Electrocardiogram Signal Analysis and Simulations for Non-Invasive Diagnosis - Model-Based and Data-Driven Approaches for the Estimation of Ionic Concentrations and Localization of Excitation Origins

Das Elektrokardiogramm (EKG) ist die Standardtechnik zur Messung der elektrischen Aktivität des Herzens. EKG-Geräte sind verfügbar, kostengünstig und erlauben zudem eine nichtinvasive Messung. Das ist insbesondere wichtig für die Diagnose von kardiovaskulären Erkrankungen (KVE). Letztere sind mit verursachten Kosten von 210 Milliarden Euro eine der Hauptbelastungen für das Gesundheitssystem in Europa und dort der Grund für 3,9 Millionen Todesfälle – dies entspricht 45% aller Todesfälle. Neben weiteren Risikofaktoren spielen chronische Nierenerkrankungen und strukturelle Veränderungen des Herzgewebes eine entscheidende Rolle für das Auftreten von KVE. Deshalb werden in dieser Arbeit zwei Pathologien, die in Verbindung zu KVE stehen, betrachtet: Elektrolytkonzentrationsveränderungen bei chronisch Nierenkranken und ektope Foki, die autonom Erregungen iniitieren. In beiden Projekten ist die Entwicklung von Methoden mithilfe von simulierten Signalen zur Diagnoseunterstützung das übergeordnete Ziel. Im ersten Projekt helfen simulierte EKGs die Signalverarbeitungskette zur EKG-basierten Schätzung der Ionenkonzentrationen von Kalium und Calcium zu optimieren. Die Erkenntnisse dieser Optimierung fließen in zwei patienten-spezifische Methoden zur Kaliumkonzentrationsschätzung ein, die wiederum mithilfe von Patientendaten ausgewertet werden. Die Methoden lieferten im Mittel einen absoluten Fehler von 0,37 mmol/l für einen patienten-spezifischen Ansatz und 0,48 mmol/l für einen globalen Ansatz mit zusätzlicher patienten-spezifischer Korrektur. Die Vorteile der Schätzmethoden werden gegenüber bereits existierender Ansätze dargelegt. Alle entwickelten Algorithmen sind ferner unter einer Open-Source-Lizenz veröffentlicht. Das zweite Projekt zielte auf die Lokalisierung von ektopen Foki mithilfe des EKGs ohne die Nutzung der individuellen Patientengeometrie. 1.766.406 simulierte EKG-Signale (Body Surface Potential Maps (BSPMs)) wurden zum Trainieren von zwei Convolutional Neural Networks (CNNs) erzeugt. Das erste CNN sorgt für die Schätzung von Anfang und Ende der Depolarisation der Ventrikel. Das zweite CNN nutzt die Information der Depolarisation im BSPM zur Schätzung des Erregungsurpsrungs. Der spezielle Aufbau des CNNs ermöglicht die Darstellung mehrerer Lösungen, wie sie durch Mehrdeutigkeiten im BSPM vorliegen können. Der kleinste Median des Lokalisierungsfehlers lag bei 1,54 mm für den Test-Datensatz der simulierten Signale, bzw. bei 37 mm für Patientensignale. Somit erlaubt die Kombination beider CNNs die verlässliche Lokalisierung von ektopen Foki auch anhand von Patientendaten, obwohl Patientendaten vorher nicht im Training genutzt wurden. Die Resultate dieser zwei Projekte demonstrieren, wie EKG-Simulationen zur Entwicklung und Verbesserung von EKG-Signalverarbeitungsmethoden eingesetzt werden und bei der Diagnosefindung helfen können. Zudem zeigt sich das Potential der Kombination von Simulationen und CNNs, um einerseits die zumeist raren klinischen Signale zu ersetzen und andererseits Modelle zu finden, die für mehrere Patienten/-innen gültig sind. Die vorgestellten Methoden bergen die Möglichkeit, die Diagnosestellungen zu beschleunigen und mit hoher Wahrscheinlichkeit den Therapieerfolg der Patienten zu verbessern

Non-invasive Localization of the Ventricular Excitation Origin Without Patient-specific Geometries Using Deep Learning

Ventricular tachycardia (VT) can be one cause of sudden cardiac death affecting 4.25 million persons per year worldwide. A curative treatment is catheter ablation in order to inactivate the abnormally triggering regions. To facilitate and expedite the localization during the ablation procedure, we present two novel localization techniques based on convolutional neural networks (CNNs). In contrast to existing methods, e.g. using ECG imaging, our approaches were designed to be independent of the patient-specific geometries and directly applicable to surface ECG signals, while also delivering a binary transmural position. One method outputs ranked alternative solutions. Results can be visualized either on a generic or patient geometry. The CNNs were trained on a data set containing only simulated data and evaluated both on simulated and clinical test data. On simulated data, the median test error was below 3mm. The median localization error on the clinical data was as low as 32mm. The transmural position was correctly detected in up to 82% of all clinical cases. Using the ranked alternative solutions, the top-3 median error dropped to 20mm on clinical data. These results demonstrate a proof of principle to utilize CNNs to localize the activation source without the intrinsic need of patient-specific geometrical information. Furthermore, delivering multiple solutions can help the physician to find the real activation source amongst more than one possible locations. With further optimization, these methods have a high potential to speed up clinical interventions. Consequently they could decrease procedural risk and improve VT patients' outcomes.Comment: 14 pages, 9 figures. Abstract was shortened for arXi

Effects of Serum Calcium Changes on the Cardiac Action Potential and the ECG in a Computational Model

Patients suffering from end stage of chronic kid ney disease (CKD) often undergo haemodialysis to normaliz the electrolyte concentrations. Moreover, cardiovascula disease (CVD) is the main cause of death in CKD patients To study the connection between CKD and CVD, we investi gated the effects of an electrolyte variation on cardiac signal (action potential and ECG) using a computational model. In first step, simulations with the Himeno et al. ventricular cel model were performed on cellular level with different extra cellular sodium ([Na+]o), calcium ([Ca2+]o) and potassium ([K+]o) concentrations as occurs in CKD patients. [Ca2+]o an [K+]o changes caused variations in different features describ ing the morphology of the AP. Changes due to a [Na+]o varia tion were not as prominent. Simulations with [Ca2+]o varia tions were also carried out on ventricular ECG level and 12-lead ECG was computed. Thus, a multiscale simulato from ion channel to ECG reproducing the calcium-dependen inactivation of ICaL was achieved. The results on cellular an ventricular level agree with results from literature. Moreover we suggest novel features representing electrolyte change that have not been described in literature. These results coul be helpful for further studies aiming at the estimation of ioni concentrations based on ECG recordings

Structural and electrophysiological determinants of atrial cardiomyopathy identify remodeling discrepancies between paroxysmal and persistent atrial fibrillation

Background: Progressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency. Methods: Consecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency. Results: In training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm$^2$) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study. Conclusion: Among 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF

Mechano‐electrical interactions and heterogeneities in wild‐type and drug‐induced long QT syndrome rabbits

Electromechanical reciprocity – comprising electro-mechanical (EMC) and mechano-electric coupling (MEC) – provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions – such as (drug-induced) acquired long QT syndrome (aLQTS) – might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC in vivo, we used tissue phase mapping cardiac MRI and a 24-lead ECG vest in healthy (control) and IKr-blocker E-4031-induced aLQTS rabbit hearts. MEC was studied in vivo by acutely increasing cardiac preload, and ex vivo by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT-interval, RTn370) was prolonged compared to control (P < 0.0001) with increased spatial and temporal RT heterogeneity (P < 0.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico-basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (P < 0.0001). Additionally, regional RT-dispersion increased in aLQTS. Motion-correction allowed us to determine APD-prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload-changes prevented a clear analysis of MEC ex vivo. Mechano-induced RT-prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT-related arrhythmogenesis, warranting further mechanistic investigations

Polarized blazar X-rays imply particle acceleration in shocks

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier1,2,3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI