Abstract:

Cardiologists measure electric signals inside the human heart aiming at a better diagnosis and optimized therapy of atrial arrhythmias like atrial flutter and atrial fibrillation. The catheters that are used for this purpose are improving: now they are able to pick up the electric signals at up to 64 positions inside the heart simultaneously. The patterns of electric depolarization are sometimes very simple, comparable to plane waves. But in case of patients with severe atrial arrhythmias they can be quite complex: U-turns around a line of block, ectopic centres, break throughs, reentry circuits, rotors, fractionated signals and chaotic patterns are often observed. Methods of biosignal analysis can support the cardiologists in classifying the signals and extract information of high diagnostic relevance. Computer models of the electrophysiology of the human heart can serve to design better algorithms for data analysis and to test algorithms, because the ground truth is known.

Abstract:

AIMS: P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. METHODS AND RESULTS: Atrial excitation was triggered from seven different EAS in a cohort of eight anatomically personalized computational models. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed and separated by left and right atrial contributions. Mid-septal EAS yielded the highest PTF-V1. More anterior/superior and more inferior EAS yielded lower absolute PTF-V1 values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via Bachmann's Bundle (BB) for anterior/superior EAS and shifted towards posterior IACs for more inferior EAS. Non-conducting posterior IACs increased PTF-V1 by up to 150% compared to intact posterior IACs for inferior EAS. LA contribution to the P-wave integral was 24% on average. CONCLUSION: The electrical contributor's site of earliest activation and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites independent from LA size. This should be considered for interpretation of electrocardiographical signs of LA abnormality and LA enlargement.

Abstract:

Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way toward tailored therapies in the last years. To fully leverage in silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurately and reliably. In this work, two classes of optimization approaches are evaluated: gradient-based trust-region-reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that neither of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration.

Abstract:

Whole-chamber mapping using a 64-pole basket catheter (BC) has become a featured approach for the analysis of excitation patterns during atrial fibrillation. A flexible catheter design avoids perforation but may lead to spline bunching and influence coverage. We aim to quantify the catheter deformation and endocardial coverage in clinical situations and study the effect of catheter size and electrode arrangement using an in silico basket model. Atrial coverage and spline separation were evaluated quantitatively in an ensemble of clinical measurements. A computational model of the BC was implemented including an algorithm to adapt its shape to the atrial anatomy. Two clinically relevant mapping positions in each atrium were assessed in both clinical and simulated data. The simulation environment allowed varying both BC size and electrode arrangement. Results showed that interspline distances of more than 20 mm are common, leading to a coverage of less than 50% of the left atrial (LA) surface. In an ideal in silico scenario with variable catheter designs, a maximum coverage of 65% could be reached. As spline bunching and insufficient coverage can hardly be avoided, this has to be taken into account for interpretation of excitation patterns and development of new panoramic mapping techniques.

Abstract:

P-wave assessment is frequently used in clinical practice to recognize atrial abnormalities. However, the use of P-wave criteria to diagnose specific atrial abnormalities such as left atrial enlargement has shown to be of limited use since these abnormalities can be difficult to distinguish using P-wave criteria to date. Hence, a mechanistic understanding how specific atrial abnormalities affect the P-wave is desirable. In this study, we investigated the effect of left atrial hypertrophy on P-wave morphology using an in silico approach. In a cohort of four realistic patient models, we homogeneously increased left atrial wall thickness in up to seven degrees of left atrial hypertrophy. Excitation conduction was simulated using a monodomain finite element approach. Then, the resulting transmembrane voltage distribution was used to calculate the corresponding extracellular potential distribution on the torso by solving the forward problem of electrocardiography. In our simulation setup, left atrial wall thickening strongly correlated with an increased absolute value of the P-wave terminal force (PTF) in Wilson lead V1 due to an increased negative amplitude while P-wave duration was unaffected. Remarkably, an increased PTF-V1 has often been associated with left atrial enlargement which is defined as a rather increased left atrial volume than a solely thickened left atrium. Hence, the observed contribution of left atrial wall thickness changes to PTF-V1 might explain the poor empirical correlation of left atrial enlargement with PTF-V1.

Abstract:

Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intrac- ardiac electrograms (IEGMs) provide real-time informa- tion regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and inter- pretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenom- ena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was com- pared to an existing one and to clinical measurements of ve patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogo- nal catheter orientation, the presence of a second necrotic core in the near- eld of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.

Abstract:

P-wave morphology correlates with the risk for atrial fibrillation (AF). Left atrial (LA) enlargement could ex- plain both the higher risk for AF and higher P-wave ter- minal force (PTF) in ECG lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypoth- esize that LA hypertrophy, i.e. a thickening of the myocar- dial 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, atrial excitation propagation was simulated in a cohort of four anatomically individualized models in- cluding rule-based myocyte orientation and spatial elec- trophysiological heterogeneity using the monodomain ap- proach. The LA wall was thickened symmetrically in steps of 0.66 mm by up to 3.96 mm. 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 mod- els. During the early P-wave stemming from sources in the RA, no changes were observed. Once the LA got activated, the voltage in V1 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 neg- ative terminal phase increased. PTF-V1 and LA wall thick- ening showed a correlation of 0.95. The P-wave duration was almost unaffected by LA wall thickening (∆ ≤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.

Abstract:

P-wave morphology correlates with the risk for AF. Left atrial (LA) enlargement could explain both the higher risk for AF and higher P-wave terminal force (PTF) in lead V1. However, PTF-V1 has been shown to correlate poorly with LA size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IAC), which both show tremendous variability. Atrial excitation was triggered from seven different EAS on the epicardial surface around the sinus node region in eight anatomically personalized computational models including rule-based myocyte orientation and spatial electrophysiological heterogeneity. EAS1 was located midway between the tip of the right atrial appendage (RAA) and its junction with the superior vena cava (SVC), EAS2 at the superior part of the anterior wall, and EAS3 at the junction of the RAA and the SVC. EAS4 to EAS7 were uniformly distributed along the crista terminalis between EAS3 and orifice of the inferior vena cava (EAS7). IACs connected the atria at Bachmann’s bundle, coronary sinus and posteriorly. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed using realistic, heterogeneous torso models. Mid-septal EAS yielded the highest PTF-V1 measured as the product of the duration and the maximal amplitude of the negative phase of the P-wave in V1. More anterior/superior and more inferior EAS yielded lower absolute values deviating by a factor of up to 2.0 for adjacent EAS. Earliest right-to-left activation was conducted via BB for EAS1-3 and shifted towards posterior IACs for EAS 4-7. Non-conducting posterior IACs increased PTF-V1 by up to 150%. The electrical contributors EAS and intactness of posterior IACs affect PTF-V1 significantly by changing LA breakthrough sites. This should be considered when assessing LA anatomy based on the ECG.

Abstract:

Aim: P-wave morphology correlates with the risk for AF. Left atrial enlargement could explain both the higher risk for AF and higher P-wave terminal force in lead V1 (PTF-V1). However, PTF-V1 has been shown to correlate poorly with left atrial size. We hypothesize that PTF-V1 is also affected by the earliest activated site (EAS) in the right atrium and its proximity to inter-atrial connections (IACs), which both show tremendous variability. Methods: Atrial excitation was triggered from seven different EASs (Fig 1A,B) in eight anatomically personalized computational models including rule-based fiber orientation and spatial electrophysiological heterogeneity. IACs connected the atria at Bachmann’s bundle, coronary sinus, and posteriorly. The posterior IACs were non-conductive in a second set of simulations. Body surface ECGs were computed using realistic, heterogeneous torso models of the same subjects. Results: Mid-septal EASs yielded the highest PTF-V1 measured as the product of the duration and the maximal amplitude of the negative phase of the P-wave in V1. More anterior/superior and more inferior EASs yielded lower absolute values deviating by a factor of up to 2.0 for adjacent EAS (Fig 1C). Earliest right-to-left activation was conducted via BB for EAS1-EAS3 and shifted towards posterior IACs for EAS4-EAS7. Non- conducting posterior IACs increased PTF-V1 by up to 150% (Fig 1D). Conclusions: Location of EAS in the right atrium and its proximity to functioning IACs affect PTF-V1 independently of the left atrial size and further support the caution that needs to be exercised when interpreting electrocardiographically signs of left atrial abnormality, which include PTF-V1.

Abstract:

The goal of this research was to classify cardiac excitation patterns during atrial fibrillation (AFib). For this purpose, virtual models of intracardiac mapping catheters were moved across in-silico cardiac tissue to extract local activation times (LATs) of each catheter electrode from simulated cardiac action potential (AP) signals. The resulting LAT patterns consisting of the LATs of all electrodes resemble patterns measured in clinical cases. The LATs represent the input information for features that were used to separate four different excitation patterns during AFib. Those four excitation patterns were plane wave, ectopic focus (spherical wave), rotor (spiral wave) and block. A feature selection algorithm was used to investigate the features concerning their power to classify the different simulated excitation patterns. The scores of the selected features were used to train and optimize a support vector machine (SVM). The optimized and cross-validated SVM was then used to classify the simulated cardiac excitation patterns. The achieved overall classification accuracy of this SVM model was 98.4 %.

Abstract:

The monodomain model and finite element method are often used together to compute electrical excitation conduction in cardiac tissue. It is known that the choice of using mass lumping as well as the used ionic current integration method affect the resulting conduction velocities (CVs), especially at coarse resolutions. We describe how the regularity of node arrangement in tetrahedral grids also affects simulated CVs in a similar magnitude. We compare activation times (ATs) over a distance of 21.4 mm at different resolutions to a high resolution reference solution from a previously published benchmark. We show that triangulated grids are able to be within 10% of the reference solution up to a grid resolution of 0.6 mm, while results from regular grids already diverge by more than that at 0.4 mm. At 0.7 mm, a regular grid yields an AT of 80.01 ms, where a triangulated grid with less nodes results in 47.52 ms (reference solution 42.82 ms). We investigate how gradual perturbation of nodes from a regular grid effects AT, finding that CV monotonically increases with degree of node perturbation.