Multiorgan inflammatory syndrome associated with SARS-CoV-2 in a child. / Multiorgan inflammatorisk syndrom assosiert med sars-CoV-2 hos et barn.

This case report describes a child with heart failure and incipient multiorgan failure following infection with SARS-CoV-2. This is not COVID-19, but a delayed immune response known as multiorgan inflammatory syndrome. We have treated a number of children with this condition, and similar cases have been reported internationally. Patients can quickly become seriously ill, with high fever, gastrointestinal symptoms and cardiogenic shock.

Progressive loss of bone mass in children with Fontan circulation.

OBJECTIVE: We investigated bone mineral density (BMD) at different ages after the Fontan completion, and we evaluated the relationship between BMD, vitamin D levels, and pertinent patient variables. METHODS: A cross-sectional sample of 64 patients was examined with dual-energy X-ray absorptiometry (DXA) scans to determine BMD. Of these patients, 24 were also examined with BoneXpert software to determine bone mass density (BMX), expressed as the bone health index (BHI). Blood samples from all patients were analyzed. Patients were divided into three different age groups; A: 4-9 years old (n = 22), B: 10-15 years old (n = 21), and C: 16-18 years old (n = 21). RESULTS: Overall, BMD z scores were (mean ± SD): -1.0 ± 1.3 for the lumbar spine and -0.2 ± 1.2 for the total body. Groups B and C had significantly lower z score values compared to group A. Of patients in group C, 35% had z score values ≤-2 SD of the mean of the healthy population. There was no difference related to systemic ventricular anatomy (left or right); however, patients with lateral tunnels had lower BMD than patients with extra cardiac conduits. Overall, the BHI z score was (mean ± SD): -1.2 ± 0.9, but low BMX did not correlate with low BMD. The 25-hydroxy vitamin D level was 58 ± 30 nmol/L. Vitamin D levels decreased with age: in group C, 33.3% of patients exhibited vitamin D deficiencies. Vitamin D levels were not correlated with bone mineral densities. CONCLUSION: BMD levels decreased with age in patients with Fontan circulation. Different bone components were involved. Vitamin D levels also decreased with age, but they were not consistently associated with bone mineral densities. The single factor most predictive of low BMD was a lateral tunnel Fontan, compared to an extra cardiac Fontan.

Advanced glycation end products in children with type 1 diabetes and early reduced diastolic heart function.

BACKGROUND: Reduced diastolic function is an early sign of diabetes cardiomyopathy in adults and is associated with elevated levels of HbA1c and advanced glycation end products (AGEs). OBJECTIVE: To assess the associations between early reduced diastolic function and elevated levels of HbA1c and AGEs in children and adolescents with type 1 diabetes (T1D). METHODS: One hundred fourty six T1D patients (age 8-18 years) without known diabetic complications were examined with tissue Doppler imaging and stratified into two groups according to diastolic function. A clinical examination and ultrasound of the common carotid arteries were performed. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured by immunoassay. RESULTS: At inclusion, 36 (25%) participants were stratified into a low diastolic function group (E'/A'-ratio < 2.0). Compared to the rest of the T1D children, these participants had higher body mass index (BMI), 22.8 (SD = 4.0) vs. 20.1 (SD = 3.4) kg/m2, p < 0.001, higher systolic blood pressure 104.2 (SD = 8.7) vs. 99.7 (SD = 9.3) mmHg, p = 0.010, and higher diastolic blood pressure, 63.6 (SD = 8.3) vs. 59.9 (SD = 7.9) mmHg, p = 0.016. The distensibility coefficient was lower, 0.035 (SD = 0.010) vs. 0.042 (SD = 0.02) kPa-1, p = 0.013, Young's modulus higher, 429 (SD = 106) vs. 365 (SD = 143), p = 0.009, and MG-H1 higher, 163.9 (SD = 39.2) vs. 150.3 (SD = 33.4) U/ml, p = 0.046. There was no difference in carotid intima-media thickness between the groups. There were no associations between reduced diastolic function and years from diagnosis, HBA1c, mean HBA1c, CRP or calculated glycemic burden. Logistic regression analysis showed that BMI was an independent risk factor for E'/A'-ratio as well as a non-significant, but relatively large effect size for MG-H1, indicating a possible role for AGEs. CONCLUSIONS: Early signs of reduced diastolic function in children and adolescents with T1D had higher BMI, but not higher HbA1c. They also had elevated serum levels of the advanced glycation end product MG-H1, higher blood pressure and increased stiffness of the common carotid artery, but these associations did not reach statistical significance when tested in a logistic regression model.

Early reduced myocardial diastolic function in children and adolescents with type 1 diabetes mellitus a population-based study.

BACKGROUND: Reduced diastolic myocardial function is an early sign of diabetic cardiomyopathy. The aim of this study was to test the hypothesis that children and adolescents with type 1 diabetes mellitus (T1D), but without other known complications, have early reduced diastolic myocardial function diagnosed with echocardiographic color tissue Doppler imaging (cTDI). METHODS: cTDI examination was carried out in 173 T1D patients and 62 age-matched controls. The T1D-patients were 8-18 years old with (mean (SD)) diabetes duration of 5.6 (3.4) years and HbA1c of 8.4 (1.3). All were treated with either insulin pumps or 4-6 daily insulin injections. cTDI early (E') and late (A') peak diastolic velocities and systolic peak velocity were measured from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus. RESULTS: Myocardial diastolic function was reduced in the T1D-patients with higher peak A'-velocity and lower E'/A'-ratio in all registrations. Overall mean (SD) mitral E'/A'-ratio was 2.3 (0.5) in T1D and 2.7 (0.6) in the controls (p < 0001). The overall mitral E'/A'-ratio was negative associated with blood pressure (BP) and body mass index (BMI). Stratifying all participants into three groups according to BMI (<25, 25-75, >75 centile, respectively), the T1D had lower E'/A'-values in all stratified groups, except for in the highest BMI-group where both T1D and controls had the lowest E'/A'-ratio. Systolic function did not differ in any of the measurements. There were no associations with sex, diabetes duration, carotid artery intima-media-thickness, vessel elasticity or HbA1c. CONCLUSION: Diabetic children and adolescents using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher BP and higher BMI.

The myocardial function during and after whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy, a cohort study.

BACKGROUND: Therapeutic hypothermia has become standard treatment for moderate and severe neonatal hypoxic-ischemic encephalopathy (HIE) to reduce cerebral morbidity and mortality. The effect on the heart is incompletely explored. AIM: To assess the myocardial function during and after whole-body therapeutic hypothermia for HIE. STUDY DESIGN: Observational cohort study. SUBJECTS: Forty-four infants with HIE cooled for 72hours were compared with 48 healthy term infants and 20 normothermic infants with HIE. OUTCOME MEASURES: Tissue Doppler deformation indices of myocardial function (peak systolic strain, peak systolic strain-rate, early diastole strain-rate and strain-rate in atrial systole) during (days 1 and 3) and after (day 4) therapeutic hypothermia. RESULTS: On days one and three all indices in both HIE groups were lower than the corresponding indices in the healthy infants. The two HIE groups had similar indices, except peak systolic strain-rate on days 1 and 3 and strain-rate in atrial systole on day 1. All strain-rate indices improved from day 3 to 4 (after rewarming) in the cooled group and achieved similar values to those in healthy infants on day 3. All indices were higher in the cooling-group after rewarming than in the normothermic infants with HIE on day 3, except early diastolic strain-rate. CONCLUSIONS: Infants with HIE had similarly impaired myocardial function during days 1-3 whether normothermic or hypothermic. The myocardial function improved significantly at day 4 (after rewarming), approaching the day 3 levels in the healthy neonates.

Longitudinal strain and strain rate by tissue Doppler are more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated neonates.

The function of the heart was studied in 20 asphyxiated term neonates by measuring the longitudinal peak systolic strain and peak systolic strain rate by tissue Doppler in 18 segments of the heart on days 1, 2, and 3 of life. The fractional shortening was assessed at each examination as well. Measurements were compared against measurements in 48 healthy term neonates examined by the same protocol. The function of the heart was lower in the asphyxiated neonates - peak systolic strain (mean (95% confidence interval) -19.4% (-20.4, -18.5), peak systolic strain rate -1.65 (-1.74, -1.56) per second) than in the healthy term neonates (peak systolic strain -21.7% (-22.3, -21.0), peak systolic strain rate -1.78 (-1.84, -1.74) per second; p < 0.001). Fractional shortening was similar in the asphyxiated (29.2% (26.8, 31.5)) and healthy term neonates (29.0% (27.9, 30.1); p = 0.874). The peak systolic strain differed significantly between the asphyxiated and healthy term neonates for the left basal and right basal groups of segments (p < 0.05) but not for the left apical, right apical, septum apical, or septum basal groups of segments. The peak systolic strain rate differed significantly only for the septum apical group of segments. The differences were largest on the second day of life. Measurements were similar in asphyxiated neonates with elevated and normal cardiac troponin T levels. The peak systolic strain and strain rate were in this study more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated term neonates.

Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the cardiac myosin binding protein C.

BACKGROUND: Myosin binding protein C (MyBPC) is essential for the structure of the sarcomeres in striated muscle. There is one cardiac specific isoform and two skeletal muscle specific isoforms. Mutations in MYBPC3 encoding the cardiac isoform cause cardiomyopathy. METHODS AND RESULTS: We have identified an infant with fatal cardiomyopathy due to a homozygous mutation, p.R943X, in MYBPC3. The patient also had an unexpected skeletal myopathy. The patient expressed the cardiac specific MyBPC isoform in skeletal muscle at transcript and protein levels. Numerous muscle fibres expressing the mutant cardiac isoform showed structural abnormalities with disorganisation of sarcomeres and depletion of myosin thick filaments. CONCLUSIONS: The surprising identification of a skeletal myopathy in this patient was due to aberrant expression of mutant cardiac MyBPC in skeletal muscle.

Tissue Doppler derived longitudinal strain and strain rate during the first 3 days of life in healthy term neonates.

Tissue Doppler derived longitudinal strain and strain rate were studied in 48 healthy term neonates by measuring peak systolic strain (PSS) and peak systolic strain rate (PSSR) in 18 heart segments on day 1-3 of life. The mean PSS for each examination was -21.8% (-22.1, -21.4) [mean (95%CI)], and the mean PSSR was -1.78/s (-1.81, -1.74). Age (d), fetal shunts, and heart rate had negligible impact on measurements for any segment. The fractional shortening had negligible impact on septum and left heart segments and the pulmonary artery pressure had no impact on the right heart segments. Values varied significantly between segments and individuals, and were lower (closer to zero) in images of low quality than in images of high quality (p < 0.05). Both apical and basal segments values were lower in the septum and higher in the right ventricle than in the left ventricle (p < 0.05), except for no difference between the basal left and right segments PSSR. Apical segments values were higher than basal segments values in the right ventricle (p < 0.05) but not in the septum or the left ventricle. At present, PSS and PSSR are more feasible for quantifying differences between segment groups and patient groups than between individuals and segments within individuals.

Pulse oximetry screening as a complementary strategy to detect critical congenital heart defects.

OBJECTIVE: To compare strategies with and without first-day of life pulse oximetry screening to detect critical congenital heart defects (CCHDs). STUDY DESIGN: Population based study including all live born infants in Norway in 2005 and 2006 (n = 116 057). Postductal (foot) arterial oxygen saturation (SpO(2)) was measured in apparently healthy newborns after transferral to the nursery, with SpO(2) < 95% as cut-off point. Out of 57 959 live births in the hospitals performing pulse oximetry screening, 50 008 (86%) were screened. RESULTS: A total of 136 CCHDs (1.2 per 1000) were diagnosed, 38 (28%) of these prenatally. Of the CCHDs detected after birth, 44/50 (88%) were detected before discharge in the population offered pulse oximetry screening (25 by pulse oximetry), compared to 37/48 (77%) in the non-screened population (p = 0.15). Median times for diagnosing CCHDs in-hospital before discharge were 6 and 16 h after birth respectively (p < 0.0001). In the screened population 6/50 (12%) CCHDs were missed and recognized after discharge because of symptoms. Two of the six missed cases failed the pulse oximetry screening, but were overlooked (echocardiography not performed before discharge). If these cases had been recognized, 4/50 (8%) would have been missed compared to 11/48 (23%) in the non-screened population (p = 0.05). Of the cases missed, 14/17 (82%) had left-sided obstructive lesions. CONCLUSION: First-day of life pulse oximetry screening provides early in-hospital detection of CCHDs and may reduce the number missed and diagnosed after discharge.

Feasibility and reliability of strain and strain rate measurement in neonates by optimizing the analysis parameters settings.

The optimal combination of region-of-interest (ROI) size and strain length (SL) allowing two-segment strain and strain rate analyses in term neonates was investigated. The impact of different ROI sizes and SLs on the strain and strain rate beat-to-beat variation (BBV) was assessed in 80 good-quality tissue velocity images. Both BBVs decreased with increased ROI length and with increased SL (p < 0.05). There were no significant differences in the BBVs for ROI width 2, 3 and 4 mm (p > 0.05). Among the combinations eligible for two segment analysis, the lowest BBVs were found using SL 10 mm, ROI length 1 mm and ROI width 3 mm. Using this combination, the mean difference between the single-cycle value and two-cycle compound value for peak systolic strain rate was 6.2%, peak systolic strain was 2.9% and end systolic strain was 3.2% of the two-cycle compound mean values. Hence, strain and strain rate measurement in tissue velocity images in neonates is feasible and reliable.

Congenital mydriasis combined with aneurysmal dilatation of a persistent ductus arteriosus Botalli: a rare syndrome.

Abstract. A child with congenital mydriasis and aneurismal dilatation of persistent ductus arteriosus is described. We discuss congenital mydriasis as a separate entity and in combination with heart diseases.

[Follow-up of children with atrioventricular septal defect]. / Oppfølging av barn med atrioventrikulaer septumdefekt.

BACKGROUND: Atrioventricular septal defect (AVSD) is a complex congenital heart disease with an incidence of 0.1-0.2 per cent. We wanted to produce an overview of all children in our catchment area born with AVSD in a defined period of time and to evaluate our follow up routines in respect of AVSD. MATERIAL AND METHODS: The medical case-notes of 53 children born with AVSD between 1983 and 1995 were examined. RESULTS: Eleven children had died. 42 were offered an extended examination. 36 of the 53 children (68%) had Down's syndrome; 77% (28/36) of these had complete AVSD versus 52% (9/17) of the children without Down's syndrome. The difference was not statistically significant. Children with Down's syndrome had lower maximal oxygen uptake (p = 0.01) and lower maximal pulse rate (p = 0.02). We did not find any significant association with degree of atrioventricular insufficiency, size of left atrium or pro-atrial natriuretic peptide (pro-ANP). Moreover, no association existed between the degree of atrioventricular incompetence and exercise tolerance tested on the treadmill. ECG, 24-hour ambulatory taped ECG, blood tests and chest X-ray gave no additional information. INTERPRETATION: Children with AVSD who have been operated on, should be examined ambulatory every year or every second year. Clinical examination and echocardiography seem to be the most important aspect of the evaluation.