Sudden unexpected death in children with congenital heart defects.

AIMS: Congenital heart defects (CHDs) are the most common birth defects and are an important cause of death in children. The fear of sudden unexpected death has led to restrictions of physical activity and competitive sports. The aim of the present study was to investigate the rate of sudden unexpected deaths unrelated to surgery in children 2-18 years old with CHDs and, secondarily, to determine whether these deaths were related to cardiac disease, comorbidity, or physical activity. METHODS AND RESULTS: To identify children with CHDs and to determine the number of deaths, data concerning all 9 43 871 live births in Norway in 1994-2009 were retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry for Congenital Heart Defects and the Norwegian Cause of Death Registry. Survivors were followed through 2012, and information for the deceased children was retrieved from medical records at Norwegian hospitals. Among 11 272 children with CHDs, we identified 19 (0.2%) children 2-18 years old who experienced sudden unexpected deaths unrelated to cardiac surgery. A cardiac cause of death was identified in seven of these cases. None of the children died during physical activity, whereas two children survived cardiac arrest during sports. CONCLUSION: Sudden unexpected death was infrequent among children with CHDs who survived 2 years of age. Comorbidity was common among the children who died. This study indicates that sudden unexpected death in children with CHDs rarely occurs during physical activity.

Disease activity and left ventricular structure in patients with rheumatoid arthritis.

OBJECTIVE: Increased left ventricular (LV) wall thickness/internal diameter ratio (relative wall thickness) was recently reported in RA patients. The aim of this study was to assess the association between LV relative wall thickness and RA disease activity. METHODS: Clinical and echocardiographic data from 129 RA patients without established cardiovascular disease and 102 controls were used. RA disease activity was assessed by different composite scores and active RA defined by the Simplified Disease Activity Index (SDAI) level exceeding the cut-off for remission (SDAI >3.3). RESULTS: The RA patients were on average 61.3 years old, 77% were women and 67% had active RA (SDAI >3.3). Patients with active RA had greater LV relative wall thickness and included more patients with treated hypertension (all P < 0.05), but had LV mass index and blood pressure comparable to patients in remission. Having active RA by the SDAI score (ß = 0.20, P = 0.008) was also independently associated with greater LV relative wall thickness after adjusting for systolic blood pressure, wall stress, age and sex in a multivariate model. This association was robust also in secondary models including other disease activity composite scores such as the Clinical Disease Activity Index and 28-joint DAS. CONCLUSION: Among RA patients, higher disease activity was independently associated with greater LV relative wall thickness, reflecting subclinical heart disease. The findings point to the importance of disease activity control in RA patients to prevent progression to clinical heart disease.

Agalsidase benefits renal histology in young patients with Fabry disease.

The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.

[Cardiovascular risk assessment for the use of ADHD drugs in children]. / Kardiovaskulær risikovurdering ved bruk av AD/HD-medikamenter hos barn.

BACKGROUND: Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has generally been regarded as safe. ECG screening of healthy children and adolescents before initiating this type of treatment appears to be usual in Norway, despite recommendations that ECGs should only be undertaken in individuals who are at risk. The purpose of this article is to clarify relevant guidelines for cardiovascular risk assessment for the use of ADHD drugs in children and adolescents, as well as to propose practical recommendations. METHOD: The article is based on a literature search in PubMed completed on 1 October 2013, and on the author's own clinical experience and discretionary assessments. RESULTS: The use of CNS stimulants and atomoxetine is associated with a slight rise in blood pressure and pulse rate, as well as small changes in QT interval. A small percentage of patients (5-10%) experience a clinically significant rise in blood pressure and pulse rate. Sudden death does not appear to occur more frequently in children and adolescents taking ADHD drugs in therapeutic doses than in children and adolescents who do not use such drugs. There is little knowledge available on the long-term effects of ADHD drugs on the cardiovascular system of otherwise healthy individuals, or on the risk related to the use of ADHD drugs in children and adolescents with cardiac disease. The drugs are thought to increase the risk of sudden cardiac death in some arrhythmia syndromes. INTERPRETATION: Our assessment is that caution should be exercised in the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias. We recommend clinical examination and a thorough medical history review in order to identify individuals at risk before initiating drug therapy, and also suggest that it is not necessary for healthy children to be given an ECG examination before introducing ADHD drugs. In children with known cardiac disease, arrhythmia or risk factors for cardiac disease, ADHD treatment should be undertaken in consultation with a medical specialist with competence in pediatric cardiology.

Design and rationale for the PREVAIL study: effect of e-Health individually tailored encouragements to physical exercise on aerobic fitness among adolescents with congenital heart disease--a randomized clinical trial.

Intensive exercise may be an important part of rehabilitation in patients with congenital heart disease (CHD). However, performing regular physical exercise is challenging for many adolescent patients. Consequently, effective exercise encouragements may be needed. Little is known on the effect of e-Health encouragements on physical fitness, physical activity, and health-related quality of life in adolescents. This trial is a nationwide interactive e-Health rehabilitation study lasting 1 year, centered on interactive use of mobile phone and Internet technology. We hypothesize that e-Health encouragements and interactive monitoring of intensive exercise for 1 year can improve physical fitness, physical activity, and health-related quality of life. Two hundred sixteen adolescents (age, 13-16 years) with surgically corrected complex CHD but without significant hemodynamic residual defects and no restrictions to participate in physical activity are in the process of being enrolled by invitation after informed consent. Physical fitness is measured as the maximal oxygen uptake (Vo(2)) at baseline and after 12 months by an assessor blinded to the randomization group. After baseline testing, the patients are 1:1 randomized to an intervention group or a control group. Individually fully automated tailored e-Health encouragements--SMS, Internet, and mobile applications--aimed at increasing physical activity are delivered to the participants in the intervention group once a week. The Bandura's Social Cognitive Theory inspires the behavioral theoretical background. The e-Health intervention and the Godfrey cycle ergometer protocol have been feasibility tested and seem applicable to adolescents with CHD. The trial is expected to contribute with new knowledge regarding how physical activity in adolescents with CHD can be increased and, possibly, comorbidity be reduced.

Left ventricular function in children and adults after renal transplantation in childhood.

BACKGROUND: Renal transplantation improves left ventricular (LV) function, but cardiovascular mortality remains elevated. The aim of this cross-sectional study was to determine whether subclinical abnormalities of LV longitudinal function also persist in patients who underwent renal transplant in childhood. METHODS: Conventional and speckle tracking echocardiography was performed in 68 renal transplant recipients (34 children and 34 adults, median 9.8 years (range 2.0-28.4 years) after first transplantation and 68 age- and sex-matched healthy controls. RESULTS: Mean age at first transplantation was 8.8 ± 4.8 years. Forty-three percent had a pre-emptive transplant. Of the remaining, 70% received haemodialysis and 30% peritoneal dialysis on average for 6.9 months. Thirty-one percent of paediatric and 35% of adult patients had hypertension. LV mass index was increased in adult patients (92 ± 24 vs 75 ± 11 g/m(2), P< 0.01). LV diastolic function and exercise capacity were impaired in both paediatric and adult patients. LV longitudinal peak systolic strain and strain rate were comparable in patients and controls. In multivariate analysis, systolic blood pressure and LV diastolic relaxation were the main covariates of LV peak systolic strain and strain rate (all P < 0.01). CONCLUSIONS: Patients who underwent renal transplantation in childhood have abnormal LV diastolic function and impaired exercise capacity, despite preserved LV longitudinal systolic deformation.

Cardiorespiratory fitness in young adults with a history of renal transplantation in childhood.

Limited knowledge exists on cardiorespiratory fitness (CR fitness) in adults having a renal transplant (Rtx) during childhood. Our aim was to assess CR fitness (V0(2peak)) with a maximal treadmill test in former Rtx children reaching adulthood (ped-tx, n = 31), compared to patients Rtx as adults (adult-tx, n = 17) and healthy controls (HC, n = 36). Median age was 26.9 (19-41), 28.6 (23.5-34) and 33.5 (20-42) years, respectively. Median time since first Rtx was 18.1 (7-29) and 3.7 (1.2-12.6) years. Body composition was measured by dual-energy X-ray absorptiometry (DXA). V0(2peak) was median 37.9 (12.5-56.3), 40.8 (26.5-57.5), and 44.4 (29.5-65.6) ml kg (-1)min (-1) in the ped-tx, adult-tx, and HC, respectively. Ped-tx had significantly lower V0(2peak) compared to HC (p = 0.01). Adult-tx had higher exercise capacity (test duration) compared to ped-tx (median 10.5 (7.5-16) and 9 (6-14) min, respectively (p = 0.016). In multiple linear regression analysis, test duration, fat-free mass (FFM, kg) and Hgb (g/dl) were significant predictors of V0(2peak) explaining 86% of its variance. There was no significant difference between ped-tx and adult-tx in V0(2peak.) CR fitness depicts long-term health outcome in Rtx patients both in regard to physical functioning and is a plausible indirect marker of CV health.

A novel mitochondrial ND5 (MTND5) gene mutation giving isolated exercise intolerance.

We describe a patient with isolated exercise intolerance caused by a new, maternally inherited mutation in mitochondrial DNA. The heteroplasmic T>C transition at position 13271 in MTND5 affects a highly conserved base and segregates with the disease, being present at highest levels in skeletal muscle fibres showing abnormal mitochondrial accumulation. This is the 15th mutation affecting the MTND5 subunit of respiratory chain complex I and confirms this protein as an important site for disease with phenotypes ranging from MELAS and infantile encephalopathies to isolated syndromes affecting a single tissue such as Leber hereditary optic neuropathy and now skeletal muscle.

Renal biopsy findings in children and adolescents with Fabry disease and minimal albuminuria.

BACKGROUND: Information concerning renal pathological characteristics in Fabry disease in childhood is limited. Our objective is to define renal morphological abnormalities in children and adolescents with Fabry disease and minimal proteinuria. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 9 symptomatic patients (7 males, 2 females; age range, 7 to 18 years); 2 patients had received enzyme replacement therapy for 2 years. OUTCOMES & MEASUREMENTS: Renal morphological changes assessed by using light and electron microscopy. RESULTS: All patients had acroparesthesia and typical eye changes, 7 showed hypohidrosis, 7 had gastrointestinal problems, and 2 had typical angiokeratomas. Mean albumin-creatinine ratio was 38 mg/g [corrected] (range, 5.3 to 104.3 mg/g). [corrected] Measured glomerular filtration rate was normal in all patients. Light microscopy showed changes in glomerular, tubulointerstitial, or vascular compartments alone or in combination in 7 patients. Electron microscopy showed lesions in all patients. LIMITATIONS: Small sample size. CONCLUSIONS: Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate. The combination of acroparesthesia and mild albuminuria, glomerular endothelial cell deposits, and arteriopathy may constitute a clinical and morphological combination heralding a potentially progressive renal disease.

Validation of a Modified Triage Scale in a Norwegian Pediatric Emergency Department.

OBJECTIVE: Triage is a tool developed to identify patients who need immediate care and those who can safely wait. The aim of this study was to assess the validity and interrater reliability of a modified version of the pediatric South African triage scale (pSATS) in a single-center tertiary pediatric emergency department in Norway. METHODS: This prospective, observational study included all patients with medical conditions, referred to the pediatric emergency department of a tertiary hospital in Norway from September 1, 2015, to November 17, 2015. Their assigned triage priority was compared with rate of hospitalization and resource utilization. Validity parameters were sensitivity, specificity, positive and negative predictive value, and percentage of over- and undertriage. Interrater agreement and accuracy of the triage ratings were calculated from triage performed by nurses on written case scenarios. RESULTS: During the study period, 1171 patients arrived at the hospital for emergency assessment. A total of 790 patients (67 %) were triaged and included in the study. The percentage of hospital admission increased with increasing level of urgency, from 30 % of the patients triaged to priority green to 81 % of those triaged to priority red. The sensitivity was 74 %, the specificity was 48 %, the positive predictive value was 52 %, and the negative predictive value was 70 % for predicting hospitalization. The level of over- and undertriage was 52 % and 26 %, respectively. Resource utilization correlated with higher triage priority. The interrater agreement had an intraclass correlation coefficient of 0.99 by Cronbach's alpha, and the accuracy was 92 %. CONCLUSIONS: The modified pSATS had a moderate sensitivity and specificity but showed good correlation with resource utilization. The nurses demonstrated excellent interrater agreement and accuracy when triaging written case scenarios.

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents.

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

[Fluid management and the risk of cerebral oedema in children with diabetic ketoacidosis]. / Vaeskebehandling og risiko for hjerneødem hos barn med diabetisk ketoacidose.

BACKGROUND: Cerebral oedema is a rare but life-threatening complication of diabetic ketoacidosis in children. MATERIAL AND METHODS: This paper presents a case report on an infant with diabetic ketoacidosis and in an extreme hyperosmolar and hypernatremic state. Considerations regarding appropriate fluid management and the osmotic role of serum sodium are discussed. Recommendations for treatment are given based on available guidelines and published evidence. INTERPRETATION: Intracellular swelling of the brain seems to be caused by water moving along osmotic gradients. In diabetic ketoacidosis, sodium and glucose are the dominant osmotic forces. It is important to understand the relation between serum osmolarity, sodium and glucose, as appropriate fluid treatment might prevent this potentially fatal complication.

[Do patients with ventricular septal defect need endocarditis prophylaxis?]. / Trenger pasienter med ventrikkelseptumdefekt endokardittprofylakse?

BACKGROUND: Patients with ventricle septal defect are considered at higher risk of infectious endocarditis than the population in general. According to guidelines, these patients should receive prophylactic antibiotics prior to invasive procedures. Recently, several studies have been published that challenge this view. MATERIAL AND METHODS: Based on searches in Medline, we discuss the risk of endocarditis and indication for antibiotic prophylaxis in patients with this defect. RESULTS: Patients with perimembranous and subvalvular defects have higher risk of endocarditis than the population in general. The proportion of patients developing endocarditis in relation to invasive procedures is low. Prophylactic antibiotics are only partially effective. INTERPRETATION: The proportion of preventable cases of endocarditis is low, and the prophylaxis does not give sufficient protection. Studies suggest that only patients at the highest risk should receive prophylactics.

[Evaluation of cardiac murmurs in children]. / Vurdering av barn med hjertebilyder.

BACKGROUND: Many normal children have heart murmurs, but most children do not have heart disease. Differentiation of innocent murmurs from those due to structural heart disease, pathological murmurs, is largely clinical. MATERIAL AND METHODS: This review is based upon the authors' own studies and PubMed searches. RESULTS: An appropriate history and a properly conducted physical examination can identify children at risk of significant heart disease. INTERPRETATION: If a murmur cannot clearly be labelled as innocent based on characteristics like sound quality, intensity, location and response to posture, then referral to a paediatric cardiologist is indicated. Other indications for referral are any sign or symptom of cardiovascular disease such as shortness of breath, cyanosis or decreased exercise tolerance. In addition, children with syndromes should, because of their high risk of congenital heart disease, be referred to a paediatric cardiologist for further evaluation.

[Intravenous enzyme substitution therapy in children with Fabry's disease]. / Intravenøs enzymsubstitusjonsbehandling ved Fabrys sykdom hos barn.

BACKGROUND: Fabry's disease is a X-linked lysosomal storage disorder with accumulation of globotriaosylceramide primarily in vascular endothelial cells, affecting mainly skin, kidney, heart and brain. Symptoms may appear in 7-8-year-old children as burning pain in hands and feet; organ damage usually becomes evident in adult age. Intravenous enzyme replacement therapy has recently become available. PATIENTS: Two brothers, 13.5 and 15 years old, had typical symptoms with acroparesthesia, fever, abdominal pain and diarrhoea. There were high levels of urinary globotriaosylceramide, low levels of alfagalactosidase A in leukocytes, and a single-nucleotide deletion in position 10671 of the alfagalactosidase gene (GLA). Both brothers showed slightly abnormal echocardiography and one had typical changes on cerebral MRI. Enzyme replacement therapy with alfagalactosidase A (Replagal) was started in November 2001. After one year of therapy there was clearly clinical improvement with no fever and diarrhoea and less pain. The urinary excretion of globotriaosylceramide was reduced. No adverse effects were recorded. INTERPRETATION: During 12 months of intravenous enzyme replacement therapy in two adolescent subjects with Fabry's disease we observed clinical improvement and no adverse effects. We recommend greater awareness of Fabry's disease in paediatrics as well as in adult medicine.

Prevalence of migraine in adults with cyanotic congenital heart disease.

OBJECTIVE: There is an increased prevalence of patent foramen ovale in patients with migraine, leading to the suggestion that migraine is more common in patients with potential right-to-left shunts. The aim of this study was to investigate the prevalence of migraine in adults with large right-to-left shunts because of cyanotic congenital heart disease. DESIGN AND PATIENTS: In total, 29 cyanotic adult patients with congenital heart disease answered a questionnaire to determine the prevalence of migraine with or without aura. A total of 38 matched acyanotic patients with congenital heart disease served as controls. A subgroup of 18 acyanotic patients also underwent bubble contrast echocardiography to look for patent foramen ovale. RESULTS: Twenty (69%) of the cyanotic patients had migraine, the majority 17 (59%) having migraine with aura. Twenty-two (58%) of the 38 acyanotic patients had migraine, of whom 16 (42%) had migraine with aura. Nine (50%) of the 18 acyanotic patients who consented to an echocardiogram had patent foramen ovale. Of those with patent foramen ovale, 8 (89%) had migraine and 6 (67%) had migraine with aura. CONCLUSION: There is an increased prevalence of migraine with aura in both cyanotic and acyanotic patients with congenital heart disease. The high prevalence of migraine in acyanotic patients with congenital heart disease may be due to an increased prevalence of patent foramen ovale.

Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy?

BACKGROUND: Abnormal left ventricular (LV) deformation is an independent predictor of poor cardiovascular outcome in end-stage renal disease. Studies in early-stage chronic kidney disease (CKD) have not been performed despite the known graded inverse relationship between glomerular filtration rate and adverse cardiovascular events. METHODS: Forty patients with CKD stage 2 or 3 and no history of cardiovascular disease or diabetes and 30 healthy controls underwent Doppler myocardial imaging for longitudinal deformation (strain/strain rate). RESULTS: There were no differences in LV ejection fraction or systolic tissue Doppler velocities between patients with CKD and controls. In CKD, mean global strain (-15% +/- 4% vs -17% +/- 3%, P <.01) and mean global strain rate were reduced compared with controls (-0.88 +/- 0.16 vs -1.06 +/- 0.31, P <.05). Peak systolic strain was reduced in the basal lateral (-13.9% +/- 0.9% vs -17.9% +/- 1.02%, P <.01), basal septal (-17.1% +/- 0.8% vs -19.4% +/- 0.77%, P <.05), and mid-septal (-16.4% +/- 0.78% vs -18.9% +/- 0.88%, P <.05) walls with more basal postsystolic shortening (P <.01). Peak systolic strain rate was reduced in the basal lateral, mid-lateral, and mid-septal segments (P <.05). CONCLUSION: Conventional measures of systolic function are preserved in early-stage CKD, but systolic deformation is abnormal, consistent with an adverse cardiovascular prognosis.

Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg.

BACKGROUND: Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54. CONCLUSION: Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease. TRIAL REGISTRATION: International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534].

Recommendations for participation in competitive and leisure sports in patients with congenital heart disease: a consensus document.

BACKGROUND: Physical activity is important for patients with congenital heart disease. The aim of this paper is to provide a consensus document for participation in competitive or leisure sport activity in children and adults with congenital heart disease. METHODS: The recommendations are based on expert consensus meetings, personal experience of the contributing authors and an updated review of the literature regarding exercise performance and risk stratification in patients with congenital heart disease. RESULTS: Physical performance and exercise tolerance is close to normal in patients with simple lesions with successful repair or no need for therapy. Most patients with complex lesions have some degree of residual disease, making them less suitable for participation in competitive sport. CONCLUSION: Regular exercise at recommended levels can be performed and should be encouraged in all patients with congenital heart disease. Many can attend sports with no restrictions. Special concern should be given to those patients with a significant ventricular dysfunction or recent history or risk of arrhythmia.