Multimodal Characterization of the Atrial Substrate - Risks and Rewards of Electrogram and Impedance Mapping

The treatment of atrial rhythm disorders such as atrial fibrillation has remained a major challenge predominantly for patients with severely remodeled substrate. Individualized ablation strategies beyond pulmonary vein isolation in combination with real-time assess- ment of ablation lesion formation have been striven for insistently. Current approaches for identifying arrhythmogenic regions predominantly rely on electrogram-based features such as activation time and voltage or electrogram fractionation as a surrogate for tissue pathology. Despite bending every effort, large-scale clinical trials have yielded ambiguous results on the efficacy of various substrate mapping approaches without significant improvement of patient outcomes. This work focuses on enhancing the understanding of electrogram features and local impedance measurements in the atria towards the extraction of clinically relevant and predic- tive substrate characteristics. Features were extracted from intra-atrial electrograms with particular reference to the un- derlying excitation patterns to address morphological alterations caused by structural and functional changes. The noise level of unipolar electrograms was estimated and reduced by tailored filtering to enhance unipolar signal quality. Electrogram features exhibited nar- row distributions for healthy substrate across patients while a wide range was observed for pathologically altered excitation. Additionally, local impedance was investigated as a novel parameter and mapping modality. Having been introduced to the medical device market recently for monitoring ablative lesion formation, initial clinical experiences with local impedance-enabled catheters lack comple- mentary systematic investigations. Confounding factors and the potential for application as a tool for substrate mapping need elucidation. This work pursued a trimodal approach combining in human, in vitro, and in silico experiments to quantitatively understand the effect of distinct ambient conditions on the measured local impedance. Forward simulations of the spread of the electrical field with a finite element approach as well as the application of inverse solution methods to reconstruct tissue conductivity were implemented in silico. Adequate preprocessing steps were developed for measurements in human to eliminate artefacts automatically. Two clinical studies on local impedance as an indicator for ablation lesion formation and on local impedance based substrate mapping were conducted. Local impedance recordings identified both previously ablated and native scar areas irrespective of local excitation. A highly detailed in silico environment for local impedance measurements was validated with in vitro recordings and provided quantitative insights into the influence of changes in clinically relevant scenarios. Inverse reconstruction of relative tissue conductivity yielded promising results in silico. This work demonstrates that local impedance mapping shows great potential to comple- ment electrogram-based substrate mapping. A validated in silico environment for local impedance measurements can facilitate and optimize the development of next generation local impedance-enabled catheters. Conduction velocity, electrogram features, and recon- structed tissue conductivity suggest to be promising candidates for enhancing future clinical mapping systems

Quantitative assessment of ventricular far field removal techniques for clinical unipolar electrograms

The incidence of atrial tachycardia steadily increases in industrial nations. During invasive electrophysiological studies, a cathetermeasureselectrograms within the atrium to assist detailed diagnosis and treatment planning. With unipolar and bipolar electrograms, two different acquisition modes are clinically available.Unipolar electrograms have several advantages over bipolarelectrograms. However, unipolar electrograms are more affected by noise and the ventricular far field. Therefore, only bipolar electrograms are typicallyused in clinical settings.A recently published ventricular far field removal technique models the ventricular far field by a set of dipoles and yieldedpromising results in a simulation study.However, the method lacks quantitative clinical validation.Therefore, we adapted thetechnique to clinical needsand applied it todatasetsoftwo patientsusing four different lengths of the removal window.Results were compared quantitatively by a tailored residual error measure.The used method resulted in a median reduction of the ventricular far field by approximately89% using a removal window of optimal length forbothpatients.The results showedthatthe dipole methodprovides an alternative to other VFF removal techniques in clinical practice because itcan reveal AA originally hidden by VFF without leading to a prolongation of the electrophysiological study

Separating atrial near fields and atrial far fields in simulated intra-Atrial electrograms

The detailed characterization of complex forms of atrial flutter relies on the correct interpretation of intra-atrial electrograms. For this, the near fieldcomponents, which represent the local electrical activity, are decisive. However, far field components arising from distant electrical sources in the atria can obscure the diagnosis.We developed a method to separate and characterize atrial near field and atrial far field components from bipolar intra-atrial electrograms. First, a set of bipolar electrograms was created by simulating different propagation scenarios representing common clinical depolarizationpatterns. Second, near and far fields were detected as active segments usinga non-linear energy operator-based approach. Third, the maximum slope and the spectralpower were extracted as features for all active segments. Active segments were grouped accounting for both the timing and the location of their occurrence. In a last step, the active segments were classified in near and far fields by comparing their feature values to a threshold.All active segments were detected correctly. On average, near fields showed 15.1x larger maximum slopes and 40.4x larger spectral powers above 100 Hz than far fields. For 135 active segments detected in 72 bipolar electrograms, 5.2% and 6.7% were misclassified using the maximum slope and the spectral power, respectively. All active segments were classified correctly if only one near field segment was assumed to occur per electrogram.The separation of atrial near andatrial far fields was successfully developed and applied to in silico electrograms.Theseinvestigations providea promising basis fora future clinical study to ultimatelyfacilitatethe precise clinical diagnosis of atrial flutter

Improving Clinical ECG-based Atrial Fibrosis Quantification With Neural Networks Through in silico P waves From an Extensive Virtual Patient Cohort

Fibrotic atrial cardiomyopathy is characterized by a replacement of healthy atrial tissue with diffuse patches exhibiting slow electrical conduction properties and altered myocardial tissue structure, which provides a substrate for the maintenance of reentrant activity during atrial fibrillation (AF). Therefore, an early detection of atrial fibrosis could be a valuable risk marker for new-onset AF episodes to select asymptomatic subjects for screening, allowing for timely intervention and optimizing therapy planning. We examined the potential of estimating the fibrotic tissue volume fraction in the atria based on P waves of the 12-lead ECG recorded in sinus rhythm in a quantitative and noninvasive way. Our dataset comprised 68,282 P waves from healthy subjects and 42,227 P waves from AF patients with low voltage areas in the atria, as well as 642,400 simulated P waves of a virtual cohort derived from statistical shape models with different extents of the left atrial myocardium replaced by fibrosis. The root mean squared error for estimating the left atrial fibrotic volume fraction on a clinical test set with a neural network trained on features extracted from simulated and clinical P waves was 16.57 %. Our study shows that the 12-lead ECG contains valuable information on atrial tissue structure. As such it could potentially be employed as an inexpensive and widely available tool to support AF risk stratification in clinical practic

In Silico Study of Local Electrical Impedance Measurements in the Atria - Towards Understanding and Quantifying Dependencies in Human

Background: Electrical impedance measurements have become an accepted tool for monitoring intracardiac radio frequency ablation. Recently, the long-established generator impedance was joined by novel local impedance measurement capabilities with all electrical circuit terminals being accommodated within the catheter. Objective: This work aims at in silico quantification of distinct influencing factors that have remained challenges due to the lack of ground truth knowledge and the superposition of effects in clinical settings. Methods: We introduced a highly detailed in silico model of two local impedance enabled catheters, namely IntellaNav MiFi™ OI and IntellaNav Stablepoint™, embedded in a series of clinically relevant environments. Assigning material and frequency specific conductivities and subsequently calculating the spread of the electrical field with the finite element method yielded in silico local impedances. The in silico model was validated by comparison to in vitro measurements of standardized sodium chloride solutions. We then investigated the effect of the withdrawal of the catheter into the transseptal sheath, catheter-tissue interaction, insertion of the catheter into pulmonary veins, and catheter irrigation. Results: All simulated setups were in line with in vitro experiments and in human measurements and gave detailed insight into determinants of local impedance changes as well as the relation between values measured with two different devices. Conclusion: The in silico environment proved to be capable of resembling clinical scenarios and quantifying local impedance changes. Significance: The tool can assists the interpretation of measurements in humans and has the potential to support future catheter development

Effect of Contact Force on Local Electrical Impedance in Atrial Tissue - an In Silico Evaluation

Regions with pathologically altered substrate have been identified as potential drivers for atrial fibrillation (AF) maintenance. Recently, local impedance (LI) measurements have gained attention as surrogate for atrial substrate assessment as it does not rely on electrical activity of the heart. However, an appropriate electrode-tissue contact force (CF) is needed and its effect on the LI measurements has not yet been characterized in depth. In this study, we applied several CF to a catheter in contact with a tissue patch modeled as healthy and scar atrial myocardium whose thickness was varied in anatomical ranges to study the impact of the mechanical deformation the LI measurements. When applying CF between 0 and 6 g, in silico LI ranged from 160 Ω to 175 Ω in healthy myocardium, whereas 148 Ω and 151 Ω for scar tissue. Increasing CF in scar tissue up to 25 g, increased LI up to 156 Ω. The model was validated against clinically measured LI at different CF from AF patients. Simulation results applying identical CF in both tissues yielded lower LI values in scar. Moreover, LI increased in healthy and scar tissue when the thickness and CF were increased. Given the results of our study, we conclude that in silico experiments can not only distinguish between healthy and scar tissue by combining CF and LI, but also that our simulation environment represents clinical LI measurements with and without mechanical deformation in a tissue model

Local Electrical Impedance Mapping of the Atria: Conclusions on Substrate Properties and Confounding Factors

The treatment of atrial fibrillation and other cardiac arrhythmias as a major cause of cardiovascular hospitalization has remained a challenge predominantly for patients with severely remodeled substrate. Individualized ablation strategies are extremely important both for pulmonary vein isolation and subsequent ablations. Current approaches to identifying arrhythmogenic regions rely on electrogram-based features such as activation time and voltage. Novel technologies now enable clinical assessment of the local impedance as tissue property. Previous studies demonstrated its use for ablation monitoring and indicated its potential to differentiate healthy substrate, scar, and pathological tissue. This study investigates the potential of local electrical impedance-based substrate mapping of the atria for human in-vivo data. The presented pipeline for impedance mapping particularly contains options for dealing with undesirable effects originating from cardiac motion, catheter motion, or proximity to other intracardiac devices. Bloodpool impedance was automatically determined as a patient-specific reference. Full-chamber, left atrial impedance maps were drawn up from interpolating the measured impedances to the atrial endocardium. Finally, the origin and magnitude of oscillations of the raw impedance recording were probed into. The most dominant reason for exclusion of impedance samples was the loss of endocardial contact. With median elevations above the bloodpool impedance between 29 and 46 Ω, the impedance within the pulmonary veins significantly exceeded the remaining atrial walls presenting median elevations above the bloodpool impedance between 16 and 20 Ω. Previous ablation lesions were distinguished from their surroundings by a significant drop in local impedance while the corresponding regions did not differ for the control group. The raw impedance was found to oscillate with median amplitudes between 6 and 17 Ω depending on the patient. Oscillations were traced back to an interplay of atrial, ventricular, and respiratory motion. In summary, local impedance measurements demonstrated their capability to distinguish pathological atrial tissue from physiological substrate. Methods to limit the influence of confounding factors that still hinder impedance mapping were presented. Measurements at different frequencies or the combination of multiple electrodes could lead to further improvement. The presented examples indicate that electrogram- and impedance-based substrate mapping have the potential to complement each other toward better patient outcomes in future

The Oceanographer transform fault revisited - preliminary results from a micro-seismicity survey reveals extensional tectonics at ridge-transform intersections

European Geosciences Union (EGU) General Assembly, 23-27 May 2022, Vienna, AustriaFracture zones were recognized to be an integral part of the seabed long before plate tectonics was established. Later, plate tectonics linked fracture zones to oceanic transform faults, suggesting that they are the inactive and hence fossil trace of transforms. Yet, scientist have spent little time surveying them in much detail over the last three decades. Recent evidence (Grevemeyer, I., Rüpke, L.H., Morgan, J.P., Iyer, K, and Devey, C.W., 2021, Extensional tectonics and two-stage crustal accretion at oceanic transform faults, Nature, 591, 402–407, doi:10.1038/s41586-021-03278-9) suggests that the traditional concept of transform faults as being conservative (non-accretionary) plate boundary faults might be wrong. Instead, transform faults are always deeper than the associated fracture zones and numerical modelling results suggest that transform faults seem to suffer from extensional tectonics below their strike-slip surface fault zone. During the cruise M170 of the German research vessel METEOR early in 2021, we aimed to test this hypothesis by collecting, in a pilot study, micro-seismicity data from the Oceanographer transform fault which offsets the Mid-Atlantic Ridge by 120-km south of the Azores near 35°N. Preliminary analysis of 10-days of seismicity data recorded at 26 ocean-bottom-seismometers and hydrophones showed 10-15 local earthquakes per day. Along the transform fault the distribution of micro-earthquakes and focal mechanisms support strike-slip motion. However, at both ridge-transform intersections seismicity does not mimic a right-angular plate boundary; instead, seismicity occurs below the inside corner and focal mechanism indicate extensional tectonics. Therefore, micro-seismicity supports features found in numerical simulations, revealing that transform faults have an extensional as well as a strike-slip componentPeer reviewe