Modeling ventricular repolarization gradients in normal cases using the equivalent dipole layer.

Background Electrical activity underlying the T-wave is less well understood than the QRS-complex. This study investigated the relationship between normal T-wave morphology and the underlying ventricular repolarization gradients using the equivalent dipole layer (EDL). Methods Body-surface-potential-maps (BSPM, 67­leads) were obtained in nine normal cases. Subject specific MRI-based anatomical heart/torso-models with electrode positions were created. The boundary element method was used to account for the volume conductor effects. To simulate the measured T-waves, the EDL was used to apply different ventricular repolarization gradients: a) transmural, b) interventricular c) apico-basal and d) all three gradients (a-c) combined. The combined gradient (d) was optimized using an inverse procedure (Levenberg-Marquardt). Correspondence between simulated and measured T-waves was assessed using correlation coefficient (CC) and relative difference (RD). Results Realistic T-waves were simulated if repolarization times of: (a) the epicardium were smaller than the endocardium; (b) the left ventricle were smaller than the right ventricle and (c) the apex increased towards the base. The apico-basal gradient resulted in the highest correspondence between measured and simulated T-waves (CC = 0.84(0.81-0.91);RD = 0.68(0.60-0.71)) compared to a transmural gradient (CC = 0.77(0.71-0.80);RD = 1.46(0.82-1.75)) and an interventricular gradient (CC = 0.71(0.67-0.80);RD = 0.85(0.75-0.87)). All three gradients combined further improved the correspondence between measured and simulated T-waves (CC = 0.83(0.82-0.89);RD = 0.60(0.51-0.63)), especially after optimization (CC = 0.96(0.94-0.98);RD = 0.27(0.22-0.34)). Conclusion The application of all repolarization gradients combined resulted in the largest agreement between simulated and measured T-waves, followed by the apico-basal repolarization gradient. With these findings, we will optimize our EDL-based inverse procedure to assess repolarization abnormalities.

Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.

Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.

Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.

Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.

Ex vivo Validation of Noninvasive Epicardial and Endocardial Repolarization Mapping.

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity. Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region. Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms. Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.

Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.

This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.

In silico validation of electrocardiographic imaging to reconstruct the endocardial and epicardial repolarization pattern using the equivalent dipole layer source model.

The solution of the inverse problem of electrocardiology allows the reconstruction of the spatial distribution of the electrical activity of the heart from the body surface electrocardiogram (electrocardiographic imaging, ECGI). ECGI using the equivalent dipole layer (EDL) model has shown to be accurate for cardiac activation times. However, validation of this method to determine repolarization times is lacking. In the present study, we determined the accuracy of the EDL model in reconstructing cardiac repolarization times, and assessed the robustness of the method under less ideal conditions (addition of noise and errors in tissue conductivity). A monodomain model was used to determine the transmembrane potentials in three different excitation-repolarization patterns (sinus beat and ventricular ectopic beats) as the gold standard. These were used to calculate the body surface ECGs using a finite element model. The resulting body surface electrograms (ECGs) were used as input for the EDL-based inverse reconstruction of repolarization times. The reconstructed repolarization times correlated well (COR > 0.85) with the gold standard, with almost no decrease in correlation after adding errors in tissue conductivity of the model or noise to the body surface ECG. Therefore, ECGI using the EDL model allows adequate reconstruction of cardiac repolarization times. Graphical abstract Validation of electrocardiographic imaging for repolarization using forward calculated body surface ECGs from simulated activation-repolarization sequences.

Assessment of the equivalent dipole layer source model in the reconstruction of cardiac activation times on the basis of BSPMs produced by an anisotropic model of the heart.

Promising results have been reported in noninvasive estimation of cardiac activation times (AT) using the equivalent dipole layer (EDL) source model in combination with the boundary element method (BEM). However, the assumption of equal anisotropy ratios in the heart that underlies the EDL model does not reflect reality. In the present study, we quantify the errors of the nonlinear AT imaging based on the EDL approximation. Nine different excitation patterns (sinus rhythm and eight ectopic beats) were simulated with the monodomain model. Based on the bidomain theory, the body surface potential maps (BSPMs) were calculated for a realistic finite element volume conductor with an anisotropic heart model. For the forward calculations, three cases of bidomain conductivity tensors in the heart were considered: isotropic, equal, and unequal anisotropy ratios in the intra- and extracellular spaces. In all inverse reconstructions, the EDL model with BEM was employed: AT were estimated by solving the nonlinear optimization problem with the initial guess provided by the fastest route algorithm. Expectedly, the case of unequal anisotropy ratios resulted in larger localization errors for almost all considered activation patterns. For the sinus rhythm, all sites of early activation were correctly estimated with an optimal regularization parameter being used. For the ectopic beats, all but one foci were correctly classified to have either endo- or epicardial origin with an average localization error of 20.4 mm for unequal anisotropy ratio. The obtained results confirm validation studies and suggest that cardiac anisotropy might be neglected in clinical applications of the considered EDL-based inverse procedure.