesthesia. Entry site was percutaneous in three patients and in two (and one conversion) a mini-thoracotomy was used. Sheaths were placed (6 F) using standard Seldinger technique, followed by the procedure as required. Direct surgical closure of the puncture site was done in 4 patients and in patient 3, a percutaneous vascular occlusion device was used. RESULTS: Easy and immediate access was obtained in all patients. The paravalvular leaks were crossed within seconds and completely closed with Amplatzer occluders. In patient 3 the valve was crossed using a Brokenbrough needle and a 12-mm Amplatzer device was placed in the patch leak. Patient 4 was successfully ablated using a 7-F irrigated catheter endo- and epicardially. Complications were in the percutaneous puncture group: in one patient a coronary artery was punctured and in one a hemothorax developed. CONCLUSION: Direct left ventricular puncture offers a very useful alternative access site in selected patients to reach "inaccessible" targets for certain percutaneous interventions in patients where standard approaches may be impossible or difficult.

Radiation dose survey in a paediatric cardiac catheterisation laboratory equipped with flat-panel detectors.

Flat-panel X-ray detectors for fluoroscopy represent a modern imaging equipment that is being implemented in paediatric cardiac catheterisation laboratories. Infants and children represent a group of patients with a high radiosensitivity. A survey of 273 (126 diagnostic and 147 therapeutic) paediatric catheterisations was performed to investigate the radiation doses delivered by the new X-ray system. Statistical parameters (75th, 50th and 25th percentiles) of dose-area product (DAP) and fluoroscopy time are reported for patients divided into six age groups: 0-30 d, >1-12 m, >1-3, >3-5, >5-10 and >10-15 y. For accurate risk estimation, effective dose (E) has been determined for all patients using the PCXMC software. For diagnostic procedures, the third quartile of E ranges from 11.3 mSv for newborns to 7 mSv for children of 10-15 y. Therapeutic procedures are more complex than diagnostic. Consequently, the third quartile of E is 22.6 mSv (0-30 d), 18.6 (>1-12 m), 13.3 (>1-3 y), 21.5 (>3-5 y), 17.8 (>5-10 y) and 34.1 mSv (>10-15 y). Dose conversion factors, which relate the DAP and E, have been estimated for each age group. The results of this study may serve as a first step in the optimisation process, in order to make full use of the dose reduction potential of flat-panel systems.

Intellectual abilities in a large sample of children with Velo-Cardio-Facial Syndrome: an update.

BACKGROUND: Learning disabilities are one of the most consistently reported features in Velo-Cardio-Facial Syndrome (VCFS). Earlier reports on IQ in children with VCFS were, however, limited by small sample sizes and ascertainment biases. The aim of the present study was therefore to replicate these earlier findings and to investigate intellectual abilities in a large sample of children with VCFS. In addition, we aimed to identify factors that may contribute to within-syndrome variability in cognitive performance, such as the mode of inheritance of the deletion, sex, the presence of a heart defect and psychiatric morbidity. METHOD: IQ data of 103 children with VCFS (56 males, 47 females) were collected. Psychiatric diagnosis was additionally recorded. RESULTS: Children with VCFS had a mean full-scale IQ (FSIQ) of 73.48 (range: 50-109). There were no effects of sex, presence of a heart defect and psychiatric condition on intellectual profile. Inheritance of the deletion affected cognitive performance in VCFS, with children with familial deletions having significant lower FSIQ than children with a de novo deletion. CONCLUSIONS: Learning disabilities are very common in children with VCFS, although marked within syndrome variability is noted. One factor contributing to this variability seems to be the mode of inheritance of the deletion.

Efficiency of oxygen cost during exercise in patients with symptoms of fatigue during physical activities.

BACKGROUND: With growing age, values for oxygen uptake decrease for the same level of exercise. However, some children with normal heart and normal maximal oxygen uptake complain of exertional fatigue. AIM: To evaluate the energy expenditure during submaximal treadmill exercise. SUBJECTS AND METHODS: In 20 children with exertional fatigue (mean age at testing: 7.9 +/- 1.8 years), oxygen uptake and respiratory gas exchange were assessed breath by breath. A graded exercise test was performed until exhaustion. Patients were compared to an age- and gender-matched control group (8.4 +/- 1.9 years, p = 0.45). RESULTS: Maximal oxygen uptake in patients (48.6 +/- 7.1 mL O(2)/min/kg) was similar to normal controls (47.4 +/- 5.2 mL/min/kg, p > 0.25). The inclination of the treadmill at maximal exercise was significantly (p = 0.02) lower in patients (12.6 +/- 4.9%) versus controls (16.0 +/- 3.5%). During submaximal exercise, oxygen uptake (expressed as mL/min/kg or as a percent of maximal oxygen uptake) was significantly higher (p < 0.001) in patients compared to normal controls. CONCLUSION: Children with exertional fatigue as compared to healthy controls, have a higher oxygen uptake for the same level of exercise and therefore perform at each level of exercise closer to their maximal exercise capacity. This may in part explain subjective complaints of poor exercise tolerance.

Imminent fetal cardiac tamponade by right atrial hemangioma.

A fetus presented with a large pericardial effusion caused by a right atrial transmural tumor. Correct prenatal diagnosis by use of targeted fetal echocardiography indicated that treatment was not required until the gestational age of 36 weeks. At that time, cesarean section was performed because early signs of imminent cardiac tamponade developed ("swinging heart"). At birth, the pericardial effusion was drained with a percutaneous drain. Elective surgical resection was performed on day 6 of life. Histologically, the tumor was a benign capillary hemangioma.

Molecular cytogenetic characterization of a constitutional complex intrachromosomal 4q rearrangement in a patient with multiple congenital anomalies.

Constitutional Complex Chromosomal Rearrangements (CCRs) are very rare. While the vast majority of CCRs involve more than one chromosome, only seven cases describe CCRs with four or more breakpoints within a single chromosome. Here, we present a patient with multiple congenital anomalies and mental retardation. Array Comparative Genomic Hybridisation (array CGH), FISH and Multicolour Banding FISH revealed a de novo complex rearrangement with two deletions, a duplication and an inversion of 4q. This CCR involving at least seven breakpoints is one of the most complex rearrangements of a single chromosome reported thus far. Potential mechanisms generating such complex rearrangements are discussed.

Stenting of hypoplastic aortic segments with mild pressure gradients and arterial hypertension.

OBJECTIVE: To determine the safety, feasibility and effectiveness of stent expansion of hypoplastic aortic segments with pressure gradients in patients with arterial hypertension. DESIGN: Non-randomised prospective clinical trial. SETTING: Tertiary referral centre, congenital cardiac unit. PATIENT SELECTION: 20 consecutive patients (median age 14.5 years, range 11.6-38.8 years) with arterial hypertension and a hypoplastic segment of the aorta. Seventeen patients had successful previous arch interventions in a coarctation site. INTERVENTIONS: Stent deployment in hypoplastic arch segments. MAIN OUTCOME MEASURES: Gradient across the aortic arch; complications early and during follow up; residual hypertension. RESULTS: 23 stents were deployed: 13 in the cross and 10 in the isthmus. The mean gradient across the aortic arch decreased from 16 (SD 6) (median 17) to 3 (4) (median 1) mm Hg (p < 0.001). In a few patients a mild gradient persisted just distal to the left carotid artery due to residual orificial narrowing or acute angulation. No complications occurred during or after the procedure. During follow up of 2.2 years (range 0.2-4.8 years) arterial hypertension resolved in 10 patients and 10 required residual drug treatment with better control of blood pressures. CONCLUSIONS: Pressure loss due to residual hypoplastic aortic segments can be treated effectively and safely with stent expansion. Some patients remain mildly hypertensive and require additional drug treatment.

Late fenestration of the extracardiac conduit in a Fontan circuit by sequential stent flaring.

Recent Fontan circuits frequently involve an extracardiac conduit. We report on a new technique to create a late fenestration in such an extracardiac circuit by sequential flaring of a stent in the fenestration.