Investigation into the importance of using natural PVCs and pathological models for potential-based ECGI validation.

Introduction: Premature ventricular contractions (PVCs) are one of the most commonly targeted pathologies for ECGI validation, often through ventricular stimulation to mimic the ectopic beat. However, it remains unclear if such stimulated beats faithfully reproduce spontaneously occurring PVCs, particularly in the case of the R-on-T phenomenon. The objective of this study was to determine the differences in ECGI accuracy when reconstructing spontaneous PVCs as compared to ventricular-stimulated beats and to explore the impact of pathophysiological perturbation on this reconstruction accuracy. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, and local hyperkalemia was induced through perfusion of a high-K+ solution (8 mM) into the LAD. Recordings were taken simultaneously from the heart and tank surfaces during ventricular pacing and during spontaneous PVCs (including R-on-T), both at baseline and high K+. Epicardial potentials were reconstructed from torso potentials using ECGI. Results: Spontaneously occurring PVCs were better reconstructed than stimulated beats at baseline in terms of electrogram morphology [correlation coefficient (CC) = 0.74 ± 0.05 vs. CC = 0.60 ± 0.10], potential maps (CC = 0.61 ± 0.06 vs. CC = 0.51 ± 0.12), and activation time maps (CC = 0.86 ± 0.07 vs. 0.76 ± 0.10), though there was no difference in the localization error (LE) of epicardial origin (LE = 14 ± 6 vs. 15 ± 11 mm). High K+ perfusion reduced the accuracy of ECGI reconstructions in terms of electrogram morphology (CC = 0.68 ± 0.10) and AT maps (CC = 0.70 ± 0.12 and 0.59 ± 0.23) for isolated PVCs and paced beats, respectively. LE trended worse, but the change was not significant (LE = 17 ± 9 and 20 ± 12 mm). Spontaneous PVCs were less well when the R-on-T phenomenon occurred and the activation wavefronts encountered a line of block. Conclusion: This study demonstrates the differences in ECGI accuracy between spontaneous PVCs and ventricular-paced beats. We also observed a reduction in this accuracy near regions of electrically inactive tissue. These results highlight the need for more physiologically realistic experimental models when evaluating the accuracy of ECGI methods. In particular, reconstruction accuracy needs to be further evaluated in the presence of R-on-T or isolated PVCs, particularly when encountering obstacles (functional or anatomical) which cause line of block and re-entry.

The circle of reentry: Characteristics of trigger-substrate interaction leading to sudden cardiac arrest.

Sudden cardiac death is often caused by ventricular arrhythmias driven by reentry. Comprehensive characterization of the potential triggers and substrate in survivors of sudden cardiac arrest has provided insights into the trigger-substrate interaction leading to reentry. Previously, a "Triangle of Arrhythmogenesis", reflecting interactions between substrate, trigger and modulating factors, has been proposed to reason about arrhythmia initiation. Here, we expand upon this concept by separating the trigger and substrate characteristics in their spatial and temporal components. This yields four key elements that are required for the initiation of reentry: local dispersion of excitability (e.g., the presence of steep repolarization time gradients), a critical relative size of the region of excitability and the region of inexcitability (e.g., a sufficiently large region with early repolarization), a trigger that originates at a time when some tissue is excitable and other tissue is inexcitable (e.g., an early premature complex), and which occurs from an excitable region (e.g., from a region with early repolarization). We discuss how these findings yield a new mechanistic framework for reasoning about reentry initiation, the "Circle of Reentry." In a patient case of unexplained ventricular fibrillation, we then illustrate how a comprehensive clinical investigation of these trigger-substrate characteristics may help to understand the associated arrhythmia mechanism. We will also discuss how this reentry initiation concept may help to identify patients at risk, and how similar reasoning may apply to other reentrant arrhythmias.

Understanding repolarization in the intracardiac unipolar electrogram: A long-lasting controversy revisited.

Background: The optimal way to determine repolarization time (RT) from the intracardiac unipolar electrogram (UEG) has been a topic of debate for decades. RT is typically determined by either the Wyatt method or the "alternative method," which both consider UEG T-wave slope, but differently. Objective: To determine the optimal method to measure RT on the UEG. Methods: Seven pig hearts surrounded by an epicardial sock with 100 electrodes were Langendorff-perfused with selective cannulation of the left anterior descending (LAD) coronary artery and submersed in a torso-shaped tank containing 256 electrodes on the torso surface. Repolarization was prolonged in the non-LAD-regions by infusing dofetilide and shortened in the LAD-region using pinacidil. RT was determined by the Wyatt (tWyatt) and alternative (tAlt) methods, in both invasive (recorded with epicardial electrodes) and in non-invasive UEGs (reconstructed with electrocardiographic imaging). tWyatt and tAlt were compared to local effective refractory period (ERP). Results: With contact mapping, mean absolute error (MAE) of tWyatt and tAlt vs. ERP were 21 ms and 71 ms, respectively. Positive T-waves typically had an earlier ERP than negative T-waves, in line with theory. tWyatt -but not tAlt-shortened by local infusion of pinacidil. Similar results were found for the non-invasive UEGs (MAE of tWyatt and tAlt vs. ERP were 30 ms and 92 ms, respectively). Conclusion: The Wyatt method is the most accurate to determine RT from (non) invasive UEGs, based on novel and historical analyses. Using it to determine RT could unify and facilitate repolarization assessment and amplify its role in cardiac electrophysiology.

A novel framework for the removal of pacing artifacts from bio-electrical recordings.

BACKGROUND: Electroceuticals provide clinical solutions for a range of disorders including Parkinson's disease, cardiac arrythmias and are emerging as a potential treatment option for gastrointestinal disorders. However, pre-clinical investigations are challenged by the large stimulation artifacts registered in bio-electrical recordings. METHOD: A generalized framework capable of isolating and suppressing stimulation artifacts with minimal intervention was developed. Stimulation artifacts with different pulse-parameters in synthetic and experimental cardiac and gastrointestinal signals were detected using a Hampel filter and reconstructed using 3 methods: i) autoregression, ii) weighted mean, and iii) linear interpolation. RESULTS: Synthetic stimulation artifacts with amplitudes of 2 mV and 4 mV and pulse-widths of 50 ms, 100 ms, and 200 ms were successfully isolated and the artifact window size remained uninfluenced by the pulse-amplitude, but was influenced by pulse-width (e.g., the autoregression method resulted in an identical Root Mean Square Error (RMSE) of 1.64 mV for artifacts with 200 ms pulse-width and both 2 mV and 4 mV amplitudes). The performance of autoregression (RMSE = 1.45 ± 0.16 mV) and linear interpolation (RMSE = 1.22 ± 0.14 mV) methods were comparable and better than weighted mean (RMSE = 5.54 ± 0.56 mV) for synthetic data. However, for experimental recordings, artifact removal by autoregression was superior to both linear interpolation and weighted mean approaches in gastric, small intestinal and cardiac recordings. CONCLUSIONS: A novel signal processing framework enabled efficient analysis of bio-electrical recordings with stimulation artifacts. This will allow the bio-electrical events induced by stimulation protocols to be efficiently and systematically evaluated, resulting in improved stimulation therapies.

A generalized framework for pacing artifact removal using a Hampel filter.

Cardiac pacing is a clinical therapy widely used for treating irregular heart rhythms. Equivalent techniques for the treatment of gastric functional motility disorders hold great potential. Accurate analysis of pacing studies is often hindered by the stimulus artifacts which are superimposed on the recorded signals. This paper presents a semi-automated artifact detection method using a Hampel filter accompanied by 2 separate artifact reconstruction methods: (i) an auto-regressive model, and (ii) weighted mean to estimate the underlying signal. The developed framework was validated on synthetic and experimental signals containing large periodic pacing artifacts alongside evoked bioelectrical events. The performance of the proposed algorithms was quantified for gastric and cardiac pacing data collected in vivo. A lower mean RMS difference was achieved by the artifact segment reconstructed using the auto-regression ([Formula: see text]), method compared to the weighted mean ([Formula: see text]) method. Therefore, a more accurate artifact reconstruction was provided by the auto-regression approach. Clinical Relevance- The ability to efficiently and accurately isolate evoked bioelectrical events by eliminating large artifacts is a critical advancement for the analysis of paced recordings. The developed framework allows more efficient analysis of preclinical pacing data and thereby contributes to the advancement of pacing as a clinical therapy.

Non-Contact Intracardiac Potential Mapping Using Mesh-Based and Meshless Inverse Solvers.

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters has been used to identify ablation targets in persistent AF but is limited by poor contact and inadequate coverage of the left atrial cavity. In this paper, we investigate the accuracy with which atrial endocardial surface potentials can be reconstructed from electrograms recorded with non-contact catheters. An in-silico approach was employed in which "ground-truth" surface potentials from experimental contact mapping studies and computer models were compared with inverse potential maps constructed by sampling the corresponding intracardiac field using virtual basket catheters. We demonstrate that it is possible to 1) specify the mixed boundary conditions required for mesh-based formulations of the potential inverse problem fully, and 2) reconstruct accurate inverse potential maps from recordings made with appropriately designed catheters. Accuracy improved when catheter dimensions were increased but was relatively stable when the catheter occupied >30% of atrial cavity volume. Independent of this, the capacity of non-contact catheters to resolve the complex atrial potential fields seen in reentrant atrial arrhythmia depended on the spatial distribution of electrodes on the surface bounding the catheter. Finally, we have shown that reliable inverse potential mapping is possible in near real-time with meshless methods that use the Method of Fundamental Solutions.

Intracardiac Inverse Potential Mapping Using the Method of Fundamental Solutions.

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters can identify ablation targets in persistent AF, but is limited by poor contact and inadequate coverage. Objective: To investigate the accuracy of inverse mapping of endocardial surface potentials from electrograms sampled with noncontact basket catheters. Methods: Our group has developed a computationally efficient inverse 3D mapping technique using a meshless method that employs the Method of Fundamental Solutions (MFS). An in-silico test bed was used to compare ground-truth surface potentials with corresponding inverse maps reconstructed from noncontact potentials sampled with virtual catheters. Ground-truth surface potentials were derived from high-density clinical contact mapping data and computer models. Results: Solutions of the intracardiac potential inverse problem with the MFS are robust, fast and accurate. Endocardial surface potentials can be faithfully reconstructed from noncontact recordings in real-time if the geometry of cardiac surface and the location of electrodes relative to it are known. Larger catheters with appropriate electrode density are needed to resolve complex reentrant atrial rhythms. Conclusion: Real-time panoramic potential mapping is feasible with noncontact intracardiac catheters using the MFS. Significance: Accurate endocardial potential maps can be reconstructed in AF with appropriately designed noncontact multi-electrode catheters.

Impulse Data Models for the Inverse Problem of Electrocardiography.

OBJECTIVE: To develop, train and test neural networks for predicting heart surface potentials (HSPs) from body surface potentials (BSPs). The method re-frames traditional inverse problems of electrocardiography into regression problems, constraining the solution space by decomposing signals with multidimensional Gaussian impulse basis functions. METHODS: Impulse HSPs were generated with single Gaussian basis functions at discrete heart surface locations and projected to corresponding BSPs using a volume conductor torso model. Both BSP (inputs) and HSP (outputs) were mapped to regular 2D surface meshes and used to train a neural network. Predictive capabilities of the network were tested with unseen synthetic and experimental data. RESULTS: A dense full connected single hidden layer neural network was trained to map body surface impulses to heart surface Gaussian basis functions for reconstructing HSP. Synthetic pulses moving across the heart surface were predicted from the neural network with root mean squared error of 9.1±1.4%. Predicted signals were robust to noise up to 20 dB and errors due to displacement and rotation of the heart within the torso were bounded and predictable. A shift of the heart 40 mm toward the spine resulted in a 4% increase in signal feature localization error. The set of training impulse function data could be reduced, and prediction error remained bounded. Recorded HSPs from in-vitro pig hearts were reliably decomposed using space-time Gaussian basis functions. Activation times calculated from predicted HSPs for left-ventricular pacing had a mean absolute error of 10.4±11.4 ms. Other pacing scenarios were analyzed with similar success. CONCLUSION: Impulses from Gaussian basis functions are potentially an effective and robust way to train simple neural network data models for reconstructing HSPs from decomposed BSPs. SIGNIFICANCE: The HSPs predicted by the neural network can be used to generate activation maps that non-invasively identify features of cardiac electrical dysfunction and can guide subsequent treatment options.

Reducing Line-of-Block Artifacts in Cardiac Activation Maps Estimated Using ECG Imaging: A Comparison of Source Models and Estimation Methods.

OBJECTIVE: To investigatecardiac activation maps estimated using electrocardiographic imaging and to find methods reducing line-of-block (LoB) artifacts, while preserving real LoBs. METHODS: Body surface potentials were computed for 137 simulated ventricular excitations. Subsequently, the inverse problem was solved to obtain extracellular potentials (EP) and transmembrane voltages (TMV). From these, activation times (AT) were estimated using four methods and compared to the ground truth. This process was evaluated with two cardiac mesh resolutions. Factors contributing to LoB artifacts were identified by analyzing the impact of spatial and temporal smoothing on the morphology of source signals. RESULTS: AT estimation using a spatiotemporal derivative performed better than using a temporal derivative. Compared to deflection-based AT estimation, correlation-based methods were less prone to LoB artifacts but performed worse in identifying real LoBs. Temporal smoothing could eliminate artifacts for TMVs but not for EPs, which could be linked to their temporal morphology. TMVs led to more accurate ATs on the septum than EPs. Mesh resolution had anegligible effect on inverse reconstructions, but small distances were important for cross-correlation-based estimation of AT delays. CONCLUSION: LoB artifacts are mainly caused by the inherent spatial smoothing effect of the inverse reconstruction. Among the configurations evaluated, only deflection-based AT estimation in combination with TMVs and strong temporal smoothing can prevent LoB artifacts, while preserving real LoBs. SIGNIFICANCE: Regions of slow conduction are of considerable clinical interest and LoB artifacts observed in non-invasive ATs can lead to misinterpretations. We addressed this problem by identifying factors causing such artifacts.

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation.

A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates are difficult to detect and localize with current clinical tools. Here, we created repolarization time (RT) dispersion by regional drug infusion in perfused explanted human (n = 1) and porcine (n = 6) hearts and in a computational model of the human ventricle. Arrhythmia induction was tested with a single ventricular extrastimulus applied at the early or late RT region. Arrhythmias could only be induced from early RT regions. Vulnerability to VF increased with RT gradient steepness and with larger areas of early RT, but not with markers on the body-surface electrocardiogram. Noninvasive electrocardiographic imaging was performed in survivors of idiopathic VF (n = 11), patients with frequent premature ventricular complexes (PVCs) but no history of sudden cardiac arrest (n = 7), and controls (n = 10). In survivors of idiopathic VF, RT gradients were steeper than in controls, without differences in the clinical electrocardiogram, consistent with the ex vivo results. Patients with idiopathic VF also showed local myocardial regions with distinctly early-versus-late RT that were more balanced in size than in controls. Premature beats originated more often from the early RT regions in idiopathic VF survivors than in patients with frequent PVCs only. Thus, idiopathic VF emerges from the spatiotemporal interaction of a premature beat from an early-repolarization region with critical repolarization dispersion in that region. Electrocardiographic imaging can uncover the co-occurrence of these abnormalities.

The effect of interpolating low amplitude leads on the inverse reconstruction of cardiac electrical activity.

Electrocardiographic imaging is an imaging modality that has been introduced recently to help in visualizing the electrical activity of the heart and consequently guide the ablation therapy for ventricular arrhythmias. One of the main challenges of this modality is that the electrocardiographic signals recorded at the torso surface are contaminated with noise from different sources. Low amplitude leads are more affected by noise due to their low peak-to-peak amplitude. In this paper, we have studied 6 datasets from two torso tank experiments (Bordeaux and Utah experiments) to investigate the impact of removing or interpolating these low amplitude leads on the inverse reconstruction of cardiac electrical activity. Body surface potential maps used were calculated by using the full set of recorded leads, removing 1, 6, 11, 16, or 21 low amplitude leads, or interpolating 1, 6, 11, 16, or 21 low amplitude leads using one of the three interpolation methods - Laplacian interpolation, hybrid interpolation, or the inverse-forward interpolation. The epicardial potential maps and activation time maps were computed from these body surface potential maps and compared with those recorded directly from the heart surface in the torso tank experiments. There was no significant change in the potential maps and activation time maps after the removal of up to 11 low amplitude leads. Laplacian interpolation and hybrid interpolation improved the inverse reconstruction in some datasets and worsened it in the rest. The inverse forward interpolation of low amplitude leads improved it in two out of 6 datasets and at least remained the same in the other datasets. It was noticed that after doing the inverse-forward interpolation, the selected lambda value was closer to the optimum lambda value that gives the inverse solution best correlated with the recorded one.

3-Dimensional ventricular electrical activation pattern assessed from a novel high-frequency electrocardiographic imaging technique: principles and clinical importance.

The study introduces and validates a novel high-frequency (100-400 Hz bandwidth, 2 kHz sampling frequency) electrocardiographic imaging (HFECGI) technique that measures intramural ventricular electrical activation. Ex-vivo experiments and clinical measurements were employed. Ex-vivo, two pig hearts were suspended in a human-torso shaped tank using surface tank electrodes, epicardial electrode sock, and plunge electrodes. We compared conventional epicardial electrocardiographic imaging (ECGI) with intramural activation by HFECGI and verified with sock and plunge electrodes. Clinical importance of HFECGI measurements was performed on 14 patients with variable conduction abnormalities. From 3 × 4 needle and 108 sock electrodes, 256 torso or 184 body surface electrodes records, transmural activation times, sock epicardial activation times, ECGI-derived activation times, and high-frequency activation times were computed. The ex-vivo transmural measurements showed that HFECGI measures intramural electrical activation, and ECGI-HFECGI activation times differences indicate endo-to-epi or epi-to-endo conduction direction. HFECGI-derived volumetric dyssynchrony was significantly lower than epicardial ECGI dyssynchrony. HFECGI dyssynchrony was able to distinguish between intraventricular conduction disturbance and bundle branch block patients.

A novel method to correct repolarization time estimation from unipolar electrograms distorted by standard filtering.

Reliable patient-specific ventricular repolarization times (RTs) can identify regions of functional block or afterdepolarizations, indicating arrhythmogenic cardiac tissue and the risk of sudden cardiac death. Unipolar electrograms (UEs) record electric potentials, and the Wyatt method has been shown to be accurate for estimating RT from a UE. High-pass filtering is an important step in processing UEs, however, it is known to distort the T-wave phase of the UE, which may compromise the accuracy of the Wyatt method. The aim of this study was to examine the effects of high-pass filtering, and improve RT estimates derived from filtered UEs. We first generated a comprehensive set of UEs, corresponding to early and late activation and repolarization, that were then high-pass filtered with settings that mimicked the CARTO filter. We trained a deep neural network (DNN) to output a probabilistic estimation of RT and a measure of confidence, using the filtered synthetic UEs and their true RTs. Unfiltered ex-vivo human UEs were also filtered and the trained DNN used to estimate RT. Even a modest 2 Hz high-pass filter imposes a significant error on RT estimation using the Wyatt method. The DNN outperformed the Wyatt method in 62.75% of cases, and produced a significantly lower absolute error (p=8.99E-13), with a median of 16.91 ms, on 102 ex-vivo UEs. We also applied the DNN to patient UEs from CARTO, from which an RT map was computed. In conclusion, DNNs trained on synthetic UEs improve the RT estimation from filtered UEs, which leads to more reliable repolarization maps that help to identify patient-specific repolarization abnormalities.

Electrocardiographic Imaging of Repolarization Abnormalities.

Background Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart. Unipolar electrograms were recorded simultaneously during sinus rhythm from an epicardial sock and the torso-shaped tank within which the heart was suspended. Regional repolarization heterogeneities were introduced through perfusion of dofetilide and pinacidil into separate perfusion beds. In vivo data included torso and epicardial potentials recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, and ventricular pacing. For both data sets, ECGI accurately reconstructed T-wave electrogram morphologies when compared with those recorded by the sock (ex vivo: correlation coefficient, 0.85 [0.52-0.96], in vivo: correlation coefficient, 0.86 [0.52-0.96]) and repolarization time maps (ex-vivo: correlation coefficient, 0.73 [0.63-0.83], in vivo: correlation coefficient, 0.76 [0.67-0.82]). ECGI-reconstructed repolarization time distributions were strongly correlated to those measured by the sock (both data sets, R2 ≥0.92). Although the position of the gradient was slightly shifted by 8.3 (0-13.9) mm, the mean, max, and SD between ECGI and recorded gradient values were highly correlated (R2=0.87, 0.75, and 0.86 respectively). There was no significant difference in ECGI accuracy between ex vivo and in vivo data. Conclusions ECGI reliably and accurately maps potentially critical repolarization abnormalities. This noninvasive approach allows imaging and quantifying individual parameters of abnormal repolarization-based substrates in patients with arrhythmogenesis, to improve diagnosis and risk stratification.

The Impact of Torso Signal Processing on Noninvasive Electrocardiographic Imaging Reconstructions.

GOAL: To evaluate state-of-the-art signal processing methods for epicardial potential-based noninvasive electrocardiographic imaging reconstructions of single-site pacing data. METHODS: Experimental data were obtained from two torso-tank setups in which Langendorff-perfused hearts (n = 4) were suspended and potentials recorded simultaneously from torso and epicardial surfaces. 49 different signal processing methods were applied to torso potentials, grouped as i) high-frequency noise removal (HFR) methods ii) baseline drift removal (BDR) methods and iii) combined HFR+BDR. The inverse problem was solved and reconstructed electrograms and activation maps compared to those directly recorded. RESULTS: HFR showed no difference compared to not filtering in terms of absolute differences in reconstructed electrogram amplitudes nor median correlation in QRS waveforms (p > 0.05). However, correlation and mean absolute error of activation times and pacing site localization were improved with all methods except a notch filter. HFR applied post-reconstruction produced no differences compared to pre-reconstruction. BDR and BDR+HFR significantly improved absolute and relative difference, and correlation in electrograms (p < 0.05). While BDR+HFR combined improved activation time and pacing site detection, BDR alone produced significantly lower correlation and higher localization errors (p < 0.05). CONCLUSION: BDR improves reconstructed electrogram morphologies and amplitudes due to a reduction in lambda value selected for the inverse problem. The simplest method (resetting the isoelectric point) is sufficient to see these improvements. HFR does not impact electrogram accuracy, but does impact post-processing to extract features such as activation times. Removal of line noise is insufficient to see these changes. HFR should be applied post-reconstruction to ensure over-filtering does not occur.

Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome.

BACKGROUND: Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization. OBJECTIVE: The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance. METHODS: Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart. RESULTS: pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T-wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations. CONCLUSION: pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation.

Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study.

BACKGROUND: Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model. METHODS: Langendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (TPEAK-TEND) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites. RESULTS: After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components. CONCLUSION: Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

Novel Experimental Preparation to Assess Electrocardiographic Imaging Reconstruction Techniques.

Electrocardiographic imaging (ECGI) systems are still plagued by a myriad of controllable and uncontrollable sources of error, which makes studying and improving these systems difficult. To mitigate these errors, we developed a novel experimental preparation using a rigid pericardiac cage suspended in a torso-shaped electrolytic tank. The 256-electrode cage was designed to record signals 0.5-1.0 cm above the entire epicardial surface of an isolated heart. The cage and heart were fixed in a 192-electrode torso tank filled with electrolyte with predetermined conductivity. The resulting signals served as ground truth for ECGI performed using the boundary element method (BEM) and method of fundamental solutions (MFS) with three regularization techniques: Tikhonov zero-order (Tik0), Tikhonov second-order (Tik2), truncated singular value decomposition (TSVD). Each ECGI regularization technique reconstructed cage potentials from recorded torso potentials well with spatial correlation above 0.7, temporal correlation above 0.8, and root mean squared error values below 0.7 mV. The earliest site of activation was best identified by MFS using Tik0, which localized it to within a range of 1.9 and 4.8 cm. Our novel experimental preparation has shown unprecedented agreement with simulations and represents a new standard for ECGI validation studies.

Advantages and pitfalls of noninvasive electrocardiographic imaging.

BACKGROUND: With increasing clinical use of Electrocardiographic Imaging (ECGI), it is imperative to understand the limits of this technique. The objective of this study is to evaluate a potential-based ECGI approach for activation and repolarization mapping in sinus rhythm. METHOD: Langendorff-perfused pig hearts were suspended in a human-shaped torso tank. Electrograms were recorded with a 108-electrode sock and ECGs with 256 electrodes embedded in the tank surface. Left bundle branch block (LBBB) was developed in 4 hearts through ablation, and repolarization abnormalities in another 4 hearts through regional perfusion of dofetilide and pinacidil. Electrograms were noninvasively reconstructed and reconstructed activation and repolarization features were compared to those recorded. RESULTS: Visual consistency between ECGI and recorded activation and repolarization maps was high. While reconstructed repolarization times showed significantly more error than activation times quantitatively, patterns were reconstructed with a similar level of accuracy. The number of epicardial breakthrough sites was underestimated by ECGI and these were misplaced (>20 mm) in location. Likewise, ECGI reconstructed activation maps demonstrated artificial lines of block resulting from a W-shaped QRS waveform that were not present in recorded maps. Nevertheless, ECGI allowed identification of regions of abnormal repolarization reasonably accurately in terms of size, location and timing. CONCLUSIONS: This study validates a potential-based ECGI approach to noninvasively image activation and recovery in sinus rhythm. Despite inaccuracies in epicardial breakthroughs and lines of conduction block, other important clinical features such as regions of abnormal repolarization can be accurately derived making ECGI a valuable clinical tool.

Optical Imaging of Ventricular Action Potentials in a Torso Tank: A New Platform for Non-Invasive Electrocardiographic Imaging Validation.

Background: Non-invasive electrocardiographic imaging (ECGI) is a promising tool to provide high-resolution panoramic imaging of cardiac electrical activity noninvasively from body surface potential measurements. Current experimental methods for ECGI validation are limited to comparison with unipolar electrograms and the relatively low spatial resolution of cardiac mapping arrays. We aim to develop a novel experimental set up combining a human shaped torso tank with high-resolution optical mapping allowing the validation of ECGI reconstructions. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, with the left anterior descending artery (LAD) cannulated on a separate perfusion. Electrical signals were recorded from an 108-electrode epicardial sock and 128 electrodes embedded in the tank surface. Simultaneously, optical mapping of the heart was performed through the anterior surface of the tank. Recordings were made in sinus rhythm and ventricular pacing (n = 55), with activation and repolarization heterogeneities induced by perfusion of hot and cold solutions as well as Sotalol through the LAD. Fluoroscopy provided 3D cardiac and electrode geometries in the tank that were transformed to the 2D optical mapping window using an optimization algorithm. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGI and validated using optical activation and repolarization maps. Results: The transformation and alignment of the 3D geometries onto the 2D optical mapping window was good with an average correlation of 0.87 ± 0.10 and error of 7.7 ± 3.1 ms with activation derived from the sock. The difference in repolarization times were more substantial (error = 17.4 ± 3.7 ms) although the sock and optical repolarization patterns themselves were very similar (correlation = 0.83 ± 0.13). Validation of ECGI reconstructions revealed ECGI accurately captures the pattern of activation (correlation = 0.79 ± 0.11) and identified regions of late and/or early repolarization during different perfusions through LAD. ECGI also correctly demonstrated gradients in both activation and repolarization, although in some cases these were under or over-estimated or shifted slightly in space. Conclusion: A novel experimental setup has been developed, combining a human-shaped torso tank with optical mapping, which can be effectively used in the validation of ECGI techniques; including the reconstruction of activation and repolarization patterns and gradients.