10 research outputs found
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
Comparison of Propagation Models and Forward Calculation Methods on Cellular, Tissue and Organ Scale Atrial Electrophysiology
The bidomain model and the finite element method are an established standard to mathematically describe cardiac electrophysiology, but are both suboptimal choices for fast and large-scale simulations due to high computational costs. We investigate to what extent simplified approaches for propagation models (monodomain, reaction-Eikonal and Eikonal) and forward calculation (boundary element and infinite volume conductor) deliver markedly accelerated, yet physiologically accurate simulation results in atrial electrophysiology. Methods: We compared action potential durations, local activation times (LATs), and electrocardiograms (ECGs) for sinus rhythm simulations on healthy and fibrotically infiltrated atrial models. Results: All simplified model solutions yielded LATs and P waves in accurate accordance with the bidomain results. Only for the Eikonal model with pre-computed action potential templates shifted in time to derive transmembrane voltages, repolarization behavior notably deviated from the bidomain results. ECGs calculated with the boundary element method were characterized by correlation coefficients >0.9 compared to the finite element method. The infinite volume conductor method led to lower correlation coefficients caused predominantly by systematic overestimations of P wave amplitudes in the precordial leads. Conclusion: Our results demonstrate that the Eikonal model yields accurate LATs and combined with the boundary element method precise ECGs compared to markedly more expensive full bidomain simulations. However, for an accurate representation of atrial repolarization dynamics, diffusion terms must be accounted for in simplified models. Significance: Simulations of atrial LATs and ECGs can be notably accelerated to clinically feasible time frames at high accuracy by resorting to the Eikonal and boundary element methods
Left atrial hypertrophy increases P-wave terminal force through amplitude but not duration
P-wave morphology correlates with the risk for a trial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in ECG lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that LA hypertrophy, i.e. a thickening of the myocardial wall, also contributes to increased PTF-V1 and is part of the reason for the rather low specificity of increased PTF-V1 regarding LA enlargement. To show this, a trial excitation propagation was simulated in a cohort of four anatomically individualized models including rule-based myocyte orientation and spatial electrophysiological heterogeneity using the mono domain approach. The LA wall was thickened symmetrically in steps of 0.66mm by up to 3.96mm. Interatrial conduction was possible via discrete connections at the coronary sinus, Bachmann's bundle and posteriorly. Body surface ECGs were computed using realistic, heterogeneous torso models. During the early P-wave stemming from sources in the RA, no changes were observed. Once the LA got activated, the voltage in Vi tended to lower values for higher degrees of hypertrophy. Thus, the amplitude of the late positive P-wave decreased while the amplitude of the subsequent negative terminal phase increased. PTF-V1 and LA wall thickening showed a correlation of 0.95. The P-wave duration was almost unaffected by LA wall thickening (Δ <2 ms). Our results show that PTF-V1 is a sensitive marker for LA wall thickening and elucidate why it is superior to P-wave area. The interplay of LA hypertrophy and dilation might cause the poor empirical correlation of LA size and PTF-V1
Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology
[EN] During atrial fibrillation, cardiac tissue undergoes different remodeling processes at different scales from the molecular level to the tissue level. One central player that contributes to both electrical and structural remodeling is the myofibroblast. Based on recent experimental evidence on myofibroblasts' ability to contract, we extended a biophysical myofibroblast model with Ca2+ handling components and studied the effect on cellular and tissue electrophysiology. Using genetic algorithms, we fitted the myofibroblast model parameters to the existing in vitro data. In silico experiments showed that Ca2+ currents can explain the experimentally observed variability regarding the myofibroblast resting membrane potential. The presence of an L-type Ca2+ current can trigger automaticity in the myofibroblast with a cycle length of 799.9 ms. Myocyte action potentials were prolonged when coupled to myofibroblasts with Ca2+ handling machinery. Different spatial myofibroblast distribution patterns increased the vulnerable window to induce arrhythmia from 12 ms in non-fibrotic tissue to 22 & PLUSMN; 2.5 ms and altered the reentry dynamics. Our findings suggest that Ca2+ handling can considerably affect myofibroblast electrophysiology and alter the electrical propagation in atrial tissue composed of myocytes coupled with myofibroblasts. These findings can inform experimental validation experiments to further elucidate the role of myofibroblast Ca2+ handling in atrial arrhythmogenesis.We gratefully acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG) through DO637/22-3 and LO2093/1-1 and by the KIT-Publication Fund of the Karlsruhe Institute of Technology. This work was supported by the European High-Performance Computing Joint Undertaking EuroHPC under grant agreement No 955495 (MICROCARD) co-funded by the Horizon 2020 programme of the European Union (EU), the French National Research Agency ANR, the German Federal Ministry of Education and Research, and the Research Council of Norway.Sánchez, J.; Trenor Gomis, BA.; Saiz RodrĂguez, FJ.; Dossel, O.; Loewe, A. (2021). Fibrotic Remodeling during Persistent Atrial Fibrillation: In Silico Investigation of the Role of Calcium for Human Atrial Myofibroblast Electrophysiology. Cells. 10(11):1-15. https://doi.org/10.3390/cells10112852S115101
Isolated facial and meridional tris(bipyridine)Ru(II) for STM studies on Au(111)
Tripodal facial and meridional Ru(II) complexes comprising three conjugated legs with acetyl-protected thiol end groups are designed, synthesized and isolated for investigation on a gold surface. Preliminary ultrahigh vacuum scanning tunnelling microscopy (UHV STM) measurements of a monolayer of facial isomer deposited on Au(111) are presented
Influence of Gradient and Smoothness of Atrial Wall Thickness on Initiation and Maintenance of Atrial Fibrillation
[EN] This work uses a highly detailed computational model
of human atria to investigate the effect of spatial gradient and smoothing of atrial wall thickness on inducibility
and maintenance of atrial fibrillation (AF) episodes. An
atrial model with homogeneous thickness (HO) was used
as baseline for the generation of different atrial models
including either a low (LG) or high thickness gradient between left/right atrial free wall and the other regions. Since
the model with high spatial gradient presented non-natural
sharp edges between regions, either 1 (HG1) or 2 (HG2)
Laplacian smoothing iterations were applied. Arrhythmic
episodes were initiated using a rapid pacing protocol and
long-living rotors were detected and tracked over time.
Thresholds optimised with receiver operating characteristic analysis were used to define high gradient/curvature regions. Greater spatial gradients increased the atrial model
inducibility and unveiled additional regions vulnerable to
maintain AF drivers. In the models with heterogeneous
wall thickness (LG, HG2 and HG1), 73.5 ± 8.7% of the
long living rotors were found in areas within 1.5 mm from
nodes with high thickness gradient, and 85.0 ± 3.4% in
areas around high endocardial curvature. These findings
promote wall thickness gradient and endocardial curvature as measures of AF vulnerabilityResearch supported by the European UnionÂżs Horizon 2020 research and innovation programme under the Marie SkÂżodowska-Curie grant agreement No.766082 (MY-ATRIA project)Azzolin, L.; Luongo, G.; Rocher-Ventura, S.; Saiz RodrĂguez, FJ.; Dossel, O.; Loewe, A. (2020). Influence of Gradient and Smoothness of Atrial Wall Thickness on Initiation and Maintenance of Atrial Fibrillation. IEEE. 1-4. https://doi.org/10.22489/CinC.2020.261S1
Influence of Fibrotic Tissue Arrangement on Intracardiac Electrograms During Persistent Atrial Fibrillation
[EN] Under persistent atrial fibrillation (peAF), cardiac
tissue experiences electrophysiological and structural
remodeling. Fibrosis in the atrial tissue has an important
impact on the myocyte action potential and its
propagation. The objective of this work is to explore the
effect of heterogeneities present in the fibrotic tissue and
their impact on the intracardiac electrogram (EGM).
Human atrial myocyte and fibroblast electrophysiology
was simulated using mathematical models proposed by
Koivumäki et al. to represent electrical remodeling under
peAF and the paracrine effect of the transforming grow
factor Âż1 (TGF-Âż1). 2D tissue simulations were computed
varying the density of fibrosis (10%, 20% and 40%),
myofibroblasts and collagen were randomly distributed
with different ratios (0%-100%, 50%-50% and 100%-
0%). Results show that increasing the fibrosis density
changes the re-entry dynamics from functional to
anatomical due to a block in conduction in regions with
high fibrosis density (40%). EGM morphology was
affected by different ratios of myofibroblasts-collagen.
For low myofibroblast densities (below 50%) the duration
of active segments was shorter compared to higher
myofibroblasts densities (above 50%). Our results show
that fibrosis heterogeneities can alter the dynamics of the
re-entry and the morphology of the EGM.We gratefully acknowledge financial support by Deutsche
Forschungsgemeinschaft (DFG) under grant LO 2093/1-1.Sánchez, J.; Nothstein Mark; Unger, L.; Saiz RodrĂguez, FJ.; Trenor Gomis, BA.; Dossel, O.; Loewe, A. (2019). Influence of Fibrotic Tissue Arrangement on Intracardiac Electrograms During Persistent Atrial Fibrillation. IEEE. 1-4. https://doi.org/10.22489/CinC.2019.342S1