Search

Abstract: Nanowire gas sensors show high sensitivity towards various gases and offer great potential to improve present gas sensing. In this work, we investigate experimental results achieved with an undoped single SnO2 nanowire sensor device for CO pulses in N2 atmosphere at different operating temperatures. We calculated the reaction parameters according to the mass action law including frequency factors, activation energies, and numbers of intrinsic as well as extrinsic surface sites. With the values obtained, we then calculated the surface charge of the nanowire sensor by solving the corresponding differential equations. The simulated results agree very well with the experimental values at an operating temperature of 200¡C and hence provide good understanding of the chemical reaction. This can be used to simulate the current through the transducer and consequently the sensitivity of the device, and the parameters provided here are useful for computational procedures to provide selectivity. [Copyright &y& Elsevier]

Unlabelled: We report three children, one presenting with nephropathy, bilateral Wilms tumour (WT) and cryptorchism, one with combined nephropathy and gonadal dysgenesis and one with nephropathy which developed 13 years after a WT. The first case was recognized as typical Denys-Drash syndrome (DDS) which is characterized by the combination of nephropathy, intersex disorders and WT. The two other patients, who did not express the full spectrum of the syndrome, were older than 10 years, when they reached and stage renal failure. The fact that nephropathy in childhood is combined with such rare diseases like gonadal dysgenesis and/or WT, supports the concept of a common aetiology with DDS. Therefore, the patients were analysed for possible Wilms tumour suppressor gene (WT1) mutations. In all three individuals mutations in the heterozygous configuration could be demonstrated.Conclusion: These results provide evidence that incomplete and complete DDS are diseases of the same spectrum. WT1 analysis of more children with two symptoms of the triad of DDS should be helpful in establishing genotype-phenotype correlations and in understanding differences in the clinical picture of DDS. [ABSTRACT FROM AUTHOR]

To generate normal charts of fetal cardiac inflow velocities and to assess physiologic changes of ventricular diastolic function, velocity waveforms of tricuspid and mitral valves were studied longitudinally in 49 fetuses in 4 week intervals from 14 weeks gestation to term. Doppler tracings were analyzed for: peak early (E) and peak late (A) inflow velocities, time velocity integral (TVI) of total inflow and A-wave velocity waveforms and heart rate corrected isovolemic relaxation time. E- and A-velocity as well as total- and A-wave-TVI of both valves increased significantly with gestational age (P < 0.001). Heart rate and A/E ratio decreased significantly with gestational age (P < 0.001). The ratio of A-wave TVI to total TVI of both valves and heart rate corrected isovolemic relaxation time (IVR) was constant suggesting unchanged diastolic function. This study provides normal charts for fetal cardiac inflow velocities. After 14 weeks of gestation all inflow velocities and their respective TVI's increased linearly in the growing fetal heart. There was evidence that diastolic function did not change. Area ratios and IVR should be used to determine changes in ventricular diastolic function, rather than velocity ratios. [ABSTRACT FROM AUTHOR]

The mortality and morbidity of children with pulmonary atresia/intact ventricular septum (PA/IVS) are linked to the degree of right ventricular (RV) hypoplasia. Opening up the pulmonary valve (PV) in fetal life could result in improved growth of the R V making it amenable to biventricular repair postnatally. Successful valvulotomy of the PV was performed in a fetus with heart failure at 28 weeks. Following the procedure there was significant growth of the tricuspid valve and RV. The neonate was delivered at 38 weeks with a RV suitable for biventricular repair. In utero pulmonary valvulotomy is feasible and may change the natural history of the condition in affected fetuses with PA/IVS. [ABSTRACT FROM AUTHOR]

Background: Children with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development., Objectives: This work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1-8 years with complex CHD., Methods: PubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted., Results: Thirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs., Conclusions: Data on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Hofer, Blum, Wiltsche, Deluggi, Holzinger, Fellinger, Tulzer, Blum and Oberhuber.)

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV., (© 2024. The Author(s).)

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: In 2020, reports revealed cases called multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 or multisystem inflammatory syndrome in children. A small proportion of patients suffer from persistent left ventricular dysfunction at discharge. The primary aim was to investigate if myocardial impairment persists during follow-up in these patients., Methods: Children fulfilling the criteria for multisystem inflammatory syndrome in children with cardiac involvement hospitalized between December 2020 and February 2022 were included in this retrospective single centre study. Cardiac MRI was performed six months after the onset of symptoms to evaluate possible persistent myocardial damage., Results: Fifteen patients (80% male) with a median age of 8 years (interquartile range 4.5 - 13.5 years) were included. Upon admission, eight patients (53%) presented with reduced left ventricular function, with a median left ventricular ejection fraction of 54% (interquartile range 49.5%-61.5%) on transthoracic echocardiography. Elevated levels of cardiac-specific markers were found in 14 patients (93%). Cardiac MRI was performed in 12 patients at a median of 190.5 days after the onset of symptoms. Nine patients (75%) had normal left ventricular function, with a median left ventricular ejection fraction of 59.45%, while the remaining patients showed mildly to moderately reduced values. None of the patients showed signs of late gadolinium enhancement, indicating the absence of persistent myocardial scarring., Conclusion: During a follow-up of 6.2 months, mild to moderate cardiac impairment was revealed in 25% of patients evaluated by cardiac MRI. Although a majority of patients do not show signs of cardiac impairment, close follow-ups should be performed in a proportion of patients.

Lymphatic flow disorders are rare but devastating complications in children with congenital heart disease. T2-weighted magnetic resonance lymphography and intranodal dynamic contrast magnetic resonance lymphangiography are imaging modalities that can depict central lymphatic anatomy and flow pattern. Our objective was to describe the technical aspects and our imaging findings of central lymphatic abnormalities and their impact on patient management and outcomes: We conducted a retrospective review of 26 children with congenital heart disease who presented for lymphatic imaging between 2015 and 2020 at our institution. Eleven had postoperative chylothorax, six had plastic bronchitis, seven had protein-losing enteropathy and three had Noonan syndrome. Our lymphatic imaging demonstrated severely abnormal lymphatic flow in all of the children, but only minor abnormalities in protein-losing enteropathy. No major procedure-related complication occurred. Lymphatic interventions were performed in six patients, thoracic duct decompression in two patients and chylothorax revision in three patients. This led to symptomatic improvements in all of the patients: Lymphatic imaging is safe and essential for the diagnosis of lymphatic flow disorders and therapy planning. Our intranodal lymphangiography depicts an abnormal lymphatic flow pattern from the central lymphatics but failed to demonstrate an abnormal lymphatic flow in protein-losing enteropathy. These imaging techniques are the basis for selective lymphatic interventions, which are promising to treat lymphatic flow disorders.

The lymphatic system plays a central role in some of the most devastating complications associated with congenital heart defects. Diseases like protein-losing enteropathy, plastic bronchitis, postoperative chylothorax, and chylous ascites are now proven to be lymphatic in origin. Novel imaging modalities, most notably, noncontrast magnetic resonance lymphangiography and dynamic contrast-enhanced magnetic resonance lymphangiography, can now depict lymphatic anatomy and function in all major lymphatic compartments and are essential for modern therapy planning. Based on the new pathophysiologic understanding of lymphatic flow disorders, innovative minimally invasive procedures have been invented during the last few years with promising results. Abnormal lymphatic flow can now be redirected with catheter-based interventions like thoracic duct embolization, selective lymphatic duct embolization, and liver lymphatic embolization. Lymphatic drainage can be improved through surgical or interventional techniques such as thoracic duct decompression or lympho-venous anastomosis., (© 2023 The Author(s).)

Fetuses with critical aortic stenosis (FAS) are at high risk of progression to HLHS by the time of birth (and are thus termed "evolving HLHS"). An in-utero catheter-based intervention, fetal aortic valvuloplasty (FAV), has shown promise as an intervention strategy to circumvent the progression, but its impact on the heart's biomechanics is not well understood. We performed patient-specific computational fluid dynamic (CFD) simulations based on 4D fetal echocardiography to assess the changes in the fluid mechanical environment in the FAS left ventricle (LV) directly before and 2 days after FAV. Echocardiograms of five FAS cases with technically successful FAV were retrospectively analysed. FAS compromised LV stroke volume and ejection fraction, but FAV rescued it significantly. Calculations to match simulations to clinical measurements showed that FAV approximately doubled aortic valve orifice area, but it remained much smaller than in healthy hearts. Diseased LVs had mildly stenotic mitral valves, which generated fast and narrow diastolic mitral inflow jet and vortex rings that remained unresolved directly after FAV. FAV further caused aortic valve damage and high-velocity regurgitation. The high-velocity aortic regurgitation jet and vortex ring caused a chaotic flow field upon impinging the apex, which drastically exacerbated the already high energy losses and poor flow energy efficiency of FAS LVs. Two days after the procedure, FAV did not alter wall shear stress (WSS) spatial patterns of diseased LV but elevated WSS magnitudes, and the poor blood turnover in pre-FAV LVs did not significantly improve directly after FAV. FAV improved FAS LV's flow function, but it also led to highly chaotic flow patterns and excessively high energy losses due to the introduction of aortic regurgitation directly after the intervention. Further studies analysing the effects several weeks after FAV are needed to understand the effects of such biomechanics on morphological development., (© 2023. The Author(s).)

Background: Echocardiographic quantification of fetal cardiac strain is important to evaluate function and the need for intervention, with both two-dimensional (2D) and three-dimensional (3D) strain measurements currently feasible. However, discrepancies between 2D and 3D measurements have been reported, the etiologies of which are unclear. This study sought to determine the etiologies of the differences between 2D and 3D strain measurements., Methods: A validated cardiac motion-tracking algorithm was used on 3D cine ultrasound images acquired in 26 healthy fetuses. Both 2D and 3D myocardial strain quantifications were performed on each image set for controlled comparisons. Finite element modeling of 2 left ventricle (LV) models with minor geometrical differences were performed with various helix angle configurations for validating image processing results., Results: Three-dimensional longitudinal strain (LS) was significantly lower than 2D LS for the LV free wall and septum but not for the right ventricular (RV) free wall, while 3D circumferential strain (CS) was significantly higher than 2D CS for the LV, RV, and septum. The LS discrepancy was due to 2D long-axis imaging not capturing the out-of-plane motions associated with LV twist, while the CS discrepancy was due to the systolic motion of the heart toward the apex that caused out-of-plane motions in 2D short-axis imaging. A timing mismatch between the occurrences of peak longitudinal and circumferential dimensions caused a deviation in zero-strain referencing between 2D and 3D strain measurements, contributing to further discrepancies between the 2., Conclusions: Mechanisms for discrepancies between 2D and 3D strain measurements in fetal echocardiography were identified, and inaccuracies associated with 2D strains were highlighted. Understanding of this mechanism is useful and important for future standardization of fetal cardiac strain measurements, which we propose to be important in view of large discrepancies in measured values in the literature., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Fetuses with critical aortic stenosis, severe mitral regurgitation and left atrial enlargement are at risk to develop heart failure and intrauterine death. We present two cases with this physiology who underwent fetal aortic balloon valvuloplasty at 25 + 5 and 28 + 2 weeks as their only intervention without requiring postnatal treatment during short- to medium-term follow-up of 1.4 and 4.9 years.

Children with hypoplastic left heart syndrome share unique hemodynamic features that alter lymphatic integrity at all stages of palliation. Lymphatic congestion is almost universal in this patient group to some extent. It may lead to reversal of lymphatic flow, the development of abnormal lymphatic channels and ultimately decompression and loss of protein rich lymphatic fluid into extra lymphatic compartments in prone individuals. Some of the most devastating complications that are associated with single ventricle physiology, notably plastic bronchitis and protein losing enteropathy, have now been proven to be lymphatic in origin. Based on the new pathophysiologic concept new diagnostic and therapeutic strategies have recently been developed. Dynamic contrast magnetic resonance lymphangiography is now mainstay in diagnosis of lymphatic insufficiency and allows a thorough assessment of anatomy and function of the main lymphatic compartments through intranodal, intrahepatic and intramesenteric lymphatic imaging. Contrast enhanced ultrasound can evaluate thoracic duct patency and conventional fluoroscopic lymphangiography has been refined for evaluation of patients where magnetic resonance imaging cannot be performed. Novel lymphatic interventional techniques, such as thoracic duct embolization, selective lymphatic duct embolization and liver lymphatic embolization allow to seal abnormal lymphatic networks minimally invasive and have shown to resolve symptoms. Innominate vein turn-down procedures, whether surgical or interventional, have been designed to reduce lymphatic afterload and increase systemic preload effectively in the failing Fontan circulation. Outflow obstruction can now be managed with new microsurgical techniques that create lympho-venous anastomosis. Short term results for all of these new approaches are overall promising but evidence is sparse and long-term outcome still has to be defined. This review article aims to summarize current concepts of lymphatic flow disorders in single ventricle patients, discuss new emerging diagnostic and therapeutic strategies and point out lacks in evidence and needs for further research on this rapidly growing topic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bauer, Dori, Scala, Tulzer and Tulzer.)

Objective: Tetralogy of Fallot patients with pulmonary atresia (TOFPA) have a largely varying source of pulmonary perfusion with often hypoplastic and even absent central pulmonary arteries. A retrospective single center study was undertaken to assess outcome of these patients regarding type of surgical procedures, long-term mortality, achievement of VSD closure and analysis of postoperative interventions., Methods: 76 consecutive patients with TOFPA operated between 01.01.2003 and 31.12.2019 are included in this single center study. Patients with ductus dependent pulmonary circulation underwent primary single stage full correction including VSD closure and right ventricular to pulmonary conduit implantation (RVPAC) or transanular patch reconstruction. Children with hypoplastic pulmonary arteries and MAPCAs without double supply were predominantly treated by unifocalization and RVPAC implantation. The follow up period ranges between 0 and 16,5 years., Results: 31 patients (41%) underwent single stage full correction at a median age of 12 days, 15 patients could be treated by a transanular patch. 30 days mortality rate in this group was 6%. In the remaining 45 patients the VSD could not be closed during their first surgery which was performed at a median age of 89 days. A VSD closure was achieved later in 64% of these patients after median 178 days. 30 days mortality rate after the first surgery was 13% in this group. The estimated 10-year-survival rate after the first surgery is 80,5% ± 4,7% showing no significant difference between the groups with and without MAPCAs ( p  > 0,999). Median intervention-free interval (surgery and transcatheter intervention) after VSD closure was 1,7 ± 0,5 years [95% CI: 0,7-2,8 years]., Conclusions: A VSD closure could be achieved in 79% of the total cohort. In patients without MAPCAs this was possible at a significant earlier age ( p  < 0,01). Although patients without MAPCAs predominantly underwent single stage full correction at newborn age, the overall mortality rate and the interval until reintervention after VSD closure did not show significant differences between the two groups with and without MAPCAs. The high rate of proven genetic abnormalities (40%) with non-cardiac malformations did also pay its tribute to impaired life expectancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sames-Dolzer, Fahrnberger, Kreuzer, Mair, Gierlinger, Tulzer, Gitter, Prandstetter, Tulzer and Mair.)

In cases of fetal aortic stenosis and evolving Hypoplastic Left Heart Syndrome (feHLHS), aortic stenosis is associated with specific abnormalities such as retrograde or bidirectional systolic transverse arch flow. Many cases progressed to hypoplastic left heart syndrome (HLHS) malformation at birth, but fetal aortic valvuloplasty can prevent the progression in many cases. Since both disease and intervention involve drastic changes to the biomechanical environment, in-vivo biomechanics likely play a role in inducing and preventing disease progression. However, the fluid mechanics of feHLHS is not well-characterized. Here, we conduct patient-specific echocardiography-based flow simulations of normal and feHLHS left ventricles (LV), to understand the essential fluid dynamics distinction between the two cohorts. We found high variability across feHLHS cases, but also the following unifying features. Firstly, feHLHS diastole mitral inflow was in the form of a narrowed and fast jet that impinged onto the apical region, rather than a wide and gentle inflow in normal LVs. This was likely due to a malformed mitral valve with impaired opening dynamics. This altered inflow caused elevated vorticity dynamics and wall shear stresses (WSS) and reduced oscillatory shear index at the apical zone rather than mid-ventricle. Secondly, feHLHS LV also featured elevated systolic and diastolic energy losses, intraventricular pressure gradients, and vortex formation numbers, suggesting energy inefficiency of flow and additional burden on the LV. Thirdly, feHLHS LV had poor blood turnover, suggesting a hypoxic environment, which could be associated with endocardial fibroelastosis that is often observed in these patients., (© 2022. The Author(s).)