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Purpose The Fontan circulation carries a dismal prognosis in the long term due to its peculiar physiology and lack of a subpulmonic ventricle. Although it is multifactorial, elevated IVC pressure is accepted to be the primary cause of Fontan's high mortality and morbidity. This study presents a self-powered venous ejector pump (VEP) that can be used to lower the high IVC venous pressure in single-ventricle patients. Methods A self-powered venous assist device that exploits the high-energy aortic flow to lower IVC pressure is designed. The proposed design is clinically feasible, simple in structure, and is powered intracorporeally. The device's performance in reducing IVC pressure is assessed by conducting comprehensive computational fluid dynamics simulations in idealized total cavopulmonary connections with different offsets. The device was finally applied to complex 3D reconstructed patient-specific TCPC models to validate its performance. Results The assist device provided a significant IVC pressure drop of more than 3.2 mm Hg in both idealized and patient-specific geometries, while maintaining a high systemic oxygen saturation of more than 90%. The simulations revealed no significant caval pressure rise ( 84%) in the event of device failure, demonstrating its fail-safe feature. Conclusions A self-powered venous assist with promising in silico performance in improving Fontan hemodynamics is proposed. Due to its passive nature, the device has the potential to provide palliation for the growing population of patients with failing Fontan.

Objectives High plasma levels of the omega-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid, and docosapentaenoic acid associates with positive outcomes in adult renal transplant recipients. However, data from pediatric populations are scarce. The aim of the study was to assess the fatty acid profile in a pediatric renal transplantation cohort and to examine the associations between plasma omega-3 fatty acids and cardiovascular disease (CVD) risk factors. Methods In this cross-sectional study comprising 53 children (median age, 12.2 years; 32 boys) with a renal transplant, we assessed the prevalence of CVD risk factors as well as markers of end organ damage: carotid intima-media thickness (cIMT) and left ventricular mass index. The associations between plasma omega-3 fatty acids and CVD risk factors were assessed. Results Twenty-five (47%) patients were preemptively transplanted. Seventy-six percent had dyslipidemia and 51% had hypertension. The mean left ventricular mass index was 40.4 ± 14.3 g/m2.7, and 14% had left ventricular hypertrophy. The mean cIMT was 0.41 ± 0.04 mm. In a multivariate linear regression, EPA levels were inversely associated to blood pressure (β coeff. = −0.37, P = .007), triglycerides (β coeff. = −0.44, P = .01), and high-density lipoprotein cholesterol (β coeff. = −0.41, P = .01). Conclusion EPA levels are inversely associated with components of the metabolic syndrome, which may provide support for specific dietary advice or supplementation in this patient population. cIMT is less pronounced in our cohort than in comparable cohorts with lower rate of preemptive transplantations. Our results need replication in prospective cohorts.

Background: Patency of the coronary arteries is an issue after reports of sudden cardiac death in patients with transposition of the great arteries (TGA) operated with arterial switch (ASO). Recent studies give rise to concern regarding the use of ionising radiation in congenital heart disease, and assessment of the coronary arteries with coronary MR angiography (CMRA) might be an attractive non-invasive, non-ionising imaging alternative in these patients. Theoretically, the use of 3.0T CMRA should improve the visualisation of the coronary arteries. The objective of this study was to assess feasibility of 3.0T CMRA at the coronary artery origins by comparing image quality with non-contrast CMRA in ASO TGA patients to healthy age-matched controls, and by comparing image quality with non-contrast CMRA to contrast enhanced CMRA in the patient group. Material and methods: Twelve patients, 9-15 years (mean 11.9 years, standard deviation 1.5 years), and 12 age-matched controls (mean 12.7 years, standard deviation 1.7 years) were examined with 3D balanced steady-state free precession (SSFP). Nine of twelve patients had Gadolinium-enhanced fast low-angle shot (Gd-FLASH) performed after SSFP. Image quality at the coronary artery origins was evaluated subjectively with a 10 cm figurative visual analogue scale (fVAS) and objectively by signal-to-noise and contrast-to-noise ratio (SNR, CNR). Results: All, but one, coronary artery origins were identified. No significant difference in image quality scores was found between patients and controls with SSFP (mean values 6.5 cm—9.1 cm in patients and 7.0 cm—8.0 cm in controls, p-values > 0.1). With SSFP, intra-observer fVAS mean score was 6.7 cm—8.6 cm and with Gd-FLASH 7.7 cm—8.7 cm. CNR was higher with Gd-FLASH (p < 0.03). Intra-observer agreement index (AI) with SSFP was moderate-to-good (0.43–0.71) and with Gd-FLASH good (0.64–0.79) in all origins. Inter-observer AI was good in the left main stem (LMS) with SSFP (0.65). With Gd-FLASH inter-observer AI was good in LMS (0.78) and moderate (0.5) in the left anterior descending artery, but lacking in the other origins though with a good agreement on Bland-Altman plots. Conclusions: Our findings indicate a better, more reproducible image quality with Gd-FLASH than with non-contrast SSFP CMRA on 3.0T for evaluation of the coronary artery origins in ASO TGA children and adolescents.

In the fetus, the cardiac neural crest gives rise to both the thymus and the conotruncus of the heart. In newborn screening for severe T-cell lymphopenia neonates with congenital heart defects may be detected. In this study, we investigated the occurrence of T-cell lymphopenia in neonates with or without 22q11.2 deletion syndrome (del) suffering from heart defects. This retrospective cohort study included 125 patients with heart defects. T-cell receptor excision circles (TRECs), a measure for T-cell lymphopenia, were quantified by RT-PCR using stored newborn screening blood spots. Three patient groups were compared: non-conotruncal defects (n = 57), conotruncal defects (n = 42), and 22q11.2 del with conotruncal defects (n = 26). Significantly lower TREC values were detected in patients with 22q11.2 del and conotruncal heart defects compared to those with non-syndromic conotruncal (p p p = 0.152). Low TREC levels were obtained in neonates treated with heart surgery/intervention within 2 weeks after birth and in those with a fatal outcome (p = 0.02) independent of patient group. A correlation was found between low TREC numbers and oxygen saturation, SpO2 below 95% (p = 0.017). The SpO2 was significantly lower in the non-syndromic conotruncal group compared to non-conotruncal (p p = 0.015). No correlation was found between low neonatal TRECs and infections needing hospitalization later in life (p = 0.135). Patients with 22q11.2 del and conotruncal defects have significantly lower TREC levels compared to patients with heart defects without this syndrome.

OBJECTIVES This population-based, comprehensive, retrospective study presented the clinical outcomes of all children born in Norway between 2003 and 2017 with double outlet right ventricle (DORV). METHODS All children born with DORV between 2003 and 2017 were identified in the Oslo University Hospital registry. Patients’ characteristics, interventions, complications and deaths were recorded. Echocardiographic data were reviewed for classification according to current standards. We investigated time-dependent surgical reintervention and mortality using Kaplan–Meier analyses and determinants of treatment complications, reintervention and death using regression analyses. RESULTS Ninety-three children with DORV represented an annual median prevalence of 1.18 per 10 000 births in Norway. Six children received palliative care. With an intention to treat, a surgical route with the primary biventricular repair was followed for 62 children, staged biventricular repair for 15 and univentricular repair for 10 children. Major complications occurred in 1.0% and 6.2% of children following catheter or surgical intervention, respectively. No significant determinants of the complications were identified. Overall survival following treatment was 91.9%, 90.8%, 89.5% and 89.5% and corresponding freedom from surgical reintervention was 88.0%, 79.0%, 74.9% and 69.4% at 1, 2, 5 and 10 years, respectively. The presence of atrioventricular septal defect predicted an increased risk of mortality (hazard ratio: 7.16) but did not increase the risk of surgical reintervention. CONCLUSIONS In Norway, most children receive tailored treatment for DORV with low rates of complications, surgical reinterventions and mortality. However, atrioventricular septal defect remains a potential determinant of postoperative death.

Background:Limited data exist on training of European paediatric and adult congenital cardiologists.Methods:A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.Results:Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).Conclusion:Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

BACKGROUND Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. OBJECTIVE The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). METHODS The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. RESULTS Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. CONCLUSIONS The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. CLINICALTRIAL INTERNATIONAL REGISTERED REPORT DERR1-10.2196/35838

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p p 2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.govidentifier NCT02378857

New methods for holographic visualisation provide a true three-dimensional experience of medical images. The technique is generating great interest among surgeons.

Funding Acknowledgements South-Eastern Norway Regional Health Authority OnBehalf Center for Cardiological Innovation Background Recent studies have suggested an initial concentric remodelling in the early development of the athlete’s heart in endurance athletes. However, the development from the early to the fully developed endurance athlete’s heart has not been described in longitudinal studies. Aims This study aims to explore the morphological changes occurring in hearts of young endurance athletes transitioning through adolescence. Methods Forty-eight cross-country skiers were examined at age 12 (12.1 ± 0.2 years) and then again at age 15 (15.3 ± 0.3 years). Cardiopulmonary exercise test and echocardiography, including 3D acquisitions, was performed in all subjects at both baseline and follow-up. Results At follow-up, 31 (65%) of the endurance athletes were still active and 17 (35%) were not. No differences in cardiac morphology were identified at baseline. At 15 years of age, the active endurance athletes had greater VO2 max, 3D indexed left ventricular end-diastolic and end-systolic volumes (Table). Relative wall thickness (RWT) decreased in the active endurance athletes during follow-up (0.35 ± 0.05 to 0.31 ± 0.04, p Conclusion After an early concentric remodeling in the 12 years old athletes, those who continued regular endurance training developed eccentric changes with chamber dilatation and a drop in RWT. In contrast, those who ceased endurance training maintained a comparable wall thickness, but did not develop chamber dilatation nor experience a drop in RWT. Baseline Follow-up Active athletes (n = 31) Former athletes (n = 17) p-value Active athletes (n = 31) Former athletes (n = 17) p-value VO2 max, indexed 65 ± 7 63 ± 7 0.33 62 ± 8 57 ± 6

Funding Acknowledgements South-Eastern Norway Regional Health Authority OnBehalf Center for Cardiological Innovation Background Endurance exercise is closely correlated with physical fitness and the development of the athlete’s heart. The impact of changes in exercise-patterns in young athletes is poorly described. Aims This study aims to explore the impact of endurance training versus non-endurance training on cardiac morphology and physical fitness in young endurance athletes. Methods Forty-eight cross-country skiers were examined at age 12 (12.1 ± 0.2 years) and then again at age 15 (15.3 ± 0.3 years). Echocardiography, including 3D echocardiography, and cardiopulmonary exercise testing was performed in all participants. Self-reported data on weekly hours of endurance and weekly hours of non-endurance training was collected. Results At follow-up, thirty-one (65%) of the endurance athletes were still active and 17 (35%) were not. There was a moderate, positive correlation between weekly hours of endurance-only training and changes in VO2 max from baseline to follow-up (R = 0.55, p Conclusion Only endurance training is sufficient to induce cardiac remodeling, including dilatation of both ventricles, in highly trained adolescent athletes. Abstract 431 Figure.

Introduction: In liver surgery, medical images from pre-operative computed tomography and magnetic resonance imaging are the basis for the decision-making process. These images are used in surgery planning and guidance, especially for parenchyma-sparing hepatectomies. Though medical images are commonly visualized in two dimensions (2D), surgeons need to mentally reconstruct this information in three dimensions (3D) for a spatial understanding of the anatomy. The aim of this work is to investigate whether the use of a 3D model visualized in mixed reality with Microsoft HoloLens increases the spatial understanding of the liver, compared to the conventional way of using 2D images. Material and methods: In this study, clinicians had to identify liver segments associated to lesions. Results: Twenty-eight clinicians with varying medical experience were recruited for the study. From a total of 150 lesions, 89 were correctly assigned without significant difference between the modalities. The median time for correct identification was 23.5 [4–138] s using the magnetic resonance imaging images and 6.00 [1–35] s using HoloLens (p

Aims Proof of concept and feasibility study for preoperative diagnostic use of mixed reality (MR) holograms of individual 3D heart models from standard cardiac computed tomography angiograms (CTA) images. Optimal repair for complex congenital heart disease poses high demands on 3D anatomical imagination. Three-dimensional printed heart models are increasingly used for improved morphological understanding during surgical and interventional planning. Holograms are a dynamic and interactive alternative, probably with wider applications. Methods and results A 3D heart model was segmented from CTA images in a patient with double outlet right ventricle and transposition of the great arteries (DORV-TGA). The hologram was visualized in the wearable MR platform HoloLens® for 36 paediatric heart team members who filled out a diagnostic and quality rating questionnaire. Morphological and diagnostic output from the hologram was assessed and the 3D experience was evaluated. Locally developed app tools such as hologram rotation, scaling, and cutting were rated. Anatomy identification and diagnostic output was high as well as rating of 3D experience. Younger and female users rated the app tools higher. Conclusion This preliminary study demonstrates that MR holograms as surgical planning tool for congenital heart disease may have a high diagnostic value and contribute to understanding complex morphology. The first users experience of the hologram presentation was found to be very positive, with a preference among the female and the younger users. There is potential for improvement of the hologram manipulation tools.

Objectives A technique that uses two-dimensional images to create a knowledge-based, three-dimensional model was tested and compared to magnetic resonance imaging. Background Measurement of right ventricular volumes and function is important in the follow-up of patients after pulmonary valve replacement. Magnetic resonance imaging is the gold standard for volumetric assessment. Echocardiographic methods have been validated and are attractive alternatives. Methods Thirty patients with tetralogy of Fallot (25 ± 14 years) after pulmonary valve replacement were examined. Magnetic resonance imaging volumetric measurements and echocardiography-based three-dimensional reconstruction were performed. End-diastolic volume, end-systolic volume, and ejection fraction were measured, and the results were compared. Results Magnetic resonance imaging measurements gave coefficient of variation in the intraobserver study of 3.5, 4.6, and 5.3 and in the interobserver study of 3.6, 5.9, and 6.7 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively. Echocardiographic three-dimensional reconstruction was highly feasible (97%). In the intraobserver study, the corresponding values were 6.0, 7.0, and 8.9 and in the interobserver study 7.4, 10.8, and 13.4. In comparison of the methods, correlations with magnetic resonance imaging were r = 0.91, 0.91, and 0.38, and the corresponding coefficient of variations were 9.4, 10.8, and 14.7. Echocardiography derived volumes (mL/m2) were significantly higher than magnetic resonance imaging volumes in end-diastolic volume 13.7 ± 25.6 and in end-systolic volume 9.1 ± 17.0 (both P < .05). Conclusions The knowledge-based three-dimensional right ventricular volume method was highly feasible. Intra- and interobserver variabilities were satisfactory. Agreement with magnetic resonance imaging measurements for volumes was reasonable but unsatisfactory for ejection fraction. Knowledge-based reconstruction may replace magnetic resonance imaging measurements for serial follow-up, whereas magnetic resonance imaging should be used for surgical decision making.

Transposition of the great arteries (TGA) is generally repaired using the arterial switch operation (ASO) involving coronary transfer. The objective of this prospective study was to determine whether specific coronary Doppler patterns intra-operatively predicted adverse early myocardial events.Patients 3 months old with TGA undergoing the ASO were eligible. All patients (when feasible) underwent an intra-operative transoesophageal echo (TEE) plus an epicardial echo and had pre-op, early post-op, pre-discharge and follow-up functional echocardiograms. The primary endpoint was a composite myocardial ischaemic event (any of: post-operative ST changes, ventricular tachycardia, need for extracorporeal membrane oxygenation (ECMO). Associations of coronary Doppler flow patterns with outcomes were modelled with logistic regression models. From May 2009 to December 2012, 40 patients (29 male, birth weight 3.29 ± 0.58 kg) were recruited. n = 32 had TEE + epicardial, four TEE only, four epicardial only. Seven (18%) patients had an adverse myocardial event (five ST changes, two ventricular tachycardia (one also ECMO). There was one death. n = 3 had a coronary artery (CA) revision post-operatively, and three had re-operation for non-CA causes. By TEE, flow reversal in the left coronary artery was associated with the composite endpoint [Odds Ratio (OR) 31.5, P = 0.004], and for chest open 3 days (OR 6.67, P = 0.0537). Coronary Doppler flow patterns were similar by TEE and epicardial echo. The tissue Doppler parameters showed an early post-op decrease (P 0.001 for all measures), with full recovery at follow-up in 31/37 cases.Intra-operative evaluation of coronary artery flow patterns should be considered for patients undergoing the ASO.

Chemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. We have previously shown that the chemokine (C-X-C motif) ligand 13 (CXCL13) regulates small leucine-rich proteoglycans (SLRPs). We hypothesized that chemokines are upregulated in the pressure-overloaded RV, and that they regulate SLRPs. Mice with RV pressure overload following pulmonary banding (PB) had a significant increase in RV weight and an increase in liver weight after 1 wk. Microarray analysis (Affymetrix) of RV tissue from mice with PB revealed that CXCL10, CXCL6, chemokine (C-X3-C motif) ligand 1 (CX3CL1), chemokine (C-C motif) ligand 5 (CCL5), CXCL16, and CCL2 were the most upregulated chemokines. Stimulation of cardiac fibroblasts with these same chemokines showed that CXCL16 increased the expression of the four SLRPs: decorin, lumican, biglycan, and fibromodulin. CCL5 increased the same SLRPs, except decorin, whereas CX3CL1 increased the expression of decorin and lumican. CXCL16, CX3CL1, and CCL5 were also shown to increase the levels of glycosylated decorin and lumican in the medium after stimulation of fibroblasts. In the pressure-overloaded RV tissue, Western blotting revealed an increase in the total protein level of lumican and a glycosylated form of decorin with a higher molecular weight compared with control mice. Both mice with PB and patients with pulmonary stenosis had significantly increased circulating levels of CXCL16 compared with healthy controls measured by enzyme immunoassay. In conclusion, we have found that chemokines are upregulated in the pressure-overloaded RV and that CXCL16, CX3CL1, and CCL5 regulate expression and posttranslational modifications of SLRPs in cardiac fibroblasts. In the pressure-overloaded RV, protein levels of lumican were increased, and a glycosylated form of decorin with a high molecular weight appeared.

The objective of this study was to investigate mechanisms of exercise-induced pulmonary hypertension in patients with congenital cardiac septal defects. This was a randomized, placebo controlled, crossover drug trial in a single national pediatric cardiology centre that performs congenital cardiac defect surgery. There were 14 patients with cardiac septal defects and known exercise-induced pulmonary hypertension. The intervention consisted of 50 mg oral sildenafil versus placebo. Measurements included supine bicycle exercise echocardiography and oxygen uptake. The outcome measure was right-ventricular systolic pressure as estimated by Doppler tracings of tricuspid regurgitant jet as well as systolic and diastolic longitudinal myocardial velocities by color tissue Doppler echocardiography. Sildenafil did not change exercise right-ventricular systolic pressure during exercise; however, decreased systemic systolic pressure was seen. Enhanced biventricular longitudinal function with sildenafil compared with placebo was indicated by greater tissue Doppler velocities and displacement measurements during exercise. Finally, a less steep increase of right-ventricular pressure during exercise was associated with greater left-ventricular diastolic myocardial tissue Doppler velocity. Exercise-induced pulmonary hypertension in cardiac septal defects does not seem to have a pulmonary vasoconstrictive component, but it may be related to left-ventricular filling pressure. Furthermore, sildenafil improved biventricular systolic performance in this patient group, possibly related to decreased systemic afterload.

Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P < 0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (β= 0.9 ± 0.1; P < 0.001 and β= 1.3 ± 0.4; P < 0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (β= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

Systolic longitudinal myocardial function is important for cardiac ejection. Data describing hemodynamic determinants and the time course of myocardial longitudinal contraction as measured by tissue Doppler are lacking. Ten newborn pigs were used for invasive hemodynamic investigation. Tissue Doppler assessment of the lateral part of the mitral valve annulus during systole was performed during pharmacological modulation of inotropy, cardiac pacing, and modulations of loading conditions. The strongest association was found between peak systolic velocity (S') and peak systolic flow (PSF) and end-systolic pressure (ESP), respectively (β = 0.09 cm/mL, p < 0.001 and β = -0.07 cm/mL, p = 0.003). Displacement (D) was mostly influenced by stroke volume (SV) (β = 0.05 cm/mL, p < 0.001). Ejection time, SV, ESP, maximum first derivative of pressure (dP/dtmax), and PSF were all associated with S' and D under different states of hemodynamic modulation; however, the ratio between PSF and S', SV, and D were stable during hemodynamic modulations. Normalized cross correlations indicate that S' and D follow the same trajectory as flow and SV, respectively. In conclusion, this study provides validity of accounting systolic D in the long axis as the longitudinal contribution to SV and peak systolic tissue velocity as the longitudinal contribution to PSF.

Objective. The hypothesis was that the levels of circulating inflammatory mediators are related to the degree of volume and pressure stress on the pulmonary vasculature in children with congenital systemic to pulmonary shunts. Design. Prospective, cross-sectional study. Setting. Tertiary center covering all pediatric heart surgery and interventions in Norway. Patients. Seventy-four children, aged 0–12 years, admitted for surgical or interventional treatment of congenital systemic to pulmonary shunts. Outcome Measures. Plasma levels of eight mediators of vascular inflammation and endothelial activation, sampled from different vascular compartments. Results. Patients with the most pronounced pulmonary flow and pressure stress demonstrated no elevation of inflammatory mediator levels when compared with healthy controls. No pulmonary production or uptake of the measured markers was found. Hemodynamic explanatory factors showed weak correlations to the inflammatory marker levels by univariate analysis. Age was the only factor that significantly explained inflammatory response in the multivariate model. The presence of Down syndrome, irrespective of hemodynamic category, was associated with elevated plasma levels of soluble tumor necrosis factor receptor I, when controlling for age. Conclusions. Inflammatory mediators show no significant relationship to pulmonary hemodynamics in children with systemic to pulmonary shunts. Children with Down syndrome may have an increased inflammatory response.

Objectives. Abnormal right ventricular systolic pressure response (RVPR) during exercise has previously been demonstrated in patients with septal defects of the heart. Our study investigated whether moderate altitude affects RVPR and oxygen saturation during rest and exercise in patients with surgically closed septal defects. Design. Ten patients with surgically closed heart septal defects (six secundum atrial septal defects, four ventricular septal defects) were examined by cardiopulmonary exercise testing and by echocardiography at rest and during supine cycling at sea level. After 2 hours in a hypobaric chamber at 2500 m/8200 ft altitude, exercise echocardiography was repeated. Results. During sea level exercise four patients showed abnormal RVPR (>50 mm Hg). Acute hypoxic exposure led to right ventricular systolic pressure increase above 40 mm Hg in two patients. During altitude exercise seven patients showed abnormal RVPR. Average maximal right ventricular systolic pressure was 56.5 ± 12.7 mm Hg and average for the lowest oxygen saturation was 80.0 ± 5.7%. Two patients had simultaneous oxygen desaturation below 80% and right ventricular systolic pressure above 50 mm Hg. Conclusions. Moderate altitude affects right ventricular systolic pressure and oxygen saturation in adolescents with surgically closed ventricular or atrial septal defects. Moderate altitude may induce or aggravate abnormal RVPR and oxygen desaturation during exercise in these patients.

OBJECTIVE We examined inflammatory mediators in patients with pulmonary hypertension related to congenital systemic-to-pulmonary shunts and the change in these markers during treatment with bosentan. BACKGROUND Inflammatory mechanisms probably play a pathogenic role in idiopathic pulmonary arterial hypertension. Their involvement in pulmonary hypertension related to congenital systemic-to-pulmonary shunts is largely unknown. PATIENTS AND METHODS Plasma levels of several inflammatory mediators were determined by enzyme immunoassays in 14 children and adolescents with pulmonary hypertension related to congenital systemic-to-pulmonary shunts before and after 12 months treatment with bosentan, and compared with levels in 54 healthy controls. RESULTS The patients were characterized by increased plasma levels of von Willebrand factor ( approximately 2.5-fold), C-reactive protein ( approximately 3.5-fold), and soluble CD40 ligand ( approximately 2.5-fold) as compared with controls, representing markers of endothelial cell activation, systemic inflammation, and platelet-mediated inflammation, respectively. Patients also had significantly elevated plasma levels of osteoprotegerin ( approximately 1.6-fold). Within the study group, N-terminal pro-brain natriuretic peptide levels correlated significantly with the concentrations of C-reactive protein (r= 0.61, P < .027) and von Willebrand factor (r= 0.74, P= .004). Except for a decline in monocyte chemoattractant protein-1 and receptor activator of nuclear factor-kappaB ligand, bosentan therapy did not attenuate the systemic inflammation. CONCLUSION Children and adolescents with pulmonary hypertension related to congenital systemic-to-pulmonary shunts are characterized by enhanced systemic inflammation involving increased endothelial cell activation and platelet-mediated inflammation. These inflammatory responses seem essentially to be unmodified by bosentan, potentially representing new targets for therapy in this disorder.

Aim: This study audits the activity of the neonatal air transport team in Norway's two northernmost counties. Methods: Data on all air transports to or from the regional Neonatal Intensive Care (NICU) Unit within a 10-year period were collected. Results: Two hundred and thirty-eight acute transports were conducted during the study period; 169 referrals to the NICU and 69 transfers to national surgical and cardiac centres. Only 13 very low birth weight infants were transported; the in utero transport rate was 95% for this patient population. The adjusted risk of death and/or intracranial haemorrhage for outborn very low birth weight infants was five-fold increased compared to those not transported postnatally. Babies with congenital heart disease comprised the one-fourth of all transports. The long-term mortality was 14% for the whole study population, and 29% for infants with congenital heart disease. Only seven deaths (3.2%) were defined as being transport-related; death during or within 24 h after transport. However, preventable complications like temperature instability, hypoglycaemia and hypo-/hypercapnia occurred in 10–20% of all transports. Conclusion: The transport related mortality was low in this study, however very low birth weight infants and infants with major congenital heart disease showed a relatively poor outcome.

We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.

A technique that uses two-dimensional images to create a knowledge-based, three-dimensional model was tested and compared to magnetic resonance imaging.Measurement of right ventricular volumes and function is important in the follow-up of patients after pulmonary valve replacement. Magnetic resonance imaging is the gold standard for volumetric assessment. Echocardiographic methods have been validated and are attractive alternatives.Thirty patients with tetralogy of Fallot (25 ± 14 years) after pulmonary valve replacement were examined. Magnetic resonance imaging volumetric measurements and echocardiography-based three-dimensional reconstruction were performed. End-diastolic volume, end-systolic volume, and ejection fraction were measured, and the results were compared.Magnetic resonance imaging measurements gave coefficient of variation in the intraobserver study of 3.5, 4.6, and 5.3 and in the interobserver study of 3.6, 5.9, and 6.7 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively. Echocardiographic three-dimensional reconstruction was highly feasible (97%). In the intraobserver study, the corresponding values were 6.0, 7.0, and 8.9 and in the interobserver study 7.4, 10.8, and 13.4. In comparison of the methods, correlations with magnetic resonance imaging were r = 0.91, 0.91, and 0.38, and the corresponding coefficient of variations were 9.4, 10.8, and 14.7. Echocardiography derived volumes (mL/m(2)) were significantly higher than magnetic resonance imaging volumes in end-diastolic volume 13.7 ± 25.6 and in end-systolic volume 9.1 ± 17.0 (both P.05).The knowledge-based three-dimensional right ventricular volume method was highly feasible. Intra and interobserver variabilities were satisfactory. Agreement with magnetic resonance imaging measurements for volumes was reasonable but unsatisfactory for ejection fraction. Knowledge-based reconstruction may replace magnetic resonance imaging measurements for serial follow-up, whereas magnetic resonance imaging should be used for surgical decision making.

Data on myocardial response to exercise after pediatric heart transplant (HTx) are limited. In this study we used semi-supine bicycle ergometry (SSCE) stress echocardiography to evaluate left ventricular (LV) systolic and diastolic reserve in pediatric HTx recipients.Forty-three HTx patients and 23 controls underwent stepwise SSCE stress echocardiography. Color tissue Doppler imaging (TDI) peak systolic (s') and early diastolic (e') velocities in the LV lateral wall and basal septum, and LV peak global longitudinal and circumferential strain were measured at rest and during different stages of exercise. LV myocardial acceleration during isovolumic contraction (IVA) was measured at incremental heart rates (HRs) to determine the force-frequency relationship (FFR).At rest, compared with controls, HTx patients showed lower TDI velocities in the basal septum (s': 4.7 ± 1.1 vs 5.8 ± 0.8 cm/s, p = 0.002; e': 8.5 ± 2.1 vs 11.3 ± 1.7 cm/s, p0.001), whereas in the LV lateral wall only e' was lower (11.2 ± 2.6 vs 13.8 ± 2.3 cm/s, p0.001). LV IVA was not different between the groups (p = 0.10). LV peak global longitudinal strain was lower in HTx patients (18 ± 1.9% vs 20 ± 2.2%, p = 0.001), but peak circumferential strain was not different (p = 0.50). At peak, HR was lower in the HTx group (141 ± 12 vs 165 ± 15, p0.001), and all systolic and diastolic parameters, except circumferential strain, were lower in HTx recipients. When assessing the increase in TDI and strain values in relation to HR, the slopes were not significantly different between patients and controls.Despite resting differences in myocardial functional parameters, pediatric HTx recipients have preserved LV diastolic and systolic myocardial reserve in response to exercise.

We describe an infant with an atrioventricular septal defect and separate valvar orifices for the right and left ventricles, the so-called primum defect, who presented with serious pulmonary hypertension. Treatment with sildenafil was changed to intravenous epoprostenol due to lack of any measurable effects of the initial therapy as shown by echocardiography. The girl died three days after the change in treatment. We suggest that a mismatch between ventilation and perfusion contributed significantly to her death.

One of the major challenges in numerical simulation of hydraulic systems, is the long computation times of accumulators. In wind power applications, the accumulators must provide necessary hydraulic energy during emergency stops, while the weight of hydraulic equipment must be minimized. Therefore, precise and efficient design tools for accumulators are essential. This paper addresses the issue of understanding the dynamic phenomena in piston type accumulators, and how this leads to improved numerical accumulator models. Developing a numerical model has two challenges. First, the unsteady heat transfer between the accumulator gas and the wall has to be described. Secondly, a suitable real gas model has to be identified and employed. To verify the model, a series of experiments were conducted at Fritz Schur Energy in Glostrup, Denmark. The experiments were designed to investigate gas dynamical properties at various precharge pressures, maximum pressures, and ambient temperatures. These parameters were varied to obtain parameter independent conclusions. During controlled piston movements, hydraulic and gas pressures were measured together with the piston position and the gas temperature. It was found that the simple thermal time constant approximation by Rotthauser was suitable and stable for the application. It was also found that the Soave-Redlich-Kwong equation was overall best suited with experimental data. The Soave-Redlich-Kwong equation is as much as six times faster than the widely used Benedict-Webb-Rubin equation, independent of the ambient temperature, maximum pressure and precharge pressure. This project concludes that the Soave-Redlich-Kwong equation should be used in simulation of piston type accumulators. It is noted that the pressure available after expansion is some 5-10 bar lower than predicted by any model. Therefore, it is suggested that more research is conducted to obtain an improved model for the heat transfer. Finally, measurement quality was confirmed by comparing measured pressure data by pressure calculations based on measured temperature.

Patients with congenital heart disease and univentricular circulation are vulnerable to ventricular dysfunction. In the context of atrioventricular conduction defects, a ventricular pacemaker may be placed, possibly introducing dyssynchronous wall motion and deterioration of ventricular pump function. We describe such a case in which repositioning of the ventricular lead restored synchronicity.

Acceleration has been measured both noninvasively and invasively, during both isovolumic contraction and early ejection and has been shown to reflect contractility, especially through correlation with dP/dt(max) . In this study timing and amplitude of mitral valve annulus acceleration assessed by tissue Doppler were measured and related to diastolic and systolic events. Invasive load independent measures of contractility, based on pressure-volume relationships, were derived, and pacing was done to modulate and control heart rate. Peak systolic acceleration (pSac) of the mitral valve annulus was shown to occur slightly later but timely related to dP/dt(max) (P0.05), while peak preejection acceleration (pPac) was related to diastolic events. During inotropy and preload modulation dP/dt(max) was found to be the strongest determinant of pSac (β= 0.9 ± 0.1; P0.001 and β= 1.3 ± 0.4; P0.001, respectively, log-transformed variables). PSac increased with pacing at a higher rate (β= 0.1 ± 0.0 cm/sec(2), P = 0.03). Furthermore, pSac indexed to end-diastolic volume (EDV) was linearly correlated to load independent contractility parameters (E(max), R = 0.7; ESPVR, R = 0.7; and PRSW, R = 0.5), and proved stable toward changes in preload and afterload. The relation between dP/dt(max)/EDV and pSac/EDV was stable throughout the study. In conclusion we found that peak systolic longitudinal acceleration (pSac) of the mitral valve annulus during aortic valve opening is strongly associated with dP/dt(max). Indexed to EDV, pSac may represent a load independent noninvasive contractility parameter. We consider pSac a candidate marker of long-axis contractility which should be viewed upon as the long-axis contribution to dP/dt(max).

The hypothesis was that the levels of circulating inflammatory mediators are related to the degree of volume and pressure stress on the pulmonary vasculature in children with congenital systemic to pulmonary shunts.Prospective, cross-sectional study.Tertiary center covering all pediatric heart surgery and interventions in Norway.Seventy-four children, aged 0-12 years, admitted for surgical or interventional treatment of congenital systemic to pulmonary shunts.Plasma levels of eight mediators of vascular inflammation and endothelial activation, sampled from different vascular compartments.Patients with the most pronounced pulmonary flow and pressure stress demonstrated no elevation of inflammatory mediator levels when compared with healthy controls. No pulmonary production or uptake of the measured markers was found. Hemodynamic explanatory factors showed weak correlations to the inflammatory marker levels by univariate analysis. Age was the only factor that significantly explained inflammatory response in the multivariate model. The presence of Down syndrome, irrespective of hemodynamic category, was associated with elevated plasma levels of soluble tumor necrosis factor receptor I, when controlling for age.Inflammatory mediators show no significant relationship to pulmonary hemodynamics in children with systemic to pulmonary shunts. Children with Down syndrome may have an increased inflammatory response.

Abnormal right ventricular systolic pressure response (RVPR) during exercise has previously been demonstrated in patients with septal defects of the heart. Our study investigated whether moderate altitude affects RVPR and oxygen saturation during rest and exercise in patients with surgically closed septal defects.Ten patients with surgically closed heart septal defects (six secundum atrial septal defects, four ventricular septal defects) were examined by cardiopulmonary exercise testing and by echocardiography at rest and during supine cycling at sea level. After 2 hours in a hypobaric chamber at 2500 m/8200 ft altitude, exercise echocardiography was repeated.During sea level exercise four patients showed abnormal RVPR (50 mm Hg). Acute hypoxic exposure led to right ventricular systolic pressure increase above 40 mm Hg in two patients. During altitude exercise seven patients showed abnormal RVPR. Average maximal right ventricular systolic pressure was 56.5 ± 12.7 mm Hg and average for the lowest oxygen saturation was 80.0 ± 5.7%. Two patients had simultaneous oxygen desaturation below 80% and right ventricular systolic pressure above 50 mm Hg.Moderate altitude affects right ventricular systolic pressure and oxygen saturation in adolescents with surgically closed ventricular or atrial septal defects. Moderate altitude may induce or aggravate abnormal RVPR and oxygen desaturation during exercise in these patients.

Our study investigated the abnormal right ventricular systolic pressure response (RVPR) in young patients with isolated atrial septal defect (ASD) or ventricular septal defect (VSD). An abnormal RVPR >50 mm Hg during exercise has been identified as a precursor of pulmonary artery hypertension. The present study included a population-based selection of 44 patients (age 13 to 25 years) with either isolated VSD (n = 27) or ASD (n = 17) and without right ventricular outflow tract obstruction. Of the 44 defects, 28 had been surgically closed (17 ASDs and 11 VSDs); 16 minor VSDs were untreated. Cardiovascular exercise testing and echocardiography at rest and during exercise were performed for all patients and 88 healthy controls. The aerobic capacity was significantly reduced in all patient groups (open VSD, closed VSD, closed ASD). The measurements of right ventricular performance were significantly lower in patients with closed ASD or closed VSD compared to those of the controls and patients with open VSD. Finally, 5% of the controls, no patient with ASD, and 9 patients with VSD (33%), regardless of defect closure, had an abnormal RVPR during exercise. In conclusion, 1/3 of young patients with isolated VSD had an abnormal RVPR during exercise.

Meticulous preoperative planning is an important part of any surgery to achieve high levels of precision and avoid complications. Conventional medical 2D images and their corresponding three-dimensional (3D) reconstructions are the main components of an efficient planning system. However, these systems still use flat screens for visualisation of 3D information, thus losing depth information which is crucial for 3D spatial understanding. Currently, cutting-edge mixed reality systems have shown to be a worthy alternative to provide 3D information to clinicians. In this work, we describe development details of the different steps in the workflow for the clinical use of mixed reality, including results from a qualitative user evaluation and clinical use-cases in laparoscopic liver surgery and heart surgery. Our findings indicate a very high general acceptance of mixed reality devices with our applications and they were consistently rated high for device, visualisation and interaction areas in our questionnaire. Furthermore, our clinical use-cases demonstrate that the surgeons perceived the HoloLens to be useful, recommendable to other surgeons and also provided a definitive answer at a multi-disciplinary team meeting.