Distinct Electrogram Features and Ventricular Arrhythmia Induction Modes Between Repolarization and Conduction Heterogeneities.

BACKGROUND: Recent clinical studies have indicated the presence of localized electrical abnormalities in idiopathic ventricular fibrillation and J-wave syndrome patients. OBJECTIVES: This study aims to characterize the specific electrical signatures of localized repolarization and conduction heterogeneities and their respective role in vulnerability to arrhythmias. METHODS: Optical mapping was performed in porcine right ventricles with local: 1) repolarization shortening; 2) conduction slowing; or 3) structural heterogeneity induced by locally perfusing: 1) pinacidil (20 µmol/L, n = 13); or 2) flecainide (2 µmol/L, n = 13) via an epicardial catheter; or 3) by local epicardial tissue destruction (9 radiofrequency lesions n = 12). Electrograms were recorded (n = 5 in each group) and spontaneous and induced arrhythmias were quantified and optically mapped. RESULTS: Electrograms were normal in (1) but showed local fragmentation in 40% of preparations in (2) with greater effects observed at high pacing frequencies dependent on the wavefront direction. In (3), the structural substrate alone increased the width and number of peaks in the electrograms, and addition of flecainide induced pronounced fragmentation (≥3 peaks and ≥70 ms) in all cases. Occurrence of spontaneous arrhythmias was significantly increased in (1) and (2) (P < 0.0001 and 0.05, respectively, vs baseline) and were triggered by ectopies. Vulnerability to arrhythmias at high pacing frequencies (≥2 Hz) was the lowest in (1) and greatest in (2). CONCLUSIONS: Microstructural substrates have the most pronounced impact on electrograms, especially when combined with sodium channel blockers, whereas local action potential duration shortening does not lead to electrogram fragmentation even though it is associated with the highest prevalence of spontaneous arrhythmias.

Open-source software for respiratory rate estimation using single-lead electrocardiograms.

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing a non-proprietary method that uses minimal ECG leads, generally available from mobile cardiac monitors is highly desirable. Here, we introduce an open-source and well-documented Python-based algorithm that estimates RR requiring only single-stream ECG signals. The algorithm was first developed using ECGs from awake, spontaneously breathing adult human subjects. The algorithm-estimated RRs exhibited close linear correlation to the subjects' true RR values demonstrating an R2 of 0.9092 and root mean square error of 2.2 bpm. The algorithm robustness was then tested using ECGs generated by the ischemic hearts of anesthetized, mechanically ventilated sheep. Although the ECG waveforms during ischemia exhibited severe morphologic changes, the algorithm-determined RRs exhibited high fidelity with a resolution of 1 bpm, an absolute error of 0.07 ± 0.07 bpm, and a relative error of 0.67 ± 0.64%. This optimized Python-based RR estimation technique will likely be widely adapted for remote lung function assessment in patients with cardiopulmonary disease.

Can Stochastic Pacing Restore Heart Rate Variability in Diseased Hearts? An In-vivo Ovine Case Study.

Heart rate variability (HRV) is an important clinical parameter that depicts the autonomic balance. Diminished HRV has been associated with diseased hearts and incorporating stochasticity in pacing has been investigated as a potential mechanism for restoring the altered autonomic balance and preventing cardiac arrhythmias. We studied the change in HRV with the development of chronic myocardial infarction (MI) in adult sheep (n=16). Next, we investigated the utility of stochastic pacing in modulating HRV in-vivo in both sham and MI hearts. The propensity of the heart to the development of cardiac alternans, a known precursor to tachyarrhythmias, was studied under three different pacing techniques, namely periodic pacing, stochastic pacing and constant diastolic interval (DI) pacing in one sham and one MI sheep. Autonomic balance was observed to be altered after 6 weeks of chronic MI. Increased heart rate, QTc interval, standard deviation of the R-R intervals and LF/HF ratio was observed in MI hearts. Stochastic pacing was found to be proarrhythmic and increased T-wave alternans burden was observed with increase in stochasticity. Maintaining a constant DI on every beat demonstrated reduced alternans levels compared to both periodic and stochastic pacing.Clinical Relevance-Our results demonstrate that precise control of the diastolic interval may be more beneficial in inhibiting arrhythmias than stochastic pacing.

Image-Based Tools and Analysis for Human RVOT/RV Structures.

The right-ventricular (RV) outflow tract (RVOT) and the transition to the RV free wall are recognized sources of arrhythmia in human hearts. However, we do not fully understand myocardial tissue structures in this region. Human heart tissue was processed for optical clarity, labelled with wheat-germ agglutin (WGA) and anti-Cx43, and imaged on a custom-built line scanning confocal microscope. The 3D images were analyzed for myocyte gross structures and cell morphology. There were regions of high organization as well as rapid changes to more heterogeneous regions. Preliminary cell segmentations were used to estimate cell morphology. Observed RVOT/RV structure is consistent with known arrhythmic substrates.Clinical Relevance- New views of human tissue structure enable clearer clinical understanding of arrhythmogenic activation pathways and targets for invasive treatment such as RF ablation.

Functional Epicardial Conduction Disturbances Due to a SCN5A Variant Associated With Brugada Syndrome.

BACKGROUND: Brugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical. OBJECTIVES: This study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies. METHODS: A heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD. Postmortem genotyping was performed, and clinical examinations were done on first-degree relatives. The right ventricle was optically mapped, followed by high-field magnetic resonance imaging and histology. Connexin-43 and NaV1.5 were localized by immunofluorescence, and RNA and protein expression levels were studied. HEK-293 cell surface biotinylation assays were performed to examine NaV1.5 trafficking. RESULTS: A Brugada-related SCD diagnosis was established for the donor because of a SCN5A Brugada-related variant (p.D356N) inherited from his mother, together with a concomitant NKX2.5 variant of unknown significance. Optical mapping demonstrated a localized epicardial region of impaired conduction near the outflow tract, in the absence of repolarization alterations and microstructural defects, leading to conduction blocks and figure-of-8 patterns. NaV1.5 and connexin-43 localizations were normal in this region, consistent with the finding that the p.D356N variant does not affect the trafficking, nor the expression of NaV1.5. Trends of decreased NaV1.5, connexin-43, and desmoglein-2 protein levels were noted; however, the RT-qPCR results suggested that the NKX2-5 variant was unlikely to be involved. CONCLUSIONS: This study demonstrates for the first time that SCD associated with a Brugada-SCN5A variant can be caused by localized functionally, not structurally, impaired conduction.

Assessment of Nit-Occlud atrial septal defect occluder device healing process using micro-computed tomography imaging.

After percutaneous implantation of a cardiac occluder, a complex healing process leads to the device coverage within several months. An incomplete device coverage increases the risk of device related complications such as thrombosis or endocarditis. We aimed to assess the device coverage process of atrial septal defect (ASD) occluders in a chronic sheep model using micro-computed tomography (micro-CT). After percutaneous creation of an ASD, 8 ewes were implanted with a 16-mm Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) and were followed for 1 month (N = 3) and 3 months (N = 5). After heart explant, the device coverage was assessed using micro-CT (resolution of 41.7 µm) and was compared to histological analysis. The micro-CT image reconstruction was performed in 2D and 3D allowing measurement of the coverage thickness and surface for each device. Macroscopic assessment of devices showed that the coverage was complete for the left-side disk in all cases. Yet incomplete coverage of the right-side disk was observed in 5 of the 8 cases. 2D and 3D micro-CT analysis allowed an accurate evaluation of device coverage of each disk and was overall well correlated to histology sections. Surface calculation from micro-CT images of the 8 cases showed that the median surface of coverage was 93±8% for the left-side disk and 55±31% for the right-side disk. The assessment of tissue reactions, including endothelialisation, after implantation of an ASD occluder can rely on in vitro micro-CT analysis. The translation to clinical practice is challenging but the potential for individual follow-up is shown, to avoid thrombotic or infective complications.

Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans.

Atrial fibrillation (AF) is the most persistent arrhythmia today, with its prevalence increasing exponentially with the rising age of the population. Particularly at elevated heart rates, a functional abnormality known as cardiac alternans can occur prior to the onset of lethal arrhythmias. Cardiac alternans are a beat-to-beat oscillation of electrical activity and the force of cardiac muscle contraction. Extensive evidence has demonstrated that microvolt T-wave alternans can predict ventricular fibrillation vulnerability and the risk of sudden cardiac death. The majority of our knowledge of the mechanisms of alternans stems from studies of ventricular electrophysiology, although recent studies offer promising evidence of the potential of atrial alternans in predicting the risk of AF. Exciting preclinical and clinical studies have demonstrated a link between atrial alternans and the onset of atrial tachyarrhythmias. Here, we provide a comprehensive review of the clinical utility of atrial alternans in identifying the risk and guiding treatment of AF.

A comprehensive framework for evaluation of high pacing frequency and arrhythmic optical mapping signals.

Introduction: High pacing frequency or irregular activity due to arrhythmia produces complex optical mapping signals and challenges for processing. The objective is to establish an automated activation time-based analytical framework applicable to optical mapping images of complex electrical behavior. Methods: Optical mapping signals with varying complexity from sheep (N = 7) ventricular preparations were examined. Windows of activation centered on each action potential upstroke were derived using Hilbert transform phase. Upstroke morphology was evaluated for potential multiple activation components and peaks of upstroke signal derivatives defined activation time. Spatially and temporally clustered activation time points were grouped in to wave fronts for individual processing. Each activation time point was evaluated for corresponding repolarization times. Each wave front was subsequently classified based on repetitive or non-repetitive events. Wave fronts were evaluated for activation time minima defining sites of wave front origin. A visualization tool was further developed to probe dynamically the ensemble activation sequence. Results: Our framework facilitated activation time mapping during complex dynamic events including transitions to rotor-like reentry and ventricular fibrillation. We showed that using fixed AT windows to extract AT maps can impair interpretation of the activation sequence. However, the phase windowing of action potential upstrokes enabled accurate recapitulation of repetitive behavior, providing spatially coherent activation patterns. We further demonstrate that grouping the spatio-temporal distribution of AT points in to coherent wave fronts, facilitated interpretation of isolated conduction events, such as conduction slowing, and to derive dynamic changes in repolarization properties. Focal origins precisely detected sites of stimulation origin and breakthrough for individual wave fronts. Furthermore, a visualization tool to dynamically probe activation time windows during reentry revealed a critical single static line of conduction slowing associated with the rotation core. Conclusion: This comprehensive analytical framework enables detailed quantitative assessment and visualization of complex electrical behavior.

Investigating Electrophysiological Markers of Arrhythmogenesis in a Chronic Myocardial Infarction Ovine Model.

Cardiac alternans has been associated with an increased propensity to lethal tachyarrhythmias such as ventricular tachycardia and fibrillation (VT/VF). Myocardial infarction (MI), resulting from restricted oxygen supply to the heart, is a known substrate for VT/VF. Here, we investigate the utility of cardiac alternans as a predictor of tachyarrhythmias in a chronic MI ovine model. In-vivo electrophysiological studies were performed to assess the change in microvolt T-wave alternans (TWA) with induction of acute ischemia following coronary artery occlusion. 24-hour telemetry was performed in an ambulatory animal for 6 weeks to monitor the progression of TWA with chronic MI. At 6 weeks, ex-vivo optical mapping experiments were performed to assess the spatiotemporal evolution of alternans in sham (n=5) and chronic MI hearts (n=8). Our results demonstrate that chronic MI leads to significant electrophysiological changes in the cardiac substrate. Significant increase in TWA is observed post occlusion and a steady rise in alternans is seen with progression of chronic MI. Compared to sham, chronic MI hearts show significant presence of localized action potential amplitude alternans, which spatially evolve with an increase in pacing frequency. Clinical Relevance - Our results demonstrate that localized alternans underlie arrhythmogenesis in chronic MI hearts and microvolt TWA can serve as a biomarker of disease progression during chronic MI.

Tissue Preparation Techniques for Contrast-Enhanced Micro Computed Tomography Imaging of Large Mammalian Cardiac Models with Chronic Disease.

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of lethal arrhythmia, with high prevalence in young adults. Challenges remain in obtaining high imaging contrast at sufficient microscale resolution for preclinical models, such as large mammalian whole hearts. Moreover, tissue composition-selective contrast enhancement for three-dimensional high-resolution imaging is still lacking. Non-destructive imaging using micro-computed tomography shows promise for high-resolution imaging. The objective was to alleviate sufferance from X-ray over attenuation in large biological samples. Hearts were extracted from healthy pigs (N = 2), and sheep (N = 2) with either induced chronic myocardial infarction and fibrotic scar formation or induced chronic atrial fibrillation. Excised hearts were perfused with: a saline solution supplemented with a calcium ion quenching agent and a vasodilator, ethanol in serial dehydration, and hexamethyldisilizane under vacuum. The latter reinforced the heart structure during air-drying for 1 week. Collagen-dominant tissue was selectively bound by an X-ray contrast-enhancing agent, phosphomolybdic acid. Tissue conformation was stable in air, permitting long-duration microcomputed tomography acquisitions to obtain high-resolution (isotropic 20.7 µm) images. Optimal contrast agent loading by diffusion showed selective contrast enhancement of the epithelial layer and sub-endocardial Purkinje fibers in healthy pig ventricles. Atrial fibrillation (AF) hearts showed enhanced contrast accumulation in the posterior walls and appendages of the atria, attributed to greater collagen content. Myocardial infarction hearts showed increased contrast selectively in regions of cardiac fibrosis, which enabled the identification of interweaving surviving myocardial muscle fibers. Contrast-enhanced air-dried tissue preparations enabled microscale imaging of the intact large mammalian heart and selective contrast enhancement of underlying disease constituents.

Low-energy, single-pulse surface stimulation defibrillates large mammalian ventricles.

BACKGROUND: Strong electric shocks are the gold standard for ventricular defibrillation but are associated with pain and tissue damage. We hypothesized that targeting the excitable gap (EG) of reentry with low-energy surface stimulation is a less damaging and painless alternative for ventricular defibrillation. OBJECTIVE: The purpose of this study was to determine the conditions under which low-energy surface stimulation defibrillates large mammalian ventricles. METHODS: Low-energy surface stimulation was delivered with five electrodes that were 7 cm long and placed 1-2 cm apart on the endocardial and epicardial surfaces of perfused pig left ventricle (LV). Rapid pacing (>4 Hz) was used to induce reentry from a single electrode. A 2 ms defibrillation pulse ≤0.5 A was delivered from all electrodes with a varied time delay from the end of the induction protocol (0.1-5 seconds). Optical mapping was performed and arrhythmia dynamics analyzed. For mechanistic insight, simulations of the VF induction and defibrillation protocols were performed in silico with an LV model emulating the experimental conditions and electrodes placed 0.25-2 cm apart. RESULTS: In living LV, reentry was induced with varying complexity and dominant frequencies ranging between 3.5 to 6.2 Hz over 8 seconds postinitiation. Low-energy defibrillation was achieved with energy <60 mJ and electrode separations up to 2 cm for less complex arrhythmia. In simulations, defibrillation consistently occurred when stimulation captured >75% of the EG, which blocked reentry <2.9 mm in front of the leading reentrant wavefront. CONCLUSION: Defibrillation with low-energy, single-pulse surface stimulation is feasible with energies below the human pain threshold (100 mJ). Optimal defibrillation occurs when arrhythmia complexity is minimal and electrodes capture >75% of the EG.

It's clearly the heart! Optical transparency, cardiac tissue imaging, and computer modelling.

Recent developments in clearing and microscopy enable 3D imaging with cellular resolution up to the whole organ level. These methods have been used extensively in neurobiology, but their uptake in other fields has been much more limited. Application of this approach to the human heart and effective use of the data acquired present challenges of scale and complexity. Four interlinked issues need to be addressed: 1) efficient clearing and labelling of heart tissue, 2) fast microscopic imaging of human-scale samples, 3) handling and processing of multi-terabyte 3D images, and 4) extraction of structural information in computationally tractable structure-based models of cardiac function. Preliminary studies show that each of these requirements can be achieved with the appropriate application and development of existing technologies.

Advances in Cardiac Pacing: Arrhythmia Prediction, Prevention and Control Strategies.

Cardiac arrhythmias constitute a tremendous burden on healthcare and are the leading cause of mortality worldwide. An alarming number of people have been reported to manifest sudden cardiac death as the first symptom of cardiac arrhythmias, accounting for about 20% of all deaths annually. Furthermore, patients prone to atrial tachyarrhythmias such as atrial flutter and fibrillation often have associated comorbidities including hypertension, ischemic heart disease, valvular cardiomyopathy and increased risk of stroke. Technological advances in electrical stimulation and sensing modalities have led to the proliferation of medical devices including pacemakers and implantable defibrillators, aiming to restore normal cardiac rhythm. However, given the complex spatiotemporal dynamics and non-linearity of the human heart, predicting the onset of arrhythmias and preventing the transition from steady state to unstable rhythms has been an extremely challenging task. Defibrillatory shocks still remain the primary clinical intervention for lethal ventricular arrhythmias, yet patients with implantable cardioverter defibrillators often suffer from inappropriate shocks due to false positives and reduced quality of life. Here, we aim to present a comprehensive review of the current advances in cardiac arrhythmia prediction, prevention and control strategies. We provide an overview of traditional clinical arrhythmia management methods and describe promising potential pacing techniques for predicting the onset of abnormal rhythms and effectively suppressing cardiac arrhythmias. We also offer a clinical perspective on bridging the gap between basic and clinical science that would aid in the assimilation of promising anti-arrhythmic pacing strategies.

Clinical Potential of Beat-to-Beat Diastolic Interval Control in Preventing Cardiac Arrhythmias.

Life-threatening ventricular arrhythmias and sudden cardiac death are often preceded by cardiac alternans, a beat-to-beat oscillation in the T-wave morphology or duration. However, given the spatiotemporal and structural complexity of the human heart, designing algorithms to effectively suppress alternans and prevent fatal rhythms is challenging. Recently, an antiarrhythmic constant diastolic interval pacing protocol was proposed and shown to be effective in suppressing alternans in 0-, 1-, and 2-dimensional in silico studies as well as in ex vivo whole heart experiments. Herein, we provide a systematic review of the electrophysiological conditions and mechanisms that enable constant diastolic interval pacing to be an effective antiarrhythmic pacing strategy. We also demonstrate a successful translation of the constant diastolic interval pacing protocol into an ECG-based real-time control system capable of modulating beat-to-beat cardiac electrical activity and preventing alternans. Furthermore, we present evidence of the clinical utility of real-time alternans suppression in reducing arrhythmia susceptibility in vivo. We provide a comprehensive overview of this promising pacing technique, which can potentially be translated into a clinically viable device that could radically improve the quality of life of patients experiencing abnormal cardiac rhythms.

Epicardial course of the septopulmonary bundle: Anatomical considerations and clinical implications for roof line completion.

BACKGROUND: Gaps in the roof line have been ascribed to epicardial conduction using the septopulmonary bundle. OBJECTIVES: We sought to evaluate the frequency of septopulmonary bundle bypass during roof line ablation, to describe anatomical conditions favoring this epicardial gap, and to propose an alternative strategy when present. METHODS: One hundred consecutive patients underwent atrial fibrillation ablation. A de novo roof line was created between the superior pulmonary veins. In cases of residual gaps, a floor line was created between the inferior pulmonary veins. Microtomography imaging and histological analyses of 5 human donor hearts were performed: a specific focus was made on the dome and the posterior wall. RESULTS: Residual gaps were more frequent in roof lines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roof line in all cases. Conduction block was obtained in 67 roof lines and 28 floor lines, resulting in a 95% success rate of linear block, without "box" isolation. Between the superior pulmonary veins, the atrial myocardium was thicker and consistently displayed adipose tissue separating the septopulmonary bundle from the septoatrial bundle. CONCLUSION: Epicardial conduction across the roof line is common and requires careful electrogram analysis to detect. In such cases, a floor line can be an effective alternative strategy, with clear validation criteria. Myocardial thickness and fat interposition may explain difficulties in achieving lesion transmurality during roof line ablation.

Stretchable Conductive Fabric for Cardiac Electrophysiology Applications.

Stretchable conductive fabric (SCF) is a durable nontoxic textile material coated or blended with conductive metals. Unlike solid metal, SCF effectively conducts electricity with low resistance and maintains conductance when stretched. Thus, we hypothesized that SCF electrodes are more suitable for cardiac electrophysiology applications in beating hearts than traditional solid metal electrodes. Accordingly, we developed a straightforward protocol for fabricating customized SCF electrodes and then assessed their ability to electrically stimulate and record electrical signals from beating hearts. Compared to flexible copper electrodes, SCF electrodes had similar electrical resistance (112.50 ± 25.81 vs 157.85 ± 17.06 Ω, p = 0.09), activated cardiac tissue with lower stimulus strength (27.25 ± 3.52 vs 15.35 ± 2.15 mA, p = 0.0001), recorded stable electrograms with a higher signal-to-noise ratio (20.54 ± 1.09 vs 13.35 ± 1.46 dB, p = 0.04), and were noncorrosive and harmless to cardiac tissue or vasculature. These results support the use of SCF over metal electrodes for a wide range of cardiac electrophysiology applications in the beating heart.

Assessment of the healing process after percutaneous implantation of a cardiovascular device: a systematic review.

The healing process, occurring after intra-cardiac and intra-vascular device implantation, starts with fibrin condensation and attraction of inflammatory cells, followed by the formation of fibrous tissue that slowly covers the device. The duration of this process is variable and may be incomplete, which can lead to thrombus formation, dislodgement of the device or stenosis. To better understand this process and the neotissue formation, animal models were developed: small (rats and rabbits) and large (sheep, pigs, dogs and baboons) animal models for intra-vascular device implantation; sheep and pigs for intra-cardiac device implantation. After intra-vascular and intra-cardiac device implantation in these animal models, in vitro techniques, i.e. histology, which is the gold standard and scanning electron microscopy, were used to assess the device coverage, characterize the cell constitution and detect complications such as thrombosis. In humans, optical coherence tomography and intra-vascular ultrasounds are both invasive modalities used after stent implantation to assess the structure of the vessels, atheroma plaque and complications. Non-invasive techniques (computed tomography and magnetic resonance imaging) are in development in humans and animal models for tissue characterization (fibrosis), device remodeling evaluation and device implantation complications (thrombosis and stenosis). This review aims to (1) present the experimental models used to study this process on cardiac devices; (2) focus on the in vitro techniques and invasive modalities used currently in humans for intra-vascular and intra-cardiac devices and (3) assess the future developments of non-invasive techniques in animal models and humans for intra-cardiac devices.

Wide-area low-energy surface stimulation of large mammalian ventricular tissue.

The epicardial and endocardial surfaces of the heart are attractive targets to administer antiarrhythmic electrotherapies. Electrically stimulating wide areas of the surfaces of small mammalian ventricles is straightforward given the relatively small scale of their myocardial dimensions compared to the tissue space constant and electrical field. However, it has yet to be proven for larger mammalian hearts with tissue properties and ventricular dimensions closer to humans. Our goal was to address the feasibility and impact of wide-area electrical stimulation on the ventricular surfaces of large mammalian hearts at different stimulus strengths. This was accomplished by placing long line electrodes on the ventricular surfaces of pig hearts that span wide areas, and activating them individually. Stimulus efficacy was assessed and compared between surfaces, and tissue viability was evaluated. Activation time was dependent on stimulation strength and location, achieving uniform linear stimulation at 9x threshold strength. Endocardial stimulation activated more tissue transmurally than epicardial stimulation, which could be considered a potential target for future cardiac electrotherapies. Overall, our results indicate that electrically stimulating wide areas of the ventricular surfaces of large mammals is achievable with line electrodes, minimal tissue damage, and energies under the human pain threshold (100 mJ).

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.