Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.

In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.

Congenital heart disease does not entail an increased risk for severe COVID-19.

AIM: To analyse the risk of developing serious disease or death due to COVID-19 among patients who underwent heart surgery during childhood. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Life satisfaction, health-related quality of life and physical activity after treatment for valvular aortic 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.

Outcome after surgery for pulmonary atresia with ventricular septal defect, a long-term follow-up study.

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.

Children and Adolescents Treated for Valvular Aortic Stenosis Have Different Physical Activity Patterns Compared to Healthy Controls: A Methodological Study in a National Cohort.

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.

A national study of the outcome after treatment of critical aortic stenosis in the neonate.

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.

Survey of 23 Nordic university hospitals showed that 77% lacked written procedures for measuring and interpreting blood pressure in infants.

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.

The highest mortality rates in childhood dilated cardiomyopathy occur during the first year after diagnosis.

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.

Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.

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.

Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study.

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.

Evaluating national guidelines for the prophylactic treatment of respiratory syncytial virus in children with congenital heart disease.

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 (95% CI 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.

Long-Term Survival After Single-Ventricle Palliation: A Swedish Nationwide Cohort Study.

BACKGROUND: Long-term survival after single-ventricle palliation and the effect of dominant ventricle morphology in large, unselected series of patients are scarcely reported. METHODS AND RESULTS: This nationwide cohort study included all children undergoing operation with single-ventricle palliation during their first year of life in Sweden between January 1994 and December 2019. Data were obtained from institutional records and assessment of underlying cardiac anomaly and dominant ventricular morphology was based on complete review of medical records, surgical reports, and echocardiographic examinations. Data on vital status and date of death were retrieved from the Swedish Cause of Death Register, allowing for complete data on survival. Among 766 included patients, 333 patients (43.5%) were classified as having left or biventricular dominance, and 432 patients (56.4%) as having right ventricular (RV) dominance (of whom 231 patients had hypoplastic left heart syndrome). Follow-up was 98.7% complete (10 patients emigrated). Mean follow-up was 11.3 years (maximum, 26.7 years). Long-term survival was significantly higher in patients with left ventricular compared with RV dominance (10-year survival: 91.0% [95% CI, 87.3%-93.6%] versus 71.1% [95% CI, 66.4%-75.2%]). RV dominance had a significant impact on outcomes after first-stage palliation but was also associated with impaired survival after completed total cavopulmonary connection. In total, 34 (4.4%) patients underwent heart transplantation. Of these 34 patients, 25 (73.5%) had predominant RV morphology. CONCLUSIONS: This study provides clinically relevant knowledge about the long-term prognosis in patients with different underlying cardiac anomalies undergoing single-ventricle palliation. RV dominance had a significant impact on outcomes after initial surgical treatment but was also associated with impaired survival after completed Fontan circulation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356574.

Warfarin dose prediction in children using pharmacometric bridging--comparison with published pharmacogenetic dosing algorithms.

PURPOSE: Numerous studies have investigated causes of warfarin dose variability in adults, whereas studies in children are limited both in numbers and size. Mechanism-based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children. METHOD: An adult population pharmacokinetic/pharmacodynamic (PK/PD) model for warfarin, with CYP2C9 and VKORC1 genotype, age and target international normalized ratio (INR) as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external data set of children 0-18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children. RESULTS: Overall, the bridged model predicted INR response well in 64 warfarin-treated Swedish children (median age 4.3 years), but with a tendency to overpredict INR in children ≤2 years old. The bridged model predicted 20 of 49 children (41 %) within ± 20 % of actual maintenance dose (median age 7.2 years). In comparison, the published dosing algorithms predicted 33-41 % of the children within ±20 % of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ±20 % of actual dose to 70 %. CONCLUSION: A mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.

Outcomes in neonatal critical and non-critical aortic stenosis: a retrospective cohort study.

OBJECTIVE: To compare long-term survival, reinterventions and risk factors using strict definitions of neonatal critical and non-critical valvular aortic stenosis (VAS). DESIGN: A nationwide retrospective study using data from patient files, echocardiograms and the Swedish National Population Registry. SETTING AND PATIENTS: All 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 MEASURES: Short-term and long-term survival, aortic valve reinterventions need of valve replacements, risk factors for reintervention and event-free survival. RESULTS: We 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). CONCLUSIONS: Critical 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.

Rapid cardiovascular effects of growth hormone treatment in short prepubertal children: impact of treatment duration.

OBJECTIVE: 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. DESIGN AND PATIENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment decision in a 4-year-old-boy with left ventricular outpouching after advanced hemodynamical flow evaluation with 4Dflow CMR: A case report.

Background: The present study presents a diagnostic course for the characterization of a congenital left ventricular outpouching (LVO) in a 4-year-old boy with severe neonatal heart failure, evaluating the added value of cardiac magnetic resonance (CMR) 4Dflow. Case presentation: A boy, born at full term, presented with heart failure immediately after birth. Echocardiography showed dilated left ventricle with poor function and LVO was initially interpreted as an aneurysm. No infection, inflammation, or other cause for heart failure was found. With intensive medical treatment, the heart function returned to normal, and eventually, all medication was terminated. At follow-up, surgical treatment of the LVO was discussed but after CMR 4Dflow, a thorough evaluation of the function of the left ventricle as well as the LVO was possible and the LVO was determined a double-chambered left ventricle with a good prognosis. Conclusions: The present case demonstrates the clinical usability of CMR 4Dflow for improved decision-making and risk assessment, revealing advanced hemodynamic flow patterns with no need for operation.

Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome: 20 Years of National Data From Sweden.

Background Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation. Methods and Results This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob- LV: HR, 2.1; P=0.03). Conclusions Glob-LV and AA-MS are independent morphological risk factors for adverse short- and long- term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome.

Total anomalous pulmonary venous connection: morphology and outcome from an international population-based study.

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.