Purkinje network and myocardial substrate at the onset of human ventricular fibrillation: implications for catheter ablation.

AIMS: Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with structural cardiac abnormalities. METHODS AND RESULTS: We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes [interquartile range (IQR) 4-16] to 0 episode (IQR 0-2) (P < 0.001) at 56 ± 30 months. CONCLUSIONS: The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden. KEY QUESTION: The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown. KEY FINDING: Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients. TAKE-HOME MESSAGE: The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.

Effect of topical bovine colostrum in wound healing of corneal surface after acute ocular alkali burn in mice.

The purpose of this study was to evaluate the effect of bovine colostrum (BC) in the regeneration of corneal epithelial cells on an ocular alkali burn model. Twenty-four C57BL/6 mice were categorized into two gender/age-matched groups for treatment. Two days after inducing a corneal alkali burn in all left eyes with 4 µl of sodium hydroxide 0.15 mol/l, both eyes of group 1 were treated with BC 4 times per day, and both eyes of group 2 were treated with isotonic saline solution (SS). The epithelial defect was photographed and measured by fluorescein staining on days two, four, seven, and ten. Ocular burn damage was assessed with a pre-established classification in clock hours from the limbus. After 10 days both eyes were processed, half of the group's corneas were assessed histopathologically, and the other half was used for pro/anti-inflammatory cytokine quantification using ELISA. BC treated (Group 1) corneas revealed significantly improved fluorescein staining score for limbal involvement when compared to SS treated (Group 2) corneas at days 4 (p = 0.013), 7 (p < 0.001), and 10 (p < 0.001), respectively. No differences were noted in limbal involvement at day 2 between the two groups (p > 0.99). The overall change (difference in slope) in fluorescein staining for limbal involvement between days 2 and 10 was -0.1669 (p = 0.006). Histologic examinations and cytokine measurements of group 2 demonstrated a strong inflammatory component compared to group 1. Our data indicates that topical application of BC facilitates corneal re-epithelialization and wound healing by suppressing the inflammatory process in an ocular alkali burn model.

Steep repolarization time gradients in pig hearts cause distinct changes in composite electrocardiographic T-wave parameters.

BACKGROUND: The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T-wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T-wave markers to controlled drug-induced regional RT gradients in intact pig hearts. METHODS: Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff-perfused hearts placed inside a torso tank. From the 12-lead ECG on the torso tank, the mean, maximum, and dispersion (max-min) of QTtime , JTtime , Tpeak-end , Twidth , TQratio , dV/dtmax , Tarea , Tamp , and T-upslope duration were determined, as well as upslope end difference between leads V1 and V6 . RESULTS: Temporal T-wave parameters Tpeak-end , Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T-upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1 -V6 upslope end difference were not significantly correlated with RT gradient. CONCLUSION: Composite 12-lead ECG T-wave parameters Tpeak-end , Twidth , TQratio , upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T-wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.

Spatiotemporal approximation of cardiac activation and recovery isochrones.

BACKGROUND: The sequence of myocardial activation and recovery can be studied in detail by invasive catheter recordings of cardiac electrograms (EGMs), or noninvasive inverse reconstructions thereof with electrocardiographic imaging (ECGI). Local activation and recovery times are obtained from a unipolar EGM by the moment of maximum downslope of the QRS complex or maximum upslope of the T wave, respectively. However, both invasive and noninvasive recordings of intracardiac EGMs may suffer from noise and fractionation, making reliable detection of these deflections nontrivial. METHODS: Here, we introduce a novel method that benefits from the spatial coupling of these processes, and incorporate not only the temporal EGM deflection, but also the spatial gradients. We validated this approach in computer simulations, in animal data with ECGI and invasive electrode recordings, and illustrated its use in a clinical case. RESULTS: In the simulated data, the spatiotemporal approach was able to incorporate spatial information to better select the correct deflection in artificially fractionated EGMs and outperformed the traditional temporal-only method. In experimental data, the accuracy of time estimation from ECGI compared to invasive recordings significantly increased from R = 0.73 (activation) and R = 0.58 (recovery) with the temporal-only method to R = 0.79 (activation) and R = 0.72 (recovery) with the novel approach. Localization of the pacing origin of paced beats improved significantly from 36 mm mean error with the temporal-only approach to 23 mm with the spatiotemporal approach. CONCLUSION: The spatiotemporal method to compute activation and recovery times from EGMs outperformed the traditional temporal-only approach in which spatial information was not taken into account.

Solving Inverse Electrocardiographic Mapping Using Machine Learning and Deep Learning Frameworks.

Electrocardiographic imaging (ECGi) reconstructs electrograms at the heart's surface using the potentials recorded at the body's surface. This is called the inverse problem of electrocardiography. This study aimed to improve on the current solution methods using machine learning and deep learning frameworks. Electrocardiograms were simultaneously recorded from pigs' ventricles and their body surfaces. The Fully Connected Neural network (FCN), Long Short-term Memory (LSTM), Convolutional Neural Network (CNN) methods were used for constructing the model. A method is developed to align the data across different pigs. We evaluated the method using leave-one-out cross-validation. For the best result, the overall median of the correlation coefficient of the predicted ECG wave was 0.74. This study demonstrated that a neural network can be used to solve the inverse problem of ECGi with relatively small datasets, with an accuracy compatible with current standard methods.

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.

Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias.

Ten years ago, electrocardiographic imaging (ECGI) started to demonstrate its efficiency in clinical settings. The initial application to localize focal ventricular arrhythmias such as ventricular premature beats was probably the easiest to challenge and validates the concept. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff-Parkinson-White syndrome) is described here.

Capital and time: uncertainty and qualitative measures of inequality.

This review compares Piketty and Marx's approaches to capital and time in order to argue for the importance of qualitative measures of inequality. These latter measures emphasize varying experiences across classes and through history of uncertainty and insecurity. They explore how the social rhythms of capital profoundly affect the ability to plan a life-course. Quantitative measures such as those used by Piketty that focus on the amount of capital that accrues through time cannot capture such important phenomenon. This is especially because their calculations rest on absolute amounts of capital recorded in formal state statistics. Their limits are particularly revealed if we consider issues of: informal labour, social reproduction, and changing institutional forms of public debt. If we are to build the inter-disciplinary rapprochement between social science and economics that Piketty calls for it must be through asserting the value of qualitative measures of insecurity and its effects on decision making. These are important to track both at the macro-level of institutions and at the micro-level scale of human lives. It is, therefore, through emphasizing the existing strengths of both anthropology and history that we can meet Piketty's important challenge to make our scholarship relevant to current political and social debates.

A His bundle pacing protocol for suppressing ventricular arrhythmia maintenance and improving defibrillation efficacy.

BACKGROUND: The excitable gap (EG), defined as the excitable tissue between two subsequent wavefronts of depolarization, is critical for maintaining reentry that underlies deadly ventricular arrhythmias. EG in the His-Purkinje Network (HPN) plays an important role in the maintenance of electrical wave reentry that underlies these arrhythmias. OBJECTIVE: To determine if rapid His bundle pacing (HBP) during reentry reduces the amount of EG in the HPN and ventricular myocardium to suppress reentry maintenance and/or improve defibrillation efficacy. METHODS: In a virtual human biventricular model, reentry was initiated with rapid line pacing followed by HBP delivered for 3, 6, or 9 s at pacing cycle lengths (PCLs) ranging from 10 to 300 ms (n=30). EG was calculated independently for the HPN and myocardium over each PCL. Defibrillation efficacy was assessed for each PCL by stimulating myocardial surface EG with delays ranging from 0.25 to 9 s (increments of 0.25 s, n=36) after the start of HBP. Defibrillation was successful if reentry terminated within 1 s after EG stimulation. This defibrillation protocol was repeated without HBP. To test the approach under different pathological conditions, all protocols were repeated in the model with right (RBBB) or left (LBBB) bundle branch block. RESULTS: Compared to without pacing, HBP for >3 seconds reduced average EG in the HPN and myocardium across a broad range of PCLs for the default, RBBB, and LBBB models. HBP >6 seconds terminated reentrant arrhythmia by converting HPN activation to a sinus rhythm behavior in the default (6/30 PCLs) and RBBB (7/30 PCLs) models. Myocardial EG stimulation during HBP increased the number of successful defibrillation attempts by 3%-19% for 30/30 PCLs in the default model, 3%-6% for 14/30 PCLs in the RBBB model, and 3%-11% for 27/30 PCLs in the LBBB model. CONCLUSION: HBP can reduce the amount of excitable gap and suppress reentry maintenance in the HPN and myocardium. HBP can also improve the efficacy of low-energy defibrillation approaches targeting excitable myocardium. HBP during reentrant arrhythmias is a promising anti-arrhythmic and defibrillation strategy.

A Patchwork Method to Improve the Performance of Current Methods for Solving the Inverse Problem of Electrocardiography.

OBJECTIVE: Noninvasive electrocardiographic imaging (ECGI) reconstructs cardiac electrical activity from body surface potential measurements. However, current methods have demonstrated inaccuracies in reconstructing sinus rhythm, and in particular breakthrough sites. This study aims to combine existing inverse algorithms, making the most of their advantages while minimizing their limitations. METHOD: The "patchwork method" (PM) combines two classical numerical methods for ECGI: the method of fundamental solutions (MFS) and the finite-element method (FEM). We assume that the method with the smallest residual in the predicted torso potentials, computed using the boundary element method (BEM), provides the most accurate solution. The PM selects for each heart node and time step the method whose estimated reconstruction error is smallest. The performance of the PM was evaluated using simulated ectopic and normal ventricular beats. RESULTS: Cardiac potentials and activation maps obtained with the PM (CC = 0.63 ± 0.01 and 0.61 ± 0.05 respectively) were more accurate than MFS (CC = 0.61 ± 0.01 and 0.48 ± 0.05 respectively), FEM (CC = 0.58 ± 0.01 and 0.51 ± 0.02 respectively) or BEM (CC = 0.57 ± 0.02 and 0.49 ± 0.02 respectively). The PM also located all epicardial breakthrough sites, whereas the traditional numerical methods usually missed one. Furthermore, the PM showed its robustness and stability in the presence of Gaussian noise added to the torso potentials. CONCLUSION: The PM overcomes some of the limitations of classical numerical methods, improving the accuracy of mapping important features of activation during sinus rhythm and paced beats. SIGNIFICANCE: This novel method for optimizing ECGI solutions opens a new avenue for improving not only ECGI but also other inverse problems.

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.

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.

In-Depth Analysis of Preoperative OCT Markers as Prognostic Factors for Lamellar Macular Holes and Epiretinal Membrane Foveoschisis.

OBJECTIVE: To identify preoperative OCT markers that correlate with postoperative visual acuity (VA) changes in eyes with lamellar macular hole (LMH) and epiretinal membrane foveoschisis (ERMF) after pars plana vitrectomy (PPV). DESIGN: Cross-sectional retrospective study. SUBJECTS: Patients seen at the Wilmer Eye Institute between 2011 and 2021 with an International Classification of Diseases, Ninth Revision, or International Classification of Diseases, 10th Revision, code for "macular hole" that underwent PPV, and demonstrated all OCT criteria present for either LMH or ERMF based on the Hubschman et al (2020) classification. METHODS: Optical coherence tomography markers including hole dimensions, retinal layer continuity, and ellipsoid zone (EZ) convexity and pixelated intensity were quantified. Visual acuity immediately before PPV and at the last follow-up date available were both recorded. MAIN OUTCOME MEASURES: Preoperative OCT variables that are correlated with postoperative changes in VA. RESULTS: Forty-two eyes from 42 patients with LMH (n = 11) and ERMF (n = 31) that underwent PPV were identified. Visual acuity in the ERMF cohort significantly improved at last follow-up compared with preoperative VA (P < 0.001), whereas VA in the LMH cohort did not (P = 0.14). In the LMH cohort, retinal layer continuity at the hole edge was positively correlated with change in VA at final follow-up, whereas hole height was negatively correlated with VA. In the ERMF cohort, preoperative VA was negatively correlated with change in VA at final follow-up. CONCLUSIONS: Retinal layer continuity at the hole and hole height are novel preoperative markers that predict postoperative VA change in LMH. After identifying the type of macular lesion, surgeons should consider using these preoperative OCT markers when counseling patients on potential postoperative VA outcomes and when managing patient expectations. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

An update on visual prosthesis.

PURPOSE: To review the available evidence on the different retinal and visual prostheses for patients with retinitis pigmentosa and new implants for other indications including dry age-related macular degeneration. METHODS: The PubMed, GoogleScholar, ScienceDirect, and ClinicalTrials databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the worldwide advances in retinal prosthesis, clinical trials, status of devices and potential future directions up to December 2022. RESULTS: Thirteen devices were found to be current and were ordered by stimulation location. Six have active clinical trials. Four have been discontinued, including the Alpha IMS, Alpha AMS, IRIS II, and ARGUS II which had FDA and CE mark approval. Future directions will be presented in the review. CONCLUSION: This review provides an update of retinal prosthetic devices, both current and discontinued. While some devices have achieved visual perception in animals and/or humans, the main issues impeding the commercialization of these devices include: increased length of time to observe outcomes, difficulties in finding validated meaures for use in studies, unknown long-term effects, lack of funding, and a low amount of patients simultaneously diagnosed with RP lacking other comorbid conditions. The ARGUS II did get FDA and CE mark approval so it was deemed safe and also effective. However, the company became more focused on a visual cortical implant. Future efforts are headed towards more biocompatible, safe, and efficacious devices.

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.

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.