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ObjectiveTo compare long-term survival, reinterventions and risk factors using strict definitions of neonatal critical and non-critical valvular aortic stenosis (VAS).DesignA nationwide retrospective study using data from patient files, echocardiograms and the Swedish National Population Registry.Setting and patientsAll neonates in Sweden treated for isolated VAS 1994–2018. We applied the following criteria for critical aortic stenosis: valvular stenosis with duct-dependent systemic circulation or depressed left ventricular function (fractional shortening ≤27%). Indication for treatment of non-critical VAS was Doppler mean gradient >50 mm Hg.Main outcome measuresShort-term and long-term survival, aortic valve reinterventions need of valve replacements, risk factors for reintervention and event-free survival.ResultsWe identified 65 patients with critical VAS and 42 with non-critical VAS. The majority of the neonates were managed by surgical valvotomy. Median follow-up time was 13.5 years, with no patients lost to follow-up. There was no 30-day mortality. Long-term transplant-free survival was 91% in the critical stenosis group and 98% in the non-critical stenosis group (p=0.134). Event-free survival was 40% versus 67% (p=0.002) in the respective groups. Median time from the initial treatment to reintervention was 3.6 months versus 3.9 years, respectively (p=0.008).ConclusionsCritical VAS patients had significantly higher need for reintervention during the first year of life, lower event-free survival and lower freedom from aortic valve replacement at age ≥18 years, compared with neonates with non-critical stenosis.

Objective:To investigate health-related quality of life and life satisfaction in children and adolescents treated for isolated congenital valvular aortic stenosis compared to healthy peers. Our second aim was to investigate the relationship between objectively measured physical activity, health-related quality of life and life satisfaction in the same group.Methods:Forty-eight patients, 8–18 years of age, were recruited, as well as 43 healthy peers matched for age, gender and residential area. Health-related quality of life was assessed by the KIDSCREEN-52 self-report and parent proxy report, and life satisfaction was evaluated with the Satisfaction With Life Scale. Physical activity was measured with an accelerometer for 7 days. Sports participation was self-reported.Results:No differences in the health-related quality of life domains were found between patients and controls in the self-reports. In the proxy reports, parents of the adolescents rated their child’s autonomy lower than did the parents of the healthy controls. A negative relationship was found between moderate to vigorous physical activity, sports participation, life satisfaction and the psychological well-being domain in adolescent patients. In children there was a positive relationship between moderate physical activity and the physical and psychological well-being domains.Conclusion:Overall, children and adolescents treated for valvular aortic stenosis reported similar life satisfaction and health-related quality of life as their healthy peers. The negative relationships between intense physical activity and sports participation with health-related quality of life and life satisfaction in adolescent patients might be explained by both physical and psychological factors in these teenagers with complex, lifelong heart disease.

To analyse the risk of developing serious disease or death due to COVID-19 among patients who underwent heart surgery during childhood.A retrospective combined register and patient file study. We identified all individuals who had undergone surgery for congenital heart disease in childhood between 1994 and 2019 in our Local Surgical Register that covers half of the Swedish population. This effort was cross-tabulated with the diagnosis of COVID-19 entered in the National Register of Diagnoses in Sweden from 1 March 2020 to 1 March 2021. Severe disease was defined as treatment at an intensive care unit (ICU).We identified 3950 individuals, and the median age at follow-up was 16 years (1-44). A total of 32 patients were diagnosed with COVID-19. Five of them were hospitalised for more than 2 days (5-32 days). Two adults required treatment at an ICU; both had additional comorbidity and one died. The corresponding number of ICU stays for this age range in Sweden was 2020 approximately 0.13/1000 person-years, reported from The Swedish Intensive Care Registry.There was no increased rate of severe COVID-19 among individuals who had undergone surgery for congenital heart disease in childhood. Additional comorbidity is related to outcome.

Aim To study the long‐term outcome after surgery for pulmonary atresia and ventricular septal defect (PA‐VSD), and to determine association between the contribution of major aorto‐pulmonary collateral arteries (MAPCAs) to the pulmonary blood flow, comorbidity and cause of death. Methods Patients who had undergone surgery for PA‐VSD from January 1st 1994 to December 31st 2017 were studied retrospectively. Survival was cross‐checked against the Swedish National Population Register. Results Seventy patients were identified, giving an incidence of 5.3 newborns per 100 000 live births. In 41 patients (59%) the pulmonary blood flow originated from a patent ductus arteriosus (PDA), while 29 patients (41%) had contribution of the pulmonary blood flow from MAPCAs. Extracardiac disease was found in 34 patients (49%), 16 of whom had 22q11‐microdeletion syndrome (23%). Survival at follow‐up was similar in patients with and without MAPCAs (72.4% vs. 75.6%, n.s.), with a median follow‐up time of 14.3 years (3.2–41.8 years). No difference was found in mortality in patients with or without any syndrome or extracardiac disease. Conclusion Long‐term survival did not differ between those with and without MAPCAs and no difference in mortality was seen in patients with and without concomitant extracardiac disease or any kind of syndrome.

Previous research in children and adolescents with congenital heart defects presents contradictory findings concerning their physical activity (PA) level, due to methodological limitations in the PA assessment. The aim of the present cross-sectional study was to compare PA in children and adolescents treated for valvular aortic stenosis with healthy controls using an improved accelerometer method. Seven-day accelerometer data were collected from the hip in a national Swedish sample of 46 patients 6–18 years old treated for valvular aortic stenosis and 44 healthy controls matched for age, gender, geography, and measurement period. Sports participation was self-reported. Accelerometer data were processed with the new improved Frequency Extended Method and with the traditional ActiGraph method for comparison. A high-resolution PA intensity spectrum was investigated as well as traditional crude PA intensity categories. Children treated for aortic stenosis had a pattern of less PA in the highest intensity spectra and had more sedentary time, while the adolescent patients tended to be less physically active in higher intensities overall and with less sedentary time, compared to the controls. These patterns were evident using the Frequency Extended Method with the detailed PA intensity spectrum, but not to the same degree using the ActiGraph method and traditional crude PA intensity categories. Patients reported less sports participation than their controls in both age-groups. Specific differences in PA patterns were revealed using the Frequency Extended Method with the high-resolution PA intensity spectrum in Swedish children and adolescents treated for valvular aortic stenosis.

BackgroundInfants with congenital heart disease (CHD) have an increased risk of morbidity and mortality during a respiratory syncytial virus (RSV) infection. The aim of this study was to estimate the cost-effectiveness of palivizumab as RSV-prophylaxis among infants with CHD, including the effect of delayed heart surgery and asthma.MethodsA simulation model with data from the literature and health care authorities including costs and utilities was developed to estimate costs and health effects over a lifetime for a cohort of CHD infants receiving palivizumab compared to no RSV-prophylaxis.ResultsThe prophylaxis treatment incurred a cost of 3664 EUR per treated infant. However, due to cost-savings from primarily avoiding hospitalizations (5145 EUR/treated infant) and avoiding heart complications due to delayed heart surgery (2082 EUR/treated infant), the RSV-prophylaxis treatment resulted in a total cost-saving of 3833 EUR per treated infant. At the same time, the prophylaxis-treated cohort accumulated more life-years and higher quality of life than the non-prophylaxis cohort.ConclusionThis study confirms that RSV-prophylaxis in severe CHD infants less than one year of age is cost beneficial. Avoiding delayed heart surgeries is an important benefit of prophylaxis and should be taken into consideration.

Objective:This study describes short-term and long-term outcome after treatment of critical valvular aortic stenosis in neonates in a national cohort, with surgical valvotomy as first choice intervention.Methods:All neonates in Sweden treated for critical aortic stenosis between 1994 and 2016 were included. Patient files were analysed and cross-checked against the Swedish National Population Registry as of December 2017, giving complete survival data. Diagnosis was confirmed by reviewing echo studies. Critical aortic stenosis was defined as valvular stenosis with duct-dependent systemic circulation or depressed left ventricular function. Primary outcome was all-cause mortality and secondary outcomes were reintervention and aortic valve replacement.Results:Sixty-one patients were identified (50 boys, 11 girls). Primary treatment was surgical valvotomy in 52 neonates and balloon valvotomy in 6. Median age at initial treatment was 5 days (0–26), and median follow-up time was 10.8 years (0.14–22.6). There was no 30-day mortality but four late deaths. Freedom from reintervention was 66%, 61%, 54%, 49%, and 46% at 1, 5, 10, 15, and 20 years, respectively. Median time to reintervention was 3.4 months (4 days to 17.3 years). Valve replacement was performed in 23 patients (38%).Conclusions:Surgical valvotomy is a safe and reliable treatment in these critically ill neonates, with no 30-day mortality and long-term survival of 93% in this national study. At 10 years of age, reintervention was performed in 54% and at end of follow-up 38% had had an aortic valve replacement.

Aim The aim of the study was to assess the incidence, mortality and morbidity of dilated cardiomyopathy (DCM) and noncompaction of the left ventricle (LVNC) in Swedish children. Methods We reviewed hospital records of all children with dilated cardiomyopathy (DCM) or left ventricular noncompaction cardiomyopathy (LVNC) up to the age of 18 in the healthcare region of western Sweden from 1991 to 2015. Results In total, 69 cases (61% males) were identified. The combined incidence of DCM and LVNC was 0.77 (95% CI 0.59‐0.96) per 100 000 person years. Children were divided into six groups, and their outcomes were analysed depending on their aetiology. Idiopathic DCM was reported in 43%, and familial dilated and left ventricular noncompaction aetiology was present in 32%. DCM due to various diseases occurred in 8%. DCM associated with neuromuscular diseases was present in 16%. The overall risk of death or receiving transplants in children with idiopathic and familial DCM was 30% over the study period, and 21% died in the first year after diagnosis. Conclusion The combined incidence of DCM and LVNC was similar to previous reports. Most children with idiopathic DCM presented during infancy, and mortality was highest during the first year after diagnosis.

Providing continuous follow-up care to patients with congenital heart disease (CHD) remains a challenge in many settings. Previous studies highlight that patients with CHD experience discontinuation of follow-up care, but mainly describe a single-centre perspective, neglecting inter-institutional variations. Hospital-related factors above and beyond patient-related factors are believed to affect continuity of care. The present multicentre study therefore investigated (i) proportion of "no follow-up care"; (ii) transfer destinations after leaving paediatric cardiology; (iii) variation in proportions of no follow-up between centres; (iv) the association between no follow-up and outpatient volumes, and (v) its relationship with staffing resources at outpatient clinics.An observational, multicentre study was conducted in seven university hospitals. In total, 654 adolescents with CHD, born between 1991 and 1993, with paediatric outpatient visit at age 14-18 years were included. Transfer status was determined 5 years after the intended transfer to adult care (23y), based on medical files, self-reports and registries.Overall, 89.7% of patients were receiving adult follow-up care after transfer; 6.6% had no follow-up; and 3.7% were untraceable. Among patients in follow-up care, only one remained in paediatric care and the majority received specialist adult CHD care. Significant variability in proportions of no follow-up were identified across centres. Higher outpatient volumes at paediatric outpatient clinics were associated with better continued follow-up care after transfer (OR = 1.061; 95% CI = 1.001 - 1.124). Medical staffing resources were not found predictive.Our findings support the theory of hospital-related factors influencing continuity of care, above and beyond patient-related characteristics.

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006-2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

Objective: Fontan surgery is performed in children with univentricular heart defects. Previous data regarding permanent pacemaker implantation frequency and indications in Fontan patients are limited and conflicting. We examined the prevalence of and risk factors for pacemaker treatment in a consecutive national cohort of patients after Fontan surgery in Sweden. Methods: We retrospectively reviewed all Swedish patients who underwent Fontan surgery from 1982 to 2017 (n = 599). Results: After a mean follow-up of 12.2 years, 13% (78/599) of the patients with Fontan circulation had received pacemakers. Patients operated with the extracardiac conduit (EC) type of total cavopulmonary connection had a significantly lower prevalence of pacemaker implantation (6%) than patients with lateral tunnel (LT; 17%). Mortality did not differ between patients with (8%) and without pacemaker (5%). The most common pacemaker indication was sinus node dysfunction (SND) (64%). Pacemaker implantation due to SND was less common among patients with EC. Pacemaker implantation was significantly more common in patients with mitral atresia (MA; 44%), double outlet right ventricle (DORV; 24%) and double inlet left ventricle (DILV; 20%). In contrast, patients with pulmonary atresia with intact ventricular septum and hypoplastic left heart syndrome were significantly less likely to receive a pacemaker (3% and 6%, respectively). Conclusions: Thirteen percent of Fontan patients received a permanent pacemaker, most frequently due to SND. EC was associated with a significantly lower prevalence of pacemaker than LT. Permanent pacemaker was more common in patients with MA, DORV, and DILV. (Less)

Aim This study determined the use of standardised procedures for infant noninvasive blood pressure (NIBP) measurements in the Nordic countries and aimed to identify factors included in the standardisation and interpretation of NIBP measurements in infants. Methods A cross-sectional electronic questionnaire survey was sent to 84 physicians in all 23 university hospitals in Sweden, Norway, Denmark, Finland and Iceland and was completed from February to March 2017. The survey contained respondent characteristics, the presence and description of standardised procedures for NIBP measurements, daily practice of NIBP measurements and methodological considerations and interpretation of NIBP measurements in a healthy six-month-old child. Results We received responses from 55 of 84 physicians working in all 23 Nordic university hospitals, in paediatric cardiology (n = 22), general paediatrics (n = 16), paediatric nephrology (n = 14) and other fields (n = 3). Less than a quarter (23%) said their hospital issued specific NIBP procedures relating to infants and they referred to 19 different sources of information. The factors that were most commonly assessed for interpretation were age (100%), arousal state (78%) and cuff size (76%). Conclusion Most of the university hospital units treating children lacked age-specific written procedures for measuring and interpreting infant NIBP, and there is a strong need for common Nordic guidelines.

OBJECTIVES This study presents short- and long-term follow-up after treatment for isolated valvular aortic stenosis in children with surgical valvotomy as the preferred 1st intervention. METHODS All patients aged 0-18 years treated between 1994 and 2013 at our centre were reviewed regarding the mode of first treatment, mortality, reinterventions and the need for aortic valve replacement. RESULTS A total of 113 patients were identified in local registries. There were 44 neonates, 31 infants and 38 children. The mean follow-up period was 11 years (range 2-22 years). No early deaths and only 2 late deaths were reported. Of the 113 patients, 92 patients had open surgical valvotomy as the 1st intervention. Freedom from reintervention was 80%, 69%, 61%, 57% and 56% at 1, 5, 10, 15 and 20 years, respectively. The main indication for reintervention was valvular stenosis. Freedom from aortic valve replacement was 67%. CONCLUSIONS Surgical valvotomy of aortic stenosis in this long-term follow-up study resulted in no 30-day mortality and

Down syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall’s corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes.

The overall aim was to assess the reliability and accomplish a limited validation of the Pediatric Quality of Life Inventory 3.0 Cardiac Module Scales (PedsQL 3.0), Swedish version, in a sample of Swedish children diagnosed with congenital heart defects (CHD). A secondary aim was to assess whether the children's health-related quality of life (HRQOL) was affected by gender, age, severity of the CHD, surgical intervention and whether the child self-report and parent proxy-report were consistent. A total of 126 families at The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, participated in the study. The PedsQL Inventory 4.0 Generic Core Scales (PedsQL 4.0) and the PedsQL 3.0 were administered to 94 children (aged 5–18 years) with CHD and 126 parents (of children with CHD aged 2–18 years). The results showed that the internal consistency of the PedsQL 3.0 reached or exceeded Cronbach's alpha values of 0.70 for both child self-report and parent proxy-report. The PedsQL 4.0 and ...

Aim Children with congenital heart defects (CHD) who suffer from cognitive impairments and school difficulties need to be identified as early as possible in order to set appropriate interventions in place that may enhance the school situation and quality of life for these children. Identifying children and adolescents at risk for cognitive difficulties requires specific screening tools. This study assessed such a tool – Pediatric Quality of Life Inventory Cardiac Module subscale: Cognitive Problems – to investigate whether proxy reported and self-reported cognitive problems were associated with measured intellectual functioning in children and adolescents with CHD treated with surgery or by catheter interventions. Method The sample consisted of 184 children/adolescents aged 3, 5, 9, and 15 years. The severity of the CHD diagnoses was categorized into three groups (mild, moderate, or severe) for all age groups. For all the age groups, we collected proxy ratings of cognitive problems, and for the 5-, 9-, and 15-year-olds, we also collected self-reported cognitive problems. Intellectual functioning was measured with the Wechsler intelligence scales. The control variables were socioeconomic status and severity of diagnosis. Results A strong association was found between the parent’s ratings of cognitive problems and the children’s and adolescents’ results on the Wechsler scales. This association was present for all ages, including the 3-year-olds. As for the self-reports, an association was only found between the 15-year-olds self-report of cognitive problems and their results on the Wechsler scales. Conclusion To identify children with cognitive problems as early as at the age of 3 years, parent-rated Pediatrics Quality of Life subscale: Cognitive Problems can be used as a screening tool. For 15-year-olds, the self-report ratings can be used as a screening tool. We also suggest a cutoff score of 80 for both the 15-year olds as well as the proxy reports. If the score falls below 80 the child should be formally evaluated using standardized cognitive test.

Background Studies suggest that children with congenital heart defects (CHD) are at risk for adverse intellectual functioning. However, factors related to lower intellectual functioning in this group are largely unknown. This study describes intellectual functioning in children with CHD in relation to severity of the heart defect, the child’s age, and the socioeconomic status of the family (SES). Methods Two hundred twenty-eight children treated with surgery or by catheter technique were tested using the Wechsler intelligence scales to determine full scale IQ (FSIQ). FSIQ was then analyzed in relation to age (3-, 5-, 9-, and 15-year olds), severity of the diagnosis (mild, moderate, and severe), and SES (low, medium, and high). The median age was 70 months (5.8 years) with a range of 162 months [30 months (2.5 years) to 192 months (16.0 years)]. Results The total mean score on FSIQ was 100.8 (SD = 14.5). Children with severe CHD had significantly lower FSIQ than children with mild and moderate CHD, and 9- and 15-year olds had significantly lower FSIQ compared to the 3-year olds. Children from families with low SES had significantly lower FSIQ than children from medium SES and high SES families. No interaction between severity of diagnosis, age, and SES was found for FSIQ. Conclusion Eighty-three percent of the children with CHD performed at or above average with respect to FSIQ. SES and severity of diagnosis had significant main effects on FSIQ. These factors should be considered when planning interventions and follow-up programs for children with CHD.

Background— Late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO. Methods and Results— We conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence. Conclusions— Preoperative clinical and morphological features are important risk factors for postoperative PVO and survival.

The outcome for all children born in Sweden between January 1, 1980 and December 31, 2008 with ventriculo-coronary arterial communications (VCACs) and pulmonary atresia with intact ventricular septum (PAIVS) was assessed. Fifty-one subjects, 42%, of all 125 children born with PAIVS had identifiable VCACs. Cumulative survival after surgery was 67%, as compared with 73% for all subjects born with PAIVS (n.s.). Survival improved over time, and there was no late death after 3years of age. Median follow-up time was 12years (range 1–28years). At follow-up, 33 subjects were alive (12 female/21 male) with the following repairs: six had a biventricular repair, one had 1.5 ventricle repair, 25 were palliated with a single ventricle repair (final stage in 20), and one had a heart transplantation. Notably after decompression ( n =9 survivors), the disease in the coronary arteries did not progress, although four subjects in this group had large VCACs. In the group of subjects with single ventricle repair and large VCACs, eleven were found to have stenoses in the coronary arteries. The disease in the coronary arteries in this group, however, often progressed with an adverse effect on myocardial perfusion. Four of the survivors had documented myocardial infarctions.

Objective: To describe clinical features, morphology, management and outcome of pulmonary vein stenosis (PVS) in childhood. Design and setting: Retrospective international collaborative study involving 19 paediatric cardiology centres in the UK, Ireland and Sweden. Patients: Cases of PVS presenting between 1 January 1995 and 31 December 2004 were identified. Cases where pulmonary veins connected to a morphological left atrium were included. Functionally univentricular hearts and total anomalous pulmonary venous connection were excluded. All available data and imaging were reviewed. Results: 58 cases were identified. In 22 cases (38%) there was premature delivery. 46 (79%) had associated cardiac lesions; 16 (28%) had undergone previous cardiac surgery before PVS diagnosis. 16 children (28%) had a syndrome or significant extracardiac abnormality. 36 presented with unilateral disease of which 86% was on the left. Where there was adequate sequential imaging, disease progression was shown with discrete stenosis leading to diffusely small pulmonary veins. Collateral vessels often developed. 13 patients had no intervention. Initial intervention was by catheter in 17 and surgery in 28. Overall 3-year survival was 49% (95% CI 35% to 63%) with patients undergoing initial surgical intervention having greater freedom from death or re-intervention (hazard ratio 0.44, 95% CI 0.2 to 0.99, p = 0.023). Conclusions: PVS is a complex disease of uncertain cause and frequently associated with prematurity. Early intervention may be indicated to deter irreversible secondary changes.

Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate. A mutation screen of the coding regions of ACTC1 revealed a founder mutation predicting an M123V substitution in affected individuals of both pedigrees. Functional analysis of ACTC1 with an M123V substitution shows a reduced affinity for myosin, but with retained actomyosin motor properties. We also screened 408 sporadic patients with CHDs and identified a case with ASD and a 17-bp deletion in ACTC1 predicting a non-functional protein. Morpholino (MO) knockdown of ACTC1 in chick embryos produces delayed looping and reduced atrial septa, supporting a developmental role for this protein. The combined results indicate, for the first time, that ACTC1 mutations or reduced ACTC1 levels may lead to ASD without signs of cardiomyopathy.

Early cardiac complications after autologous bone marrow transplantation (ABMT) were recorded for 49 children with haematological malignancies. There was no procedure-related mortality and only two cases of early post-transplant cardiac complications of clinical relevance, both of which were reversible. For 35 long-time survivors (median follow-up 7 y) serial evaluations before and after ABMT included ECG, chest radiography, echocardiography and equilibrium radionuclide ventriculography (RVG). One patient had frequent supraventricular ectopic beats after ABMT, a finding not previously noted. The mean left ventricular diastolic diameter (LVDD) was 104% of expected before ABMT (95% confidence interval 99-110). During the first year post-transplant LVDD was about 110% of expected, but thereafter normalization occurred. The mean shortening fraction before ABMT was 31% (CI 29-34), compared with the mean value of 34% for healthy children in our laboratory, and it ranged between 29% and 33% during the follow-up period. Mean left ventricular ejection fraction determined by RVG was 65% (CI 61-69) and mean right ventricular ejection fraction was 46% (CI 43-49) before ABMT, and they did not change during follow-up. It is encouraging that these heavily pre-treated children could be autografted without serious cardiac complications or deterioration in myocardial performance in a 5-10-y prospect, but longer follow-up is needed for a final evaluation.

Aim: To determine what proportion of newborns with critical heart defects are discharged undiagnosed from the maternity ward. Methods: Data were retrieved retrospectively for infants born in our referral area from 1993 to 2001 and undergoing surgical or catheter-based intervention before 2 mo of age because of critical heart defects. Results: 259 full-term infants had critical heart defects. Duct-dependent systemic circulation was present in 129, duct-dependent pulmonary circulation in 106, and 24 infants were not duct dependent but critically ill. In 51 infants (20%) the heart defect was not suspected before discharge from the maternity ward. Such late detection occurred more often in infants with duct-dependent systemic circulation (30%) and in children with defects that were not duct dependent (38%) than in children with duct-dependent pulmonary circulation (4%) (p

Background We hypothesized that blood cardioplegia preserves myocardial metabolism and function more effectively than St Thomas' crystalloid cardioplegia in infant cardiac surgery. Methods Thirty infants with atrioventricular septal defects were randomly allocated to either blood or crystalloid intermittent cold (4°C) cardioplegia. Arterial and coronary sinus blood was analyzed for lactate and oxygen. Cardiac output (thermodilution) and left ventricular function (echocardiography) were evaluated. Results The lactate concentration in coronary sinus blood early after bypass was significantly higher after crystalloid cardioplegia than after blood cardioplegia (2.1 ± 0.3 vs 1.3 ± 0.1 mmol/L, p = 0.006), with a significant myocardial release of lactate after crystalloid but not after blood cardioplegia. Oxygen extraction (arterial–coronary sinus O 2 content) was higher early after crystalloid cardioplegia (3.02 ± 0.13 vs 2.35 ± 0.22 mmol/L, p = 0.01), possibly reflecting a difference in oxygen debt. The cardiac index was higher after blood cardioplegia (4.9 ± 0.3 vs 4.0 ± 0.3 L/min −1/ m −2 , p = 0.04) and echocardiographic grading of left ventricular function was better (4.1 ± 0.17 vs 3.5 ± 0.22 arbitrary units, p = 0.046). Conclusions This study indicates that blood cardioplegia preserves myocardial metabolism and function more effectively than crystalloid cardioplegia in infant cardiac surgery. The clinical significance of this finding is uncertain, but the more than 20% increase in cardiac index in the critical phase during weaning from bypass may be advantageous.

Objective: To measure quality of life in children with pulmonary atresia and intact ventricular septum, and make comparisons with a healthy group of children from the general Swedish population. An additional aim was to compare quality of life in two subgroups, children undergoing biventricular and univentricular repair, the latter by establishment of the Fontan circulation. Methods: Quality of life was measured using a mailed questionnaire, taking into consideration the three spheres of personal, interpersonal, and external living conditions. In all, 52 children received the questionnaire, and the answers were compared with those of a random sample of 1856 healthy Swedish children. Results: We received responses from 42 children and parents. The overall differences between groups were small, and no difference was found when comparing the children undergoing univentricular as opposed to biventricular surgical repair. In terms of personal quality of life, we found a higher level of psychosomatic complaints, and lower satisfaction with their own and parent–child activities, in those with the congenital anomaly than in their normal peers. In terms of the interpersonal sphere, more time was available for those with malformed hearts, but the experience of support from the relatives was significantly lower. Conclusions: Overall, quality of life was equal between children with pulmonary atresia and intact ventricular septum and the children in the reference group. The personal psychological conditions were less favourable for children with pulmonary atresia and intact ventricular septum. The perceived lack of support from relatives was also higher in these families. No difference was found when comparing the children undergoing univentricular and biventricular surgical repair.

To study the outcome of all children born with pulmonary atresia and intact ventricular septum in Sweden between 1980 and 1999.Retrospective study of medical records with review of the initial, preoperative angiocardiographic and echocardiographic examinations.A total of 84 children were born with pulmonary atresia and intact ventricular septum, giving an incidence of 4.2 per 100,000 live births. In all, 77 were operated on with a 1-year survival rate of 75%. Thirty-six children had ventriculocoronary communications, with a 1-year survival rate of 50%. At the end of the study period, 52 children were alive, 32 with biventricular repair, and 19 with univentricular repair. Follow-up time was 14 days-20 years (median, 6 years). Statistical analysis of incremental risk factors for death showed statistical significance for low birth weight, male sex, muscular pulmonary atresia, and having a systemic-to-pulmonary shunt as the sole initial intervention.Complete national data of all patients born with pulmonary atresia and intact ventricular septum during 1980-1999 in Sweden revealed a total mortality in accordance with previous reports for results for surgery. Further improvements demand a thorough preoperative investigation of the cardiac anatomy, particularly of the ventriculocoronary communications, to enable right ventricular decompression whenever possible.

OBJECTIVE—To study short and long term results after surgical closure of isolated ventricular septal defects (VSDs) from 1976 to 1996, especially in relation to changes in preoperative evaluation during this period. DESIGN—Retrospective study. SETTING—Tertiary referral centre for paediatric cardiac care. PATIENTS—All children under 18 years of age who had corrective surgery for VSD between 1976 and 1996. MAIN OUTCOME MEASURES—Preoperative evaluation, indications for surgery, diagnostic errors, and early and late results. RESULTS—A significant decrease in the use of invasive preoperative studies in favour of non-invasive methods was found; from 1976 to 1990, a total of 109/110 patients had preoperative invasive study as compared to 43/167 from 1991 to 1996 (p

OBJECTIVES—To describe the evaluation, decision making, and care of children with a complete atrioventricular septal defect (CAVSD). STUDY DESIGN—Retrospective study of 136 consecutive cases from 1970 to 1996. RESULTS—A total of 115 (85%) children had Down's syndrome. Denial of surgery without obvious medical reasons was more common in the early years, as was parental refusal of offered surgery and institutional care of the children. Improved results in later years encouraged surgical treatment for all these patients, but more liberal attitudes towards patients with Down's syndrome preceded the improved results. The use of echocardiography as a screening method for all newborns with Down's syndrome made it possible to plan for correction within the 1st months of life. CONCLUSIONS—Changing attitudes in society and widespread use of echocardiography have significantly improved the management of children with a CAVSD and Down's syndrome.

UNLABELLED Respiratory syncytial virus (RSV) infection is the leading cause of infection of the lower respiratory tract in infants, and is also the leading cause of hospitalization during the first year of life. In this issue of Acta Paediatrica, Meberg and Bru report on the incidence and estimated costs of hospitalizations for RSV infections in children with congenital heart disease from a specified region in Norway. CONCLUSION Incidence figures of hospitalization due to RSV infection in this high-risk group of infants were similar to the results from several other reports. The cost-benefit analysis of prophylaxis against RSV infection in infants with congenital heart disease, using the monoclonal antibody palivizumab, should also take into account potential savings attributable to such prophylaxis.

The procedure of total cavopulmonary connexion includes trans-section and closure of the pulmonary trunk, the systemic venous blood flow being directed to the pulmonary vascular bed by an anastomosis of the superior caval vein with the right pulmonary artery. Following this procedure, there remains a small residual pulmonary trunk. The purpose of our study was to obtain information about the fate of this residual trunk and its contained pulmonary valve. Using transthoracic echocardiography, we examined 29 patients (mean age 7 years 4 months) after a total cavopulmonary connexion (mean interval 17 months). We were able to obtain adequate visualization of the pulmonary valve and the pulmonary trunk in 23 of the patients. Pulmonary regurgitation was demonstrated by colour Doppler echocardiography in 13 pts (57%). Formation of thrombus in the residual pulmonary trunk was detected in one patient (4%) 6 months after the operation. One cerebrovascular embolic event occurred in a patient who had pulmonary regurgitation without formation of thrombus in the residual trunk 3 months after the total cavopulmonary connexion. Our findings show that pulmonary regurgitation is frequently present in patients after total cavopulmonary connexion. Although formation of thrombus in the residual pulmonary trunk seems to be less common, we recommend surgical closure of the pulmonary valve during this procedure so as to exclude the residual pulmonary trunk as a possible source of systemic emboli.

Aim: This is the first study to evaluate compliance with the 2003 Swedish national guidelines for prophylactic treatment of respiratory syncytial virus (RSV) in children with congenital heart disease (CHD). We estimated the relative risk (RR) of children with CHD being hospitalised with a RSV infection, studied the extent to which RSV prophylactic treatment with palivizumab corresponded to the guidelines and determined the morbidity of children with CHD who developed RSV infection despite prophylaxis. Methods: This national observational study comprised prospectively registered data on 219 children with CHD treated with palivizumab, medical records on RSV cases and information on hospitalisation rates of children with CHD and RSV infection. Results: The calculated RR of children with CHD being hospitalised with RSV infection was 2.06 (950/0 Cl 1.6-2.6; p < 0.0001) compared with children without CHD. Approximately half of the patients (49%) born before the RSV season and 25% born during the RSV season did not start treatment as recommended by the guidelines. Conclusion: Having CHD increased the rate and estimated RR of children being hospitalised with RSV infection. The guidelines were not followed for about half of the children born before a RSV season and a quarter of the children born during a RSV season and need updating.

Previous studies show that growth hormone (GH) treatment increases cardiac dimensions in short children with GH deficiency (GHD) and has diverse cardiac effects in children with idiopathic short stature (ISS). This study was performed to assess the effect of GH on the cardiovascular system in short children with a broad range of GH secretion and GH sensitivity/responsiveness.In this prospective, multicentre study, short prepubertal children diagnosed with isolated GHD (89) or ISS (38) were followed during 2 years of GH treatment. They were randomized to receive either a standard (43 μg/kg/day) or an individualized GH dose (range 17-100 μg/kg/day) based on GH responsiveness estimated by a prediction model and distance to target height. Echocardiography, blood pressure and electrocardiography were performed at baseline, 3, 12 and 24 months.Left ventricular mass (LVM) indexed to body surface area increased significantly during 2 years of GH treatment in both GHD and ISS irrespective of randomized dose. This change was already apparent at 3 months, when standard deviation scores (SDS) of wall thickness and diameter were increased. At 24 months, left ventricular diameter SDS remained increased, whereas myocardial thickness SDS returned to baseline values. There was no impairment of systolic or diastolic function. There was no correlation with treatment dose and LVM SDS at 24 months.Irrespective of GH status, there was a rapid increase in LVM during GH treatment in short children. At 3 months, wall thickness and diameter were increased, whereas only diameter remained increased at 24 months.

Objective: Pulmonary venous obstruction (PVO) is an important cause of late mortality in total anomalous pulmonary venous connection (TAPVC). We aimed to describe current practices for the management of postoperative PVO and the efficacy of the different interventional procedures. Methods: We conducted a retrospective international collaborative population-based study involving 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. Patients with TAPVC born between January 1, 1998, and December 31, 2004, were identified. Patients with functionally univentricular circulation or atrial isomerism were excluded. All available data and images were reviewed. Results: Of 406 patients undergoing repair of TAPVC, 71 (17.5%) had postoperative PVO. The diagnosis was made within 6 months of surgery in 59 (83%) of the 71 patients. In 12, serial imaging documented change in appearance of the pulmonary veins. Good-sized pulmonary veins can progress to diffusely small veins and rarely atresia. Patients presenting after 6 months had less severe disease; all are alive at most recent follow-up. Fifty-six (13.8%) of 406 patients underwent intervention for postoperative PVO: 44 had surgical treatment and 12 had an initial catheter intervention. One half underwent 1 or more reinterventions. Three-year survival for patients with postoperative PVO was 58.7%(95% confidence intervals, 46.2%-69.2%) with a trend that those having a surgical strategy did better (P = .083). Risk factors for death included earlier presentation after TAPVC repair, diffusely small pulmonary veins at presentation of postoperative PVO, and an increased number of lung segments affected by obstruction. Conclusions: Postoperative PVO tends to appear in the first 6 months after TAPVC repair and can be progressive. Early intervention for PVO may be indicated before irreversible secondary changes occur. (J Thorac Cardiovasc Surg 2013;145:1255-62)

To investigate physical activity, sports participation and aerobic fitness in children who have undergone surgery for congenital heart defects.Children who had undergone surgery for congenital heart defects and healthy controls in the Gothenburg area were invited to participate in the study. All participants were aged 9-11 or 14-16 years. The activity monitor ActiReg was used to assess physical activity. Participants were interviewed about their participation in sports and performed a maximal exercise test on a bicycle with measured oxygen uptake.A total of 32 and 25 patients, and 61 and 45 controls, in the two age-groups were included, respectively. The patients had a wide range of severity of congenital heart defects. The physical activity level was similar in the patients and the controls. The rate of sports participation was high for both patients and controls; 80-94% of all participants took part in sports at least once a week. The majority of the patients were considered to have at least a moderate level of aerobic fitness.Although children who have undergone surgery for congenital heart defects have a similar level of physical activity compared with that of healthy children, some of them may require support to participate in exercise and vigorous physical activity.

The objective of this study was to assess exercise performance in subjects born in Sweden between 1980 and 1995 and undergoing surgery for pulmonary atresia and intact ventricular septum and to identify determinants of exercise performance. Twenty-seven subjects, 16 with biventricular repair and 11 with univentricular palliation, and 28 age- and sex-matched controls completed cardiopulmonary exercise and lung function testing. Peak oxygen uptake was determined using a symptom-limited ramp bicycle exercise protocol. Regression analysis was performed to identify predictors of peak oxygen uptake (V'O(2)), The index group had lower peak V'O(2) (1.4 [median 0.8; range 2.5] l/min) than controls (1.9 [0.7; 3.1]; p < 0.05). Subjects without ventriculocoronary arterial communications (VCAC), corrected to biventricular circulation, had higher peak V'O(2), than the remaining index subjects. Decreased total lung capacity, low minute ventilation, and high physiologic dead space measured at peak exercise were all independent determinants of low peak V'O(2) Exercise capacity is generally decreased in subjects with pulmonary atresia and intact ventricular septum, although there are marked interindividual differences. Good exercise capacity was found in subjects without VCAC who had undergone biventricular repair. Decreased lung function was an unfavourable predictor of exercise capacity.

GH may exert direct growth-promoting and metabolic actions on target tissues, but most of its effects are mediated by circulating (endocrine) or local (auto-/paracrine) IGF-I. The GH/IGF-I system has an important role in cardiac development and in maintaining the structure and function of the heart. A subgroup of children with pronounced heart defects will eventually need transplants, owing to congestive heart failure. Since the symptoms are often severe and may progress while waiting for surgery, it is necessary to develop supportive medical treatment. GH has been proposed as a therapeutic agent in adults with heart failure, but to date studies are lacking on children and more information is necessary. We have examined the expression of IGF-I mRNA and GH-receptor (GH-R) mRNA in children undergoing surgery for congenital heart disease. Eighteen children scheduled for open-heart surgery were included in the study. Right auricular biopsies were taken at the time of venous catheterization preceding cardiac bypass. The specimens were analysed using realtime PCR. We were able to show expression of both IGF-I mRNA and GH-R mRNA in the pediatric heart. The relative expressions were intercorrelated (r=0.75, p

We describe the results of myocardial perfusion scintigraphy performed 4 to 15 years after surgery in 12 patients with pulmonary atresia and intact ventricular septum. We used single photon emission computed tomography after injection of technetium Tc-99m tetrofosmin at submaximal exercise test. The patients, 7 girls and 5 boys, with a mean age of 11 years, and a range from 6 to 19 years, had either undergone biventricular repair, in 5 cases, or univentricular palliation in the remaining 7. This second group included 4 patients with ventriculo-coronary arterial communications. Of the children, 3 with biventricular repair and 6 with univentricular palliation had perfusion defects. Children with biventricular repair had perfusion defects in the ventricular septum, while those having univentricular palliation also had defects located to the left ventricular free wall. All children with ventriculo-coronary arterial communications had perfusion defects both in the ventricular septum and in the left ventricular free wall.

Aim: The myocardial uptake of substrates in children has only been investigated on a small scale. The purpose of this study was to define myocardial substrate uptake in relation to the arterial supply of substrates, age, growth and oxygen saturation. Methods: Thirty patients with congenital heart disease, aged 3 months to 16 years, were studied during cardiac catheterization. Arterial and coronary sinus blood was analyzed for the major fuel metabolites and amino acids. Results: The uptake of all major substrates correlated significantly with the arterial supply: free fatty acids (r = 0.52, p = 0.004), β-hydroxybutyrate (r = 0.74, p < 0.0001), lactate (r = 0.70, p < 0.0001) and glucose (r = 0.48, p = 0.01). Free fatty acids were the dominant substrate, irrespective of age, growth and saturation. With age, there was an increase in the uptake of lactate (r = 0.61, p = 0.0004) and a decrease in the uptake of β-hydroxybutyrate (r =–0.41, p = 0.02). In multivariate analyses, these changes were explained by the arterial supply of the substrates, while age per se did not contribute significantly. Conclusion: The uptake of myocardial metabolites correlated with the arterial supply. Free fatty acids were the dominant substrate at all ages. The uptake of lactate and β-hydroxybutyrate, although varying with age, was also determined by the arterial supply.

To evaluate the feasibility of detecting duct-dependent congenital heart disease before hospital discharge by using pulse oximetry.Case-control study.A supra-regional referral centre for paediatric cardiac surgery in Sweden.200 normal term newborns with echocardiographically normal hearts (median age 1.0 d) and 66 infants with critical congenital heart disease (CCHD; median age 3 d).Pulse oximetry was performed in the right hand and one foot using a new-generation pulse oximeter (NGoxi) and a conventional-technology oximeter (CToxi).With the NGoxi, normal newborns showed a median postductal saturation of 99% (range 94-100%); intra-observer variability showed a mean difference of 0% (SD 1.3%), and inter-observer variability was 0% (SD 1.5%). The CToxi recorded a significantly greater proportion of postductal values below 95% (41% vs 1%) in the normal newborns compared with NGoxi (p0.0001). The CCHD group showed a median postductal saturation of 90% (45-99%) with the NGoxi. Analysis of distributions suggested a screening cut-off of95%; however, this still gave 7/66 false-negative patients, all with aortic arch obstruction. Best sensitivity was obtained by adding one further criterion: saturation of95% in both hand and foot or a difference of+/-3% between hand and foot. These combined criteria gave a sensitivity of 98.5%, specificity of 96.0%, positive predictive value of 89.0% and negative predictive value of 99.5%.Systematic screening for CCHD with high accuracy requires a new-generation oximeter, and comparison of saturation values from the right hand and one foot substantially improves the detection of CCHD.