Non-invasive localization of post-infarct ventricular tachycardia exit sites to guide ablation planning: a computational deep learning platform utilizing the 12-lead electrocardiogram and intracardiac electrograms from implanted devices.

AIMS: Existing strategies that identify post-infarct ventricular tachycardia (VT) ablation target either employ invasive electrophysiological (EP) mapping or non-invasive modalities utilizing the electrocardiogram (ECG). Their success relies on localizing sites critical to the maintenance of the clinical arrhythmia, not always recorded on the 12-lead ECG. Targeting the clinical VT by utilizing electrograms (EGM) recordings stored in implanted devices may aid ablation planning, enhancing safety and speed and potentially reducing the need of VT induction. In this context, we aim to develop a non-invasive computational-deep learning (DL) platform to localize VT exit sites from surface ECGs and implanted device intracardiac EGMs. METHODS AND RESULTS: A library of ECGs and EGMs from simulated paced beats and representative post-infarct VTs was generated across five torso models. Traces were used to train DL algorithms to localize VT sites of earliest systolic activation; first tested on simulated data and then on a clinically induced VT to show applicability of our platform in clinical settings. Localization performance was estimated via localization errors (LEs) against known VT exit sites from simulations or clinical ablation targets. Surface ECGs successfully localized post-infarct VTs from simulated data with mean LE = 9.61 ± 2.61 mm across torsos. VT localization was successfully achieved from implanted device intracardiac EGMs with mean LE = 13.10 ± 2.36 mm. Finally, the clinically induced VT localization was in agreement with the clinical ablation volume. CONCLUSION: The proposed framework may be utilized for direct localization of post-infarct VTs from surface ECGs and/or implanted device EGMs, or in conjunction with efficient, patient-specific modelling, enhancing safety and speed of ablation planning.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

An in-silico assessment of efficacy of two novel intra-cardiac electrode configurations versus traditional anti-tachycardia pacing therapy for terminating sustained ventricular tachycardia.

The implanted cardioverter defibrillator (ICD) is an effective direct therapy for the treatment of cardiac arrhythmias, including ventricular tachycardia (VT). Anti-tachycardia pacing (ATP) is often applied by the ICD as the first mode of therapy, but is often found to be ineffective, particularly for fast VTs. In such cases, strong, painful and damaging backup defibrillation shocks are applied by the device. Here, we propose two novel electrode configurations: "bipolar" and "transmural" which both combine the concept of targeted shock delivery with the advantage of reduced energy required for VT termination. We perform an in silico study to evaluate the efficacy of VT termination by applying one single (low-energy) monophasic shock from each novel configuration, comparing with conventional ATP therapy. Both bipolar and transmural configurations are able to achieve a higher efficacy (93% and 85%) than ATP (45%), with energy delivered similar to and two orders of magnitudes smaller than conventional ICD defibrillation shocks, respectively. Specifically, the transmural configuration (which applies the shock vector directly across the scar substrate sustaining the VT) is most efficient, requiring typically less than 1 J shock energy to achieve a high efficacy. The efficacy of both bipolar and transmural configurations are higher when applied to slow VTs (100% and 97%) compared to fast VTs (57% and 29%). Both novel electrode configurations introduced are able to improve electrotherapy efficacy while reducing the overall number of required therapies and need for strong backup shocks.

Conceptual Intra-Cardiac Electrode Configurations That Facilitate Directional Cardiac Stimulation for Optimal Electrotherapy.

OBJECTIVE: Electrotherapy remains the most effective direct therapy against lethal cardiac arrhythmias. When an arrhythmic event is sensed, either strong electric shocks or controlled rapid pacing is automatically applied directly to the heart via an implanted cardioverter defibrillator (ICDs). Despite their success, ICDs remain a highly non-optimal therapy: the strong shocks required for defibrillation cause significant extra-cardiac stimulation, resulting in pain and long-term tissue damage, and can also limit battery life. When used in anti-tachycardia pacing mode, ICDs are also often ineffective, as the pacing electrode can be far away from the centre of the arrhythmia, making it hard for the paced wave to interrupt and terminate it. METHODS: In this paper, we present two conceptual intra-cardiac directional electrode configurations in silico based on novel arrangements of pairs of positive-negative electrodes. Both configurations have the potential to cause preferential excitation on specific regions of the heart. RESULTS: We demonstrate how the properties of the induced field varies spatially around the electrodes and how it depends upon the specific arrangements of dipole electrode pairs. The results show that when tested within anatomically-realistic rabbit ventricular models, both electrode configurations produce strong virtual electrodes on the targeted endocardial surfaces, with weaker virtual electrodes produced elsewhere. CONCLUSIONS: The proposed electrode configurations may facilitate targeted far-field anti-tachycardia pacing and/or defibrillation, which may be useful in cases where conventional anti-tachycardia pacing fails. In addition, the conceptual electrode designs intrinsically confine the electric field to the immediate vicinity of the electrodes, and may, thus, minimize pain due to unnecessary extra-cardiac stimulation.

Left ventricular activation-recovery interval variability predicts spontaneous ventricular tachyarrhythmia in patients with heart failure.

BACKGROUND: Enhanced beat-to-beat variability of repolarization is strongly linked to arrhythmogenesis and is largely due to variation in ventricular action potential duration (APD). Previous studies in humans have relied on QT interval measurements; however, a direct relationship between beat-to-beat variability of APD and arrhythmogenesis in humans has yet to be demonstrated. OBJECTIVE: This study aimed to explore the beat-to-beat repolarization dynamics in patients with heart failure at the level of ventricular APD. METHODS: Forty-three patients with heart failure and implanted cardiac resynchronization therapy - defibrillator devices were studied. Activation-recovery intervals as a surrogate for APD were recorded from the left ventricular epicardial lead while pacing from the right ventricular lead to maintain a constant cycle length. RESULTS: During a mean follow-up of 23.6±13.6 months, 11 patients sustained ventricular fibrillation/ventricular tachycardia (VT/VF) and received appropriate implantable cardioverter-defibrillator therapies (antitachycardia pacing or shock therapy). Activation-recovery interval variability (ARIV) was significantly greater in patients with subsequent VT/VF than in those without VT/VF (3.55±1.3 ms vs 2.77±1.09 ms; P=.047). Receiver operating characteristic curve analysis (area under the curve 0.71; P=.046) suggested high- and low-risk ARIV groups for VT/VF. Kaplan-Meier survival analysis demonstrated that the time until first appropriate therapy for VT/VF was significantly shorter in the high-risk ARIV group (P=.028). ARIV was a predictor for VT/VF in the multivariate Cox model (hazard ratio 1.623; 95% confidence interval 1.1-2.393; P=.015). CONCLUSION: Increased left ventricular ARIV is associated with an increased risk of VT/VF in patients with heart failure.

An activation-repolarization time metric to predict localized regions of high susceptibility to reentry.

BACKGROUND: Initiation of reentrant ventricular tachycardia (VT) involves complex interactions between front and tail of the activation wave. Recent experimental work has identified the time interval between S2 repolarization proximal to a line of functional block and S2 activation at the adjacent distal side as a critical determinant of reentry. OBJECTIVES: We hypothesized that (1) an algorithm could be developed to generate a spatial map of this interval ("reentry vulnerability index" [RVI]), (2) this would accurately identify a site of reentry without the need to actually induce the arrhythmia, and (3) it would be possible to generate an RVI map in patients during routine clinical procedures. METHODS: An algorithm was developed that calculated RVI between all pairs of electrodes within a given radius. RESULTS: The algorithm successfully identified the region with increased susceptibility to reentry in an established Langendorff pig heart model and the site of reentry and rotor formation in an optically mapped sheep ventricular preparation and computational simulations. The feasibility of RVI mapping was evaluated during a clinical procedure by coregistering with cardiac anatomy and physiology of a patient undergoing VT ablation. CONCLUSION: We developed an algorithm to calculate a reentry vulnerability index from intervals between local repolarization and activation. The algorithm accurately identified the region of reentry in 2 animal models of functional reentry. The clinical application was demonstrated in a patient with VT and identified the area of reentry without the need of inducing the arrhythmia.

Development of an anatomically detailed MRI-derived rabbit ventricular model and assessment of its impact on simulations of electrophysiological function.

Recent advances in magnetic resonance (MR) imaging technology have unveiled a wealth of information regarding cardiac histoanatomical complexity. However, methods to faithfully translate this level of fine-scale structural detail into computational whole ventricular models are still in their infancy, and, thus, the relevance of this additional complexity for simulations of cardiac function has yet to be elucidated. Here, we describe the development of a highly detailed finite-element computational model (resolution: approximately 125 microm) of rabbit ventricles constructed from high-resolution MR data (raw data resolution: 43 x 43 x 36 microm), including the processes of segmentation (using a combination of level-set approaches), identification of relevant anatomical features, mesh generation, and myocyte orientation representation (using a rule-based approach). Full access is provided to the completed model and MR data. Simulation results were compared with those from a simplified model built from the same images but excluding finer anatomical features (vessels/endocardial structures). Initial simulations showed that the presence of trabeculations can provide shortcut paths for excitation, causing regional differences in activation after pacing between models. Endocardial structures gave rise to small-scale virtual electrodes upon the application of external field stimulation, which appeared to protect parts of the endocardium in the complex model from strong polarizations, whereas intramural virtual electrodes caused by blood vessels and extracellular cleft spaces appeared to reduce polarization of the epicardium. Postshock, these differences resulted in the genesis of new excitation wavefronts that were not observed in more simplified models. Furthermore, global differences in the stimulus recovery rates of apex/base regions were observed, causing differences in the ensuing arrhythmogenic episodes. In conclusion, structurally simplified models are well suited for a large range of cardiac modeling applications. However, important differences are seen when behavior at microscales is relevant, particularly when examining the effects of external electrical stimulation on tissue electrophysiology and arrhythmia induction. This highlights the utility of histoanatomically detailed models for investigations of cardiac function, in particular for future patient-specific modeling.