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Clinical application of strain in neonates requires an understanding of which image acquisition and processing parameters affect strain values. Previous studies have examined frame rate, transmitting frequency, and vendor heterogeneity. However, there is a lack of human studies on how user-regulated spatial and temporal smoothing affect strain values in 36 neonates. This study examined nine different combinations of spatial and temporal smoothing on peak systolic left ventricular longitudinal strain in 36 healthy neonates. Strain values were acquired from four-chamber echocardiographic images in the software-defined epicardial, midwall, and endocardial layers in the six standard segments and average four-chamber stain. Strain values were compared using repeated measure ANOVAs. Overall, spatial smoothing had a larger impact than temporal smoothing, and segmental strain values were more sensitive to smoothing settings than average four-chamber strain. Apicoseptal strain decreased by approximately 4% with increasing spatial smoothing, corresponding to a 13–19% proportional change (depending on wall layer). Therefore, we recommend clinicians be mindful of smoothing settings when assessing segmental strain values. Supplementary Information The online version contains supplementary material available at 10.1007/s00246-020-02536-3.

Purpose: Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy.Methods: Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. Results: We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from -20.7 ± 3.6% to -18.0 ± 4.4% (pConclusions: Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.

Reference values for left ventricular systolic strain in healthy neonates are necessary for clinical application of strain. The objectives of this systematic review were to identify echocardiographic studies that presented left ventricular strain values in healthy neonates, perform a meta-analysis for speckle tracking-derived global longitudinal strain, and identify areas that require further investigation. A structured search was applied to MEDLINE, Embase, and Cochrane Central Register of Clinical Trials in search of echocardiographic studies that presented left ventricular strain in healthy neonates. 244 studies were identified, of which 16 studies including speckle tracking and tissue Doppler strain in the longitudinal, radial, and circumferential directions passed the screening process. Out of these 16 studies, a meta-analysis was performed on the 10 studies that reported speckle tracking global longitudinal strain. Mean speckle tracking-derived global longitudinal strain was 21.0% (95% Confidence Interval 19.6-22.5%, strain given as positive values). When the studies were divided into subgroups, mean speckle tracking global longitudinal strain from the four-chamber view was 19.5% (95% Confidence Interval 18.0-21.0%) and that derived from all three apical views was 22.5% (95% CI 20.6-24.7%), indicating that global longitudinal strain from the four-chamber view is slightly lower than global longitudinal strain from all three apical views. Neonatal strain values were close to strain values in older subjects found in previous meta-analyses. Further studies are recommended that examine strain rate, segmental strain values, strain derived from short axis views, and strain in the first few hours after birth.

Background:Young adults with heart disease constitute a growing group with the risk of cognitive and physical impairment. The knowledge of their academic performance and mental and physical health is, however, scant. This study aimed to compare young adults with CHDs or arrhythmia with their peers.Methods:Information on physical health (Somatic Symptom Scale-8), mental health problems (Hopkins Symptoms Checklist-25), quality of life (Satisfaction With Life Scale), physical activity, and academic performance was collected online in a national cross-sectional survey in Norway among students in higher education (the SHoT2018 study).Results:Among 50,054 students, 172 (0.34%) reported CHD and 132 (0.26%) arrhythmias. Students reporting arrhythmias scored significantly higher than the control group on somatic symptoms (OR = 2.3 (95% CI: 1.62–3.27)), anxiety (OR = 1.60 (1.08–2.37)), depression (OR = 1.49 (1.05–2.11)), self-harm, and suicide attempt (OR = 2.72 (1.56–4.75)), and lower quality of life (OR 1.64 (1.16–2.32)) and more loneliness (OR = 1.99 (1.28–3.10)) compared to participants without heart disease. Participants with CHD reported an increased somatic symptom burden (OR = 1.58 (1.16–2.16)). Despite a tendency to a higher score, this group did not differ significantly from the control group on anxiety or depression, quality of life, or loneliness. However, the risk of self-harm thoughts and suicidality was significantly increased (OR for suicide attempt 2.22 (1.3–3.77)). There was no difference between the groups on academic performance.Conclusions:Although Norwegian students with heart disease reported more somatic symptoms, their academic progress was not reduced compared to students without heart disease. Students with CHD or arrhythmias showed an increased risk of self-harm thoughts and suicidality.

Schistosomiasis is a tropical infectious disease in which early diagnosis and treatment can prevent serious illness. This study examined the incidence and diagnosis of schistosomiasis in Norwegian exchange students who had been exposed to freshwater in Africa.Students (n = 318) from Bergen and Oslo who had travelled to Africa as part of an exchange programme in the period 2003-18, were contacted and included in the study if they had been exposed to freshwater during their stay. A routine workup was performed comprising Schistosoma antibody testing, microscopy and/or PCR analysis of urine and faeces, dipstick urinalysis, and blood samples for analysis of eosinophilic granulocytes, creatinine and total IgE. Time, place and type of exposure were recorded in a questionnaire, along with symptoms.Schistosoma antibodies were detected in 46 (30 %) of the 151 students included in the study. None of the seropositive individuals had eggs detected in their urine or faeces, and none had eosinophilia. Two students reported cercarial dermatitis, while one had symptoms consistent with acute schistosomiasis. Rafting was the only form of freshwater exposure reported by 22 (55 %) of the 40 seropositive individuals.A large proportion of the students who had been exposed to freshwater were diagnosed with schistosomiasis. The majority reported no symptoms. Rafting was the most common form of exposure. All were diagnosed by serologic tests, while other routine diagnostic tests for schistosomiasis proved less useful. Serological analysis should be the preferred form of testing for the diagnosis of schistosomiasis in travellers.

Background Schistosomiasis is a tropical infectious disease in which early diagnosis and treatment can prevent serious illness. This study examined the incidence and diagnosis of schistosomiasis in Norwegian exchange students who had been exposed to freshwater in Africa. Material and method Students (n = 318) from Bergen and Oslo who had travelled to Africa as part of an exchange programme in the period 2003-18, were contacted and included in the study if they had been exposed to freshwater during their stay. A routine workup was performed comprising Schistosoma antibody testing, microscopy and/or PCR analysis of urine and faeces, dipstick urinalysis, and blood samples for analysis of eosinophilic granulocytes, creatinine and total IgE. Time, place and type of exposure were recorded in a questionnaire, along with symptoms. Results Schistosoma antibodies were detected in 46 (30 %) of the 151 students included in the study. None of the seropositive individuals had eggs detected in their urine or faeces, and none had eosinophilia. Two students reported cercarial dermatitis, while one had symptoms consistent with acute schistosomiasis. Rafting was the only form of freshwater exposure reported by 22 (55 %) of the 40 seropositive individuals. Interpretation A large proportion of the students who had been exposed to freshwater were diagnosed with schistosomiasis. The majority reported no symptoms. Rafting was the most common form of exposure. All were diagnosed by serologic tests, while other routine diagnostic tests for schistosomiasis proved less useful. Serological analysis should be the preferred form of testing for the diagnosis of schistosomiasis in travellers.

The aims of this study was to assess the effect of using a four chamber versus a three plane model on speckle tracking derived global longitudinal strain, the effects of drift compensation, the effect of assessing strain in different layers and finally the interplay between these aspects for the assessment of strain in neonates. Speckle tracking derived longitudinal strain was obtained from 22 healthy neonates. ANOVA, Bland–Altman analyses, coefficients of variation and assessment of intraclass correlation coefficients were conducted to assess the effect of the abovementioned aspects as well as assess both inter-observer and intra-observer variability. Neither the use of the three plane model versus the four chamber model nor the use of drift compensation had a substantial effect on global longitudinal strain (less than 1%, depending on which layer was being assessed). A gradient was seen with increasing strain from the epicardial to endocardial layers, similar to what is seen in older subjects. Finally, drift compensation introduced more discrepancy in segmental strain values compared to global longitudinal strain. Global longitudinal strain in healthy neonates remains reasonably consistent regardless of whether the three plane or four chamber model is used and whether drift compensation is applied. Its value increases when one moves from the endocardial to the epicardial layer. Finally, drift compensation introduces more discrepancy for regional measures of longitudinal strain compared to global longitudinal strain.

Investigate cardiorespiratory outcomes in children surviving previable preterm premature rupture of membranes (PV-PPROM) before 22 weeks’ gestational age (GA) with minimum 2 weeks latency. Single institution, follow-up of retrospectively identified children who were born after PV-PPROM during 2000–2004, and individually matched preterm-born controls. Eleven PV-PPROM and matched control children were included at mean age of 10.5 and 10.7 years. Rupture of membranes occurred at mean GA 182 and 276 weeks and birth at 283 and 286 weeks, respectively. Compared to controls, the PV-PPROM group had significantly poorer lung function, findings on echocardiography indicating mild pulmonary hypertension, and lower peak oxygen consumption. Chart reviews suggested more motor difficulties and a tendency towards more problems with learning and attention. The findings highlight a preterm-born sub-group in need of targeted long-term monitoring and possibly interventions regarding future cardiorespiratory and neurodevelopmental function.

Congenital heart defects (CHD) constitute the largest group of congenital malformations. In most families, only one person has CHD; however, the risk of CHD increases for children born into families already affected. In this study, all births from 1994 through 2009 were identified in the Medical Birth Registry of Norway, including supplemental information on CHD from clinical and administrative registers, as part of the CVDNOR project. By using the unique personal identification number of each parent we were able to link 16,078 pairs of twins, 445,584 pairs of full siblings, and 106,840 pairs of half-siblings. Sibling recurrence risk ratio (RRR) was calculated using CHD status in the oldest sibling as exposure and CHD status in the younger sibling as outcome, adjusted for year of birth, maternal age, and maternal diabetes. Among full sibling pairs with CHD in the older sibling, the younger sibling had CHD in 4.1% compared to 1.1% of the pairs without CHD in the older sibling (adjusted RRR 3.6; 95% confidence interval (CI) 3.1-4.1). In same-sex twins the RRR was 14.0 (95% CI 10.6-18.6), and in opposite-sex twins the RRR was 11.9 (95% CI 7.1-19.9). For half-siblings the RRR was 1.5 (95% CI 0.8-2.8). When restricting to severe types of CHD, the RRR was 6.9 (95% CI 4.9-9.8) for full siblings. In 50% of the pairs with recurrent CHD, the siblings had similar types of CHD. The high relative risk of recurrence indicates that familial risk factors are important in the etiology of CHD.

Background Children with combined mental and somatic conditions pose a challenge to specialized health services. These cases are often characterized by multi-referrals, frequent use of health services, poor clinical and cost effectiveness, and a lack of coordination and consistency in the care. Reorganizing the health services offered to these children seems warranted. Patient reported experiences give important evidence for evaluating and developing health services. The aim of the present descriptive study was to explore how to improve specialist health services for children with multiple referrals for somatic and mental health conditions. Based on parent reported experiences of health services, we attempted to identify key areas of improvement. Methods As part of a larger, ongoing project; “Transitioning patients’ Trajectories”, we asked parents of children with multiple referrals to both somatic and mental health departments to provide their experiences with the services their children received. Parents/guardians of 250 children aged 6–12 years with multi-referrals to the Departments of Pediatrics and Child and Adolescent Mental Health at Haukeland University Hospital between 2013 and 2015 were invited. Their experience was collected through a 14 items questionnaire based on a generic questionnaire supplied with questions from parents and health personnel. Possible associations between overall experience and possible predictors were analyzed using bivariate regression. Results Of the 250 parents invited, 148 (59%) responded. Mean scores on single items ranged from 3.18 to 4.42 on a 1–5 scale, where five is the best possible experience. In the multiple regression model, perception of wait time (r = .56, CI = .44–.69 / β = 0.16, CI = .05–.28), accommodation of consultations (r = .71, CI = .62–.80 / β = 0.25, CI = .06–.45 / β = 0.27, CI = .09–.44), providing adequate information about the following treatment (r = .66, CI = .55–.77 / β = 0.26, CI = .09–.43), and collaboration between different departments at the hospital (r = .68, CI = .57–.78 / β = 0.20, CI = -.01–.40) were all statistically significantly associated with parents overall experience of care. Conclusions The study support tailored interdisciplinary innovations targeting wait time, accommodation of consultations, communication regarding the following treatment and collaboration within specialist health services for children with multi-referrals to somatic and mental specialist health care services.

Aim To identify children with complex medical needs by examining their patterns of hospital care. Methods We conducted a retrospective population‐based study on 18 577 patients aged 6‐12 years from the Haukeland University Hospital register over a 3‐year period (from 2013 to 2015). Data were structured to examine the temporal patterns and sequences of referrals, care episodes and diagnoses, including flow across medical specialties. Results Over a third of patients had repeated referrals, and 14.9% of all had three or more. Furthermore, 9.3% of patients were referred to both somatic and mental healthcare services. Patients with such combined referrals had a higher number of referrals as well as a higher number of different diagnoses. Overall, there was a high frequency of non‐specific diagnoses, and 34.8% of patients still had a non‐specific main diagnosis at the end of their hospital contact. Conclusion This study demonstrates an increased risk for complex care pathways in children with multiple referrals. Interdisciplinary patterns of referrals were relatively common, particularly for patients in mental health care. These findings highlight the importance of developing interdisciplinary‐based approaches for patients with complex complaints. publishedVersion

Background/Hypothesis: Cardiopulmonary exercise testing (CPET) is used in the assessment of function and prognosis of cardiopulmonary health in children with cardiac and pulmonary diseases. Techniques, such as cardiac MRi, and PET-scan, can be performed simultaneously with exercise testing. Thus, it is desirable to have a broader knowledge about children’s normal cardiopulmonary function in different body postures and exercise modalities. The aim of this study was to investigate the effect of different body positions on cardiopulmonary function in healthy subjects performing CPETs.Materials and Methods: Thirty-one healthy children aged 9, 12, and 15 years did four CPETs: one treadmill test with a modified Bruce protocol and three different bicycle tests with different body postures, sitting, tilted 45°, and lying flat (0°). For the bicycle tests, a 20-watt ramp protocol with a pedal frequency of 60 ± 5 rotations per minute was used. Continous ECG and breath-by-breath V.O2 measurements was done throughout the tests. Cardiac structure and function including aortic diameter were evaluated by transthoracic echocardiography prior to the tests. Doppler measurements of the blood velocity in the ascending aorta were measured prior to and during the test. Prior to every test, the participants performed pulmonary function tests with maximum voluntary ventilation test.Results: There is a significantly (p < 0.05) lower peak V.O2 in all bicycle tests compared with the treadmill test. There is lower corrected peak V.O2 (ml kg−0.67 min−1), but not relative peak V.O2 (ml kg−1 min−1), in the supine compared with the upright bicycle test. There are no differences in peak stroke volume or cardiac output between the bicycle modalities when calculated from aortic blood flow. Peak heart rate decreases from both treadmill to upright bicycle and from upright bicycle to the supine test (0°).Conclusion: There are no differences in peak cardiac output between the upright bicycle test and supine bicycle tests. Heart rate and corrected peak V.O2 are lower in the supine test (0°) than the upright bicycle test. In the treadmill test, it is a higher absolute and relative peak V.O2. Despite the latter differences, we are convinced that both upright and supine bicycle tests are apt in the clinical setting when needed.

Summary Background Contractility and elasticity of the myocardium are important variables for detecting anomalies that may influence pump function. It is important to assess both wall motion and blood flow to detect regional left ventricular (LV) dysfunction and abnormal flow patterns. This study discusses four-dimensional (4D) phase-contrast magnetic resonance imaging (MRI) for simultaneous quantification and visualization of LV wall motion and blood flow. Methods In thirteen healthy subjects, a three-directional retrospective cardiac triggered phase-shift velocity mapping technique was used to acquire velocity data of the LV throughout the cardiac cycle. All short-axis slices of the LV wall were segmented in six sectors of 60° starting from the anterior hinge point between the right and left ventricles, from base to apex. Velocity data in resultant, radial, circumferential and longitudinal directions were calculated and presented as coloured three-directional vectors. Results Our findings showed a reduction in maximum wall velocities from base to apex, whereas for the radial and circumferential directions no significant differences were noted (13·1 ± 2·7 and 13·0 ± 2·9 cm s−1, respectively. P = 0·9). The longitudinal maximum velocities (21·0 ± 0·6 cm s−1) were significantly higher than the radial and circumferential components (P = 0·002). We found that the inclination angle of the resultant blood flow was changed towards the left ventricular outflow tract during systole. Conclusions Using this 4D MRI velocity mapping technique, we present an improved method for quantification and visualization of ventricular wall velocities in the radial, circumferential and longitudinal directions, as well as for the intracavity blood flow.

Background The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Methods Information on all births registered in the Medical Birth Registry of Norway, 1994–2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Results Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Conclusions Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development.

Aim We investigated the prevalence of Down syndrome in a nationwide birth cohort, focusing on congenital heart defects (CHDs), their associations with extracardiac malformations (ECM) and survival. Methods National registers were used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated with hospital diagnoses. We estimated birth defect frequencies in Down syndrome and the general population, the association between CHDs and ECM and hazard ratios for death from different combinations of CHDs and ECM. Results Down syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no other malformations. The five-year survival for Down syndrome increased from 91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was 92.0% with CHD and 97.4% without. Compared with Down syndrome children without CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs, without or with ECM, but 4-7 times higher in those with severe CHDs without ECM and 13-28 times higher in those with severe CHDs and ECM. Conclusion Down syndrome childhood survival improved, but mortality remained high with severe CHDs and extracardiac defects.

Background: The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several European countries and Canada are not fully understood. We present CHD prevalence among live births, stillbirths, and terminated pregnancies in an entire nation over a period of 16 years. Methods: Information on all births in the Medical Birth Registry of Norway, 1994-2009, was updated with information on CHD from the hospitals' Patient Administrative Systems, the National Hospital's clinical database for children with heart disease, and the Cause of Death Registry. Individuals with heart defects were assigned specific cardiac phenotypes. Results: Among 954,413 births, 13,081 received a diagnosis of CHD (137.1 per 10,000 births, 133.2 per 10,000 live births). The prevalence per 10,000 births was as follows: heterotaxia, 1.6; conotruncal defects, 11.6; atrioventricular septal defects, 5.6; anomalous pulmonary venous return, 1.1; left outflow obstructions, 8.7; right outflow obstructions, 5.6; septal defects, 65.5; isolated patent ductus arteriosus, 24.6; and other specified or unspecified CHD, 12.7. Excluding preterm patent ductus arteriosus, the CHD prevalence was 123.4 per 10,000; per year, the prevalence increased with 3.5% (95% CI 2.5-4.4) in 1994-2005 and declined with 9.8%(−16.7 to −2.4) from2005 onwards. SevereCHDprevalencewas 30.7 per 10,000; per-year increase was 2.3% (1.1-3.5) in 1994-2004, and per-year decrease was 3.4% (−6.6 to −0.0) in 2004-2009. Numbers included severe CHD in stillbirths and terminated pregnancies. Conclusions: The birth prevalence of CHD declined from around 2005. Specifically, the prevalence of severe CHD was reduced by 3.4% per year from 2004 through 2009. (Am Heart J 2014;168:956-64.) publishedVersion

This was to describe oral health in children with congenital heart defects (CHD), to evaluate association of different background variables with oral health, and to compare caries prevalence at dentine level with caries data in the general population. In this cross-sectional study, 5-year-old children in Western Norway with a need for lifelong follow-up due to CHD were invited to participate (n = 100). Children born in 2005, 2006, and 2007 underwent a comprehensive oral health examination during the period 2010–2012. Caries prevalence at the dentine level was compared with data available for 5-year-old children from the general population of Western Norway (n = 18,974). The response rate was 67 %. Caries prevalence in children with CHD at d1–5mft was 37.3 % and at d3–5mft 25.4 %. Few children (n = 4) had experienced fillings, indicating an unmet need for operative treatment. Enamel lesions (d1–2s) exceeded dentine lesions (d3–5s) in the study group, 60 % versus 40 %, indicating a significant need of non-operative treatment. At dentine level, caries prevalence in children with CHD was significantly higher than in children in the general population (25.4 versus 18.3 %). Erosion was more prevalent than caries (50.7 versus 37.3 %). In total, 37.3 % of all children had d3–5mfs caries, erosion (grades 3 or 4), developmental defects of enamel (DDE) with post-eruptive breakdown of enamel and exposure into dentine, or combinations of the diagnoses. Investigated background factors did not significantly affect caries, erosion, or DDE. More than a third of the children with CHD were found to have an oral health status that may imply risk for systemic hazardous effects.

Aims The aims of this study are (i) to assess how dental health workers of the Public Dental Service, PDS, carry out endocarditis prophylaxis related to dental treatment for children and adolescents with congenital heart defects (CHD) and to identify factors influencing their appropriate use of guidelines and (ii) to assess how dental health workers perceive any characteristics of patients with CHD. Methods This cross-sectional study was based on self-administered questionnaires mailed to all dentists and hygienists in the PDS in three Norwegian counties. Results The response rates among dentists (n = 130) and dental hygienists (n = 54) were, respectively, 63% and 68%. The findings revealed an over-prescription of endocarditis antibiotics to patients with CHD. Most of the background variables investigated did not influence the responders' prescription decision for appropriate use of the current guidelines on the topic. The only significant factor was whether or not the respondent considered that the endocarditis prophylaxis guidelines were consistent and easy to follow. Compared with healthy children, dental healthcare workers felt less confident when providing dental treatment to children with CHD. Conclusion There is room for improved education about children with CHD in dentistry and dental education.

This study aimed to investigate whether coarctation of the aorta in infancy indicates an altered vascular reactivity in the peripheral and coronary arteries apart from the secondary effect of hypertension or other complications of the disease. Patients with repaired coarctation of the aorta have a high prevalence of premature cardiovascular complications. The etiology still is not fully understood, and the cause is most likely multifactorial. Endothelial function was assessed by peripheral flow mediated dilation (FMD) and coronary flow reserve (CFR) in a study of 10 control subjects and 10 patients with a successfully repaired coarctation of the aorta (mean age, 20.9 years; 20.5 years after repair). No one had re- or rest-coarctation of the aorta, hypertension, pathologic blood pressure response during exercise, or associated cardiac malformations such as bicuspid aortic valve. CFR was achieved by phase-contrast velocity encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min). FMD was measured in the brachial artery before and after 5 min of arterial occlusion. A normal CFR and FMD was found in both groups. Most studies have been conducted with large, unselected groups. The current study group represented the best outcome of the coarctation spectrum (i.e., patients with no evidence of a residual gradient across the coarctation site or systemic hypertension). The findings reassuringly suggest that significant endothelial dysfunction and atherosclerotic changes were not present in this selected cohort.

This study aimed to evaluate CFR by assessing blood flow in the coronary sinus and systemic endothelial function measured by FMD of the brachial artery in an open prospective study of 10 control subjects and 10 patients (ages, 15–25 years) who have undergone surgical TOF repair. Reduced ventricular function, impaired exercise capacity, and ventricular arrhythmia have been proposed as risk factors for sudden cardiac death after surgical repair of TOF. Some of this may be related to impaired myocardial perfusion. A 3.0T GE Signa Excite scanner was used to achieve phase-contrast, velocity-encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min). FMD was measured in the brachial artery before arterial occlusion and 5 min afterward. The TOF group demonstrated significantly higher volumetric blood flow in the coronary sinus (282 ± 63 ml/min) than the normal control subjects at rest (184 ± 57 ml/min) (P = 0.006). During adenosine infusion, this difference disappeared. The CFR was 2.00 ± 0.43 in the control group and 1.19 ± 0.34 in the TOF group (P = 0.002). No correlation between FMD and CFR was observed in the study group (r s = 0.61, n = 8, P = 0.15). This study showed a reduced CFR due to a higher blood flow of the subject at rest in the TOF group. This reduced CFR may disable a normal adaptation to increased oxygen demand during exercise and increase myocardial vulnerability to reduced blood supply postoperatively for TOF patients with coronary heart disease.

Background Long QT syndrome is an inherited heart-rhythm disorder characterized by an increased risk of ventricular tachycardia and sudden death. Genetic testing is available. Material and methods The article is based on an anonymous family with a history of long QT syndrome, the authors experience with this patient group and a Pubmed search for literature from the period 1957 - 2007. Results An 8-year-old boy suffers syncope at a sports event, and this leads to genetic counseling and molecular genetic testing of his first-and second-degree relatives. Knowledge about genetic risk of sudden death in a family can trigger genetic testing and health preventive treatment of children, but can also have substantial psychosocial and ethical consequences for the family and for the health-care personnel involved. Interpretation Living with a genetic risk can be very emotionally challenging for the individuals and families, and "The Norwegian Act of Biotechnology in Human Medicine, etc" that regulates clinical genetic activities is extensive. An important question is whether the current Act allows communication of genetic information to persons other than the patient.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

Objective: To investigate the association between pregestational or gestational diabetes and offspring risk of congenital heart defects and the association between large-for-gestational-age birth weight and risk of cardiac defects in offspring of diabetic women. Methods: Information on pregestational and gestational diabetes, cardiac defects, and birth weight among all births in Norway in 1994–2009 was ascertained from the Medical Birth Registry of Norway, national health registries, and the Cardiovascular Disease in Norway project. The relative risk (RR) compared offspring risk of cardiac defects for maternal diabetes with offspring risk in nondiabetic mothers adjusted for year of birth, maternal age, and parity. Results: Among 914,427 births (live births, stillbirths, terminated pregnancies), 5,618 (0.61%) were complicated by maternal pregestational diabetes and 9,726 (1.06%) by gestational diabetes. Congenital heart defects were identified in 10,575 offspring. The prevalence of cardiac defects differed between groups: 344 of 10,000 births to women with pregestational diabetes, 172 of 10,000 to women with gestational diabetes, and 114 of 10,000 in women without diabetes (adjusted RRs 2.92, 95% confidence interval [CI] 2.54–3.36 and 1.47, 95% CI 1.26–1.71). During the study period, the adjusted RRs for congenital heart defects did not change. The risk of cardiac defects in neonates very large for gestational age (birth weight greater than 3 standard deviations above the mean) was compared with neonates with birth weight appropriate for gestational age. For pregestational diabetes, the prevalences of offspring cardiac defects were 561 compared with 248 per 10,000 births (adjusted RR 2.23, 95% CI 1.39–3.59) and for gestational diabetes 388 compared with 132 per 10,000 (adjusted RR 2.73, 95% CI 1.53–4.85). Conclusion: The increased risk of having a child with a congenital heart defect has not changed for diabetic women in Norway since 1994. Among women with pregestational or gestational diabetes, having a large-for-gestational-age neonate was associated with a two- to threefold increased risk of cardiac defects compared with neonates with normal birth weight. acceptedVersion

BackgroundVentricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Previous studies indicate an increased risk of endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension, arrhythmias and sudden death in patients with isolated VSDs. The present nationwide cohort study reports mortality and cardiac complications requiring hospitalisation or intervention in children with isolated VSDs.Methods and resultsMedical information concerning all 943 871 live births in Norway in 1994–2009 was retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry of Congenital Heart Defects and the Norwegian Cause of Death Registry. Isolated VSDs were identified in 3495 children without known chromosomal aberrations or extracardiac malformations. Surgical or catheter-based treatment of VSD was performed in 181 (5.2%) cases. Twelve (0.3%) children with VSDs died before 2013. There was no operative mortality, and no excess mortality in children with isolated VSDs compared with children without VSDs (adjusted HR 0.8 (0.5 to 1.4), p=0.48). The following conditions were recorded as possible cardiac complications of the VSDs: endocarditis in 3 children (0.9‰), aortic regurgitation in 12 children (3.4‰), left ventricular outflow tract obstructions in no children (0.0‰), pulmonary hypertension in 1 child (0.3‰) and arrhythmias in 16 children (4.6‰).ConclusionsThe entire group of children with isolated VSDs had a favourable prognosis without excess mortality. Cardiac complications requiring hospitalisation or intervention, including endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension and arrhythmias, were infrequent during childhood.Trial registration numberNCT02026557.

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study.Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR).Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8).Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development.

Background The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Methods Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999–2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Results Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Conclusions Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

Coarctation of the aorta represents 5-7% of congenital heart defects. Symptoms and prognosis depend on the degree of stenosis, age at surgery, surgical method and the presence of other heart defects. Postoperative complications are hypertension, restenosis and an abnormal blood pressure response during exercise. This study includes 41 patients, 15-40 years old, operated in the period 1975-1996. All were exercised on a treadmill until maximal oxygen consumption was achieved. Blood pressure was measured in the right arm and leg before and immediately after exercise, and in the right arm during exercise. Oxygen consumption was monitored and we defined an aerobic phase, an isocapnic buffering phase and a hypocapnic hyperventilation phase. The resting systolic blood pressure correlates with the resting systolic blood pressure difference between right arm and leg. A resting systolic blood pressure difference between the right arm and leg of 0.13 kPa (1 mmHg) to 2.67 kPa (20 mmHg) corresponds with a slight increase in resting systolic blood pressure. This rise in blood pressure increases the aerobic phase of the exercise test, helping the patients to achieve higher maximal oxygen consumption. A resting systolic blood pressure difference of more than 2.67 kPa (20 mmHg) corresponds with severe hypertension and causes reduction in the aerobic phase and maximal oxygen consumption. Resting systolic blood pressure and resting systolic blood pressure difference between the right arm and leg are not indicators for blood pressure response during exercise. Exercise testing is important to reveal exercise-induced hypertension and to monitor changes in transition from aerobic to anaerobic exercise and limitation to exercise capacity.

Patients after repair of tetralogy of Fallot are at increased risk of arrhythmic death. Clinical data suggest that pulmonary regurgitation predisposes to these arrhythmias, although the cellular electrophysiologic effects of pulmonary regurgitation are unknown. We induced pulmonary regurgitation in lambs, and 3 mo later, having quantified the pulmonary regurgitant (PR) fraction, studied right ventricular mechanical and electrophysiologic properties in vivo and in vitro. The PR fraction was greater in PR (75 +/- 10%) than in sham-operated animals (8 +/- 4%; p0.01). In vivo, monophasic action potential duration and activation time, at rest and during acute right ventricular stretch, were similar in both groups. However, the dispersion of activation time was greater in PR animals at rest (13 +/- 1.1 versus 8 +/- 1.1 ms; p0.05). Furthermore, the dispersion of activation increased during right ventricular stretch in PR, but not in sham-operated animals. In vitro, myocardial force-frequency responses were similar in both groups, indicating preserved systolic performance, but mechanical restitution studies showed a prolonged refractory period (447 +/- 22 versus 370 +/- 26 ms; p0.05) and a decreased recovery time constant (184 +/- 19 versus 265 +/- 20 ms; p0.001) in PR animals, indicating altered calcium cycling. Furthermore, the myocardial conduction velocity was reduced in PR animals (31 +/- 3.58 versus 47.9 +/- 5.1 cm/s; p0.01), resulting from a 2-fold increase in intracellular resistance (437.25 +/- 125.93 versus 194 +/- 43.27 Omega. cm; p = 0.025). Chronic PR leads to inhomogeneity of right ventricular activation, alters myocardial calcium cycling, reduces conduction velocity, and increases intracellular resistivity. These may contribute to the development of arrhythmias associated with PR, including those in patients after tetralogy repair.

Patients successfully operated for coarctation of the aorta are frequently subjected to altered blood pressure (BP) at rest and BP response during exercise. The relationship between these variables and blood flow, peak velocity, restenosis and other morphological features of the thoracic aorta as revealed by magnetic resonance imaging (MRI) was evaluated.Fifty-one patients subjected to coarctectomy of the aorta were examined by MRI. In addition, a control group of 23 healthy volunteers was evaluated. Morphology of the aorta was demonstrated with both ECG-triggered SE imaging and gadolinium-enhanced MR aortography. Flow-weighted MRI was applied for quantitative flow and velocity measurements.Structural alteration of the aorta was more commonly seen in those patients having increased BP at rest or altered BP response during exercise than those with a normal BP profile. The luminal diameter of the narrowest site of the aorta was decreased in all patient groups. Accordingly, the peak velocity at the corresponding site was significantly (p0.01) increased. However, blood flow was significantly (p0.01) decreased among those patients with normal BP profile compared with the other patient groups as well as the controls.Other structural changes than restenosis may contribute as well to the altered BP profile of patients subjected to coarctectomy. Reduced blood flow appears to correlate with normal BP profile, whereas the peak velocity measurements that are obtained by MRI are not able to differentiate between the patient groups. The comprehensive and reliable data obtained by non-invasive techniques, i.e. MRI and Doppler, may replace catheterization when deciding the need for intervention.

Haemoptysis was the presenting symptom in a 27-year-old male. He had undergone a Mustard operation for connection of complete transposition at the age of 2 years. For 6 months prior to admission, he had complained of dyspnoea without chestpain, and swelling of the fingers during hard physical work. Chest radiography and computer tomographic scans showed normal features of the pulmonary parenchyma, and no sign of cardiomegaly or vascular stasis. Fiberoptic bronchoscopy demonstrated a blood clot in the upper right bronchus, without any associated abnormalities of the bronchial tree. Doppler echocardiography showed obstruction of the superior caval vein, which was verified by cardiac catheterization. Balloon dilation at the site of obstruction increased the diameter of the vein from 0.5 to 1.7 cm, and the mean pressure in the superior caval vein was reduced significantly from 18 to 10 mmHg. The haemoptysis did not recur, and no complaints of dyspnoea or swelling of fingers during physical activity was reported 2 years later. Transthoracic echocardiography undertaken at this time revealed no obstruction of the superior caval vein. We conclude that hemoptysis is a rare complication of increased venous pressure in the upper body of patients with superior caval venous obstruction, which can be treated by balloon dilation or stenting.

For the last three decades, two-dimensional (2D) echocardiography and Doppler echocardiography have been the primary imaging modalities for the diagnosis and management of heart disease in infants, children, and adolescents. These methods are non-invasive, highly sensitive, and cost-effective, and widely available, making them very useful in clinical work. During this period, the anatomic and hemodynamic abnormalities associated with different congenital and acquired pediatric heart diseases have been well outlined by echocardiography. Recent advances in computer technology, signal processing, and transducer design have allowed the capabilities of pediatric echocardiography to be expanded beyond qualitative 2D imaging and blood flow Doppler analysis. New modalities such as three-dimensional echocardiography, tissue Doppler imaging and speckle tracking echocardiography have been used to evaluate parameters such as ventricular volume, myocardial velocity, regional strain, and strain rate, providing new insight into cardiovascular morphology and ventricular systolic and diastolic function. Accordingly, a comprehensive and sophisticated quantification of ventricular function is now part of most echocardiography protocols. Use of measurements adjusted for body size and age is common practice today. These developments have further strengthened the position of echocardiography in pediatric cardiology.

Objective Blood pressure measurements during exercise are difficult to obtain but are used widely in clinical practice. The objective of this study was to investigate the repeatability of blood pressure measurements and gas exchange parameters during treadmill exercise. Methods Participants were 10 healthy and nonsmoking men (age: 26.1 ± 3.6 years). Each participant performed two identical treadmill tests until exhaustion. The blood pressure was measured in the right arm before, at 4-min intervals during and just after the exercise test. Oxygen consumption, carbon dioxide production and ventilation were measured continuously breath-by-breath. Blood lactic acid concentration was measured repeatedly. Results We found that blood pressure measurements during treadmill exercise are difficult to obtain. Systolic blood pressure increases with the exercise time. Diastolic blood pressure remains constant throughout the incrementing exercise test. Systolic blood pressure measurements are more repeatable than those of diastolic blood pressure measurements. We found that maximal oxygen consumption, obtained by an incrementing treadmill test, is highly repeatable and more repeatable than submaximal exercise parameters. Conclusion Blood pressure monitoring during exercise testing may provide important clinical information that could aid in identifying patients at risk of developing chronic hypertension.

Distribution of ribosomes throughout the myocardium of normal and infarcted rat hearts was studied by immunofluorescence and laser confocal scanning microscopy. In addition, sections were labelled with peroxidase or immunogold particles for electron microscopic examination. Ligation of the proximal free left coronary artery produced severe myocardial ischaemia, and after 6 days of ligation most of the left ventricular wall was necrotic and partially replaced by granulation tissue. Immunofluorescence microscopy revealed the presence of ribosomes throughout the non-necrotic myocardium. Some cardiac muscle cells located in subendocardial areas and in the border areas surrounding the infarct were particularly intensely stained. Cells constituting the granulation tissue frequently exhibited strong ribosomal immunostaining. Within longitudinally sectioned cardiac muscle cells, ribosomes were organized in strands oriented along the long axis of the cell as well as in a cross-striated pattern. By double labelling of muscle cells with antibodies against ribosomes and Z-line-associated proteins (desmin or alpha-actinin), it was shown that the cross-striated bands of anti-ribosomal staining coincided with the I-bands along the myofibrils. Immunoelectron microscopy confirmed a wide distribution of ribosomes throughout the intermyofibrillar and subsarcolemmal sarcoplasm, and some labelling was also observed within the I-band. The present results indicate that ribosomes are distributed in a characteristic pattern throughout the sarcoplasm of cardiac muscle cells in association with the myofibrils. Furthermore, it is suggested that within viable cardiac muscle cells located adjacent to the infarct, protein synthesis is increased; this might be an important factor in regional development of compensatory hypertrophy of the surviving cardiac muscle cells.

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.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.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), P0.01). 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 P0.01).Patients who underwent renal transplantation in childhood have abnormal LV diastolic function and impaired exercise capacity, despite preserved LV longitudinal systolic deformation.