Heart ventricular activation in VAT difference maps from children with chronic kidney disease

Children with chronic kidney disease (CKD) are affected by cardiovascular complications, including disturbances in the intraventricular conduction system. Body surface potential mapping (BSPM) is a non-invasive method of assessing the cardioelectrical field. Our aim was to investigate conduction disturbances in young CKD patients using ventricular activation time (VAT) maps. Our study comprised 22 CKD children (mean age: 13.1 ± 2.5 years) treated conservatively and 29 control patients. For each child 12-lead electrocardiogram (ECG) readings were taken, and blood pressure and serum concentrations of iPTH, Pi, t-Ca, creatinine, Fe+3, ferritin, and Hb, as well as eGFR were measured. All children underwent registration in the 87-lead BSPM system, and group-mean VAT maps and a difference map, which presents statistically significant differences between the groups, were created. The VAT map distribution in CKD patients revealed abnormalities specific to left anterior fascicle block. The difference map displays the areas of intergroup VAT changes, which are of discriminative value in detecting intraventricular conduction disturbances. Intraventricular conduction impairments in the left bundle branch may occur in children with CKD. BSPM enables conduction disturbances in CKD children to be detected earlier than using 12-lead ECG. The difference map derived from the group-mean isochrone maps precisely localizes the sites of disturbed conduction in the heart intraventricular conduction system

A 50% Reduction of Excitability but Not of Intercellular Coupling Affects Conduction Velocity Restitution and Activation Delay in the Mouse Heart

Computer simulations suggest that intercellular coupling is more robust than membrane excitability with regard to changes in and safety of conduction. Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by approximately 50%. In this retrospective study we assessed the effect of reduced membrane excitability or intercellular coupling on conduction in mouse models of reduced excitability or intercellular coupling. Epicardial activation mapping of LV and RV was performed on Langendorff-perfused mouse hearts having the following: 1) Reduced excitability: Scn5a haploinsufficient mice; and 2) reduced intercellular coupling: Cx43(CreER(T)/fl) mice, uninduced (50% Cx43) or induced (10% Cx43) with Tamoxifen. Wild type (WT) littermates were used as control. Conduction velocity (CV) restitution and activation delay were determined longitudinal and transversal to fiber direction during S(1)S(1) pacing and S(1)S(2) premature stimulation until the effective refractory period. In both animal models, CV restitution and activation delay in LV were not changed compared to WT. In contrast, CV restitution decreased and activation delay increased in RV during conduction longitudinal but not transverse to fiber direction in Scn5a heterozygous animals compared to WT. In contrast, a 50% reduction of intercellular coupling did not affect either CV restitution or activation delay. A decrease of 90% Cx43, however, resulted in decreased CV restitution and increased activation delay in RV, but not LV. Reducing excitability but not intercellular coupling by 50% affects CV restitution and activation delay in RV, indicating a higher safety factor for intercellular coupling than excitability in R

Noninvasive mapping of repolarization:Validation in healthy and diseased hearts

The initiation and maintenance of (reentrant) arrhythmias is facilitated by local heterogeneities in cardiac activation and repolarization. Detection of these heterogeneities by cardiac mapping is important for guiding local therapy and for early risk stratification of patients, and is presently mostly performed by invasive techniques. A non-invasive method for localization of functional heterogeneities may help the treatment of patients with life threatening ventricular arrhythmias, may support risk stratification and may help to reduce mortality caused by these arrhythmias. This thesis investigates a non-invasive method to determine and localize functional repolarization heterogeneities based on potentials measured at the body surface. It demonstrates that parameters that highlight multiple repolarization moments in the standard 12-lead ECG, better characterize the underlying repolarization gradient than the single time point of latest global repolarization (QTtime). For further localization of possible heterogeneities, this thesis uses the equivalent dipole layer (EDL) method for the solution of the inverse problem of electrocardiography; the mathematical reconstruction of cardiac electrical activity from body surface electrograms and a geometric model of the torso. The accuracy was investigated in in-silico, ex-vivo, and in-vivo settings, showing good correlations with gold standard repolarization times, even in the presence of noise, abnormal repolarization or myocardial infarction. In addition, comparison of the EDL method with the more commonly used epicardial potential (EP) method shows that both methods provide accurate reconstruction of cardiac activation and repolarization patterns and beat origins, with the EDL method showing a better correlation for activation timings and beat origins than the EP method. Although the use of this technique for noninvasive mapping of repolarization is promising, we provide directions for future research to improve accuracy of inverse reconstruction

The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail

BACKGROUND: Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail. RESULTS: GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user-friendly graphical user interface. GEMS is implemented using MATLAB®, which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite). CONCLUSIONS: This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping

Recombinant human collagen-based microspheres mitigate cardiac conduction slowing induced by adipose tissue-derived stromal cells

Background Stem cell therapy to improve cardiac function after myocardial infarction is hampered by poor cell retention, while it may also increase the risk of arrhythmias by providing an arrhythmogenic substrate. We previously showed that porcine adipose tissue-derived-stromal cells (pASC) induce conduction slowing through paracrine actions, whereas rat ASC (rASC) and human ASC (hASC) induce conduction slowing by direct coupling. We postulate that biomaterial microspheres mitigate the conduction slowing influence of pASC by interacting with paracrine signaling. Aim To investigate the modulation of ASC-loaded recombinant human collagen-based microspheres, on the electrophysiological behavior of neonatal rat ventricular myocytes (NRVM). Method Unipolar extracellular electrograms, derived from microelectrode arrays (8x8 electrodes) containing NRVM, co-cultured with ASC or ASC loaded microspheres, were used to determine conduction velocity (CV) and conduction heterogeneity. Conditioned medium (Cme) of (co)cultures was used to assess paracrine mechanisms. Results Microspheres did not affect CV in control (NRVM) monolayers. In co-cultures of NRVM and rASC, hASC or pASC, CV was lower than in controls (14.4+/-1.0, 13.0+/-0.6 and 9.0+/-1.0 vs. 19.5+/-0.5 cm/s respectively, p Conclusion The application of recombinant human collagen-based microspheres mitigates indirect paracrine conduction slowing through interference with a secondary autocrine myocardial factor

Software design for analysis of multichannel intracardial and body surface electrocardiograms

Analysis of multichannel ECG recordings (body surface maps (BSMs) and intracardial maps) requires special software. We created a software package and a user interface on top of a commercial data analysis package (MATLAB) by a combination of high-level and low-level programming. Our software was created to satisfy the needs of a diverse group of researchers. It can handle a large variety of recording configurations. It allows for interactive usage through a fast and robust user interface, and batch processing for the analysis of large amounts of data. The package is user-extensible, includes routines for both common and experimental data processing tasks, and works on several computer platforms. The source code is made intelligible using software for structured documentation and is available to the users. The package is currently used by more than ten research groups analysing ECG data worldwide. (C) 2002 Elsevier Science Ireland Ltd. All rights reserve

Harmonizing Heartbeats: A translational approach towards preventing life-threatening ventricular arrhythmias

Cardiovascular diseases remain a leading cause of mortality worldwide, with sudden cardiac death, characterized by ventricular arrhythmias such as ventricular tachycardia (VT) or ventricular fibrillation (VF), being a significant contributor due to its abrupt onset and frequency. The Implantable Cardioverter-Defibrillator (ICD) stands as a crucial intervention to detect and terminate these life-threatening arrhythmias. While studies have demonstrated the survival benefits of ICD therapy, it does not address the underlying causes of arrhythmias and is associated with psychological challenges and reduced quality of life for recipients. Ideally, the ICD would not only terminate existing arrhythmias but also predict and prevent future occurrences, allowing for preemptive therapies like accelerated pacing. Short-Term Variability of Repolarization (STV) emerged as a potential predictive parameter for ventricular arrhythmias, reflecting the repolarization reserve of the heart. Understanding the protective effect of accelerated pacing on arrhythmia onset is crucial before implementing STV-guided pacing to prevent arrhythmias. This thesis focuses on improving the treatment of life-threatening ventricular arrhythmias by translating preclinical findings into clinical applications. Preclinical investigations utilized two animal models: the chronic atrioventricular block (CAVB) dog model and the ischemic pig model. These models elucidated the antiarrhythmic mechanisms of accelerated pacing and tested the feasibility of STV-guided pacing through ICDs to prevent arrhythmias. Additionally, methods for automatically measuring STV in ICDs were explored in both animal models. Clinical studies aimed to translate preclinical findings to human patients, examining changes in STV preceding spontaneous ventricular arrhythmias in ICD patients. The potential of pacing to reduce STV and the performance of an automatic STV algorithm on human signals measured with an ICD lead were evaluated. The preclinical section focused on the CAVB dog model and demonstrated that Torsade de Pointes (TdP) arrhythmias could be induced reproducibly, offering insights into new antiarrhythmic strategies. The increase in STV before TdP onset and its reduction during accelerated pacing suggested its potential as a predictive marker for pacing guidance. Moreover, research in the ischemic pig model underscored the importance of STV as a predictor of ventricular arrhythmias, highlighting the potential for automatic monitoring of arrhythmia risk through ICDs and other cardiac devices. In the clinical section, Holter registrations in ICD patients revealed an increase in STV preceding ventricular arrhythmias, validating its role as a predictive marker. Development of methods to automatically measure STV in intracardiac electrogram signals showed promise for clinical use, demonstrating reliability and the potential to guide pacing interventions effectively. In conclusion, STV emerges as a promising marker for monitoring impending ventricular arrhythmias through ICDs, offering avenues for preventive interventions like accelerated pacing. This represents a significant advancement in ICD therapies, providing personalized approaches to prevent life-threatening arrhythmias. This thesis contributes to a deeper understanding of the complex mechanisms behind ventricular arrhythmias and proposes innovative, personalized clinical approaches to prevent them