Development of an AI based automated analysis of pediatric Apple Watch iECGs.

Introduction: The Apple Watch valuably records event-based electrocardiograms (iECG) in children, as shown in recent studies by Paech et al. In contrast to adults, though, the automatic heart rhythm classification of the Apple Watch did not provide satisfactory results in children. Therefore, ECG analysis is limited to interpretation by a pediatric cardiologist. To surmount this difficulty, an artificial intelligence (AI) based algorithm for the automatic interpretation of pediatric Apple Watch iECGs was developed in this study. Methods: A first AI-based algorithm was designed and trained based on prerecorded and manually classified i.e., labeled iECGs. Afterward the algorithm was evaluated in a prospectively recruited cohort of children at the Leipzig Heart Center. iECG evaluation by the algorithm was compared to the 12-lead-ECG evaluation by a pediatric cardiologist (gold standard). The outcomes were then used to calculate the sensitivity and specificity of the Apple Software and the self-developed AI. Results: The main features of the newly developed AI algorithm and the rapid development cycle are presented. Forty-eight pediatric patients were enrolled in this study. The AI reached a specificity of 96.7% and a sensitivity of 66.7% for classifying a normal sinus rhythm. Conclusion: The current study presents a first AI-based algorithm for the automatic heart rhythm classification of pediatric iECGs, and therefore provides the basis for further development of the AI-based iECG analysis in children as soon as more training data are available. More training in the AI algorithm is inevitable to enable the AI-based iECG analysis to work as a medical tool in complex patients.

Effects of combined drought and pathogen stress on growth, resistance and gene expression in young Norway spruce trees.

Drought-induced mortality is a major direct effect of climate change on tree health, but drought can also affect trees indirectly by altering their susceptibility to pathogens. Here, we report how a combination of mild or severe drought and pathogen infection affected the growth, pathogen resistance and gene expression in potted 5-year-old Norway spruce trees [Picea abies (L.) Karst.]. After 5 weeks of drought, trees were inoculated with the fungal pathogen Endoconidiophora polonica. Combined drought-pathogen stress over the next 8 weeks led to significant reductions in the growth of drought-treated trees relative to well-watered trees and more so in trees subjected to severe drought. Belowground, growth of the smallest fine roots was most affected. Aboveground, shoot diameter change was most sensitive to the combined stress, followed by shoot length growth and twig biomass. Both drought-related and some resistance-related genes were upregulated in bark samples collected after 5 weeks of drought (but before pathogen infection), and gene expression levels scaled with the intensity of drought stress. Trees subjected to severe drought were much more susceptible to pathogen infection than well-watered trees or trees subjected to mild drought. Overall, our results show that mild drought stress may increase the tree resistance to pathogen infection by upregulating resistance-related genes. Severe drought stress, on the other hand, decreased tree resistance. Because drought episodes are expected to become more frequent with climate change, combined effects of drought and pathogen stress should be studied in more detail to understand how these stressors interactively influence tree susceptibility to pests and pathogens.

Into the Blue: First in Man Data on Diving Physiology in Fontan Patients.

Swimming and diving are popular recreational activities. As congenital heart disease, especially patients with univentricular hearts after Fontan palliation are thought to have reduced physiologic capacities for compensation of submersion-associated physiologic demands, current guidelines put restraints on this group of patients. Although these restrictions on doctoral advice place a significant burden on affected patients, it is especially interesting that these guideline recommendations are merely based on physiologic assumptions, i.e., expert consensus. A recent study by Paech et al. presented the first in vivo data on the effects of immersion in Fontan patients, stating no major adverse events in their study group as well as comparable physiologic adaption as reported in the literature for healthy people. Yet, submersion was not reflected in this study, and the current study therefore aimed to conduct a first study for the evaluation of the effects of submersion and apnea diving in Fontan patients. A control group of healthy adults as well as patients recruited from the Heart Center Leipzig, Department of pediatric cardiology underwent a standardized diving protocol including a static as well as dynamic apnea phase. Physiologic data were recorded. This study presents the first structured data on diving physiology in Fontan patients compared to healthy probands. There were no adverse events. The physiologic response to diving seems to be comparable between healthy probands and Fontan patients. Although, healthy probands did reach a much better performance, the basic mechanisms of physiologic adaption seem comparable.

Accuracy of the Apple Watch Oxygen Saturation Measurement in Adults and Children with Congenital Heart Disease.

As new customer health devices have been spread throughout the consumer market in recent years, it now needs to be evaluated if they also fulfill the requirements of clinical use. The Apple Watch Series 6 provides a new health feature with its oxygen saturation measurement. The aim of this prospective, investigator-initiated, single-arm study was to compare transcutaneous oxygen saturation measurements using the Apple Watch 6 with the conventional method of pulse oximetry in patients with congenital heart disease. Patients of any age presenting at the Leipzig Heart Center, Department for pediatric cardiology, were included. After obtaining informed consent, the routine oxygen saturation measurement with the pulse oximeter was taken and simultaneously three measurements with the Apple Watch. A total of 508 patients were enrolled. Comparing children and adults in terms of measurement success shows a statistically significant difference with a higher proportion of unsuccessful measurements in children, but no difference concerning correct versus incorrect Apple Watch measurements. Noticeable, strapping on the watch properly around the patient's wrists significantly improved the measurements compared to a watch only laid on. The study demonstrated that oxygen saturation measurement with the Apple Watch 6 is not yet up to the medical standard of pulse oximetry, too large a proportion of the measurements remain either unsuccessful or incorrect. While a high proportion of unsuccessful measurements in children can be attributed to movement, the cause in adults usually remains unclear. Further influencing factors on a correct, or successful measurement could not be found.

Accuracy of the Apple Watch iECG in Children With and Without Congenital Heart Disease.

The development of smart technologies paves the way for new diagnostic modalities. The Apple Watch provides an FDA approved iECG function for users from 22 years of age. Yet, there are currently no data on the accuracy of the Apple Watch iECG in children. While arrhythmias are a frequent phenomenon in children, especially those with congenital heart disease, the increasing spread of smart watches provides the possibility to use a smart watch as mobile event recorder in case of suspected arrhythmia. This may help to provide valuable information to the treating physician, without having the patient to come to the hospital. Necessary treatment adjustments might be provided without timely delay. The aim of this study was therefore to evaluate the agreement of measured values of rate, interval, and amplitude with those obtained by a diagnostic quality ECG recording to an Apple Watch iECG in children with and without congenital heart disease. In this prospective, single-arm study, consecutive patients aged 0-16 years presenting to the Heart Center Leipzig, Department for pediatric cardiology were included. After obtaining informed consent from participants' parents, a 12-lead ECG and an iECG using an Apple Watch were performed. Cardiac rhythm was classified, amplitudes and timing intervals were measured and analyzed in iECG and 12-lead ECG for comparability. These measurements were performed blinded to the patients' history by two experienced pediatric cardiologists. Patient demographic data, medical and cardiac history were assessed. 215 children between 0 and 16 years were enrolled. Comparison of amplitudes and timing intervals between ECG and iECG showed excellent correlation (K > 0.7, p < 0.01) in all parameters except for the p-waves. Automatic rhythm classification was inferior to manual interpretation of ECG / iECG, while iECG interpretation was reliable in 94.86% of cases. The study demonstrates equal quality of the Apple Watch derived iECG compared to a lead I in 12-lead ECG in children of all age groups and independent from cardiac anatomy.

The Fontan and the Sea: First-in-Man Data on Swimming and Diving Physiology in Fontan Patients.

While swimming represents a popular recreational activity, the immersion of the human body into the water requires a complex physiologic adaption of the whole cardiopulmonary and circulatory system. While this sport is regarded as beneficial, especially in cardiovascular patients, current guidelines hypothesized a possible hazardous effect of swimming and especially diving in patients with univentricular hearts after Fontan palliation. Yet, actual data to underline or contradict these assumptions are lacking. Therefore, this study aimed to conduct a first feasibility study for the evaluation of these effects on Fontan physiology and elucidate the gap of evidence currently preventing patients after Fontan palliation from being restricted from swimming or diving on doctoral advice. Patients recruited from the Heart Center Leipzig, Department of pediatric cardiology, underwent spiroergometry treadmill testing followed by a spiroergometry swimming stress test in a counter current pool. Physiologic data were recorded. A short apnea diving test was performed. The current study found similar physiologic reactions comparing treadmill and swimming exercise stress testing. Heart rate response and oxygen uptake were comparable on land and in the water. This study presents the first-in-man data on swimming and diving in Fontan patients. In this small study cohort of three Fontan patients, there were no adverse events triggered by swimming and breath-hold diving seen. Basically, the physiologic response to exercise was comparable on land and in the water.

Drug-Induced Loss of Preexcitation in Pediatric Patients with WPW Pattern During Electrophysiologic Study.

Ablation of accessory pathways (AP) is one of the most often performed procedures in pediatric electrophysiology. In pediatric patients these procedures are mostly performed in anaesthesia or sedation. In some of these patients who are referred for electrophysiologic (EP) study, we could observe disappearance of the preexcitation, i.e. antegrade conduction of an AP during introduction of sedation. As a suppression of AP conduction capacities has been reported as negative side effect of propofol and other anaesthetics, the aim of this study was to evaluate risk factors for drug-induced suppression of AP conduction properties. Consecutive, pediatric patients with Wolff-Parkinson-White (WPW) pattern referred for EP study in the period of 2016-2017 were reviewed in retrospect. Patients with complex congenital heart disease were excluded. An entire chart review including ECG, bicycle stress testing, and periprocedural data was performed. In 4 of 37 patients included into the study, loss of preexcitation could be observed during sedation. Data analysis showed weaker conduction capacities of the AP as a risk factor (p = 0.009). Interestingly, absolute (p = 0.11) or adjusted to body weight (p = 0.92) drug doses were not a relevant risk factor. Patients with WPW and weaker conduction capacities of the AP, as implied by an early disappearance of preexcitation during exercise stress testing, seem to be more prone to drug-induced suppression of an AP.

Catheter ablation in ASymptomatic PEDiatric patients with ventricular preexcitation: results from the multicenter "CASPED" study.

BACKGROUND: As there are limited data about the clinical practice of catheter ablation in asymptomatic children and adolescents with ventricular preexcitation on ECG, we performed the multicenter "CASPED" (Catheter ablation in ASymptomatic PEDiatric patients with Ventricular Preexcitation) study. METHODS AND RESULTS: In 182 consecutive children and adolescents aged between 8 and 18 years (mean age 12.9 ± 2.6 years; 65% male) with asymptomatic ventricular preexcitation, a total of 196 accessory pathways (APs) were targeted. APs were right sided (62%) or left sided (38%). The most common right-sided AP location was the posteroseptal region (38%). Ablation was performed using radiofrequency (RF) energy (93%), cryoablation (4%) or both (3%). Mean procedure time was 137.6 ± 62.0 min with a mean fluoroscopy time of 15.6 ± 13.8 min. A 3D mapping or catheter localization system was used in 32% of patients. Catheter ablation was acutely successful in 166/182 patients (91.2%). Mortality was 0% and there were no major periprocedural complications. AP recurrence was observed in 14/166 patients (8.4%) during a mean follow-up time of 19.7 ± 8.5 months. A second ablation attempt was performed in 20 patients and was successful in 16/20 patients (80%). Overall, long-term success rate was 92.3%. CONCLUSION: In this retrospective multicenter study, the outcome of catheter ablation for asymptomatic preexcitation in children and adolescents irrespective of antegrade AP conduction properties is summarized. The complication rate was low and success rate was high, the latter mainly depending on pathway location. The promising results of the study may have future impact on the ongoing risk-benefit discussion regarding catheter ablation in the setting of asymptomatic preexcitation in children and adolescents.

Quantifying in situ phenotypic variability in the hydraulic properties of four tree species across their distribution range in Europe.

Many studies have reported that hydraulic properties vary considerably between tree species, but little is known about their intraspecific variation and, therefore, their capacity to adapt to a warmer and drier climate. Here, we quantify phenotypic divergence and clinal variation for embolism resistance, hydraulic conductivity and branch growth, in four tree species, two angiosperms (Betula pendula, Populus tremula) and two conifers (Picea abies, Pinus sylvestris), across their latitudinal distribution in Europe. Growth and hydraulic efficiency varied widely within species and between populations. The variability of embolism resistance was in general weaker than that of growth and hydraulic efficiency, and very low for all species but Populus tremula. In addition, no and weak support for a safety vs. efficiency trade-off was observed for the angiosperm and conifer species, respectively. The limited variability of embolism resistance observed here for all species except Populus tremula, suggests that forest populations will unlikely be able to adapt hydraulically to drier conditions through the evolution of embolism resistance.

Advanced capabilities for materials modelling with Quantum ESPRESSO.

Quantum EXPRESSO is an integrated suite of open-source computer codes for quantum simulations of materials using state-of-the-art electronic-structure techniques, based on density-functional theory, density-functional perturbation theory, and many-body perturbation theory, within the plane-wave pseudopotential and projector-augmented-wave approaches. Quantum EXPRESSO owes its popularity to the wide variety of properties and processes it allows to simulate, to its performance on an increasingly broad array of hardware architectures, and to a community of researchers that rely on its capabilities as a core open-source development platform to implement their ideas. In this paper we describe recent extensions and improvements, covering new methodologies and property calculators, improved parallelization, code modularization, and extended interoperability both within the distribution and with external software.

QRS Width as a Predictor of Right Ventricular Remodeling After Percutaneous Pulmonary Valve Implantation.

Recent data showed a right ventricular dyssynchrony in patients with tetralogy of Fallot (TOF). Percutaneous pulmonary valve implantation (PPVI) has become an important procedure to treat a pulmonary stenosis and/or regurgitation of the right ventricular outflow tract in these patients. Despite providing good results, there is still a considerable number of nonresponders to PPVI. The authors speculated that electrical dysfunction of the right ventricle plays an underestimated role in the outcome of patients after PPVI. This study aimed to investigate the influence of right ventricular electrical dysfunction, i.e., right bundle branch block (RBBB) on the RV remodeling after PPVI. The study included consecutive patients after correction of TOF with or without RBBB, who had received a PPVI previously at the Heart Center of the University of Leipzig, Germany during the period from 2012 to 2015. 24 patients were included. Patients without RBBB, i.e., with narrow QRS complexes pre-intervention, had significantly better RV function and had smaller right ventricular volumes. Patients with pre-interventionally QRS width below 150 ms showed a post-interventional remodeling of the right ventricle with the decreasing RV volumes (p = 0.001). The parameters of LV function and volume as well as RV ejection fraction remained unaffected by RBBB. The presented data indicate that the QRS width seems to be a valuable parameter in the prediction of right ventricular remodeling after PPVI, as it represents both electrical and mechanical functions of the right ventricle and may serve as an additional parameter for optimal timing of a PPVI.

Rate Control by Transoesophageal Atrial Overdrive Pacing for Refractory Supraventricular Tachycardia with Severe Ventricular Dysfunction: A Bridge to Recovery.

Tachyarrhythmia-induced cardiomyopathy (TIC) is a rare, yet life-threatening phenomenon in children. TIC has been defined as myocardial dysfunction that is entirely or partially reversible after control of the responsible tachyarrhythmia and is typically caused by an incessant supraventricular tachycardia. In cases of unsuccessful termination of the tachycardia, cardiogenic shock may occur. Several authors favour the use of mechanical circulatory support in such cases. Particularly with regard to these partly severe cases, the authors would like to present the option of transoesophageal overdrive pacing (TOP) as a tool for initial heart rate control and hemodynamic stabilization of patients with TIC refractory to conventional strategies of tachycardia termination. Chart review for patients receiving TOP during the last 5 years in two centres was performed. A case series of successful TOP including technique and outcomes is depicted. Rate control through TOP is a safe and effective option to restore acceptable hemodynamics in infants with refractory supraventricular tachycardia and severe impairment of ventricular function. It presents the possibility of immediate heart rate control and offers time for myocardial recovery and safe implementation of antiarrhythmic drug therapy.

Functional K-doping of eumelanin thin films: Density functional theory and soft x-ray spectroscopy experiments in the frame of the macrocyclic protomolecule model [corrected].

We demonstrate the possibility to achieve the doping of eumelanin thin films through K(+) incorporation during the electrodeposition of the film. K-doping changes the optical properties of the eumelanin thin films, reducing the energy gap from 1.0 to 0.6 eV, with possible implications for the photophysical properties. We have identified the doping-related occupied and unoccupied electronic states and their spectral weight using resonant photoemission spectroscopy (ResPES) and x-ray absorption at the C and N K-edges (near edge x-ray absorption fine spectroscopy, NEXAFS). All data are consistently interpreted by ab initio calculations of the electronic structure within the frame of the macrocycle model developed for the eumelanin protomolecule. Our analysis puts in evidence the intercalation of K with one specific oligomer (a tetramer composed of one indolequinone and 3 hydroquinone monomers) in correspondence of the nitrogen macrocycle. The predicted variation of the tetramer spacing is also in agreement with the recent x-ray diffraction experiments. The charge donation from K to N and C atoms gives rise to new electronic states at the top of the valence band and in NEXAFS resonances of the unoccupied orbitals. The saturation of the tetramer macrocycles leaves an excess of K that bind to N and C atoms in alternative configurations, as witnessed by the occurrence of additional spectral features in the carbon-related ResPES measurements.

Atrioventricular conduction time in fetuses assessed by Doppler echocardiography.

We performed measurement of mechanical atrioventricular conduction time intervals in human fetuses assessed by Doppler echocardiography and provided reference values. We found that atrioventricular conduction time interval was prolonged with gestational age and decreased with increasing fetal heart rate. No correlation between gestational age and heart rate was found. Using normal limits established by this study, mechanical atrioventricular interval >135 ms in the 20(th) week and/or >145 ms in the 26(th) week of gestation could be suspected of having the first-degree AV block. We compared reference values with fetuses of mothers with anti-SSA Ro/SSB La autoantibodies, being in risk of isolated congenital heart block development. One of 21 fetuses of mothers with positive autoantibodies was affected by prolonged atrioventricular interval according to the established limits, with sinus rhythm after the birth.

[Characteristics of gene pools of three Pinus pumila (Pall.) Regel populations at the range margins].

Genetic variation of Siberian dwarf pine Pinus pumila (Pall.) Regel was characterized in three marginal populations in southwestern, southern and eastern parts of the natural species range (Transbaikalia, Primorye, Kamchatka) using isozyme analysis. Analysis involving 16 isozyme loci encoding ten enzyme systems was conducted. Our results confirm that P. pumila is among the most polymorphic species in the family Pinus. Three marginal populations exhibited high genetic variation (P95 = 68.8%, Ho = 0.247, He = 0.291). Populations heterogeneity and significantly high level of divergence in coniferous (F(ST) = 0.050, D(N) = 0.044) reflect their genetic originality. In summary, it was shown that the level of genetic variation characteristic for P. pumila in other parts of the not only is reproduced in the populations examined but even is close to maximum there.

Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. OBJECTIVE: To record current practice and results of CRT in paediatric and congenital heart disease. DESIGN: Retrospective multicentre European survey. SETTING: Paediatric cardiology and cardiac surgery centres. PATIENTS: One hundred and nine patients aged 0.24-73.8 (median 16.9) years with structural congenital heart disease (n = 87), congenital atrioventricular block (n = 12) and dilated cardiomyopathy (n = 10) with systemic left (n = 69), right (n = 36) or single (n = 4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n = 25) or associated with pacing (n = 84). INTERVENTIONS: CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109). MAIN OUTCOME MEASURES: Functional improvement and echocardiographic change in systemic ventricular function. RESULTS: The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p<0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p<0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p<0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p = 0.002) and poor NYHA class (p = 0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p<0.001). Results were independent of the number of patients treated in each contributing centre. CONCLUSION: Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate.

Electronic excitations in synthetic eumelanin aggregates probed by soft X-ray spectroscopies.

Electronic excitations of condensed phase eumelanin aggregates are investigated with soft X-ray spectroscopies. Resonant photoemission data indicate that mechanisms of charge delocalization may occur when electrons are excited about 3 eV above the first unoccupied electronic level. An average, lower limit value of 1.6 fs was estimated for the lifetime of the excited C 1s-pi* states.

Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects.

The acute hemodynamic effect of atrioventricular (AV) and inter/intraventricular (IV) resynchronization accomplished by temporary pacing using multiple epicardial pacing wires was evaluated in 20 children (aged 3.4 months to 14.0 years) after surgery for congenital heart defects fulfilling the following criteria: (1) presence of AV and/or IV conduction delay, and (2) need for inotropic support. AV resynchronization (n = 13) was achieved by AV delay optimization during atrial synchronous right ventricular outflow tract pacing. IV resynchronization (n = 14) was accomplished by atrial synchronous pacing from the right ventricular lateral wall in 7 patients with right bundle branch block and normal AV conduction and by atrial synchronous multisite ventricular pacing in another 7 patients with previously performed AV resynchronization. Compared with baseline values, AV resynchronization resulted in an increase in arterial systolic, mean, and pulse pressures by 7.2 +/- 8.3% (p <0.01), 8.6 +/- 8.1% (p <0.005), and 6.9 +/- 13.5% (p = NS), respectively. IV resynchronization used either alone or added to previously performed AV resynchronization led to a pressure increase of 7.0 +/- 4.7%, 5.9 +/- 4.7%, and 9.4 +/- 7.8%, respectively (p <0.001 for all). The combined effect of AV and IV resynchronization resulted in a systolic, mean, and pulse pressure increase of 10.2 +/- 5.0% (range 4.0 to 19.1), 8.6 +/- 5.4% (range 0.8 to 14.8), and 15.2 +/- 8.5% (range 6.1 to 33.3), respectively (p <0.001 for all). The increase in systolic arterial pressure after IV resynchronization was positively correlated with the initial QRS duration (r = 0.62, p <0.05) and extent of QRS shortening (r = 0.66, p <0.05). In conclusion, resynchronization pacing led to a significant increase in arterial blood pressure and was a useful adjunct to the treatment of acute postoperative heart failure in patients with AV and/or IV conduction delay.

[Aortic reconstruction in neonates with hypoplastic left heart syndrome] . / Rekonstrukce aorty u novorozencu se syndromem hypoplastického levého srdce.

The surgical technique and tactics of the Norwood operation in neonates with hypoplastic left heart syndrome represent a surgical challenge. The Norwood operation was performed from the midline sternotomy approach, in extracorporeal circulation and deep hypothermic circulatory arrest was used for reconstruction of the hypoplastic aorta. Operation consisted of reconstruction of the "neoaorta" and the aortic arch from the original hypoplastic ascendent aorta, pulmonary trunk and a patch cut from a pulmonary homograft or pericardium, excision of the atrial septum and an arterial shunt from a Goretex vascular graft 3.5 or 4 mm in diameter. In patients with well developed aortic arch it was possible to reconstruct the aorta using Damus-Kaye-Stansel operation without circulatory arrest. Out of 12 operated patients with this defect, two (16.7%) died during the early postoperative period, one patient died late. The postoperative course was often complicated. In 6 (50.0%) patients the second step of Norwood operation, the bidirectional cavopulmonary anastomosis, was performed without mortality. According to our experience, it was necessary to prepare patients adequately before the first surgery. Perfect reconstruction of the aorta and a well functioning shunt had the crucial significance.